Antitumor activities of Grifola frondosa (Maitake) polysaccharide: A meta-analysis based on preclinical evidence and quality assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: The antitumor effects of Grifola frondosa/maitake polysaccharide (GFP) have been reported in many preclinical studies, especially in vivo experiments. The present meta-analysis aimed to provide an in vivo evidence and theoretical basis for future clinical trials by assessing the efficacy and underlying mechanisms of GFP in tumor treatment. MATERIALS AND METHODS: English and Chinese databases were examined to include animal experiments to study the antitumor activity of GFP. Literature screening, data extraction, and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In addition, the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias (RoB) tool was used to assess the risk of bias of the included animal studies. RESULTS: Potentially relevant studies (442) were identified, and finally 24 eligible studies (all in English) were included. The meta-analysis revealed that GFP has significant effects in inhibiting tumor growth (high dose: mean difference (MD) = -1.34, 95% confidence interval (CI) = [-1.73, -0.95]; low dose: MD = -5.68, 95% CI = [-7.27, -4.09]), improving tumor remission rate (odds ratio = 25.59, 95% CI = [9.08, 72.11]), and enhancing immune function in both cellular (CD4+ T cell percentage: MD = 3.03, 95% CI = [1.16, 4.90]; CD8+ T cell percentage: MD = 1.10, 95% CI = [-0.29, 2.49]) and humoral immunity (MD and [95% CI] of interleukin (IL)-2, IL-12 and tumor necrosis factor-α were 7.86 [6.29, 9.44], 35.95 [5.18, 66.72], and 10.03 [8.71, 11.36], respectively), and the differences between the two groups of the above indicators were statistically significant (all P < 0.01) except CD8+ T cell percentage. Additionally, the quality of the included studies was not high, and the risk of bias mainly concentrated on selection, detection, and reporting biases. CONCLUSION: GFP is a potential candidate for tumor treatment and clinical trials. TRIAL REGISTRATION: The review protocol for this study was registered with the PROSPERO database before beginning the review process (CRD42018108897).

Drug screening identified gemcitabine inhibiting hepatitis E virus by inducing interferon-like response via activation of STAT1 phosphorylation.

Exposure to hepatitis E virus (HEV) bears a high risk of developing chronic infection in immunocompromised patients, including organ transplant recipients and cancer patients. We aim to identify effective anti-HEV therapies through screening and repurposing safe-in-human broad-spectrum antiviral agents. In this study, a safe-in-human broad-spectrum antiviral drug library comprising of 94 agents was used. Upon screening, we identified gemcitabine, a widely used anti-cancer drug, as a potent inhibitor of HEV replication. The antiviral effect was confirmed in a range of cell culture models with genotype 1 and 3 HEV strains. As a cytidine analog, exogenous supplementation of pyrimidine nucleosides effectively reversed the antiviral activity of gemcitabine, but the level of pyrimidine nucleosides per se does not affect HEV replication. Surprisingly, similar to interferon-alpha (IFNα) treatment, gemcitabine activates STAT1 phosphorylation. This subsequently triggers activation of interferon-sensitive response element (ISRE) and transcription of interferon-stimulated genes (ISGs). Cytidine or uridine effectively inhibits gemcitabine-induced activation of ISRE and ISGs. As expected, JAK inhibitor 1 blocked IFNα, but not gemcitabine-induced STAT1 phosphorylation, ISRE/ISG activation, and anti-HEV activity. These effects of gemcitabine were completely lost in STAT1 knockout cells. In summary, gemcitabine potently inhibits HEV replication by triggering interferon-like response through STAT1 phosphorylation but independent of Janus kinases. This represents a non-canonical antiviral mechanism, which utilizes the innate defense machinery that is distinct from the classical interferon response. These results support repurposing gemcitabine for treating hepatitis E, especially for HEV-infected cancer patients, leading to dual anti-cancer and antiviral effects.

Extraction, Structural Characterization, and Biological Functions of Lycium Barbarum Polysaccharides: A Review.

Lycium barbarum polysaccharides (LBPs), as bioactive compounds extracted from L. barbarum L. fruit, have been widely explored for their potential health properties. The extraction and structural characterization methods of LBPs were reviewed to accurately understand the extraction method and structural and biological functions of LBPs. An overview of the biological functions of LBPs, such as antioxidant function, antitumor activity, neuroprotective effects, immune regulating function, and other functions, were summarized. This review provides an overview of LBPs and a theoretical basis for further studying and extending the applications of LBPs in the fields of medicine and food.

Infection dynamics of hepatitis E virus in naturally infected pigs in a Chinese farrow-to-finish farm.

To analyze the changes that occur in pigs during hepatitis E virus (HEV) infection, 256 serial serum samples were obtained from 32 pigs from one pig farm at ages 0 (cord blood), 15, 30, 60, 75, 90, 120, and 150 days. All HEV markers were assayed in these samples and showed that total anti-HEV antibodies and IgG formed two peaks. The first peak occurred at 0-60 days and the second after 75 days. No markers of infection, such as HEV RNA, antigen and anti-HEV IgM, were detectable during the first peak. Most newborn piglets (< 24 h of age) were negative for total anti-HEV and IgG. However, colostrum from all of the sows had evidence of these antibodies. Thus, the anti-HEV in the first peak was assumed to be acquired from maternal milk. Some infectious markers were positive at the beginning of second peak. PCR products were cloned and sequenced and the results indicated those sequences belonged to HEV genotype 4. The antibody present during the second peak may be induced by natural infection with HEV. In conclusion, pigs are susceptible to HEV infection and may remain infectious after the first peak of anti-HEV antibody.