Altered TLR7 Expression-Mediated Immune Modulation Is Supportive of Persistent Replication and Intrauterine Transmission of HBV.

Hepatitis B Virus (HBV) is posing as a serious public health threat mainly due to its asymptomatic nature of infection in pregnancy and vertical transmission. Viral sensing toll-like receptors (TLR) and Interleukins (IL) are important molecules in providing an antiviral state. The study aimed to assess the role of TLR7-mediated immune modulation, which might have an impact in the intrauterine transmission of HBV leading to mother to child transmission of the virus. We investigated the expression pattern of TLR7, IL-3, and IL-6 by RT-PCR in the placentas of HBV-infected pregnant women to see their role in the intrauterine transmission of HBV. We further validated the expression of TLR7 in placentas using Immunohistochemistry. Expression analysis by RT-PCR of TLR7 revealed significant downregulation among the Cord blood (CB) HBV DNA positive and negative cases with mean ± standard deviation (SD) of 0.43 ± 0.22 (28) and 1.14 ± 0.57 (44) with p = 0.001. IL-3 and IL-6 expression revealed significant upregulation in the CB HBV DNA-positive cases with p = 0.001. Multinomial logistic regression analysis revealed that TLR7 and IL-3 fold change and mother HBeAg status are important predictors for HBV mother to child transmission. Immunohistochemistry revealed the decreased expression of TLR7 in CB HBV DNA-positive cases. This study reveals that the downregulation of TLR7 in the placenta along with CB HBV DNA-positive status may lead to intrauterine transmission of HBV, which may lead to vertical transmission of HBV.

Integrative Placental Multi-Omics Analysis Reveals Perturbed Pathways and Potential Prognostic Biomarkers in Gestational Hypertension.

BACKGROUND: Gestational hypertension (GH) is a severe complication that occurs after 20 weeks of pregnancy; however, its molecular mechanisms are not yet fully understood. OBJECTIVE: Through this case-control discovery phase study, we aimed to find disease-specific candidate placental microRNAs (miRNAs) and metabolite markers for differentiating GH by integrating next-generation sequencing and metabolomics multi-omics analysis of placenta. Using small RNA sequencing and metabolomics of placental tissues of healthy pregnant (HP, n = 24) and GH subjects (n = 20), the transcriptome and metabolome were characterized in both groups. RESULTS: The study identified a total of 44 downregulated placental miRNAs which includes three novel, three mature and 38 precursor miRNAs. Six miRNAs including three mature (hsa-miR-181a-5p, hsa-miR-498-5p, and hsa-miR-26b-5p) and three novel (NC_000016.10_1061, NC_000005.10_475, and NC_000001.11_53) were considered for final target prediction and functional annotation. Integrative analysis of differentially expressed miRNAs and metabolites yielded five pathways such as purine, glutathione, glycerophospholipid, inositol phosphate and ß-alanine to be significantly perturbed in GH. We present fourteen genes (LPCAT1, LPCAT2, DGKH, PISD, GPAT2, PTEN, SACM1L, PGM2, AMPD3, AK7, AK3, CNDP1, IDH2, and ODC1) and eight metabolites (xanthosine, xanthine, spermine, glycine, CDP-Choline, glyceraldehyde 3-phosphate, ß-alanine, and histidine) with potential to distinguish GH and HP. CONCLUSION: The differential expression of miRNAs, their target genes, altered metabolites and metabolic pathways in GH patients were identified for the first time in our study. Further, the altered miRNAs and metabolites were integrated to build their inter-connectivity network. The findings obtained from our study may be used as a valuable source to further unravel the molecular pathways associated with GH and also for the evaluation of prognostic markers.

Altered expression of endosomal Toll-like receptors and HBeAg seropositivity may act synergistically towards the vertical transmission of HBV.

PROBLEM: Hepatitis B is one of the leading causes of mortality in India. Despite the mass vaccination programme, the burden of the infection is still increasing due to its vertical transmission. Asymptomatic nature of hepatitis B virus (HBV) infection owing to immune tolerance among pregnant women is a major issue in this regard. METHOD OF STUDY: As such, this study aims to investigate the potential role of altered Toll-like receptor (TLR) expression (TLR-3, 7 and 9) along with peripheral blood HBeAg status in attaining differential cord blood (CB) HBV DNA status. RESULT: Expression analysis reveals an overall downregulation of expression with mean ± SD value 1.14 ± 1.05, 0.86 ± 0.5 and 0.71 ± 0.4 (TLR 3, 7 and 9, respectively) upon comparison with healthy women. Further stratification based on CB HBV DNA status; the downregulation of expression was found to be significantly (p < .05) associated with positive CB HBV DNA status apart from peripheral HBeAg status. One hundred percent HBeAg positive parturiting women exhibit positive CB HBV DNA. Pearson's correlation analysis reveals a positive correlation between CB HBV DNA status and altered TLR expression, HBeAg status and mother HBV DNA status and as such can be associated with the potential risk of HBV vertical transmission. CONCLUSION: This study suggests that the downregulation of TLR 3, 7 and 9 may be a risk factor for potential vertical transmission of HBV.

Creation and Destruction of Jobs in Urban Labour Market: Role of Gender, Caste and Religion in India.

This study analyses labour market transitions from job to jobless or jobless to job by using Periodic Labour Force Survey (PLFS) of India in urban labour market by applying first-order Markov process in constructing transition matrices and panel logit regression model using personal level information from the PLFS in India for 2019-20. While education is assumed to be the most important factor influencing the process of transitions in the labour market, the circumstance variables like gender, caste and religion are expected to have significant effects on it in a country like India. The empirical results show a significant difference in labour market transitions between men and women. The movement of workers between job status was very low and the major part of the transition occurred in the form of job losses for each type of workers both among men and women and also among all working age group and young age group.

Social Identity, Gender and Unequal Opportunity of Earning in Urban India: 2017-2018 to 2019-2020.

This study measures inequality of opportunity in earnings of different types of workers living in urban locations by using methodology similar to those developed in Ferreira and Gignoux (Review of Income and Wealth 57: 622-657, 2011) with household-level data taken from Periodic the Labour Force Surveys. In calculating the index of unequal opportunity, we use ex ante concept of equal opportunity, and gender, social status and parent's education as circumstance variables. Shapley decomposition is performed to find out the relative roles of the circumstance variables in unequal opportunity in earnings. This empirical exercise reveals that a substantial part (nearly one-fourth) of total earning inequality is accounted for by inequality of opportunity in urban India. Parental education plays a significant role in contributing to unequal opportunity for regular salaried and self-employed workers, and gender difference is very much important in explaining unequal earning opportunity for casual wage workers.

Estimation of parabens and bisphenols in maternal products and urinary concentrations in Indian pregnant women: daily intake and health risk assessment.

The presence of parabens and bisphenols in maternal products and usage during pregnancy have raised serious concern about their possible harm to pregnant women. The concentrations of six parabens and eight bisphenols were quantified by high-performance liquid chromatography-tandem mass spectrometry in the samples of commercially available herbal-based ayurvedic maternal products and urine of healthy pregnant women from Assam, India. Methyl paraben (MP) and bisphenol AF (BPAF) were found to be more dominant in the maternal products, whereas MP, bisphenol A (BPA), and BPAF were dominant in urine samples of healthy pregnant women. The sum of the mean concentrations of all forms of parabens and bisphenols in maternal products were 48,308.50 ng/g and 542.42 ng/g, respectively, and urine 101.33 ng/mL and 23.42 ng/mL, respectively. The estimated daily intake (EDI) of total parabens and bisphenols in maternal products were 7378.02 and 19.78 ng/kg body weight/day, respectively. EDI of total parabens and bisphenols from urinary concentrations were 690.12 and 111.33 µg/kg body weight/day, respectively. The concentrations of butyl (BP) and heptyl (HP) parabens have a significant positive correlation with birth weight. The hazard quotient (HQ) value of MP, EP, and BPA was less than 1, and margin of exposure (MOE) identified potential risk associated with propyl paraben. Results from Monte-Carlo risk assessment analysis did not exceed the acceptable daily intake (ADI). Our results showed that higher concentrations of parabens and bisphenols are present in maternal products and the urine of healthy pregnant women. Hence maternal products containing bisphenols and parabens should be used cautiously during pregnancy to avoid maternal and fetal complications.