Department Of Human Genetics And Molecular Medicine
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Item Design, Synthesis, and Anticancer Evaluation of Hemithioindigos via Inhibition of Human Topoisomerases(John Wiley and Sons Inc, 2023-11-06T00:00:00) Kaur, Manpreet; Suman, Prabhat; Arora, Sahil; Singh, Tashvinder; Munshi, Anjana; Singh, Sandeep; Kumar, RajHemithioindigos were designed as topoisomerase inhibitors, synthesized, and evaluated for their anticancer properties against lung (A549) and breast (MDA-MB-468 and MCF7) cancer cell lines. Among all the synthetics, three compounds exerted potential anticancer effects on A549 (lung) and MCF7 (breast) cancer cell lines at low micromolar concentrations. The results revealed that two of these compounds blocked the cancer cells at the G1/S phase, while the third compound showed moderate G2/M inhibition, leading to necrotic cell death. Finally, the topoisomerase inhibition assays revealed their potent Topo I/II inhibitory actions as one of the primary anticancer mechanisms. Molecular docking studies further corroborated these findings. � 2023 Wiley-VCH GmbH.Item Neuroimaging Genomics a Predictor of Major Depressive Disorder (MDD)(Springer, 2023-11-22T00:00:00) Jindal, Manav; Chhetri, Aakash; Ludhiadch, Abhilash; Singh, Paramdeep; Peer, Sameer; Singh, Jawahar; Brar, Rahatdeep Singh; Munshi, AnjanaDepression is a complex psychiatric disorder influenced by various genetic and environmental factors. Strong evidence has established the contribution of genetic factors in depression through twin studies and the heritability rate for depression has been reported to be 37%. Genetic studies have identified genetic variations associated with an increased risk of developing depression. Imaging genetics is an integrated approach where imaging measures are combined with genetic information to explore how specific genetic variants contribute to brain abnormalities. Neuroimaging studies allow us to examine both structural and functional abnormalities in individuals with depression. This review has been designed to study the correlation of the significant genetic variants with different regions of neural activity, connectivity, and structural alteration in the brain as detected by imaging techniques to understand the scope of biomarkers in depression. This might help in developing novel therapeutic interventions targeting specific genetic pathways or brain circuits and the underlying pathophysiology of depression based on this integrated approach can be established at length. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Betaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO?1/NLRP3 and TGF-? expression(John Wiley and Sons Inc, 2023-10-16T00:00:00) Patel, Dhaneshvaree; Yadav, Poonam; Singh, Sumeet K.; Tanwar, Sampat S.; Sehrawat, Abhishek; Khurana, Amit; Bhatti, Jasvinder S.; Navik, UmashankerDoxorubicin (Dox) is an anthracycline antibiotic used to treat various cancers and shows severe toxicity in multiple organ systems, including kidneys. Evidence shows that betaine's antioxidant and anti-inflammatory properties could prevent the onset of several disorders. Hence, the present study aims to investigate the therapeutic potential of betaine on Dox-induced nephrotoxicity (DIN). Nephrotoxicity was induced in male Sprague Dawley rats using Dox at a dose of 4 mg/kg (cumulative dose: 20 mg/kg) by the intraperitoneal route and cotreated with betaine through oral gavage (200 and 400 mg/kg) for 28 days. At the end of the experiment, biochemical, oxidative stress parameters, histopathology, and qRT-PCR were performed. DIN was indicated by elevated serum creatinine, urea, and decreased albumin levels representing kidney damage; the histopathological lesions (increased capsular space, renal tubule damage, and fibrosis) in renal tissues supported these biochemical findings. Interestingly, betaine treatment improves these alterations in Dox-treated rats. Further, betaine treatment decreases the lipid peroxidation and nitrite concentration and increases the superoxide dismutases and catalase enzyme concentration in Dox-treated rats. Fascinatingly, at the molecular level, DIN in rats shows upregulation of the Nrf2/HO-1 gene, while betaine treatment attenuated its expression along with the downregulation of inflammatory genes (NLRP3, TLR-4, TNF-?, and IL-6) and fibrosis-related genes (TGF-? and Acta2) expression in Dox-treated rats. These results showed that betaine has reno-protective properties by reducing inflammatory and fibrotic mediators and enhancing antioxidant capacity in the renal tissue of rats treated with Dox. We believe betaine can be exploited as a dietary supplement to attenuate DIN. � 2023 Wiley Periodicals LLC.Item Nanotheranostics revolutionizing neurodegenerative diseases: From precision diagnosis to targeted therapies(Editions de Sante, 2023-10-16T00:00:00) Joshi, Riya; Missong, Hemi; Mishra, Jayapriya; Kaur, Satinder; Saini, Sumant; Kandimalla, Ramesh; Reddy, P. Hemachandra; Babu, Arockia; Bhatti, Gurjit Kaur; Bhatti, Jasvinder SinghNeurodegenerative disorders pose a significant burden on global healthcare systems, and the development of effective therapeutics and diagnostics remains a critical challenge. Nanotheranostics, the integration of nanotechnology-based diagnostic and therapeutic modalities, has emerged as a promising strategy to address these challenges. This review article provides a comprehensive analysis of the latest advancements in nanotheranostics for the treatment and monitoring of neurological disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The application of targeted drug delivery systems, gene therapy, and non-invasive imaging techniques are explored in-depth, highlighting the potential of nanotheranostics to revolutionize the management of neurological disorders. The article delves into the design and synthesis of various nanocarriers, such as liposomes, dendrimers, and polymeric nanoparticles, which enable the targeted delivery of therapeutic agents across the blood-brain barrier. Gene therapy approaches, including CRISPR/Cas9 and RNA interference demonstrating the potential of nanotheranostics to enable precise genetic modifications in the treatment of neurological disorders. Additionally, non-invasive imaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), are examined in the context of their integration with nanotheranostics for real-time monitoring of treatment efficacy and disease progression. The review also identifies current challenges and limitations in the field of nanotheranostics, such as toxicity, immunogenicity, and issues with large-scale production. Furthermore, it outlines future research directions and potential strategies to overcome these limitations, paving the way for the clinical translation of nanotheranostics as next-generation therapeutics in neurological disorders. � 2023Item Genetic Variants of Steroidogenesis and Gonadotropin Pathways and Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-analysis(Mary Ann Liebert Inc., 2023-10-25T00:00:00) Sharma, Priya; Singh, Abhilash Kumar; Senapati, Sabyasachi; Kapoor, Harmanpreet Singh; Goyal, Lajya Devi; Kaur, Balpreet; Kamra, Pooja; Khetarpal, PreetiGenetic variants are predisposing factors to polycystic ovary syndrome (PCOS), a multifactorial condition that often gets triggered due to various environmental factors. The study investigates the association of the variants of genes that are involved in the steroidogenesis pathway or gonadotropin pathway with the risk of PCOS. Appropriate keywords for predetermined genes were used to search in PubMed, Google Scholar, Science Direct, and Central Cochrane Library up to January 11, 2023. PROSPERO (CRD42022275425). Inclusion criteria: (a) case�control study; (b) genotype or allelic data. Exclusion criteria were: (a) duplicate studies; (b) clinical trials, systematic reviews, meta-analysis or conference abstract, case reports; (c) other than the English language; (d) having insufficient data; e) genetic variants for which meta-analysis has been reported recently and does not have a scope of the update. Various genetic models were applied as per data availability. Overall 12 variants of 7 genes were selected for the analysis. Relevant data were extracted from 47 studies which include 10,584 PCOS subjects and 16,150 healthy controls. Meta-analysis indicates a significant association between TOX3 rs4784165 [ORs = 1.08, 95% CI (1.00�1.16)], HMGA2 rs2272046 [ORs = 2.73, 95% CI (1.97�3.78)], YAP1 rs1894116 [OR = 1.22, 95% CI (1.13�1.33)] and increased risk of PCOS. Whereas FSHR rs2268361 [ORs = 0.84, 95% CI (0.78�0.89)] is associated with decreased PCOS risk. When sensitivity analysis was carried out, the association became significant for CYP19 rs700519 and FSHR rs6165 under an additive model. In addition, C9Orf3 rs3802457 became significantly associated with decreased PCOS risk with the removal of one study. Insignificant association was observed for CYP19A (rs2470152), FSHR (rs2349415, rs6166), C9Orf3 (rs4385527), GnRH1 (rs6185) and risk of PCOS. Our findings suggest association of CYP19A (rs700519), TOX3 (rs4784165), HMGA2 (rs2272046), FSHR (rs6165, rs2268361), C9orf3 (rs3802457), and YAP1 (rs1894116) with risk for PCOS. � Mary Ann Liebert, Inc.Item Melittin: a possible regulator of cancer proliferation in preclinical cell culture and animal models(Springer Science and Business Media Deutschland GmbH, 2023-11-03T00:00:00) Haque, Shafiul; Hussain, Arif; Joshi, Hemant; Sharma, Ujjawal; Sharma, Bunty; Aggarwal, Diwakar; Rani, Isha; Ramniwas, Seema; Gupta, Madhu; Tuli, Hardeep SinghBackground: Melittin is a water-soluble cationic peptide derived from bee venom that has been thoroughly studied for the cure of different cancers. However, the unwanted interactions of melittin produce hemolytic and cytotoxic effects that hinder their therapeutic applications. To overcome the shortcomings, numerous research groups have adopted different approaches, including conjugation with tumor-targeting proteins, gene therapy, and encapsulation in nanoparticles, to reduce the non-specific cytotoxic effects and potentiate their anti-cancerous activity. Purpose: This article aims to provide mechanistic insights into the chemopreventive activity of melittin and its nanoversion in combination with standard anti-cancer drugs for the treatment of cancer. Methods: We looked over the pertinent research on melittin's chemopreventive properties in online databases such as PubMed and Scopus. Conclusion: In the present article, the anti-cancerous effects of melittin on different cancers have been discussed very nicely, as have their possible mechanisms of action to act against different tumors. Besides, it interacts with different signal molecules that regulate the diverse pathways of cancerous cells, such as cell cycle arrest, apoptosis, metastasis, angiogenesis, and inflammation. We also discussed the recent progress in the synergistic combination of melittin with standard anti-cancer drugs and a nano-formulated version of melittin for targeted delivery to improve its anticancer potential. Graphical abstract: [Figure not available: see fulltext.] � 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Item Genetic variants of metabolism and inflammatory pathways, and PCOS risk �Systematic review, meta-analysis, and in-silico analysis(Elsevier B.V., 2023-09-14T00:00:00) Sharma, Priya; Bhatia, Kabir; Singh Kapoor, Harmanpreet; Kaur, Balpreet; Khetarpal, PreetiImportance: Identification of genetic risk factors for PCOS susceptibility. Objective: To identify genetic risk variants of the genes involved in metabolic or inflammatory pathways. Data sources: Relevant literature was identified and extracted from PubMed, Central Cochrane Library, Google Scholar, and Science Direct by using a set of keywords related to pre-determined genes up to 06 May 2023. Study selection and synthesis: PRISMA guidelines were followed to design the protocol which is registered in PROSPERO (CRD42023422501). Pooled odds ratio (OR) and 95% confidence interval (95% CI) for different gene variants were calculated under different genetic models (dominant model, recessive model, additive model, and allele model) by using Review Manager software 4.2. Main outcomes: Metabolic genetic variants FTO rs9939609, IL-6 rs1800795 and CAPN10 rs3842570, rs2975760, and RAB5B rs705702 are associated with PCOS risk. Results: Forty-four relevant articles have been identified for genes involved in metabolic (n = 23) or inflammatory pathways (n = 21). There is a significant association (p < 0.05) of IL-6 rs1800795 and FTO rs9939609 with increased risk.CAPN10 rs2975760 Ins allele is suggested as a protective factor among only the non-Asian population. Also, a significant association of CAPN10 rs2975760 and RAB5B rs705702 with increased risk among the Asian population is suggested. However, no significant association could be found between CAPN10 rs3792267, rs5030952, and SUMO1P1 rs2272046, and the risk of PCOS in any of the subpopulations analysed. In silico analysis suggests the deleterious effect of IL-6 rs1800795. Conclusion: and relevance: The study suggests the role of various genetic variants for genetic predisposition to PCOS among different subpopulations. � 2023 Elsevier B.V.Item Potential use of cidofovir, brincidofovir, and tecovirimat drugs in fighting monkeypox infection: recent trends and advancements(Springer Science and Business Media Deutschland GmbH, 2023-10-14T00:00:00) Rani, Isha; Joshi, Hemant; Sharma, Ujjawal; Kaur, Jagjit; Sood, Shivani; Ramniwas, Seema; Chauhan, Abhishek; Abdulabbas, Hadi Sajid; Tuli, Hardeep SinghRecent years have witnessed the rise of more recent pandemic outbreaks including COVID-19 and monkeypox. A multinational monkeypox outbreak creates a complex situation that necessitates countermeasures to the existing quo. The first incidence of monkeypox was documented in the 1970s, and further outbreaks led to a public health emergency of international concern. Yet as of right now, neither vaccines nor medicines are certain to treat monkeypox. Even the inability of conducting human clinical trials has prevented thousands of patients from receiving effective disease management. The current state of the disease�s understanding, the treatment options available, financial resources, and lastly international policies to control an epidemic state are the major obstacles to controlling epidemics. The current review focuses on the epidemiology of monkeypox, scientific ideas, and available treatments, including potential monkeypox therapeutic methods. As a result, a thorough understanding of monkeypox literature will facilitate in the development of new therapeutic medications for the prevention and treatment of monkeypox. � 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Item A duodenal mucosa transcriptome study identified reduced expression of a novel gene CDH18 in celiac disease(Elsevier B.V., 2023-10-09T00:00:00) Banerjee, Pratibha; Sood, Ajit; Midha, Vandhana; Narang, Vikram; Grover, Jasmine; Senapati, SabyasachiBackground: Celiac disease (CD) a complex immune disease that affects duodenal mucosa. Identification of tissue specific biomarkers is expected to improve the existing biopsy based CD diagnosis. Aims: To investigate the differentially expressed genes (DEGs) in duodenal mucosa tissue to identify clinically relevant gene expression pattern in CD. Methods: Whole RNA extracted from the duodenal biopsies of three CD patients and four non-CD controls were sequenced. Significant DEGs were identified. Prioritized DEGs were validated using qRT-PCR in an independent group (CD=23; Control=26). Enriched pathways were analyzed, protein-protein interaction networks were evaluated. Results: 923 DEGs comprising of 135 up-regulated, and 788 down-regulated genes, with p-value?0.05; log2FC>2 or <-2 were identified. A novel down-regulated gene CDH18 (p = 0.03; log2FC=?0.74) was identified. Previously known CXCL9 was replicated. CDH18, a trans-membrane protein was found to interact with other CDH proteins, ?/? catenins, and other membrane transporters such as SLC and ABCB. Pathways and protein networks contributing in channel activity (p = 2.15E-12), membrane transporters (p = 2.15E-12), and cellular adhesion (p = 8.05E-6) were identified. Conclusions: CDH18, a novel DEG identified in the present study is a pivotal gene involved in maintaining epithelial membrane organization and integrity. The functional significance of lower expression of CDH18 in pathogenesis of CD warranted to be investigated. CDH18 expression could be tested for its effectiveness in diagnostic, prognostic and therapeutic purposes. � 2023 Editrice Gastroenterologica Italiana S.r.l.Item Artificial Intelligence Bringing Newer Paradigms in the Diagnosis, Treatment, and Management of Psoriasis(Springer, 2023-10-04T00:00:00) Sharma, Ravi Kant; Sharma, Manu Rashmi; Mahendra, Aneet; Sharma, Ujjawal; Singh, Simranjit; Ramniwas, Seema; Sharma, Anil KumarPurpose of Review: As we know, psoriasis is the most prevalent chronic inflammatory skin condition due to aberrant immune response which is characterized by clearly demarcated red or pink thick raised skin plaques sometimes covered with dry thin silvery white scales, formed due to the cytokine-driven hyperproliferation of epidermal keratinocytes. The abnormal functioning of immune-inflammatory pathways can cause various systemic conditions including cardiovascular diseases, chronic renal disease, and metabolic syndrome. Recent Findings: In comparison to other dermatological conditions, psoriasis has greater impact on the mental health of patients leading to increased risk of psychiatric comorbidities such as depression and anxiety.�The Articial intellingence could automate the analysis and provide contextual relevance, enhance clinical reliability,�assist the clinicians in communicating objectively, minimize human fatigue related errors, decrease mortality rates,�save medical expenditures and help in easy and early diagnosis of diseases including psoriasis. Summary: Therefore, development of better approaches for the diagnosis of psoriasis and determination of its classification type and severity are necessary for disease control and management and are the need of the hour. The artificial intelligence (AI) applications in medicine and healthcare are recently emerging due to advanced computing technologies and availability of abundant data on a variety of diseases including psoriasis. Hence, AI will certainly be a boon for the early detection and management of psoriasis patients necessitating further research in this area. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.