Dammjosefsen6434

ker to predict the survival of KIRC. Moreover, patients with high or low-risk score might be sensitive to immune drugs at different immune checkpoints.Purpose This study aims to illustrate the cellular landscape in the aorta of experimental aortic dissection (AD) and elaborate on the smooth muscle cells (SMCs) heterogeneity and functions among various cell types. Methods Male Apolipoprotein deficient (ApoE-/-) mice at 28 weeks of age were infused with Ang II (2,500 ng/kg/min) to induce AD. Aortas from euthanized mice were harvested after 7 days for 10×Genomics single-cell RNA sequencing (scRNA-seq), followed by the identification of cell types and differentially expressed genes (DEGs). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted. Results AD was successfully induced in ApoE-/- mice. scRNA-seq identified 15 cell clusters and nine cell types, including non-immune cells (endothelials, fibroblasts, and SMCs) and immune cells (B cells, natural killer T cell, macrophages, dendritic cells, neutrophils, and mast cells). The relative numbers of SMCs were remarkably changed, and seven core DEGs (ACTA2,IL6,CTGF,BGN,ITGA8,THBS1, and CDH5) were identified in SMCs. Moreover, we found SMCs can differentiate into 8 different subtypes through single-cell trajectory analysis. Conclusion scRNA-seq technology can successfully identify unique cell composition in experimental AD. To our knowledge, this is the first study that provided the complete cellular landscape in AD tissues from mice, seven core DEGs and eight subtypes of SMCs were identified, and the SMCs have evolution from matrix type to inflammatory type.Transcobalamin (TC) deficiency is a rare autosomal recessive disease characterized by megaloblastic anemia. It is caused by cellular vitamin B12 depletion, which subsequently results in elevated levels of homocysteine and methylmalonic acid. This disease is usually diagnosed by genetic analysis of the TCN2 gene. Here, we described a 2.2-month-old Chinese girl with TC deficiency presenting with diarrhea, fever and poor feeding. Whole-exome sequencing detected a pair of compound-heterozygous mutations in TCN2 gene, c.754-12C>G and c.1031_1032delGA (p.R344Tfs*20). To our knowledge, it is the first time that they were identified and reported in TC deficiency. This study contributes to a better understanding of the TC deficiency, expanding the spectrum of TCN2 mutations in this disorder and also supporting the early diagnosis and proper treatment of similar cases in the future.Background Homozygous and compound heterozygous mutations in HTRA1 cause cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Recently, heterozygous pathogenic variants in HTRA1 were described in patients with autosomal dominant cerebral small vessel disease (CSVD). Here, we investigated the genetic variants in a cohort of Chinese patients with CSVD. Methods A total of 95 Chinese index patients with typical characteristics of CSVD were collected. Whole exome sequencing was performed in the probands, followed by Sanger sequencing. Pathogenicity prediction software was applied to evaluate the pathogenicity of the identified variants. Results We detected five heterozygous HTRA1 pathogenic variants in five index patients. These pathogenic variants included four known variants (c.543delT, c.854C>T, c.889G>A, and c.824C>T) and one novel variant (c.472 + 1G>A). Among them, c.854C>T, c.824C>T, and c.472 + 1G>A have never been reported in China and c.889G>A was once reherited pattern.Protozoan diseases seriously affect the health of human beings, livestock and poultry and lead to high economic and medical costs. Extracellular vesicles (EVs) are membranous structures formed through biological processes that play important roles in immune regulation. Studies have shown that parasites transmit information to hosts through EVs to modulate host immune responses. The major roles played by EVs released from parasites involve facilitating parasitization of the host. In this review, we discuss relevant recently obtained data on EVs secreted by different kinds of protozoa, including their molecular mechanisms, and discuss the roles played by EVs in the occurrence and development of parasitic diseases.Matrix metalloproteinase 9 (MMP9) is an important member of the matrix metalloproteinase family and plays a key role in balancing extracellular matrix proteins. Studies have shown that the homozygous mutations in MMP9 can lead to metaphyseal anadysplasia type 2 (MANDP2, OMIM#613073). The clinical phenotype of this disease is limited and there were only five reported cases of MANDP2 associated with homozygous MMP9 mutations from three families. In this study, we described a case of a fetus with skeletal system malformation. The main clinical manifestations include the short bilateral femur, absence of right fibula, and curved ipsilateral tibia with short length. Importantly, two novel compound heterozygous variants of the MMP9 gene (NM_004,994.3 c.151C > T and c.929del) were found through the trio whole exome sequencing and Sanger sequencing. This is the first report that identified the compound heterozygous variants of the MMP9 gene associated with metaphyseal dysplasia type 2.[This corrects the article DOI 10.3389/fgene.2022.919301.].Clostridium difficile (C. buy Devimistat difficile) is a multi-strain, spore-forming, Gram-positive, opportunistic enteropathogen bacteria, majorly associated with nosocomial infections, resulting in severe diarrhoea and colon inflammation. Several antibiotics including penicillin, tetracycline, and clindamycin have been employed to control C. difficile infection, but studies have suggested that injudicious use of antibiotics has led to the development of resistance in C. difficile strains. However, many proteins from its genome are still considered uncharacterized proteins that might serve crucial functions and assist in the biological understanding of the organism. In this study, we aimed to annotate and characterise the 6 C. difficile strains using in silico approaches. We first analysed the complete genome of 6 C. difficile strains using standardised approaches and analysed hypothetical proteins (HPs) employing various bioinformatics approaches coalescing, including identifying contigs, coding sequences, phage sequences, CRISPR-Cas9 systems, antimicrobial resistance determination, membrane helices, instability index, secretory nature, conserved domain, and vaccine target properties like comparative homology analysis, allergenicity, antigenicity determination along with structure prediction and binding-site analysis. This study provides crucial supporting information about the functional characterization of the HPs involved in the pathophysiology of the disease. Moreover, this information also aims to assist in mechanisms associated with bacterial pathogenesis and further design candidate inhibitors and bona fide pharmaceutical targets.Although there are a number of discoveries from genome-wide association studies (GWAS) for obesity, it has not been successful in linking GWAS results to biology. We sought to discover causal genes for obesity by conducting functional studies on genes detected from genetic association analysis. Gene-based association analysis of 917 individual exome sequences showed that HOGA1 attains exome-wide significance (p-value less then 2.7 × 10-6) for body mass index (BMI). The mRNA expression of HOGA1 is significantly increased in human adipose tissues from obese individuals in the Genotype-Tissue Expression (GTEx) dataset, which supports the genetic association of HOGA1 with BMI. Functional analyses employing cell- and animal model-based approaches were performed to gain insights into the functional relevance of Hoga1 in obesity. Adipogenesis was retarded when Hoga1 was knocked down by siRNA treatment in a mouse 3T3-L1 cell line and a similar inhibitory effect was confirmed in mice with down-regulated Hoga1. Hoga1 antisense oligonucleotide (ASO) treatment reduced body weight, blood lipid level, blood glucose, and adipocyte size in high-fat diet-induced mice. In addition, several lipogenic genes including Srebf1, Scd1, Lp1, and Acaca were down-regulated, while lipolytic genes Cpt1l, Ppara, and Ucp1 were up-regulated. Taken together, HOGA1 is a potential causal gene for obesity as it plays a role in excess body fat development.Objective Benign prostatic hyperplasia (BPH) is the most common urological disease in elderly men. The transforming growth factor beta 1 (TGFβ1) plays an important role in the proliferation and differentiation of BPH stroma. However, it is not clear yet which important pathways and key genes are the downstream of TGFβ1 acting on prostatic stromal cells. Methods GSE132714 is currently the newer, available, and best high-throughput sequencing data set for BPH disease and includes the largest number of BPH cases. We examined the TGFβ1 expression level in BPH and normal prostate (NP) by analyzing the GSE132714 data set as well as carrying out immunohistochemistry of 15 BPH and 15 NP samples. Primary prostatic stromal cells (PrSCs) were isolated from five fresh BPH tissues. RNA sequencing and bioinformatics analysis were used to reveal important pathways and hub genes associated with TGFβ1 stimulation on PrSCs. Results TGFβ1 was upregulated in BPH stroma compared to NP stroma. A total of 497 genes (244 upregulated and 253 downregulated) were differentially expressed in PrSCs with and without TGFβ1 stimulation. The Gene Ontology revealed that differentially expressed genes (DEGs) were mainly enriched in progesterone secretion, interleukin-7 receptor binding, and CSF1-CSF1R complex. The Wnt signaling pathway, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, and Hippo signaling pathway were screened based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. FN1, SMAD3, CXCL12, VCAM1, and ICAM1 were selected as hub genes according to the degree of connection from the protein-protein interaction (PPI) network. Conclusion This study sheds some new insights into the role of TGFβ1 in BPH stroma and provides some clues for the identification of potential downstream mechanisms and targets.Breast cancer (BC) has continued to be the leading cause of cancer deaths in women, accompanied by highly molecular heterogeneity. N6-methyladenosine (m6A), a methylation that happens on adenosine N6, is the most abundant internal mRNA modification type in eukaryotic cells. Functionally, m6A methylation is a reversible modification process and is regulated by 3 enzymes with different functions, namely "writer", "reader", and "eraser". Abnormal m6A modifications trigger the expression, activation, or inhibition of key signaling molecules in critical signaling pathways and the regulatory factors acting on them in BC. These m6A-related enzymes can not only be used as markers for accurate diagnosis, prediction of prognosis, and risk model construction, but also as effective targets for BC treatment. Here, we have emphasized the roles of different types of m6A-related enzymes reported in BC proliferation, invasion, and metastasis, as well as immune regulation. The comprehensive and in-depth exploration of the molecular mechanisms related to m6A will benefit in finding effective potential targets and effective stratified management of BC.