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。     

Exploring the impacts of organisational structure,policy and practice on the health inequalities of marginalised communities: Illustrative cases from the UK healthcare system

This paper explores how organisational structure, policies and practices in healthcare can inadvertently disadvantage marginalised populations (e.g. individuals from ethnic minority backgrounds) and reinforce health inequalities. We draw upon three diverse UK healthcare settings (long term care institutions, high security hospitals and community pharmacies) to illustrate how systemic injustices negatively impact on access to care, treatment and health outcomes. The first case study considers the care of older people within nursing homes; specifically the disempowering effects of this service structure and impacts of choice reduction upon health and their access to health provision. The second case study explores the impact of security restrictions upon patients within high security hospitals, focusing particularly on the maintenance of relationships and support networks outside of the hospital. The third and final case study, draws upon a national community pharmacy medicine management service to illustrate ways in which policies and guidelines inadvertently obstruct patients' engagement with the service within a community setting. We draw upon these settings to highlight inequalities within different contexts and to illustrate the ways in which well intended services can inadvertently disadvantage marginalised communities in multiple ways.     

The spatial dimensions of medication management by home-dwelling older adults after hospital discharge

Ageing in place raises pressing questions about medication practices at home. Understanding how medication practices are integrated into older adults’ domestic settings requires an interest in where activities linked to medication take place and why. This study aimed to describe the medication practices and spatial dimensions of medication management for home-dwelling older adults after hospital discharge, using a qualitative research design. Semi-structured interviews were carried out with ten older adults aged 65 years old or more and discharged home from hospital, together with nine informal caregivers. Thematic content analysis identified two main themes dealing with the spatial dimensions of medication management in this specific context: the process of integrating medication changes into routines and familiar spaces, and the individual and collective management of medication changes linked to a renegotiation of the boundaries between public and private spaces.     

Intimate Saboteurs

Background: The bariatric patient exists in dynamic relationship with family members and friends who have considerable influence upon the patient and his or her surgical outcome. When family members and friends behave as intimate saboteurs, they attempt to hamper, hurt, or subvert the bariatric patient's goal of achieving and maintaining a healthy body weight. Successful or not, intimate saboteurs provide significant treatment challenges for the patient and the treatment team. Methods and Patients: Patient profiles provide examples of intimate sabotage. The psychological construct of Family Systems Theory is used as a plausible explanation for the sabotage of friends and family. Conclusions: Multidisciplinary professionals treating the bariatric patient must be aware of the critical influence of intimate saboteurs and the tactics they use to sabotage. Treatment guidelines recommended by Family Systems Theory are presented as strategies to mitigate the influence of intimate saboteurs.     

艾灸联合弥可保治疗糖尿病周围神经病变40例

目的评价艾灸联合弥可保治疗糖尿病周围神经病变的疗效。方法对糖尿病周围神经病变患者80例按1∶1比例等分为联合组和对照组,两组基于等同的基础治疗之上,联合组用艾灸联合弥可保治疗,对照组单纯用弥可保治疗,疗程3个月,比较治疗前后的神经传导速度变化和症状改善情况。结果联合组和对照组神经传导速度均改善,以联合组改善更明显;联合组和对照组显效、有效、无效分别是52.5%、32.5%、15.0%和35.0%、27.5%、37.5%,组间差异有统计学意义(P<0.01或P<0.05)。结论建立于基础治疗之上的艾灸联合弥可保治疗糖尿病周围神经病变优于单纯弥可保治疗。