Mast cell stabilization with sodium cromoglycate modulates pulmonary vessel wall remodeling during four-day hypoxia in rats.

AIM OF THE STUDY: In rats, the environment with low content of oxygen induces hypoxic pulmonary hypertension. Remodeling of pulmonary resistance arteries is particularly triggered by the mast cell degranulation products, e.g., rodent-like interstitial collagenase (matrix metalloproteinase 13). Administration of sodium cromoglycate leads to stabilization of mast cell granules, and thus to the modified remodeling process. MATERIALS AND METHODS: During four-day hypoxia, we treated rats with sodium cromoglycate. Pulmonary vascular remodeling was assessed as well as counts of periarterial pulmonary mast cells, both total and matrix metalloproteinase 13-positive ones. RESULTS: Four-day hypoxia induced remodeling of both resistance arteries and large conduit arteries. We have found increase in the tunica media thickness of resistance arteries. Tunica adventitia thickness of both resistance arteries and large conduit arteries with a diameter of over 300 µm increased as well; the latter ones revealed increase in the number of vasa vasorum in their walls. Mast cell stabilization suppressed hypoxic pulmonary vascular remodeling in resistance pulmonary arteries. Four-day hypoxia led to changes in distribution of toluidine blue-detected and MMP-13 positive periarterial mast cells; this redistribution was also influenced by the administration of sodium cromoglycate. CONCLUSIONS: The number of pulmonary periarterial mast cells seemingly decreases during hypoxia due to their degranulation, which disables their identification. Large conduit arteries do not affect final blood pressure in the pulmonary vascular bed; however, their structure changes substantially under hypoxia. Such remodeling changes are not mediated by mast cell products only since they have occurred in spite of stabilization of mast cell granules.

Short-term Outcomes of Water Vapor Therapy (Rezum) for BPH/LUTS in the First Czech Cohort.

PURPOSE: To evaluate the short-term results of water vapor therapy (Rezum) for BPH/LUTS in the first cohort of Czech patients. MATERIALS AND METHODS: Patients with BPH and moderate to severe LUTS (N = 76) who underwent Rezum treatment from December 2019 to July 2020 were included in the prospective study. Prior to the procedure, they completed the IPSS and OABv8 questionnaires and underwent uroflowmetry, transrectal ultrasound of the prostate, and PSA sampling. The parameters before and 3 months after the procedure were compared and statistically evaluated. RESULTS: The study protocol was completed by 92% of patients (N = 70). We observed a significant increase in Qmax (median 17.7 vs. 8.8 mL/s, P < .001), Qave (9 vs. 4.5 mL/s, P = .001) and voided volume (241 vs. 171 mL, P < .001) and a significant reduction in post-void residual (average 17.5 vs. 67.7 mL), prostate volume (39.3 vs. 62.3 mL) and total PSA (median 1.9 vs. 2.5 ng/mL, resp. P values < .001). There was also a significant decrease in OABv8 score (average 7.6 vs. 16.6, P < .001) and IPSS QoL (1.6 vs. 4.0, P = .037). The improvement in the IPSS score was apparent, yet statistically insignificant (6.8 vs. 16, P = .079). CONCLUSION: Water vapor therapy is an effective and safe method of BPH/LUTS treatment in the short-term.

MicroRNAs in the pathogenesis of renal cell carcinoma and their diagnostic and prognostic utility as cancer biomarkers.

PURPOSE: To provide information about the role of microRNAs in the pathogenesis of renal cell carcinoma (RCC) and their diagnostic and prognostic utility as cancer biomarkers. METHODS: A literature search was performed in the PubMed and Web of Science databases using the keywords "renal cancer/renal cell carcinoma/kidney cancer" and "miR*/miRNA*/microRNA*". Articles dealing with the role of miRNAs in the pathogenesis of RCC, diagnostic miRNAs and prognostic miRNAs were separated. RESULTS: MiRNAs act both as oncogenes and tumor suppressors. They regulate apoptosis, cell growth, migration, invasion, proliferation, colony formation and angiogenesis through target proteins involved in several signaling pathways, and they are involved in key pathogenetic mechanisms such as hypoxia (HIF/VHL dependent) and epithelial-to-mesenchymal transition. Differentially expressed miRNAs can discriminate either tumor tissue from healthy renal tissue or different RCC subtypes. Circulating miRNAs are promissing as diagnostic biomarkers of RCC. Information about urinary miRNAs associated with RCC is sparse. Detection of a relapse is another implication of diagnostic miRNAs. The expression profiles of several miRNAs correlate with the prognosis of RCC patients. Comparison between primary tumor tissue and metastasis may help identify high-risk primary tumors. Finally, response to target therapy can be estimated thanks to differences in miRNA expression in tissue and serum of therapy-resistant versus therapy-sensitive patients. CONCLUSIONS: Our understanding of the role of microRNAs in RCC pathogenesis has been increasing dramatically. Identification and validation of their gene targets may have direct impact on developing microRNA-based anticancer therapy. Several microRNAs can serve as diagnostic and prognostic biomarkers.