[Mechanism of regulation of CNP rat model by oxalis decoction via cGAS-STING signaling pathway].

OBJECTIVE: To investigate the therapeutic mechanism of oxalis decoction on CNP rats by regulating cGAS-STING signaling pathway. METHODS: Thirty specific pathogen-free SD male rats were randomly divided into normal control group (NC), model control group (MC), and oxalis decoction group (OD),with 10 rats in each group.The left and right anterior abdominal lobes of each group were surgically exposed.The normal control group was injected by the same volume of normal saline.After the model was successfully established,the OD group was given ï¼»9.37g/(kg·d)ï¼½ by gavage once a day, and the NC and MC groups were given ï¼»0.01/(mｌ/g)ï¼½ normal saline by gavage. From the 7th day of administration, the body weight of the rats in each group was recorded every 7 days for dynamic comparison. After 50 days of administration, the prostate index of the rats in each group was calculated, the morphological and pathological changes of the prostate tissue were observed by HE staining,and the expression levels of tumor necrosis factorα(TNF-α), interleukin-1ß(IL-1ß)and IL-6 in serum were detected by ELISA. RT-qPCR was used to detect the mRNA expression of cGAS, STING, TRAF6 and HSP70 in prostate tissue of rats in each group. RESULTS: Versus the NC group and OD group, the prostate organ index in MC group was significantly higher than that in other groups (P<0.01). Versus the NC group, the HE staining results of the MC group showed that the prostate gland structure was disordered, and the interstitial and acinar epithelium were extensively edema, accompanied by a large number of lymphocyte infiltration, cell swelling, loose cytoplasm, and a small number of foam cells. Versus the MC group, HE staining showed that the edema of interstitial and acinar epithelial cells in the rat prostate tissue was reduced after the OD group intervention, and the inflammatory cell infiltration in the interstitium was significantly reduced.Versus to NC group, the expression levels of TNF-α,IL-1ßandIL-6 in MC group were significantly increased（P<0.01 ).Versus to MC group,the expression levels of TNF-α, IL-1ß and IL-6 in OD group were decreased (P<0.05). Versus the NC group, the mRNA expression of cGAS, STING and TRAF6 in the MC group was significantly up-regulated,and HSP70mRNA was significantly down-regulated(P<0.01).Versus the MC group,the OD group had significantly decreased mRNA expression of cGAS, STING and TRAF6 and significantly increased mrna expression of HSP70(P<0.05). CONCLUSIONS: CNP has autoimmune disorders that cause inflammatory responses.The key target for CNP treatment is to regulate innate immunity.The treatment with oxalis decoction can significantly improve the prostate organ index and pathological changes in CNP rats, which may be related to the down-regulation of cGAS-STING innate immune signaling pathway and the inhibition of inflammatory mediators secretion.

[Action mechanisms of Xiaoluowan (II) in the treatment of epididymitis: A network pharmacology-based study].

OBJECTIVE: To explore the potential action mechanisms of Xiaoluowan (II) (XLW-II) in the treatment of epididymitis through a network pharmacology approach. METHODS: We searched various databases for relevant targets associated with epididymitis and XLW-II and obtained the common targets of epididymitis and XLW-II on the Venny platform. We acquired the protein-protein interactions (PPI) using the STRING data and had them visualized with the Cytoscape software. After topological analysis, we retrieved the key targets, followed by gene ontology (GO) and KEGG pathway enrichment analyses using the DAVID database. RESULTS: A total of 2 38 drug targets, 2 150 disease targets and 85 common targets were identified. The core targets for the treatment of epididymitis with XLW-II identified by PPI network analysis included TNF, IL6, IL1B, MMP9, AKT1, PTGS2 and TP53. GO function analysis revealed the involvement of the common targets in such biological processes as response to hypoxia, regulation of apoptotic processes, inflammatory response, and positive regulation of the MAPK cascade. KEGG pathway analysis suggested that the signaling pathways such as the cancer pathway, PI3K-Akt pathway, protein glycosylation pathway in cancer, Ras pathway and chemokine pathway might be related to the action mechanisms of XLW-II in the treatment of epididymitis. CONCLUSION: The potential targets and signaling pathways of Xiaoluowan (II) in the treatment of epididymitis were identified on the basis of network pharmacology, which has provided a novel insight into its action mechanisms and offered a new direction for further relevant studies.

[Research on the mechanism of Miao ethnicity medicine formula of Oxalis corniculata against chronic non-bacterial prostatitis].

Objective： To explore the mechanism of Miao ethnicity medicine formula of Oxalis corniculata against chronic non-bacterial prostatitis. Methods: The rat model of chronic abacterial prostatitis was induced by stimulation with 2% sterile carrageenan solution. After modeling, the rats were randomly divided into two groups, Model control group (Model group) and oxalis group. Another normal control group was set up. The rats in the Model group and the normal control group were given 0.01ml/g normal saline by gavage, and the rats in the oxalis alis group were given 1ml/100g (1 g/kg) of Oxalis corniculata L warm water decoction by gavage once a day for 28 days. Twenty-four hours after the last administration, 10ml blood was collected from the abdominal aorta of the rats, and prostate tissue samples were collected from the rats. hematoxylin-eosin (HE) staining was used to observe the morphological structure of the prostate in normal and prostatitis rats. ELISA was used to detect the levels of serum and prostate cytokines. The protein expressions of 4-HNE , ALDH2 and FGF2 were detected by Western blot. Results: Compared with the blank group, the model group showed obvious hyperplasia of fibrous tissue in the interstitium of the prostate tissue, disordered glandular structure, papillary hyperplasia of epithelial cells in the acini, infiltration of a small amount of lymphocytes, monocytes and other inflammatory cells in the acini, and increased pathological scores. The protein expressions of 4-HNE , ALDH2 , MCP-1 and FGF2 in prostate tissue were significantly increased. Compared with the model group, the prostate tissue of the oxalis group was slightly damaged, with a small amount of fibrous hyperplasia and inflammatory cell infiltration. The protein expressions of 4-HNE , ALDH2 , MCP-1 and FGF2 were decreased in prostate tissue. Conclusion： Oxalis corniculata L can effectively repair the pathological morphology of prostate tissue in rats with CNP, and its mechanism may be related to activating 4-HNE protein and reducing oxidative stress injury of prostate tissue in rats.

[Exploring the mechanism of levocarnitine in the treatment of epididymitis based on network pharmacology and molecular docking technology].

OBJECTIVE: To explore the potential mechanism of action of levocarnitine in the treatment of epididymitis based on network pharmacology and experimental research. METHODS: The target proteins related to epididymitis and levocarnitine were retrieved through multiple databases, and the common targets were obtained using Venny software. The protein-protein interactions were obtained using the STRING database. Cytoscape software was used for visualization, and key targets were selected after topological analysis. GO and KEGG pathway enrichment analysis was performed using the DAVID database. Molecular docking was performed using Autodock Vina. RESULTS: A total of 130 drug targets and 2 151 disease targets were obtained, with 47 common targets. Protein-protein interaction network analysis identified core targets of levocarnitine in the treatment of epididymitis, including AKT1, HSP90AA1, ALB, CASP3, GSK3B, and GSR. KEGG pathway analysis suggested that metabolic pathways, lipid metabolism and atherosclerosis, cancer pathways, fluid shear stress and atherosclerosis, measles, chemical carcinogens-reactive oxygen species, purine metabolism, PI3K-Akt, and other signaling pathways may be associated with the mechanism of levocarnitine in the treatment of epididymitis. CONCLUSION: This study revealed through network pharmacology that levocarnitine may act on multiple signaling pathways by targeting AKT1, HSP90AA1, ALB, CASP3, GSK3B, GSR, etc., thereby potentially exerting therapeutic effects on epididymitis.

[Low-intensity extracorporeal shockwave therapy improves symptoms of erectile dysfunction: A preliminary study].

OBJECTIVE: To verify the effect and safety of low-intensity extracorporeal shockwave therapy (Li-ESWT) in improving the symptoms of ED, and provide some reference for further related large-scale clinical trials. METHODS: Twenty-six patients diagnosed with ED received Li-ESWT with an energy of 0.09 mJ/mm2 for 20 minutes once a week for 6 four-week courses. Before and at 3, 6, 9, and 12 months after treatment, we obtained the IIEF-5 and Erectile Hardness Scale (EHS) scores of the patients using questionnaires, recorded the incidence of treatment-related adverse reactions, compared the erectile function of the patients before and after treatment, and evaluated the effect and safety of Li-ESWT in improving ED-related symptoms. RESULTS: Compared with the baseline, the IIEF-5 scores of the patients were significantly increased (P < 0.01) while the EHS scores slightly increased at 3 months after Li-ESWT treatment (P > 0.05), both IIEF-5 and EHS scores were dramatically increased at 6 months (P < 0.01), and both significantly higher than at 3 months. At 9 months, EHS scores remained remarkably higher than the baseline (P < 0.01) although IIEF-5 scores slightly lower than at 6 months. At 12 months, however, IIEF-5 scores decreased, though still significantly higher than the baseline (P < 0.01), and EHS scores became lower than at 6 and 9 months (P < 0.05) but still markedly higher than before treatment (P < 0.05). Adverse reactions observed during the intervention mainly included pruritus (4.35%), pain (2.90%), paresthesia (2.17%), and petechiae/ecchymosis (2.90%). CONCLUSION: Li-ESWT can increase the IIEF-5 and EHS scores and improve the clinical symptoms of ED patients, with a low incidence of adverse reactions during the treatment.

[Mechanism of Xiaoluanwan(II) in treating mouse epididymitis through the regulation of NLRP3 inflammasome].

OBJECTIVE: This study aimed to investigate the mechanism of Xiaoluanwan(II) in treating lipopolysaccharide(LPS)-induced epididymitis and its impact on the NLRP3 inflammasome. METHODS: The murine epididymitis model was established through local injection of LPS. The study included a control group (n=5), a model group (n=5), a model group treated with Xiaoluanwan(II) (Ⅱ) (n=5), and a saline group treated with Xiaoluanwan(II) (n=5). After 14 consecutive days of oral administration of Xiaoluanwan(II) or physiological saline, pathological changes in the epididymal tissues, expression levels of NLRP3 inflammasome and Caspase-1, as well as associated protein levels were examined. RESULTS: Compared to the model group, Xiaoluanwan(II) significantly alleviated inflammatory cell infiltration and lesions, as evidenced by a reduction in the protein expression levels of NLRP3, Caspase-1, Cleaved-Caspase-1, IL-1ß, IL-18, GSDMD, and p-p38 MAPK (P<0.05 or P<0.01), thereby mitigating the inflammatory response. CONCLUSION: Xiaoluanwan(II) alleviates epididymal inflammation and ameliorates mouse epididymal epithelial injury by modulating the NLRP3-mediated cell pyroptosis pathway.