The role of hydrogen sulfide regulation of pyroptosis in different pathological processes.

Pyroptosis is one kind of programmed cell death in which the cell membrane ruptures and subsequently releases cell contents and pro-inflammatory cytokines including IL-1ß and IL-18. Pyroptosis is caused by many types of pathological stimuli, such as hyperglycemia (HG), oxidative stress, and inflammation, and is mediated by gasdermin (GSDM) protein family. Increasing evidence indicates that pyroptosis plays an important role in multiple diseases, such as cancer, kidney diseases, inflammatory diseases, and cardiovascular diseases. Therefore, the regulation of pyroptosis is crucial for the occurrence, development, and treatment of many diseases. Hydrogen sulfide (H2S) is a biologically active gasotransmitter following carbon monoxide (CO) and nitrogen oxide (NO) in mammalian tissues. So far, three enzymes, including 3-mercaptopyruvate sulphurtransferase (3-MST), cystathionine γ- Lyase (CSE), and Cystine ß-synthesis enzyme (CBS), have been found to catalyze the production of endogenous H2S in mammals. H2S has been reported to have multiple biological functions including anti-inflammation, anti-oxidative stress, anti-apoptosis and so on. Hence, H2S is involved in various physiological and pathological processes. In recent years, many studies have demonstrated that H2S plays a critical role by regulating pyroptosis in various pathological processes, such as ischemia-reperfusion injury, alcoholic liver disease, and diabetes cardiomyopathy. However, the relevant mechanism has not been completely understood. Therefore, elucidating the mechanism by which H2S regulates pyroptosis in diseases will help understand the pathogenesis of multiple diseases and provide important new avenues for the treatment of many diseases. Here, we reviewed the progress of H2S regulation of pyroptosis in different pathological processes, and analyzed the molecular mechanism in detail to provide a theoretical reference for future related research.

Discovery of Unique Bis-Substituted Aromatic Amide Derivatives as Novel Highly Potent Antibiotics for Combating Methicillin-Resistant Staphylococcus aureus (MRSA).

Due to the increasing antibiotic resistance, developing novel antimicrobials to fight infections caused by resistant bacteria is imperative. Herein, a series of novel bis-substituted aromatic amides were designed and synthesized through modifying the hit compound 1, and their antimicrobial activities were evaluated. Among them, compound 4t, as the most potent lead, exhibited excellent antimicrobial activities against Gram-positive bacteria, including clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, while keeping weak hemolytic and mammalian cytotoxic activities. Furthermore, compound 4t displayed rapid bactericidal capabilities, low tendency to produce resistance, and favorable capacities to destroy bacterial biofilms. Further explorations indicated that compound 4t induces bacterial death by binding to cardiolipin (CL) on the bacterial membrane, disrupting the cell membrane, and facilitating the accumulation of reactive oxygen species (ROS). Additionally, compound 4t showed remarkable anti-MRSA activity in vivo, demonstrating compound 4t could be developed as a potential candidate to combat MRSA infections.

A new technique for the obliterative urethral strictures.

There have been a troublesome problem to treat with obliterative urethral strictures, the challenge is how to reduce wound of surgery and improve therapeutic success rates. In this study, we reported single-hospital institution case-series including 97 patients with obliterative urethral strictures were enrolled with "three lines lie within one imaginary plane (TLLWOIP)" to treat with patients with the obliterative urethral strictures. Perioperative variables and success rates were evaluated. Urinary flow rate, residual urine (RU) volume and quality-of-life score (QoLs) of patients were analyzed. In the obliterative urethral strictures, postoperative maximum urinary flow rate was 24.36 ± 10.69 ml, and postoperative RU volume and QoLs outcomes were significantly lower than preoperative outcomes with TLLWOIP. A total of success rate was 62.9% with TLLWOIP. Our results suggested that it was ideal candidates for initial treatment with TLLWOIP for the obliterative urethral strictures.

K channel expression in prostate epithelium and its implications in men with chronic prostatitis.

OBJECTIVE: To investigate the effect of the Kv1.3 K(+) channel on the pathogenesis of chronic prostatitis. MATERIALS AND METHODS: The expression of the Kv1.3 K(+) channel in prostatic epithelia was detected using streptavidin/peroxidase immunohistochemistry in tissue samples from 75 men with benign prostatic hyperplasia, including 42 with and 33 without chronic inflammation. All of the men were sampled in our hospital between January 2000 and December 2003. RESULTS: There was strong and moderate immunostaining in 14 of the prostatic epithelial specimens with inflammation and in 21 from patients without inflammation, compared to 28 and 12 with low staining, respectively (chi-squared, P < 0.05). CONCLUSIONS: The expression of the Kv1.3 K(+)channel was lower in prostatic epithelial cells from patients with chronic inflammation than from those without. Opening the Kv1.3 K(+) channel could promote the efflux of K(+) from the cells, causing an increase in [K(+)] in the prostate cavity. The increase in [K(+)] can then infiltrate the stroma through the epithelial gap, exciting the nerve fibres and causing pain and other clinical symptoms.

[Investigation and analysis of chronic prostatitis and sexual dysfunction].

OBJECTIVE: To investigate the prevalence of sexual dysfunction in chronic prostatitis patients and its relation with patients' age and the course of disease. METHODS: Questionnaire surveys were completed by 2 000 subjects who met the criteria for chronic prostatitis after clinical examination and expressed prostatic secretion analysis. Included in the questionnaire were: (1) age, height, weight, occupation, course of disease and treatment received; (2) NIH-CPSI; and (3) IIEF-5. RESULTS: The prevalence of sexual dysfunction in patients with chronic prostatitis was 49.0% : 26.2% of the subjects with premature ejaculation, 15.0% with erectile dysfunction and 7.7% with both premature ejaculation and erectile dysfunction. CONCLUSION: The prevalence of sexual dysfunction in patients with chronic prostatitis is high, which is negatively correlated with both the age of the patients (P < 0.001) and the course of the disease (P < 0.001).

Prevalence of sexual dysfunction in Chinese men with chronic prostatitis.

OBJECTIVE: To investigate the prevalence and risk factors of sexual dysfunction in Chinese men with chronic prostatitis. PATIENTS AND METHODS: A questionnaire survey was conducted among 2000 men diagnosed as having chronic prostatitis using the National Institutes of Health Chronic Prostatitis Index and analysis of expressed prostatic secretions. The survey was designed to elicit information about age, height, weight, occupation and history of disease and treatment. The erectile capacity of the men was assessed using the five-question version of the International Index of Erectile Function. RESULTS: Of the 2000 men with chronic prostatitis selected, 1786 completed the survey; the overall prevalence of sexual dysfunction in these patients was 49%. The prevalence of premature ejaculation and erectile dysfunction accounted for 26% and 15%, respectively; 7.7% had both premature ejaculation and erectile dysfunction. There was a negative correlation between prevalence and age, and with the duration of chronic prostatitis (both P < 0.001). CONCLUSIONS: The prevalence rate of sexual dysfunction in Chinese men with chronic prostatitis is high and related to age.