Metabolomics and molecular docking-directed anti-obesity study of the ethanol extract from Gynostemma pentaphyllum (Thunb.) Makino.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) is an oriental herb documented to treat many diseases, including obesity, hyperlipidemia, metabolic syndromes and aging. However, the anti-obesity mechanism of G. pentaphyllum remains poorly understood. AIM OF THE STUDY: To reveal the anti-obesity mechanism of G. pentaphyllum Extract (GPE) in High-Fat Diet (HFD)-induced obese mice through untargeted metabolomics, Real-Time Quantitative PCR (RT-qPCR), and immunohistochemical experiments. Additionally, to tentatively identify the active constituents through LC-MS/MS and molecular docking approaches. MATERIALS AND METHODS: GPE was prepared using ethanol reflux and purified by HP-20 macroporous resins. The components of GPE were identified by Liquid Chromatography- Mass Spectrometry (LC-MS) system. Forty-two C57BL/6 J mice were randomly and evenly divided into six groups, with seven mice in each group: the control group, obese model group, Beinaglutide group (positive control), and GPE low, medium, and high-dose groups (50 mg/kg, 100 mg/kg, and 200 mg/kg of 80% ethanol extract). Body weight, liver weight, blood glucose, blood lipids, and liver histopathological changes were assessed. Untargeted metabolomics was employed to characterize metabolic changes in obese mice after GPE treatment. The expression of genes related to differential metabolites was verified using Real-Time Quantitative PCR (RT-qPCR) and immunohistochemical experiments. The constituents with anti-obesity effects from GPE were tentatively identified through molecular docking approaches. RESULTS: A total of 17 compounds were identified in GPE. GPE significantly lowered body weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in obese mice and reduced liver weight and hepatic steatosis. Serum metabolomics identified 20 potential biomarkers associated with GPE treatment in obese mice, primarily related to tryptophan metabolism. GPE treatment downregulated the expression of Slc6a19 and Tph1 and upregulated Ucp1 expression. Molecular docking illustrated that compounds such as 20(R)-ginsenoside Rg3, Araliasaponin I, Damulin B, Gypenoside L, Oleifolioside B, and Tricin7-neohesperidoside identified in GPE exhibited favorable interaction with Tph1. CONCLUSION: The extract of G. pentaphyllum can inhibit the absorption of tryptophan and its conversion to 5-HT through the Slc6a19/Tph1 pathway, upregulating the expression of Ucp1, thereby promoting thermogenesis in brown adipose tissue, facilitating weight loss, and mitigating symptoms of fatty liver. Triterpenoids such as Araliasaponin I, identified in GPE, could be the potential inhibitor of Tph1 and responsible for the anti-obesity activities.

Bibliometrics and visualization analysis of literature on male hypogonadism from 2000 to 2023: research focus and frontiers.

Male hypogonadism can seriously affect male health and fertility, yet comprehensive bibliometric and visualization analyses of research in this area have been lacking. This study aimed to examine the distribution of literature, identify research hotspots, and discern development trends in male hypogonadism by analyzing 4026 English documents published between 2000 and 2023 using bibliometric and visual analyses. The results indicated a significant increase in publications and citations related to male hypogonadism over the past two decades, with the United States, the University of Florence, Maggi M, and the Journal of Clinical Endocrinology & Metabolism recognized as the most productive and highly cited country, institution, author, and journal, respectively. The article titled "The GPR54 gene as a regulator of puberty" received the highest number of citations. The keywords were categorized into four distinct clusters, including the etiology and pathogenesis of male hypogonadism, symptoms of late-onset hypogonadism, testosterone replacement therapy and its contraindications, the correlation between male hypogonadism and metabolic syndrome (MetS), obesity, and the epidemiology of male hypogonadism. The most frequently co-occurring keywords were "hypogonadism", "testosterone", and "men", while "oxidative stress" was the most prominent burst keyword. The analysis also identified "male infertility" and "oxidative stress" as the primary burst keywords in the last five years, indicating their emerging high-interest topics. Overall, this study provides a comprehensive overview of male hypogonadism research, offering valuable insights for researchers interested in this area, including potential collaborators, current research hotspots, and future research directions.

Novel DNAH1 Mutation Loci Lead to Multiple Morphological Abnormalities of the Sperm Flagella and Literature Review.

The protein encoded by dynein axonemal heavy chain 1 (DNAH1) is a part of dynein, which regulates the function of cilia and sperm flagella. The mutant of DNAH1 causes the deletion of inner dynein arm 3 in the flagellum, leading to multiple morphological abnormalities of the sperm flagella (MMAF) and severe asthenozoospermia. However, instead of asthenozoospermia and MMAF, the result caused by the mutation of DNAH1 remains unknown. Here we report a male infertility patient with severe asthenozoospermia and teratozoospermia. We found two heterozygous mutations in DNAH1 (c.6912C>A and c.7076G>T) and which were reported to be associated with MMAF for the first time. We next collected and analyzed 65 cases of DNAH1 mutation and found that the proportion of short flagella is the largest, while the bent flagella account for the smallest, and the incidence of head deformity is not high in the sperm of these patients. Finally, we also analyzed 31 DNAH1 mutation patients who were treated with intracytoplasmic sperm injection (ICSI) and achieved beneficial outcomes. We hope our research will be helpful in the diagnosis and treatment of male infertility caused by DNAH1 mutation.

[Acupoint injection of Shuxuetong for chronic prostatitis / chronic pelvic pain syndrome complicated by premature ejaculation].

OBJECTIVE: To observe the clinical efficacy of acupoint injection of Shuxuetong (SXT) in the treatment of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) complicated by premature ejaculation (PE). METHODS: A total of 78 cases of CP/CPPS complicated by PE were randomly assigned to receive acupuncture injection of SXT (n = 38) and placebo acupuncture as the control (n = 40) for two 15-day courses. The therapeutic effects were evaluated based on the patients' scores on National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) and Premature Ejaculation Diagnostic Tool (PEDT) before and after treatment. RESULTS: Compared with the controls, the SXT group showed a significantly higher total effectiveness rate based on either NIH-CPSI (27.5% vs 63.2%, P < 0.05) or PEDT (25% vs 47.4%, P < 0.05) and a lower deterioration rate (17.5% vs 7.9%, P < 0.05). Statistically significant differences were observed between the baselines and post-treatment scores on NIH-CPSI in the SXT group (24.82 ± 5.89 vs 15.45 ± 6.74, P < 0.05) and the controls (26.10 ± 6.59 vs 22.10 ± 8.42, P < 0.05) as well as on PEDT in the SXT group (14.87 ± 3.70 vs 10.29 ± 4.25, P < 0.05) and the controls (14.98 ± 3.09 vs 13.00 ± 4.53, P < 0.05), and both the NIH-CPSI and PEDT scores were markedly lower in the SXT than in the control group after treatment (P < 0.05). Linear regression analysis exhibited a positive correlation between the NIH-CPSI and PEDT scores before and after treatment in the SXT group (R = 0.340, P < 0.037) but not in the control group (R = 0.133, P < 0.413). CONCLUSIONS: Acupoint injection of Shuxuetong can significantly improve the symptoms of CP/CPPS and CP/CPPS-induced PE as well.