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.     

Marr and Reductionism

David Marr's three-level method for completely understanding a cognitive system and the importance he attaches to the computational level are so familiar as to scarcely need repeating. Fewer seem to recognize that Marr defends his famous method by criticizing the “reductionistic approach.” This sets up a more interesting relationship between Marr and reductionism than is usually acknowledged. I argue that Marr was correct in his criticism of the reductionists of his time—they were only describing (cellular activity), not explaining (cognitive functions). But a careful metascientific account of reductionistic neuroscience over the past two decades reveals that Marr's criticisms no longer have force. Contemporary neuroscience now explains cognition directly, although in a fashion—causal-mechanistically—quite different than Marr recommended. So while Marr was correct to reject the reductionism of his day and offer an alternative method for genuinely explaining cognition, contemporary cognitive scientists now owe us a new defense of Marr's famous method and the advantages of its explanations over the type now pursued successfully in current reductionist neuroscience. There are familiar reasons for thinking that this debt will not be paid easily.     

直丝弓矫治器和Begg矫治器治疗安氏Ⅱ类1分类错[牙合]畸形疗效比较

目的:对比不同矫治器对错[牙合]畸形患者面高度及前后牙咬合关系的影响。方法:选取于笔者医院接受矫治的83例错[牙合]畸形患者,根据患者矫治器类型分为直丝弓组和Begg组,分别为42例和41例。比较并分析两组患者治疗前后牙咬合关系、硬组织、磨牙及面高度的变化情况。结果:矫治后,两组患者OJ-PPV、OB-PP、LMA-MPV、LMA-MPV均降低,Begg矫治组OJ-PPV水平显著高于直丝弓矫治组,OB-PP、LMA-MPV、LMA-MPV水平显著低于直丝弓矫治组,差异均具有统计学意义(P<0.05);两组患者LAFH、LAFH/TAFH、PFH/TAFH水平均升高,其中Begg矫治组患者LAFH水平显著低于直丝弓矫治组,差异均具有统计学意义(P<0.05);两组患者LMA-MP、LMC-MP水平均升高,差异具有统计学意义(P<0.05);矫治前后,两组患者SNA、SNA、ANB水平均无统计学差异(P>0.05)。结论:两种矫治器对错[牙合]畸形患者硬组织变化均无明显影响,其中Begg矫治对患者前后牙咬合关系改善作用更强,直丝弓对患者面高度的改善能力更强。     

MicroARN: la biología molecular como herramienta de predicción en preeclampsia

Preeclampsia is a disease with a significant incidence worldwide that is directly associated with 15% of maternal deaths. This is usually characterized by the presence of hypertension and proteinuria, which manifests itself from the middle of pregnancy. MicroRNAs are single-stranded RNA molecules that act primarily by degrading transcribed messenger RNA or inhibiting microRNA translation. Placental microRNAs play a role in the growth and function of the placenta, their potential use as diagnostic biomarkers is considered feasible due to the ability to enter the maternal circulation and be detectable in maternal plasma.     

常见植物药对结肠癌的防治作用及其作用机制

植物药对结肠癌具有良好的防治作用。姜黄素、多糖(苹果多糖、香菇多糖)、皂苷(重楼皂苷、人参皂苷)、白藜芦醇、槲皮素等植物药可通过不同信号通路抑制结肠癌细胞的增殖,促进细胞凋亡。此外,植物药还具有抗炎、抗氧化、抗血管生成、减轻化疗药物不良反应、逆转肿瘤细胞耐药等作用。了解植物药对结肠癌的防治作用及其可能的作用机制,能为结肠癌的临床防治提供更多的理论依据及治疗思路。     

Impact des troubles orthopédiques sur la ventilation du sujet IMC/polyhandicapé

Cerebral Palsy motor disorder triggers orthopedic complications. These complications do develop by themselves and gradually degrade the motor function. The functioning of the ventilatory pump is no exception to this process. Other orthopedic impairments are impacting more indirectly ventilation. Some orthopedic treatments used for PC people are likely to worsen this clinical situation, temporarily or more permanently. Any therapeutic intervention must include two essential points: acting previously to realign posture and considering interactions of treatments on different functions.