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Molecular mechanisms and translational biology of uremic pruritus in chronic kidney disease: A critical analysis of recent advances

Mon, 01 Dec 2025 00:00:00 GMT

Title: Molecular mechanisms and translational biology of uremic pruritus in chronic kidney disease: A critical analysis of recent advances Authors: Kumar Singh, Adarsh; Kaul, Anupma; Ranjan Behera, Manas; Asif, Shafaque; Tondon, Ruchika; Prasad, Pallavi Abstract: Uremic pruritus (UP) is a prevalent and distressing complication in patients with chronic kidney disease (CKD), particularly those undergoing dialysis. Once considered a peripheral symptom of skin dryness or electrolyte imbalance, UP is now recognized as a complex condition involving neuroimmune dysregulation, inflammatory signaling, and altered skin barrier function. Recent experimental studies have identified key molecular mediators such as interleukin-31 (IL-31), tumor necrosis factor-alpha (TNF-α), transient receptor potential channels (TRPV1, TRPA1), and opioid receptor imbalances that contribute to the pathogenesis of pruritus in CKD. Animal models and in vitro assays have provided crucial insights into the mechanisms underlying itch generation and neuronal sensitization. This review critically examines recent advances in the molecular biology of UP and explores translational strategies targeting these pathways. Emphasis is placed on experimental findings from the last decade and their relevance in identifying therapeutic targets. Understanding these mechanisms may help guide future development of personalized treatments and improve quality of life for affected patients. Page(s): 973-979

Mechanistic insights into diesel exhaust-induced lung cancer cell survival through AhR signaling

Mon, 01 Dec 2025 00:00:00 GMT

Title: Mechanistic insights into diesel exhaust-induced lung cancer cell survival through AhR signaling Authors: Bagde, Ankita; Katarkar, Atul; Srimuruganandam, B; Krishnamurthi, K Abstract: Diesel exhaust (DE), a Group I human carcinogen, is a major environmental pollutant that significantly contributes to global lung cancer burden. Nitro-polycyclic aromatic hydrocarbons (PAHs), particularly 1-nitropyrene (1NP) and its metabolite 1-aminopyrene (1AP), are key markers of DE exposure. Although DE has been strongly linked to genomic instability, the molecular mechanism underlying this process remains poorly understood, especially the role of aryl hydrocarbon receptor (AhR) in promoting lung cancer cell survival and carcinogenesis. To address this gap, we examined the effect of 1NP/1AP in A549 cells. Exposure to 1NP/1AP significantly induced reactive oxygen species (ROS, P<0.01) and DNA damage (P<0.0001, as evaluated using Dichloro-dihydro-fluorescein diacetate and the comet assay, respectively. AhR activation was confirmed by AhR nuclear translocation (immunofluorescence, P <0.0001) and CYP-gene expression by qRT-PCR analysis (P <0.0001). Despite such genomic instability, A549 cells continued to exhibit colony formation, migration, and spheroid growth, which were not significantly altered. Conversely, inhibition of AhR activity enhanced apoptosis (P<0.0001), and markedly reduced cell migration, colony formation, and spheroid growth (P <0.001). Furthermore, an increased γ-H2AX expression was positively correlated with DNA damage (P<0.001), suggesting that AhR activation may regulate DNA damage repair and facilitate the survival of A549 cells under 1NP/1AP insult. Our findings highlight the previously unexplored role of AhR in promoting DNA repair and lung cancer cell survival and suggest that AhR inhibition may serve as a promising therapeutic strategy for preventing DE-induced lung carcinogenesis. Page(s): 980-992

In vitro validation of novel drug candidate EGFR inhibitor in treatment of colorectal cancer employing 2D and 3D cell culture techniques

Mon, 01 Dec 2025 00:00:00 GMT

Title: In vitro validation of novel drug candidate EGFR inhibitor in treatment of colorectal cancer employing 2D and 3D cell culture techniques Authors: Krishnan K, Amrutha; George Valavi, Sudha; Joy, Amitha Abstract: Colorectal cancer (CRC) is deemed to be the third leading cause of cancer-related deaths worldwide with an overall mortality rate of 10%. One of the major causes of CRC is overexpression of EGFR, and currently, there are very few effective medications available to target it. This study intends to validate the potency of 2-((1,6-dimethyl-4-oxo-1,4- dihydropyridin-3-yl)oxy)-N-(1H-indol-4-yl)acetamide (E1) which has previously been reported as an effective EGFR inhibitor via in silico approaches. Anticancer investigation, toxicity analysis, indirect ELISA studies, clonogenic assay, livedead assay, Reactive Oxygen Species (ROS) assay, and flow cytometry analysis were conducted. Compound E1 inhibited colorectal cancer cells by 38% at an LC50 of 156.0365 μg/mL, while inhibiting normal cells by only 15% at an LC50 of 418.3150 μg/mL. Activity of BRAF (downstream antibody of EGFR in the MAPK pathway) was reduced three-fold compared to control samples, demonstrating the compound's efficacy. Colony formation ability of the cancer cells was reduced by four-fold while the ROS contents were declined by 23 times in the presence of E1. Cell cycle arrest was confirmed at G0/G1 phase through flow cytometry analysis. RT-PCR studies also confirmed the EGFR inhibition ability of E1. 3D cell culture validation of E1 established strong anticancer inhibition ability for the compound E1. The nominated compound E1 thus can be considered as a novel and potential EGFR inhibitor. Page(s): 993-1001

Implication of CA 15-3, CEA and mammary gland temperature in diagnosis and management of canine mammary tumor

Mon, 01 Dec 2025 00:00:00 GMT

Title: Implication of CA 15-3, CEA and mammary gland temperature in diagnosis and management of canine mammary tumor Authors: Ali Khan, Safar; O Kalim, M; K Tiwari, S; Sannat, C; Parveen, Kaiser; Pal1, Shubham; Sahu, Harsha Abstract: This study was conducted to explore the diagnostic potential of serum biomarkers such as CA 15-3 and CEA, along with mammary tissue infrared temperature in canine mammary tumor (CMT). Total thirty five suspected cases of CMTs were evaluated by histopathology. Further CA 15-3, CEA, and mammary tissue infrared temperature value was figured out and correlated with clinical picture of CMTs. Mammary tissue infrared temperature as well as CA 15-3 and CEA values were significantly higher in dogs with CMTs than healthy dogs. These values were also higher in malignant cases as compared to benign cases. Diagnostic sensitivity of CA 15-3, CEA and infrared thermography were 94.29%, 54.28% and 88.57%, whereas specificity were 87.5%, 87.5% and 100%, respectively for CMTs. CA 15-3 stronglyassociated with tumor progression, malignancy, CEA level, mammary tissue temperature, number of mammary gland involvement, ulceration, tumor size and tumor weight. Post-surgery reduction in serum concentration of tumor markers and mammary gland temperature were recorded in recovered animals. Thus, expression of CA 15-3 and CEA tumor markers along with mammary tissue infrared temperature could provide valuable diagnostic significance regarding nature of tumor and start of treatment regimen in CMTs. Page(s): 1002-1009