Further Investigation on the Role of Selenium Deficiency in the Aetiology and Pathogenesis of Keshan Disease

Selenium supplements were not able to restore the ultrastructural changes in the myocardiurn of latent Keshan disease patients taken by using cardiac catheter endomyocardial biopsy. Observations on the changes of seleniurn status and the incidence of Keshan disease showed that new latent and naturally-occurring chronic cases were found in the endemic area even after selenium levels had been elevated in the residents to the levels typical in the non-endemic area. These results indicate that although selenium deficiency might be a primary pathogenetic geogen in the occurrence of Keshan disease, it is rather a conditional predisposing factor than a specific or initiative aetiologic factor for the occurrence of Keshan disease. Selenium supplmentation could apparently alleviate the higher platelet responsiveness of residents in the endemic area, which might contribute to eliminating the basis for the occurrence of the multifocal perivascular necroses in myocardium of acute and subacute Keshan disease

Pathogenesis of motor neuron disease

OBJECTIVE: To summarize and analyze the factors and theories related to the attack of motor neuron disease, and comprehensively investigate the pathogenesis of motor neuron disease. DATA SOURCES: A search of Pubmed database was undertaken to identify articles about motor neuron disease published in English from January 1994 to June 2006 by using the keywords of 'neurodegenerative diseases'. Other literatures were collected by retrieving specific journals and articles. STUDY SELECTION: The data were checked primarily, articles related to the pathogenesis of motor neuron disease were involved, and those obviously irrelated to the articles were excluded. DATA EXTRACTION: Totally 54 articles were collected, 30 of them were involved, and the other 24 were excluded. DATA SYNTHESIS: The pathogenesis of motor neuron disease has multiple factors, and the present related theories included free radical oxidation, excitotoxicity, genetic and immune factors, lack of neurotrophic factor, injury of neurofilament, etc. The studies mainly come from transgenic animal models, cell culture in vitro and patients with familial motor neuron disease, but there are still many restrictions and disadvantages. CONCLUSION: It is necessary to try to find whether there is internal association among different mechanisms, comprehensively investigate the pathogenesis of motor neuron diseases, in order to provide reliable evidence for the clinical treatment.

Untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease induced by high-temperature-processed feed in Sprague-Dawley rats

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)has become one of the most common chronic liver diseases in the world.In our early clinical data and questionnaire analysis of NAFLD,it was found that the body mass index of some patients did not meet the diagnostic criteria for overweight or obesity.The consumption of high-temperature-processed foods such as fried food,hot pot and barbecue is closely related to the occurrence of nonobese NAFLD.Reducing the intake of this kind of food can reduce disease severity and improve prognosis.AIM To explore the untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease in Sprague-Dawley rats induced by high-temperatureprocessed feed.METHODS Fifty-four male Sprague-Dawley rats were divided into three groups:The control group received a standard diet;the nonfried soybeans(NDFS)group received 60%NDFS and 40%basic feed and the dry-fried soybeans(DFS)group received 60%DFS and 40%basic feed.Six rats were sacrificed at week 4,8,and 12 in each group.The food intake,body weight,Lee’s index,liver index,serological index and hepatic histopathology were assessed.Untargeted metabolomics characteristics were used to analyze the changes in liver metabolites of rats at week 12.Correlations between metabolites and pathology scores between the DFS and control groups and between the DFS and NDFS groups were analyzed.We selected some of the metabolites,both within the pathway and outside of the pathway,to explain preliminarily the difference in liver pathology in the three groups of rats.RESULTS There were no statistically significant differences in the food intake,body weight,Lee's index or serological index between the DFS group and the control group(P>0.05).At week 8 and week 12,the steatosis scores in the DFS group were significantly higher than those in the other two groups(P<0.05).At week 12,the liver index of the DFS group was the lowest(NDFS group vs DFS group,P<0.05).The fibrosis score in the DFS group was significantly higher than those in the other two groups(P<0.05).The correlation analysis of the liver pathology score and differential metabolites in the DFS and NDFS groups showed that there were 10 strongly correlated substances:Five positively correlated substances and five negatively correlated substances.The positively correlated substances included taurochenodeoxycholate-3-sulfate,acetylcarnitine,20a,22bdihydroxycholesterol,13E-tetranor-16-carboxy-LTE4 and taurocholic acid.The negatively correlated substances included choline,cholesterane-3,7,12,25-tetrol-3-glucuronide,nicotinamide adenine dinucleotide phosphate,lysoPC[16:1(9Z)]and glycerol 3-phosphate.The correlation analysis of the liver pathology score and differential metabolites in the DFS and control groups showed that there were 13 strongly correlated substances:Four positively correlated substances and 9 negatively correlated substances.The positively correlated substances included 4-hydroxy-6-eicosanone,3-phosphoglyceric acid,13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid and taurochenodeoxycholate-3-sulfate.The negatively correlated substances included lysoPC[16:1(9Z)],S-(9-hydroxy-PGA1)-glutathione,lysoPC[20:5(5Z,8Z,11Z,14Z,17Z)],SM(d18:1/14:0),nicotinamide adenine dinucleotide phosphate,5,10-methylene-THF,folinic acid,N-lactoylglycine and 6-hydroxy-5-methoxyindole glucuronide.CONCLUSION We successfully induced liver damage in rats by using a specially prepared hightemperature-processed feed and explored the untargeted metabolomics characteristics.

基于正交质谱的N-糖组谱揭示哈夫病潜在病原学

食用煮熟的小龙虾可能导致哈夫病(HD),该病被认为是由不明毒素引起的,而病因尚不清楚。N-糖组的剖析将促进破译疾病的分子机制,而HD相关的糖基化从未被探索过。2019-2020年期间,本研究团队招募了来自武汉市疾病预防控制中心的90份HD患者和对照组血清样本。本文中,采用基于高通量的正交质谱对HD中血清和血清衍生的IgG的N-糖组谱进行了表征。数据显示,HD与总血清糖蛋白的核心岩藻糖基化和单半乳糖醇化升高有关。血清IgG水平是HD患者的良好指标。此外,IgG的差异半乳糖基化和唾液酸化与HD密切相关。值得注意的是,IgG1和IgG2的半乳糖基化和唾液酸化的变化具有亚类特异性。有意义的是,IgG2或IgG3/4的唾液酸化和半乳糖基化改变与HD的临床标志物密切相关。本研究表明差异化IgG N-糖基化与HD的关联,为这种罕见疾病的病因提供了新的见解。

Role of extracellular vesicles in lung diseases

Extracellular vesicles(EVs)are anuclear particles composed of lipid bilayers that contain nucleic acids,proteins,lipids,and organelles.EVs act as an important mediator of cell-to-cell communication by transmitting biological signals or components,including lipids,proteins,messenger RNAs,DNA,microRNAs,organelles,etc,to nearby or distant target cells to activate and regulate the function and phenotype of target cells.Under physiological conditions,EVs play an essential role in maintaining the homeostasis of the pulmonary milieu but they can also be involved in promoting the pathogenesis and progression of various respiratory diseases including chronic obstructive pulmonary disease,asthma,acute lung injury/acute respiratory distress syndrome,idiopathic pulmonary fibrosis(IPF),and pulmonary artery hypertension.In addition,in multiple preclinical studies,EVs derived from mesenchymal stem cells(EVs)have shown promising therapeutic effects on reducing and repairing lung injuries.Furthermore,in recent years,researchers have explored different methods for modifying EVs or enhancing EVs-mediated drug delivery to produce more targeted and beneficial effects.This article will review the characteristics and biogenesis of EVs and their role in lung homeostasis and various acute and chronic lung diseases and the potential therapeutic application of EVs in the field of clinical medicine.

Wilson's Disease in China

Wilson＇s disease（WD） is an autosomal recessive disorder of copper metabolism. Its incidence is higher in China than in western countries. ATP7 B is the causative gene and encodes a P-type ATPase, which participates in the synthesis of holoceruloplasmin and copper excretion. Disease-causing variants of ATP7 B disrupt the normal structure or function of the enzyme and cause copper deposition in multiple organs,leading to diverse clinical manifestations. Given the variety of presentations, misdiagnosis is not rare. Genetic diagnosis plays an important role and has gradually become a routine test in China. The first Chinese spectrum of disease-causing mutations of ATP7 B has been established. As a remediable hereditary disorder, most WD patients have a good prognosis with an early diagnosis and chelation treatment. However, clinical trials are relatively few in China, and most treatments are based on the experience of experts and evidences from other countries. It is necessary to study and develop appropriate regimens specific for Chinese WD patients.

Patient-derived iPSC models of Friedreich ataxia:a new frontier for understanding disease mechanisms and therapeutic application

Friedreich ataxia(FRDA)is a rare genetic multisystem disorder caused by a pathological GAA trinucleotide repeat expansion in the FXN gene.The numerous drawbacks of historical cellular and rodent models of FRDA have caused difficulty in performing effective mechanistic and translational studies to investigate the disease.The recent discovery and subsequent development of induced pluripotent stem cell(iPSC)technology provides an exciting platform to enable enhanced disease modelling for studies of rare genetic diseases.Utilising iPSCs,researchers have created phenotypically relevant and previously inaccessible cellular models of FRDA.These models enable studies of the molecular mechanisms underlying GAA-induced pathology,as well as providing an exciting tool for the screening and testing of novel disease-modifying therapies.This review explores how the use of iPSCs to study FRDA has developed over the past decade,as well as discussing the enormous therapeutic potentials of iPSC-derived models,their current limitations and their future direction within the field of FRDA research.

Preferential loss of gut-homing a4β7 CD4＋T cells and their circulating functional subsets in acute HIV-1 infection

Preferential infection and depletion of gut-homing a4β7 CD4＋ T cells in the blood are observed in chronic HIV/SIV infection. The dynamic change in gut-homing a4p7 CD4＋ T cells and their functional subsets during the acute stages of HIV-1 infection are less documented. Therefore, we conducted a cohort study to investigate whether acute HIV-1 infection induced abnormalities in gut-homing a4β7 CD4＋ T cells and their functional subsets. We examined the frequency, absolute number, and functionality of gut-homing a4β7 CD4＋ T cells in 26 acute HIV-l-infected patients compared with 20 healthy individuals. We found that circulating gut-homing a4β7 CD4＋ T cells were preferentially depleted during acute HIV-1 infection and were positively correlated with absolute CD4＋ T-cell count in blood. Notably, Th17 and Thl cell subsets of gut-homing CD4＋ T cells were also decreased, which resulted in an imbalance of T helper cells （Th 1）-regulatory T cells （Treg） and Treg.Th 17 ratios. Gut-homing Th17 and Thl cells were also positively correlated with the absolute number of total CD4＋ T cells and gut-homing CD4＋ T cells. The gut-homing Treg：Th17 ratio was inversely correlated with the CD4＋ T-cell count. Taken together, the analyses of our acute HIV-1 cohort demonstrate that gut-homing a4β7 CD4＋ T cells and their functional subsets were profoundly depleted during acute HIV-1 infection, which may have resulted in the persistent loss of circulating CD4＋ T cells and an imbalance of Thl-Treg and Treg.Th17 ratios and contribute to HIV-1 disease pathogenesis.