Background. The expression of the let-7 family microRNAs in the myocardium of streptozotocin-induced diabetic rats was measured, and the cardioprotection of inhibition of let-7 microRNAs against ischemia-reperfusion i...
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Background. The expression of the let-7 family microRNAs in the myocardium of streptozotocin-induced diabetic rats was measured, and the cardioprotection of inhibition of let-7 microRNAs against ischemia-reperfusion injury was investigated. Methods. The diabetic rats and nondiabetic rats were subjected to 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion. The infarct size was determined by triphenyltetrazolium chloride staining. The expression of let-7 was measured by quantitative real-time polymerase chain reaction, and expressions of insulin receptor (InsR), insulin-like growth factor-1 receptor (IGF-1R), glucose transporter type 4 (GLUT4), and the phosphorylation states of Akt and the mammalian target of rapamycin (mTOR) were analyzed using Western blot. Inhibition of let-7 was performed by local transfection of lentivirus gene transfer vectors containing let-7 antimiR. Results. compared with nondiabetic rats, the expression of let-7 was enhanced in the myocardium of diabetic rats (p = 0.029), whereas expressions of InsR, IGF-1R, and GLUT4 were decreased after ischemia-reperfusion (p < 0.01). Local transfection of the let-7 antimiR markedly inhibited the expression of let-7 (p = 0.038) and improved expressions of InsR, IGF-1R, and GLUT4 in the myocardium of diabetic rats (p < 0.01). The infarct size of diabetic rats was much higher than that of nondiabetic rats (p < 0.0001). Transfection of the let-7 antimiR significantly reduced the infarct size of diabetic rats (p < 0.0001), and such an antiinfarct effect was abolished completely by pretreatment of Akt inhibitor LY294002 or mTOR inhibitor rapamycin. conclusions. Inhibition of the let-7 family microRNAs improves glucose uptake and insulin resistance in the diabetic myocardium and induces cardioprotection against ischemia-reperfusion injury through Akt and mTOR pathways. (c) 2016 by The Society of Thoracic Surgeons
This paper presents an implementation of a tool used for generating declarations required by LuaJIT compiler to bind programs written in Lua with programs written in c. The implementation is based on clang compiler. I...
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ISBN:
(纸本)9781509000555
This paper presents an implementation of a tool used for generating declarations required by LuaJIT compiler to bind programs written in Lua with programs written in c. The implementation is based on clang compiler. It's purpose is to enable easier and faster development of programs written in Lua that rely on code written in c.
Introduction: Simple animal models have enabled great progress in uncovering the disease mechanisms of amyotrophic lateral sclerosis (ALS) and are helping in the selection of therapeuticcompounds through chemical gen...
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Introduction: Simple animal models have enabled great progress in uncovering the disease mechanisms of amyotrophic lateral sclerosis (ALS) and are helping in the selection of therapeuticcompounds through chemical genetic *** covered: Within this article, the authors provide a concise overview of simple model organisms, c. elegans, Drosophila and zebrafish, which have been employed to study ALS and discuss their value to ALS drug discovery. In particular, the authors focus on innovative chemical screens that have established simple organisms as important models for ALS drug *** opinion: There are several advantages of using simple animal model organisms to accelerate drug discovery for ALS. It is the authors' particular belief that the amenability of simple animal models to various genetic manipulations, the availability of a wide range of transgenic strains for labelling motoneurons and other cell types, combined with live imaging and chemical screens should allow for new detailed studies elucidating early pathological processes in ALS and subsequent drug and target discovery.
Diabetes mellitus(DM) that occurs because of chronic liver disease(cLD) is known as hepatogenous diabetes(HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely st...
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Diabetes mellitus(DM) that occurs because of chronic liver disease(cLD) is known as hepatogenous diabetes(HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely studied for long time. Patients suffering from this condition have low frequency of risk factors of type 2 DM. Its incidence is higher in cLD of viral, alcoholic and cryptogenic etiology. Its pathophysiology relates to liver damage, pancreatic dysfunction, interactions between hepatitis c virus(HcV) and glucose metabolism mechanisms and genetic susceptibility. It associates with increased rate of liver complications and hepatocellular carcinoma, and decreased 5-year survival rate. It reduces sustained virological response in HcV infected patients. In spite of these evidences, the American Diabetes Association does not recognize HD. In addition, the impact of glucose control on clinical outcomes of patients has not been evaluated. Treatment of diabetes may be difficult due to liver insufficiency and hepatotoxicity of antidiabetic drugs. Notwithstanding, no therapeutic guidelines have been implemented up to date. In this editorial, authors discuss the reasons why they think that HD may be a neglected pathological condition and call attention to the necessity for more clinical research on different fields of this disease.
Hepatocellular carcinoma(Hcc) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis...
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Hepatocellular carcinoma(Hcc) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis virus infections are now recognized as the chief etiology of Hcc; however, the precise mechanism is still enigmatic till now. The inflammation triggered by the cytokine-mediated immune response, was reported to be the closest factor of Hcc development. cytokines are immunoregulatory proteins produced by immune cells, functioning as orchestrators of the immune response. Genes of cytokines and their receptors are known to be polymorphic, which give rise to variations in their genes. These variations have a great impact on the expression levels of the secreted cytokines. Therefore, cytokine gene polymorphisms are involved in the molecular mechanisms of several diseases. This piece of work aims to shed much light on the role of cytokine gene polymorphisms as genetic host factor in hepatitis related Hcc.
Heat shock proteins (HSPs) are highly chaperonic molecules that give immediate response during any stress, tissue damage or bacterial infections. In the present study, the role of HSPs upon bacterial encounter is stud...
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Heat shock proteins (HSPs) are highly chaperonic molecules that give immediate response during any stress, tissue damage or bacterial infections. In the present study, the role of HSPs upon bacterial encounter is studied by applying external heat induction to live caenorhabditis elegans. Heat shock was observed to increase the life span of wild type c. elegans upon pathogenic encounter, indicating a role of HSPs in bacterial infection and immunity. Similar increase in resistance towards pathogenesis observed in long-lived c. elegans daf-2 mutants and the increase in the lifespan indicated a role for the insulin/IGF-1 signaling (IIS) pathway in HSP-mediated pathogenic resistance. The microscopic observation of c. elegans after external heat induction and sequential exposure of pathogens indicated reduction of egg viability. Results of Real-time PcR and immunoblotting analysis of candidate genes revealed that heat shock and IIS pathways collaborate in the observed pathogenic resistance and further suggested SGK-1 to be the possible factor linking both these pathways. In addition, survival assays carried out using mutants equips us with supporting evidence that HSP and HSF-1 are necessary for the accelerated lifespan of c. elegans. Our findings thus confirm that crosstalk between HSPs and SGK-1 influences c. elegans longevity.
Antibiotics are newly emerging organic pollutants in manure, soil, vegetables and water. Animal manure application might be leading to the accumulation of antibiotics in the farmland. However, the effect of sulphameth...
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Antibiotics are newly emerging organic pollutants in manure, soil, vegetables and water. Animal manure application might be leading to the accumulation of antibiotics in the farmland. However, the effect of sulphamethazine (SMZ) on the soil microbial community was scarcely investigated. This study was aimed to evaluate the impact of SMZ on poultry manure, on the structure and function of microbial community, carbon mineralisation, and changes in nitrogen forms in soil via an incubation experiment lasting 56d. The treatments consisted of poultry manure at 1% wt (PM), PM containing 20mgkg(-1) SMZ (PM+20SMZ) and PM containing 100mgkg(-1) SMZ (PM+100SMZ), along with the untreated soil (control). Solid phase extraction was performed to measure the SMZ concentration in soils using high-pressure liquid chromatography. The cumulative cO2-c was increased in all treated soils over the incubation period compared to the control. The PM+100SMZ had the highest increase in cumulative cO2-c from the soil at 56d of incubation. The treatment of PM+20SMZ showed a short-term decrease in nitrification rate in the soils at 1d by altering the microbial community composition with 17% dissimilarity and decreasing the abundance of bacteria compared to PM-treated soil. The PM+100SMZ increased c mineralisation in the soil.
Microsporidia are ubiquitous parasites that infect a wide range of animal hosts, and these fungal-related microbes undergo their entire replicative lifecycle inside of host cells. Despite being widespread in the envir...
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Microsporidia are ubiquitous parasites that infect a wide range of animal hosts, and these fungal-related microbes undergo their entire replicative lifecycle inside of host cells. Despite being widespread in the environment and causing medical and agricultural harm, virtually nothing is known about the host factors important to facilitate their growth and development inside of host cells. Here, we perform a genetic screen to identify host transcription factors important for development of the microsporidian pathogen Nematocida parisii inside intestinal cells of its natural host, the nematode caenorhabditis elegans. Through this screen, we identified the c. elegans Myc family of transcription factors as key host regulators of microsporidia growth and development. The Mad-like transcription factor MDL-1, and the Max-like transcription factors MXL-1 and MXL-2 promote pathogen levels, while the Myc-Mondo-like transcription factor MML-1 inhibits pathogen levels. We used epistasis analysis to show that MDL-1 and MXL-1, which are thought to function as a heterodimer, appear to be acting canonically. In contrast, MXL-2 and MML-1, which are also thought to function as a heterodimer, appear to be acting in separate pathways (noncanonically) in the context of pathogen infection. We also found that both MDL-1::GFP and MML-1::GFP are expressed in intestinal cells during infection. These findings provide novel insight into the host transcription factors that regulate microsporidia development.
Background: Macanao's population in Venezuela has perhaps the greatest incidence of USH1B known in Latin America (79 cases per 100,000 population);however, until now no mutation in the MYO7A gene had been reported...
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Background: Macanao's population in Venezuela has perhaps the greatest incidence of USH1B known in Latin America (79 cases per 100,000 population);however, until now no mutation in the MYO7A gene had been reported for this *** and Methods: This study aimed to evaluate the entire coding region of the MYO7A gene by direct sequencing of PcR products obtained from patients clinically diagnosed with ***: A novel mutation named c.6079_6081del was detected on exon 45 of the MYO7A gene, causing the loss of a single histidine amino acid at codon 2027 (p.H2027del) located within the second FERM domain of the human protein myosin VIIA. Three patients with clinical diagnosis of USH1B were detected positive in homozygosis for the c.6079_6081del mutation;whereas six people from the same affected family were heterozygotes and three other family members were ***: We suggest that this new mutation named c.6079_6081del (p.H2027del) is the main cause of deaf-blindness found in this family clinically diagnosed as USH1B. Additional studies should be performed on this population to determine whether the c.6079_6081del mutation is the main cause of USH1B for the rest of the population.
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