Neurokinin B Administration Induces Dose Dependent Proliferation of Seminal Vesicles in Adult Rats.

BACKGROUND: Neurokinin B; an endogenous decapeptide, mediates its reproductive physiological actions through gonadotropin releasing hormone. Despite the potential role of Neurokinin B on seminal vesicles, its effects on seminal vesicles in adult male mammals remain elusive. We aimed to investigate the potentials of variable doses of Neurokinin B, its agonist and antagonist on histomorphology and expression of NK3R on seminal vesicles, and secretory activity of seminal vesicles in adult male rats. METHODS: Adult male Sprague Dawley rats (n=10 in each group) were administered intraperitoneally with Neurokinin B in three variable doses: 1 µg, 1 ηg and 10 ρg while, Senktide (Neurokinin B agonist) and SB222200 (Neurokinin B antagonist) in 1 µg doses consecutively for 12 days. After 12 days of peptide treatment, half of the animals (n=05) in each group were sacrificed while remaining half (n=05) were kept for another 12 days without any treatment to investigate treatment reversal. Seminal vesicles were dissected and excised tissue was processed for light microscopy, immunohistochemistry and estimation of seminal fructose levels. RESULTS: Treatment with Neurokinin B and Senktide significantly increased while SB222200 slightly decrease the seminal vesicles weight, epithelial height and seminal fructose levels as compared to control. Light microscopy revealed increased epithelial height and epithelial folding as compared to control in all Neurokinin B and Senktide treated groups while decreased in SB222200. Effects of various doses of Neurokinin B, Senktide and SB222200 on seminal vesicles weight, epithelial height, seminal fructose levels and histomorphology were reversed when rats were maintained without treatments. Immuno-expression of Neurokinin B shows no change in treatment and reversal groups. CONCLUSION: Continuous administration of Neurokinin B and Senktide effect positively while SB222200 have detrimental effects on cellular morphology, epithelial height and seminal fructose levels in seminal vesicles. Effects of peptide treatments depicted a reversal towards control group when rats were kept without any treatment.

Identifying and validating MMP family members (MMP2, MMP9, MMP12, and MMP16) as therapeutic targets and biomarkers in kidney renal clear cell carcinoma (KIRC).

Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that carries a substantial risk of morbidity and mortality. The MMP family assumes a crucial role in tumor invasion and metastasis. This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) through a comprehensive approach encompassing both computational and molecular analyses. STRING, Cytoscape, UALCAN, GEPIA, OncoDB, HPA, cBioPortal, GSEA, TIMER, ENCORI, DrugBank, targeted bisulfite sequencing (bisulfite-seq), conventional PCR, Sanger sequencing, and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC. By performing STRING and Cytohubba analyses of the 24 MMP gene family members, MMP2 (matrix metallopeptidase 2), MMP9 (matrix metallopeptidase 9), MMP12 (matrix metallopeptidase 12), and MMP16 (matrix metallopeptidase 16) genes were denoted as hub genes having highest degree scores. After analyzing MMP2, MMP9, MMP12, and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines, interestingly, all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls. The notable effect of the up-regulated MMP2, MMP9, MMP12, and MMP16 was also documented on the overall survival (OS) of the KIRC patients. Moreover, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes (MMP2, MMP9, MMP12, and MMP16). In addition to this, hub genes were involved in various diverse oncogenic pathways. The MMP gene family members (MMP2, MMP9, MMP12, and MMP16) may serve as therapeutic targets and prognostic biomarkers in KIRC.