Association of reduced maternal sHLA-G5 isoform levels and elevated TNF-α/IL-4 cytokine ratio with Recurrent Pregnancy Loss: A study on South Indian women.

Inflammation is of critical importance in successful implantation during pregnancy. However, the establishment of maternal immune tolerance towards semi-allograft foetus is more exigent and is achieved predominantly by human leukocyte antigen-G (HLA-G) isoforms with a special emphasis on soluble HLA-G5 (sHLA-G5). Constant inflammation and lack of resolution by anti-inflammatory milieu, due to aberrant expression of critical immunoregulatory molecules such as sHLA-G5 and dysfunctional T helper cells 1 and 2 (Th1-Th2) cytokine shift, can lead to adverse pregnancy outcomes including recurrent pregnancy loss (RPL). Serum samples of 270 pregnant women (135 healthy parous and 135 with a history of RPL) were evaluated for the concentrations of sHLA-G5, interleukin-4 (IL-4) and tumour necrosis factor-alpha (TNF-α) using sandwich enzyme-linked immunosorbent assay (ELISA) and found elevated levels of sHLA-G5 and IL-4 in controls and higher TNF-α levels and TNF-α:IL-4 ratio in patients (P < .05). Stratified data analysis based on the time of sample collection, that is the first and second trimesters exhibited higher sHLA-G5 and IL-4 in both first and second trimesters in controls than patients, while they displayed lower levels concerning TNF-α and TNF-α:IL-4 ratio (P < .05). However, within patients and controls in the first or second trimesters, there was a significant variation concerning sHLA-G5 alone. Further, the outcome of pregnancies studied in the present investigation revealed a significant elevation in sHLA-G5 levels among women with successful pregnancies compared with women who experienced pregnancy loss, therefore, concluding the potential application of sHLA-G5 isoform as a marker in assisting improved pregnancy outcomes.

The making of the Women in Biology forum (WiB) at Bioclues.

The Women in Biology forum (WiB) of Bioclues (India) began in 2009 to promote and support women pursuing careers in bioinformatics and computational biology. WiB was formed in order to help women scientists deprived of basic research, boost the prominence of women scientists particularly from developing countries, and bridge the gender gap to innovation. WiB has also served as a platform to highlight the work of established female scientists in these fields. Several award-winning women researchers have shared their experiences and provided valuable suggestions to WiB. Headed by Mohanalatha Chandrasekharan and supported by Dr. Reeta Rani Singhania and Renuka Suravajhala, WiB has seen major progress in the last couple of years particularly in the two avenues Mentoring and Research, off the four avenues in Bioclues: Mentoring, Outreach, Research and Entrepreneurship (MORE). In line with the Bioclues vision for bioinformatics in India, the WiB Journal Club (JoC) recognizes women scientists working on functional genomics and bioinformatics, and provides scientific mentorship and support for project design and hypothesis formulation. As a part of Bioclues, WiB members practice the group's open-desk policy and its belief that all members are free to express their own thoughts and opinions. The WiB forum appreciates suggestions and welcomes scientists from around the world to be a part of their mission to encourage women to pursue computational biology and bioinformatics.

Can circulating levels of transforming growth factor-ß1 in early pregnancy serve as a predictive marker of unfavourable outcome?

INTRODUCTION: Transforming Growth Factor (TGF-ß1) is an anti-inflammatory pleiotropic cytokine, crucial for maternal immune tolerance towards semi-allograft. It acts as a mediator in achieving successful implantation and maintenance of pregnancy. METHODS: A total of 300 samples; 150 with Recurrent Pregnancy Loss (RPL) and 150 with no pregnancy loss, in their first trimester were evaluated for circulating levels of TGF-ß1 using Enzyme-Linked Immunosorbent Assay (ELISA). Further, the Receiver Operating Characteristics (ROC) analysis was performed to assess the potential of TGF-ß1 in the risk prediction of RPL and the prognostic importance in the form of favourable and unfavourable outcome in the existing pregnancy. RESULTS: The results showed significant elevated levels in women without the history of RPL compared to those with the history of RPL (4783.60 ± 522.95 vs. 4252.18 ± 672.26 pg/mL, p < 0.0001).Further evaluation of follow up data of women with the history of RPL, based on favourable (78%) and unfavourable (22%) outcome of the existent pregnancy showed significantly higher TGF-ß1 in women with favourable pregnancy outcome in comparison with those who had a foetal loss (4877.12 ± 460.04 vs. 4075.91 ± 616.17 pg/mL, <0.0001). Furthermore, the Receiver Operating Characteristics (ROC) analysis revealed sufficient importance for risk assessment and very good marker to predict unfavourable event (AUC-0.85, SE = 67%, SP = 88%, p < 0.0001). CONCLUSION: Certainly TGF-ß1 appears to have predictive importance; however additional studies with large sample size are warranted for further validation.

UP-regulated levels of sHLA-G in women with a history of RPL in mid-gestation presumably to achieve ongoing pregnancy.

PROBLEM: Recurrent Pregnancy Loss (RPL) is a disorder characterized by two or more pregnancy losses within 20th week of gestation. Globally 1-5% of the couples are affected, 50% of these cases are with unknown etiology. HLA-G, an Immuno-modulatory molecule is a non-classical MHC-1 protein, expressed abundantly on extravillous trophoblastic cells, responsible for spiral artery remodeling, maintaining maternal immune tolerance and fetal growth by adjusting pro and anti-inflammatory milieu during different gestational phases. METHOD OF STUDY: In the present case-control study CD4+HLA-G+ tTreg cells were enumerated by flow cytometry and estimation of the circulating levels of sHLA-G in the blood samples of 300 mid-gestation pregnant women with (iRPL) and without history of RPL (nRPL) by Enzyme-linked Immunosorbent assay was done. The cases included 92 primary and 58 secondary RPL cases RESULTS: A significant reduction in number of tTregs and elevated levels of circulating sHLA-G in iRPL (.03, 200.9) versus nRPL (.09, 90.32) was observed. Further, the primary cases showed higher circulating sHLA-G and no difference in relation to CD4+HLA-G+ tTregs compared to the secondary cases. Receiver operating curve (ROC) characteristics of sHLA-G (AUC = .8) was superior to CD4+HLA-G+ (AUC = .7) for iRPL patients over nRPL group. CONCLUSIONS: Our results are suggestive of the over-expression of sHLA-G which may be caused due to its shedding from surface of trophoblast as a compensatory mechanism to save the on-going pregnancy. To realize the present outcome, studies are required on on-going pregnancy follow-up cases with favorable and unfavorable pregnancy outcome.

Association of FOXP3 rs3761548 polymorphism and its reduced expression with unexplained recurrent spontaneous abortions: A South Indian study.

PROBLEM: Fork Head Box Protein 3 (FOXP3) is an X-linked gene, codes for a master transcription regulatory protein that controls the development and function of immunosuppressive T regulatory (Treg) cells. They are crucial mediators of maternal foetal tolerance and successful pregnancy outcome. The aim of the study is to evaluate the association of FOXP3 rs3761548 functional polymorphism and to assess the serum concentrations of full-length FOXP3 protein in Unexplained Recurrent Spontaneous Abortions (URSA) patients of Southern India. METHOD OF STUDY: The study included blood samples from 150 URSA patients and 150 healthy, pregnant parous women. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism was done for rs3761548 FOXP3 genotyping. Serum concentrations of full-length FOXP3 protein were estimated by enzyme-linked immunosorbent assay. RESULTS: The frequencies of mutant A allele, CA and AA genotypes of rs3761548 functional polymorphism were significantly elevated in patients compared to healthy, pregnant parous women and exhibited a two, three and twofold increased risk respectively towards URSA. Serum concentrations of full-length FOXP3 protein were high in controls compared to patients (10.14 ± .30 vs. 8.84 ± 1.73 ng/ml; p < .05). CONCLUSION: Our results advocate an association of FOXP3 rs3761548 polymorphism and reduced expression of full-length FOXP3 protein with URSA.

Systems Challenges of Hepatic Carcinomas: A Review.

Hepatocellular Carcinoma (HCC) is ubiquitous in its prevalence in most of the developing countries. In the era of systems biology, multi-omics has evinced an extensive approach to define the underlying mechanism of disease progression. HCC is a multifactorial disease and the investigation of progression of liver cirrhosis becomes much extensive with cultivating omics approaches. We have performed a comprehensive review about such challenges in multi-omics approaches that are concerned to identify the immunological, genetics and epidemiological factors associated with HCC.