Browsing by Author "Arpit Sharma"

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Antitumor potential of ivermectin against T-cell lymphoma-bearing hosts
(Springer, 2025) Alok Shukla; Arpit Sharma; Shivani Gupta; Abha Mishra; Amit Kumar Singh
Ivermectin, a broad-spectrum antiparasitic agent from the ivermectin family, has shown promising anticancer potential. Originally developed for veterinary and human use against parasitic infections, ivermectin demonstrated significant antitumor effects in our study against tumor cells (Dalton’s lymphoma cells). A dose-dependent decrease in tumor cell viability was observed following 24-h treatment with ivermectin, with an IC₅₀ value calculated at 10.55 µg/mL. In comparison, the standard anticancer drug cisplatin exhibited a slightly higher cytotoxic potency, with an IC₅₀ of 8.32 µg/mL under the same treatment duration. Flow cytometric analysis revealed that ivermectin induced cell cycle arrest in the G0–G1 phase. Apoptotic tumor cell death was confirmed via Annexin V/PI staining, further supported by nuclear condensation, a hallmark of apoptosis, visualized through both confocal microscopy and flow cytometry. The apoptosis was determined to be mitochondrial-dependent, as evidenced by a decline in mitochondrial membrane potential (ΔΨm) observed through JC-1 assay. The treatment increased DAPI-positive cells and exhibited severe chromatin condensation. Additionally, cell death was validated using Acridine Orange and Propidium Iodide staining, which highlighted increased cell membrane rupture and death through apoptosis and necrosis. Mitochondrial dependent apoptosis further supported by increased ROS production upon ivermectin treatment. Moreover, In vivo, ivermectin treatment led to a substantial reduction in tumor size in tumor-bearing mice, along with normalization of spleen size, body weight, and improvement histopathology of liver. These findings collectively support the therapeutic potential of ivermectin as a repurposed anticancer agent, acting through multiple mechanisms including cell cycle arrest, ROS generation, mitochondrial dysfunction, and apoptosis. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
Artificial intelligence-driven optimization of biohydrogen production: ANN-GA, RSM, and python synergy for novel Alcaligenes ammonioxydans utilizing sugarcane bagasse
(Elsevier Ltd, 2025) Shruti Sharadrao Raut; Arpit Sharma; Ankit Keshariya; Vansh Agarwal; Rohit Kumar; Abha Mishra
Biohydrogen (bioH2) production through dark fermentation presents a promising and sustainable alternative to fossil fuels, especially when utilizing lignocellulosic agricultural residues. In this study, sugarcane bagasse (SB) was selected as the feedstock due to its high carbohydrate content, abundant availability, and low cost, making it an ideal substrate for microbial bioH2 production. A newly isolated and efficient bioH2-producing bacterium, Alcaligenes ammonioxydans SRAM was employed to ferment the pretreated bagasse under anaerobic conditions. To optimize bioH2 yield, four critical process parameters substrate concentration, inoculum ratio, acid pretreatment concentration, and pH were systematically investigated using a Central Composite Design (CCD). Two advanced modelling approaches, Response Surface Methodology (RSM) and Artificial Neural Networks (ANN), were used to develop predictive frameworks based on the experimental data. ANN models were developed in MATLAB and Python, demonstrating superior performance over RSM by accurately capturing complex nonlinear interactions with significantly lower prediction errors. To enhance the optimization process, the ANN model was further integrated with a Genetic Algorithm (GA), resulting in a hybrid ANN-GA model implemented in Python. This hybrid approach effectively determined the optimal conditions for maximum bioH2 production, achieving a minimal prediction error of 0.02. The optimized parameter set included a substrate concentration of 48.98 g/L, an inoculum ratio of 8.21 % v/v, an acid concentration of 3.56 % v/v, and a pH of 7.02. This study clearly highlights the potential of A. ammonioxydans SRAM for high-efficiency bioH2 production and presents a robust ANN-GA-based optimization framework for enhancing bioH2 yields from SB, advancing the transition to renewable energy sources. © 2025 Elsevier Ltd
DDX3X dynamics, glioblastoma's genetic landscape, therapeutic advances, and autophagic interplay
(Springer, 2024) Arpit Sharma; Shruti S. Raut; Alok Shukla; Shivani Gupta; Amit Singh; Abha Mishra
Glioblastoma is one of the most aggressive and deadly forms of cancer, posing significant challenges for the medical community. This review focuses on key aspects of Glioblastoma, including its genetic differences between primary and secondary types. Temozolomide is a major first-line treatment for Glioblastoma, and this article explores its development, how it works, and the issue of resistance that limits its effectiveness, prompting the need for new treatment strategies. Gene expression profiling has greatly advanced cancer research by revealing the molecular mechanisms of tumors, which is essential for creating targeted therapies for Glioblastoma. One important protein in this context is DDX3X, which plays various roles in cancer, sometimes promoting it or otherwise suppressing it. Additionally, autophagy, a process that maintains cellular balance, has complex implications in cancer treatment. Understanding autophagy helps to identify resistance mechanisms and potential treatments, with Chloroquine showing promise in treating Glioblastoma. This review covers the interplay between Glioblastoma, DDX3X, and autophagy, highlighting the challenges and potential strategies in treating this severe disease. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
From development to clinical success: the journey of established and next-generation BTK inhibitors
(Springer, 2025) Shivani Gupta; Arpit Sharma; Alok Shukla; Abha Mishra; Amit Kumar Singh
Over the past decade, Bruton’s tyrosine kinase (BTK) has emerged as a pivotal therapeutic target for B-cell malignancies and autoimmune diseases, given its essential role in B-cell development and function. Dysregulation of BTK signalling is implicated in a range of hematologic cancers, including Waldenström’s macroglobulinaemia (WM), mantle cell lymphoma (MCL), and chronic lymphocytic leukaemia (CLL). The development of BTK inhibitors (BTKIs), starting with ibrutinib, has revolutionized the treatment of these malignancies by inhibiting B-cell receptor (BCR) signalling and inducing apoptosis in malignant B-cells. Despite the impressive clinical efficacy of ibrutinib, challenges such as resistance mutations and off-target effects remain. To address these issues, next-generation BTKIs, including acalabrutinib, orelabrutinib, zanubrutinib, and pirtobrutinib, have been developed, offering improved specificity and reduced toxicity profiles. This review highlights the therapeutic potential of BTK-targeted therapies in treating B-cell malignancies, discusses recent advancements with FDA-approved BTKIs, and explores the latest clinical outcomes from ongoing trials of novel inhibitors. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
Lignocellulosic biomass-driven biohydrogen production: Innovations, challenges, and future prospects for a sustainable green hydrogen economy
(Elsevier Ltd, 2025) Shruti Sharadrao Raut; Arpit Sharma; Abha Mishra
Hydrogen (H2) is a clean and sustainable energy carrier that can help decrease dependence on fossil fuels. When produced from renewable or low-carbon sources, it can substantially lower greenhouse gas emissions by substituting conventional fossil fuel-based energy systems. H2 production, derived from renewable sources, offers a promising alternative to conventional H2 generation methods. This review provides a comprehensive overview of the various biological methods employed for H2 production, including dark fermentation, photofermentation, and biophotolysis. Each of these methods has distinct advantages and limitations in terms of efficiency, scalability, and operational conditions. A wide range of feedstocks has been explored for H2 production, including first-generation biomass, such as sugar- and starch-based crops, as well as second-generation lignocellulosic biomass, such as agricultural residues and organic waste. Factors such as pH, temperature, feedstock composition, microbial strains, and nutrient availability critically affect the H2 yield and production efficiency. Additionally, pretreatment methods for complex feedstocks are crucial for enhancing H2 yields by improving substrate accessibility for microbial conversion. The review also addresses the challenges of H2 storage and transport, which are critical for its integration into the energy economy. Advanced technologies for H2 storage, including compression, liquefaction, and chemical storage in metal hydrides and liquid organic H2 carriers (LOHCs), are discussed. The efficient and safe transport of H2 over long distances remains a key technical hurdle, necessitating innovations in pipeline infrastructure and storage materials. This review highlights recent advancements and ongoing research aimed at overcoming these challenges, ultimately contributing to the development of a sustainable H2 economy. © 2025 Hydrogen Energy Publications LLC
Nano-Bioremediation via Biochar, Zeolite Nanocomposites for Water Quality Enhancement: A Review
(John Wiley and Sons Inc, 2025) Shruti Sharadrao Raut; Arpit Sharma; Abha Mishra
The emergence of biochar–zeolite composite nanomaterials marks major advancement in wastewater treatment, offering an efficient and eco-friendly alternative to traditional remediation technologies. These hybrids combine the high surface area and functional groups of biochar derived from biomass pyrolysis with zeolite's superior ion-exchange capacity, thermal stability, and tunable porosity. While biochar shows promise for pollutant adsorption, its performance can be limited under high contaminant loads and challenging recovery. To overcome this, biochar is modified with nanomaterials to enhance surface properties, structural integrity, magnetic behavior, and catalytic functionality, enabling efficient pollutant removal and easier separation. Likewise, nanoscale zeolites excel at selectively removing heavy metals, dyes, and pharmaceuticals. When integrated, these composites exhibit synergistic effects by coupling broad-spectrum adsorption with targeted ion exchange. Their biocompatibility and compatibility with microbial systems make them ideal for nanobioremediation. This review compiles key findings, recent advancements, and applications of biochar–zeolite nanocomposites to guide future research. © 2025 Water Environment Federation.
Silibinin: a natural flavonoid with multifaceted anticancer potential and therapeutic challenges
(Springer, 2025) Snigdha Singh; Arpit Sharma; Tanu Pandey; Shivani Gupta; Alok Shukla; Santosh Kumar Singh; Amit Kumar Singh
Silibinin, the principal bioactive flavonolignan of Silybum marianum (milk thistle), has emerged as a promising natural agent with multifaceted anticancer potential. Extensive preclinical studies demonstrate its diverse pharmacological properties, including antioxidant, anti-inflammatory, and chemopreventive activities, which collectively contribute to its antitumor effects. At the molecular level, silibinin exerts cytotoxicity through the induction of apoptosis, involving both extrinsic (death receptor-mediated) and intrinsic (mitochondria-dependent) pathways. It modulates key signaling cascades such as EGFR, STAT3, and PI3K/AKT/mTOR, leading to suppression of proliferation, angiogenesis, invasion, and modulation of autophagy, stemness and Senescence. Importantly, silibinin acts as a modulator of apoptosis by restoring the balance between pro- and anti-apoptotic proteins, thereby sensitizing cancer cells to programmed cell death. Evidence across multiple malignancies, including hepatocellular carcinoma, breast, lung, and colorectal cancers etc, highlights its broad-spectrum therapeutic relevance. Clinical studies, though limited, suggest that silibinin may enhance the efficacy of standard chemotherapeutic, radiotherapeutic, and targeted regimens while reducing associated toxicities, underscoring its role as a synergistic adjuvant. However, challenges such as poor bioavailability, variable pharmacokinetics, and limited large-scale clinical validation constrain its translational application. To address these limitations, novel strategies such as nanocarrier-based delivery, structural modifications, and combination therapies are being actively investigated. Overall, silibinin represents a compelling natural flavonoid with dual preventive and therapeutic roles in oncology, though future research must overcome pharmacological barriers to fully harness its clinical potential. (Figure presented.) © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
Structure-guided discovery of a novel BTK inhibitor inducing apoptosis and G1 phase arrest in tumor cells
(Springer Nature, 2025) Alok Shukla; Arpit Sharma; Shivani Gupta; Shruti Sharadrao Raut; Abha Mishra; S. Hemalatha; Amit Kumar Singh
Bruton’s tyrosine kinase (BTK) is a pivotal component of multiple signaling pathways in hematopoietic cells and serves as a critical pharmacological target in B-cell malignancies. Despite the availability of clinically approved BTK inhibitors, therapeutic resistance and limited efficacy in certain patient populations necessitate the discovery of novel candidates. In this study, virtual high-throughput screening of the ZINC database was employed to identify potential BTK inhibitors. Compounds were prioritized based on molecular docking scores, binding patterns, and free energy calculations. ZINC000045971961 (ZINC1961) emerged as a promising lead compound, forming stable hydrogen bonds with Glu475 and Met477 key residues also targeted by the reference inhibitor Ibrutinib. Molecular dynamics simulations and MM/GBSA free energy analysis further confirmed the stability and favorable binding affinity of ZINC1961. Biological evaluation in primary tumor cells demonstrated potent cytotoxicity, with an IC50 of 80 ± 0.5 µM, and pronounced apoptosis confirmed by AO/EB/DAPI triple staining, Annexin-V/PI assay, and scanning electron microscopy. Additionally, ZINC1961 induced G1 phase cell cycle arrest, contributing to its antiproliferative effects. Collectively, these findings not only highlight ZINC1961 as a novel BTK inhibitor but also underscore the power of integrative in silico and in vitro approaches in accelerating early-stage cancer drug discovery. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2025.