Browsing by Author "Sonal Tiwari"

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Association of intronic variants (Apal and Bsml) of vitamin D receptor gene with uterine leiomyoma among North Indian women
(Elsevier B.V., 2025) Sonal Tiwari; Rakesh Kumar Gupta; Sakshi Agarwal; Amita Diwakar; Arun K. Bind; Pawan Kumar Dubey
Background: Understanding the genetic factors involved in the Uterine Leiomyoma (UL) development is crucial for exploring the complexities of UL disorders. This study aimed to examine genetic association between UL incidence and intronic polymorphisms of vitamin D receptor gene in north Indian population. Methodology: Total 200 subjects (100 healthy women and 100 with uterine leiomyomas) of age- and gender-matched control subjects, were genotyped for BsmI (rs1544410) and ApaI (rs7975232) polymorphisms in the VDR gene using TETRA ARMS PCR, followed by Sanger sequencing validation. Levels of VDR mRNA and vitamin D were also assessed through quantitative real-time PCR and ELISA respectively. The association of these variants with leiomyomas was analyzed, along with clinico-pathological (obesity) association. Results: ApaI revealed a significant association with UL, especially for the TG genotype (OR = 2.38; 95 % CI, 1.26–––4.51; p = 0.003). In a similar manner, ApaI is associated with an increased risk for UL with all three genetic models. Comparing VDR ApaI polymorphism between obese and non-obese patients revealed that AC genotype was significantly (OR = 3.71; 95 % CI, 1.53––9.11; p = 0.002) associated with a reduced risk of UL in non-obese patients. The expression of VDR mRNA was two times lower in patients with UL (p < 0.001), along with decreased serum vitamin D levels (p < 0.001). A significant association was also observed between VDR ApaI variant with reduced mRNA expression, vitamin D level and obesity. However, no associations were observed among Bsm1 VDR genotypes and ULs. Conclusion: This study found significant association between the VDR intronic ApaI polymorphism (rs7975232) and the incidence of UL. This VDR variant showed significant association with reduced VDR mRNA expression and serum vitamin D levels in UL patients. However, no significant association was observed between BsmI VDR polymorphism (rs1544410) and UL in North Indian women. © 2025 Elsevier B.V.
Genetic association of vitamin D receptor polymorphisms (ApaI, BsmI, and FokI) with gestational diabetes mellitus in North Indian women: a case–control study
(BioMed Central Ltd, 2025) Rakesh Kumar Gupta; Sonal Tiwari; Sakshi Agarwal; Amita Diwakar; Pawan Kumar Dubey
Background: Gestational diabetes mellitus (GDM) affects nearly 14% of pregnancies and imposes an increased risk of adverse outcomes for both pregnant women and their developing babies. This study examined the genetic association of vitamin D receptor (VDR) variants (ApaI, BsmI, and FokI) with GDM in the North Indian population. Methods: Tetra-ARMS PCR was used for genotyping of VDR variants followed by Sanger sequencing validation. The genotypes of VDR variants, Odds ratio (OR) and confidence interval (CI) were further analyzed in GDM and determined by different genetic models. Results: The C allele of ApaI (rs7975232) genotype significantly associated with increased risk of GDM compared to the TT genotype carrying pregnant women. The A allele of BsmI, and A allele of FokI genotypes was found as a risk factor for GDM. Sanger sequencing confirmed the changes in ApaI (T/C), BsmI (A/G), and FokI (A/G) gene sequence which linked to GDM. The circulatory vitamin D3 levels were significantly lower in GDM patients whereas, homozygous genotypes of ApaΙ (CC, P < 0.0884), BsmI (GG, P < 0.8192) and FokI (GG, P < 0.0303) was associated with vitamin D deficiency. On other hand, mother age, blood glucose and glycated haemoglobin (HbA1c) were significantly higher in the GDM group vs. the control group. Conclusion: VDR ApaI (rs7975232) and FokI (rs2228570) polymorphisms, HbA1c level, and vitamin D are associated with the risk of GDM in the north Indian population. Considering the impact of vitamin D3 level, it is suggested that pregnant Indian women must consider vitamin D supplementation during pregnancy. © The Author(s) 2025.
Shatavarin-IV rescues the Di (2-ethylhexyl) phthalate (DEHP) induced oxidative stress in rat granulosa cells in vitro
(Elsevier Inc., 2024) Vivek Pandey; Alka Sharma; Sonal Tiwari; Yashvant Patel; Jayhind Kumar Chauhan; Safiya Ayesha; Alakh N. Sahu; Rashmi Gupta; Anima Tripathi; Pawan K. Dubey
Studies provide notable evidence that oxidative stress (OS) mediated reactive oxygen species (ROS) disturb reproductive health. We have shown in our previous publication that exposure of Di-(2-ethylhexyl) phthalate (DEHP), induces OS mediated ROS generation which inhibits steroid synthesis. In the present study, we demonstrated the ameliorative/protective effects of one of the steroidal saponins, i.e., Shatavarin-IV, isolated from the roots of Asparagus racemosus against DEHP induced OS in rat granulosa cells. Granulosa cells were exposed with DEHP alone (400 μM), Shatavarin-IV alone (8 μg/ml), and a combination of DEHP + Shatavarin-IV (400 μM + 8 μg/ml) in vitro for 24 hrs. Intracellular ROS, OS/hypoxia, mitochondrial membrane potential, steroid-responsive genes expression were analyzed. The results revealed that the effective dose of DEHP (400 µg) significantly increased OS compared to the control by increasing ROS levels, mitochondrial membrane potential, and β-galactosidase activity with a higher level of apoptotic genes (Bax, Caspase-3) expression at mRNA level. Further, DEHP significantly (p < 0.05) reduced mRNA expression of steroidogenic responsive genes (StAR, CYP17A1, and CYP19A1) in granulosa cells treated with above combination compared to control. Interestingly, co-treatment of DEHP + Shatavarin-IV significantly suppressed the DEHP induced OS, ROS, β-galactosidase levels and enhanced steroidogeneic and apoptotic gene expression activities, which suggests that Shatavarin-IV rescued DEHP-induced changes that may useful for the prevention of DEHP- induced reproductive toxicity. © 2024 Elsevier Inc.
THPM (1,2,3,4-Tetrahydro pyrimidine) and Berberine Exhibit Synergistic Impact on Inhibition of Cell Migration and Colonization Through ROS-Mediated Apoptotic Pathways in the Breast Cancer Cells
(John Wiley and Sons Inc, 2025) Rakesh Kumar Gupta; Ambarish Priyadarshan; Sonal Tiwari; Yashvant Patel; Arun K. Bind; Garima Tripathi; Anima Tripathi; Abhijeet Kumar; Pawan Kumar Dubey
Breast cancer is one of the major causes of death in females worldwide. Considering the polypharmacological trend, small molecules like pyrimidine along with berberine, a bioactive anticancer agent may act as effective anticancer drugs having multiple targets with minimal side effects. However, it has never been tested. The present work discloses the efficacy of the combination of 1,2,3,4,-Tetrahydro pyrimidine (THPM) and Berberine (BBR) in inhibiting cancer progression in human breast cancer cell line, i.e., MCF-7. THPM were synthesized and characterized, and their anti-cancerous potential was evaluated by in silico study. The MCF-7 cells were exposed in vitro with THPM (200 µM), BBR (20 µM/ml) alone or in combination of THPM + BBR (200 µm + 20 µm/ml) for 24 h. Intracellular ROS, annexin-V staining, cell migration, colony formation assay, and gene expression analysis were performed. THPM and BBR both exhibited solid binding affinity against the BCL-2 protein. Interestingly, co-treatment of THPM + BBR significantly increased ROS level, annexin-V positive cells, the expression level of Bax, and Caspase-3 and inhibited migration and proliferation of MCF-7 cells. In conclusion, co-treatment of THPM + BBR exhibits a synergistic impact via inhibiting cell proliferation and inducing ROS-mediated apoptosis in MCF-7 cells suggesting that THPM and BBR could be used as novel therapeutic agents against breast cancer. © 2025 Wiley-VCH GmbH.