TY  - JOUR
AU  - Kolaković, Ana
AU  - Bundalo, Maja
AU  - Đurić, Tamara
AU  - Končar, Igor
AU  - Stanković, Aleksandra
AU  - Živković, Maja
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13103
AB  - Background/Aim. The renin-angiotensin system (RAS) is linked to the development of atherosclerosis (As), including its initiation and progression. Besides the well-known angio-tensin-converting enzyme (ACE), two newer RAS family members are related to vascular remodeling - ACE2 as a homolog of ACE and collectrin [transmembrane protein 27 (TMEM27)] as a homolog of ACE2. Up to now, a limited number of studies have examined the expression of these RAS components in advanced carotid plaque (CP) tissue based on the sex of the patients and plaque phenotypes (PPs). There are two ultrasonographically defined PPs - the hypoechogenic plaque (HoP) and the hyperechogenic plaque (HerP) phenotype. The aim of the study was to investigate whether there was a correlation between the expression of RAS components in the CP and the sex and PPs of patients. Methods. We examined 74 patients with advanced CP who underwent carotid endarterectomy. The intraplaque expression of RAS components was determined with the real-time polymerase chain reaction, using the TaqMan® gene expression assays and Western blot. A two-way ANOVA followed by a post-hoc Tukey test was performed for the statistical analysis of results. Results. No interaction was recorded between the sex of the patients and PPs in influencing the relative expression of ACE and TMEM27 messenger RNA (mRNA) (p > 0.05). In 56.06% of plaque samples, no expression of ACE2 mRNA was detected. Among the plaques where ACE2 mRNA expression was detected, its expression level was higher in females with the HoP phenotype compared to females with the HerP phenotype (p < 0.001). In patients with the HoP phenotype, females had higher expression of ACE2 mRNA than males (p < 0.05). In the male study group, ACE protein levels were significantly lower in the HoP phenotype compared to the HerP phenotype (p < 0.001). Fe-males with the HoP phenotype had significantly higher ACE protein levels than males with the HoP phenotype (p < 0.0001). Conclusion. Our results revealed alterations in the expression levels of ACE and ACE2, at the mRNA and protein levels, in advanced carotid As. These alterations are impacted by sex and PP and may indicate a switch from the balanced RAS/ACE/ACE2 axis in the healthy blood vessel to the unbalanced axis in vascular remodeling due to As.
AB  - Renin-angiotenzin sistem (RAS) povezan je sa
razvojem ateroskleroze (As), uključujući njen nastanak i
progresiju. Pored dobro poznatog angiotenzinkonvertujućeg enzima (angiotensin-converting enzyme – ACE),
dva nova člana RAS familije povezana su sa
remodelovanjem zidova krvnih sudova – ACE2 kao
homolog ACE i kolektrin [transmembrane protein 27
(TMEM27)] kao homolog ACE2. Do sada je mali broj
studija ispitivao ekspresiju komponenti RAS sistema u tkivu
uznapredovalog karotidnog plaka (KP) u odnosu na pol
bolesnika i fenotip plaka (FP). Postoje dva tipa KP
definisana primenom ultrazvuka – fenotip hipoehogenog
plaka (HoP) i fenotip hiperehogenog plaka (HerP). Cilj rada
bio je da se ispita da li postoji korelacija između ekspresije
komponenti RAS u KP i pola i FP bolesnika. Metode.
Ispitano je 74 bolesnika sa uznapredovalim KP koji su bili
podvrgnuti operativnoj proceduri karotidne
endarterektomije. Ekspresija komponenti RAS sistema u
tkivu plaka utvrđena je lančanom reakcijom polimeraze u
realnom vremenu (real-time polymerase chain reaction)primenom eseja TaqMan® tehnologije i metode Western blota. Dvosmerna analiza varijanse i Tukey post-hoc test korišćen su za statističku obradu rezultata. Rezultati. Nije utvrđena
interakcija FP i pola bolesnika u uticaju na relativnu
ekspresiju informacione RNK (iRNK) za ACE i TMEM27
(p > 0,05). U 56,06% uzoraka plaka nije detektovana
ekspresija iRNK za ACE2. U plakovima u kojima je
detektovana ekspresija iRNK za ACE2, njen nivo bio je viši
kod žena sa HoP u poređenju sa ženama sa HerP (p <
0,001). U grupi bolesnika sa fenotipom HoP, žene su imale
viši nivo iRNK za ACE2 nego muškarci (p < 0,05). U grupi
muškaraca, nivoi ekspresije ACE proteina bili suznačajno
niži u fenotipu HoP u poređenju sa HerP (p < 0,001). Žene
sa fenotipom HoP imale su značajno viši nivo ACE
proteina u poređenju sa muškarcima sa HoP (p < 0,0001).
Zaključak. Naši rezultati pokazali su da postoje promene
nivoa ekspresije ACE i ACE2, na nivou proteina i iRNK u
uznapredovaloj karotidnoj As. Te promene zavise od pola i
FP i mogu ukazivati na to da balans ose RAS/ACE/ACE2
koji postoji u zdravom krvnom sudu postaje poremećen
tokom remodelovanja zida krvnog suda usled As.
T2  - Vojnosanitetski pregled
T1  - The expression of renin-angiotensin system components in human carotid plaque
T1  - Ekspresija komponenti renin-angiotenzin sistema u humanom karotidnom plaku
DO  - 10.2298/VSP221028014K
ER  - 

@article{
author = "Kolaković, Ana and Bundalo, Maja and Đurić, Tamara and Končar, Igor and Stanković, Aleksandra and Živković, Maja",
year = "2024",
abstract = "Background/Aim. The renin-angiotensin system (RAS) is linked to the development of atherosclerosis (As), including its initiation and progression. Besides the well-known angio-tensin-converting enzyme (ACE), two newer RAS family members are related to vascular remodeling - ACE2 as a homolog of ACE and collectrin [transmembrane protein 27 (TMEM27)] as a homolog of ACE2. Up to now, a limited number of studies have examined the expression of these RAS components in advanced carotid plaque (CP) tissue based on the sex of the patients and plaque phenotypes (PPs). There are two ultrasonographically defined PPs - the hypoechogenic plaque (HoP) and the hyperechogenic plaque (HerP) phenotype. The aim of the study was to investigate whether there was a correlation between the expression of RAS components in the CP and the sex and PPs of patients. Methods. We examined 74 patients with advanced CP who underwent carotid endarterectomy. The intraplaque expression of RAS components was determined with the real-time polymerase chain reaction, using the TaqMan® gene expression assays and Western blot. A two-way ANOVA followed by a post-hoc Tukey test was performed for the statistical analysis of results. Results. No interaction was recorded between the sex of the patients and PPs in influencing the relative expression of ACE and TMEM27 messenger RNA (mRNA) (p > 0.05). In 56.06% of plaque samples, no expression of ACE2 mRNA was detected. Among the plaques where ACE2 mRNA expression was detected, its expression level was higher in females with the HoP phenotype compared to females with the HerP phenotype (p < 0.001). In patients with the HoP phenotype, females had higher expression of ACE2 mRNA than males (p < 0.05). In the male study group, ACE protein levels were significantly lower in the HoP phenotype compared to the HerP phenotype (p < 0.001). Fe-males with the HoP phenotype had significantly higher ACE protein levels than males with the HoP phenotype (p < 0.0001). Conclusion. Our results revealed alterations in the expression levels of ACE and ACE2, at the mRNA and protein levels, in advanced carotid As. These alterations are impacted by sex and PP and may indicate a switch from the balanced RAS/ACE/ACE2 axis in the healthy blood vessel to the unbalanced axis in vascular remodeling due to As., Renin-angiotenzin sistem (RAS) povezan je sa
razvojem ateroskleroze (As), uključujući njen nastanak i
progresiju. Pored dobro poznatog angiotenzinkonvertujućeg enzima (angiotensin-converting enzyme – ACE),
dva nova člana RAS familije povezana su sa
remodelovanjem zidova krvnih sudova – ACE2 kao
homolog ACE i kolektrin [transmembrane protein 27
(TMEM27)] kao homolog ACE2. Do sada je mali broj
studija ispitivao ekspresiju komponenti RAS sistema u tkivu
uznapredovalog karotidnog plaka (KP) u odnosu na pol
bolesnika i fenotip plaka (FP). Postoje dva tipa KP
definisana primenom ultrazvuka – fenotip hipoehogenog
plaka (HoP) i fenotip hiperehogenog plaka (HerP). Cilj rada
bio je da se ispita da li postoji korelacija između ekspresije
komponenti RAS u KP i pola i FP bolesnika. Metode.
Ispitano je 74 bolesnika sa uznapredovalim KP koji su bili
podvrgnuti operativnoj proceduri karotidne
endarterektomije. Ekspresija komponenti RAS sistema u
tkivu plaka utvrđena je lančanom reakcijom polimeraze u
realnom vremenu (real-time polymerase chain reaction)primenom eseja TaqMan® tehnologije i metode Western blota. Dvosmerna analiza varijanse i Tukey post-hoc test korišćen su za statističku obradu rezultata. Rezultati. Nije utvrđena
interakcija FP i pola bolesnika u uticaju na relativnu
ekspresiju informacione RNK (iRNK) za ACE i TMEM27
(p > 0,05). U 56,06% uzoraka plaka nije detektovana
ekspresija iRNK za ACE2. U plakovima u kojima je
detektovana ekspresija iRNK za ACE2, njen nivo bio je viši
kod žena sa HoP u poređenju sa ženama sa HerP (p <
0,001). U grupi bolesnika sa fenotipom HoP, žene su imale
viši nivo iRNK za ACE2 nego muškarci (p < 0,05). U grupi
muškaraca, nivoi ekspresije ACE proteina bili suznačajno
niži u fenotipu HoP u poređenju sa HerP (p < 0,001). Žene
sa fenotipom HoP imale su značajno viši nivo ACE
proteina u poređenju sa muškarcima sa HoP (p < 0,0001).
Zaključak. Naši rezultati pokazali su da postoje promene
nivoa ekspresije ACE i ACE2, na nivou proteina i iRNK u
uznapredovaloj karotidnoj As. Te promene zavise od pola i
FP i mogu ukazivati na to da balans ose RAS/ACE/ACE2
koji postoji u zdravom krvnom sudu postaje poremećen
tokom remodelovanja zida krvnog suda usled As.",
journal = "Vojnosanitetski pregled",
title = "The expression of renin-angiotensin system components in human carotid plaque, Ekspresija komponenti renin-angiotenzin sistema u humanom karotidnom plaku",
doi = "10.2298/VSP221028014K"
}

Kolaković, A., Bundalo, M., Đurić, T., Končar, I., Stanković, A.,& Živković, M.. (2024). The expression of renin-angiotensin system components in human carotid plaque. in Vojnosanitetski pregled.
https://doi.org/10.2298/VSP221028014K

Kolaković A, Bundalo M, Đurić T, Končar I, Stanković A, Živković M. The expression of renin-angiotensin system components in human carotid plaque. in Vojnosanitetski pregled. 2024;.
doi:10.2298/VSP221028014K .

Kolaković, Ana, Bundalo, Maja, Đurić, Tamara, Končar, Igor, Stanković, Aleksandra, Živković, Maja, "The expression of renin-angiotensin system components in human carotid plaque" in Vojnosanitetski pregled (2024),
https://doi.org/10.2298/VSP221028014K . .

TY  - JOUR
AU  - Stefanović, Milan
AU  - Stojković, Ljiljana
AU  - Životić, Ivan
AU  - Dinčić, Evica
AU  - Stanković, Aleksandra
AU  - Živković, Maja
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12715
AB  - Multiple sclerosis (MS), a noncurable autoimmune neurodegenerative disease, requires constant research that could improve understanding of both environmental and genetic factors that lead to its occurrence and/or progression. Recognition of the genetic basis of MS further leads to an investigation of the regulatory role of genetic variants on gene expression. Among risk variants for MS, Ikaros zinc finger 3 (IKZF3) gene variant rs12946510 was identified as one of the top-ranked and the expression quantitative trait loci (eQTL) for genes residing in chromosomal locus 17q12- 21. The study aimed to investigate the association of gene expression of the immunologically relevant genes, which map to indicated locus, ORMDL3, GSDMB, and IKZF3, with MS and rs12946510 genotype, taking into account disease phase, clinical parameters of disease progression, and severity and immunomodulatory therapy. We used TaqMan® technology for both allelic discrimination and gene expression determination in 67 relapsing MS patients and 50 healthy controls. Decreased ORMDL3 and GSDMB mRNA levels had significant associations with MS and rs12946510 TT rare homozygote among patients. Significant positive correlations between ORMDL3 and GSDMB mRNA expression were observed in both patients and controls. We detected the significant between-effect of sex and rs12946510 on the expression of ORMDL3 in the patient group and interferon β therapy and rs12946510 on GSDMB expression. Our results show the association of ORMDL3 and GSDMB mRNA expression with the clinical manifestation of MS and confirm that IKZF3 rs12946510 exerts the eQTL effect on both genes in multiple sclerosis. Besides providing novel insight related to MS phases and interferon β therapy, the study results confirm previous studies on regulatory genetic variants, autoimmunity, and MS.
T2  - Heliyon
T1  - Expression levels of GSDMB and ORMDL3 are associated with relapsing-remitting multiple sclerosis and IKZF3 rs12946510 variant
VL  - 10
IS  - 3
SP  - e25033
DO  - 10.1016/j.heliyon.2024.e25033
ER  - 

@article{
author = "Stefanović, Milan and Stojković, Ljiljana and Životić, Ivan and Dinčić, Evica and Stanković, Aleksandra and Živković, Maja",
year = "2024",
abstract = "Multiple sclerosis (MS), a noncurable autoimmune neurodegenerative disease, requires constant research that could improve understanding of both environmental and genetic factors that lead to its occurrence and/or progression. Recognition of the genetic basis of MS further leads to an investigation of the regulatory role of genetic variants on gene expression. Among risk variants for MS, Ikaros zinc finger 3 (IKZF3) gene variant rs12946510 was identified as one of the top-ranked and the expression quantitative trait loci (eQTL) for genes residing in chromosomal locus 17q12- 21. The study aimed to investigate the association of gene expression of the immunologically relevant genes, which map to indicated locus, ORMDL3, GSDMB, and IKZF3, with MS and rs12946510 genotype, taking into account disease phase, clinical parameters of disease progression, and severity and immunomodulatory therapy. We used TaqMan® technology for both allelic discrimination and gene expression determination in 67 relapsing MS patients and 50 healthy controls. Decreased ORMDL3 and GSDMB mRNA levels had significant associations with MS and rs12946510 TT rare homozygote among patients. Significant positive correlations between ORMDL3 and GSDMB mRNA expression were observed in both patients and controls. We detected the significant between-effect of sex and rs12946510 on the expression of ORMDL3 in the patient group and interferon β therapy and rs12946510 on GSDMB expression. Our results show the association of ORMDL3 and GSDMB mRNA expression with the clinical manifestation of MS and confirm that IKZF3 rs12946510 exerts the eQTL effect on both genes in multiple sclerosis. Besides providing novel insight related to MS phases and interferon β therapy, the study results confirm previous studies on regulatory genetic variants, autoimmunity, and MS.",
journal = "Heliyon",
title = "Expression levels of GSDMB and ORMDL3 are associated with relapsing-remitting multiple sclerosis and IKZF3 rs12946510 variant",
volume = "10",
number = "3",
pages = "e25033",
doi = "10.1016/j.heliyon.2024.e25033"
}

Stefanović, M., Stojković, L., Životić, I., Dinčić, E., Stanković, A.,& Živković, M.. (2024). Expression levels of GSDMB and ORMDL3 are associated with relapsing-remitting multiple sclerosis and IKZF3 rs12946510 variant. in Heliyon, 10(3), e25033.
https://doi.org/10.1016/j.heliyon.2024.e25033

Stefanović M, Stojković L, Životić I, Dinčić E, Stanković A, Živković M. Expression levels of GSDMB and ORMDL3 are associated with relapsing-remitting multiple sclerosis and IKZF3 rs12946510 variant. in Heliyon. 2024;10(3):e25033.
doi:10.1016/j.heliyon.2024.e25033 .

Stefanović, Milan, Stojković, Ljiljana, Životić, Ivan, Dinčić, Evica, Stanković, Aleksandra, Živković, Maja, "Expression levels of GSDMB and ORMDL3 are associated with relapsing-remitting multiple sclerosis and IKZF3 rs12946510 variant" in Heliyon, 10, no. 3 (2024):e25033,
https://doi.org/10.1016/j.heliyon.2024.e25033 . .

TY  - JOUR
AU  - Mitrović, Kristina
AU  - Životić, Ivan
AU  - Kolić, Ivana
AU  - Žakula, Jelena
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Jovanović, Ivan
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12889
AB  - Background The majority of CAKUT-associated CNVs overlap at least one miRNA gene, thus affecting the cellular levels of the corresponding miRNA. We aimed to investigate the potency of restitution of CNV-affected miRNA levels to remediate the dysregulated expression of target genes involved in kidney physiology and development in vitro.  Methods Heterozygous MIR484 knockout HEK293 and homozygous MIR185 knockout HEK293 cell lines were used as models depicting the deletion of the frequently affected miRNA genes by CAKUT-associated CNVs. After treatment with the corresponding miRNA mimics, the levels of the target genes have been compared to the non-targeting control treatment. For both investigated miRNAs, MDM2 and PKD1 were evaluated as common targets, while additional 3 genes were investigated as targets of each individual miRNA (NOTCH3, FIS1 and APAF1 as hsa-miR-484 targets and RHOA, ATF6 and CDC42 as hsa-miR-185-5p targets).  Results Restitution of the corresponding miRNA levels in both knockout cell lines has induced a change in the mRNA levels of certain candidate target genes, thus confirming the potential to alleviate the CNV effect on miRNA expression. Intriguingly, HEK293 WT treatment with investigated miRNA mimics has triggered a more pronounced effect, thus suggesting the importance of miRNA interplay in different genomic contexts.  Conclusions Dysregulation of multiple mRNA targets mediated by CNV-affected miRNAs could represent the underlying mechanism behind the unresolved CAKUT occurrence and phenotypic variability observed in CAKUT patients. Characterizing miRNAs located in CNVs and their potential to become molecular targets could eventually help in understanding and improving the management of CAKUT.
T2  - BMC Genomics
T1  - A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT
VL  - 25
IS  - 1
SP  - 218
DO  - 10.1186/s12864-024-10121-8
ER  - 

@article{
author = "Mitrović, Kristina and Životić, Ivan and Kolić, Ivana and Žakula, Jelena and Živković, Maja and Stanković, Aleksandra and Jovanović, Ivan",
year = "2024",
abstract = "Background The majority of CAKUT-associated CNVs overlap at least one miRNA gene, thus affecting the cellular levels of the corresponding miRNA. We aimed to investigate the potency of restitution of CNV-affected miRNA levels to remediate the dysregulated expression of target genes involved in kidney physiology and development in vitro.  Methods Heterozygous MIR484 knockout HEK293 and homozygous MIR185 knockout HEK293 cell lines were used as models depicting the deletion of the frequently affected miRNA genes by CAKUT-associated CNVs. After treatment with the corresponding miRNA mimics, the levels of the target genes have been compared to the non-targeting control treatment. For both investigated miRNAs, MDM2 and PKD1 were evaluated as common targets, while additional 3 genes were investigated as targets of each individual miRNA (NOTCH3, FIS1 and APAF1 as hsa-miR-484 targets and RHOA, ATF6 and CDC42 as hsa-miR-185-5p targets).  Results Restitution of the corresponding miRNA levels in both knockout cell lines has induced a change in the mRNA levels of certain candidate target genes, thus confirming the potential to alleviate the CNV effect on miRNA expression. Intriguingly, HEK293 WT treatment with investigated miRNA mimics has triggered a more pronounced effect, thus suggesting the importance of miRNA interplay in different genomic contexts.  Conclusions Dysregulation of multiple mRNA targets mediated by CNV-affected miRNAs could represent the underlying mechanism behind the unresolved CAKUT occurrence and phenotypic variability observed in CAKUT patients. Characterizing miRNAs located in CNVs and their potential to become molecular targets could eventually help in understanding and improving the management of CAKUT.",
journal = "BMC Genomics",
title = "A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT",
volume = "25",
number = "1",
pages = "218",
doi = "10.1186/s12864-024-10121-8"
}

Mitrović, K., Životić, I., Kolić, I., Žakula, J., Živković, M., Stanković, A.,& Jovanović, I.. (2024). A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT. in BMC Genomics, 25(1), 218.
https://doi.org/10.1186/s12864-024-10121-8

Mitrović K, Životić I, Kolić I, Žakula J, Živković M, Stanković A, Jovanović I. A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT. in BMC Genomics. 2024;25(1):218.
doi:10.1186/s12864-024-10121-8 .

Mitrović, Kristina, Životić, Ivan, Kolić, Ivana, Žakula, Jelena, Živković, Maja, Stanković, Aleksandra, Jovanović, Ivan, "A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT" in BMC Genomics, 25, no. 1 (2024):218,
https://doi.org/10.1186/s12864-024-10121-8 . .

TY  - JOUR
AU  - Đorđević, Ana
AU  - Živković, Maja
AU  - Bošković, Maja
AU  - Dekleva, Milica
AU  - Stanković, Goran
AU  - Stanković, Aleksandra
AU  - Đurić, Tamara
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10617
AB  - Galectin-3 is encoded by LGALS-3, located in a unique haplotype block in Caucasians. According to the Tagger server, rs4040064, rs11628437, and rs7159490 cover 82% (r2 > 0.8) of the genetic variance of this HapBlock. Our aims were to examine the association of their haplotypes with first myocardial infarction (MI), changes in left ventricular echocardiographic parameters over time, and impact on plasma galectin-3 and LGALS-3 mRNA in peripheral blood mononuclear cells, both 6 months post-MI. The study group consisted of 546 MI patients and 323 controls. Gene expression was assessed in 92 patients and plasma galectin-3 in 189 patients. Rs4040064, rs11628437, rs7159490, and LGALS-3 mRNA expression were detected using TaqMan® technology. Plasma galectin-3 concentrations were determined by the ELISA method. We found that the TGC haplotype could have a protective effect against MI (adjusted OR 0.19 [0.05–0.72], p = 0.015) and that the GAC haplotype had significantly higher galectin-3 concentrations (48.3 [37.3–59.4] ng/mL vs. 18.9 [14.5–23.4] ng/mL, p < 0.0001), both in males and compared to the referent haplotype GGC. Higher plasma Gal-3 was also associated with higher NYHA class and systolic dysfunction. Our results suggest that variants tagging LGALS-3 HapBlock could reflect plasma Gal-3 levels 6 months post-MI and may have a potential protective effect against MI in men. Further replication, validation, and functional studies are needed.
T2  - Genes
T1  - Variants Tagging LGALS-3 Haplotype Block in Association with First Myocardial Infarction and Plasma Galectin-3 Six Months after the Acute Event
VL  - 14
IS  - 1
SP  - 109
DO  - 10.3390/genes14010109
ER  - 

@article{
author = "Đorđević, Ana and Živković, Maja and Bošković, Maja and Dekleva, Milica and Stanković, Goran and Stanković, Aleksandra and Đurić, Tamara",
year = "2023",
abstract = "Galectin-3 is encoded by LGALS-3, located in a unique haplotype block in Caucasians. According to the Tagger server, rs4040064, rs11628437, and rs7159490 cover 82% (r2 > 0.8) of the genetic variance of this HapBlock. Our aims were to examine the association of their haplotypes with first myocardial infarction (MI), changes in left ventricular echocardiographic parameters over time, and impact on plasma galectin-3 and LGALS-3 mRNA in peripheral blood mononuclear cells, both 6 months post-MI. The study group consisted of 546 MI patients and 323 controls. Gene expression was assessed in 92 patients and plasma galectin-3 in 189 patients. Rs4040064, rs11628437, rs7159490, and LGALS-3 mRNA expression were detected using TaqMan® technology. Plasma galectin-3 concentrations were determined by the ELISA method. We found that the TGC haplotype could have a protective effect against MI (adjusted OR 0.19 [0.05–0.72], p = 0.015) and that the GAC haplotype had significantly higher galectin-3 concentrations (48.3 [37.3–59.4] ng/mL vs. 18.9 [14.5–23.4] ng/mL, p < 0.0001), both in males and compared to the referent haplotype GGC. Higher plasma Gal-3 was also associated with higher NYHA class and systolic dysfunction. Our results suggest that variants tagging LGALS-3 HapBlock could reflect plasma Gal-3 levels 6 months post-MI and may have a potential protective effect against MI in men. Further replication, validation, and functional studies are needed.",
journal = "Genes",
title = "Variants Tagging LGALS-3 Haplotype Block in Association with First Myocardial Infarction and Plasma Galectin-3 Six Months after the Acute Event",
volume = "14",
number = "1",
pages = "109",
doi = "10.3390/genes14010109"
}

Đorđević, A., Živković, M., Bošković, M., Dekleva, M., Stanković, G., Stanković, A.,& Đurić, T.. (2023). Variants Tagging LGALS-3 Haplotype Block in Association with First Myocardial Infarction and Plasma Galectin-3 Six Months after the Acute Event. in Genes, 14(1), 109.
https://doi.org/10.3390/genes14010109

Đorđević A, Živković M, Bošković M, Dekleva M, Stanković G, Stanković A, Đurić T. Variants Tagging LGALS-3 Haplotype Block in Association with First Myocardial Infarction and Plasma Galectin-3 Six Months after the Acute Event. in Genes. 2023;14(1):109.
doi:10.3390/genes14010109 .

Đorđević, Ana, Živković, Maja, Bošković, Maja, Dekleva, Milica, Stanković, Goran, Stanković, Aleksandra, Đurić, Tamara, "Variants Tagging LGALS-3 Haplotype Block in Association with First Myocardial Infarction and Plasma Galectin-3 Six Months after the Acute Event" in Genes, 14, no. 1 (2023):109,
https://doi.org/10.3390/genes14010109 . .

TY  - JOUR
AU  - Mačak, Nataša
AU  - Jovanović, Ivan G.
AU  - Živković, Maja
AU  - Mitrović, Kristina
AU  - Cvetković, Mirjana
AU  - Kostić, Mirjana
AU  - Stanković, Aleksandra
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11165
AB  - Congenital anomalies of the kidney and urinary tract (CAKUT) represent structural and functional urinary system malformations and take place as one of the most common congenital malformations with an incidence of 1:500. Ureteral obstruction-induced hydronephrosis is associated with renal fibrosis and chronic kidney diseases in the pediatric CAKUT. We aimed to construct interaction network of previously bioinformatically associated miRNAs with CAKUT differentially expressed genes in order to prioritize those associated with fibrotic process and to experimentally validate the expression of selected miRNAs in CAKUT patients compared to control group. We constructed interaction network of hsa-miR-101-3p, hsa-miR-101-5p and hsa-miR-29c-3p that showed significant association with fibrosis. The top enriched molecular pathway was extracellular matrix-receptor interaction (adjusted p = .0000263). We experimentally confirmed expression of three miRNAs (hsa-miR-29c-3p, hsa-miR-101-3p and hsa-miR-101-5p) in obstructed ureters (ureteropelvic junction obstruction and primary obstructive megaureter) and vesicoureteral reflux. The hsa-miR-29c-3p was shown to have lower expression in both patient groups compared to controls. Relative levels of hsa-miR-101-5p and hsa-miR-101-3p showed significant positive correlations in both groups of patients. Statistically significant correlation was observed between hsa-miR-101 (-3p and -5p) and hsa-miR-29c-3p only in the obstructed group. The significant downregulation of anti-fibrotic hsa-miR-29c-3p in obstructive CAKUT could explain activation of genes involved in fibrotic processes. As miRNAs are promising candidates in therapeutic approaches our results need further measurement of fibrotic markers or assessment of extent of fibrosis and functional evaluation of hsa-miR-29c.
T2  - Nucleosides, Nucleotides & Nucleic Acids
T1  - Downregulation of fibrosis related hsa-miR-29c-3p in human CAKUT
VL  - 42
IS  - 12
SP  - 945
EP  - 958
DO  - 10.1080/15257770.2023.2218430
ER  - 

@article{
author = "Mačak, Nataša and Jovanović, Ivan G. and Živković, Maja and Mitrović, Kristina and Cvetković, Mirjana and Kostić, Mirjana and Stanković, Aleksandra",
year = "2023",
abstract = "Congenital anomalies of the kidney and urinary tract (CAKUT) represent structural and functional urinary system malformations and take place as one of the most common congenital malformations with an incidence of 1:500. Ureteral obstruction-induced hydronephrosis is associated with renal fibrosis and chronic kidney diseases in the pediatric CAKUT. We aimed to construct interaction network of previously bioinformatically associated miRNAs with CAKUT differentially expressed genes in order to prioritize those associated with fibrotic process and to experimentally validate the expression of selected miRNAs in CAKUT patients compared to control group. We constructed interaction network of hsa-miR-101-3p, hsa-miR-101-5p and hsa-miR-29c-3p that showed significant association with fibrosis. The top enriched molecular pathway was extracellular matrix-receptor interaction (adjusted p = .0000263). We experimentally confirmed expression of three miRNAs (hsa-miR-29c-3p, hsa-miR-101-3p and hsa-miR-101-5p) in obstructed ureters (ureteropelvic junction obstruction and primary obstructive megaureter) and vesicoureteral reflux. The hsa-miR-29c-3p was shown to have lower expression in both patient groups compared to controls. Relative levels of hsa-miR-101-5p and hsa-miR-101-3p showed significant positive correlations in both groups of patients. Statistically significant correlation was observed between hsa-miR-101 (-3p and -5p) and hsa-miR-29c-3p only in the obstructed group. The significant downregulation of anti-fibrotic hsa-miR-29c-3p in obstructive CAKUT could explain activation of genes involved in fibrotic processes. As miRNAs are promising candidates in therapeutic approaches our results need further measurement of fibrotic markers or assessment of extent of fibrosis and functional evaluation of hsa-miR-29c.",
journal = "Nucleosides, Nucleotides & Nucleic Acids",
title = "Downregulation of fibrosis related hsa-miR-29c-3p in human CAKUT",
volume = "42",
number = "12",
pages = "945-958",
doi = "10.1080/15257770.2023.2218430"
}

Mačak, N., Jovanović, I. G., Živković, M., Mitrović, K., Cvetković, M., Kostić, M.,& Stanković, A.. (2023). Downregulation of fibrosis related hsa-miR-29c-3p in human CAKUT. in Nucleosides, Nucleotides & Nucleic Acids, 42(12), 945-958.
https://doi.org/10.1080/15257770.2023.2218430

Mačak N, Jovanović IG, Živković M, Mitrović K, Cvetković M, Kostić M, Stanković A. Downregulation of fibrosis related hsa-miR-29c-3p in human CAKUT. in Nucleosides, Nucleotides & Nucleic Acids. 2023;42(12):945-958.
doi:10.1080/15257770.2023.2218430 .

Mačak, Nataša, Jovanović, Ivan G., Živković, Maja, Mitrović, Kristina, Cvetković, Mirjana, Kostić, Mirjana, Stanković, Aleksandra, "Downregulation of fibrosis related hsa-miR-29c-3p in human CAKUT" in Nucleosides, Nucleotides & Nucleic Acids, 42, no. 12 (2023):945-958,
https://doi.org/10.1080/15257770.2023.2218430 . .

TY  - CONF
AU  - Životić, Ivan
AU  - Mitrović, Kristina
AU  - Kolić, Ivana
AU  - Seke, Mariana
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Jovanović, Ivan
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12465
AB  - Introduction: Congenital anomalies of the kidney and urinary tracts(CAKUT) are a diverse spectrum of defects with complex etiology and not fully explained genetic background. miRNA-containing copy number variants (CNVs) are described as genetic risk factor for the disease development. We aimed to identify miRNAs with the maximum regulatory coverage of previously reported differentially expressed genes in CAKUT tissue compared to controls and bioinformatically characterize a set of these miRNAs which are located in common CNVs. Methods: Differentially expressed genes were identified from ureter tissue transcriptome open data GSE83946 from 15 CAKUT patients and 7 healthy controls, generated in house previously. miRPathDB v2.0 was used for identification of miRNAs with maximum coverage of DEGs(miRNAs which complimentarily regulate all DEGs). Mapping of maximum coverage miRNAs onto common CNVs (frequency >0.2) was performed using UCSC genome browser and gnomAD database. miRNA mapping common CNVs were further bioinformatically analyzed using miRPathDB v2.0. Results: In a maximum coverage set of 50 miRNAs interacting with DEGs in CAKUT, we have identified 3 miRNA geneslocated in the common CNVs(hsa-miR-663b, hsa-miR-3180-3p and hsa-miR-1302). Using Reactome database we identified all three miRNAsto be significantly enriched in the pathway Neuronal System: -log(p-value)>2.326 for hsa-miR-1302; -log(p-value)>1.556 for hsa-miR-3180-3p; and -log(pvalue)>1.703 for hsa-miR-663b. Conclusion: CAKUT is characterized with variable penetrability and expressivity and often followed with other comorbiditiessuch as neurodevelopmental disorders. miRNAsinvolved in DEG networks and prone to CNV effects could present modulating factors of the disease phenotype. Further studies should provide additional evidence about hsa-miR-1302, hsa-miR-3180-3p and hsa-miR-663b involvements in CAKUT etiology
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts
T1  - Identification of micro RNA from common copy number variants as risk factors for CAKUT
SP  - 62
EP  - 62
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12465
ER  - 

@conference{
author = "Životić, Ivan and Mitrović, Kristina and Kolić, Ivana and Seke, Mariana and Živković, Maja and Stanković, Aleksandra and Jovanović, Ivan",
year = "2023",
abstract = "Introduction: Congenital anomalies of the kidney and urinary tracts(CAKUT) are a diverse spectrum of defects with complex etiology and not fully explained genetic background. miRNA-containing copy number variants (CNVs) are described as genetic risk factor for the disease development. We aimed to identify miRNAs with the maximum regulatory coverage of previously reported differentially expressed genes in CAKUT tissue compared to controls and bioinformatically characterize a set of these miRNAs which are located in common CNVs. Methods: Differentially expressed genes were identified from ureter tissue transcriptome open data GSE83946 from 15 CAKUT patients and 7 healthy controls, generated in house previously. miRPathDB v2.0 was used for identification of miRNAs with maximum coverage of DEGs(miRNAs which complimentarily regulate all DEGs). Mapping of maximum coverage miRNAs onto common CNVs (frequency >0.2) was performed using UCSC genome browser and gnomAD database. miRNA mapping common CNVs were further bioinformatically analyzed using miRPathDB v2.0. Results: In a maximum coverage set of 50 miRNAs interacting with DEGs in CAKUT, we have identified 3 miRNA geneslocated in the common CNVs(hsa-miR-663b, hsa-miR-3180-3p and hsa-miR-1302). Using Reactome database we identified all three miRNAsto be significantly enriched in the pathway Neuronal System: -log(p-value)>2.326 for hsa-miR-1302; -log(p-value)>1.556 for hsa-miR-3180-3p; and -log(pvalue)>1.703 for hsa-miR-663b. Conclusion: CAKUT is characterized with variable penetrability and expressivity and often followed with other comorbiditiessuch as neurodevelopmental disorders. miRNAsinvolved in DEG networks and prone to CNV effects could present modulating factors of the disease phenotype. Further studies should provide additional evidence about hsa-miR-1302, hsa-miR-3180-3p and hsa-miR-663b involvements in CAKUT etiology",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts",
title = "Identification of micro RNA from common copy number variants as risk factors for CAKUT",
pages = "62-62",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12465"
}

Životić, I., Mitrović, K., Kolić, I., Seke, M., Živković, M., Stanković, A.,& Jovanović, I.. (2023). Identification of micro RNA from common copy number variants as risk factors for CAKUT. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts, 62-62.
https://hdl.handle.net/21.15107/rcub_vinar_12465

Životić I, Mitrović K, Kolić I, Seke M, Živković M, Stanković A, Jovanović I. Identification of micro RNA from common copy number variants as risk factors for CAKUT. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts. 2023;:62-62.
https://hdl.handle.net/21.15107/rcub_vinar_12465 .

Životić, Ivan, Mitrović, Kristina, Kolić, Ivana, Seke, Mariana, Živković, Maja, Stanković, Aleksandra, Jovanović, Ivan, "Identification of micro RNA from common copy number variants as risk factors for CAKUT" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia : Book of abstracts (2023):62-62,
https://hdl.handle.net/21.15107/rcub_vinar_12465 .

TY  - CONF
AU  - Živković, Maja
AU  - Kostić, S.
AU  - Stojković, Ljiljana
AU  - Kolić, Ivana
AU  - Stanković, Aleksandra
AU  - Dinčić, E.
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12466
AB  - Last decade provided multiple evidence that link disturbances in metabolic processes and energy metabolism with diseases of central nervous system and neurodegeneration. Initial phases of insulin resistance (IR) are present in natural course of multiple sclerosis (MS) and leptin was recognized as a player in MS pathophysiology and moreover cognitive decline. We aimed to investigate association of genetic variants in leptin (LEP) rs7799039, its receptor LEPR rs1137101 and proliferator-activated receptor gamma co-activator 1-alpha (PGCA1A) rs8192678 with IR parameters (HOMA-IR index, area under the curve for insulin and glucose, Cederholm insulin sensitivity index (ISIced), the insulinogenic index in the first 30 min of oral glucose tolerance test (OGTT) in patients with MS. Seventy eight relapsing-remitting patients in clinical remission, free of corticosteroids for at least three months, were included in the study. None of the 3 variants’ genotypes were associated with HOMA-IR index, area under the curve for insulin and glucose and the insulinogenic index in the first 30 min of OGTT. PGC1A variant was significantly associated with ISIced (Kruskal-Wallis ANOVA, p = 0.04). Leptin gene variant was significantly associated with impaired GT (p=0.029 adjusted for gender and other two variants). None of the variant showed association with IR. In conclusion, we found that genetic variants in leptin signalling pathway affect glucose tolerance and insulin sensitivity in patients with MS. As both, leptin and PGC1A have role in preventing neuronal death and reducing oxidative stress neuronal damage current results favour further investigation toward preserving cognitive status and neuroprotection in MS.
C3  - CONy : 17th World Congress on Controversies in Neurology : Abstract book
T1  - Leptin signalling genetic variants and insulin resistance in multiple sclerosis patients
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12466
ER  - 

@conference{
author = "Živković, Maja and Kostić, S. and Stojković, Ljiljana and Kolić, Ivana and Stanković, Aleksandra and Dinčić, E.",
year = "2023",
abstract = "Last decade provided multiple evidence that link disturbances in metabolic processes and energy metabolism with diseases of central nervous system and neurodegeneration. Initial phases of insulin resistance (IR) are present in natural course of multiple sclerosis (MS) and leptin was recognized as a player in MS pathophysiology and moreover cognitive decline. We aimed to investigate association of genetic variants in leptin (LEP) rs7799039, its receptor LEPR rs1137101 and proliferator-activated receptor gamma co-activator 1-alpha (PGCA1A) rs8192678 with IR parameters (HOMA-IR index, area under the curve for insulin and glucose, Cederholm insulin sensitivity index (ISIced), the insulinogenic index in the first 30 min of oral glucose tolerance test (OGTT) in patients with MS. Seventy eight relapsing-remitting patients in clinical remission, free of corticosteroids for at least three months, were included in the study. None of the 3 variants’ genotypes were associated with HOMA-IR index, area under the curve for insulin and glucose and the insulinogenic index in the first 30 min of OGTT. PGC1A variant was significantly associated with ISIced (Kruskal-Wallis ANOVA, p = 0.04). Leptin gene variant was significantly associated with impaired GT (p=0.029 adjusted for gender and other two variants). None of the variant showed association with IR. In conclusion, we found that genetic variants in leptin signalling pathway affect glucose tolerance and insulin sensitivity in patients with MS. As both, leptin and PGC1A have role in preventing neuronal death and reducing oxidative stress neuronal damage current results favour further investigation toward preserving cognitive status and neuroprotection in MS.",
journal = "CONy : 17th World Congress on Controversies in Neurology : Abstract book",
title = "Leptin signalling genetic variants and insulin resistance in multiple sclerosis patients",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12466"
}

Živković, M., Kostić, S., Stojković, L., Kolić, I., Stanković, A.,& Dinčić, E.. (2023). Leptin signalling genetic variants and insulin resistance in multiple sclerosis patients. in CONy : 17th World Congress on Controversies in Neurology : Abstract book.
https://hdl.handle.net/21.15107/rcub_vinar_12466

Živković M, Kostić S, Stojković L, Kolić I, Stanković A, Dinčić E. Leptin signalling genetic variants and insulin resistance in multiple sclerosis patients. in CONy : 17th World Congress on Controversies in Neurology : Abstract book. 2023;.
https://hdl.handle.net/21.15107/rcub_vinar_12466 .

Živković, Maja, Kostić, S., Stojković, Ljiljana, Kolić, Ivana, Stanković, Aleksandra, Dinčić, E., "Leptin signalling genetic variants and insulin resistance in multiple sclerosis patients" in CONy : 17th World Congress on Controversies in Neurology : Abstract book (2023),
https://hdl.handle.net/21.15107/rcub_vinar_12466 .

TY  - CONF
AU  - Stanković, Aleksandra
AU  - Jovanović, Ivan G.
AU  - Dinčić, E.
AU  - Vojinović, S.
AU  - Stojković, Ljiljana S.
AU  - Đorđević, Ana
AU  - Kuveljić, Jovana
AU  - Živković, Maja
PY  - 2023
UR  - https://web.archive.org/web/20240131090652/https://cony2023.comtecmed.com/e-posters/
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12641
AB  - Molecular background and biomarkers of highly heterogenous and hardly predictable disease progression among relapse-onset MS patients are of high research interest. In the current pilot study, we aimed to employ next-generation sequencing to investigate the expression of whole small non-coding microRNAs (miRNome) in two groups of MS patients with highly distinctive progression phenotype: one with fast progressing, severely disabling course vs. mild course of MS, longitudinally followed 10 years. Peripheral blood mononuclear cells (PBMC) miRNome data was obtained from mild phenotype MS (n=4 patients) and progressive phenotype MS (n=5 patients), using TakaraBio SMARTer smRNA-Seq Kit on iSeq100 (Illumina). Pre-processing of raw sequencing data, quality control and miRNA differential expression analysis was performed using sRNAtoolbox pipeline. Functional interpretation of differentially expressed miRNA target genes was done in DIANA-miRPathv3.0. Tarbase v8.0 served as a resource of miRNA:gene interactions. Achieved read depth was approximately 1 million raw reads/sample, allowing detection of up to 92 mature miRNAs after genome alignment and miRbase v22 annotation. Differential expression analysis identified the significant upregulation of hsa-miR-23c (log2FC=4.29, Padj= 0.03) in progressive phenotype. Top significantly enriched KEGG pathways in hsa-miR-23c targets suggested regulation of molecular pathways involved in autoimmunity (antigen presentation, Epstein-Barr virus infection) and cancer. In conclusion, this pilot study indicates phenotype-related differences in expression of miRNAs, molecules with high regulatory and biomarker properties. Although detected in PBMC, has-miR-23c is highly expressed in the brain and target MS relevant genes such as, HLA (A, B, C), transferrin receptor, Nrf2, recently proposed to play important role in neurodegeneration.
C3  - 17th World Congress on Controversies in Neurology (CONy) : e-posters
T1  - Insight in miRNome of severe multiple sclerosis: Pilot study of distinctive relapse-onset MS phenotypes
SP  - 427
EP  - 427
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12641
ER  - 

@conference{
author = "Stanković, Aleksandra and Jovanović, Ivan G. and Dinčić, E. and Vojinović, S. and Stojković, Ljiljana S. and Đorđević, Ana and Kuveljić, Jovana and Živković, Maja",
year = "2023",
abstract = "Molecular background and biomarkers of highly heterogenous and hardly predictable disease progression among relapse-onset MS patients are of high research interest. In the current pilot study, we aimed to employ next-generation sequencing to investigate the expression of whole small non-coding microRNAs (miRNome) in two groups of MS patients with highly distinctive progression phenotype: one with fast progressing, severely disabling course vs. mild course of MS, longitudinally followed 10 years. Peripheral blood mononuclear cells (PBMC) miRNome data was obtained from mild phenotype MS (n=4 patients) and progressive phenotype MS (n=5 patients), using TakaraBio SMARTer smRNA-Seq Kit on iSeq100 (Illumina). Pre-processing of raw sequencing data, quality control and miRNA differential expression analysis was performed using sRNAtoolbox pipeline. Functional interpretation of differentially expressed miRNA target genes was done in DIANA-miRPathv3.0. Tarbase v8.0 served as a resource of miRNA:gene interactions. Achieved read depth was approximately 1 million raw reads/sample, allowing detection of up to 92 mature miRNAs after genome alignment and miRbase v22 annotation. Differential expression analysis identified the significant upregulation of hsa-miR-23c (log2FC=4.29, Padj= 0.03) in progressive phenotype. Top significantly enriched KEGG pathways in hsa-miR-23c targets suggested regulation of molecular pathways involved in autoimmunity (antigen presentation, Epstein-Barr virus infection) and cancer. In conclusion, this pilot study indicates phenotype-related differences in expression of miRNAs, molecules with high regulatory and biomarker properties. Although detected in PBMC, has-miR-23c is highly expressed in the brain and target MS relevant genes such as, HLA (A, B, C), transferrin receptor, Nrf2, recently proposed to play important role in neurodegeneration.",
journal = "17th World Congress on Controversies in Neurology (CONy) : e-posters",
title = "Insight in miRNome of severe multiple sclerosis: Pilot study of distinctive relapse-onset MS phenotypes",
pages = "427-427",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12641"
}

Stanković, A., Jovanović, I. G., Dinčić, E., Vojinović, S., Stojković, L. S., Đorđević, A., Kuveljić, J.,& Živković, M.. (2023). Insight in miRNome of severe multiple sclerosis: Pilot study of distinctive relapse-onset MS phenotypes. in 17th World Congress on Controversies in Neurology (CONy) : e-posters, 427-427.
https://hdl.handle.net/21.15107/rcub_vinar_12641

Stanković A, Jovanović IG, Dinčić E, Vojinović S, Stojković LS, Đorđević A, Kuveljić J, Živković M. Insight in miRNome of severe multiple sclerosis: Pilot study of distinctive relapse-onset MS phenotypes. in 17th World Congress on Controversies in Neurology (CONy) : e-posters. 2023;:427-427.
https://hdl.handle.net/21.15107/rcub_vinar_12641 .

Stanković, Aleksandra, Jovanović, Ivan G., Dinčić, E., Vojinović, S., Stojković, Ljiljana S., Đorđević, Ana, Kuveljić, Jovana, Živković, Maja, "Insight in miRNome of severe multiple sclerosis: Pilot study of distinctive relapse-onset MS phenotypes" in 17th World Congress on Controversies in Neurology (CONy) : e-posters (2023):427-427,
https://hdl.handle.net/21.15107/rcub_vinar_12641 .

TY  - CONF
AU  - Dekleva, Milica
AU  - Martinović, M.
AU  - Stevanović, Angelina
AU  - Živković, Maja
AU  - Đorđević, Ana
AU  - Đurić, Tamara
AU  - Stanković, Aleksandra
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12854
AB  - Background: Right ventricular (RV) dysfunction is recognized as a cardinal prognostic marker in heart failure (HF) patients. Myocardial infarction (MI) is often followed by unrecognized RV dysfunction, which can be associated with worse outcome. It is recently shown that the ratio between TAPSE and PASP (RV/PA) may depict cardiopulmonary hemodynamics better than the two parameters alone. Aim: To evaluate the interactions between left ventricular (LV) and RV function in early phase of MI and to assess the prognostic significance of RV/PA coupling in patients with first MI during 5 years follow up. Methods: The prospective study included 144 patients with the first MI treated with the primary percutaneous coronary intervention (p PCI) who underwent Doppler echocardiography within 2±1 days of MI. LV function analysis included: LV ejection fraction (EF), ratio between early diastolic velocity and tissue annular velocity (E/e) and global longitudinal strain (GLS). RV function and RV-PA interaction was expressed as ratio between TAPSE and PASP. During the five-year follow-up, major cardiovascular events and especially hospitalization for HF were analyzed. Results: Progressive RV/PA uncoupling was associated with higher degree of LV impairment and dysfunction (EF p<0.001, E/e p=0.002, GLS p<0.001) and severity of mitral regurgitation (p=0.013). Lower baseline RV/PA coupling significantly reflects the frequency of hospitalizations for HF in the population of patients with first MI during five-year follow-up (0.62 v.s.0.51, p=0.021). After multivariate adjustment RV/PA remained an independent predictor of all major cardiac events (MACE) after five years (OR 14.0 [1.5–130.8], p=0.019). Conclusion: A lower baseline RV-PA coupling, reflecting a higher degree of LV-induced pulmonary hypertension and secondary RV-dysfunction, is associated with decline of LV function in early phase of MI, and is independently associated with worse prognosis after five years. The value of RV-PA ratio as an prognstic marker warrants further investigation.
C3  - European Heart Journal
T1  - Right ventricular-pulmonary artery coupling in the early stages of infarction could optimize patient risk stratification over five years
VL  - 44
IS  - Supplement 2
SP  - ehad655.067
DO  - 10.1093/eurheartj/ehad655.067
ER  - 

@conference{
author = "Dekleva, Milica and Martinović, M. and Stevanović, Angelina and Živković, Maja and Đorđević, Ana and Đurić, Tamara and Stanković, Aleksandra",
year = "2023",
abstract = "Background: Right ventricular (RV) dysfunction is recognized as a cardinal prognostic marker in heart failure (HF) patients. Myocardial infarction (MI) is often followed by unrecognized RV dysfunction, which can be associated with worse outcome. It is recently shown that the ratio between TAPSE and PASP (RV/PA) may depict cardiopulmonary hemodynamics better than the two parameters alone. Aim: To evaluate the interactions between left ventricular (LV) and RV function in early phase of MI and to assess the prognostic significance of RV/PA coupling in patients with first MI during 5 years follow up. Methods: The prospective study included 144 patients with the first MI treated with the primary percutaneous coronary intervention (p PCI) who underwent Doppler echocardiography within 2±1 days of MI. LV function analysis included: LV ejection fraction (EF), ratio between early diastolic velocity and tissue annular velocity (E/e) and global longitudinal strain (GLS). RV function and RV-PA interaction was expressed as ratio between TAPSE and PASP. During the five-year follow-up, major cardiovascular events and especially hospitalization for HF were analyzed. Results: Progressive RV/PA uncoupling was associated with higher degree of LV impairment and dysfunction (EF p<0.001, E/e p=0.002, GLS p<0.001) and severity of mitral regurgitation (p=0.013). Lower baseline RV/PA coupling significantly reflects the frequency of hospitalizations for HF in the population of patients with first MI during five-year follow-up (0.62 v.s.0.51, p=0.021). After multivariate adjustment RV/PA remained an independent predictor of all major cardiac events (MACE) after five years (OR 14.0 [1.5–130.8], p=0.019). Conclusion: A lower baseline RV-PA coupling, reflecting a higher degree of LV-induced pulmonary hypertension and secondary RV-dysfunction, is associated with decline of LV function in early phase of MI, and is independently associated with worse prognosis after five years. The value of RV-PA ratio as an prognstic marker warrants further investigation.",
journal = "European Heart Journal",
title = "Right ventricular-pulmonary artery coupling in the early stages of infarction could optimize patient risk stratification over five years",
volume = "44",
number = "Supplement 2",
pages = "ehad655.067",
doi = "10.1093/eurheartj/ehad655.067"
}

Dekleva, M., Martinović, M., Stevanović, A., Živković, M., Đorđević, A., Đurić, T.,& Stanković, A.. (2023). Right ventricular-pulmonary artery coupling in the early stages of infarction could optimize patient risk stratification over five years. in European Heart Journal, 44(Supplement 2), ehad655.067.
https://doi.org/10.1093/eurheartj/ehad655.067

Dekleva M, Martinović M, Stevanović A, Živković M, Đorđević A, Đurić T, Stanković A. Right ventricular-pulmonary artery coupling in the early stages of infarction could optimize patient risk stratification over five years. in European Heart Journal. 2023;44(Supplement 2):ehad655.067.
doi:10.1093/eurheartj/ehad655.067 .

Dekleva, Milica, Martinović, M., Stevanović, Angelina, Živković, Maja, Đorđević, Ana, Đurić, Tamara, Stanković, Aleksandra, "Right ventricular-pulmonary artery coupling in the early stages of infarction could optimize patient risk stratification over five years" in European Heart Journal, 44, no. Supplement 2 (2023):ehad655.067,
https://doi.org/10.1093/eurheartj/ehad655.067 . .

TY  - JOUR
AU  - Đorđević, Ana D.
AU  - Živković, Maja
AU  - Končar, Igor
AU  - Stanković, Aleksandra
AU  - Kuveljić, Jovana
AU  - Đurić, Tamara
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10046
AB  - ObjectivesGalectin-3 affects a variety of biological processes. It is encoded by LGALS-3, located in unique haplotype block in Caucasians. Most of the studies regarding the gal-3 role in atherosclerosis are focused exclusively on protein/mRNA levels. Genetic analyses of LGALS-3 are scarce. We sought to thoroughly examine the genetic background of gal-3 and to analyze tag variants that cover more than 80% variability of the LGALS-3 containing hap-block in association with carotid plaque presence (CPP). According to Tagger server, rs4040064 G/T, rs11628437 G/A and rs7159490 C/T cover 82% (r2 > 0.8) of the genetic variance of this hap-block. Our aims were to investigate possible association of rs4040064, rs11628437 and rs7159490 haplotypes with CPP in patients with advanced carotid atherosclerosis (CA) and to analyze their possible effect on LGALS-3 mRNA expression in carotid plaques.Materials and methodsStudy group consisted of 468 patients and 296 controls. Rs4040064, rs11628437, rs7159490 and LGALS-3 mRNA expression were detected by TaqMan® technology.ResultsWe have found that haplotype TAC was associated with the cerebrovascular insult (CVI) occurrence (OR = 1.68, 95% CI = 1.09-2.58, p = 0.02), compared to the referent haplotype. OR was adjusted for hypertension, age and BMI. TAC also showed higher, but not statistically significant, LGALS-3 expression in carotid plaques.ConclusionsOur results suggest that rs4040064, rs11628437 and rs7159490 bear no association with CPP, neither they affect LGALS-3 mRNA in carotid plaques. However, we showed a significant association of haplotype TAC with the CVI occurrence in CA patients from Serbia. Replication and validation of our results are required.
T2  - Journal of Stroke and Cerebrovascular Diseases
T2  - Journal of Stroke and Cerebrovascular DiseasesJournal of Stroke and Cerebrovascular Diseases
T1  - Tag Variants of LGALS-3 Containing Haplotype Block in Advanced Carotid Atherosclerosis
VL  - 31
IS  - 1
SP  - 106212
DO  - 10.1016/j.jstrokecerebrovasdis.2021.106212
ER  - 

@article{
author = "Đorđević, Ana D. and Živković, Maja and Končar, Igor and Stanković, Aleksandra and Kuveljić, Jovana and Đurić, Tamara",
year = "2022",
abstract = "ObjectivesGalectin-3 affects a variety of biological processes. It is encoded by LGALS-3, located in unique haplotype block in Caucasians. Most of the studies regarding the gal-3 role in atherosclerosis are focused exclusively on protein/mRNA levels. Genetic analyses of LGALS-3 are scarce. We sought to thoroughly examine the genetic background of gal-3 and to analyze tag variants that cover more than 80% variability of the LGALS-3 containing hap-block in association with carotid plaque presence (CPP). According to Tagger server, rs4040064 G/T, rs11628437 G/A and rs7159490 C/T cover 82% (r2 > 0.8) of the genetic variance of this hap-block. Our aims were to investigate possible association of rs4040064, rs11628437 and rs7159490 haplotypes with CPP in patients with advanced carotid atherosclerosis (CA) and to analyze their possible effect on LGALS-3 mRNA expression in carotid plaques.Materials and methodsStudy group consisted of 468 patients and 296 controls. Rs4040064, rs11628437, rs7159490 and LGALS-3 mRNA expression were detected by TaqMan® technology.ResultsWe have found that haplotype TAC was associated with the cerebrovascular insult (CVI) occurrence (OR = 1.68, 95% CI = 1.09-2.58, p = 0.02), compared to the referent haplotype. OR was adjusted for hypertension, age and BMI. TAC also showed higher, but not statistically significant, LGALS-3 expression in carotid plaques.ConclusionsOur results suggest that rs4040064, rs11628437 and rs7159490 bear no association with CPP, neither they affect LGALS-3 mRNA in carotid plaques. However, we showed a significant association of haplotype TAC with the CVI occurrence in CA patients from Serbia. Replication and validation of our results are required.",
journal = "Journal of Stroke and Cerebrovascular Diseases, Journal of Stroke and Cerebrovascular DiseasesJournal of Stroke and Cerebrovascular Diseases",
title = "Tag Variants of LGALS-3 Containing Haplotype Block in Advanced Carotid Atherosclerosis",
volume = "31",
number = "1",
pages = "106212",
doi = "10.1016/j.jstrokecerebrovasdis.2021.106212"
}

Đorđević, A. D., Živković, M., Končar, I., Stanković, A., Kuveljić, J.,& Đurić, T.. (2022). Tag Variants of LGALS-3 Containing Haplotype Block in Advanced Carotid Atherosclerosis. in Journal of Stroke and Cerebrovascular Diseases, 31(1), 106212.
https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.106212

Đorđević AD, Živković M, Končar I, Stanković A, Kuveljić J, Đurić T. Tag Variants of LGALS-3 Containing Haplotype Block in Advanced Carotid Atherosclerosis. in Journal of Stroke and Cerebrovascular Diseases. 2022;31(1):106212.
doi:10.1016/j.jstrokecerebrovasdis.2021.106212 .

Đorđević, Ana D., Živković, Maja, Končar, Igor, Stanković, Aleksandra, Kuveljić, Jovana, Đurić, Tamara, "Tag Variants of LGALS-3 Containing Haplotype Block in Advanced Carotid Atherosclerosis" in Journal of Stroke and Cerebrovascular Diseases, 31, no. 1 (2022):106212,
https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.106212 . .

TY  - JOUR
AU  - Mitrović, Kristina
AU  - Životić, Ivan
AU  - Kolić, Ivana
AU  - Đorđević, Ana
AU  - Žakula, Jelena
AU  - Filipović Tričković, Jelena G.
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Jovanović, Ivan G.
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10469
AB  - Rare copy number variants (CNVs) are among the most common genomic disorders underlying CAKUT. miRNAs located in rare CNVs represent well-founded functional variants for human CAKUT research. The study aimed to identify and functionally interpret miRNAs most frequently affected by rare CNVs in CAKUT and to estimate the overall burden of rare CNVs on miRNA genes in CAKUT. The additional aim of this study was to experimentally confirm the effect of a rare CNV in CAKUT on candidate miRNA’s expression and the subsequent change in mRNA levels of selected target genes. A database of CAKUT-associated rare CNV regions, created by literature mining, was used for mapping of the miRNA precursors. miRNAs and miRNA families, most frequently affected by rare CAKUT-associated CNVs, have been subjected to bioinformatic analysis. CNV burden analysis was performed to identify chromosomes with over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT. A functional study was performed on HEK293 MIR484+/- KO and HEK293 WT cell lines, followed by the analysis of relative miRNA and mRNA target gene levels. 80% of CAKUT patients with underlying rare CNV had at least one miRNA gene overlapping the identified CNV. Network analysis of the most frequently affected miRNAs has revealed the dominant regulation of the two miRNAs, hsa-miR-484 and hsa-miR-185-5p. Additionally, miR-548 family members have shown substantial enrichment in rare CNVs in CAKUT. An over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT was observed in multiple chromosomes, such as chr16, chr20, and chr21. A significant 0.37 fold downregulation of hsa-miR-484, followed by a notable upregulation of MDM2 and APAF1 and downregulation of NOTCH3 was detected in HEK293 MIR484+/- KO compared to HEK293 WT cell lines, supporting the study hypothesis. miRNA genes are frequently affected by rare CNVs in CAKUT patients. Understanding the potential of CNV-affected miRNAs to participate in CAKUT as genetic drivers represent a crucial implication for the development of novel therapeutic approaches.
T2  - Scientific Reports
T1  - Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT
VL  - 12
IS  - 1
SP  - 17746
DO  - 10.1038/s41598-022-22749-1
ER  - 

@article{
author = "Mitrović, Kristina and Životić, Ivan and Kolić, Ivana and Đorđević, Ana and Žakula, Jelena and Filipović Tričković, Jelena G. and Živković, Maja and Stanković, Aleksandra and Jovanović, Ivan G.",
year = "2022",
abstract = "Rare copy number variants (CNVs) are among the most common genomic disorders underlying CAKUT. miRNAs located in rare CNVs represent well-founded functional variants for human CAKUT research. The study aimed to identify and functionally interpret miRNAs most frequently affected by rare CNVs in CAKUT and to estimate the overall burden of rare CNVs on miRNA genes in CAKUT. The additional aim of this study was to experimentally confirm the effect of a rare CNV in CAKUT on candidate miRNA’s expression and the subsequent change in mRNA levels of selected target genes. A database of CAKUT-associated rare CNV regions, created by literature mining, was used for mapping of the miRNA precursors. miRNAs and miRNA families, most frequently affected by rare CAKUT-associated CNVs, have been subjected to bioinformatic analysis. CNV burden analysis was performed to identify chromosomes with over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT. A functional study was performed on HEK293 MIR484+/- KO and HEK293 WT cell lines, followed by the analysis of relative miRNA and mRNA target gene levels. 80% of CAKUT patients with underlying rare CNV had at least one miRNA gene overlapping the identified CNV. Network analysis of the most frequently affected miRNAs has revealed the dominant regulation of the two miRNAs, hsa-miR-484 and hsa-miR-185-5p. Additionally, miR-548 family members have shown substantial enrichment in rare CNVs in CAKUT. An over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT was observed in multiple chromosomes, such as chr16, chr20, and chr21. A significant 0.37 fold downregulation of hsa-miR-484, followed by a notable upregulation of MDM2 and APAF1 and downregulation of NOTCH3 was detected in HEK293 MIR484+/- KO compared to HEK293 WT cell lines, supporting the study hypothesis. miRNA genes are frequently affected by rare CNVs in CAKUT patients. Understanding the potential of CNV-affected miRNAs to participate in CAKUT as genetic drivers represent a crucial implication for the development of novel therapeutic approaches.",
journal = "Scientific Reports",
title = "Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT",
volume = "12",
number = "1",
pages = "17746",
doi = "10.1038/s41598-022-22749-1"
}

Mitrović, K., Životić, I., Kolić, I., Đorđević, A., Žakula, J., Filipović Tričković, J. G., Živković, M., Stanković, A.,& Jovanović, I. G.. (2022). Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT. in Scientific Reports, 12(1), 17746.
https://doi.org/10.1038/s41598-022-22749-1

Mitrović K, Životić I, Kolić I, Đorđević A, Žakula J, Filipović Tričković JG, Živković M, Stanković A, Jovanović IG. Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT. in Scientific Reports. 2022;12(1):17746.
doi:10.1038/s41598-022-22749-1 .

Mitrović, Kristina, Životić, Ivan, Kolić, Ivana, Đorđević, Ana, Žakula, Jelena, Filipović Tričković, Jelena G., Živković, Maja, Stanković, Aleksandra, Jovanović, Ivan G., "Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT" in Scientific Reports, 12, no. 1 (2022):17746,
https://doi.org/10.1038/s41598-022-22749-1 . .

TY  - JOUR
AU  - Bošković, Maja
AU  - Živković, Maja
AU  - Korićanac, Goran
AU  - Tepavčević, Snežana
AU  - Zec, Manja
AU  - Debeljak-Martačić, Jasmina
AU  - Stanković, Aleksandra
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10485
AB  - Increased fructose consumption has been linked with chronic inflammation and metabolic syndrome (MetS). Activation of the renin-angiotensin system (RAS) and NF-κB have been detected in MetS. Walnuts are a rich source of polyunsaturated omega-3 fatty acids (n-3 PUFA) that were suggested to exert anti-inflammatory effects related to cardio-metabolic health. We hypothesized that walnut supplementation has the capacity to revert unfavorable fructose-rich diet (FRD)-induced activation of cardiac RAS and NF-κB in male rats. Due to the lack of similar studies, we investigated the effects of walnut supplementation (6 weeks) on the expression of four RAS molecules (ACE, ACE2, AT1R, and AT2R) and NF-κB in rat heart after FRD (10% w/v, 9 weeks). In addition, we followed the changes in the n-6/n-3 PUFA ratio in the total pool of heart lipids after both treatments to elucidate the walnut effects on fatty acids in the heart. 36 animals (9 per group) participated in the experiment. FRD significantly increased the ACE protein level in the heart (p < 0.001). Walnut supplementation significantly increased the ACE2 protein level in the heart of FRD (p < 0.001). In addition, walnut supplementation showed a significant main effect on the arachidonic acid/eicosapentaenoic acid ratio (p = 0.004). Walnut supplementation significantly reduced this ratio, in comparison with both, the control group (C vs. FW, p < 0.05) and the FRD group (F vs. FW, p < 0.05). However, walnut treatment failed to revert the significant effect of fructose (p < 0.001) on the elevation of NF-κB protein level. Our results suggest a beneficial effect of walnut supplementation on ACE2 protein level and n-6/n-3 PUFA level in the heart of the animal model of MetS. Such results highlight the approach of omega-3-rich walnut supplementation in the stimulation of endogenous production of favorable molecules in the heart which could be an affordable nutritional treatment formaintenance of cardio-metabolic health.
T2  - Frontiers in Physiology
T1  - Walnut supplementation after fructose-rich diet is associated with a beneficial fatty acid ratio and increased ACE2 expression in the rat heart
VL  - 13
DO  - 10.3389/fphys.2022.942459
ER  - 

@article{
author = "Bošković, Maja and Živković, Maja and Korićanac, Goran and Tepavčević, Snežana and Zec, Manja and Debeljak-Martačić, Jasmina and Stanković, Aleksandra",
year = "2022",
abstract = "Increased fructose consumption has been linked with chronic inflammation and metabolic syndrome (MetS). Activation of the renin-angiotensin system (RAS) and NF-κB have been detected in MetS. Walnuts are a rich source of polyunsaturated omega-3 fatty acids (n-3 PUFA) that were suggested to exert anti-inflammatory effects related to cardio-metabolic health. We hypothesized that walnut supplementation has the capacity to revert unfavorable fructose-rich diet (FRD)-induced activation of cardiac RAS and NF-κB in male rats. Due to the lack of similar studies, we investigated the effects of walnut supplementation (6 weeks) on the expression of four RAS molecules (ACE, ACE2, AT1R, and AT2R) and NF-κB in rat heart after FRD (10% w/v, 9 weeks). In addition, we followed the changes in the n-6/n-3 PUFA ratio in the total pool of heart lipids after both treatments to elucidate the walnut effects on fatty acids in the heart. 36 animals (9 per group) participated in the experiment. FRD significantly increased the ACE protein level in the heart (p < 0.001). Walnut supplementation significantly increased the ACE2 protein level in the heart of FRD (p < 0.001). In addition, walnut supplementation showed a significant main effect on the arachidonic acid/eicosapentaenoic acid ratio (p = 0.004). Walnut supplementation significantly reduced this ratio, in comparison with both, the control group (C vs. FW, p < 0.05) and the FRD group (F vs. FW, p < 0.05). However, walnut treatment failed to revert the significant effect of fructose (p < 0.001) on the elevation of NF-κB protein level. Our results suggest a beneficial effect of walnut supplementation on ACE2 protein level and n-6/n-3 PUFA level in the heart of the animal model of MetS. Such results highlight the approach of omega-3-rich walnut supplementation in the stimulation of endogenous production of favorable molecules in the heart which could be an affordable nutritional treatment formaintenance of cardio-metabolic health.",
journal = "Frontiers in Physiology",
title = "Walnut supplementation after fructose-rich diet is associated with a beneficial fatty acid ratio and increased ACE2 expression in the rat heart",
volume = "13",
doi = "10.3389/fphys.2022.942459"
}

Bošković, M., Živković, M., Korićanac, G., Tepavčević, S., Zec, M., Debeljak-Martačić, J.,& Stanković, A.. (2022). Walnut supplementation after fructose-rich diet is associated with a beneficial fatty acid ratio and increased ACE2 expression in the rat heart. in Frontiers in Physiology, 13.
https://doi.org/10.3389/fphys.2022.942459

Bošković M, Živković M, Korićanac G, Tepavčević S, Zec M, Debeljak-Martačić J, Stanković A. Walnut supplementation after fructose-rich diet is associated with a beneficial fatty acid ratio and increased ACE2 expression in the rat heart. in Frontiers in Physiology. 2022;13.
doi:10.3389/fphys.2022.942459 .

Bošković, Maja, Živković, Maja, Korićanac, Goran, Tepavčević, Snežana, Zec, Manja, Debeljak-Martačić, Jasmina, Stanković, Aleksandra, "Walnut supplementation after fructose-rich diet is associated with a beneficial fatty acid ratio and increased ACE2 expression in the rat heart" in Frontiers in Physiology, 13 (2022),
https://doi.org/10.3389/fphys.2022.942459 . .

TY  - CONF
AU  - Dekleva, Milica
AU  - Đurić, Tamara
AU  - Đorđević, Ana
AU  - Soldatović, Ivan A.
AU  - Stanković, Aleksandra
AU  - Stevanović, Angelina
AU  - Živković, Maja
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10710
AB  - Cardiac remodeling after the first myocardial infarction (MI) appears to be more successful in women than in men, but more frequently associated with heart failure (HF) development. Galectin-3 expression is upregulated in remodeling and failing myocardium and circulatory level is activated in hypertrophy, fibrosis and inflammation.This study aimed to investigate the potential role of sex differences in the following: risk factors, structural and functional left ventricle (LV) changes, coronary angiography, expression of Galectin-3 and it's circulating level for HF occurrence during 6 months in patients after first MI.The prospective study included patients with the first MI treated with the primary percutaneous coronary intervention (p PCI) who underwent Doppler echocardiography within 2±1 days of MI and after 6 months. Relative LGALS-3 mRNA expression in peripheral blood were detected by TaqMan® technology. Expression and concentration of Galectin-3 was obtained by ELISA method. Presence of HF was confirmed by clinical examination and Doppler echocardiography. Assessment of p PCI and description of coronary angiography was performed at the patient's admission time.The study included 137 men and 44 women, who were significantly older (57.8 vs. 54.4, p=0.034), with higher LDL cholesterol (3.54±0.93 vs. 4.03±1.27, p=0.027) without differences among angiographic characteristics and medications. In the acute phase of MI, the significantly lower indexed LV volumes were found in women compared to men (EDLVI: 58.3 vs. 49.6, p<0.001, ESLVI: 33.84 vs. 26.83, p<0.001), but the grade of LV remodeling (delta LVDVI, delta LVESVI) during 6 months and changes in LV ejection fraction (deltaLVEF) were similar (p=ns). Incidence of LV hypertrophy and HF development was significantly higher in women 70% vs. 44.6%, p=0.034, 37.5% vs.19.3%, p=0.02). Females have had a higher degree of LV diastolic dysfunction (DD) in the early and late phase after MI (p=0.038, p=0.027). There were significant correlations between grade of DD and level of Gal-3 expression (p=0.001). The relative expression of LGALS-3 mRNA in peripheral blood was higher in females (p=0.007) with upregulation of circulating Gal-3 in females (44.66 vs. 16.30, p<0.001) and in HF patients (31.1 vs. 21.2, p=0.025).Sex specific actions such as LV hypertrophy, diastolic dysfunction, upregulation of Galectin-3 expression and higher circulating level may explain more incidence of HF in female. Difference in model and determinants of HF between men and women can be important for further therapy including Gelectin-3 inhibition.Type of funding sources: None.
C3  - European Heart Journal
T1  - Sex related difference in heart failure development in patients after first myocardial infarction; role of galectine-3
VL  - 43
IS  - Supplement 2
SP  - ehac544.816
DO  - 10.1093/eurheartj/ehac544.816
ER  - 

@conference{
author = "Dekleva, Milica and Đurić, Tamara and Đorđević, Ana and Soldatović, Ivan A. and Stanković, Aleksandra and Stevanović, Angelina and Živković, Maja",
year = "2022",
abstract = "Cardiac remodeling after the first myocardial infarction (MI) appears to be more successful in women than in men, but more frequently associated with heart failure (HF) development. Galectin-3 expression is upregulated in remodeling and failing myocardium and circulatory level is activated in hypertrophy, fibrosis and inflammation.This study aimed to investigate the potential role of sex differences in the following: risk factors, structural and functional left ventricle (LV) changes, coronary angiography, expression of Galectin-3 and it's circulating level for HF occurrence during 6 months in patients after first MI.The prospective study included patients with the first MI treated with the primary percutaneous coronary intervention (p PCI) who underwent Doppler echocardiography within 2±1 days of MI and after 6 months. Relative LGALS-3 mRNA expression in peripheral blood were detected by TaqMan® technology. Expression and concentration of Galectin-3 was obtained by ELISA method. Presence of HF was confirmed by clinical examination and Doppler echocardiography. Assessment of p PCI and description of coronary angiography was performed at the patient's admission time.The study included 137 men and 44 women, who were significantly older (57.8 vs. 54.4, p=0.034), with higher LDL cholesterol (3.54±0.93 vs. 4.03±1.27, p=0.027) without differences among angiographic characteristics and medications. In the acute phase of MI, the significantly lower indexed LV volumes were found in women compared to men (EDLVI: 58.3 vs. 49.6, p<0.001, ESLVI: 33.84 vs. 26.83, p<0.001), but the grade of LV remodeling (delta LVDVI, delta LVESVI) during 6 months and changes in LV ejection fraction (deltaLVEF) were similar (p=ns). Incidence of LV hypertrophy and HF development was significantly higher in women 70% vs. 44.6%, p=0.034, 37.5% vs.19.3%, p=0.02). Females have had a higher degree of LV diastolic dysfunction (DD) in the early and late phase after MI (p=0.038, p=0.027). There were significant correlations between grade of DD and level of Gal-3 expression (p=0.001). The relative expression of LGALS-3 mRNA in peripheral blood was higher in females (p=0.007) with upregulation of circulating Gal-3 in females (44.66 vs. 16.30, p<0.001) and in HF patients (31.1 vs. 21.2, p=0.025).Sex specific actions such as LV hypertrophy, diastolic dysfunction, upregulation of Galectin-3 expression and higher circulating level may explain more incidence of HF in female. Difference in model and determinants of HF between men and women can be important for further therapy including Gelectin-3 inhibition.Type of funding sources: None.",
journal = "European Heart Journal",
title = "Sex related difference in heart failure development in patients after first myocardial infarction; role of galectine-3",
volume = "43",
number = "Supplement 2",
pages = "ehac544.816",
doi = "10.1093/eurheartj/ehac544.816"
}

Dekleva, M., Đurić, T., Đorđević, A., Soldatović, I. A., Stanković, A., Stevanović, A.,& Živković, M.. (2022). Sex related difference in heart failure development in patients after first myocardial infarction; role of galectine-3. in European Heart Journal, 43(Supplement 2), ehac544.816.
https://doi.org/10.1093/eurheartj/ehac544.816

Dekleva M, Đurić T, Đorđević A, Soldatović IA, Stanković A, Stevanović A, Živković M. Sex related difference in heart failure development in patients after first myocardial infarction; role of galectine-3. in European Heart Journal. 2022;43(Supplement 2):ehac544.816.
doi:10.1093/eurheartj/ehac544.816 .

Dekleva, Milica, Đurić, Tamara, Đorđević, Ana, Soldatović, Ivan A., Stanković, Aleksandra, Stevanović, Angelina, Živković, Maja, "Sex related difference in heart failure development in patients after first myocardial infarction; role of galectine-3" in European Heart Journal, 43, no. Supplement 2 (2022):ehac544.816,
https://doi.org/10.1093/eurheartj/ehac544.816 . .

TY  - CONF
AU  - Mitrović, Kristina
AU  - Kolić, Ivana
AU  - Životić, Ivan
AU  - Filipović Tričković, Jelena G.
AU  - Đorđević, Ana
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Jovanović, Ivan G.
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10830
AB  - Introduction: miR-548 family members, located on all human chromosomes except chr19 and chrY, regulate podocyte differentiation in vitro, important for kidney development. Rare copy number variants (rCNVs) are the common genetic cause of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) and could harbour miRNAs. The aim of this study was to investigate to which extent rCNVs associated with CAKUT harbour miR-548 members.
Materials and Methods: Extensive literature review was conducted to collect data of pathogenic and likely pathogenic rCNVs in CAKUT patients. UCSC genome browser tool was employed for mapping of miR-548 members onto collected rCNV regions and gnomAD SV controls database. Bioinformatic analysis was conducted using miRPathDB2 tool.
Results: We generated CAKUT database of pathogenic CNVs in 79 chromosome regions from 191 patient and likely pathogenic CNVs in 74 regions from 87 patients. Pathogenic rCNVs of seventeen patients, located on 7 chromosomes, contained at least one miR-548 member. Likely pathogenic rCNVs of 4 patients, located on 3 chromosomes, contained one of miR-548 members. Bioinformatic analysis implied the role of mapped miRNAs in the regulation of processes associated with CAKUT. In controls, only hsa-mir-548i-3 (out of 73 precursors) was mapped on polymorphic CNVs (af>1%) and wasn’t identified in patients.
Conclusions: miR-548 members located in rCNVs should be investigated in future studies as potential genetic drivers of CAKUT development, beyond protein coding genes.
C3  - European Journal of Human Genetics
T1  - Are miR-548 family members potential genetic drivers of CAKUT
VL  - 30
IS  - Suppl. 1
SP  - 331
DO  - 10.1038/s41431-021-01026-1
ER  - 

@conference{
author = "Mitrović, Kristina and Kolić, Ivana and Životić, Ivan and Filipović Tričković, Jelena G. and Đorđević, Ana and Živković, Maja and Stanković, Aleksandra and Jovanović, Ivan G.",
year = "2022",
abstract = "Introduction: miR-548 family members, located on all human chromosomes except chr19 and chrY, regulate podocyte differentiation in vitro, important for kidney development. Rare copy number variants (rCNVs) are the common genetic cause of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) and could harbour miRNAs. The aim of this study was to investigate to which extent rCNVs associated with CAKUT harbour miR-548 members.
Materials and Methods: Extensive literature review was conducted to collect data of pathogenic and likely pathogenic rCNVs in CAKUT patients. UCSC genome browser tool was employed for mapping of miR-548 members onto collected rCNV regions and gnomAD SV controls database. Bioinformatic analysis was conducted using miRPathDB2 tool.
Results: We generated CAKUT database of pathogenic CNVs in 79 chromosome regions from 191 patient and likely pathogenic CNVs in 74 regions from 87 patients. Pathogenic rCNVs of seventeen patients, located on 7 chromosomes, contained at least one miR-548 member. Likely pathogenic rCNVs of 4 patients, located on 3 chromosomes, contained one of miR-548 members. Bioinformatic analysis implied the role of mapped miRNAs in the regulation of processes associated with CAKUT. In controls, only hsa-mir-548i-3 (out of 73 precursors) was mapped on polymorphic CNVs (af>1%) and wasn’t identified in patients.
Conclusions: miR-548 members located in rCNVs should be investigated in future studies as potential genetic drivers of CAKUT development, beyond protein coding genes.",
journal = "European Journal of Human Genetics",
title = "Are miR-548 family members potential genetic drivers of CAKUT",
volume = "30",
number = "Suppl. 1",
pages = "331",
doi = "10.1038/s41431-021-01026-1"
}

Mitrović, K., Kolić, I., Životić, I., Filipović Tričković, J. G., Đorđević, A., Živković, M., Stanković, A.,& Jovanović, I. G.. (2022). Are miR-548 family members potential genetic drivers of CAKUT. in European Journal of Human Genetics, 30(Suppl. 1), 331.
https://doi.org/10.1038/s41431-021-01026-1

Mitrović K, Kolić I, Životić I, Filipović Tričković JG, Đorđević A, Živković M, Stanković A, Jovanović IG. Are miR-548 family members potential genetic drivers of CAKUT. in European Journal of Human Genetics. 2022;30(Suppl. 1):331.
doi:10.1038/s41431-021-01026-1 .

Mitrović, Kristina, Kolić, Ivana, Životić, Ivan, Filipović Tričković, Jelena G., Đorđević, Ana, Živković, Maja, Stanković, Aleksandra, Jovanović, Ivan G., "Are miR-548 family members potential genetic drivers of CAKUT" in European Journal of Human Genetics, 30, no. Suppl. 1 (2022):331,
https://doi.org/10.1038/s41431-021-01026-1 . .

TY  - CONF
AU  - Životić, Ivan
AU  - Kolić, Ivana
AU  - Popić, Kristina
AU  - Filipović Tričković, Jelena G.
AU  - Đorđević, Ana
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Jovanović, Ivan G.
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10831
AB  - Introduction: Genetic studies of congenital anomalies of the kidney and urinary tract (CAKUT) have demonstrated variable penetrability and expressivity of the associated genetic defects. Previously, it was shown that deletions of 17q12 and 22q11.2 regions were specific for kidney anomalies (KA) while 16p11.2 and 1q21.1 loci showed extensive pleiotropy in CAKUT phenotypes. CNVs affecting miRNA gene dosage have been described to have functional influence on gene expression. We aimed to conduct comprehensive in silico analysis using publicly available databases to analyze miRNA content of CAKUT-associated CNVs in quoted chromosomal loci with regard to pleiotropy.  Methods: Extensive literature review was conducted to collect data about pathogenic rCNVs associated with CAKUT. UCSC genome browser tool was employed for mapping miRNAs onto collected rCNV regions.  Results: Analysis of CNVs in CAKUT included four studies counting more than 2500 patients. In further analysis we included 191 patients harboring pathogenic CNVs. Surprisingly, CAKUT pleiotropic regions (16p11.2, 1q21.2) did not contain any miRNA. 22q11.2 showed the densest miRNAs content (n = 21).  Conclusions: Absence of miRNAs may potentially pronounce the pleiotropy of the CAKUT genetic defects, thus leading to the variety of phenotypes. Contrary, abundancy of miRNAs in 22q11.2 might be associated with reproducible phenotype, such as KA, producing the functional effect when deleted. This assumption agrees with recent results of miRNA expression variability in 22q11.2 deletion syndrome.
C3  - European Journal of Human Genetics
T1  - miRNA-free rare pathogenic CNVs could drive toward variable CAKUT phenotypes
VL  - 30
IS  - Suppl. 1
SP  - 331
DO  - 10.1038/s41431-021-01026-1
ER  - 

@conference{
author = "Životić, Ivan and Kolić, Ivana and Popić, Kristina and Filipović Tričković, Jelena G. and Đorđević, Ana and Živković, Maja and Stanković, Aleksandra and Jovanović, Ivan G.",
year = "2022",
abstract = "Introduction: Genetic studies of congenital anomalies of the kidney and urinary tract (CAKUT) have demonstrated variable penetrability and expressivity of the associated genetic defects. Previously, it was shown that deletions of 17q12 and 22q11.2 regions were specific for kidney anomalies (KA) while 16p11.2 and 1q21.1 loci showed extensive pleiotropy in CAKUT phenotypes. CNVs affecting miRNA gene dosage have been described to have functional influence on gene expression. We aimed to conduct comprehensive in silico analysis using publicly available databases to analyze miRNA content of CAKUT-associated CNVs in quoted chromosomal loci with regard to pleiotropy.  Methods: Extensive literature review was conducted to collect data about pathogenic rCNVs associated with CAKUT. UCSC genome browser tool was employed for mapping miRNAs onto collected rCNV regions.  Results: Analysis of CNVs in CAKUT included four studies counting more than 2500 patients. In further analysis we included 191 patients harboring pathogenic CNVs. Surprisingly, CAKUT pleiotropic regions (16p11.2, 1q21.2) did not contain any miRNA. 22q11.2 showed the densest miRNAs content (n = 21).  Conclusions: Absence of miRNAs may potentially pronounce the pleiotropy of the CAKUT genetic defects, thus leading to the variety of phenotypes. Contrary, abundancy of miRNAs in 22q11.2 might be associated with reproducible phenotype, such as KA, producing the functional effect when deleted. This assumption agrees with recent results of miRNA expression variability in 22q11.2 deletion syndrome.",
journal = "European Journal of Human Genetics",
title = "miRNA-free rare pathogenic CNVs could drive toward variable CAKUT phenotypes",
volume = "30",
number = "Suppl. 1",
pages = "331",
doi = "10.1038/s41431-021-01026-1"
}

Životić, I., Kolić, I., Popić, K., Filipović Tričković, J. G., Đorđević, A., Živković, M., Stanković, A.,& Jovanović, I. G.. (2022). miRNA-free rare pathogenic CNVs could drive toward variable CAKUT phenotypes. in European Journal of Human Genetics, 30(Suppl. 1), 331.
https://doi.org/10.1038/s41431-021-01026-1

Životić I, Kolić I, Popić K, Filipović Tričković JG, Đorđević A, Živković M, Stanković A, Jovanović IG. miRNA-free rare pathogenic CNVs could drive toward variable CAKUT phenotypes. in European Journal of Human Genetics. 2022;30(Suppl. 1):331.
doi:10.1038/s41431-021-01026-1 .

Životić, Ivan, Kolić, Ivana, Popić, Kristina, Filipović Tričković, Jelena G., Đorđević, Ana, Živković, Maja, Stanković, Aleksandra, Jovanović, Ivan G., "miRNA-free rare pathogenic CNVs could drive toward variable CAKUT phenotypes" in European Journal of Human Genetics, 30, no. Suppl. 1 (2022):331,
https://doi.org/10.1038/s41431-021-01026-1 . .

TY  - CONF
AU  - Kolić, Ivana
AU  - Mitrović, Kristina
AU  - Životić, Ivan
AU  - Đorđević, Ana
AU  - Filipović-Tričković, Jelena
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Jovanović, Ivan
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12684
AB  - Background/Objectives: Rare copy number variants (rCNVs) are the common genetic cause of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).1 miRNAs located in rCNVs represent well-founded functional variants for human CAKUT research. However, the impact of rCNVs on miRNA genes in CAKUT is unknown. Thus, burden assessment was performed to identify chromosomes with non-random representation of miRNA genes in rCNVs associated with CAKUT. Methods: A comprehensive literature mining of rCNV regions associated with CAKUT was performed. The total cumulative length of rCNVs per chromosome was the sum of corresponding CNV-DNA regions, taking into account overlapping. Mapping of miRNAs onto cumulative rCNV regions gave counts of affected miRNA loci. The correlation analysis was performed between the number of miRNA genes overlapping rCNVs, and the fractional lengths of cumulative rCNVs regions in relation to the chromosome size. Results: A statistically significant positive correlation was observed for duplications and deletions respectively (Spearman correlation p<0.0001, r=0.9, r=0.8). However, a deviation from the best fit line for chromosome 16, for both rare duplications and deletions, was observed due to the high overrepresentation of miRNA genes in identified rCNVs. Conclusion: The current finding of the high overall burden of rCNVs on miRNA genes in chromosome 16 suggests that miRNAs located on this chromosome could serve as candidates for the investigation of miRNA role in CAKUT development.
C3  - 54th European Society of Human Genetics (ESHG) : Book of abstracts
T1  - Assessing the burden of rare CNVs on miRNA genes in CAKUT
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12684
ER  - 

@conference{
author = "Kolić, Ivana and Mitrović, Kristina and Životić, Ivan and Đorđević, Ana and Filipović-Tričković, Jelena and Živković, Maja and Stanković, Aleksandra and Jovanović, Ivan",
year = "2022",
abstract = "Background/Objectives: Rare copy number variants (rCNVs) are the common genetic cause of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).1 miRNAs located in rCNVs represent well-founded functional variants for human CAKUT research. However, the impact of rCNVs on miRNA genes in CAKUT is unknown. Thus, burden assessment was performed to identify chromosomes with non-random representation of miRNA genes in rCNVs associated with CAKUT. Methods: A comprehensive literature mining of rCNV regions associated with CAKUT was performed. The total cumulative length of rCNVs per chromosome was the sum of corresponding CNV-DNA regions, taking into account overlapping. Mapping of miRNAs onto cumulative rCNV regions gave counts of affected miRNA loci. The correlation analysis was performed between the number of miRNA genes overlapping rCNVs, and the fractional lengths of cumulative rCNVs regions in relation to the chromosome size. Results: A statistically significant positive correlation was observed for duplications and deletions respectively (Spearman correlation p<0.0001, r=0.9, r=0.8). However, a deviation from the best fit line for chromosome 16, for both rare duplications and deletions, was observed due to the high overrepresentation of miRNA genes in identified rCNVs. Conclusion: The current finding of the high overall burden of rCNVs on miRNA genes in chromosome 16 suggests that miRNAs located on this chromosome could serve as candidates for the investigation of miRNA role in CAKUT development.",
journal = "54th European Society of Human Genetics (ESHG) : Book of abstracts",
title = "Assessing the burden of rare CNVs on miRNA genes in CAKUT",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12684"
}

Kolić, I., Mitrović, K., Životić, I., Đorđević, A., Filipović-Tričković, J., Živković, M., Stanković, A.,& Jovanović, I.. (2022). Assessing the burden of rare CNVs on miRNA genes in CAKUT. in 54th European Society of Human Genetics (ESHG) : Book of abstracts.
https://hdl.handle.net/21.15107/rcub_vinar_12684

Kolić I, Mitrović K, Životić I, Đorđević A, Filipović-Tričković J, Živković M, Stanković A, Jovanović I. Assessing the burden of rare CNVs on miRNA genes in CAKUT. in 54th European Society of Human Genetics (ESHG) : Book of abstracts. 2022;.
https://hdl.handle.net/21.15107/rcub_vinar_12684 .

Kolić, Ivana, Mitrović, Kristina, Životić, Ivan, Đorđević, Ana, Filipović-Tričković, Jelena, Živković, Maja, Stanković, Aleksandra, Jovanović, Ivan, "Assessing the burden of rare CNVs on miRNA genes in CAKUT" in 54th European Society of Human Genetics (ESHG) : Book of abstracts (2022),
https://hdl.handle.net/21.15107/rcub_vinar_12684 .

TY  - JOUR
AU  - Đurić, Tamara
AU  - Kuveljić, Jovana
AU  - Đorđević, Ana
AU  - Dekleva, Milica
AU  - Stanković, Goran
AU  - Stanković, Aleksandra
AU  - Živković, Maja
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10382
AB  - Background Myocardial infarction (MI) leads to ischemia and afterward to left ventricular (LV) remodeling. Matrix metalloproteinase−1 (MMP1) and −3 (MMP3) belong to the family of endopeptidases and together they can dissolve most of the components of the extracellular matrix. MMP1 and MMP3 variants have been investigated solely in association with ischemic heart disease and LV dysfunction, but not in haplotype. The aims of this study were to investigate the association of haplotypes inferred from MMP1 rs1799750 (−1607 1G/2G; NC_000011.9:g.102670497del) and MMP3 rs35068180 (−1612 5A/6A; NC_000011.9:g.102715952dup) with MI and their effect on the change in echocardiographic parameters of LV structure and function in patients within 6 months after MI. Methods The study included 325 patients with the first MI and 283 healthy controls. Gene variants were detected by PCR-RFLP method. Parameters of LV structure and function were assessed by conventional 2D echocardiography, 3–5 days and 6 months after the first MI, on a subgroup of 160 patients. Haplotype analysis was performed with Thesias software. Results Haplotypes 2G-5A and 1G-6A were significantly and independently associated with MI compared with the reference haplotype 2G-6A (adjusted, p = 0.009 and p = 0.026, respectively). After Bonferroni correction for multiple testing, MMP1 and MMP3 haplotypes lost their association with the change in LV long diameter and stroke volume within 6 months after MI. Conclusion MMP1 and MMP3 haplotypes are strongly associated with MI. Further studies are needed to validate this result and to examine their association with echocardiographic parameters of LV structure and function after MI.
T2  - Molecular Genetics & Genomic Medicine
T1  - Association of MMP1 and MMP3 haplotypes with myocardial infarction and echocardiographic parameters of the left ventricle
VL  - 10
IS  - 9
SP  - e2022
DO  - 10.1002/mgg3.2022
ER  - 

@article{
author = "Đurić, Tamara and Kuveljić, Jovana and Đorđević, Ana and Dekleva, Milica and Stanković, Goran and Stanković, Aleksandra and Živković, Maja",
year = "2022",
abstract = "Background Myocardial infarction (MI) leads to ischemia and afterward to left ventricular (LV) remodeling. Matrix metalloproteinase−1 (MMP1) and −3 (MMP3) belong to the family of endopeptidases and together they can dissolve most of the components of the extracellular matrix. MMP1 and MMP3 variants have been investigated solely in association with ischemic heart disease and LV dysfunction, but not in haplotype. The aims of this study were to investigate the association of haplotypes inferred from MMP1 rs1799750 (−1607 1G/2G; NC_000011.9:g.102670497del) and MMP3 rs35068180 (−1612 5A/6A; NC_000011.9:g.102715952dup) with MI and their effect on the change in echocardiographic parameters of LV structure and function in patients within 6 months after MI. Methods The study included 325 patients with the first MI and 283 healthy controls. Gene variants were detected by PCR-RFLP method. Parameters of LV structure and function were assessed by conventional 2D echocardiography, 3–5 days and 6 months after the first MI, on a subgroup of 160 patients. Haplotype analysis was performed with Thesias software. Results Haplotypes 2G-5A and 1G-6A were significantly and independently associated with MI compared with the reference haplotype 2G-6A (adjusted, p = 0.009 and p = 0.026, respectively). After Bonferroni correction for multiple testing, MMP1 and MMP3 haplotypes lost their association with the change in LV long diameter and stroke volume within 6 months after MI. Conclusion MMP1 and MMP3 haplotypes are strongly associated with MI. Further studies are needed to validate this result and to examine their association with echocardiographic parameters of LV structure and function after MI.",
journal = "Molecular Genetics & Genomic Medicine",
title = "Association of MMP1 and MMP3 haplotypes with myocardial infarction and echocardiographic parameters of the left ventricle",
volume = "10",
number = "9",
pages = "e2022",
doi = "10.1002/mgg3.2022"
}

Đurić, T., Kuveljić, J., Đorđević, A., Dekleva, M., Stanković, G., Stanković, A.,& Živković, M.. (2022). Association of MMP1 and MMP3 haplotypes with myocardial infarction and echocardiographic parameters of the left ventricle. in Molecular Genetics & Genomic Medicine, 10(9), e2022.
https://doi.org/10.1002/mgg3.2022

Đurić T, Kuveljić J, Đorđević A, Dekleva M, Stanković G, Stanković A, Živković M. Association of MMP1 and MMP3 haplotypes with myocardial infarction and echocardiographic parameters of the left ventricle. in Molecular Genetics & Genomic Medicine. 2022;10(9):e2022.
doi:10.1002/mgg3.2022 .

Đurić, Tamara, Kuveljić, Jovana, Đorđević, Ana, Dekleva, Milica, Stanković, Goran, Stanković, Aleksandra, Živković, Maja, "Association of MMP1 and MMP3 haplotypes with myocardial infarction and echocardiographic parameters of the left ventricle" in Molecular Genetics & Genomic Medicine, 10, no. 9 (2022):e2022,
https://doi.org/10.1002/mgg3.2022 . .

TY  - JOUR
AU  - Jovanović, Ivan G.
AU  - Živković, Maja
AU  - Ješić, Snežana
AU  - Stanković, Aleksandra
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10115
AB  - Objective Cholesteatoma is a challenging chronic pathology of the middle ear for which pharmacologic therapies have not been developed yet. Cholesteatoma occurrence depends on the interplay between genetic and environmental factors while master regulators orchestrating disease progression are still unknown. Therefore, in this review, we will discuss the diagnostic and therapeutic potential of non-coding RNAs (ncRNA) as a new class of regulatory molecules. Methods We have comprehensively reviewed all articles investigating ncRNAs, specifically micro RNAs (miRNAs) and long ncRNAs (lncRNA/circRNA) in cholesteatoma tissue. Results Candidate miRNA approaches indicated that miR-21 and let-7a are the major miRNAs involved in cholesteatoma growth, migration, proliferation, bone destruction, and apoptosis. Regulatory potential for the same biological processes was also observed for miR-203a. The NF-kB/miR-802/PTEN regulatory network was in relation to observed miR-21 activity in cholesteatoma as well. High throughput approaches revealed additional ncRNAs implicated in cholesteatoma pathology. Competitive endogenous RNA (ceRNA) analysis highlighted lncRNA/circRNA that could be “endogenous sponge” for miR-21 and let-7a based on the hypothesis that RNA transcripts can communicate with and regulate each other by using shared miRNA response elements. Conclusion In this review, we summarize the discoveries and role of ncRNA in major pathways in cholesteatoma and highlight the potential of miRNA-based therapeutics in the treatment of cholesteatoma. Level of Evidence: NA.
T2  - Laryngoscope Investigative Otolaryngology
T2  - Laryngoscope Investigative Otolaryngology
T1  - Non-coding RNA and cholesteatoma
VL  - 7
IS  - 1
SP  - 60
EP  - 66
DO  - 10.1002/lio2.728
ER  - 

@article{
author = "Jovanović, Ivan G. and Živković, Maja and Ješić, Snežana and Stanković, Aleksandra",
year = "2022",
abstract = "Objective Cholesteatoma is a challenging chronic pathology of the middle ear for which pharmacologic therapies have not been developed yet. Cholesteatoma occurrence depends on the interplay between genetic and environmental factors while master regulators orchestrating disease progression are still unknown. Therefore, in this review, we will discuss the diagnostic and therapeutic potential of non-coding RNAs (ncRNA) as a new class of regulatory molecules. Methods We have comprehensively reviewed all articles investigating ncRNAs, specifically micro RNAs (miRNAs) and long ncRNAs (lncRNA/circRNA) in cholesteatoma tissue. Results Candidate miRNA approaches indicated that miR-21 and let-7a are the major miRNAs involved in cholesteatoma growth, migration, proliferation, bone destruction, and apoptosis. Regulatory potential for the same biological processes was also observed for miR-203a. The NF-kB/miR-802/PTEN regulatory network was in relation to observed miR-21 activity in cholesteatoma as well. High throughput approaches revealed additional ncRNAs implicated in cholesteatoma pathology. Competitive endogenous RNA (ceRNA) analysis highlighted lncRNA/circRNA that could be “endogenous sponge” for miR-21 and let-7a based on the hypothesis that RNA transcripts can communicate with and regulate each other by using shared miRNA response elements. Conclusion In this review, we summarize the discoveries and role of ncRNA in major pathways in cholesteatoma and highlight the potential of miRNA-based therapeutics in the treatment of cholesteatoma. Level of Evidence: NA.",
journal = "Laryngoscope Investigative Otolaryngology, Laryngoscope Investigative Otolaryngology",
title = "Non-coding RNA and cholesteatoma",
volume = "7",
number = "1",
pages = "60-66",
doi = "10.1002/lio2.728"
}

Jovanović, I. G., Živković, M., Ješić, S.,& Stanković, A.. (2022). Non-coding RNA and cholesteatoma. in Laryngoscope Investigative Otolaryngology, 7(1), 60-66.
https://doi.org/10.1002/lio2.728

Jovanović IG, Živković M, Ješić S, Stanković A. Non-coding RNA and cholesteatoma. in Laryngoscope Investigative Otolaryngology. 2022;7(1):60-66.
doi:10.1002/lio2.728 .

Jovanović, Ivan G., Živković, Maja, Ješić, Snežana, Stanković, Aleksandra, "Non-coding RNA and cholesteatoma" in Laryngoscope Investigative Otolaryngology, 7, no. 1 (2022):60-66,
https://doi.org/10.1002/lio2.728 . .

TY  - JOUR
AU  - Stojković, Goran
AU  - Jovanović, Ivan G.
AU  - Dimitrijević, Milovan
AU  - Jovanović, Jasmina
AU  - Tomanović, Nada
AU  - Stanković, Aleksandra
AU  - Arsović, Nenad
AU  - Boričić, Ivan
AU  - Zeljić, Katarina
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10217
AB  - Objectives This study aimed to experimentally validate dysregulated expression of miRNA candidates selected through updated meta-analysis of most commonly deregulated miRNAs in oral cancer and to explore their diagnostic and prognostic potential. Materials and methods Five miRNAs (miR-31-3p, miR-135b-5p, miR-18a-5p, miR-30a-5p and miR-139-5p) from updated meta-signature were selected for validation by qRT-PCR method in 35 oral cancer clinical specimens and adjacent non-cancerous tissue. Results Updated meta-analysis has identified 13 most commonly deregulated miRNAs in oral cancer. Seven miRNAs were consistently up-regulated (miR-21-5p, miR-31-3p, miR-135b-5p, miR-31-5p, miR-424-5p, miR-18a-5p and miR-21-3p), while five were down-regulated (miR-139-5p, miR-30a-3p, miR-375-3p, miR-376c-3p and miR-30a-5p). Increased expression of miR-31-3p and miR-135b-5p, and decreased expression of miR-139-5p and miR-30a-5p were confirmed in oral cancer compared to adjacent non-cancerous tissue. A three miRNAs combination (miR-31-3p, miR-139-5p and miR-30a-5p) gave the most promising diagnostic potential for discriminating oral cancer from non-cancerous tissue (AUC: 0.780 [95% CI: 0.673–0.886], p < 0.0005, sensitivity 94.3%, specificity 51.4%). High expression of miR-135b-5p, miR-18a-5p and miR-30a-5p was associated with poor survival (p = 0.003, p = 0.048, p = 0.016 respectively). Conclusion miR-31-3p, miR-139-5p and miR-30a-5p panel was confirmed as a potential diagnostic biomarker when distinguishing oral cancer from non-cancerous tissue. miR-135b-5p, miR-18a-5p and miR-30a-5p might serve as potential biomarkers of poor survival of oral cancer patients.
T2  - Oral Diseases
T1  - Meta-signature guided investigation of miRNA candidates as potential biomarkers of oral cancer
VL  - inpress
SP  - 1
EP  - 15
DO  - 10.1111/odi.14185
ER  - 

@article{
author = "Stojković, Goran and Jovanović, Ivan G. and Dimitrijević, Milovan and Jovanović, Jasmina and Tomanović, Nada and Stanković, Aleksandra and Arsović, Nenad and Boričić, Ivan and Zeljić, Katarina",
year = "2022",
abstract = "Objectives This study aimed to experimentally validate dysregulated expression of miRNA candidates selected through updated meta-analysis of most commonly deregulated miRNAs in oral cancer and to explore their diagnostic and prognostic potential. Materials and methods Five miRNAs (miR-31-3p, miR-135b-5p, miR-18a-5p, miR-30a-5p and miR-139-5p) from updated meta-signature were selected for validation by qRT-PCR method in 35 oral cancer clinical specimens and adjacent non-cancerous tissue. Results Updated meta-analysis has identified 13 most commonly deregulated miRNAs in oral cancer. Seven miRNAs were consistently up-regulated (miR-21-5p, miR-31-3p, miR-135b-5p, miR-31-5p, miR-424-5p, miR-18a-5p and miR-21-3p), while five were down-regulated (miR-139-5p, miR-30a-3p, miR-375-3p, miR-376c-3p and miR-30a-5p). Increased expression of miR-31-3p and miR-135b-5p, and decreased expression of miR-139-5p and miR-30a-5p were confirmed in oral cancer compared to adjacent non-cancerous tissue. A three miRNAs combination (miR-31-3p, miR-139-5p and miR-30a-5p) gave the most promising diagnostic potential for discriminating oral cancer from non-cancerous tissue (AUC: 0.780 [95% CI: 0.673–0.886], p < 0.0005, sensitivity 94.3%, specificity 51.4%). High expression of miR-135b-5p, miR-18a-5p and miR-30a-5p was associated with poor survival (p = 0.003, p = 0.048, p = 0.016 respectively). Conclusion miR-31-3p, miR-139-5p and miR-30a-5p panel was confirmed as a potential diagnostic biomarker when distinguishing oral cancer from non-cancerous tissue. miR-135b-5p, miR-18a-5p and miR-30a-5p might serve as potential biomarkers of poor survival of oral cancer patients.",
journal = "Oral Diseases",
title = "Meta-signature guided investigation of miRNA candidates as potential biomarkers of oral cancer",
volume = "inpress",
pages = "1-15",
doi = "10.1111/odi.14185"
}

Stojković, G., Jovanović, I. G., Dimitrijević, M., Jovanović, J., Tomanović, N., Stanković, A., Arsović, N., Boričić, I.,& Zeljić, K.. (2022). Meta-signature guided investigation of miRNA candidates as potential biomarkers of oral cancer. in Oral Diseases, inpress, 1-15.
https://doi.org/10.1111/odi.14185

Stojković G, Jovanović IG, Dimitrijević M, Jovanović J, Tomanović N, Stanković A, Arsović N, Boričić I, Zeljić K. Meta-signature guided investigation of miRNA candidates as potential biomarkers of oral cancer. in Oral Diseases. 2022;inpress:1-15.
doi:10.1111/odi.14185 .

Stojković, Goran, Jovanović, Ivan G., Dimitrijević, Milovan, Jovanović, Jasmina, Tomanović, Nada, Stanković, Aleksandra, Arsović, Nenad, Boričić, Ivan, Zeljić, Katarina, "Meta-signature guided investigation of miRNA candidates as potential biomarkers of oral cancer" in Oral Diseases, inpress (2022):1-15,
https://doi.org/10.1111/odi.14185 . .

TY  - JOUR
AU  - Barišić, Anita
AU  - Stanković, Aleksandra
AU  - Stojković, Ljiljana
AU  - Pereza, Nina
AU  - Ostojić, Saša
AU  - Peterlin, Ana
AU  - Peterlin, Borut
AU  - Vraneković, Jadranka
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10022
AB  - Despite considerable effort aimed at decreasing the incidence of spontaneous preterm birth (SPTB), it remains the leading cause of infant mortality and morbidity. The aim of this study was to evaluate maternal LINE-1 DNA methylation (DNAm), along with DNMT polymorphisms and factors proposed to modulate DNAm, in patients who delivered early preterm. This case-control study included women who delivered spontaneously early preterm (23–336/7 weeks of gestation), and control women. DNAm was analyzed in peripheral blood lymphocytes by quantification of LINE-1 DNAm using the MethyLight method. There was no significant difference in LINE-1 DNAm between patients with early PTB and controls. Among the investigated predictors, only the history of previous PTB was significantly associated with LINE-1 DNAm in PTB patients (β = −0.407; R2 = 0.131; p = 0.011). The regression analysis showed the effect of DNMT3B rs1569686 TT+TG genotypes on LINE-1 DNAm in patients with familial PTB (β = −0.524; R2 = 0.275; p = 0.037). Our findings suggest novel associations of maternal LINE-1 DNA hypomethylation with DNMT3B rs1569686 T allele. These results also contribute to the understanding of a complex (epi)genetic and environmental relationship underlying the early PTB.
T2  - Biological Research For Nursing
T1  - Maternal LINE-1 DNA Methylation in Early Spontaneous Preterm Birth
VL  - 24
IS  - 1
SP  - 85
EP  - 93
DO  - 10.1177/10998004211043571
ER  - 

@article{
author = "Barišić, Anita and Stanković, Aleksandra and Stojković, Ljiljana and Pereza, Nina and Ostojić, Saša and Peterlin, Ana and Peterlin, Borut and Vraneković, Jadranka",
year = "2022",
abstract = "Despite considerable effort aimed at decreasing the incidence of spontaneous preterm birth (SPTB), it remains the leading cause of infant mortality and morbidity. The aim of this study was to evaluate maternal LINE-1 DNA methylation (DNAm), along with DNMT polymorphisms and factors proposed to modulate DNAm, in patients who delivered early preterm. This case-control study included women who delivered spontaneously early preterm (23–336/7 weeks of gestation), and control women. DNAm was analyzed in peripheral blood lymphocytes by quantification of LINE-1 DNAm using the MethyLight method. There was no significant difference in LINE-1 DNAm between patients with early PTB and controls. Among the investigated predictors, only the history of previous PTB was significantly associated with LINE-1 DNAm in PTB patients (β = −0.407; R2 = 0.131; p = 0.011). The regression analysis showed the effect of DNMT3B rs1569686 TT+TG genotypes on LINE-1 DNAm in patients with familial PTB (β = −0.524; R2 = 0.275; p = 0.037). Our findings suggest novel associations of maternal LINE-1 DNA hypomethylation with DNMT3B rs1569686 T allele. These results also contribute to the understanding of a complex (epi)genetic and environmental relationship underlying the early PTB.",
journal = "Biological Research For Nursing",
title = "Maternal LINE-1 DNA Methylation in Early Spontaneous Preterm Birth",
volume = "24",
number = "1",
pages = "85-93",
doi = "10.1177/10998004211043571"
}

Barišić, A., Stanković, A., Stojković, L., Pereza, N., Ostojić, S., Peterlin, A., Peterlin, B.,& Vraneković, J.. (2022). Maternal LINE-1 DNA Methylation in Early Spontaneous Preterm Birth. in Biological Research For Nursing, 24(1), 85-93.
https://doi.org/10.1177/10998004211043571

Barišić A, Stanković A, Stojković L, Pereza N, Ostojić S, Peterlin A, Peterlin B, Vraneković J. Maternal LINE-1 DNA Methylation in Early Spontaneous Preterm Birth. in Biological Research For Nursing. 2022;24(1):85-93.
doi:10.1177/10998004211043571 .

Barišić, Anita, Stanković, Aleksandra, Stojković, Ljiljana, Pereza, Nina, Ostojić, Saša, Peterlin, Ana, Peterlin, Borut, Vraneković, Jadranka, "Maternal LINE-1 DNA Methylation in Early Spontaneous Preterm Birth" in Biological Research For Nursing, 24, no. 1 (2022):85-93,
https://doi.org/10.1177/10998004211043571 . .

TY  - JOUR
AU  - Stojković, Ljiljana
AU  - Zec, Manja
AU  - Živković, Maja
AU  - Bundalo, Maja
AU  - Bošković, Maja
AU  - Glibetić, Marija
AU  - Stanković, Aleksandra
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9865
AB  - Cardiovascular disease (CVD) is associated with alterations in DNA methylation and polyunsaturated fatty acid (PUFA) profile, both modulated by dietary polyphenols. The present parallel, placebo-controlled study (part of the original clinical study registered as NCT02800967 at www.clinicaltrials.gov) aimed to determine the impact of 4-week daily consumption of polyphenol-rich Aronia melanocarpa juice (AMJ) treatment on Long Interspersed Nucleotide Element-1 (LINE-1) methylation in peripheral blood leukocytes and on plasma PUFAs, in subjects (n = 54, age range of 40.2 ± 6.7 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure, and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation (folate intake levels, MTHFR C677T gene variant, anthropometric and metabolic parameters) modulated the LINE-1 methylation levels upon the consumption of polyphenol-rich aronia juice. Experimental analysis of LINE-1 methylation was done by MethyLight method. MTHFR C677T genotypes were determined by the polymerase chain reaction–restriction fragment length polymorphism method, and folate intake was assessed by processing the data from the food frequency questionnaire. PUFAs were measured by gas–liquid chromatography, and serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using Statistica software package. In the comparison after vs. before the treatment period, in dyslipidemic women (n = 22), we observed significant decreases in LINE-1 methylation levels (97.54 ± 1.50 vs. 98.39 ± 0.86%, respectively; P = 0.01) and arachidonic acid/eicosapentaenoic acid ratio [29.17 ± 15.21 vs. 38.42 (25.96–89.58), respectively; P = 0.02]. The change (after vs. before treatment) in LINE-1 methylation directly correlated with the presence of MTHFR 677T allele, average daily folate intake, and the change in serum low-density lipoprotein cholesterol but inversely correlated with the change in serum triacylglycerols (R = 0.72, R2 = 0.52, adjusted R2 = 0.36, P = 0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich aronia juice consumption achieved through the modifications of DNA methylation pattern and PUFAs in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of both DNA methylation and PUFA profile may become targets for new approaches in the prevention of CVD.
T2  - Frontiers in Nutrition
T1  - Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women
VL  - 8
DO  - 10.3389/fnut.2021.689055
ER  - 

@article{
author = "Stojković, Ljiljana and Zec, Manja and Živković, Maja and Bundalo, Maja and Bošković, Maja and Glibetić, Marija and Stanković, Aleksandra",
year = "2021",
abstract = "Cardiovascular disease (CVD) is associated with alterations in DNA methylation and polyunsaturated fatty acid (PUFA) profile, both modulated by dietary polyphenols. The present parallel, placebo-controlled study (part of the original clinical study registered as NCT02800967 at www.clinicaltrials.gov) aimed to determine the impact of 4-week daily consumption of polyphenol-rich Aronia melanocarpa juice (AMJ) treatment on Long Interspersed Nucleotide Element-1 (LINE-1) methylation in peripheral blood leukocytes and on plasma PUFAs, in subjects (n = 54, age range of 40.2 ± 6.7 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure, and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation (folate intake levels, MTHFR C677T gene variant, anthropometric and metabolic parameters) modulated the LINE-1 methylation levels upon the consumption of polyphenol-rich aronia juice. Experimental analysis of LINE-1 methylation was done by MethyLight method. MTHFR C677T genotypes were determined by the polymerase chain reaction–restriction fragment length polymorphism method, and folate intake was assessed by processing the data from the food frequency questionnaire. PUFAs were measured by gas–liquid chromatography, and serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using Statistica software package. In the comparison after vs. before the treatment period, in dyslipidemic women (n = 22), we observed significant decreases in LINE-1 methylation levels (97.54 ± 1.50 vs. 98.39 ± 0.86%, respectively; P = 0.01) and arachidonic acid/eicosapentaenoic acid ratio [29.17 ± 15.21 vs. 38.42 (25.96–89.58), respectively; P = 0.02]. The change (after vs. before treatment) in LINE-1 methylation directly correlated with the presence of MTHFR 677T allele, average daily folate intake, and the change in serum low-density lipoprotein cholesterol but inversely correlated with the change in serum triacylglycerols (R = 0.72, R2 = 0.52, adjusted R2 = 0.36, P = 0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich aronia juice consumption achieved through the modifications of DNA methylation pattern and PUFAs in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of both DNA methylation and PUFA profile may become targets for new approaches in the prevention of CVD.",
journal = "Frontiers in Nutrition",
title = "Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women",
volume = "8",
doi = "10.3389/fnut.2021.689055"
}

Stojković, L., Zec, M., Živković, M., Bundalo, M., Bošković, M., Glibetić, M.,& Stanković, A.. (2021). Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women. in Frontiers in Nutrition, 8.
https://doi.org/10.3389/fnut.2021.689055

Stojković L, Zec M, Živković M, Bundalo M, Bošković M, Glibetić M, Stanković A. Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women. in Frontiers in Nutrition. 2021;8.
doi:10.3389/fnut.2021.689055 .

Stojković, Ljiljana, Zec, Manja, Živković, Maja, Bundalo, Maja, Bošković, Maja, Glibetić, Marija, Stanković, Aleksandra, "Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women" in Frontiers in Nutrition, 8 (2021),
https://doi.org/10.3389/fnut.2021.689055 . .

TY  - JOUR
AU  - Živković, Maja
AU  - Bubić, Maja
AU  - Kolaković, Ana
AU  - Dekleva, Milica
AU  - Stanković, Goran
AU  - Stanković, Aleksandra
AU  - Đurić, Tamara
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9842
AB  - Glutathione S-transferases (GSTs) are the family of enzymes involved in the second line of defense against oxidative stress (OS). The lack of GSTT1/GSTM1 enzyme quantity or activity, due to the presence of homozygous deletion compromises antioxidative defense resulting in OS. OS is the critical mechanism in the pathophysiology of atherosclerosis, coronary artery disease, and myocardial infarction (MI). The increase in reactive oxygen species together with the process of apoptosis plays a role in left ventricular remodeling (LVR) after MI. The associations of GSTT1 and GSTM1 gene polymorphisms with the risk of MI are inconsistent. The aim was to analyze the association of GSTT1/GSTM1 null genotypes with first MI and LVR 8 months after the MI. The study involved 330 controls and 438 consecutive patients with symptoms and signs of first MI. The subgroup of 150 MI patients was prospectively followed up for 6 months. Evidence of maladaptive LVR was obtained by 2D Doppler echocardiography 3-5 days and 6 months after the MI. A multiplex polymerase chain reaction was used to detect the deletion in GSTT1 and GSTM1 genes. GSTM1 null genotype was significantly and independently associated with first MI (adjusted OR = 1.45 95% CI 1.03-2.03, p = 0.03). Association of double null genotypes with maladaptive LVR in patients 6 months after the first MI was no longer significant after adjustment for factors that differed significantly between patients with and without maladaptive LVR. This study demonstrated the association of GSTM1 null genotypes with the risk of MI in the Serbian population.
T2  - Free Radical Research
T1  - The association of glutathione S-transferase T1 and M1 deletions with myocardial infarction
VL  - 55
IS  - 3
SP  - 267
EP  - 274
DO  - 10.1080/10715762.2021.1931166
ER  - 

@article{
author = "Živković, Maja and Bubić, Maja and Kolaković, Ana and Dekleva, Milica and Stanković, Goran and Stanković, Aleksandra and Đurić, Tamara",
year = "2021",
abstract = "Glutathione S-transferases (GSTs) are the family of enzymes involved in the second line of defense against oxidative stress (OS). The lack of GSTT1/GSTM1 enzyme quantity or activity, due to the presence of homozygous deletion compromises antioxidative defense resulting in OS. OS is the critical mechanism in the pathophysiology of atherosclerosis, coronary artery disease, and myocardial infarction (MI). The increase in reactive oxygen species together with the process of apoptosis plays a role in left ventricular remodeling (LVR) after MI. The associations of GSTT1 and GSTM1 gene polymorphisms with the risk of MI are inconsistent. The aim was to analyze the association of GSTT1/GSTM1 null genotypes with first MI and LVR 8 months after the MI. The study involved 330 controls and 438 consecutive patients with symptoms and signs of first MI. The subgroup of 150 MI patients was prospectively followed up for 6 months. Evidence of maladaptive LVR was obtained by 2D Doppler echocardiography 3-5 days and 6 months after the MI. A multiplex polymerase chain reaction was used to detect the deletion in GSTT1 and GSTM1 genes. GSTM1 null genotype was significantly and independently associated with first MI (adjusted OR = 1.45 95% CI 1.03-2.03, p = 0.03). Association of double null genotypes with maladaptive LVR in patients 6 months after the first MI was no longer significant after adjustment for factors that differed significantly between patients with and without maladaptive LVR. This study demonstrated the association of GSTM1 null genotypes with the risk of MI in the Serbian population.",
journal = "Free Radical Research",
title = "The association of glutathione S-transferase T1 and M1 deletions with myocardial infarction",
volume = "55",
number = "3",
pages = "267-274",
doi = "10.1080/10715762.2021.1931166"
}

Živković, M., Bubić, M., Kolaković, A., Dekleva, M., Stanković, G., Stanković, A.,& Đurić, T.. (2021). The association of glutathione S-transferase T1 and M1 deletions with myocardial infarction. in Free Radical Research, 55(3), 267-274.
https://doi.org/10.1080/10715762.2021.1931166

Živković M, Bubić M, Kolaković A, Dekleva M, Stanković G, Stanković A, Đurić T. The association of glutathione S-transferase T1 and M1 deletions with myocardial infarction. in Free Radical Research. 2021;55(3):267-274.
doi:10.1080/10715762.2021.1931166 .

Živković, Maja, Bubić, Maja, Kolaković, Ana, Dekleva, Milica, Stanković, Goran, Stanković, Aleksandra, Đurić, Tamara, "The association of glutathione S-transferase T1 and M1 deletions with myocardial infarction" in Free Radical Research, 55, no. 3 (2021):267-274,
https://doi.org/10.1080/10715762.2021.1931166 . .

TY  - CONF
AU  - Stojković, Goran
AU  - Jovanović, Ivan G.
AU  - Stanković, Aleksandra
AU  - Dimitrijević, Milovan
AU  - Zeljić, Katarina
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11015
AB  - Oral cancer is the most prevalent type of head and neck cancer, characterized by rising incidence, high relapse occurrence and low survival. There is a high demand for the identification of novel and sensitive diagnostic and prognostic molecular biomarkers of oral cancer. MicroRNAs (miRNAs) are considered as promising candidates. Previously conducted meta-analysis on high throughput miRNA profiling in oral cancer emphasized consistent down-regulation of miR-30a-5p and miR-139-5p. We aimed to validate these findings in oral cancer clinical samples and to test the diagnostic and prognostic potential of these miRNAs. Bioinformatical prediction of investigated miRNAs target genes was executed through the intersection of multiple miRNA target prediction algorithms. Enrichment analysis of miRNA target genes was performed using miRPathDB V2.0 software on GO:BP database. RNA was isolated from oral cancer and adjacent noncancerous tissue from 30 patients by miRVana kit. cDNA was synthesized by TaqMan microRNA reverse transcription kit. TaqMan gene expression kit was used for relative quantification of miRNAs normalized to RNU6B. Relative expression was calculated by comparative Ct method. The diagnostic potential was estimated by the ROC curve analysis. Expression of miR-30a-5p and miR-139-5p was dichotomized as high or low by the median. Association with clinicopathological features and miRNAs expression was calculated by χ2 test. Bioinformatical analysis demonstrated both enrichment of miR-30a-5p and miR-139-5p targets in biological processes associated with cancer pathology and complementarity in regulation of these processes thus ensuring non-redundant regulation. Both miRNA were significantly down-regulated in oral cancer compared to non-cancerous tissue (Wilcoxon test: p=0.0004, p=0.001, respectively). According to the ROC curve analysis, both miRNAs might be used as potential tools for discrimination between cancerous and non-cancerous tissue (miR-30a-5p AUC=0.677, p=0.019; miR-139-5p AUC=0.656, p=0.038). There was a significant correlation between the expression of miR-30a-5p and miR-139-5p in cancerous tissue (Spearman rank test r=0.901, p<0.0001). None of the analyzed miRNAs was associated with stage, nodal status, tumour size and overall survival (p>0.05) which indicates that miR-30a-5p and miR-139-5p can’t be used as prognostic biomarkers of oral cancer. Our results suggest that miR-30a-5p and miR-139-5p might be used as good diagnostic biomarkers for discrimination between oral cancer and non-cancerous tissue.
PB  - Department of Biology and Ecology : Faculty of Sciences University of Novi Sad
C3  - Biologia Serbica : Belgrade BioInformatics Conference : BelBi2021 : program and the book of abstracts; June 21-25
T1  - Bioinformatic characterization and validation of miR-30a-5p and miR-139-5p as diagnostic and prognostic biomarkers of oral cancer
VL  - 43
IS  - 1
SP  - 102
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11015
ER  - 

@conference{
author = "Stojković, Goran and Jovanović, Ivan G. and Stanković, Aleksandra and Dimitrijević, Milovan and Zeljić, Katarina",
year = "2021",
abstract = "Oral cancer is the most prevalent type of head and neck cancer, characterized by rising incidence, high relapse occurrence and low survival. There is a high demand for the identification of novel and sensitive diagnostic and prognostic molecular biomarkers of oral cancer. MicroRNAs (miRNAs) are considered as promising candidates. Previously conducted meta-analysis on high throughput miRNA profiling in oral cancer emphasized consistent down-regulation of miR-30a-5p and miR-139-5p. We aimed to validate these findings in oral cancer clinical samples and to test the diagnostic and prognostic potential of these miRNAs. Bioinformatical prediction of investigated miRNAs target genes was executed through the intersection of multiple miRNA target prediction algorithms. Enrichment analysis of miRNA target genes was performed using miRPathDB V2.0 software on GO:BP database. RNA was isolated from oral cancer and adjacent noncancerous tissue from 30 patients by miRVana kit. cDNA was synthesized by TaqMan microRNA reverse transcription kit. TaqMan gene expression kit was used for relative quantification of miRNAs normalized to RNU6B. Relative expression was calculated by comparative Ct method. The diagnostic potential was estimated by the ROC curve analysis. Expression of miR-30a-5p and miR-139-5p was dichotomized as high or low by the median. Association with clinicopathological features and miRNAs expression was calculated by χ2 test. Bioinformatical analysis demonstrated both enrichment of miR-30a-5p and miR-139-5p targets in biological processes associated with cancer pathology and complementarity in regulation of these processes thus ensuring non-redundant regulation. Both miRNA were significantly down-regulated in oral cancer compared to non-cancerous tissue (Wilcoxon test: p=0.0004, p=0.001, respectively). According to the ROC curve analysis, both miRNAs might be used as potential tools for discrimination between cancerous and non-cancerous tissue (miR-30a-5p AUC=0.677, p=0.019; miR-139-5p AUC=0.656, p=0.038). There was a significant correlation between the expression of miR-30a-5p and miR-139-5p in cancerous tissue (Spearman rank test r=0.901, p<0.0001). None of the analyzed miRNAs was associated with stage, nodal status, tumour size and overall survival (p>0.05) which indicates that miR-30a-5p and miR-139-5p can’t be used as prognostic biomarkers of oral cancer. Our results suggest that miR-30a-5p and miR-139-5p might be used as good diagnostic biomarkers for discrimination between oral cancer and non-cancerous tissue.",
publisher = "Department of Biology and Ecology : Faculty of Sciences University of Novi Sad",
journal = "Biologia Serbica : Belgrade BioInformatics Conference : BelBi2021 : program and the book of abstracts; June 21-25",
title = "Bioinformatic characterization and validation of miR-30a-5p and miR-139-5p as diagnostic and prognostic biomarkers of oral cancer",
volume = "43",
number = "1",
pages = "102",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11015"
}

Stojković, G., Jovanović, I. G., Stanković, A., Dimitrijević, M.,& Zeljić, K.. (2021). Bioinformatic characterization and validation of miR-30a-5p and miR-139-5p as diagnostic and prognostic biomarkers of oral cancer. in Biologia Serbica : Belgrade BioInformatics Conference : BelBi2021 : program and the book of abstracts; June 21-25
Department of Biology and Ecology : Faculty of Sciences University of Novi Sad., 43(1), 102.
https://hdl.handle.net/21.15107/rcub_vinar_11015

Stojković G, Jovanović IG, Stanković A, Dimitrijević M, Zeljić K. Bioinformatic characterization and validation of miR-30a-5p and miR-139-5p as diagnostic and prognostic biomarkers of oral cancer. in Biologia Serbica : Belgrade BioInformatics Conference : BelBi2021 : program and the book of abstracts; June 21-25. 2021;43(1):102.
https://hdl.handle.net/21.15107/rcub_vinar_11015 .

Stojković, Goran, Jovanović, Ivan G., Stanković, Aleksandra, Dimitrijević, Milovan, Zeljić, Katarina, "Bioinformatic characterization and validation of miR-30a-5p and miR-139-5p as diagnostic and prognostic biomarkers of oral cancer" in Biologia Serbica : Belgrade BioInformatics Conference : BelBi2021 : program and the book of abstracts; June 21-25, 43, no. 1 (2021):102,
https://hdl.handle.net/21.15107/rcub_vinar_11015 .

TY  - CONF
AU  - Đorđević, Ana M.
AU  - Dekleva, Milica
AU  - Živković, Maja
AU  - Stanković, Aleksandra
AU  - Kuveljić, Jovana
AU  - Đurić, Tamara
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12729
AB  - After myocardial infarction (MI) and consequential ischemia, the heart undergoes a set of geometric and functional changes. In the early days after injury, these changes, defined as cardiac remodeling, are the powerful factor that preserves cardiac function and promotes survival. However, it may continue for months after MI and eventually lead to adverse remodeling with impaired systolic function and reduced myocardial contractility and further cardiovascular complications, such as heart failure (HF). Left ventricular (LV) ejection fraction (EF) is widely used as an index of systolic function in cardiac patients. However, global myocardial strain has been found to be superior to the conventional parameters, such as LVEF, in terms of assessment of cardiac performance after MI. Galectin-3 (gal-3) is a multifunctional protein involved in a variety of physiological and pathological processes, affecting the entire cardiovascular continuum of MI. Gal-3 is encoded by a LGALS-3 gene, located in a unique, 300 kb long haplotype block in Caucasians. Gal-3 serum level has been approved as a diagnostic marker for risk stratification and prognosis evaluation of HF patients according to the ACC/AHA/HFSA Guideline for the management of HF. The purpose of the present prospective study was to analyze the possible association of tag genetic variants of the haplotype block containing LGALS-3 with changes in cardiac parameters, LVEF and global radial strain (GRS), within 6 months post-MI. The study enrolled 120 patients with first acute MI that were prospectively followed-up 6 months after MI. According to Tagger server, rs4040064 G/T, rs11628437 G/A and rs7159490 C/T variants cover 82% (r2>0.8) of phenotypic variance of the aforementioned haplotype block. Tag variants were detected and genotyped by commercially available assays for allelic discrimination. Echocardiography examinations were performed at admission and 6 months post-MI. Change (Δ) of cardiac parameters was calculated as a difference between the value at 6-month follow-up and baseline value (at admission). The referent haplotype is set by the software for carrying haplotype association analysis and represents the most frequent haplotype in the studied groups. Bonferroni correction for multiple testing was performed and p values <0.025 were considered as statistically significant.We found that, compared to the reference GGC haplotype, GAT haplotype had significantly higher expected phenotypic mean [95% CI] of ΔGRS (3.77 [1.28 - 6.25] vs. −5.34 [−12.69 - 2.01], respectively, p=0.025) and ΔLVEF (0.84 [−1.88 - 3.56] vs. −12.91 [−17.30 - −8.53], respectively, p=0.00001), in the direction of decrease of GRS and LVEF 6 months after MI in patients bearing GAT haplotype. Our findings suggest that GAT haplotype bears the risk for diminished LV transmural contractility and radial systolic function: In order to reach a definitive conclusion, our exploratory results should be further validated on a larger sample
C3  - European Journal of Hear Failure
T1  - LGALS-3 containing haplotype block tag variants in association with cardiac parameters changes within six months after the first acute myocardial infarction
VL  - 23
IS  - Suppl. S2
SP  - 311
EP  - 311
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12729
ER  - 

@conference{
author = "Đorđević, Ana M. and Dekleva, Milica and Živković, Maja and Stanković, Aleksandra and Kuveljić, Jovana and Đurić, Tamara",
year = "2021",
abstract = "After myocardial infarction (MI) and consequential ischemia, the heart undergoes a set of geometric and functional changes. In the early days after injury, these changes, defined as cardiac remodeling, are the powerful factor that preserves cardiac function and promotes survival. However, it may continue for months after MI and eventually lead to adverse remodeling with impaired systolic function and reduced myocardial contractility and further cardiovascular complications, such as heart failure (HF). Left ventricular (LV) ejection fraction (EF) is widely used as an index of systolic function in cardiac patients. However, global myocardial strain has been found to be superior to the conventional parameters, such as LVEF, in terms of assessment of cardiac performance after MI. Galectin-3 (gal-3) is a multifunctional protein involved in a variety of physiological and pathological processes, affecting the entire cardiovascular continuum of MI. Gal-3 is encoded by a LGALS-3 gene, located in a unique, 300 kb long haplotype block in Caucasians. Gal-3 serum level has been approved as a diagnostic marker for risk stratification and prognosis evaluation of HF patients according to the ACC/AHA/HFSA Guideline for the management of HF. The purpose of the present prospective study was to analyze the possible association of tag genetic variants of the haplotype block containing LGALS-3 with changes in cardiac parameters, LVEF and global radial strain (GRS), within 6 months post-MI. The study enrolled 120 patients with first acute MI that were prospectively followed-up 6 months after MI. According to Tagger server, rs4040064 G/T, rs11628437 G/A and rs7159490 C/T variants cover 82% (r2>0.8) of phenotypic variance of the aforementioned haplotype block. Tag variants were detected and genotyped by commercially available assays for allelic discrimination. Echocardiography examinations were performed at admission and 6 months post-MI. Change (Δ) of cardiac parameters was calculated as a difference between the value at 6-month follow-up and baseline value (at admission). The referent haplotype is set by the software for carrying haplotype association analysis and represents the most frequent haplotype in the studied groups. Bonferroni correction for multiple testing was performed and p values <0.025 were considered as statistically significant.We found that, compared to the reference GGC haplotype, GAT haplotype had significantly higher expected phenotypic mean [95% CI] of ΔGRS (3.77 [1.28 - 6.25] vs. −5.34 [−12.69 - 2.01], respectively, p=0.025) and ΔLVEF (0.84 [−1.88 - 3.56] vs. −12.91 [−17.30 - −8.53], respectively, p=0.00001), in the direction of decrease of GRS and LVEF 6 months after MI in patients bearing GAT haplotype. Our findings suggest that GAT haplotype bears the risk for diminished LV transmural contractility and radial systolic function: In order to reach a definitive conclusion, our exploratory results should be further validated on a larger sample",
journal = "European Journal of Hear Failure",
title = "LGALS-3 containing haplotype block tag variants in association with cardiac parameters changes within six months after the first acute myocardial infarction",
volume = "23",
number = "Suppl. S2",
pages = "311-311",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12729"
}

Đorđević, A. M., Dekleva, M., Živković, M., Stanković, A., Kuveljić, J.,& Đurić, T.. (2021). LGALS-3 containing haplotype block tag variants in association with cardiac parameters changes within six months after the first acute myocardial infarction. in European Journal of Hear Failure, 23(Suppl. S2), 311-311.
https://hdl.handle.net/21.15107/rcub_vinar_12729

Đorđević AM, Dekleva M, Živković M, Stanković A, Kuveljić J, Đurić T. LGALS-3 containing haplotype block tag variants in association with cardiac parameters changes within six months after the first acute myocardial infarction. in European Journal of Hear Failure. 2021;23(Suppl. S2):311-311.
https://hdl.handle.net/21.15107/rcub_vinar_12729 .

Đorđević, Ana M., Dekleva, Milica, Živković, Maja, Stanković, Aleksandra, Kuveljić, Jovana, Đurić, Tamara, "LGALS-3 containing haplotype block tag variants in association with cardiac parameters changes within six months after the first acute myocardial infarction" in European Journal of Hear Failure, 23, no. Suppl. S2 (2021):311-311,
https://hdl.handle.net/21.15107/rcub_vinar_12729 .

TY  - JOUR
AU  - Kuveljić, Jovana
AU  - Đurić, Tamara
AU  - Stanković, Goran
AU  - Dekleva, Milica
AU  - Stanković, Aleksandra
AU  - Alavantić, Dragan
AU  - Živković, Maja
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9541
AB  - Background: Myocardial infarction (MI) and underlining atherosclerosis are the main causes of death worldwide. Phosphatase and actin regulator 1 (PHACTR1) variants have been associated with early onset MI, coronary artery disease and carotid dissection. PHACTR1 mRNA expression has been detected in tissues and cells related to atherosclerosis. Nonetheless, the true effect of PHACTR1 on vascular diseases is still unknown. Our aim was to examine the association of PHACTR1 intronic variants, rs9349379, rs2026458 and rs2876300, with MI and multi-vessel disease (MVD) and to assess their effect on PHACTR1 and EDN1 mRNA expression in PBMCs of patients six months after MI. Methods: The study enrolled 537 patients with the first MI and 310 controls. Gene expression was assessed in 74 patients six months after MI and 37 healthy controls. Rs9349379, rs2026458, rs2876300 and relative mRNA expressions were detected by TaqMan® technology. Results: The significant association between PHACTR1 variants and MI was not found, either individually or in haplotype. A higher frequency of rs2876300G-allele in MVD was rendered not significant after Bonferroni correction. PHACTR1 mRNA was significantly increased in PBMCs of patients six months after MI compared to controls (p = 0.02). Patients that carry ACG haplotype have increased PHACTR1 mRNA expression in PBMCs (p = 0.04). There was no effect of PHACTR1 variants on EDN1 mRNA expression. Conclusion: Our findings suggest that PHACTR1 intronic variants may have a role in severity and progression of coronary atherosclerosis. Future research is needed to clarify the mechanism underlying the role of PHACTR1 in coronary atherosclerosis and MI. © 2021 Elsevier B.V.
T2  - Gene
T1  - Association of PHACTR1 intronic variants with the first myocardial infarction and their effect on PHACTR1 mRNA expression in PBMCs
VL  - 775
SP  - 145428
DO  - 10.1016/j.gene.2021.145428
ER  - 

@article{
author = "Kuveljić, Jovana and Đurić, Tamara and Stanković, Goran and Dekleva, Milica and Stanković, Aleksandra and Alavantić, Dragan and Živković, Maja",
year = "2021",
abstract = "Background: Myocardial infarction (MI) and underlining atherosclerosis are the main causes of death worldwide. Phosphatase and actin regulator 1 (PHACTR1) variants have been associated with early onset MI, coronary artery disease and carotid dissection. PHACTR1 mRNA expression has been detected in tissues and cells related to atherosclerosis. Nonetheless, the true effect of PHACTR1 on vascular diseases is still unknown. Our aim was to examine the association of PHACTR1 intronic variants, rs9349379, rs2026458 and rs2876300, with MI and multi-vessel disease (MVD) and to assess their effect on PHACTR1 and EDN1 mRNA expression in PBMCs of patients six months after MI. Methods: The study enrolled 537 patients with the first MI and 310 controls. Gene expression was assessed in 74 patients six months after MI and 37 healthy controls. Rs9349379, rs2026458, rs2876300 and relative mRNA expressions were detected by TaqMan® technology. Results: The significant association between PHACTR1 variants and MI was not found, either individually or in haplotype. A higher frequency of rs2876300G-allele in MVD was rendered not significant after Bonferroni correction. PHACTR1 mRNA was significantly increased in PBMCs of patients six months after MI compared to controls (p = 0.02). Patients that carry ACG haplotype have increased PHACTR1 mRNA expression in PBMCs (p = 0.04). There was no effect of PHACTR1 variants on EDN1 mRNA expression. Conclusion: Our findings suggest that PHACTR1 intronic variants may have a role in severity and progression of coronary atherosclerosis. Future research is needed to clarify the mechanism underlying the role of PHACTR1 in coronary atherosclerosis and MI. © 2021 Elsevier B.V.",
journal = "Gene",
title = "Association of PHACTR1 intronic variants with the first myocardial infarction and their effect on PHACTR1 mRNA expression in PBMCs",
volume = "775",
pages = "145428",
doi = "10.1016/j.gene.2021.145428"
}

Kuveljić, J., Đurić, T., Stanković, G., Dekleva, M., Stanković, A., Alavantić, D.,& Živković, M.. (2021). Association of PHACTR1 intronic variants with the first myocardial infarction and their effect on PHACTR1 mRNA expression in PBMCs. in Gene, 775, 145428.
https://doi.org/10.1016/j.gene.2021.145428

Kuveljić J, Đurić T, Stanković G, Dekleva M, Stanković A, Alavantić D, Živković M. Association of PHACTR1 intronic variants with the first myocardial infarction and their effect on PHACTR1 mRNA expression in PBMCs. in Gene. 2021;775:145428.
doi:10.1016/j.gene.2021.145428 .

Kuveljić, Jovana, Đurić, Tamara, Stanković, Goran, Dekleva, Milica, Stanković, Aleksandra, Alavantić, Dragan, Živković, Maja, "Association of PHACTR1 intronic variants with the first myocardial infarction and their effect on PHACTR1 mRNA expression in PBMCs" in Gene, 775 (2021):145428,
https://doi.org/10.1016/j.gene.2021.145428 . .