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Abstract Background Studies have reported that polyphyllin I (PPI) had effective anti-tumor activity against hepatocellular carcinoma (HCC). However, the precise molecular mechanism of this action and the direct target remain unclear. The aim of this study was to discover the molecular targets and the exact mechanism of PPI in the treatment of HCC. Methods Various HCC cells and Zebrafish xenotransplantation models were used to examine the efficacy of PPI against HCC. A proteome microarray, surface plasmon resonance (SPR) analysis, small molecule transfection, and molecular docking were conducted to confirm the direct binding targets of PPI. Transcriptome and Western blotting were then used to determine the exact responding mechanism. Finally, the anticancer effect and its precise mechanism, as well as the safety of PPI, were verified using a mouse tumor xenograft study. Results The results demonstrated that PPI had significant anticancer activity against HCC in both in vitro studies of two cells and the zebrafish model. Notably, PPI selectively enhanced the action of the Zinc finger and BTB domain-containing 16 (ZBTB16) protein by directly binding to it. Furthermore, specific knockdown of ZBTB16 markedly attenuated PPI-dependent inhibition of HCC cell proliferation and migration caused by overexpression of the gene. The transcriptome and Western blotting also confirmed that the interaction between ZBTB16 and PPI also activated the PPARγ/RXRα pathway. Finally, the mouse experiments confirmed the efficacy and safety of PPI to treat HCC. Conclusions Our results indicate that ZBTB16 is a promising drug target for HCC and that PPI as a potent ZBTB16 agonist has potential as a therapeutic agent against HCC by regulating the ZBTB16/PPARγ/RXRα signaling axis.

Evodiae Fructus (EF), an herbal medicine, possesses remarkable anti-inflammatory and analgesic properties. It exhibits insecticidal activity as a potent insecticide candidate. However, the toxic characteristics of EF and the underlying mechanisms have not been comprehensively elucidated comprehensively. Thus, we comprehensively explored the toxic components of EF and established the relationship between the therapeutic and toxic effects of EF, encouraging its therapeutic use. We found that evodiamine (EVO), one of the main ingredients of EF, can truly reflect its analgesic properties. In phenotype observation trials, low doses of EVO (< 35 ng/mL) exhibited distinct analgesic activity without any adverse effects in zebrafish. However, EVO dose-dependently led to gross morphological abnormalities in the liver, followed by pericardial edema, and increased myocardial concentrations. Furthermore, the toxic effects of EVO decreased after processing in liver microsomes but increased after administering CYP450 inhibitors in zebrafish, highlighting the prominent effect of CYP450s in EVO-mediated hepatotoxicity. EVO significantly changed the expression of genes enriched in multiple pathways and biological processes, including lipid metabolism, inflammatory response, tight junction damage, and cell apoptosis. Importantly, the PPAR/PI3K/AKT/NF-кB/tight junction-mediated apoptosis pathway was confirmed as a critical functional signaling pathway inducing EVO-mediated hepatotoxicity. This study provided a typical example of the overall systematic evaluation of traditional Chinese medicine (TCM) and its active ingredients with significant therapeutic effects and simultaneous toxicities, especially metabolic toxicities.

Birds are sensitive to heavy metal pollution, and lead (Pb) contamination can negatively affect their liver and gut. Therefore, we used budgerigars to examine liver and gut toxicosis caused by Pb exposure in bird, and the possible toxic mechanisms. The findings showed Pb exposure increased liver weight and decreased body weight. Moreover, histopathological and immunofluorescence assay results demonstrated obvious liver damage and cell apoptosis increased in Pb- treated budgerigars. Quantitative polymerase chain reaction (qPCR) results also showed Pb caused an increase in apoptosis by inhibiting the PPAR-γ/PI3K/Akt pathway. The gut microbe analyses indicated Firmicutes, Proteobacteria, and Bacteroidetes were dominant microbial phyla, and Network analysis results shown Arthrobacter, Bradyrhizobium and Alloprevotella as the hubs of Modules I, II, and III, respectively. Phenylpropanoids and polyketides, Organoheterocyclic compounds, Organic oxygen compounds, and Organic nitrogen compounds were dominant metabolite superclasses. Tauroursodeoxycholic acid, taurochenodeoxycholic acid (sodium salt), and 2-[2-(5-bromo-2-pyridyl)diaz-1-enyl]-5-(diethylamino)phenol were significantly enriched in the Pb-treated group. It showed that 41 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologues and 183 pathways differed between the Pb-treated and control budgerigars using microbial and metabolomic data. Moreover, orthogonal partial least-squares discrimination analysis (OPLS-DA) based on microbial and metabolite indicated distinct clusters in the Pb-treated and control groups. Additionally, the correlation analysis results indicated that a positive correlation for the Pb-treated and control groups between gut microbiota and metabolomic data, respectively. Furthermore, the microenvironment of the gut and liver were found to affect each other, and this study demonstrated heavy metal especially Pb may pose serious health risks to birds through the “gut–liver axis” too.

BackgroundCardiovascular disease (CVD) and cancer are the first and second causes of death in over 130 countries across the world. They are also among the top three causes in almost 180 countries worldwide. Cardiovascular complications are often noticed in cancer patients, with nearly 20% exhibiting cardiovascular comorbidities. Physical exercise may be helpful for cancer survivors and people living with cancer (PLWC), as it prevents relapses, CVD, and cardiotoxicity. Therefore, it is beneficial to recommend exercise as part of cardio-oncology preventive care.ObjectiveWith the progress of deep learning algorithms and the improvement of big data processing techniques, artificial intelligence (AI) has gradually become popular in the fields of medicine and healthcare. In the context of the shortage of medical resources in China, it is of great significance to adopt AI and machine learning methods for prescription recommendations. This study aims to develop an interpretable machine learning-based intelligent system of exercise prescription for cardio-oncology preventive care, and this paper presents the study protocol.MethodsThis will be a retrospective machine learning modeling cohort study with interventional methods (i.e., exercise prescription). We will recruit PLWC participants at baseline (from 1 January 2025 to 31 December 2026) and follow up over several years (from 1 January 2027 to 31 December 2028). Specifically, participants will be eligible if they are (1) PLWC in Stage I or cancer survivors from Stage I; (2) aged between 18 and 55 years; (3) interested in physical exercise for rehabilitation; (4) willing to wear smart sensors/watches; (5) assessed by doctors as suitable for exercise interventions. At baseline, clinical exercise physiologist certificated by the joint training program (from 1 January 2023 to 31 December 2024) of American College of Sports Medicine and Chinese Association of Sports Medicine will recommend exercise prescription to each participant. During the follow-up, effective exercise prescription will be determined by assessing the CVD status of the participants.Expected outcomesThis study aims to develop not only an interpretable machine learning model to recommend exercise prescription but also an intelligent system of exercise prescription for precision cardio-oncology preventive care.EthicsThis study is approved by Human Experimental Ethics Inspection of Guangzhou Sport University.Clinical trial registrationhttp://www.chictr.org.cn, identifier ChiCTR2300077887.

Aims: Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis. Methods: Cell Counting Kit-8 was used to evaluate the effect of berberine on the proliferation of RA fibroblast-like synoviocyte (RA-FLS) cells. The effect of berberine on matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa-Β ligand (RANKL), tumour necrosis factor alpha (TNF-α), and other factors was determined by enzyme-linked immunoassay (ELISA) kit. Transcriptome technology was used to screen related pathways and the potential targets after berberine treatment, which were verified by reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot (WB) technology. Results: Berberine inhibited proliferation and adhesion of RA-FLS cells, and significantly reduced the expression of MMP-1, MMP-3, RANKL, and TNF-α. Transcriptional results suggested that berberine intervention mainly regulated forkhead box O (FOXO) signal pathway, prolactin signal pathway, neurotrophic factor signal pathway, and hypoxia-inducible factor 1 (HIF-1) signal pathway. Conclusion: The effect of berberine on RA was related to the regulation of RAS/mitogen-activated protein kinase/FOXO/HIF-1 signal pathway in RA-FLS cells. Cite this article: Bone Joint Res 2023;12(2):91–102.

ABSTRACT Drug-resistant tuberculosis (TB) poses a major threat to global TB control; consequently, there is an urgent need to develop novel anti-TB drugs or strategies. Host-directed therapy (HDT) is emerging as an effective treatment strategy, especially for drug-resistant TB. This study evaluated the effects of berbamine (BBM), a bisbenzylisoquinoline alkaloid, on mycobacterial growth in macrophages. BBM inhibited intracellular Mycobacterium tuberculosis (Mtb) growth by promoting autophagy and silencing ATG5, partially abolishing the inhibitory effect. In addition, BBM increased intracellular reactive oxygen species (ROS), while the antioxidant N-acetyl-L-cysteine (NAC) abolished BBM-induced autophagy and the ability to inhibit Mtb survival. Furthermore, the increased intracellular Ca2+ concentration induced by BBM was regulated by ROS, and BAPTA-AM, an intracellular Ca2+-chelating agent, could block ROS-mediated autophagy and Mtb clearance. Finally, BBM could inhibit the survival of drug-resistant Mtb. Collectively, these findings provide evidence that BBM, a Food and Drug Administration (FDA)–approved drug, could effectively clear drug-sensitive and -resistant Mtb through regulating ROS/Ca2+ axis-mediated autophagy and has potential as an HDT candidate for TB therapy. IMPORTANCE It is urgent to develop novel treatment strategies against drug-resistant TB, and HDT provides a promising approach to fight drug-resistant TB by repurposing old drugs. Our studies demonstrate, for the first time, that BBM, an FDA-approved drug, not only potently inhibits intracellular drug-sensitive Mtb growth but also restricts drug-resistant Mtb by promoting macrophage autophagy. Mechanistically, BBM activates macrophage autophagy by regulating the ROS/Ca2+ axis. In conclusion, BBM could be considered as an HDT candidate and may contribute to improving the outcomes or shortening the treatment course of drug-resistant TB.

This review explored the potential of edible insects to address the challenges of malnutrition and food security. Although grain production in China has met the Food and Agriculture Organization standards, the shortage of protein supply is still a big issue. Moreover, expanding livestock farming is considered unsustainable and environmentally unfriendly. Edible insects have become an alternative with higher sustainable and ecological properties. There are 324 species of insects currently consumed in China, and they have high nutritional value, with a rich source of protein and unsaturated fatty acids. Insect farming provides numerous benefits, including green feeds for livestock, poultry, and aquaculture, sustainable organic waste management, as well as industrial and pharmaceutical raw materials. The food toxicological evaluations conducted in China indicated that edible insects are safe for general consumption by the Chinese, but allergies and other related food safety issues should not be ignored. Consumer acceptance is another barrier to overcome, with different schemas between China and Western countries. More research on the potential functions of edible insects and their product development may enhance their acceptance in China. Overall, incorporating edible insects into our diet is a promising solution to address challenges related to protein supply and food security. To ensure safety and sustainability, appropriate legislation, quality regulations, large-scale insect farms, and acceptable processing techniques are necessary. Moreover, more scientific research and social awareness are required to promote the culture and utilization of edible insects in China.

Objectives The main focus of this study was to investigate the effect of the coronavirus disease (COVID-19) pandemic on the mental health condition and sleep quality of college students in Macao. In addition, the students’ behaviours during the pandemic, such as drinking alcohol, taking sleeping pills, and seeking psychological counselling were analyzed. Method A cross-sectional survey of mental health and sleep quality status, as well as the possible behavioral risk factors, was conducted among the college students of Macao in August, 2020 during the COVID-19 pandemic. An online self-report questionnaire survey method was applied to assess the general demographics and related lifestyle behaviors of students. The general mental health condition and sleep quality were evaluated through the General Health Questionnaire (GHQ-12) and Pittsburgh Sleep Quality Index (PSQI) questionnaires, respectively. The main statistical methods included the Chi-square test, Bonferroni correction, and Pearson correlation. Data analysis was performed using SPSS Version 24.0. Results A total of 980 students were investigated in the study, of which 977 completed the survey. During the COVID-19 pandemic period, overall college students in Macao were psychologically well adjusted and reported good quality of sleep. However, female students were in poorer psychological condition than males (P < 0.05). Moreover, the students over 20 years of age had poorer sleep quality than students aged less than or equal to 20 (P < 0.05). The significant differences were found among the students in different study majors for the mental health status and sleep quality (both P < 0.05), which were associated with certain behaviors, such as drinking alcohol, taking sleeping pills, and seeking for help in psychological counselling during the COVID-19 pandemic period. Conclusions Poor mental health status could be either the consequence or cause of sleep disturbance, which might further affected physical health. Therefore, regular assessment of mental health condition and sleep quality of college students is particularly necessary during public health emergencies, such as the COVID-19 pandemic, and appropriate intervention should be provided to the students.

In order to develop the strategy more suitable campus-based coronavirus disease 2019 (COVID-19) prevention programs for undergraduate students, it is critical to identify discrepancies in knowledge of COVID-19 prevention among students from different campuses in China. The present study examined the difference in preventive knowledge about COVID-19 pandemic in undergraduate students from two cities of Guangdong-Hong Kong-Macao Greater Bay Area (GBA), Macao Special Administrative Region (SAR), which had very few cases of COVID-19 patients, and Zhuhai, which is borders Macao SAR. In August 2020, two cohorts of undergraduate students from universities in Macao (n = 977) and Zhuhai (n = 2,818) were recruited for online. The self-rating questionnaire was used to gain information about their knowledge in COVID-19 prevention. Macao and Zhuhai students had similar correct rates in terms of heat inactivation conditions of SARS-CoV-2, (76.8% vs. 76.9%, P = 0.950), etiquette when coughing and sneezing (75.9% vs. 75.0%, P = 0.562), and use of disposable masks (92.2% vs. 90.6%, P = 0.126). However, students from Macao had significantly higher rates in correct use of disinfectants against SARS-CoV-2 (24.6% vs. 17.5%, P < 0.001) and in the route of transmission of SARS-CoV-2 (84.5% vs. 79.6%, P < 0.001) than those from Zhuhai. In conclusion, the knowledge level of COVID-19 prevention differs among undergraduate students from Macao and Zhuhai, which warrants an appropriate region-specific health education strategie for COVID-19 prevention.

Biotransformation of the neo-clerodane diterpene, scutebarbatine F (1), by Streptomyces sp. CPCC 205437 was investigated for the first time, which led to the isolation of nine new metabolites, scutebarbatine F1–F9 (2–10). Their structures were determined by extensive high-resolution electrospray ionization mass spectrometry (HRESIMS) and NMR data analyses. The reactions that occurred included hydroxylation, acetylation, and deacetylation. Compounds 2–4 and 8–10 possess 18-OAc fragment, which were the first examples of 13-spiro neo-clerodanes with 18-OAc group. Compounds 7–10 were the first report of 13-spiro neo-clerodanes with 2-OH. Compounds 1–10 were biologically evaluated for the cytotoxic, antiviral, and antibacterial activities. Compounds 5, 7, and 9 exhibited cytotoxic activities against H460 cancer cell line with inhibitory ratios of 46.0, 42.2, and 51.1%, respectively, at 0.3 μM. Compound 5 displayed a significant anti-influenza A virus activity with inhibitory ratio of 54.8% at 20 μM, close to the positive control, ribavirin.