Department of Pharmacy
Permanent URI for this collectionhttp://localhost:4000/handle/123456789/1931
Browse
7 results
Search Results
Item Significance of LncRNAs in AKI-to-CKD transition: a therapeutic and diagnostic viewpoint(Elsevier, 2024-04) Gaikwad, Anil Bhanudas; Majumder, SyamantakAcute kidney injury to chronic kidney disease (AKI-to-CKD) transition is a complex intermingling of characteristics of both AKI and CKD. Pathophysiologically, the transition lasts seven days after the AKI episode and thereafter silently progresses towards CKD. Growing reports confirm that the AKI-to-CKD transition is heavily regulated by epigenetic modifiers. Long non-coding RNAs (lncRNAs) share a diverse role in gene regulation at transcriptional and translational levels and have been reported to be involved in the regulation and progression of AKI-to-CKD transition. Several lncRNAs have been considered potential biomarkers for diagnosing kidney disease, including AKI and CKD. Targeting lncRNAs gives a promising therapeutic strategy against kidney diseases. The primitive role of lncRNA in the progression of the AKI-to-CKD transition is yet to be fully understood. As known, the lncRNAs could be used as a biomarker and a therapeutic target to halt the CKD development and progression after AKI. This review aims to deepen our understanding of the current knowledge regarding the involvement of lncRNAs in the AKI-to-CKD transition. This review primarily discusses the role of lncRNAs and the change in their mechanisms during different stages of kidney disease, such as in AKI, AKI-to-CKD transition, and CKD. Further, we have discussed the potential diagnostic and pharmacological outcomes of targeting lncRNAs to prevent or slow the progression of AKI-to-CKD transition.Item Acyl-coa synthetase long-chain isoenzymes in kidney diseases: mechanistic insights and therapeutic implications(Wiley, 2024-08) Gaikwad, Anil BhanudasLong-chain acyl-CoA synthetases (ACSLs) are pivotal enzymes in fatty acid metabolism, essential for maintaining cellular homeostasis and energy production. Recent research has uncovered their significant involvement in the pathophysiology of various kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), and renal cell carcinoma (RCC). While ACSL1, ACSL3, ACSL4, and ACSL5 have been extensively studied for their roles in processes such as ferroptosis, lipid peroxidation, renal fibrosis, epithelial-mesenchymal transition, and tumor progression, the role of ACSL6 in kidney diseases remain largely unexplored. Notably, these isoenzymes exhibit distinct functions in different kidney diseases. Therefore, to provide a comprehensive understanding of their involvement, this review highlights the molecular pathways influenced by ACSLs and their roles in modulating cell death, inflammation, and fibrosis during kidney disease progression. By examining these mechanisms in detail, this review underscores the potential of ACSLs as biomarkers and therapeutic targets, advocating for further research to elucidate the precise roles of individual ACSL isoenzymes in kidney disease progression. Understanding these mechanisms opens new avenues for developing targeted interventions and improving therapeutic outcomes for patients with kidney diseases.Item A therapeutic approach to identify leading molecules from natural products and therapeutic targets in CKD by network pharmacology(Elsevier, 2024-12) Gaikwad, Anil BhanudasChronic kidney disease (CKD), a condition characterized by diminished kidney function, affects approximately 10 % of the population worldwide. With its high mortality rate of ∼1.2 million, CKD poses a high global burden. The complexity increases severalfold due to its vast variety of aetiologies and relatively limited treatment options that, too, are associated with adverse effects. The continuous deterioration of the kidneys makes them reliant on external purification systems i.e., dialysis or whole kidney transplantation, both having certain limitations, making CKD one of the highly prevalent diseases across the globe. The multi-faceted disease requires multi-targeted therapies that can potentially improve CKD care. Natural products have long been considered the “holy grail” for many diseases, including CKD; their multi-targeting nature, fewer side effects, and ability to target multiple pathways have caught attention. The complexity increases when a single phytopharmaceutical cures a disease by acting on various targets and affecting diverse mechanisms. Identifying therapeutic targets and lead molecules thus becomes difficult and, at times, a big task! The network pharmacology (NP) tool has shifted this drug discovery paradigm towards a “multi-drug, multi-target” approach to underscore responsible molecular interconnections that unwind the therapeutic potential of natural products against CKD by predicting potential therapeutic targets and underlined molecular mechanisms. Applying NP for natural products in CKD can be a time-saving and cost-effective strategy. The present review emphasizes prominent classes of natural products and lead molecules obtained from herbal preparations, their explored multi-targeted effects against CKD, and novel targets predicted and validated using the NP approach.Item Wnt/beta-catenin modulation: A promising frontier in chronic kidney disease management(Wiley, 2024-08) Gaikwad, Anil BhanudasBeing amongst the leading factors of death and distress, chronic kidney disease (CKD) has affected around 850 million people globally. The Wnt/β-catenin axis is vital for maintaining kidney homeostasis, from nephron generation to overall management. The β-catenin growth factor is typically not expressed in the adult kidney; however, its expression is found to increase under stress and injury conditions. It is categorised as canonical and non-canonical based on β-catenin availability, which mounts promising targets for ameliorating CKD. Hence, modulation of the Wnt/β-catenin signalling for CKD management is of utmost relevance.Item Novel dysregulated long non-coding RNAs in the acute kidney injury-to-chronic kidney diseases transition unraveled by transcriptomic analysis(The British Pharmacological Society, 2024-11) Gaikwad, Anil Bhanudas; Majumder, SyamantakAcute kidney injury (AKI)-to-chronic kidney disease (CKD) transition involves a complex pathomechanism, including inflammation, apoptosis, and fibrosis where long non-coding RNAs (lncRNAs) play a crucial role in their regulation. However, to date, only a few lncRNAs have been discovered to be involved in the AKI-to-CKD transition. Therefore, this study aims to investigate the dysregulated lncRNAs in the AKI-to-CKD transition in vitro and in vivo. To mimic AKI-to-CKD transition both in vivo and in vitro, bilateral ischemia-reperfusion (IR) kidney injury was performed in Wistar rats (male), and normal rat kidney epithelial cell (NRK52E) cells were treated with exogenous transforming growth factor-β1 (TGF-β1). Further processing and analysis of samples collected from these studies (e.g., biochemical, histopathology, immunofluorescence, and RNA isolation) were also performed, and transcriptomic analysis was performed to identify the dysregulated lncRNAs. Rats subjected to IR showed a significant increase in kidney injury markers (creatinine, blood urea nitrogen (BUN), kidney injury molecule-1(KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) along with altered cell morphology). Apoptosis, inflammation, and fibrosis markers were markedly increased during the AKI-to-CKD transition. Furthermore, transcriptomic analysis revealed 62 and 84 unregulated and 95 and 92 downregulated lncRNAs in vivo and in vitro, respectively. Additionally, functional enrichment analysis revealed their involvement in various pathways, including the tumor necrosis factor (TNF), wingless-related integration site (Wnt), and hypoxia-inducible factor-1 (HIF-1) signaling pathways. These identified dysregulated lncRNAs significantly contribute to AKI-to-CKD transition, and their knockin/out can aid in developing targeted therapeutic interventions against AKI-to-CKD transition.Item Advances in CRISPR-Cas systems for kidney diseases(Elsevier, 2025) Gaikwad, Anil BhanudasRecent advances in CRISPR-Cas systems have revolutionised the study and treatment of kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), lupus nephritis (LN), and polycystic kidney disease (PKD). CRISPR-Cas technology offers precise and versatile tools for genetic modification in monogenic kidney disorders such as PKD and Alport syndrome. Recent advances in CRISPR technology have also shown promise in addressing other kidney diseases like AKI, CKD, and DKD. CRISPR-Cas holds promise to edit genetic mutations underlying these conditions, potentially leading to more effective and long-lasting treatments. Furthermore, the adaptability of CRISPR-Cas systems allows for developing tailored therapeutic strategies that specifically target the genetic and molecular mechanisms contributing to different kidney diseases. Beyond DNA modifications, CRISPR-Cas technologies also enable editing noncoding RNA, such as lncRNAs and miRNAs, in kidney diseases. Despite these advancements, significant challenges persist, including delivery efficiency to specific kidney cells and potential off-target effects. However, the rapid progress in CRISPR-Cas technology suggests a transformative impact on the future management of kidney diseases, offering the potential for enhanced patient outcomes through personalised and precise therapeutic approaches. This chapter highlights the recent advancement of CRISPR-Cas systems and their potential applications in various kidney diseases.Item Repurposing the familiar: future treatment options against chronic kidney disease(OUP, 2025-01) Gaikwad, Anil BhanudasChronic kidney disease (CKD) is a serious health issue with rising morbidity and mortality rates. Despite advances in understanding its pathophysiology, effective therapeutic options are limited, necessitating innovative treatment approaches. Also, current frontline treatments that are available against CKD are not uniformly effective and often come with significant side effects. Therefore, identifying new therapeutic targets or improving existing treatments for CKD is crucial. Drug repurposing is a promising strategy in the drug discovery process that involves screening existing approved drugs for new therapeutic applications.