Lindgaarddencker0560

ese findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but rather likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischemia. Further studies are needed to define whether these pathologies, if present in patients who survive COVID-19, might contribute to chronic neurological problems.Acute kidney injury (AKI) is a complex syndrome with an abrupt decrease of kidney function, which is associated with high morbidity and mortality. Sepsis is the common cause of AKI. Mounting evidence has demonstrated that long non-coding RNAs (lncRNAs) play critical roles in the development and progression of sepsis-induced AKI. In this study, we aimed to illustrate the function and mechanism of lncRNA SNHG14 in lipopolysaccharide (LPS)-induced AKI. We found that SNHG14 was highly expressed in the plasma of sepsis patients with AKI. SNHG14 inhibited cell proliferation and autophagy and promoted cell apoptosis and inflammatory cytokine production in LPS-stimulated HK-2 cells. Functionally, SNHG14 acted as a competing endogenous RNA (ceRNA) to negatively regulate miR-495-3p expression in HK-2 cells. EN4 Furthermore, we identified that HIPK1 is a direct target of miR-495-3p in HK-2 cells. We also revealed that the SNHG14/miR-495-3p/HIPK1 interaction network regulated HK-2 cell proliferation, apoptosis, autophagy, and inflammatory cytokine production upon LPS stimulation. In addition, we demonstrated that the SNHG14/miR-495-3p/HIPK1 interaction network regulated the production of inflammatory cytokines (TNF-α, IL-6, and IL-1β) via modulating NF-κB/p65 signaling in LPS-challenged HK-2 cells. In conclusion, our findings suggested a novel therapeutic axis of SNHG14/miR-495-3p/HIPK1 to treat sepsis-induced AKI.Parkinson's disease is a common neurodegenerative disease in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alteration in gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the central nervous system, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries and alterations of the gut microbiota in Parkinson's disease, and highlight current mechanistic insights on the microbiota-gut-brain axis in disease pathophysiology. We discuss the interactions between production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we also draw attention to diet modification, use of probiotics and prebiotics and fecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is highly correlated with metabolic disease. NAFLD results from environmental exposures acting on a susceptible polygenic background. This study performed the largest multiethnic investigation of exonic variation associated with NAFLD and correlated metabolic traits and diseases. An exome array meta-analysis was carried out among eight multiethnic population-based cohorts (n = 16 492) with computed tomography (CT) measured hepatic steatosis. A fixed effects meta-analysis identified five exome-wide significant loci (P  less then  5.30x10-7); including a novel signal near TOMM40/APOE. Joint analysis of TOMM40/APOE variants revealed the TOMM40 signal was attributed to APOE rs429358-T; APOE rs7412 was not associated with liver attenuation. Moreover, rs429358-T was associated with higher serum alanine aminotransferase, liver steatosis, cirrhosis, triglycerides and obesity; as well as, lower cholesterol and decreased risk of myocardial infarction (MI) and Alzheimer's disease (ad) in phenome-wide association analyses in the Michigan Genomics Initiative, United Kingdom Biobank and/or public datasets. These results implicate APOE in imaging-based identification of NAFLD. This association may or may not translate to non-alcoholic steatohepatitis (NASH); however, these results indicate a significant association with advanced liver disease and hepatic cirrhosis. These findings highlight allelic heterogeneity at the APOE locus and demonstrate an inverse link between NAFLD and ad at the exome level in the largest analysis to date.Over the last decade, remarkable progress has been made towards elucidating the origin and genomic landscape of childhood high-grade brain tumors. It has become evident that pediatric high-grade gliomas (pHGGs) differ from adult HGGs with respect to multiple defining aspects including DNA copy number, gene expression profiles, tumor locations within the central nervous system, and genetic alterations such as somatic histone mutations. Despite these advances, clinical trials for children with glioma have historically been based on ineffective adult regimens that fail to take into consideration the fundamental biological differences between the two. Additionally, although our knowledge of the intrinsic cellular mechanisms driving tumor progression has considerably expanded, little is known concerning the dynamic tumor immune microenvironment (TIME) in pHGGs. In this review, we explore the genetic and epigenetic landscape of pHGGs and how this drives the creation of specific tumor sub-groups with meaningful survival outcomes. Further, we provide a comprehensive analysis of the pHGG TIME and discuss emerging therapeutic efforts aimed at exploiting the immune functions of these tumors.Genes are expressed to proteins for a wide variety of fundamental biological processes at the cellular and organismal levels. However, a protein rarely functions alone, but rather acts through interactions with other proteins to maintain normal cellular and organismal functions. Therefore, it is important to analyze the protein-protein interactions to determine functional mechanisms of proteins, which can also guide to develop therapeutic targets for treatment of diseases caused by altered protein-protein interactions leading to cellular/organismal dysfunctions. There is a large number of methodologies to study protein interactions in vitro, in vivo and in silico, which led to the development of many protein interaction databases, and thus, have enriched our knowledge about protein-protein interactions and functions. However, many of these interactions were identified in vitro, but need to be verified/validated in living cells. Furthermore, it is unclear whether these interactions are direct or mediated via other proteins.