Mccartneyhardin9913

5-Methylcytosine (m5C) methylation is an important RNA modification pattern that can participate in oncogenesis and progression of cancers by affecting RNA stability, expression of oncogenes, and the activity of cancer signaling pathways. Alterations in the expression pattern of long non-coding RNAs (lncRNAs) are potentially correlated with abnormalities in the m5C regulation features of cancers. Our aim was to reveal the mechanisms by which lncRNAs regulated the m5C process, to explore the impact of aberrant regulation of m5C on the biological properties of lower-grade gliomas (LGG), and to optimize current therapeutic. By searching 1017 LGG samples from the Cancer Genome Atlas and Chinese Glioma Genome Atlas, we first clarified the potential impact of m5C regulators on LGG prognosis in this study and used univariate Cox analysis and least absolute shrinkage and selection operator regression to explore clinically meaningful lncRNAs. Consequently, we identified four lncRNAs, including LINC00265, CIRBP-AS1, GDNF-AS1, and ZBTB20-AS4, and established a novel m5C-related lncRNAs signature (m5CrLS) that was effective in predicting prognosis. Notably, mutation rate, WHO class II, IDH mutation, 1p/19q co-deletion and MGMT promoter methylation were increased in the low m5CrLS score group. Patients with increased m5CrLS scores mostly showed activation of tumor malignancy-related pathways, increased immune infiltrating cells, and decreased anti-tumor immune function. Besides, the relatively high expression of immune checkpoints also revealed the immunosuppressed state of patients with high m5CrLS scores. In particular, m5CrLS stratification was sensitive to assess the efficacy of LGG to temozolomide and the responsiveness of immune checkpoint blockade. In conclusion, our results revealed the molecular basis of LGG, provided valuable clues for our understanding of m5C-related lncRNAs, and filled a gap between epigenetics and tumor microenvironment.Mediator of IRF3 activation (MITA) is a significant signal adaptor in the retinoic acid-inducible gene-I like receptor (RLR) signaling pathway and plays an important role in the innate immune system. As a transcription factor, nuclear factor kappa B (NF-κB) can be available in many signaling pathways including the RLR signaling pathway and relative to biological processes like immune responses. In this study, it is determined that IRF4b and IRF8 can have a negative effect on NF-κB signaling pathway mediated by MITA in fish. Firstly, it is found that IRF4b and IRF8 have an inhibitory function on MITA-mediated NF-κB signaling pathway. It is interesting that IRF4b and IRF8 have similar functions to achieve precise downregulated and the degradation of MITA through the ubiquitin-proteasome pathway. IRF is taken as the core domain of IRF4b or IRF8 for the downregulation to MITA. This study provides data on MITA-mediated NF-κB signaling pathway in teleost fish and provides new insights into the regulatory mechanism in fish immune system.Myalgic encephalomyelitis, or chronic fatigue syndrome (ME/CFS) is a serious disease whose cause has yet to be identified. Objective markers of the disease are also not well understood and would serve as important tools in diagnosis and management. One potential biomarker or transmitter of immune signals in ME/CFS is the extracellular vesicle (EV) compartment. These small, membrane bound particles have been shown to play a key role in intercellular signaling. Our laboratory has focused on methods of detection of EVS in clinical samples. In this study we explored whether the prevalence of EVs in the plasma of participants with mild or severe ME/CFS differed from the plasma of healthy control participants. By staining for multiple cell surface molecules, plasma EVs could be fingerprinted as to their cell of origin. Our study revealed a significant correlation between severe ME/CSF and levels of EVs bearing the B cell marker CD19 and the platelet marker CD41a, though these changes were not significant after correction for multiple comparisons. These findings point to potential dysregulation of B cell and platelet activation or homeostasis in ME/CFS, which warrants validation in a replication cohort and further exploration of potential mechanisms underlying the association.Largemouth bass iridovirus (LMBV) can cause high mortality and lead to heavy economic loss in the cultivation of largemouth bass, but there was no effective treatment. Here, the present study constructed a recombinant Pichia pastoris expressing LMBV major capsid protein (MCPD). The recombinant GS115-pW317-MCPD was then used to immunize largemouth bass via oral administration, and mucosal immune response mediated by immunoglobulins (Igs) was measured after oral immunization. Serum antibody levels were measured by ELISA, neutralizing antibody titers were determined by serum neutralization test (SNT), antigen presentation-related gene expressions were detected by RT-PCR, and the histopathological characteristics of immunized fish were assessed after challenging with 0.1 ml 107.19 TCID50/ml LMBV. The relative percentage survival (RPS) was also determined. Our results showed that the serum antibody titers of immunized fish were significantly higher than that of control groups (P 0.05). The RPS of fish orally immunized with 1.0 × 108 CFU/g GS115-pW317-MCPD was reached up to 41.6% after challenge with 0.1 ml 109.46 TCID50/ml LMBV. Moreover, orally immunizing with GS115-pW317-MCPD can relieve the pathological damage caused by LMBV. Therefore, GS115-pW317-MCPD showed a promising potential against LMBV.Mesenchymal stem cells (MSCs), as the most common cell source for stem cell therapy, play an important role in the modulation of innate and adaptive immune responses and have been widely used in clinical trials to treat autoimmune and inflammatory diseases. Recent experimental and clinical studies have shown that MSC-derived extracellular vesicles (MSC-EVs) can inhibit the activation and proliferation of a variety of proinflammatory cells, such as Th1, Th17 and M1 macrophages, reducing the secretion of proinflammatory cytokines, while promoting the proliferation of anti-inflammatory cells, such as M2 macrophages and Tregs, and increasing the secretion of anti-inflammatory cytokines, thus playing a role in immune regulation and exhibiting immunomodulatory functions. read more Besides MSC-EVs are more convenient and less immunogenic than MSCs. There is growing interest in the role of MSC-EVs in liver diseases owing to the intrinsic liver tropism of MSC-EVs. In this review, we focus on the immunomodulatory effects of MSC-EVs and summarize the pivotal roles of MSC-EVs as a cell-free therapy in liver diseases, including NAFLD, AIH, acute liver failure, liver fibrosis and hepatic ischemia-reperfusion injury. Moreover, we provide a concise overview of the potential use and limits of MSC-EVs in clinical application.With the increasing incidence and prevalence, Crohn's disease (CD) has become one of the most challenging diseases in both diagnosis and treatment of gastroenterology. Evaluation of the disease activity and mucosal healing guides clinical decisions regarding subsequent therapy for CD. In this study, we enrolled a total of 144 patients with CD and 239 healthy controls were enrolled. Clinical characteristics and laboratory parameters of enrolled subjects were retrieved from the electronic medical record database of our hospital. Serum cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). Mucosa expression levels of inflammatory agents were measured by quantitative RT-PCR (qRT-PCR). We identified two neutrophil-based indexes, the neutrophil-to-albumin ratio (NAR) and neutrophil-to-bilirubin ratio (NBR), both of which had not yet been explored in CD or UC. NAR and NBR were significantly increased in patients with CD compared to those in healthy controls, and both indexes showed significantly positive correlations with CD activity and inflammatory load. In note, NAR and NBR showed better performance than blood neutrophil percentage, serum albumin, or bilirubin alone in these scenarios. More importantly, both NAR and NBR discriminated CD patients who completely or partially responded to infliximab (IFX) induction therapy from those with primary non-response. Our observations suggest that NAR and NBR may serve as promising biomarkers in the diagnosis and prediction of response to IFX therapy in CD.Medulloblastoma is the most common childhood brain cancer. Mainstay treatments of radiation and chemotherapy have not changed in decades and new treatment approaches are crucial for the improvement of clinical outcomes. To date, immunotherapies for medulloblastoma have been unsuccessful, and studies investigating the immune microenvironment of the disease and the impact of current therapies are limited. Preclinical models that recapitulate both the disease and immune environment are essential for understanding immune-tumor interactions and to aid the identification of new and effective immunotherapies. Using an immune-competent mouse model of aggressive Myc-driven medulloblastoma, we characterized the brain immune microenvironment and changes induced in response to craniospinal irradiation, or the medulloblastoma chemotherapies cyclophosphamide or gemcitabine. The role of adaptive immunity in disease progression and treatment response was delineated by comparing survival outcomes in wildtype C57Bl/6J and in mandard-of-care medulloblastoma therapies. These populations therefore present a favorable target for immunotherapy in combination with front-line treatments.Major histocompatibility complex class II (MHC II) is an essential immune regulatory molecule that plays an important role in antigen presentation and T-cell development. Abnormal MHC II expression can lead to immunodeficiency, clinically termed as type II bare lymphocyte syndrome (BLS), which usually results from mutations in the MHC II transactivator (CIITA) and other coactivators. Here, we present a new paradigm for MHC II deficiency in mice that involves a spontaneous point mutation on H2-Aa. A significantly reduced population of CD4+ T cells was observed in mice obtained from the long-term homozygous breeding of autophagy-related gene microtubule-associated protein 1 light chain 3 β (Map1lc3b, Lc3b) knockout mice; this phenotype was not attributed to the original knocked-out gene. MHC II expression was generally reduced, together with a marked deficiency of H2-Aa in the immune cells of these mice. Using cDNA and DNA sequencing, a spontaneous H2-Aa point mutation that led to false pre-mRNA splicing, deletion of eight bases in the mRNA, and protein frameshift was identified in these mice. These findings led to the discovery of a new type of spontaneous MHC II deficiency and provided a new paradigm to explain type II BLS in mice.The significance of antibody-identified epitopes stimulating humoral alloimmunity is not well understood in the identification of non-permissive human leukocyte antigen (HLA) mismatching patterns in hematopoietic stem cell transplantation (HSCT). This was a retrospective study in a cohort of 9,991 patients who underwent their first HSCT for hematologic malignancies from unrelated bone marrow donors in the Transplant Registry Unified Management Program (TRUMP). HLA eplet mismatches (EMM) were quantified using HLAMatchmaker (HLAMM). The median age of patients was 48 years (range, 16 to 77). The number of EMM in recipient-donor pairs in our study population ranged from 0 to 37 in HLA class I (median, 0) and 0 to 60 in HLA class II (median, 1). In addition to the known high-risk mismatch patterns in the Japanese cohort, HLA-C EMM in the GVH direction was associated with a significantly higher risk for grade III-IV aGVHD, leading to a higher risk of non-relapse mortality and lower overall survival (compared with HLA-C matched patients, HR 1.