山海螺本草考证与临床研究进展简

目的：考证山海螺文献记载,综述其临床研究进展。方法：通过查阅古今文献,考证历代本草学对山海螺的记述,汇总其功效报道。结果：山海螺别名有：羊乳（根）、四叶参、奶党、奶树、白河车等,古代本草著作中作为＂羊乳＂的一种,山海螺为肺经药,兼入肝、脾经,是治疗气虚伴有阴津亏乏、痰结肿疡的良药,有扶正之功,无恋邪之弊,补中可清,清中有宣,润而不腻。结论：中医临床应用山海螺有悠久历史,其功效不断被发掘和完善,特别是治疗肿瘤疾患方面具有广阔应用和开发前景。     

Orexin A decreases lipid peroxidation and apoptosis in a novel hypothalamic cell model

Current data support the idea that hypothalamic neuropeptide orexin A (OxA; hypocretin 1) mediates resistance to high fat diet-induced obesity. We previously demonstrated that OxA elevates spontaneous physical activity (SPA), that rodents with high SPA have higher endogenous orexin sensitivity, and that OxA-induced SPA contributes to obesity resistance in rodents. Recent reports show that OxA can confer neuroprotection against ischemic damage, and may decrease lipid peroxidation. This is noteworthy as independent lines of evidence indicate that diets high in saturated fats can decrease SPA, increase hypothalamic apoptosis, and lead to obesity. Together data suggest OxA may protect against obesity both by inducing SPA and by modulation of anti-apoptotic mechanisms. While OxA effects on SPA are well characterized, little is known about the short- and long-term effects of hypothalamic OxA signaling on intracellular neuronal metabolic status, or the physiological relevance of such signaling to SPA. To address this issue, we evaluated the neuroprotective effects of OxA in a novel immortalized primary embryonic rat hypothalamic cell line. We demonstrate for the first time that OxA increases cell viability during hydrogen peroxide challenge, decreases hydrogen peroxide-induced lipid peroxidative stress, and decreases caspase 3/7 induced apoptosis in an in vitro hypothalamic model. Our data support the hypothesis that OxA may promote obesity resistance both by increasing SPA, and by influencing survival of OxA-responsive hypothalamic neurons. Further identification of the individual mediators of the anti-apoptotic and peroxidative effects of OxA on target neurons could lead to therapies designed to maintain elevated SPA and increase obesity resistance.     

Hazardous effects of sanguinarine on maturation of mouse oocytes,fertilization, and fetal development through apoptotic processes

Previously, we reported that sanguinarine, a phytoalexin with antimicrobial, anti‐oxidant, anti‐inflammatory and pro‐apoptotic effects, is a risk factor for normal embryonic development that triggers apoptotic processes in the inner cell mass of mouse blastocysts, causing decreased embryonic development and cell viability. In the current study, we investigated the deleterious effects of sanguinarine on mouse oocyte maturation, in vitro fertilization (IVF), and subsequent pre‐ and postimplantation development both in vitro and in vivo. Notably, sanguinarine significantly impaired mouse oocyte maturation, decreased IVF rates, and inhibited subsequent embryonic development in vitro. Preincubation of oocytes with sanguinarine during in vitro maturation induced an increase in postimplantation embryo resorption and a decrease in mouse fetal weight. In an in vivo animal model, 1 to 5 μM sanguinarine, provided in drinking water, caused a decrease in oocyte maturation and IVF, and led to deleterious effects on early embryonic development. Importantly, preincubation of oocytes with a caspase‐3‐specific inhibitor effectively blocked sanguinarine‐triggered deleterious effects, clearly implying that embryonic injury induced by sanguinarine is mediated by a caspase‐dependent apoptotic mechanism. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 946–955, 2015.     

Editor's Choice: Birth month affects lifetime disease risk: a phenome-wide method

Objective An individual’s birth month has a significant impact on the diseases they develop during their lifetime. Previous studies reveal relationships between birth month and several diseases including atherothrombosis, asthma, attention deficit hyperactivity disorder, and myopia, leaving most diseases completely unexplored. This retrospective population study systematically explores the relationship between seasonal affects at birth and lifetime disease risk for 1688 conditions.Methods We developed a hypothesis-free method that minimizes publication and disease selection biases by systematically investigating disease-birth month patterns across all conditions. Our dataset includes 1 749 400 individuals with records at New York-Presbyterian/Columbia University Medical Center born between 1900 and 2000 inclusive. We modeled associations between birth month and 1688 diseases using logistic regression. Significance was tested using a chi-squared test with multiplicity correction.Results We found 55 diseases that were significantly dependent on birth month. Of these 19 were previously reported in the literature (P < .001), 20 were for conditions with close relationships to those reported, and 16 were previously unreported. We found distinct incidence patterns across disease categories.Conclusions Lifetime disease risk is affected by birth month. Seasonally dependent early developmental mechanisms may play a role in increasing lifetime risk of disease.     

Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases

Vision is the sense that we use to navigate the world around us. Thus it is not surprising that blindness is one of people's most feared maladies. Heritable diseases of the retina, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world, collectively affecting as many as one-third of all people over the age of 75, to some degree. For decades, scientists have dreamed of preventing vision loss or of restoring the vision of patients affected with retinal degeneration through drug therapy, gene augmentation or a cell-based transplantation approach. In this review we will discuss the use of the induced pluripotent stem cell technology to model and develop various treatment modalities for the treatment of inherited retinal degenerative disease. We will focus on the use of iPSCs for interrogation of disease pathophysiology, analysis of drug and gene therapeutics and as a source of autologous cells for cell transplantation and replacement.     

κ Opioid receptor ligands regulate angiogenesis in development and in tumours

Opioid systems mainly regulate physiological functions such as pain, emotional tone and reward circuitry in neural tissues (brain and spinal cord). These systems are also found in extraneural tissues (ganglia, gut, spleen, stomach, lung, pancreas, liver, heart, blood and blood vessels), and recent studies have elucidated their roles in various organs. The current review focuses on the roles of opioid systems in blood vessels, especially angiogenesis, during development and tumour malignancy. The balance between endogenous activators and inhibitors of angiogenesis delicately maintains a normally quiescent vasculature to sustain homeostasis. Disturbance of this balance causes pathogenic angiogenesis and, especially in tumours, several activators such as VEGF are highly expressed in the tumour microenvironment and strongly induce tumour angiogenesis, the so-called angiogenic switch. Recently, we demonstrated that κ opioid receptor agonists function as anti-angiogenic factors, which impede the angiogenic switch, in vascular development and tumour angiogenesis by inhibiting the expression of receptors for VEGF. In clinical medicine, angiogenesis inhibitors that target VEGF signalling such as bevacizumab are used as anti-cancer drugs. Although therapies that inhibit tumour angiogenesis have been highly successful for tumour therapy, most patients eventually develop resistance to this anti-angiogenic therapy. Thus, we must identify novel targets for anti-angiogenic agents to sustain inhibition of angiogenesis for tumour therapy. The regulation of responses to κ opioid receptor ligands could be useful for controlling vascular formation under physiological conditions and in cancers, and thus could offer therapeutic benefits beyond the relief of pain.

LINKED ARTICLES

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2     

甲基汞通过miRNA对人胚胎神经干细胞细胞周期相关基因表达的调控

[目的]通过研究甲基汞对人胚胎神经干细胞miRNA表达的影响,探讨低剂量甲基汞对神经干细胞细胞周期调控基因的调节作用. [方法]以0、10、50 nmol/L甲基汞染毒人胚胎神经干细胞24h后,用MTT法测定甲基汞对细胞活力影响,应用逆转录多聚酶链反应(RT-PCR)检测甲基汞对细胞周期调控基因(p16、p21)的mRNA的表达水平影响,利用实时荧光定量多聚酶链反应技术检测调控p16、p21的miRNA(miR-24、miR-106a)的表达情况. [结果]50 nmol/L甲基汞染毒组细胞活力降低为对照组的53.5％,差异有统计学意义(P＜0.05);p16与p21基因的mRNA表达水平随着甲基汞染毒浓度的升高而升高,差异均有统计学意义(P＜0.05),但10 nmol/L与50 nmol/L组的p16基因表达差异无统计学意义.miR-24、miR-106a的表达水平随着甲基汞染毒浓度的升高而降低,差异有统计学意义(P＜0.05). [结论]50 nmol/L的甲基汞可以引起人胚胎神经干细胞增殖抑制,并可能通过miRNA调节细胞周期调控基因的表达.