A worldwide decline in the quality of human semen is currently occurring. In mammals, sperm are produced from diploid stem-cell spermatogonia by spermatogenesis in testes and become mature in epididymis. Nevertheless, these biological processes can be affected by Gram-negative bacterial infection mediated by lipopolysaccharide (LPS), the major endotoxin of Gram-negative bacteria. It is well known that LPS can disturb spermatogenesis and affect sperm maturation and quality in vivo. However, the effect of LPS on the ejaculated mature sperm in vitro remains unclear. Thus, this study aimed to assess the in vitro toxicity of LPS on human sperm function and to elucidate the underlying mechanism. Human sperm were incubated with LPS (0.1-100 μg/ml) for 1-12 h in vitro and, subsequently, sperm viability, motility and capacitation, and the acrosome reaction were examined. LPS dose-dependently inhibited total and progressive motility and the ability to move through a viscous medium of the sperm but did not affect sperm viability, capacitation, and the acrosome reaction. To explore the underlying mechanism of LPS's actions, we examined the effects of LPS on the intracellular concentrations of cyclic adenosine monophosphate (cAMP) and calcium ([Ca 2+ ] i ) and protein-tyrosine phosphorylation of human sperm, which are key regulators of human sperm function. LPS decreased intracellular cAMP dose-dependently but had no effect on [Ca 2+ ] i and protein-tyrosine phosphorylation of human sperm. These findings suggest that LPS inhibits human sperm motility by decreasing intracellular cAMP.
Chemoresistance seriously hinders the treatment efficiency of human cancers, including prostate cancer (PCa). Multiple long noncoding RNAs (lncRNAs) were involved in drug resistance in PCa. We aimed to explore the function of transient receptor potential cation channel subfamily M member 2 (TRPM2) antisense RNA (TRPM2-AS) in paclitaxel (PTX) resistance in PCa. Our results showed that TRPM2-AS was increased in PTX-resistant PCa cells. TRPM2-AS knockdown accelerated cell apoptosis and inhibited cell proliferation, migration, invasion, and PTX resistance in PTX-resistant PCa cells. MiR-497-5p was bound to TRPM2-AS and its inhibition reversed the effects of TRPM2-AS knockdown on cell progression and PTX resistance in PTX-resistant PCa cells. FOXK1 was identified as a target of miR-497-5p and FOXK1 overexpression showed similar effects on cell progression and PTX resistance with miR-497-5p inhibition in PTX-resistant PCa cells. In conclusion, TRPM2-AS knockdown suppressed cell progression and PTX resistance in PTX-resistant PCa cells by miR-497-5p/FOXK1 axis.
Background: Valid cancer screening and treatment monitoring are critical for cancer patients. Although genitourinary system cancers have a high recurrence rate, when diagnosed, patients undergo surgery promptly. We sought to explore sensitive and noninvasive screening and postoperative recurrence monitoring methods, such as circulating tumor cells (CTCs) or tumor susceptibility gene detection, to determine their appropriateness for genitourinary system cancers.Methods: We adopted multiple detection methods. Enrichment-immunofluorescence in situ hybridization (SE-iFISH) was employed to detect CTCs from the peripheral blood of patients, and Agena Bioscience MassARRAY was used to detect single-nucleotide polymorphisms (SNPs) in tumor susceptibility genes from urine cells.Results: In our research, CTCs showed a 76.92% positivity rate among 26 genitourinary system cancer patients, and the number of CTCs was consistent with the stage of cancer. In monitoring for bladder cancer (BC) recurrence, CTCs were more prevalent than urine cytology (66.67% vs. 41.67%). To our surprise, urine cellular XPC (rs2228001, A2815C) and XRCC1 (rs25487, G1196A) polymorphisms were specifically found in cancer patients but not in patients with inflammation or in healthy individuals. XPC polymorphism (rs2228001, A2815C) rates were 30.77%, 40%, and 50% in bladder cancer, renal carcinoma, and prostate cancer patients, respectively, and those for XRCC1 (rs25487, G1196A) were 3.85%, 20%, and 25%, respectively.Conclusions: As a common biomarker, CTCs showed remarkable performance in cancer screening and monitoring. The noninvasive panel comprising CTCs and XPC (rs2228001, A2815C) and XRCC1 (rs25487, G1196A) polymorphisms showed high sensitivity (positive rate: 92.86%) and is suitable for genitourinary system cancer screening.
People who are not familiar with data mining algorithms can't use general data mining systems, because these data mining systems must rely on experts to give the algorithm to operate data mining. To make more people can use data mining systems conveniently; data mining system based on Case Based Reasoning was put forward in the paper. In this system, cases were organized under fuzzy quotient space model instead of traditional case index tree. Quotient space theory can divide orient universe into different grain size world, when retrieving case, it doesn't need to compare with all the cases in case base like index tree, which can improve retrieval efficiency and accurate rate. Experiment indicates the average effect was improved by 51.81 percent; it will become higher if the case base becomes bigger.
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