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Spontaneous preterm birth (sPTB) is a global health concern and it is the most prevalent cause of infant mortality and morbidity with occurrence rate of 5 – 18% worldwide. Studies suggest infection and infection-driven activation of inflammatory responses are the potential risk factors for sPTB. MicroRNAs (miRNAs) are thought to control the expression of several immune genes, making them crucial components of the intricate immune regulatory network and the dysregulation of miRNAs in placenta has been associated to several pregnancy-related complications. However, studies on possible role of miRNAs in immunomodulation of cytokine signalling in infection-associated sPTB are scarce. Present study aimed to investigate expression/ correlation of a few circulating miRNAs (miR-223, −150-5p, −185-5p, −191-5p), miRNA target genes and associated cytokines in sPTB women found infected with Chlamydia trachomatis / Mycoplasma hominis / Ureaplasma urealyticum. Non-heparinized blood and placental sample were collected from 140 sPTB and 140 term women visiting Safdarjung hospital, New Delhi (India) for conducting PCR and RT-PCR for pathogen detection and miRNA/ target gene/ cytokine expression, respectively. Common target genes of differentially expressed miRNAs were obtained from databases. The correlation between select target genes/ cytokines and serum miRNAs was determined by Spearman's rank correlation. 43 sPTB were infected with either pathogen and a significant upregulation of serum miRNAs was observed. However, miR-223 and 150–5p showed maximum fold-change (4.78 and 5.58, respectively) in PTB versus control group. IL-6ST, TGF-β R3 and MMP-14 were important target genes among 454 common targets, whereas, IL-6 and TGF-β were associated cytokines. miR-223 and 150–5p showed significant negative correlation with IL-6ST/ IL-6/ MMP-14 and positive correlation with TGF-β R3/ TGF-β. A significant positive correlation was found between IL-6ST and IL-6, TGF-β R3 and TGF-β. However, miR-185–5p and 191–5p were not significantly correlated. Although post-transcriptional validation is required, yet on the basis of mRNA findings, the study concludes that miR-223 and 150–5p are apparently of clinical importance in regulation of inflammatory processes during infection-associated sPTB. • Significant upregulation of miRs with highest fold-change in miR-223 and miR-150–5p. • Significant upregulation of miRs target genes and associated cytokines. • miR-223 and miR-150–5p were negatively correlated with IL-6ST, IL-6 and MMP-14. • miR-223 and miR-150–5p were positively correlated with TGF-βR3 and TGF-β. • miR-223 and miR-150–5p play immunomodulatory function during pre-mature labour. [ABSTRACT FROM AUTHOR]

Study aimed to characterize the expression of antioxidant genes SOD1 and SOD2 in Chlamydia trachomatis-induced recurrent spontaneous aborters and further determine their role by in silico analysis. First void urine was collected from 130 non-pregnant women with history of recurrent spontaneous abortion (RSA) (Group I) and 130 non-pregnant women (Group II; control) attending Obstetrics and Gynecology Department, SJH, New Delhi, India. C. trachomatis detection was performed by conventional PCR in urine. Gene expression of SOD1 and SOD2 was performed by quantitative real-time PCR. Further, its interacting partners were studied by in silico analysis. 22 patients were positive for C. trachomatis in Group I. Significant upregulation was observed for SOD2 gene in C. trachomatis-infected RSA patients while SOD1 was found to be downregulated. Increased concentration of oxidative stress biomarkers 8-hydroxyguanosine and 8-isoprostane was found in C. trachomatis-infected RSA patients. Protein–protein interaction (PPI) of SOD proteins and its interacting partners viz.; CCS, GPX1, GPX2, GPX3, GPX4, GPX5, GPX7, GPX8, CAT, PRDX1, TXN, SIRT3, FOXO3, and AKT1 were found to be involved in MAPK, p53 and foxo signaling pathways. Molecular pathways involved in association with SODs indicate reactive oxygen species (ROS) detoxification, apoptotic pathways and cell cycle regulation. Overall data revealed alleviated levels of SOD2 gene and decreased expression of SOD1 gene in response to C. trachomatis-infection leading to production of oxidative stress and RSA. [ABSTRACT FROM AUTHOR]

Studies behind mechanisms of Chlamydia trachomatis -induced recurrent spontaneous abortion is still in its infancy. Possible strategy for preventing recurrent spontaneous abortion at molecular level is needed. Despite its multifactorial aetiology, Chlamydia trachomatis is important cause of RSA. However, mechanism leading to RSA in C. trachomatis -positive patients is not understood and novel strategies are needed. It is hypothesized that microRNAs play important role in RSA regulation during infection. Study aimed to elucidate expression/role of urine-circulating miRs-320b, 221-3p, 146b-5p,-16,-24,-559 in recurrent spontaneous aborters with C. trachomatis infection and to find their target genes by bioinformatic analysis. First-void urine was collected from 30 non-pregnant women with RSA (Group I) and 30 non-pregnant women with ≥2 successful deliveries (Group II; Controls) attending Department of Obstetrics and Gynaecology, Vardhman Mahavir Medical College, Safdarjung hospital, New Delhi (India). PCR was performed to detect C. trachomatis. Expression of miRNAs was studied by quantitative real-time PCR while target genes/functional annotations were predicted by GO/KEGG databases. Data was statistically evaluated. 05 RSA patients were C. trachomatis -positive. Group I was subdivided into Group Ia (C. trachomatis -positive RSA; n = 5) and Group Ib (C. trachomatis -negative RSA; internal controls). miR-320b, -221-3p, −146b-5p, −16, −24 were significantly upregulated (miR-16 showed maximum 4.3 fold-change) while miR-559 was downregulated (0.5 fold-change) in Group Ia versus controls ('p'<0.001). Bioinformatic analysis revealed that target genes of miRNAs in RSA are involved in apoptosis and AMPK signalling pathways. Results showed differential expression of miRNAs implyingmiR-16 and miR-559 as potential biomarkers of RSA in infected women. Furthermore, network of genes of differentially expressed miRNAs regulates RSA by targeting gene function in apoptosis, cell adhesion and angiogenesis. • Micro-RNAs play important role in regulation of recurrent spontaneous abortion (RSA) during Chlamydia trachomatis infection. • miR-320b, -221-3p, −146b-5p, −16, −24 were upregulated; however, miR-559 was downregulated in infected aborters. • miR-16 showed maximum 4.3 fold-change while miR-559 showed 0.5 fold-change ('p' < 0.001) in infected patients. • Differential expression of miRNAs revealed miR-16 and miR-559 as potential biomarkers of RSA in Chlamydia -infected women. • Bioinformatic analysis revealed that target genes of miRNAs in RSA are involved in apoptosis and AMPK signalling pathways. [ABSTRACT FROM AUTHOR]