NPC1 is a protein localized on the lysosome membrane regulating intracellular cholesterol transportation and maintaining normal lysosome function. GWAS studies have found that variants in T2D was a pancreatic islet expression quantitative trait locus, suggesting a potential role of NPC1 in T2D islet pathophysiology. Two-week-old mice and wild type littermates were employed to examine pancreatic β cell morphology and functional changes induced by loss of .
View Article and Find Full Text PDFFront Mol Neurosci
December 2022
Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disease, and its diagnosis is dependent on behavioral manifestation, such as impaired reciprocal social interactions, stereotyped repetitive behaviors, as well as restricted interests. However, ASD etiology has eluded researchers to date. In the past decades, based on strong genetic evidence including mutations in a single gene, gene editing technology has become an essential tool for exploring the pathogenetic mechanisms of ASD constructing genetically modified animal models which validates the casual relationship between genetic risk factors and the development of ASD, thus contributing to developing ideal candidates for gene therapies.
View Article and Find Full Text PDFBackground: Globally, Alzheimer's Disease (AD) accounts for the majority of dementia, making it a public health concern. AD treatment is limited due to the limited understanding of its pathogenesis. Recently, more and more evidence shows that ferroptosis lead to cell death in the brain, especially in the regions of the brain related to dementia.
View Article and Find Full Text PDFObjectives: To evaluate the immunogenicity of the third dose of inactivated SARS-CoV-2 vaccine in rheumatoid arthritis (RA) patients and explore the effect of RA drugs on vaccine immunogenicity.
Methods: We recruited RA patients ( = 222) and healthy controls (HC, = 177) who had been injected with a third dose of inactivated SARS-CoV-2 vaccine, and their neutralizing antibody (NAb) titer levels were assessed.
Results: RA patients and HC were age- and gender-matched, and the mean interval between 3rd vaccination and sampling was comparable.
Objectives: Attenuated humoral response to mRNA SARS-CoV-2 vaccines has been reported in some patients with autoimmune disease, e.g., rheumatoid arthritis (RA).
View Article and Find Full Text PDFStudies have shown that the cholesterol-lowering medicine statins alter the gut microbiome, induce chronic metabolic inflammation, and disrupt glycemic homeostasis. In this study, we aimed to investigate whether effects of atorvastatin (Ator) on gut microbiome and metabolic inflammation could be causally correlated. Mice at 8-week age were fed with high-fat diet (HFD) or HFD with Ator (HFD+Ator) for 16 weeks.
View Article and Find Full Text PDFThe incidence rates of depression are increasing year by year. As one of the main clinical manifestations of depression, sleep disorder is often the first complication. This complication may increase the severity of depression and lead to poor prognosis in patients.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
December 2021
Rapamycin insensitive companion of mechanistic target of Rapamycin (Rictor), the key component of mTOR complex 2 (mTORC2), controls both β-cell proliferation and function. We sought to study whether long chain acyl-CoA synthetase 4 (Acsl4) worked downstream of Rictor/mTORC2 to maintain β-cell functional mass. We found Acsl4 was positively regulated by Rictor at transcriptional and posttranslational levels in mouse β-cell.
View Article and Find Full Text PDFGraves' disease (GD) is a common autoimmune disease that affects the thyroid gland. As a new class of modulators of gene expression, long noncoding RNAs (lncRNAs) have been reported to play a vital role in immune functions and in the development of autoimmunity and autoimmune disease. The aim of this study is to identify lncRNAs in CD4+ T cells as potential biomarkers of GD.
View Article and Find Full Text PDFAims/hypothesis: Bile-acid (BA) signalling is crucial in metabolism homeostasis and has recently been found to mediate the therapeutic effects of glucose-lowering treatments, including α-glucosidase inhibitor (AGI). However, the underlying mechanisms are yet to be clarified. We hypothesised that BA signalling may be required for the glucose-lowering effects and metabolic benefits of AGI.
View Article and Find Full Text PDFStatins are cholesterol-lowering agents that increase the incidence of diabetes and impair glucose tolerance via their detrimental effects on nonhepatic tissues, such as pancreatic islets, but the underlying mechanism has not been determined. In atorvastatin (ator)-treated high-fat diet-fed mice, we found reduced pancreatic β-cell size and β-cell mass, fewer mature insulin granules, and reduced insulin secretion and glucose tolerance. Transcriptome profiling of primary pancreatic islets showed that ator inhibited the expression of pancreatic transcription factor, mechanistic target of rapamycin (mTOR) signaling, and small G protein (sGP) genes.
View Article and Find Full Text PDFThe aim was to investigate the lncRNA KB-1471A8.2 function in ovarian cancer progression and paclitaxel resistance. The expression and distribution of KB-1471A8.
View Article and Find Full Text PDFOvarian cancer remains the most fatal gynecologic malignancy worldwide due to delayed diagnosis as well as recurrence and drug resistance. Thus, the development of new tumor-related molecules with high sensitivity and specificity to replace or supplement existing tools is urgently needed. Cancer-testis antigens (CTAs) are exclusively expressed in normal testis tissues but abundantly found in several types of cancers, including ovarian cancer.
View Article and Find Full Text PDFMost ovarian cancer patients are chemosensitive initially, but finally relapse with acquired chemoresistance. Multidrug-resistance is the extremely terrible situation. The mechanism for the acquired chemoresistance of ovarian cancer patients is still not clear.
View Article and Find Full Text PDFOphthalmic Physiol Opt
September 2010
The purpose of this study was to assess whether age-related chromatic sensitivity changes are associated with corresponding changes in hue perception in a large sample of colour-normal observers over a wide age range (n = 185; age range: 18-75 years). In these observers we determined both the sensitivity along the protan, deutan and tritan line; and settings for the four unique hues, from which the characteristics of the higher-order colour mechanisms can be derived. We found a significant decrease in chromatic sensitivity due to ageing, in particular along the tritan line.
View Article and Find Full Text PDF