Browsing by Author "Snehil Budhwar"

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Altered cord serum 25-hydroxyvitamin D signaling and placental inflammation is associated with pre-term birth
(Blackwell Publishing Ltd, 2020) Snehil Budhwar; Priyanka Verma; Rachna Verma; Shreshtha Gupta; Sangeeta Rai; Singh Rajender; Kiran Singh
Problem: Vitamin D is well-known for having anti-inflammatory and immunomodulatory properties. Impaired maternal vitamin D status has been known to increase the risk of adverse pregnancy outcomes like pre-term birth. The present study aims to evaluate the impact of fetal cord serum 25-hydroxyvitamin D-mediated signaling in mediating inflammatory responses in placenta during pre-term birth. Method of study: For the above purpose, cord serum 25 hydroxyvitamin D 25(OH)D were measured in term (n = 20) and pre-term (n = 20) born babies using ELISA. Vitamin D downstream signaling has also been checked in placenta (VDR, CYP27B1, cathelicidin LL37) along with expression of inflammatory markers (S100A8, HMGB1, TLR2, p-NF-kappaB) using Western blotting and immunohistochemistry. Pearson correlation model was used to do correlation study. Results: Compared with term born babies (59.31 ± 3.476), decline in cord serum 25(OH)D levels is observed in pre-term born babies (22.26 ± 1.083, P = <0.0001) that showed strong positive correlation with gestational age (r =.9368***) and birthweight (r =.9559***). On the other hand, vitamin D signaling markers were found to be downregulated and inflammatory markers were upregulated in placental tissue of pre-term born babies. Conclusion: Thus, our study demonstrated that insufficient cord 25(OH)D levels may disturb the homeostasis of inflammation in placenta. Altered cord serum 25(OH)D mediated anti-inflammatory signaling may be acting as trigger signals in modulating inflammatory responses in placenta and eliciting premature activation of spontaneous labor in pre-term birth. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Altered crosstalk of estradiol and progesterone with Myeloid-derived suppressor cells and Th1/Th2 cytokines in early miscarriage is associated with early breakdown of maternal-fetal tolerance
(Blackwell Publishing Ltd, 2019) Priyanka Verma; Rachna Verma; Rohini R. Nair; Snehil Budhwar; Anuradha Khanna; Nisha Rani Agrawal; Ruchi Sinha; Ruchi Birendra; Singh Rajender; Kiran Singh
Problem: Decline in myeloid-derived suppressor cells (MDSCs) and Th2 cytokines levels lead to early miscarriage (EM) but how the hormonal milieu of the body regulates MDSCs and Th1/Th2 cytokine balance is still a matter of investigation. Method of study: Peripheral blood and decidua samples were collected from 20 EM patients, and 20 healthy pregnant women opted for elective abortion. MDSCs and G-MDSCs levels were analyzed in peripheral blood mononuclear cells, and Th1/Th2 cytokines levels were determined in serum via flow cytometry. Estrogen (E2), Progesterone (P4), and Testosterone levels were measured via ELISA. Further, proliferation and apoptosis in decidual samples were checked via immunoblot/immunohistochemistry of estrogen receptor -α (ER-α), STAT-3/pSTAT-3, and caspase-3, respectively. Results: Our results clearly indicate that in EM patients; decline in E2 and P4 significantly correlates with decline in MDSCs, particularly with subtype granulocytic MDSCs (G-MDSCs) and skewness of the Th1/Th2 cytokines balance toward Th1 response. Downregulation of ER- α and increased caspase-3 expression in endometrium decidua signifies poor endometrial receptivity in EM. STAT-3 activation regulates proliferation, differentiation and suppressive potency of MDSCs. In decidua of EM, significantly lower expression of pSTAT-3 indicates that these processes pertaining to MDSCs are compromised. Conclusion: Altogether, this unfavorable systemic milieu may drive toward early breakdown of maternal-fetal tolerance in EM. Therefore, regulated crosstalk of E2, P4 with MDSCs and balanced Th1/Th2 cytokines is prerequisite for successful pregnancy. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Estradiol correlates with the accumulation of Monocytic Myeloid-Derived Suppressor Cells in Pre-term birth: A possible explanation of immune suppression in pre-term babies
(Elsevier Ireland Ltd, 2021) Snehil Budhwar; Rachna Verma; Priyanka Verma; Renu Bala; Sangeeta Rai; Kiran Singh
Synergistic interplay of immune endocrine interaction is prerequisite for an effective maternal fetal tolerance. Pre-term birth (PTB) may be a consequence of altered immune-endocrine crosstalk during third trimester resulting in early breakdown of this tolerance. Myeloid derived suppressor cells (MDSCs), a heterogenous population of immature immune cells are increased in pregnant women and healthy newborns, but their role in PTB still remains obscure. We now report that granulocytic MDSCs (G-MDSCs) is decreased in women delivering prematurely, suggesting their potential role in maintaining maternal fetal tolerance. Interestingly, in contrast statistically significant increase in MDSCs and monocytic MDSCs (M-MDSCs) along with positive correlation with cord serum estradiol (E2), and overexpressed ER-α in placental tissue suggested E2 mediated accumulation of M-MDSCs in PTB babies. MDSCs mediated immune suppression is accompanied with subsequent decline in total T cells and its subtypes: Th and Tc in PTB babies, which signifies their potential contribution towards the impaired immune system of PTB babies. © 2021 Elsevier B.V.
Fertilization failure and gamete health: Is there a link?
(Frontiers in Bioscience, 2017) Snehil Budhwar; Vertika Singh; Priyanka Verma; Kiran Singh
Fertilization is a hallmark event of sexual reproduction marked by the fusion of male and female gamete to form zygote. It is a highly complex, yet a robust process that is intricately regulated by various signalling molecules. A healthy fertilization is determined by the quality of zygote which is contingent on the health of egg and sperm. The relationship between infertility and gametic health can be reciprocal. On one hand gametogenesis has to be dynamic and unremitting to sustain the reproductive health, while on the other hand it has to be error free for proper embryonic development. Complex cellular interactions make gametogenesis highly vulnerable to extrinsic as well as intrinsic intrusions. Molecular disparities during these phases may result in complete fertilization failure. Present review provides an overview of the regulation of gametogenesis, determinants of healthy gamete, players at fertilization window and what may go wrong during the development of zygote to embryo leading to implantation failure. We have outlined different 'windows' of vulnerability during gametogenesis supported by evidences affecting the fertility potential of both the partners.
Fetal hyperhomocysteinemia is associated with placental inflammation and early breakdown of maternal-fetal tolerance in pre-term birth
(John Wiley and Sons Inc, 2022) Renu Bala; Rachna Verma; Snehil Budhwar; Nikita Prakash; Shikha Sachan
Problem: Hyperhomocysteinemia (hypHcy) due to impaired folate metabolism is shown to be a risk factor for preterm birth (PTB) and low birth weight (LBW) in mothers. However, the relationship of fetal hypHcy with adverse pregnancy outcomes is under-represented. The present study aims to investigate the association of fetal hypHcy with oxidative stress and placental inflammation that can contribute to an early breakdown of maternal-fetal tolerance in pre-term birth (PTB). Methods: Cord blood and placenta tissue were collected from PTB and term infant group. Levels of homocysteine, folic acid, vitamin B12 and oxidative stress markers (MDA, T-AOC, 8-OHdG) were measured in cord blood serum using ELISA and respective standard assay kits. Relative expression of candidate genes (TNF-α, IL-6, IL1-β, VEGF-A, MMP2 and MMP9) was also checked using RT-PCR and immunoblotting/immunohistochemistry. Results: PTB infants showed significantly higher levels of homocysteine (P =.02) and lower levels of vitamin B12 (P =.005) as compared to term infants. We also found that PTB infants with hypHcy had lower T-AOC (P =.003) and higher MDA (P =.04) levels as compared to term infants with normal homocysteine levels. The mRNA and protein levels of TNF-α, VEGF-A, MMP2 and MMP9 were significantly higher in hypHcy PTB infants. Conclusion: Our results show that fetal hypHcy is associated with oxidative stress and an increase in inflammatory markers in the placenta. Thus, in conclusion, our study demonstrates that fetal hypHcy during pregnancy is a potential risk factor that may initiate an early breakdown of uterine quiescence due to activation of inflammatory processes leading to PTB. © 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Impact of socio-demographic variables on antenatal services in eastern Uttar Pradesh, India
(Taylor and Francis Ltd., 2021) Renu Bala; Ajay Singh; Vertika Singh; Priyanka Verma; Snehil Budhwar; Om Prakash Shukla; Gyan Prakash Singh; Kiran Singh
We investigated the impact of socio-demographic variables on antenatal care (ANC) utilization and the low birth weight of a child. Data were collected from 300 pregnant females. Only 22.5% of females received full antenatal care (≥4 visits). Our results showed that female’s age at marriage and education plays a significant role in improving ANC. We observed an overall decrease in the utilization of services provided during each antenatal visit. ANC visits from the first trimester decrease the risk of having a baby with low birth weight. Awareness programs and educating families about pregnancy care are recommended to improve ANC utilization. © 2020 Taylor & Francis Group, LLC.
Interleukin-17 gene polymorphisms and the risk of early miscarriage: A case-control study and meta-analysis
(Elsevier B.V., 2018) Priyanka Verma; Rohini R. Nair; Snehil Budhwar; Vertika Singh; Renu Bala; Anuradha Khanna; Nisha R. Agarwal; Punam Rai; Singh Rajender; Kiran Singh
Previous reports clearly suggest that IL-17 have important role in development of systemic and peripheral inflammation in early miscarriage (EM). In the present study, we have investigated the association between genetic variants in IL-17A, IL-17F and susceptibility to EM. We recruited 135 EM patients and 150 controls and used PCR-RFLP method for genotyping the polymorphisms of IL-17A, rs4711998 (−832 A/G), rs8193036 (−692C/T) and IL-17F rs763780 (7488 T/C). No significant difference was observed for all the three polymorphic sites between the EM patients and control group in terms of genotypic (rs4711998, χ2 = 1.95, p = 0.37; rs8193036, χ2 = 1.91, p = 0.38; rs763780, χ2 = 2.45, p = 0.29), and allelic frequencies (rs4711998, OR = 1.19, 95% CI = 0.84 to 1.67, p = 0.35; rs8193036,OR = 1.18, 95% CI = 0.58 to 2.06, p = 0.75; rs763780, OR = 1.5, 95% CI = 0.93 to 2.71, p = 0.11). Further, meta-analysis of IL-17F (rs763780) variant with EM also revealed non-significant association of IL-17F (rs763780) variant with EM in the presence of mutant genotype (CC) via random effect model (p = 0.70, OR = 1.30, 95% CI =0.33–5.11). © 2018
S100 proteins: An emerging cynosure in pregnancy & adverse reproductive outcome
(Wolters Kluwer Medknow Publications, 2018) Rachna Verma; Priyanka Verma; Snehil Budhwar; Kiran Singh
S100 proteins are calcium (Ca 2+ )-binding proteins and these have an important function in progression, manifestation and therapeutic aspects of various inflammatory, metabolic and neurodegenerative disorders. Based on their involvement in intracellular or extracellular regulatory effects, S100 proteins are classified into three subgroups: one subgroup is specialized in exerting only intracellular effects, other performs both intracellular and extracellular functions and the third subgroup members only display extracellular regulatory effects. S100 proteins are expressed particularly in vertebrates and have cell-specific expression. Functionally, S100 proteins act through their surface receptors and regulate cell functions in autocrine or paracrine mode. Receptor for advanced glycation end products (RAGEs) and toll-like receptor 4 are the main surface receptors. S100 proteins participate in the regulation of cellular differentiation, proliferation, apoptosis and inflammation along with Ca 2+ homeostasis, energy metabolism and cellular migration, and perform the respective functions through their interaction with transcription factors, nucleic acids, enzymes, receptors, cytoskeleton system, etc. Currently, their role in adverse pregnancy outcomes and compromised reproductive health is being explored. These proteins are present in amniotic fluid, endometrium tissue and foetal brain; therefore, it is quite likely that alterations in the expression levels of S100 family members will be affecting the particular function they are involved in and ultimately affecting the pregnancy in adverse manner. The current review discusses about an association of S100 proteins in pregnancy disorders such as endometriosis, intrauterine growth retardation and miscarriage. © 2019 Indian Journal of Medical Research.
The Yin and Yang of myeloid derived suppressor cells
(Frontiers Media S.A., 2018) Snehil Budhwar; Priyanka Verma; Rachna Verma; Sangeeta Rai; Kiran Singh
In recent years, most of our knowledge about myeloid derived suppressor cells (MDSCs) has come from cancer studies, which depicts Yin side of MDSCs. In cancer, inherent immunosuppressive action of MDSCs favors tumor progression by inhibiting antitumor immune response. However, recently Yang side of MDSCs has also been worked out and suggests the role in maintenance of homeostasis during non-cancer situations like pregnancy, obesity, diabetes, and autoimmune disorders. Continued work in this area has armored the biological importance of these cells as master regulators of immune system and prompted scientists all over the world to look from a different perspective. Therefore, explicating Yin and Yang arms of MDSCs is obligatory to use it as a double edged sword in a much smarter way. This review is an attempt toward presenting a synergistic coalition of all the facts and controversies that exist in understanding MDSCs, bring them on the same platform and approach their "Yin and Yang" nature in a more comprehensive and coherent manner. © 2007 - 2018 Frontiers Media S.A.