肠道菌群代谢物在心血管疾病中的作用

肠道菌群在人体疾病的发生发展中具有重要作用。肠道菌群代谢宿主摄入饮食形成的代谢产物,穿透肠上皮屏障或以其他方式进入体循环,进而激活一系列信号通路影响宿主生理过程。肠道菌群代谢物多种多样,各种代谢物如何进入体循环影响心血管系统及其在心血管疾病中发挥作用的分子机制,目前已有大量研究报道。本文就几种常见肠道菌群代谢物在高血压、动脉粥样硬化及心力衰竭等心血管疾病中的作用和分子机制进行综述,为心血管疾病的治疗提供新的方向。     

天芪降糖胶囊对糖耐量减低患者脂肪代谢组学的影响

目的研究天芪降糖胶囊对糖耐量减低患者血清代谢物的影响,探讨天芪降糖胶囊的作用途径。方法应用UPLC／TOF-MS液质联用分析方法,建立人血清代谢指纹谱,进行主成分分析（PCA）和偏最小二乘法-判别分析（PLS-DA）,观察天芪降糖胶囊的干预效果。结果治疗3个月、6个月后受试者血清代谢物发生了明显变化,天芪降糖胶囊参与机体在磷脂、糖脂、核苷、肉碱等代谢水平的修复过程。结论应用代谢组学方法,可以从整体出发研究天芪降糖胶囊对机体的作用,从小分子代谢物变化衡量其疗效。     

代谢组学技术在变应性鼻炎研究中的应用

近年来,变应性鼻炎发病率越来越高,而其诊断及治疗效果仍缺乏客观的代谢物评价指标.代谢组学通过分析生物体内源性或外源性小分子代谢物,已经成为研究过敏性疾病病因和识别潜在生物标志物的有力工具.本文从临床人群和动物模型等方面介绍代谢组学技术在变应性鼻炎研究的应用进展,旨在推动变应性鼻炎代谢组学研究的发展.     

基于代谢组学的多囊卵巢综合征研究进展

雄激素过多、排卵障碍、胰岛素抵抗和肥胖是多囊卵巢综合征(PCOS)主要特征。然而, 其发病机制并未完全明确。因此, 研究可能与PCOS有关的代谢途径, 并寻找其代谢标志物十分重要。代谢组学的应用为PCOS发病机制的研究提供了新方向。代谢组学是一种十分有价值且正在发展中的技术, 可以发现新的代谢物, 探索内分泌和代谢性疾病的潜在生物标志物。另外, 代谢组学技术还可以提高PCOS的诊疗效果。本文旨在总结近期代谢组学在PCOS中的应用以及研究进展, 从代谢物、代谢途径等方面进行阐述。     

原发性高血压相关代谢组学的初步研究

背景高血压是基因与环境共同作用的结果,而代谢异常在高血压的发生发展中的作用及其机制尚不明确。目的开展原发性高血压相关代谢组学研究,根据分析物质与能量代谢产物差异,探讨原发性高血压可能发病机制。方法应用最新代谢物检测设备超高效液相色谱-飞行时间串联质谱(Agilent 6520UPLC-Q-TOF LC/MS)对原发性高血压患者(高血压组)15例与健康志愿者(对照组)15名分析其血清中代谢产物。在通过主成分分析得到的代谢产物分子中选定差异有统计学意义的代谢产物分子,并对其进行二次鉴定,随后与已知代谢组数据库进行比较,得到具有显著差异的分子式所代表的代谢物质名称。最后,将上述确定的差异代谢产物与已知代谢途径库比较,即生物信息还原,从中挖掘出与原发性高血压相关的异常代谢物及代谢途径,获得高血压相关代谢标志物。结果高血压组和对照组共30个样本中,均出现的代谢化合物共有451种;其中31种代谢物丰度在两组间的差异有统计学意义(P0.05)。根据代谢物相关性及稳定性等筛选出13种代谢标志物进行2次鉴定,得出3种与原发性高血压发生发展密切相关的异常代谢标志物:与对照组相比,高血压组中异丙酚及美托洛尔酸丰度下调,氟他胺丰度上调(均P0.05)。本研究提示高血压发病可能与以下3种基因表达改变相关:1内皮型一氧化氮合酶基因(NOS3)变异,使NOS3含量改变,可能通过影响异丙酚的代谢而影响血压;2一氧化氮合酶2基因(NOS2)变异使NOS2表达异常,与氟他胺代谢差异相关,从而导致高血压的发生。3β2肾上腺素能受体基因(ADRB2)表达改变,使ADRB2含量改变,随之引起其调节代谢通路中美托洛尔酸的含量下调而引发高血压。结论对代谢标志物的差异分析表明,有3种代谢标志物与原发性高血压发生发展密切相关:与对照组比较,高血压组异丙酚及美托洛尔酸丰度下调,氟他胺丰度上调。     

氢谱磁共振代谢组学在2型糖尿病特征代谢物监测中的应用

目的应用氢谱磁共振(~1H-NMR)代谢组学方法研究2型糖尿病(T2DM)患者尿液中小分子代谢物代谢轮廓的变化。方法选择T2DM患者98例及健康对照组82例,利用~1H-NMR方法检测尿液的代谢轮廓,结合偏最小二乘判别分析法的模式识别分析方法,比较两组尿液中小分子代谢物差异。结果尿液的偏最小二乘判别分析法得分图显示与T2DM有关的特征代谢物包括乙酸、乳酸、牛磺酸、乙酰乙酸、葡萄糖、丙氨酸、甲基丙二酸、肌酐、柠檬酸、三甲胺等。结论糖代谢紊乱、氧化应激、氨基酸及脂类代谢异常、维生素缺乏在T2DM及其并发症的发生发展中起到重要作用。~1H-NMR代谢组学方法,可以全景监测小分子代谢终端产物的变化,符合T2DM代谢性疾病的特点。     

磁共振对代谢综合征患者血浆代谢组学分析的作用

目的从代谢组学角度研究代谢综合征(MS)的特征代谢物,并探讨其在疾病发生、发展演变过程中的整体作用机制。方法采集36例受试者的血浆,包括正常人(n=11)、MS高危患者(n=13)和MS患者(n=12),采用1 H NMR技术检测血浆的代谢谱,并对谱图的积分数据进行主成分分析(PCA)和偏最小二乘法判别分析(PLS-DA),以辨识血浆代谢产物的变化,识别并分析出特征代谢物的组分。结果代谢组学可以成功区分正常组、MS高危组、MS患者组,通过对各组特征代谢物的比较和分析,可知脂代谢异常在代谢综合征演变过程中起着重要的桥梁作用,代谢综合征的发生是机体多个系统功能改变共同造成的结果,体内碳水化合物、糖类、脂类、蛋白质等代谢紊乱是代谢综合征发病的关键环节。结论代谢组学能较清晰地反映代谢综合征血浆样本间的代谢差异和变化,作为一种新的技术手段研究代谢综合征具有重要的应用价值。     

血液代谢标志物在原发性肝癌治疗反应及预后预测中的应用

原发性肝癌是全球严重的癌症负担之一。代谢重编程是癌症的一种表型，血液代谢标志物与代谢重编程密切相关，可以预测肝癌患者复发风险和生存期情况或评估肝癌治疗反应，对于分层管理患者、制订合理治疗策略以及改善患者预后具有重要意义。本文回顾了近年来关于肝癌治疗反应评估和预后预测的血液代谢组学研究，归纳了具有预测意义的血液代谢物并简述其作用机制，分析了该领域的研究现状、存在问题和发展前景。认为芳香族氨基酸、脂质、胆汁酸等代谢物对肝癌预后预测有重要的临床应用价值，且代谢组学技术在寻找有用代谢物方面具有巨大潜力，但存在技术限制、研究不足、多重影响因素等许多有待解决的问题。     

代谢组学及其在风湿病学领域的应用

代谢组学(metabonomics)是对生物体中体液或组织代谢物在病理生理刺激和遗传因素改变条件下的系统分析,在过去的10年里,代谢组学与其他组学相比能直接分析表现型及其差异的优势,使它在药物的研发、分子医学和其他生态平衡物技术领域得以迅速的发展[1].     

高脂血症性胰腺炎患者尿样的代谢组学

目的 基于气相色谱质谱的代谢组学分析方法,研究高脂血症性胰腺炎(HLP)患者尿样.通过对其尿样代谢物组的分析和生物标记物的发现,寻找HLP的代谢变化,探讨代谢组学在急性胰腺炎(AP)中的应用.方法 取24例HLP患者尿样及40例年龄、性别匹配的正常健康人尿样,样品经预处理、衍牛和气相色谱质谱分析后,利用正交偏最小方差判别分析(OPISA-DA)的方法,观察健康组和HLP组的代谢轮廓差异.结果 上述方法能清晰地将HLP患者和健康人样本分开,通过NIST、Wiley等谱库搜索分析了21个代谢物(可信度＞700).其中用标准品鉴定之后,发现与健康组比较HLP患者尿样中烟酸、乌头酸、柠檬酸、马尿酸、对一羟基苯乙酸、对-羟基苯丙酸含量下降;色氨酸、酪氨酸、酪胺、棕榈油脂、硬脂酸等物质含量上升.代谢组学研究显示HLP患者三羧酸循环、肠道菌群结构、脂肪代谢及氨基酸代谢等发生改变.结论 HLP患者和正常人尿样代谢谱之间存在差异,而且可能从代谢组学分析中找出特异的标志性代谢产物,阐释该疾病的代谢变化;表明利用代谢组学研究尿液中的代谢物,可以为HLP的诊断和发病机制提供一个可借鉴的手段;代谢组学分析是一种有良好发展前景的研究方法.     

Glucose and insulin concentration in amniotic fluid and in maternal blood in early and in late pregnancy

Glucose concentration in the amniotic fluid decreases towards the end of gestation, whereas the insulin concentration increases. The ratio between fetal (amniotic fluid) glucose to maternal glucose is reduced by about 50% at the end of pregnancy, whereas the ratio of C peptide is increased four times. The higher glucose concentration in amniotic fluid in early pregnancy could be explained by a lower fetal metabolic rate in the early stage of development and a low insulin activity of the fetus.     

Osteoporosis in celiac disease and in endocrine and reproductive disorders

As the increase in lifespan brings to light diseases that were previously not clinically detectable, osteoporosis has become an issue of worldwide significance. The disease is marked by a loss of bone mass; the bones become less dense, fragile and more prone to fracturing. Because it is regulated by endocrine and environmental factors, osteoporosis presents a multifactorial etiopathogenesis, with the genetic component accounting for 70% of an individual variation in bone mass density （BMD）, the principal determinant, with age, of fracture risk. Pathological conditions such as celiac disease （CD） exacerbate the process of bone loss, so that the occurrence of osteoporosis in celiac subjects is of particular note： indeed, the screening of osteoporosis patients for this disease is advisable, since it may be the only sign of undiagnosed CD. An increase in interleukin IL-1β, of the IL-1 system, in the relatives of celiac patients confirms the genetic predisposition to osteoporosis and its presence is evidence of an association between the two conditions. The direct effect on the bones of CD is secondary to poor absorption of calcium and vitamin D. In women osteoporosis is indirectly associated with early menopause and amenorrhea, and it may follow prolonged breast-feeding and frequent pregnancies, while in men it is associated with hypogonadism and GH deficit. These endocrine and non-endocrine factors exert their effects on bones by modulating the RANK/RANK-L/OPG system. An appropriate lifestyle from adolescence onwards, together with early diagnosis of and treatment for CD and primaryand secondary endocrine pathologies are important for the prevention of damage to the bones.     

Anti-malarial efficacy of pyronaridine and artesunate in combination in vitro and in vivo

Pyronaridine is a Mannich base anti-malarial with demonstrated efficacy against drug resistant Plasmodium falciparum, P. vivax, P. ovale and P. malariae. However, resistance to pyronaridine can develop quickly when it is used alone but can be considerably delayed when it is administered with artesunate in rodent malaria models. The aim of this study was to evaluate the efficacy of pyronaridine in combination with artesunate against P. falciparum in vitro and in rodent malaria models in vivo to support its clinical application. Pyronaridine showed consistently high levels of in vitro activity against a panel of six P. falciparum drug-sensitive and resistant strains (Geometric Mean IC50=2.24 nM, 95% CI=1.20-3.27). In vitro interactions between pyronaridine and artesunate showed a slight antagonistic trend, but in vivo compared to pyronaridine and artesunate administered alone, the 3:1 ratio of the combination, reduced the ED90 of artesunate by approximately 15.6-fold in a pyronaridine-resistant P. berghei line and by approximately 200-fold in an artesunate-resistant line of P. berghei. Complete cure rates were achieved with doses of the combination above or equal to 8 mg/kg per day against P. chabaudi AS. These results indicate that the combination had an enhanced effect over monotherapy and lower daily doses of artesunate could be used to obtain a curative effect. The data suggest that the combination of pyronaridine and artesunate should have potential in areas of multi-drug resistant malaria.     

Differentiation pathways in carcinogenesis and in chemo- and radioresistance

Cancer stem cells (CSCs) share many features with embryonic stem cells (ESCs) such as the ability for self-renewal and differentiation. Signaling pathways that are involved in these processes are also involved in chemo- and radioresistance (e.g. Wnt, Notch and Hedgehog pathways). This review is focused on the influence of three important differentiation pathways on carcinogenesis and on chemo- and radioresistance in ESCs and CSCs.     

Telemedicine and Advances in Urban and Rural Healthcare Delivery in Africa

Telecardiology holds great promise for Africa, from tele-echocardiography and tele-ECG s, to home monitoring and text messaging for medication adherence monitoring. The burden of disease is great and there is an extreme shortage of health professionals. Telemedicine can provide access to scarce specialist care, improve the quality of care in rural areas and reduce the need for rural patients to travel to seek medical attention. International cross border service can alleviate the shortage of doctors. But telecardiology, and telemedicine uptake in general, has been poor in Africa. Legal and ethical issues around local and cross border telemedicine have not been resolved. The literature was reviewed and obstacles to telemedicine in Africa and current telemedicine activities in Africa, are described. There are few sustained telemedicine services in Africa with the exception of tele-education. There is an expectation that mobile phones will facilitate a range of telemedicine activities in Africa. Africa needs telemedicine.