Causal associations of BAFF-R on IgD+ CD24- B cell immune cell trait with hepatocellular carcinoma and the mediating role of phenylacetylglutamate levels: a Mendelian randomization study.

We conducted a bi-directional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between immune cell traits and hepatocellular carcinoma (HCC) and identified the mediating factor of metabolites. The exposure factors were immune cell traits, the mediators were metabolites, and the outcome variable was HCC. Inverse-variance weighted method (IVW) was the main method. Weighted median, MR-Egger regression, weighted mode, simple mode, and MR pleiotropy residual sum and outlier (MRPRESSO) methods were used as complementary methods. The results were tested by using the Bayesian weighted Mendelian randomization (BWMR) approach in our MR study. Subsequently, the potential mediating effect was investigated by conducting a two-step mediation analysis. We identified 26 traits with suggestive correlations between immune cell traits and HCC, with 4 immune cell traits among them having causal correlations with HCC. There were no causal correlations between HCC and immune cell traits in the reverse MR analysis. In the mediation analysis, we found a positive causal association between B cell-activating factor receptors (BAFF-R) on IgD+ CD24- B cell and HCC [IVW: odd ratio (OR), 0.845; 95% CI, 0.759-0.942; p = 0.002]. Phenylacetylglutamate (PAG) levels mediated 7.353% of the causal pathway from BAFF-R on IgD+ CD24- B cell and HCC. In conclusion, BAFF-R on IgD+ CD24- B cell lowers risk of HCC, with PAG levels playing a mediating role.

Integrating transcriptomics and network pharmacology to reveal the mechanisms of total Rhizoma Coptidis alkaloids against nonalcoholic steatohepatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic steatohepatitis (NASH) has emerged as a major cause of cirrhosis and hepatocellular carcinoma, posing a significant threat to public health. Rhizoma Coptidis, a traditional Chinese medicinal herb has been shown to have significant curative effects on liver diseases. Total Rhizoma Coptidis Alkaloids (TRCA) is a primarily alkaloid mixture extracted from Rhizoma Coptidis, and its constituents are widely accepted to have hepatoprotective effects. AIM OF THE STUDY: This work aimed to investigate the efficacy and potential mechanisms of TRCA in ameliorating NASH through both in vitro experiments and in vivo mouse models. MATERIALS AND METHODS: The study employed a mice model induced by a high-fat diet (HFD) to evaluate the effectiveness and pharmacological mechanisms of TRCA in alleviating NASH. Transcriptomic sequencing and network pharmacology were used to explore the possible targets and mechanisms of TRCA to ameliorate NASH. Further validation was performed in free fatty acid (FFA)-induced human hepatocytes (LO2) and human hepatocellular carcinoma cells (HepG2). RESULTS: TRCA effectively ameliorated the main features of NASH such as lipid accumulation, hepatitis and hepatic fibrosis in the liver tissue of mice induced by HFD, as well as improved glucose tolerance and insulin resistance in mice. Combined with transcriptomic and network pharmacological analyses, 68 core targets associated with the improvement of NASH by TRCA were obtained. According to the KEGG results, the core targets were significantly enriched in the PI3K-AKT signaling pathway whereas TRCA ameliorated the aberrant down-regulation of the PI3K-AKT signaling pathway induced by HFD. Furthermore, the five highest-ranked genes were obtained by PPI network analysis. Moreover, our findings suggest that TRCA may impede the progression of HFD-induced NASH by regulating the expression of PPARG, MMP9, ALB, CCL2, and EGFR. CONCLUSIONS: TRCA can ameliorate HFD-induced liver injury by modulating aberrant downregulation of the PI3K-AKT signaling pathway. Key proteins such as PPARG, MMP9, ALB, CCL2, and EGFR may be critical targets for TRCA to ameliorate NASH. This finding supports using Rhizoma Coptidis, a well-known herbal medicine, as a potential therapeutic agent for NASH.

Jatrorrhizine from Rhizoma Coptidis exerts an anti-obesity effect in db/db mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity is closely related to diabetes. Jatrorrhizine (JAT) from Rhizoma Coptidis (RC) can reduce blood glucose and lipid levels. However, the molecular mechanisms for JAT's anti-obesity effect are still not clear. AIM OF THE STUDY: To explore the effect of JAT in the treatment of obesity and the underlying molecular mechanisms. MATERIALS AND METHODS: db/db mice were used as a typical obese animal model in current study. The anti-obesity effects of five alkaloids from RC were compared by feeding the mice for 8 weeks with a dosage of 105 mg/kg while the dose-dependent study (35 mg/kg and 105 mg/kg) of JAT on obese mice was conducted in another 8-week-long animal experiment. Meanwhile, RNA-seq analysis, in vitro experiments, and western blotting were utilized to predict and confirm the potential pathway that JAT participated in improving obesity. RESULTS: The experimental results demonstrated that five RC alkaloids caused different degrees of weight loss in db/db obese mice. Among them, JAT showed the best effect. It could significantly reduce the body weight, blood lipid levels, and epididymal fat weight of db/db mice. H&E and Oil red O staining results showed that it could also dramatically improve liver lipid metabolism. The results from RNA-seq suggested that JAT had significantly altered 207 DEGs for the treatment of obesity, among which IRS1 changed the most. Next, GO and KEGG analysis enriched four major lipid metabolism-related pathways: biosynthesis of unsaturated fatty acids, PI3K-AKT signaling pathway, metabolic pathways, and fatty acid elongation. Finally, in vitro experiments and western blotting proved that JAT regulated the expression of IRS1/PI3K/AKT pathway-related proteins in a dose-dependent manner to address obesity. CONCLUSIONS: In conclusion, JAT from RC has an effect on treating obesity, and its anti-obesity effect may be exerted via the IRS1/PI3K/AKT signaling pathway.

Comparison of a novel chemiluminescence immunoassay with the passive agglutination method for the diagnosis of Mycoplasma pneumoniae infection in children.

OBJECTIVE: The purpose of this study was to evaluate a newly developed chemiluminescence immunoassay (CLIA) and compare it to passive agglutination (PA) for the diagnosis of pneumonia caused by Mycoplasma pneumoniae in children. METHOD: A total of 291 children suspected of M. pneumoniae infections were enrolled. Serum samples were obtained from routine diagnostic requests, and specific antibodies were simultaneously detected by PA and CLIA. Cohen's kappa was used to assess the agreement between the PA and CLIA assays, multivariate logistic regression analysis was used to evaluate risk factors for the discordance between the PA and CLIA assays. RESULTS: The positive rate was 62.2% (181/291) for PA and 61.2% (178/291) for CLIA (P = 0.08). The specificity, sensitivity, negative, and positive predictive values of CLIA for M. pneumoniae infection were 80.09%, 86.7%, 78.8%, and 88.2%, respectively, with the PA test considered as the diagnostic standard. The correlation of the CLIA and PA assays was 76.8%, and the Kappa coefficient was 0.80. Significant correlations were found between the PA titers and the results of MP-IgM (R = 0.88, P < .05) and MP-IgG (R = 0.84, P < .05) detected by CLIA. CONCLUSIONS: A high degree of consistency was found between the PA and CLIA methods in detecting M. pneumoniae infections. CLIA is a reliable and rapid method and might be a promising alternative assay to PA for the diagnosis of M. pneumoniae infections.

Surveillance of Antibiotic Susceptibility Patterns of Neisseria gonorrhoeae from 2013 to 2015 in Guangxi Province, China.

Neisseria gonorrhoeae is a sexually transmitted pathogen highly prevalent worldwide with an increasing trend of resistance to antimicrobial treatment. We conducted this study to trace the susceptibility of N. gonorrhoeae to penicillin (PC), spectinomycin (SPCM), ciprofloxacin (CPFX), azithromycin (AZM), cefixime (CFIX), and ceftriaxone (CTRX) in Guangxi province. In total, 303 N. gonorrhoeae isolates were obtained from patients infected with N. gonorrhoeae in 6 cities in Guangxi during 2013-2015, and the antibiotic susceptibility patterns were analyzed by an agar dilution assay. The results showed that N. gonorrhoeae was susceptible to treatment with cephalosporins, including CTRX (99.7% of isolates), CFIX (99%), SPCM (100%), and AZM (96.4%), and this is the first report of antibiotic susceptibility for AZM surveillance of N. gonorrhoeae in Guangxi. Penicillinase-producing N. gonorrhoeae (PPNG) isolates increased in prevalence from 37% in 2013 to 64% in 2015 (P = 0.068), and tetracycline-resistant N. gonorrhoeae (TRNG) prevalence increased from 23% in 2013 to 44% in 2015 (P = 0.071). High resistance of N. gonorrhoeae to PC was associated with infection in patients at ages 25 to 30 years (P ＜ 0.05), whereas PPNG positivity (P ＜ 0.01), and TRNG positivity were risk factors for CPFX resistance (P = 0.0407). Our study provides plausible evidence for therapeutic strategies and N. gonorrhoeae infection control and prevention in Guangxi, China.

Nutrient deprivation enhances lipid content in marine microalgae.

The lipid content of microalgae is important for biodiesel production. In this study, we determined photosynthetic performance, biomass composition and lipid production of marine unicellular microalgae Chaetoceros muelleri (Bacillariophyceae) and Dunaliella salina (Chlorophyceae) cultured under different nutrient deprivation conditions. The results showed the highest lipid content of C. muelleri (46.32±3.53%) and D. salina (54.15±2.71%) could be achieved by nitrogen and complete nutrient deprivation, respectively. Analysis of fatty acid methyl esters (FAMEs) profile under those conditions revealed that the lipid accumulated by the two species was suitable to produce biodiesel. From these studies, we concluded that C. muelleri and D. salina would be highly suitable candidates for biodiesel production.