Drug-induced kidney injury (DIKI) refers to kidney damage resulting from the administration of medications. The aim of this project was to identify reliable urinary microRNA (miRNAs) biomarkers that can be used as potential predictors of DIKI before disease diagnosis. This study quantified a panel of six miRNAs (miRs-210-3p, 423-5p, 143-3p, 130b-3p, 486-5p, 193a-3p) across multiple time points using urinary samples from a previous investigation evaluating effects of a nephrotoxicant in cynomolgus monkeys. Exosome-associated miRNA exhibited distinctive trends when compared to miRNAs quantified in whole urine, which may reflect a different urinary excretion mechanism of miRNAs than those released passively into the urine. Although further research and mechanistic studies are required to elucidate how these miRNAs regulate signaling in disease pathways, we present, for the first time, data that several miRNAs displayed strong correlations with histopathology scores, thus indicating their potential use as biomarkers to predict the development of DIKI in preclinical studies and clinical trials. Also, these findings can potentially be translated into other non-clinical species or human for the detection of DIKI.
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http://dx.doi.org/10.1016/j.yrtph.2024.105668 | DOI Listing |
Pathol Res Pract
January 2025
Department of Pathology, Faculty of Medicine, Suez University, Suez, Egypt.
Urinary bladder cancer (UBC) is the ninth most common cancer worldwide. Despite the reliance of UBC therapy on definite pathological grading and classifications, the clinical response among patients varies widely. The molecular basis of this type of cancer appeals to considerable research; hence, new diagnostic and therapeutic options are introduced.
View Article and Find Full Text PDFNan Fang Yi Ke Da Xue Xue Bao
January 2025
ZHANG Zhongjing School of Chinese Medicine, Rheumatology and Immunology, Nanyang Traditional Chinese Medicine Hospital, Nanyang 473004, China.
Objectives: To investigate the protective effect of Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism.
Methods: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting.
Indian J Pathol Microbiol
October 2024
Department of Pathology, Sichuan Taikang Hospital, Chengdu, China.
Objective: To explore more and better liquid biopsy markers of exosomal microRNAs (exo-miRNAs) in renal interstitial fibrosis (RIF) and to preliminary investigate the biological functions and signaling pathways involved in these markers.
Materials And Methods: High-throughput miRNA sequencing was performed on blood and urine exo-miRNAs from three RIF patients and three healthy volunteers, and differential expression analysis and bioinformatic processing were performed.
Results: There were 13 differentially expressed exo-miRNA (DEexo-miRNA) between RIF and healthy blood, and 20 DEexo-miRNAs in urine.
Biomolecules
December 2024
Department of Medicine and Feinstein Institute for Medical Research, Zucker School of Medicine, Hempstead, NY 11549, USA.
Patients carrying APOL1 risk alleles (G1 and G2) have a higher risk of developing Focal Segmental Glomerulosclerosis (FSGS); we hypothesized that escalated levels of miR193a contribute to kidney injury by activating renin-angiotensin system (RAS) in the APOL1 milieus. Differentiated podocytes (DPDs) stably expressing vector (V/DPD), G0 (G0/DPDs), G1 (G1/DPDs), and G2 (G2/DPDs) were evaluated for renin, Vitamin D receptor (VDR), and podocyte molecular markers (PDMMs, including WT1, Podocalyxin, Nephrin, and Cluster of Differentiation [CD]2 associated protein [AP]). G0/DPDs displayed attenuated renin but an enhanced expression of VDR and Wilms Tumor [WT]1, including other PDMMs; in contrast, G1/DPDs and G2/DPDs exhibited enhanced expression of renin but decreased expression of VDR and WT1, as well as other PDMMs (at both the protein and mRNA levels).
View Article and Find Full Text PDFEClinicalMedicine
December 2024
Department of Pathology and Genetics, Laboratory of Cancer Medical Science, Hokuto Hospital, Obihiro, Hokkaido, Japan.
Background: Pancreatic cancer is highly aggressive and has a low survival rate primarily due to late-stage diagnosis and the lack of effective early detection methods. We introduce here a novel, noninvasive urinary extracellular vesicle miRNA-based assay for the detection of pancreatic cancer from early to late stages.
Methods: From September 2019 to July 2023, Urine samples were collected from patients with pancreatic cancer (n = 153) from five distinct sites (Hokuto Hospital, Kawasaki Medical School Hospital, National Cancer Center Hospital, Kagoshima University Hospital, and Kumagaya General Hospital) and non-cancer participants (n = 309) from two separate sites (Hokuto Hospital and Omiya City Clinic).
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