Metabolomic analysis has been used to characterize the effects and mechanisms of drugs for nonalcoholic fatty liver disease (NAFLD) at the metabolic level. Nuciferine is an active component derived from folium nelumbinis and has been demonstrated to have beneficial effects on a highfat diet (HFD) induced hepatic steatosis model. However, the effect of the altered metabolites of nuciferine on NAFLD has not yet been elucidated. In this study, we established a NAFLD rat model using HFD and treated with nuciferine. The lipid content levels, pro-inflammatory cytokines, and oxidative stress were investigated to access the therapeutic effects of nuciferine. Additionally, the metabolic regulatory mechanisms of nuciferine on NAFLD were analyzed using untargeted metabolomics. Gene expression of the key enzymes related to the changed metabolic pathways following nuciferine intervention was also investigated. The results showed that nuciferine treatment significantly reduced the body weight, levels of lipids, and liver enzymes in the blood and improved the hepatic steatosis in the NAFLD rat model. Nuciferine treatment also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the levels of methane dicarboxylic aldehyde (MDA) in the liver. Nuciferine treatment decreased the serum levels of interleukin (IL)-6, IL-1b, and tumor necrosis factor-alpha (TNF-a) and upregulated the gene expression of IL-6, IL-1b, and TNF-a in the liver. Metabolomic analysis indicated a metabolism disorder in the NAFLD rat model reflected in a dysfunction of the glycerophospholipid, linoleic acid, alpha-linolenic acid, arginine and proline metabolism. Conversely, treatment with nuciferine improved the metabolic disorder in the NAFLD rat model. Nuciferine treatment also regulated the gene expression of key enzymes related to the glycerophospholipid, linoleic acid, and alpha-linolenic acid metabolism pathways in the liver. In conclusion, our study demonstrated an amelioration of the metabolic disorders following nuciferine treatment in NAFLD rat model. Our study contributes to the understanding of the effects and mechanisms of drugs for complex diseases using metabolomic analysis and experimental approaches.

There is increasing evidence showing that inflammation is associated with depression in humans. Hesperidin, a natural bioflavonoid, has performed excellent effects on depression. The aim of this research was to investigate the therapeutic effect of hesperidin on chronic unpredictable mild stress (CUMS)-induced rats. The sucrose preference test (SPT), forced swimming test (FST), and open field test (OFT) were performed to measure the depression-related symptoms. The enzyme-linked immunosorbent assay (ELISA) was used to determine the concentrations of interleukin (IL)-1b, IL-6, and tumor necrosis factor (TNF)-a in the prefrontal cortex (PFC) of rats and cellular supernatant. PCR and Western blot were used to monitor the differences of NLRP3, caspase-1, ASC activation in the levels of genes and proteins in the PFC of rats and microglia. The activation of microglia was determined using immunofluorescence staining and flow cytometry assay. Our results show that hesperidin treatment significantly relieved depressive like behaviors in CUMS rats. In addition, hesperidin decreased the expression levels of IL-1b, IL-6, TNF-a, NLRP3, caspase-1, and ASC in the PFC and microglia. This study investigated that hesperidin treatment ameliorated CUMS-induced depression by suppressing microglia and inflammation.

Objective. Chaihu Jia Longgu Muli decoction (CLMD) is widely used in the treatment of poststroke depression (PSD) in China. Some evidences show that it has advantages, but there lacks reliable evidence. This study aims to systematically evaluate the efficacy and safety of CLMD in the treatment of PSD. Methods. All randomized controlled trials (RCTs) of CLMD in the treatment of PSD were searched from the following databases: PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and Chinese Biomedical Literature Service System (CBM), from their inception to May 2021. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.3 software. Results. A total of 13 RCTs involving 1665 patients were finally included in this study, among which 5 RCTs were oral CLMD alone versus antidepressants, and 8 RCTs were oral CLMD with antidepressants versus antidepressants. Meta-analysis results showed that oral administration of CLMD could improve Hamilton’s Depression Scale (HAMD) and the Modified Edinburgh-Scandinavian Stroke Scale (MESSS) scores, improve the Barthel index, and have a low rate of adverse reactions, but there was no significant difference in the total effective rate ( p = 0.21 > 0.05) and the National Institute of Health Stroke Scale (NIHSS) score ( p = 0.47 > 0.05) between the antidepressants group and the oral administration of the CLMD group. Oral CLMD combined with antidepressants could improve the total effective rate, HAMD, and MESSS score, but there was no significant difference in Barthel index ( p = 0.06 > 0.05) and the adverse reaction rate ( p = 0.14 > 0.05) between the two groups. Conclusion. Current evidence suggests that oral CLMD alone or with antidepressants is more effective and safer in the treatment of PSD than oral antidepressants. Due to the limitation of the quality and quantity of the included studies, more high-quality studies are needed to confirm the above conclusion.

An anti-CD30 antibody-drug conjugate incorporating the antimitotic agent DM1 and a stable SMCC linker, anti-CD30-MCC-DM1, was generated as a new antitumor drug candidate for CD30-positive hematological malignancies. Here, the in vitro and in vivo pharmacologic activities of anti-CD30-MCC-DM1 (also known as F0002-ADC) were evaluated and compared with ADCETRIS (brentuximab vedotin). Pharmacokinetics (PK) and the safety profiles in cynomolgus monkeys were assessed. Anti-CD30-MCC-DM1 was effective in in vitro cell death assays using CD30-positive lymphoma cell lines. We studied the properties of anti-CD30-MCC-DM1, including binding, internalization, drug release and actions. Unlike ADCETRIS, anti-CD30-MCC-DM1 did not cause a bystander effect in this study. In vivo, anti-CD30-MCC-DM1 was found to be capable of inducing tumor regression in subcutaneous inoculation of Karpas 299 (anaplastic large cell lymphoma), HH (cutaneous T-cell lymphoma) and L428 (Hodgkin’s disease) cell models. The half-lives of 4 mg/kg and 12 mg/kg anti-CD30-MCC-DM1 were about 5 days in cynomolgus monkeys, and the tolerated dose was 30 mg/kg in non-human primates, supporting the tolerance of anti-CD30-MCC-DM1 in humans. These results suggest that anti-CD30-MCC-DM1 presents efficacy, safety and PK profiles that support its use as a valuable treatment for CD30-positive hematological malignancies.

Background: Obsessive-compulsive disorder is common, chronic mental disorder, which is characterized by recurrent, unwanted, or intrusive thoughts and repetitive behaviors or mental action. Acupuncture and moxibustion, as a popular form of complementary and alternative therapy, have the advantages of low side effects, high safety, and low cost. The research showed that acupuncture and moxibustion have a good clinical efficacy on obsessive-compulsive disorder. However, there is no literature to systematically evaluate the efficacy and safety of acupuncture and moxibustion in treating obsessive-compulsive disorder. Thus, this study is aimed to evaluate the efficacy and safety of acupuncture and moxibustion for obsessive-compulsive disorder patients, providing reliable evidence for clinical application. Methods: Randomized controlled trials of acupuncture and moxibustion combined with western medicine for the treatment of obsessive-compulsive disorder will be searched in the databases including PubMed, EMBASE, the Cochrane library, Web of science, China National Knowledge Infrastructure(CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database (CBM) from inception to June, 2020. In addition, Baidu, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain the gray literature and relevant data that have not yet been published. Two qualified researchers will extract data and assess the risk of bias from included studies dependently. Statistical analysis is performed in RevMan 5.3 software. Results: The efficacy and safety of acupuncture and moxibustion combined with western medicine for obsessive-compulsive disorder will be assessed based on the total effective rate, Hamilton Anxiety Scale score, Hamilton Rating Scale for Depression score, Clinical Global Impression score, side effects, and so on. Conclusions: The proposed systematic review and meta-analysis of acupuncture and moxibustion combined with western medicine for treating obsessive-compulsive disorder is expected to provide reliable evidence for clinical application. Ethics and dissemination: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF Registration number: DOI 10.17605/OSF.IO/CDGTW