Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

基于系统药理学分析野生真菌硬皮马勃治疗肿瘤多层次作用机制＊

目的 鉴定当地民间应用普遍的野生药用真菌，并探讨其治疗肿瘤的作用机制。方法 采用形态学和分子生物学方法对一株采自定陶仿山野生药用真菌进行鉴定，确定为硬皮马勃。通过文献检索收集硬皮马勃化学成分，利用PubChem软件和TCMSP、GCS数据库得到化学成分结构信息及其药用动力学参数和相关靶点分析，通过SysDT和WES系统鉴定潜在化学成分靶点，利用CTD数据库获得靶点功能，将潜在化合物和肿瘤相关靶点导入Cytoscape3.8.0软件构建分子-靶标网络。应用DAVID数据库对肿瘤相关靶点进行GO和KEGG富集分析，揭示有关活性成分靶点所涉及的生物学过程和通路，将肿瘤相关靶点和通路导入Cytoscape3.8.0软件构建靶点-通路网络。结果 从文献中获得硬皮马勃的化学成分59个，通过ADME计算系统筛选出5个潜在活性的化合物即活性成分，预测到38个靶点，其中与肿瘤相关靶点16个。这些活性成分主要通过Toll-like receptor、PI3K-AKT、MAPK和NF-kappa B等通路参与免疫应答，抑制肿瘤细胞生长、增殖，促进其凋亡。结论 表明硬皮马勃治疗肿瘤具有多靶点、多途径协同作用的特点，并通过多层次效应达到治疗肿瘤的效果。本研究为更好理解硬皮马勃作用肿瘤的机制和肿瘤药物开发提供理论依据。     

Do social support and community engagement act as mechanisms in the association between neighbourhood income inequality and the mental health of mothers in Calgary,Canada? A mediation analysis

PurposeAccording to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada.MethodsData collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement.ResultsIncome inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = −0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = −0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = −0.13, 95%CI = −0.15, −0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = −0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = −0.17, 95%CI = −0.20, −0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = −0.14, 0.41).ConclusionThe current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.     

Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

Open in a separate window     

National level data analysis of facial lacerations in Korea using the National Health Insurance Service (NHIS) database

No national epidemiological investigations have been conducted recently regarding facial lacerations. The study was performed using the data of 3,634,229 people during the 5-year period from 2014 to 2018 archived by the National Health Information Database (NHID) of the Health Insurance Review and Assessment Service. Preschool and children under 10 years old accounted for about one-third of patients. Facial lacerations were concentrated in the “T-shaped” area, which comprised forehead, nose, lips, and the perioral area. The male to female ratio for all study subjects was 2.16:1. Age and gender are significantly related with each other (P < .001). Mean hospital stays decreased, and numbers of outpatient department visits per patient were highest for hospitals and lowest for health agencies. Over the study period, hospital costs per patient in tertiary and general hospitals increased gradually. Preschool and school-aged children are vulnerable to trauma. Male patients outnumbered female patients by a factor of more than 2. The “T-shaped’” area around forehead is vulnerable to injury. Total cost of medical care benefits per patient in tertiary hospitals was about 7 times on average than in health agencies. Regarding functional, behavioral, and aesthetic outcomes, more attention should be paid to epidemiologic data and hospital costs for facial lacerations.     

膝骨关节炎中医药系统生物学研究述评＊

膝骨关节炎（Knee Osteoarthritis， KOA）属于临床难治性疾病，其高发病率、高致残性给国民健康、社会发展造成了沉重的负担。在这种不利局面下，中医药在KOA的临床防治上发挥了巨大的作用，其根据“辨证施治”理念的指导对患者采用个体化治疗往往能够取得良好的临床疗效 。然而中医学在传统认知上作为经验医学的集成，现有的KOA中医药基础研究结果尚未完全阐明其客观化、现代化的属性，阻碍了中医药防治KOA科学内涵的揭示以及全面、系统的临床研究的开展和新药研发，如何开展完善、合理、可行的基础研究以进行KOA中医药客观化和现代化探索成为研究者不得不解决的重大难题。随着系统生物学知识结构和研究手段的完善与更新，其与中医药的结合已经成为阐释并创新中医药理论内核、突破中医药研究瓶颈的重要方法。本文通过总结、分析目前KOA中医药基础研究的现状与不足，突出系统生物学在目前KOA中医药研究中的关键作用及应用趋势，以期为今后KOA的中医药研究和发展提供新的思路与对策。     

Improving cancer-specific outcomes in solid organ transplant recipients: Where to begin?

In an article published in this issue of Cancer, D’Arcy et al link the incidence of cancer among recipients of solid organ transplantation (SOT) in the Scientific Registry of Transplant Recipients with data from regional and statewide cancer registries to examine cancer-specific mortality for common malignancies in SOT recipients. This analysis helps to illuminate the role of immune surveillance across a broad range of malignancies and compares the incidence of cancers due to virally mediated oncogenesis (lymphoma, squamous cell carcinoma of the aerodigestive epithelium, and hepatitis-induced liver cancer) with the incidence of other malignancies. The authors’ central finding is that cancer-specific mortality is significantly increased in SOT recipients in comparison with nontransplant recipients for multiple cancers, and the increased cancer incidence is not limited to the effects of viral oncogenesis. The authors document a significant increase in common epithelial malignancies that are currently treated with immune checkpoint antibodies, including melanoma, bladder cancer, colorectal cancer, cancers of the oral cavity/pharynx, kidney cancer, and lung cancer, and this supports the hypothesis that post-SOT immunosuppression affects immune surveillance in these cancers. Provocatively, the authors also document increases in the incidence and mortality of cancers not typically responsive to immune checkpoint therapies, including breast cancer and pancreatic cancer. The findings of D’Arcy et al suggest that immune surveillance controls oncogenesis and tumor progression in a broad range of malignancies and that breast cancer and pancreatic cancer could be sensitive to drugs targeting immune surveillance pathways other than those treated with currently Food and Drug Administration–approved antibodies to CTLA4 and PD-1/PD-L1.     

监测数据统计分析模型在生态学研究中的应用

近年来，环境监测、疾病监测等各种监测网络不断健全，监测系统成为开展生态学研究的重要数据来源。监测数据类型包括了横断面数据、时间序列数据和面板数据，涉及暴露、结局和混杂3个维度。针对该数据的信息属性和结构特点，相关统计学方法逐渐发展完善，出现了一些新的方法、模型。基于数据的时空属性，本文对监测数据在生态学研究中常用模型的原理、适用条件及优劣进行了综述。