Therapeutic approaches and novel antifibrotic agents in renal fibrosis: A comprehensive review.

Renal fibrosis (RF) is one of the underlying pathological conditions leading to progressive loss of renal function and end-stage renal disease (ESRD). Over the years, various therapeutic approaches have been explored to combat RF and prevent ESRD. Despite significant advances in understanding the underlying molecular mechanism(s), effective therapeutic interventions for RF are limited. Current therapeutic strategies primarily target these underlying mechanisms to halt or reverse fibrotic progression. Inhibition of transforming growth factor-ß (TGF-ß) signaling, a pivotal mediator of RF has emerged as a central strategy to manage RF. Small molecules, peptides, and monoclonal antibodies that target TGF-ß receptors or downstream effectors have demonstrated potential in preclinical models. Modulating the renin-angiotensin system and targeting the endothelin system also provide established approaches for controlling fibrosis-related hemodynamic changes. Complementary to pharmacological strategies, lifestyle modifications, and dietary interventions contribute to holistic management. This comprehensive review aims to summarize the underlying mechanisms of RF and provide an overview of the therapeutic strategies and novel antifibrotic agents that hold promise in its treatment.

Insulin Analogs and the Mode of Insulin Delivery: Recent Advances and Challenges.

Diabetes is a medical condition associated with impaired glucose regulation caused either due to insufficient insulin production or resistance to insulin (Type 2 diabetes, gestational diabetes) or the absence of insulin through the selective killing of beta cells in the pancreas (Type 1 diabetes). Irregular insulin production leads to various health complications. To prevent such complications, patients must adhere to medical recommendations before availing of any advanced insulin therapy(ies), considered productive for the treatment. Natural insulin, although highly effective in controlling blood glucose levels, patients are often at risk of developing hypoglycemia and many other complications. This has led to the development of insulin analogs, the modified variants of natural insulin having a minimal risk of causing hypoglycemia. Besides the development of analogs, the mode of insulin delivery is also considered critical in achieving better glycemic control in diabetic patients. Until recently, various exogenous insulin delivery methods were practiced, but effective glycemic control without any associated risk and ease of delivery remains a subject of paramount concern. It countered attenuation or delayed onset of diabetes-associated complications without a permanent cure, raising an unmet demand for insulin formulations and delivery methods that offer stability, biocompatibility, reproducibility, precision dosing, non-immunogenicity, and safety. The current practice utilizes non-physiological delivery methods with less invasive administration routes, offering glycemic stability and therapeutic effectiveness. This review focuses on the recent advances made and future perspectives envisioned about newer insulin therapies and delivery methods that tend to improve the management of diabetes by inculcating ideas to reduce the disease's severity and improve the quality of life.

Exome sequencing identifies ADGRG4 G-protein-coupled receptors gene as a novel cancer biomarker in ovarian cancer patients from North India.

Adhesion G protein-coupled receptor G4 (ADGRG4) is a G protein-coupled receptor (GPCR) that belongs to the adhesion family. Participation of ADGRG4 in cell adhesion and migration, signaling pathway activation, influence on angiogenesis, and modulation of immune responses are some of the possible ways through which it may contribute to oncogenesis. Conducting extensive omics studies poses budgetary challenges to small labs in peripheral areas, primarily due to restricted research funding and resource limitations. Here we propose a low-budget model for biomarker screening. A total of 11 ovarian cancer samples were sent for exome sequencing. Among various genes, ADGRG4 variants were present in all 11 samples and thus were chosen as a potential biomarker in the present population. However, the precise role of ADGRG4 in cancer is not fully understood. The present study aims to look at the association between the ADGRG4 gene variants and their risk of ovarian cancer in the North Indian region of Jammu and Kashmir, India. Overall, 235 individuals (115 cases and 120 healthy controls) were genotyped for the selected biomarker using Sanger sequencing. Logistic regression was used to assess the relationship between the variant and ovarian cancer. A statistically significant association was identified between the ADGRG4 variant rs5930932 polymorphism and the incidence of ovarian cancer among the study population. When corrected for age and BMI, the dominating OR of variant rs5930932 was 1.035 (1.003-1.069) under HWE patients (0.95) and controls (0.18), with a p-value of (0.03). According to the findings of the current investigation, the ADGRG4 gene variant rs5930932 increases the chance of developing ovarian cancer in the studied population.