Department of Biological Sciences

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Author: search.filters.author.Majumder, SyamantakHas files: No

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    The multifaceted role of lncRNA MEG3 in kidney disease: a focus on mechanisms, therapeutic and diagnostic potential
    (Elsevier, 2025-09) Majumder, Syamantak; Gaikwad, Anil Bhanudas
    Kidney disease represents a global health challenge, affecting millions of people and contributing to significant morbidity and mortality. Long noncoding RNAs are potentially emerging as regulators in cellular processes and are involved in pathophysiological alterations in kidney disease. Among these, MEG3 has gained attention for its diverse regulatory roles in fibrosis, apoptosis and inflammation. MEG3 dysregulation has been implicated in conditions like chronic kidney disease, acute kidney injury, diabetic kidney disease and renal cell carcinoma. However, its involvement in endoplasmic reticulum (ER) stress and autophagy, crosstalk in kidney disease, is poorly understood. Hence, this review aims to highlight the role of MEG3 as a therapeutic and diagnostic viewpoint in kidney disease and its regulatory mechanism in ER stress and autophagy.
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    Repurposing of CNS accumulating drugs Gemfibrozil and Doxylamine for enhanced sensitization of glioblastoma cells through modulation of autophagy
    (Springer Nature, 2025-07) Mukherjee, Sudeshna; Chowdhury, Rajdeep; Majumder, Syamantak; Chowdhury, Shibasish; Roy, Aniruddha
    GBM is one of the most aggressive malignancies, having the greatest fatality rate and average life years lost. The current standard medicine, temozolomide (TMZ), is ineffective, requiring the development of new treatments. However, identifying and introducing a novel medicine takes time and money. In this context, repurposing FDA-approved drugs can be a novel yet efficient alternative method. Here, we, therefore, investigated the differential expression signatures of genes of patients suffering from GBM from publicly available GEO datasets and constructed a connectivity map. Functional annotation and KEGG pathway analysis showed dysregulated molecular activities and pathways. Based on their gene ontologies, putative key genes and hub genes linked with the disease were identified, and the C-MAP database was scanned for FDA-approved medicinal compounds that could alter hub gene expression or associated pathways. Our in-silico investigation showed that Gemfibrozil (Gem) and Doxylamine (Doxy) might reverse GBM disease patterns by deregulating GBM-related genes. Evaluation of the GBM inhibitory potential of these drugs through in-vitro and three-dimensional spheroid assay showed promising results. These drugs were more cytotoxic than TMZ; however, they synergised with TMZ as well. Interestingly, the cellular homeostatic process autophagy which has been implicated significantly in GBM pathogenesis and therapy resistance, was found to be inhibited by the drugs Gemfibrozil and Doxylamine, signifying their prospective potential. Therefore, in this study, we, for the first time, identify drugs with the ability to cross the blood brain barrier (BBB), with potential cytotoxic effects beyond TMZ, and with autophagy inhibitory potential, which can be further explored for repurposing against GBM.
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    Evaluation of interleukin-33 & sST2 levels in type-2 diabetic mellitus patients with or without metabolic syndrome
    (Indian Journal of Medical Research, 2023) Majumder, Syamantak
    Diabetes mellitus (DM) is characterized by increase in blood glucose levels due to defective insulin secretion or insulin sensitivity. Interleukins (ILs) are known to play an important role in the pathogenesis of DM. The aim of this study was to investigate the serum concentration of IL-33 and its receptor soluble ST2 (sST2) in patients with diabetes and draw a correlation between their serum levels and different standard glycaemic indices of patients affected with type-2 diabetes with or without metabolic syndrome.
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    Chloroquine attenuates hypoxia-mediated autophagy to curb thrombosis- an ex vivo and in vivo study
    (2024-04) Mukherjee, Sudeshna; Majumder, Syamantak; Chowdhury, Shibasish; Chowdhury, Rajdeep
    Hypoxia can trigger the activation of blood platelets, leading to thrombosis. If not addressed clinically, it can cause severe complications and fatal consequences as well. The current treatment regime for thrombosis is often palliative and includes long-term administration of anticoagulants, which has the risk of over-bleeding in injury and other secondary effects as well. This demands a deeper understanding of the process and exploration of an alternative therapeutic avenue. Interestingly, recent studies demonstrate that platelets though atypical and enucleated, possess components of autophagy machinery. This cellular homeostatic process though well-studied in non-platelet cells, is under-explored in platelets.
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    14K prolactin derived 14-mer antiangiogenic peptide targets bradykinin-/nitric oxide-cGMP-dependent angiogenesis
    (FEBS Press, 2024-09) Majumder, Syamantak
    Over the past few decades, VEGF-targeted antiangiogenic therapy for cancers has gained increasing attention. Nevertheless, there are still several limitations such as the potential resistance mechanisms arising in cancer cells against these therapies and their potential adverse effects. These limitations highlight the need for novel anti-angiogenesis molecules and better understanding of the mechanisms of tumor angiogenesis. In the present study, we investigated the antiangiogenic properties of a novel 14-mer antiangiogenic peptide (14-MAP) derived from N-terminal 14 kDa buffalo prolactin and characterized its mode of action. 14-MAP at the picomolar concentration inhibited VEGF- and bradykinin (an autacoid peptide expressed in vascular tissues in pathophysiology, BK)-stimulated endothelial nitric oxide (eNO) production, cell migration, and proliferation in endothelial cells and vessel development in the chick embryo. Although this peptide inhibited both VEGF- and BK-dependent angiogenic processes, its action was more pronounced in the latter. Moreover, the interference of 14-MAP with the eNO synthase (eNOS)-cyclic GMP pathway was also identified. A combination of a low dose of Avastin, a widely used drug targeting VEGF-dependent angiogenesis, and 14-MAP significantly reduced tumor size in an in vivo model of human colon cancer. Taken together, our results suggest that 14-MAP, a BK- and eNOS-dependent antiangiogenic peptide, might be useful for overcoming the limitation of VEGF-targeted antiangiogenic therapy in cancer patients. However, further studies will be required to further characterize its mode of action and therapeutic potential.
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    Inhibition of autophagy in platelets as a therapeutic strategy preventing hypoxia induced thrombosis
    (Springer Nature, 2025-02) Mukherjee, Sudeshna; Majumder, Syamantak; Chowdhury, Shibasish; Chowdhury, Rajdeep
    Hypoxia triggers activation of platelets, leading to thrombosis. If not addressed clinically, it can cause severe complications and fatal consequences. The current treatment regime for thrombosis is often palliative and include long-term administration of anticoagulants, causing over-bleeding risk and other secondary effects as well. This demands a molecular understanding of the process and exploration of an alternative therapeutic avenue. Interestingly, recent studies demonstrate that platelets exhibit functional autophagy. This cellular homeostatic process though well-studied in non-platelet cells, is under-explored in platelets. Herein, we report autophagy activation under physiologically relevant hypoxic condition (10% O2; associated with high altitude) in ex-vivo platelets and in vivo as well. We show that autophagy inhibition using chloroquine (CQ), a repurposed FDA-approved drug, can significantly reduce platelet activation, both in ex-vivo and in-vivo settings. Further, surgical ligation of inferior vena cava (IVC) was performed to induce thrombus formation. Interestingly, CQ pre-treated rats showed reduced clotting ability in surgical animals as well. Importantly, thrombosis inhibitory dose of CQ was considerably lower than the currently used drug-acetazolamide; CQ was also found to be non-toxic to the tissues. Hence, we propose that repurposing of CQ can attenuate hypoxia-induced thrombosis through inhibition of autophagy and can be explored as an effective therapeutic alternative.
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    The emerging insight into E3 ligases as the potential therapeutic target for diabetic kidney disease
    (Elsevier, 2023-05) Majumder, Syamantak; Gaikwad, Anil Bhanudas
    Diabetic kidney disease (DKD) is a major diabetic complication and global health concern, occurring in nearly 30 % to 40 % of people with diabetes. Importantly, several therapeutic strategies are being used against DKD; however, available treatments are not uniformly effective and the continuous rise in the prevalence of DKD demands more potential therapeutic approaches or targets. Epigenetic modifiers are regarded for their potential therapeutic effects against DKD. E3 ligases are such epigenetic modifier that regulates the target gene expression by attaching ubiquitin to the histone protein. In recent years, the E3 ligases came up as a potential therapeutic target as it selectively attaches ubiquitin to the substrate proteins in the ubiquitination cascade and modulates cellular homeostasis. The E3 ligases are also actively involved in DKD by regulating the expression of several proteins involved in the proinflammatory and profibrotic pathways. Burgeoning reports suggest that several E3 ligases such as TRIM18 (tripartite motif 18), Smurf1 (Smad ubiquitination regulatory factor 1), and NEDD4-2 (neural precursor cell-expressed developmentally downregulated gene 4-2) are involved in kidney epithelial–mesenchymal transition, inflammation, and fibrosis by regulating respective signaling pathways. However, the various signaling pathways that are regulated by different E3 ligases in the progression of DKD are poorly understood. In this review, we have discussed E3 ligases as potential therapeutic target for DKD. Moreover, different signaling pathways regulated by E3 ligases in the progression of DKD have also been discussed.
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    Epigenetic, Molecular and Programming Mechanisms of Renal Physiology and Pathophysiology
    (Frontiers, 2023-02) Majumder, Syamantak
    Significant advances have been made to understand the underlying mechanisms of renal dysfunction in recent years. However, kidney disease still remains to be highly prevalent, primarily when associated with other chronic conditions such as cardiovascular disease, diabetes mellitus, and obesity. Thus, it is essential to deepen the knowledge about the molecular and pathophysiological alterations that occur with the worsening of this disorder, envisioning the adoption of strategies to at least delay its progression. In this Research Topic, a Research Topic of related articles were published that provide most recent evidence in this intriguing area. The role that non-coding RNAs (ncRNAs), especially the long non-coding RNAs (lncRNAs), play in the pathophysiological processes associated with the development of acute kidney injury (AKI) are presented by Yang et al.. In this revision, the authors showed a complete and up-to-date overview of the role of lncRNAs in AKI and a systematic review of the role of lncRNAs in AKI resulting from different etiologies. Finally, the potential use of lncRNAs as biomarkers for the early diagnosis of patients with AKI is highlighted. Additionally, it is suggested that few lncRNAs, due to their involvement in various regulatory mechanisms associated with kidney injury may represent potential therapeutic targets for AKI.
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    Regulation of shelterin proteins TERF2IP and TRF2 by H3K4me3-p65 axis drives hyperglycemia dependent endothelial senescence
    (2023-05) Majumder, Syamantak; Chowdhury, Shibasish; Dey, Smita
    Endothelial senescence has been linked to several cardiovascular diseases. Dysregulation of proteins of the shelterin complex including TRF2 and TERF2IP causes senescence as it hampers DNA repair and cell proliferation. However, whether exposure to hyperglycemia interplays with proteins of the shelterin complex thus further dictates the senescent phenotype of endothelial cells (EC) remain to be explored.
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    Developing an Ex Vivo Model of Ischemia Using Early Chick-Embryo: A Model to Study Ischemia Related Angiogenesis
    (Springer, 2012-06-19) Majumder, Syamantak
    Ischemia created in the animals were long been used as a model to study ischemia mediated effects in vivo. Pathological angiogenesis is the key hallmark of various ischemic diseases where blood vessel formation was compromised due to low blood flow. New blood vessels form in order to compensate the low blood perfusion in the ischemic area. This neovascularization and remodeling of the existent vessels protect from the consequences of ischemia associated diseases like myocardial infarction and stroke. A better understanding of the mechanisms of functional vessel formation is a pre-requisite to improve the treatment of ischemic pathologies. Therefore, the research area warrants an easily accessible model in which vessel formation can be both manipulated and studied. However, a limited number of efforts have been put forward yet to develop an ischemia models where ischemia mediated remodeling of vessels can be studied in real time. In present study, we used 4 day grown chick embryo to ligate right vitelline artery and create partial ischemia in the vascular bed of the embryo. The model has been developed based on the principle that blocking blood flow in the vascular bed will stop the nutrient and oxygen supply to the adjacent vessels and thus creating an ischemia like condition. Additionally, ischemia related changes in angiogenesis can be followed and tracked in real time in the vascular bed of the chick embryo. The present ex vivo model can be utilized in studying ischemia related angiogenesis in specific and hypoxia and/or low oxygen mediated angiogenesis in general.