Urinary MicroRNA biomarkers of nephrotoxicity in Macaca fascicularis.

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.

Effects of donor source on transcriptomic profiles of human kidney tissue.

Normal human tissue is a critical reference control in biomedical research. However, the type of tissue donor can significantly affect the underlying biology of the samples. We investigated the impact of tissue donor source type by performing transcriptomic analysis on healthy kidney tissue from three donor source types: cadavers, organ donors, and normal-adjacent tissue from surgical resections of clear cell renal cell carcinomas, and we compared the gene expression profiles to those of clear cell renal cell carcinoma samples.

Comprehensive Nonclinical Safety Assessment of Nirmatrelvir Supporting Timely Development of the SARS-COV-2 Antiviral Therapeutic, Paxlovid™.

COVID-19 is a potentially fatal infection caused by the SARS-CoV-2 virus. The SARS-CoV-2 3CL protease (Mpro) is a viral enzyme essential for replication and is the target for nirmatrelvir. Paxlovid (nirmatrelvir co-administered with the pharmacokinetic enhancer ritonavir) showed efficacy in COVID-19 patients at high risk of progressing to hospitalization and/or death.

Scientific and Regulatory Policy Committee Points to Consider: Biological Sample Retention From Nonclinical Toxicity Studies.

Samples of biologic specimens and their derivatives (eg, wet tissues, paraffin-embedded tissue blocks, histology slides, frozen tissues, whole blood, serum/plasma, and urine) are routinely collected during the course of nonclinical toxicity studies. Good Laboratory Practice regulations and/or guidance specify minimum requirements for specimen retention duration, with the caveat that retention of biologic specimens need not extend beyond the duration of sample stability. However, limited availability of published data regarding stability for various purposes following storage of each specimen type has resulted in confusion, uncertainty, and inconsistency as to the appropriate duration for storage of these specimens.

Behavioral, Histopathologic, and Molecular Biological Responses of Nanoparticle- and Solution-Based Formulations of Vincristine in Mice.

Clinical use of the chemotherapeutic agent vincristine (VCR) is limited by chemotherapy-induced peripheral neuropathy (CiPN). A new formulation of VCR encapsulated by nanoparticles has been proposed and developed to alleviate CiPN. We hypothesized in nonclinical animals that the nanoparticle drug would be less neurotoxic due to different absorption and distribution properties to the peripheral nerve from the unencapsulated free drug.