1.1. Objective: Qianliexin Capsule (QLX), a traditional Chinese medicine, has been widely used to treat Chronic Nonbacterial Prostatitis (CNP) in China. Here, metabolic profiling was utilized to clarify the bio-targets of QLX in CNP treatment. Methods:An estradiol-induced prostatitis rat model was used to mimic the hormonal imbalance-induced CNP. The urine and serum were collected to analyze metabolic profiles by ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS). Results:An anti-inflammatory role for QLX was seen in the estradiol-induced prostatitis rats, and the Lower Urinary Tract Symptoms (LUTS) were relieved by QLX. The unique metabolic profiling in CNP was significantly changed by addition of QLX. Thirty-nine metabolites identified in serum and urine, that are involved in multiply pathways, were significantly reversed by QLX in the CNP rats. Among them, glycerophospholipid metabolism, sphingolipid metabolism and fructose and mannose metabolic pathways were the most significantly influenced by QLX and were closely associated with the anti-inflammatory role of QLX in CNP. Conclusion: The changed metabolic profile after QLX addition may be associated with the pharmacologic function of QLX in CNP.

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Achaete scute-like 2 (Ascl2) is the Wnt signaling target, its regulation by other signaling is undefined. Now we demonstrated that CD133+/CD44+ cell population from HT-29 or Caco-2 cells exhibited cancer stem cell (CSC) properties with highly expressed Ascl2, which is related to the Hippo signaling pathway. YAP1 interference in CD133+/CD44+ HT-29 or Caco-2 cells reduced their proliferation, colony-forming ability and tumorsphere formation in vitro and inhibited the ‘stemness’-associated genes and Ascl2 expression. Enforcing YAP1 expression in HT-29 or Caco-2 cells triggered the opposite changes. Ascl2 interference reversed the phenotype of YAP1-enforced expressed HT-29 or Caco-2 cells. Krüppel-like factor 5 (KLF5) protein, not KLF5 mRNA levels, were increased due to YAP1 overexpression which is reported to prevent KLF5 degradation. Co-immunoprecipitation (Co-IP) assays demonstrated that YAP1 bound with KLF5 in HT-29 and Caco-2 cells. Luciferase and chromatin immunoprecipitation (ChIP) assays indicated that both YAP1 and KLF5 bound to the first two loci with GC-boxes in Ascl2 promoter and induced Ascl2 transcription. The decreased Ascl2 transcription by YAP1 interference required an intact KLF5 binding site (GC-box) within Ascl2 promoter, KLF5 knockdown reduced YAP1 binding and Ascl2 luciferase reporter activity upon YAP1 overexpression. Positive correlation among YAP1 and Ascl2 mRNA levels was observed in colorectal cancer (CRC) samples. Thus, our study demonstrated that Ascl2, a fate decider of CRC progenitor cells can be activated by the Hippo signaling pathway in CRC progenitor cells, and ensured their self-renewability.

Chronic bacterial prostatitis (CBP) is caused by bacterial infection and maintains a condition of lower urinary tract infection. It may be a cause of male infertility. However, studies showed inconsistent results regarding the effect of CBP on several parameters of semen. Hence, we conducted a meta-analysis to examine the effect of CBP on basic semen parameters. A systematic review was conducted with Medline, PubMed, EMBASE, and two Chinese databases (CNKI and WANG FANG) to identify relevant studies that involved the effect of CBP on semen parameters up to July 2014. Both RevMan5.2 and STATA 12.0 software were used for the statistical analysis. Based on the inclusion and exclusion criteria, seven studies were included. The study illustrated that sperm vitality, sperm total motility, and the percentage of progressively motile sperm from CBP patients were significantly lower than controls (SMD(95%CI) −0.81[−1.14, −0.47], −1.00[−1.28, −0.73], −0.41 [−0.70, −0.12], P<0.05, respectively). However, CBP had no significant effect on semen volume, sperm concentration and the duration of semen liquefaction. In summary, our study revealed that there was a significant negative effect of CBP on sperm vitality, sperm total motility, and the percentage of progressively motile sperm. Additional, studies with larger number of subjects are needed.

Chronic bacterial prostatitis (CBP) is an intractable disease. Although bone marrow mesenchymal stem cells (BMMSCs) are able to regulate inflammation in CBP, the effect of microbubble-mediated ultrasound- induced accumulation of BMMSCs on CBP remains unclear. To address this gap, a model of CBP was established in SD rats, which were then treated with BMMSCs alone (BMMSC group), BMMSCs with ultrasound (ultrasound group), BMMSCs with microbubble-mediated ultrasound (MMUS group) and compared with a healthy control group. A therapeutic-ultrasound apparatus was used to treat the prostate in the presence of circulating microbubbles and BMMSCs. The BMMSC distribution was assessed with in vivo imaging, and the prostate structure with light microscopy. Real-time quantitative RT-PCR, ELISA, and immunohistochemistry were used to assess the expressions of TNF-α and IL-1β. More BMMSCs were found in the prostate in the MMUS group than in the CBP, ultrasound, and BMMSC groups. Inflammatory cell infiltration, fibrous tissue hyperplasia, and tumor-like epithelial proliferation were significantly reduced in the MMUS group, as were the mRNA and protein expressions of TNF-α and IL-1β. Microbubble-mediated ultrasound-induced accumulation of BMMSCs can inhibit inflammation and decrease TNF-α and IL-1β expressions in the prostate of CBP rats, suggesting that this method may be therapeutic for CPB.