88 research outputs found
Mitochondrial division inhibitor-1 is neuroprotective in the A53T-α-synuclein rat model of Parkinson’s disease
Alpha-synuclein (α-syn) is involved in both familial and sporadic Parkinson’s disease (PD). One of the proposed pathogenic mechanisms of α-syn mutations is mitochondrial dysfunction. However, it is not entirely clear the impact of impaired mitochondrial dynamics induced by α-syn on neurodegeneration and whether targeting this pathway has therapeutic potential. In this study we evaluated whether inhibition of mitochondrial fission is neuroprotective against α-syn overexpression in vivo. To accomplish this goal, we overexpressed human A53T-α- synuclein (hA53T-α-syn) in the rat nigrostriatal pathway, with or without treatment using the small molecule Mitochondrial Division Inhibitor-1 (mdivi-1), a putative inhibitor of the mitochondrial fission Dynamin-Related Protein-1 (Drp1). We show here that mdivi-1 reduced neurodegeneration, α-syn aggregates and normalized motor function. Mechanistically, mdivi-1 reduced mitochondrial fragmentation, mitochondrial dysfunction and oxidative stress. These in vivo results support the negative role of mutant α-syn in mitochondrial function and indicate that mdivi-1 has a high therapeutic potential for PD
Spatial-temporal variations of Schistosoma japonicum distribution after an integrated national control strategy: a cohort in a marshland area of China
Genetic basis and biotechnological manipulation of sexual dimorphism and sex determination in fish
Metagenomic insights into the microbiota profiles and bioaugmentation mechanism of organics removal in coal gasification wastewater in an anaerobic/anoxic/oxic system by methanol
Coal gasification wastewater is a typical high phenol-containing, toxic and refractory industrial wastewater. Here, lab-scale anaerobic-anoxic-oxic system was employed to treat real coal gasification wastewater, and methanol was added to oxic tank as the co-substrate to enhance the removal of refractory organic pollutants. The results showed that the average COD removal in oxic effluent increased from 24.9% to 36.0% by adding methanol, the total phenols concentration decreased from 54.4 to 44.9 mg/L. GC-MS analysis revealed that contents of phenolic components and polycyclic aromatic hydrocarbons (PAHs) were decreased compared to the control and their degradation intermediates were observed. Microbial community revealed that methanol increased the abundance of phenolics and PAHs degraders such as Comamonas, Burkholderia and Sphingopyxis. Moreover, functional analysis revealed the relative abundance of functional genes associated with toluene, benzoate and PAHs degradation pathways was higher than that of control based on KEGG database
Co-infection of visceral leishmaniasis and HIV-1: a surviving case in China and review of treatment strategies
Co-infection of visceral leishmaniasis (VL) and human immunodeficiency virus type 1 (HIV-1) is known to have higher rates of initial treatment failure, relapse and mortality than in those without HIV-1 infection. Co-infection of VL and HIV-1 usually results in death by the end of treatment in previously reported cases in China. Here we report on a patient with VL and HIV-1 co-infection who received a high dose and an extended course of sodium stibogluconate treatment in addition to antiretroviral therapy (ART). This treatment regimen resulted in good control of VL and HIV-1 infection, while the conventional protocol of sodium stibogluconate treatment was not able to prevent multiple VL relapses. To the best of our knowledge, this is the first surviving case of VL and HIV-1 co-infection with this particular treatment regimen in China
Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water
Guanghong Yang,1 Zhiwei Zhou,2 Yanli Cen,1 Xiaolin Gui,1 Qibing Zeng,1 Yunxia Ao,1 Qian Li,1 Shiran Wang,1 Jun Li,1 Aihua Zhang1 1Key Laboratory of Environment Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guiyang Medical University, 2Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, Guizhou, People’s Republic of China Abstract: Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and posttranscriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury. Keywords: Fas/FasL pathway, mitochondrial pathway, liver injur
Prevalent trends in relatively high blood pressure among children and adolescents in Shandong, China
Improving cellular downlink throughput by multi-hop relay-assisted outband D2D communications
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