Browsing by Author "Pawan K. Dubey"

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A comparative analysis of phytochemicals versus synthetic drugs/nanomedicines in the treatment of uterine fibroid: a systematic review
(Korean Society of Environmental Risk Assessment and Health Science, 2024) Sonal Upadhyay; Vivek Pandey; Anima Tripathi; Alakh N. Sahu; Anjali Rani; Amita Diwakar; Lavina Chaubey; Rashmi Gupta; Pawan K. Dubey
Most women experience uterine fibroids (UFs), a common benign gynecological tumor, at some point in their reproductive age. There are several pharmacological treatments available to shrink fibroids and lessen the UF symptoms. These medications cost a lot of money, though, and frequently have serious side effects. Therefore, due to their low cost, comparable and powerful therapeutic efficiency and lower side effects, phytochemical-based medications are gaining popularity in these days. This review's goal is to provide a summary of the knowledge that is currently unavailable regarding the mechanisms of the action of various phytochemical-based medications with anti-uterine fibroid efficacy. The present results showed that dietary phytocompounds (dehydroxyelephantopin, butein, capsaicin, fisetin, kaempferol, resveratrol, silibinin and curcumin) could probably be effective as therapeutic compounds for uterine leiomyoma. These phytochemicals indicated their capability to regulate main fibroid promoting and initiating events for instance, proliferation, inflammation, angiogenesis and fibrosis in various experimental setups through modulating various signaling pathways, such as Smad 2/3, PI3K/AKT/mTOR, ERK 1/2 and β-catenin indicating that they could serve as targets for prevention and/or treatment of UFs. This review provides key molecular insights for the development of phytochemical-based novel personalized therapy for non-surgical management of UFs which may help to avoid hysterectomy. © The Author(s), under exclusive licence to Korean Society of Environmental Risk Assessment and Health Science 2023.
Assisted reproductive technologies in infertility treatment: Opportunities and challenges
(Springer Singapore, 2017) Pawan K. Dubey; Anima Tripathi; Akhtar Ali
A tremendous rise in the fertility clinics providing ART services is seen worldwide with the birth of first IVF baby (Louise Joy Brown) in 1978. ART comprises various types of medical treatments designed to assist in achieving pregnancy. IVF and other ART-associated technologies of fertilization (ICSI, IUI, PZD, SUZI, MESA, and PESA) offer an opportunity to become parent even in severe cases of infertility. These technologies have allowed millions of individuals to fulfill their parenting wish. A positive attitude combined with an appropriate treatment can help most of the infertile couples experience the joy of parenthood. This chapter provides a thorough overview of the assisted reproductive technologies with opportunities for patients and challenges for clinical professionals or researchers. © Springer Nature Singapore Pte Ltd. 2017. All rights reserved.
Bandgap engineering in TiO2/rGO 1D photonic metasurfaces as broadband solar absorber
(American Institute of Physics Inc., 2022) Yash K. Saurabh; Priyanka A. Jha; Pawan K. Dubey; Pardeep K. Jha; Prabhakar Singh
Inability to use full solar energy, especially near infrared radiation (NIR: 780-1400 nm), is one of the major limitations for solar energy harvesting due to the narrow bandgap (electronic as well as photonic). In this work, we designed the 1D photonic metasurfaces of TiO 2 with reduced graphene oxide (rGO) in an attempt to obtain broader absorption bandwidth in NIR. Further, to realize this experimentally, graphene oxide reduced TiO 2 nanocomposites are synthesized using the hydrothermal method to form a quantum well. The composites are observed in the anatase phase of TiO 2 with graphitic reflection, and microstructural studies that indicate the conversion of TiO 2 nanoparticles into nanotubes with reduced graphene oxide intercalation forming a kind of self-assembled metasurfaces. UV-vis absorption studies indicate a significant reduction in bandgap energy; typically, the indirect bandgap reduces near to zero. The experimental and numerical simulation results suggest phonon scattering dominated free carrier absorption in NIR in the TiO 2/rGO metasurface leading to wide broadband absorption (700-10 000 nm). © 2022 Author(s).
Bioengineered dual fluorescent carbon nano dots from Indian long pepper leaves for multifaceted environmental and health utilities
(Springer Science and Business Media Deutschland GmbH, 2023) Debadatta Mohapatra; Ravi Pratap; Vivek Pandey; Singh Shreya; Gaurav Gopal Naik; Subhash C. Mandal; Sunday O. Otimenyin; Pawan K. Dubey; Avanish S. Parmar; Alakh N. Sahu
In this article, we present the synthesis of Piper longum leaves–derived ethanolic carbon dots (PLECDs) using the most simplistic environmentally friendly solvothermal carbonization method. The PLECDs fluoresced pink color with maximum emission at 670 nm at 397 nm excitation. Additionally, the dried PLECDs dissolved in water showed green fluorescence with higher emission at 452 nm at 370 nm excitation. The UV spectra showed peaks in the UV region (271.25 nm and 320.79 nm) and a noticeable tail in the visible region, signifying the efficient synthesis of nano-sized carbon particles and the Mie scattering effect. Various functional groups (–OH, –N–H, –C–H, –C = C, –C–N, and –C–O) were identified using Fourier transform infrared spectroscopy (FTIR). Its nanocrystalline property was revealed by the sharp peaks in the X-ray diffraction (XRD). High-resolution transmission electron microscopy (HRTEM) photomicrograph displayed a roughly spherical structure with a mean size of 2.835 nm. The energy dispersive X-ray (EDAX) and X-ray photoelectron spectroscopy (XPS) revealed the elemental abundance of C, O, and N. The high-performance thin-layer chromatography (HPTLC) fingerprint of PLECDs showed an altered pattern than its precursor (Piper longum leaves ethanolic extract or PLLEE). The PLECDs sensed Cu2+ selectively with a limit of detection (LOD) and limit of quantification (LOQ) of 0.063 μM and 0.193 μM, respectively. It showed excellent cytotoxicity toward MDA-MB-231 (human breast cancer), SiHa (human cervical carcinoma), and B16F10 (murine melanoma) cell lines with excellent in vitro bioimaging outcomes. It also has free radical scavenging activity. The PLECDs also showed outstanding bacterial biocompatibility, pH-dependent fluorescence stability, photostability, physicochemical stability, and thermal stability. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Bioinformatics enrichment analysis of genes and pathways related to maternal type 1 diabetes associated with adverse fetal outcomes
(Elsevier Inc., 2020) Ravi Bhushan; Anjali Rani; Akhtar Ali; Vinay Kumar Singh; Pawan K. Dubey
Maternal type 1 diabetes mellitus (T1DM) may affect fetal development by altering the gene expression profile of the umbilical cord. The present study aimed to explore the T1DM-induced gene expression changes in the fetal umbilical cord. The raw gene expression profiles (ID: GSE51546) of umbilical cord tissue obtained from six normal mothers (non-diabetic) and six type 1 diabetic mothers were used to identify the differentially expressed genes. Genes that correspond to official gene symbols were selected for protein-protein interaction (PPI) and sub-network construction (combined score > 0.4). Functional annotation for Gene Ontology (GO) and pathway enrichment analysis were performed for genes involved in networking. A total of 110 differentially expressed genes were identified of which 38 were up-regulated while 72 were down-regulated. Only 37 genes were identified to significantly interact with each other. Hub genes including HSPA4, KCTD6, UBE2G1, FBXL19, and EHMT1 were up-regulated while KBTBD7, TRIM32, and NUP were down-regulated. T1DM had a major effect on the expression of genes involved in cellular death and differentiation, cell signaling and communication, protein modification and regulation of GTPase activity. Total 27 pathways were enriched and genes related to Wnt signaling, VEGF signaling, inflammation mediated by chemokine and cytokine signaling pathways, FGF signaling pathways and GnRH receptor pathways were found significantly affected by T1DM. Our results suggest that the T1DM environment seems to alter umbilical cord gene expression involved in the regulation of pathophysiology of the diabetic mother which in turn may lead to long-term consequences in various tissues in infants. This study provides insight into the molecular mechanism underlying the adverse pregnancy outcomes of maternal T1DM. © 2020 Elsevier Inc.
Carbon dots from an immunomodulatory plant for cancer cell imaging, free radical scavenging and metal sensing applications
(Future Medicine Ltd., 2021) Debadatta Mohapatra; Md. Bayazeed Alam; Vivek Pandey; Ravi Pratap; Pawan K. Dubey; Avanish S. Parmar; Alakh N. Sahu
Aim: This work aimed to develop Tinospora cordifolia stem-derived carbon dots (TCSCD) for cancer cell imaging, free radical scavenging and metal sensing applications. Method: The TCSCDs were synthesized by a simple, one-step, and ecofriendly hydrothermal carbonization method and characterized for their optical properties, morphology, hydrodynamic size, surface functionality, crystallinity, stability, bacterial biocompatibility, in vitro cellular imaging, free radical scavenging and metal sensing ability. Results: The TCSCDs exhibited excellent biocompatibility with dose-dependent bioimaging results in melanoma (B16F10) and cervical cancer (SiHa) cell lines. They exerted good free radical scavenging, Fe3+ sensing, bacterial biocompatibility, photostability, colloidal dispersion stability and thermal stability. Conclusion: The results reflect the potential of TCSCDs for biomedical and pharmaceutical applications. © 2021
Comparative study on characterization and wound healing potential of goat (Capra hircus) mesenchymal stem cells derived from fetal origin amniotic fluid and adult bone marrow
(Elsevier B.V., 2017) M.D. Pratheesh; Pawan K. Dubey; Nitin E. Gade; Amar Nath; T.B. Sivanarayanan; D.N. Madhu; Anjali Somal; Indu Baiju; T.R. Sreekumar; V.L. Gleeja; Irfan A. Bhatt; Vikash Chandra; Amarpal; Bhaskar Sharma; G. Saikumar; G. Taru Sharma
Caprine amniotic fluid (cAF) and bone marrow cells (cBM) were isolated, expanded and phenotypically characterized by mesenchymal stem cells (MSCs) specific cell surface markers. Both cell types were compared for multilineage differentiation potential by flow cytometry using specific antibodies against lineage specific markers. Furthermore, in vitro expanded cAF-MSCs showed higher expression of trophic factors viz. VEGF and TGF-β1 as compared to cBM-MSCs. Full-skin thickness excisional wounds created on either side of the dorsal midline (thoracolumbar) of New Zealand White rabbits were randomly assigned to subcutaneous injection of either fetal origin cAF-MSCs (n = 4) or adult cBM-MSCs (n = 4) or sterile PBS (control, n = 4). The rate of wound closure was found faster (p < 0.05) in cAF-MSCs treated wounds as compared with cBM-MSCs and PBS treated wounds especially on 21st day post-skin excision. Histomorphological examination of the healing tissue showed that wound healing was improved (p < 0.05) by greater epithelialization, neovascularization and collagen development in cAF-MSCs as compared to cBM-MSCs and PBS treated wounds. © 2017 Elsevier Ltd
Correction: Intervention of Phytochemicals During Endometriosis and Their Conceivable Mechanisms (Revista Brasileira de Farmacognosia, (2023), 33, 6, (1126-1140), 10.1007/s43450-023-00426-2)
(Springer Science and Business Media Deutschland GmbH, 2023) Safiya Ayesha; Alka Sharma; Jayhind Kumar Chauhan; Vivek Pandey; Garima Tripathi; Pawan K. Dubey; Anima Tripathi
The graphical abstract in the original online version of this article was incorrect. It has been corrected. © 2023, The Author(s) under exclusive licence to Sociedade Brasileira de Farmacognosia.
Deoxyelephantopin, a novel naturally occurring phytochemical impairs growth, induces G2/M arrest, ROS-mediated apoptosis and modulates lncRNA expression against uterine leiomyoma
(Elsevier Masson s.r.l., 2020) Vivek Pandey; Anima Tripathi; Anjali Rani; Pawan K. Dubey
Deoxyelephantopin (DOE), a phytochemical, extracted and purified from Elephantopus scaber, has been shown to exhibit antitumor activities. Objective of the present study was to investigate anti-tumor and apoptosis-inducing properties of DOE against uterine leiomyoma (UL) and to explore their molecular mechanisms. Primary cell cultures from fresh UL tissue were established and maintained up to 12 passages. The cells exhibited continuous proliferation with 24 -h doubling time until 12 passages and was then subjected to molecular characterization. The growth inhibitory effect of DOE on UL cells was confirmed by colony formation, cellular senescence, AO/PI and DAPI staining. Fluorescent-activated cell sorting (FACS) assay for apoptosis and cell cycle arrest analysis revealed that DOE significantly (p < 0.05) inhibited the UL cell proliferation via cell cycle arrest at G2/M phase and induced apoptosis via ROS production by lowering mitochondrial membrane potential. Subsequently, the DOE induced ROS was markedly attenuated by co-treatment of N-Acetyl-Cysteine (NAC). Our quantitative RT-PCR and western blot results showed up-regulation of Bax, Caspase-3 and down-regulation of Bcl2, P53, αSMA, COL4A2, VEGF, PCNA, Cyclin B1 and oncogenic lncRNAs (H19, HOTAIR, BANCR and ROR) in DOE treated UL cells which further strengthen our findings. In conclusion, DOE inhibits growth of UL cells via cell cycle arrest at G2/M phase, induces ROS-dependent caspase-3-mediated mitochondrial intrinsic apoptotic pathway and down-regulation of oncogenic lncRNA in UL cells. Our findings suggest that DOE deserves for further systematic investigation in the uterine leiomyoma animal model as a novel apoptosis inducer for potential applications in the prevention or treatment of uterine leiomyoma. © 2020 The Authors
Di-(2-ethylhexyl) phthalate (DEHP) inhibits steroidogenesis and induces mitochondria-ROS mediated apoptosis in rat ovarian granulosa cells
(Royal Society of Chemistry, 2019) Anima Tripathi; Vivek Pandey; Alakh N. Sahu; Alok Singh; Pawan K. Dubey
Increased oxidative stress (OS) due to ubiquitous exposure to di-(2-ethylhexyl) phthalate (DEHP) can affect the quality of oocytes by inducing apoptosis and hampering granulosa cell mediated steroidogenesis. This study was carried out to investigate whether DEHP induced OS affects steroidogenesis and induces apoptosis in rat ovarian granulosa cells. OS was induced by exposing granulosa cells to various concentrations of DEHP (0.0, 100, 200, 400 and 800 μM) for 72 h in vitro. Intracellular reactive oxygen species (ROS), oxidative stress (OS), mitochondrial membrane potential, cellular senescence, apoptosis, steroid hormones (estradiol & progesterone) and gene expression were analyzed. The results showed that an effective dose of DEHP (400 μg) significantly increased OS by elevating the ROS level, mitochondrial membrane potential, and β-galactosidase activity with higher mRNA expression levels of apoptotic genes (Bax, cytochrome-c and caspase3) and a lower level of an anti-apoptotic gene (Bcl2) as compared to the control. Further, DEHP significantly (P > 0.05) decreased the level of steroid hormones (estradiol and progesterone) in a conditioned medium and this effect was reciprocated with a lower expression (P > 0.05) of steroidogenic responsive genes (Cyp11a1, Cyp19A1, Star, ERβ1) in treated granulosa cells. Furthermore, co-treatment with N-Acetyl-Cysteine (NAC) rescues the effects of DEHP on OS, ROS, β-galactosidase levels and gene expression activities. Altogether, these results suggest that DEHP induces oxidative stress via ROS generation and inhibits steroid synthesis via modulating steroidogenic responsive genes, which leads to the induction of apoptosis through the activation of Bax/Bcl-2-cytochrome-c and the caspase-3-mediated mitochondrial apoptotic pathway in rat granulosa cells. © 2019 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
Differential gene expression profile evaluation between uterine leiomyoma and leiomyosarcoma using a machine learning approach
(KeAi Communications Co., 2023) Sonal Upadhyay; Ravi Bhushan; Anima Tripathi; Lavina Chaubey; Amita Diwakar; Pawan K. Dubey
Objective: The objective of this study is to differentiate between uterine leiomyomas (ULM) and uterine leiomyosarcomas (ULMS) by conducting molecular differential analysis and identifying potential prognostic biomarkers for diagnosis. Methods: The microarray datasets (GSEID: GSE64763 and GSE185543) were retrieved from the Gene Expression Omnibus database. Data preprocessing and differential gene expressions (DEGs) analysis were performed. The DEGs were further intersected to find the common DEGs in ULM and ULMS and further validation of selected DEGs were performed. Further, a machine learning classifier was also applied in the selection of biomarkers. Protein-protein interaction network based upon STRING v 10.5, was constructed. Additionally, Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses were also performed to dissect possible functions and pathways. Results: A total of 50 significant DEGs for ULM while 321 DEGs for ULMS have been identified with their official gene symbol. Between ULM and ULMS, a total of 14 common DEGs were identified of which 8 were up-regulated while 6 were down-regulated. The DEGs of (GSE185543) were also analyzed and the significant genes were retrieved common in both datasets for further analysis. Using a machine learning approach, 10 feature genes were identified. Using the expression profiles of these genes, a sequential minimal optimization (SMO) prediction model was built on the training set, and it accurately and reliably classified features expression in ULM and ULMS in the independent test set. Furthermore, Co- Enrichment analysis was also performed. Conclusion: The study identified several DEGs, including ZNF365, EPYC, COL11A1, SHOX2, MMP13, TNN, GPM6A, and GATA2, through cross-validation, machine learning classifier, and Co- Enrichment analysis. These candidate disease genes may provide valuable insight into the underlying mechanisms and could be used as potential diagnostic biomarkers for ULM and ULMS. However, further validation of these genes is necessary to better understand their roles in the pathogenesis of ULM and ULMS. © 2023 The Authors
Encircling granulosa cells protects against di-(2-ethylhexyl)phthalate-induced apoptosis in rat oocytes cultured in vitro
(Cambridge University Press, 2019) Anima Tripathi; Vivek Pandey; A.N. Sahu; Alok K. Singh; Pawan K. Dubey
The present study investigated if the presence of encircling granulosa cells protected against di(2-ethylhexyl)phthalate (DEHP)-induced oxidative stress in rat oocytes cultured in vitro. Denuded oocytes and cumulus-oocyte complexes (COCs) were treated with or without various doses of DEHP (0.0, 25.0, 50.0, 100, 200, 400 and 800 μM) in vitro. Morphological apoptotic changes, levels of oxidative stress and reactive oxygen species (ROS), mitochondrial membrane potential, and expression levels of apoptotic markers (Bcl2, Bax, cytochrome c) were analyzed. Our results showed that DEHP induced morphological apoptotic changes in a dose-dependent manner in denuded oocytes cultured in vitro. The effective dose of DEHP (400 Âg) significantly (P>0.05) increased oxidative stress by elevating ROS levels and the mitochondrial membrane potential with higher mRNA expression and protein levels of apoptotic markers (Bax, cytochrome c). Encircling granulosa cells protected oocytes from DEHP-induced morphological changes, increased oxidative stress and ROS levels, as well as increased expression of apoptotic markers. Taken together our data suggested that encircling granulosa cells protected oocytes against DEHP-induced apoptosis and that the presence of granulosa cells could act positively towards the survival of oocytes under in vitro culture conditions and may be helpful during assisted reproductive technique programmes. © Cambridge University Press 2019.
Evaluation of canine bone marrow-derived mesenchymal stem cells for experimental full-thickness cutaneous wounds in a diabetic rat model
(Taylor and Francis Ltd., 2021) Deepika Bist; A.M. Pawde; Amarpal; Prakash Kinjavdekar; Reena Mukherjee; K.P. Singh; Med Ram Verma; Khan Sharun; Amit Kumar; Pawan K. Dubey; Divya Mohan; Amit Verma; G. Taru Sharma
Background: The wound healing potential of canine bone marrow-derived mesenchymal stem cells (BMSCs) was evaluated in the excisional wound of streptozotocin-induced diabetic rats. Research design and methods: Xenogenic BMSCs were collected aseptically from the iliac crest of healthy canine donors under general anesthesia. Full-thickness experimental wounds (20 × 20 mm2) on the dorsum of forty-eight adult healthy Wistar white rats. The wounds were assigned randomly to three treatment groups: PBS (Group A) or BMSCs (Group B) injected into the wound margins on days 0, 7, and 14 or BMSCs (Group C) injected into the wound margins on days 7, 14, and 21 post-wounding. The degree of wound healing was evaluated based on macroscopical, hemato-biochemical, histopathological, and histochemical parameters. Results: The results indicated granulation tissue formation with reduced exudation and peripheral swelling in the treatment groups compared to the control group A. Similarly, the degree of wound contraction was significantly higher in groups B and C animals than group A on days 14 and 21 post-wounding. The transplantation of BMSCs resulted in early drying of wounds, granulation tissue appearance, and enhanced cosmetic appearance. Conclusion: The histopathological, histochemical, and gross findings suggested the therapeutic potential of xenogeneic mesenchymal stem cell therapy in managing diabetic wounds. Abbreviations: BMSCs-bone marrow-derived mesenchymal stem cells, PBS-phosphate-buffered saline, MSCs-mesenchymal stem cells, FBS-fetal bovine serum, ECM-extracellular matrix. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
Evaluation of persistence and distribution of intra-dermally administered PKH26 labelled goat bone marrow derived mesenchymal stem cells in cutaneous wound healing model
(Springer Netherlands, 2017) M.D. Pratheesh; Nitin E. Gade; Amar Nath; Pawan K. Dubey; T.B. Sivanarayanan; D.N. Madhu; T.R. Sreekumar; Amarpal; G. Saikumar; G. Taru Sharma
The current study was designed to study the persistence and distribution of caprine bone marrow derived mesenchymal stem cells (cBM-MSCs) when administered intra-dermally in experimentally induced cutaneous wounds in rabbits. MSC’s from goat bone marrow were isolated and their differentiation potential towards adipogenic and osteogenic lineages were assayed in vitro. The isolated cells were phenotypically analysed using flow cytometry for the expression of MSC specific matrix receptors (CD73, CD105 and Stro-1) and absence of hematopoietic lineage markers. Further, these in vitro expanded MSCs were stained with PKH26 lipophilic cell membrane red fluorescent dye and prepared for transplantation into cutaneous wounds created on rabbits. Five, 2 cm linear full thickness skin incisions were created on either side of dorsal midline of New Zealand white rabbits (n = 4). Four wounds in each animal were implanted intra-dermally with PKH26 labelled cBM-MSCs suspended in 500 µl of Phosphate Buffer Saline (PBS). Fifth wound was injected with PBS alone and treated as negative control. The skin samples were collected from respective wounds on 3, 7, 10 and 14 days after the wound creation, and cryosections of 6 µM were made from it. Fluorescent microscopy of these cryosections showed that the PKH26 labelled transplanted cells and their daughter cells demonstrated a diffuse pattern of distribution initially and were later concentrated towards the wound edges and finally appeared to be engrafted with the newly developed skin tissues. The labelled cells were found retained in the wound bed throughout the period of 14 days of experimental study with a gradual decline in their intensity of red fluorescence probably due to the dye dilution as a result of multiple cell division. The retention of transplanted MSCs within the wound bed even after the complete wound healing suggests that in addition to their paracrine actions as already been reported, they may have direct involvement in various stages of intricate wound healing process which needs to be explored further. © 2017, Springer Science+Business Media Dordrecht.
Expression and intracellular localization of Nanos2-homologue protein in primordial germ cells and spermatogonial stem cells
(Cambridge University Press, 2019) Vivek Pandey; Anima Tripathi; Pawan K. Dubey
The decision by germ cells to differentiate and undergo either oogenesis or spermatogenesis takes place during embryonic development and Nanos plays an important role in this process. The present study was designed to investigate the expression patterns in rat of Nanos2-homologue protein in primordial germ cells (PGCs) over different embryonic developmental days as well as in spermatogonial stem cells (SSCs). Embryos from three different embryonic days (E8.5, E10.5, E11.5) and SSCs were isolated and used to detect Nanos2-homologue protein using immunocytochemistry, western blotting, reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. Interestingly, Nanos2 expression was detected in PGCs at day E11.5 onwards and up to colonization of PGCs in the genital ridge of fetal gonads. No Nanos2 expression was found in PGCs during early embryonic days (E8.5 and 10.5). Furthermore, immunohistochemical and immunofluorescence data revealed that Nanos2 expression was restricted within a subpopulation of undifferentiated spermatogonia (As, single type A SSCs and Apr, paired type A SSCs). The same results were confirmed by our western blot and RT-PCR data, as Nanos2 protein and transcripts were detected only in PGCs from day E11.5 and in undifferentiated spermatogonia (As and Apr). Furthermore, Nanos2-positive cells were also immunodetected and sorted using flow cytometry from the THY1-positive SSCs population, and this strengthened the idea that these cells are stem cells. Our findings suggested that stage-specific expression of Nanos2 occurred on different embryonic developmental days, while during the postnatal period Nanos2 expression is restricted to As and Apr SSCs. © 2019 Cambridge University Press.
Gene variants polymorphisms and uterine leiomyoma: an updated review
(Frontiers Media SA, 2024) Sonal Upadhyay; Pawan K. Dubey
Uterine leiomyoma, commonly referred to as fibroids, is a benign tumor that develops in the muscular wall of the uterus. These growths are non-cancerous and can vary in size, ranging from tiny nodules to larger masses. Uterine leiomyomas often occur during a woman’s reproductive years and can lead to symptoms such as heavy menstrual bleeding, pelvic pain, and pressure on nearby organs. While the exact cause is not fully understood, hormonal factors, particularly estrogen and progesterone, are believed to play a role in their development. The exploration of connections between genetic variants and uterine leiomyoma has captivated scientific attention for numerous years. The results from investigations remain a subject of intrigue within the scientific community. To date, the findings regarding the relationships between single nucleotide polymorphisms (SNPs) and uterine leiomyoma have exhibited some inconsistencies. However, amidst these inconsistencies, several promising outcomes have emerged that hold the potential to shape future research endeavors. These promising leads could pave the way for the development of innovative targeted therapies and novel prognostic biomarkers. This review specifically centers on accentuating the existing literature data concerning genetic variants that have been explored for their potential connections to uterine leiomyoma. Additionally, it underscores the prospects of employing genetic variations as diagnostic and prognostic biomarkers for individuals diagnosed with uterine leiomyoma. Copyright © 2024 Upadhyay and Dubey.
Genetic variants related to insulin metabolism are associated with gestational diabetes mellitus
(Elsevier B.V., 2024) Ravi Bhushan; Shafiul Haque; Rakesh Kumar Gupta; Anjali Rani; Amita Diwakar; Sakshi Agarwal; Anima Tripathi; Pawan K. Dubey
The current study sought to investigate the associations of common genetic risk variants with gestational diabetes mellitus (GDM) risk in the north Indian population and to evaluate their utility in identifying GDM cases. A case-control study, including 300 pregnant women, was included, and clinical and pathological information was collected. The amplification-refractory mutation system (ARMS) was used for genotyping four single nucleotide polymorphisms (SNPs), namely FTO (rs9939609), PPARG2 (rs1801282), SLC30A8 (rs13266634), and TCF7L2 (rs12255372). The odds ratio and confidence interval were determined for each SNP in different genetic models. Further, attributable risk, population penetrance, and relative risk were also calculated. The risk allele A of FTO (rs9939609) poses a two times higher risk of GDM (p = 0.02, OR = 2.5). The CG and GG genotypes of PPARG2 (rs1801282) have half a lower risk of GDM. In SLC30A8 (rs13266634), the recessive model analysis showed a two times higher risk of having GDM, while the recessive model (TT vs. GG + GT) analysis in TCF7L2 (rs12255372) indicates a lower risk of GDM. Finally, the relative risk, population penetrance, and attributable risk for risk allele in all four variants was higher in GDM mothers. All four polymorphisms were found to be significantly associated with BMI, HbA1c, and insulin. Our study first time confirmed a significant association with GDM for four variants, FTO, PPARG2, SLC30A8, and TCF7L2, in the North Indian population. © 2024 Elsevier B.V.
Homology modelling and docking study of SUZ12, a subunit of PRC2 complex, with naturally occurring plant compounds
(Advanced Scientific Research, 2020) Garima Jain; Ravi Bhushan; Pawan K. Dubey; Parimal Das
PRC2 is a transcriptional repressive complex and its inhibitors have been found to have a potential role in cancer therapeutics. In this study, SUZ12-a subunit of PRC2 complex was studied with the help of protein-ligand docking for various naturally occurring plant steroids and flavonoids. The structure of SUZ12 was modeled by homology modeling tool and validated with the help of various computational tools. The best model was selected based on the percentage of residues that are present in either of favored, allowed or disallowed regions using the Ramachandran Plot. This was further followed by docking studies with plant-based flavonoids and phytosterols (Tangeritin, Apigenin, Diosgenin, Luteolin, and Guggulsterone) using Patchdock and YASARA docking software. Luteolin and Guggultserone were observed to have the highest binding energies towards SUZ12 and Tageratin scored the lowest. Luteolin, Guggulsterone, and apigenin showed binding at the zinc finger domain. Thus, this virtual screening for binding of various compounds identified that luteolin and apigenin might disrupt the secondary structure of SUZ12 protein and thus hamper the functioning of PRC2. This analysis can be further used for the designing of potent drugs against diseases caused by hyperactivation of the PRC2 complex, thereby aiding knowledge in the field of research. © 2020, Advanced Scientific Research. All rights reserved.
Identification and molecular characterization of genes modulating progression of an oocyte from M-I to M-II in rat ovary
(John Wiley and Sons Inc, 2024) Alka Sharma; Pawan K. Dubey; Pradeep Kumar; Kavindra Nath Tiwari; Anima Tripathi
Background: To achieve oocyte competence for successful fertilization, bidirectional communication between oocyte and granulosa cells is crucial. The acquisition of meiotic competency in oocyte is facilitated by various regulatory genes however, expression pattern of these genes is not well documented during meiotic transition from Metaphase-I to Metaphase-II stage. Therefore, the present research analyzed the expression pattern of regulatory genes that are involved in the transition from M-I to M-II stages in rat oocyte. Methods: The analysis of the data was conducted by applying an array of bioinformatic tools. The investigation of gene group interactions was carried out by employing the STRING database, which relies on co-expression information. The gene ontology (GO) analysis was performed utilizing the comparative GO database. Functional annotation for GO and pathway enrichment analysis were performed for genes involved in networking. The GO obtained through computational simulations was subsequently validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Results: The findings of our study suggest that there is a distinct gene expression pattern in both the oocyte and granulosa cells. This pattern indicates that oocyte-secreted factors, such as BMP15 and GDF9, play a crucial role in regulating the progression of the meiotic cell cycle from the M-I to M-II stages. We have also examined the level of mRNA expression of genes including CYP11A1, CYP19A1, and STAR, which are crucial for the steroidogenesis. Conclusions: It is fascinating to observe that the oscillatory pattern of specific key genes may hold significance in the process of in vitro oocyte maturation, specifically during the transition from the M-I to M-II stage. It might be useful for determining biomarker genes and potential pathways that play a role in attaining oocyte competency, thereby aiding in the assessment of oocyte quality for the purpose of achieving successful fertilization. © 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
In Vitro Cancer Cell Imaging, Free Radical Scavenging, and Fe3+ Sensing Activity of Green Synthesized Carbon Dots from Leaves of Piper longum
(Springer, 2023) Debadatta Mohapatra; Ravi Pratap; Vivek Pandey; Singh Shreya; Prakash Ch. Senapati; Pawan K. Dubey; Avanish S. Parmar; Alakh N. Sahu
The development of carbon dots via a green synthesis approach from natural products is one of the most researched areas nowadays. Herein, we present the synthesis of Piper longum leaves-derived aqueous carbon dots (PLACDs) via the simplest ecofriendly hydrothermal carbonization method. The PLACDs exhibited excitation-dependent emission behavior with maximum emission at 450 nm at an excitation wavelength of 365 nm. The High-Resolution Transmission Electron Microscopy results showed a quasi-spherical shape with an average size of 4.121 nm. The sharp diffractions of X-ray diffraction revealed its nanocrystalline property. The Energy Dispersive X-ray spectra reflected the presence of carbon, nitrogen, and oxygen. The Fourier-Transform Infrared Spectroscopy disclosed the existence of –OH, –C=C, –C=O, and –C–O–C groups. The PLACDs presented excellent biocompatibility against B16F10 (melanoma) and SiHa (cervical carcinoma) cells lines with concentration-dependent in vitro bioimaging results. It also exhibited antiradical activity with the IC50 value of 0.499 mg/mL and 0.051 mg/mL against DPPH and ABTS.+, respectively. It showed Fe3+ sensing with a lower limit of detection of 0.673 μM. Further, the PLACDs displayed excellent bacterial biocompatibility, pH-dependent fluorescence property, fluorescent ink property, photostability, physical, chemical, and thermal stability. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.