Mutations in a High-Grade Micropapillary Urothelial Carcinoma of the Renal Pelvis: A Case Report.

Micropapillary urothelial carcinoma (MPUC) of the renal pelvis is an upper tract urothelial carcinoma originating in the renal pelvis region. Few genetic studies are available, and the mechanism of pathogenesis of genetically driven models is unclear. We report a case of genomic alterations in MPUC of the renal pelvis and compare the results with existing literature. DNA was extracted, followed by the next-generation sequencing of 351 oncogenes and tumor suppressor genes. Targeted gene sequencing analysis revealed somatic variants in ERBB2, KMT2C, FOXA1, and germline variants in CDKN1B, ELF3, TP53, and RB1 genes. The present case study sheds light on recognizing genetic variants in high-grade MPUC of the renal pelvis. Understanding molecular mechanisms helps with better prognostication and development of more effective therapeutics and treatment.

A Randomized, Double Blind, Placebo Controlled, Crossover Study to Assess the Safety and Beneficial Effects of Cassia Tora Supplementation in Healthy Adults.

OBJECTIVE: The current clinical trial was aimed at evaluating the safety and beneficial effect of Cassia tora (C. tora) supplementation in healthy adults. DESIGN: A randomized, double blind, placebo controlled study with a crossover design was done on 60 healthy normal weight adults (age range: 20-55 yrs). The study consisted of 2 treatment phases of 24 weeks each with a washout period of 4 weeks between the phases. 30 subjects randomly allocated to the 'Placebo first' group and 30 to 'C. tora first' group and assigned to receive a dose of C. tora (330 mg) or matched placebo three times a day. Safety markers were measured at base line and at the end of both the treatment phases. Body mass index, blood pressure, fasting blood sugar, glycated hemoglobin, lipid profile and antioxidants were measured at baseline and at every three months interval. Repeated measures analysis was applied to assess the period and carryover effects of the drug over placebo on biochemistries. RESULTS: C. tora supplementation was well tolerated and no apparent changes were observed in safety markers. The net effect of C. tora in natural units over placebo was 0.83 [0.57, 1.09]- high density lipoprotein cholesterol; 27.63 [24.39, 30.88]- superoxide dismutase; 0.32 [0.28, 0.36]- catalase; 0.68 [0.56, 0.80]- glutathione peroxidase; 0.25 [0.22, 0.29]- glutathione s-transferase; 0.32 [0.29, 0.36]- glutathione and -1.08 [-1.63, -0.54]- low density lipoprotein cholesterol. CONCLUSION: The findings advocate that C. tora supplementation is safe and beneficial in elevating high density lipoprotein cholesterol and antioxidants and hence advised for consumption.

Antifibrotic effect of Centella asiatica Linn and asiatic acid on arecoline-induced fibrosis in human buccal fibroblasts.

AIM: The aim of the present study was to investigate the in vitro antifibrogenic effects of Centella asiatica Linn (CA) and its bioactive triterpene aglycone asiatic acid (AA) on arecoline-induced fibrosis in primary human buccal fibroblasts (HBF). METHODS: An ethanolic extract of CA was prepared, and AA was purchased commercially. High-performance thin-layer chromatography (HPTLC) was performed to quantify AA in the CA extract; colorimetric assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was performed to determine an half-maximal inhibitory concentration. HBF were cultured and stimulated with arecoline. The inhibitory effects of CA and AA at different concentrations were assessed using gene-expression studies on fibrosis-related markers: transforming growth factor-ß1, collagen 1 type 2, and collagen 3 type 1. The stimulatory effect of arecoline and the inhibitory effect of AA on fibroblast morphology and extracellular matrix were assessed qualitatively using Masson trichrome stain. RESULTS: The HPTLC analysis determined 1.2% AA per 100 g of CA extract. Arecoline produced a concentration-dependent increase in the fibrotic markers, treatment with CA significantly downregulated fibrotic markers at higher concentrations, and AA downregulated at lower concentrations. Arecoline altered fibroblast morphology and stained strongly positive for collagen, and AA treatment regained fibroblast morphology with faint collagen staining. CONCLUSION: CA and AA can be used as antifibrotic agents.