An integrated pathway interaction network for the combination of four effective compounds from ShengMai preparations in the treatment of cardio-cerebral ischemic diseases

Aim:

SMXZF (a combination of ginsenoside Rb1, ginsenoside Rg1, schizandrin and DT-13) derived from Chinese traditional medicine formula ShengMai preparations) is capable of alleviating cerebral ischemia-reperfusion injury in mice. In this study we used network pharmacology approach to explore the mechanisms of SMXZF in the treatment of cardio-cerebral ischemic diseases.

Methods:

Based upon the chemical predictors, such as chemical structure, pharmacological information and systems biology functional data analysis, a target-pathway interaction network was constructed to identify potential pathways and targets of SMXZF in the treatment of cardio-cerebral ischemia. Furthermore, the most related pathways were verified in TNF-α-treated human vascular endothelial EA.hy926 cells and H2O2-treated rat PC12 cells.

Results:

Three signaling pathways including the NF-κB pathway, oxidative stress pathway and cytokine network pathway were demonstrated to be the main signaling pathways. The results from the gene ontology analysis were in accordance with these signaling pathways. The target proteins were found to be associated with other diseases such as vision, renal and metabolic diseases, although they exerted therapeutic actions on cardio-cerebral ischemic diseases. Furthermore, SMXZF not only dose-dependently inhibited the phosphorylation of NF-κB, p50, p65 and IKKα/β in TNF-α-treated EA.hy926 cells, but also regulated the Nrf2/HO-1 pathway in H2O2-treated PC12 cells.

Conclusion:

NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases.     

Trypanocidal treatment of Chagas disease

Chagas disease is a neglected parasitosis caused by the protozoan parasite Trypanosoma cruzi. This infection is present in most Latin American countries, although, due to migratory movements, it is a growing cause for concern in non-endemic countries. The only two drugs currently available for its treatment—benznidazole and nifurtimox—were marketed 50 years ago. While they are very effective for acute and recent infection, and for the prevention of maternofoetal transmission, their efficacy declines in people who have chronic infection, especially those older than 18 years of age. In the presence of visceral involvement, parasiticidal treatment is of little or no value. The safety profile of both drugs is far from ideal, with frequent adverse events and high rates of drug discontinuation, mainly in adults. So far, new drugs and new strategies have not been shown to improve the results of the current nitroimidazoles, although the results are promising. In this review, we focus on the aspects that allow clinicians to make the best use of currently available drugs. In addition, we discuss new therapeutic options and ongoing research in the field.     

Fibra dietaria y microbiota,revisión narrativa de un grupo de expertos de la Asociación Mexicana de Gastroenterología

Dietary fiber intake is one of the most influential and efficacious strategies for modulating the gut microbiota. Said fiber can be digested by the microbiota itself, producing numerous metabolites, which include the short-chain fatty acids (SCFAs). SCFAs have local and systemic functions that impact the composition and function of the gut microbiota, and consequently, human health. The aim of the present narrative review was to provide a document that serves as a frame of reference for a clear understanding of dietary fiber and its direct and indirect effects on health.The direct benefits of dietary fiber intake can be dependent on or independent of the gut microbiota. The use of dietary fiber by the gut microbiota involves several factors, including the fiber's physiochemical characteristics. Dietary fiber type influences the gut microbiota because not all bacterial species have the same capacity to produce the enzymes needed for its degradation. A low-fiber diet can affect the balance of the SCFAs produced. Dietary fiber indirectly benefits cardiometabolic health, digestive health, certain functional gastrointestinal disorders, and different diseases.     

Pattern of in-hospital pediatric mortality over a 3-year period at University teaching hospitals in Iran

Introduction:

Causes of death are different and very important for policy makers in different regions. This study was designed to analyze the data for our in-patient children mortality.

Materials and Methods:

In this cross-sectional study from March 2011 to March 2013, all patients from 2 months to 18 years who died in pediatric intensive care unit, emergency room or medical pediatric wards in the teaching hospitals were studied.

Results:

From a total of 18,915 admissions during a 2-year-period, 256 deaths occurred with a mean age of 4.3 ± 5 years and mortality 1.35%. An underlying disease was present in 70.7% of the patients and in 88.5% of them the leading causes of death were related to the underlying diseases. The most common underlying diseases were congenital heart disease and cardiomyopathy in 50 (27.6%). The four main causes of deaths were sepsis (14.8%), pneumonia (14.5%), congestive heart failure (9.8%), and hepatic encephalopathy (9.8%).

Conclusion:

We may conclude that after sepsis and pneumonia, congestive heart failure, and hepatic encephalopathy are the leading causes of death. Most patients who died had underlying diseases including malignancies, heart and liver diseases as the most common causes.     

TNBS诱导炎症性肠病大鼠结肠神经元tau蛋白磷酸化以及COX-2表达的变化

目的:探讨三硝基苯磺酸(trinitrobenzene sulfonic acid,TNBS)诱导炎症性肠病(inflammatory bowel disease,IBD)模型大鼠结肠神经元tau蛋白磷酸化和环氧合酶2(COX-2)表达的变化。方法:30只健康雄性成年Wistar大鼠随机分为对照组、IBD模型组和TNBS组,每组10只,IBD模型组以TNBS乙醇连续灌肠14 d造模,对照组和TNBS组分别以等量生理盐水和TNBS灌肠;观察大鼠的一般情况和结肠病理组织学改变,用anti-Hu作为神经元标志以免疫荧光法检测结肠黏膜下神经元的数量变化,免疫荧光双染色检测结肠黏膜下神经元COX-2和磷酸化tau231、tau262的表达变化。结果:与对照组比较,IBD模型组大鼠结肠黏膜下神经元数量明显减少(P0.05),神经元tau蛋白磷酸化程度明显升高(P0.05),而TNBS组大鼠神经元数量与对照组相比无显著差别;对照组和TNBS组大鼠结肠黏膜下神经元几乎不表达COX-2,IBD模型组大鼠结肠神经细胞胞核和胞浆中均有COX-2的表达,与对照组和TNBS组相比有显著差异(P0.05)。结论:TNBS乙醇诱导IBD模型大鼠结肠黏膜下神经元减少,可能与tau蛋白高度磷酸化及COX-2表达有关。     

IgG4相关性疾病临床病理学特征分析

目的：探讨IgG4相关性疾病的病理学形态、免疫表型特征。方法观察12例IgG4相关性疾病的镜下特点,结合免疫组化EnVision两步法染色检测IgG、IgG4、CD138、CD34的表达,分析IgG4相关性疾病的病理学形态特征。结果 IgG4相关性疾病主要表现为组织弥漫性纤维化;伴大量淋巴细胞、浆细胞浸润,围绕血管神经分布;闭塞性静脉炎形成,免疫组化EnVision两步法染色IgG4阳性浆细胞与IgG阳性浆细胞比例>40%。结论 IgG4相关性疾病临床特点和影像学无特异性,易误诊为肿瘤,术前血清IgG4检测可作为疑似病例的首选方法。     

Huntington's Disease (HD): Neurodegeneration of Brodmann's Primary Visual Area 17 (BA17)

Huntington's disease (HD), an autosomal dominantly inherited polyglutamine or CAG repeat disease along with somatomotor, oculomotor, psychiatric and cognitive symptoms, presents clinically with impairments of elementary and complex visual functions as well as altered visual‐evoked potentials (VEPs). Previous volumetric and pathoanatomical post‐mortem investigations pointed to an involvement of Brodmann's primary visual area 17 (BA17) in HD. Because the involvement of BA17 could be interpreted as an early onset brain neurodegeneration, we further characterized this potential primary cortical site of HD‐related neurodegeneration neuropathologically and performed an unbiased estimation of the absolute nerve cell number in thick gallocyanin‐stained frontoparallel tissue sections through the striate area of seven control individuals and seven HD patients using Cavalieri's principle for volume and the optical disector for nerve and glial cell density estimations. This investigation showed a reduction of the estimated absolute nerve cell number of BA17 in the HD patients (71 044 037 ± 12 740 515 nerve cells) of 32% in comparison with the control individuals (104 075 067 ± 9 424 491 nerve cells) (Mann–Whitney U‐test; P < 0.001). Additional pathoanatomical studies showed that nerve cell loss was most prominent in the outer pyramidal layer III, the inner granular layers IVa and IVc as well as in the multiform layer VI of BA17 of the HD patients. Our neuropathological results in BA17 confirm and extend previous post‐mortem, biochemical and in vivo neuroradiological HD findings and offer suitable explanations for the elementary and complex visual dysfunctions, as well as for the altered VEP observed in HD patients.     

心房利钠肽与心血管疾病

心房利钠肽属于利钠肽家族,其通过与受体结合激活鸟苷酸环化酶,促进细胞内环鸟苷酸水平升高而发挥生物学功能。心房利钠肽具有利钠、利尿、舒张血管平滑肌、抑制细胞增殖等多种作用,在维持血压,水、钠平衡以及在心血管疾病的病理生理过程中发挥重要作用。