Espersengolden2032

Rheumatic diseases are extremely heterogeneous diseases with substantial risks of morbidity and mortality, and there is a pressing need in developing more safe and cost-effective treatment strategies. Peptide-based vaccination is a highly desirable strategy in treating noninfection diseases, such as cancer and autoimmune diseases, and has gained increasing attentions. This review is aimed at providing a brief overview of the recent advances in peptide-based vaccination therapy for rheumatic diseases. Tremendous efforts have been made to develop effective peptide-based vaccinations against rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), while studies in other rheumatic diseases are still limited. Peptide-based active vaccination against pathogenic cytokines such as TNF-α and interferon-α (IFN-α) is shown to be promising in treating RA or SLE. Selleck CQ inhibitor Moreover, peptide-based tolerogenic vaccinations also have encouraging results in treating RA or SLE. However, most studies available now have been mainly based on animal models, while evidence from clinical studies is still lacking. The translation of these advances from experimental studies into clinical therapy remains impeded by some obstacles such as species difference in immunity, disease heterogeneity, and lack of safe delivery carriers or adjuvants. Nevertheless, advances in high-throughput technology, bioinformatics, and nanotechnology may help overcome these impediments and facilitate the successful development of peptide-based vaccination therapy for rheumatic diseases. Copyright © 2020 Bin Wang et al.Background Ubiquitin-like modifier activating enzyme 1 (UBA1) is the first and major E1 activating enzyme in ubiquitin activation, the initial step of the ubiquitin-proteasome system. Defects in the expression or activity of UBA1 correlate with several neurodegenerative and cardiovascular disorders. However, whether UBA1 contributes to atherosclerosis is not defined. Methods and Results Atherosclerosis was induced in apolipoprotein E-knockout (Apoe-/-) mice fed on an atherogenic diet. link2 UBA1 expression, detected by immunohistochemical staining, was found to be significantly increased in the atherosclerotic plaques, which confirmed to be mainly derived from lesional CD68+ macrophages via immunofluorescence costaining. Inactivation of UBA1 by the specific inhibitor PYR-41 did not alter the main metabolic parameters during atherogenic diet feeding but suppressed atherosclerosis development with less macrophage infiltration and plaque necrosis. PYR-41 did not alter circulating immune cells determined by flow cytometry but significantly reduced aortic mRNA levels of cytokines related to monocyte recruitment (Mcp-1, Vcam-1, and Icam-1) and macrophage proinflammatory responses (Il-1β and Il-6). Besides, PYR-41 also suppressed aortic mRNA expression of NADPH oxidase (Nox1, Nox2, and Nox4) and lesional oxidative stress levels, determined by DHE staining. In vitro, PYR-41 blunted ox-LDL-induced lipid deposition and expression of proinflammatory cytokines (Il-1β and Il-6) and NADPH oxidases (Nox1, Nox2, and Nox4) in cultured RAW264.7 macrophages. Conclusions We demonstrated that UBA1 expression was upregulated and mainly derived from macrophages in the atherosclerotic plaques and inactivation of UBA1 by PYR-41 suppressed atherosclerosis development probably through inhibiting macrophage proinflammatory response and oxidative stress. Our data suggested that UBA1 might be explored as a potential pharmaceutical target against atherosclerosis. Copyright © 2020 Jiawei Liao et al.West Nile Virus (WNV) causes a debilitating and life-threatening neurological disease in humans. Since its emergence in Africa 50 years ago, new strains of WNV and an expanding geographical distribution have increased public health concerns. There are no licensed therapeutics against WNV, limiting effective infection control. Vaccines represent the most efficacious and efficient medical intervention known. Epitope-based vaccines against WNV remain significantly underexploited. Here, we use a selection protocol to identify a set of conserved prevalidated immunogenic T cell epitopes comprising a putative WNV vaccine. Experimentally validated immunogenic WNV epitopes and WNV sequences were retrieved from the IEDB and West Nile Virus Variation Database. Clustering and multiple sequence alignment identified a smaller subset of representative sequences. Protein variability analysis identified evolutionarily conserved sequences, which were used to select a diverse set of immunogenic candidate T cell epitopes. Cross-reactivity and human leukocyte antigen-binding affinities were assessed to eliminate unsuitable epitope candidates. Population protection coverage (PPC) quantified individual epitopes and epitope combinations against the world population. 3 CD8+ T cell epitopes (ITYTDVLRY, TLARGFPFV, and SYHDRRWCF) and 1 CD4+ epitope (VTVNPFVSVATANAKVLI) were selected as a putative WNV vaccine, with an estimated PPC of 97.14%. Copyright © 2020 Frances M. Waller et al.Background Patients after polytrauma regularly suffer from posttraumatic immune system destabilization, which closely influences the further clinical development. Increasing age has recently been identified as an isolated risk factor for an adverse outcome after major trauma. Higher rates and intensity of acute inflammation following severe injury suggest that deregulated inflammation may contribute to these higher rates of posttraumatic morbidity and mortality in older adults. MMP-9 and TIMP-1 have been found to play a major role in posttraumatic immune disorder in a previous genome-wide mRNA analysis. Objective The aim of this study was to evaluate the differences in serum protein dynamics in older and younger polytraumatized adults. Methods Blood samples were drawn immediately within 90 minutes after trauma and subsequently after 6, 12, 24, 48, and 72 h. Serum levels of TIMP-1 and MMP-9 were quantified using ELISA. Age groups were divided according to a cutoff of 60 years. Results 60 polytrauma patients (ISS > 16) were included ( less then 60 years, n = 49; ≥60 years, n = 49; ≥60 years, n = 11). Serum TIMP-1 and MMP-9 levels showed a highly significant serum dynamic in young and old polytrauma patients (p less then 0.001). Patients ≥ 60 years showed significantly higher overall TIMP-1 levels (p less then 0.001). Patients ≥ 60 years showed significantly higher overall TIMP-1 levels (p = 0.008). TIMP-1 levels showed a significant maximum after 72 h in the older study population. MMP-9 levels were nonsignificantly higher during the whole observational period in older polytrauma patients when compared to younger patients. Conclusion The posttraumatic immune response is characterized by significantly higher TIMP-1 levels in older polytrauma patients. This significant association between TIMP-1 levels and patients' age indicates a more extensive immune dysregulation following major trauma in older adults. Copyright © 2020 Mareen Braunstein et al.T helper (Th) cells orchestrate allergic lung inflammation in asthma pathogenesis. Th9 is a novel Th cell subset that mainly produces IL-9, a potent proinflammatory cytokine in asthma. A 7-amino acid peptide (7P) of the hypervariable region 1 (HVR1) of hepatitis C virus has been identified as an important regulator in the type 2 cytokine (IL-4, IL-5, and IL-13) immune response. However, it is unknown whether 7P regulates Th9 cell differentiation during ovalbumin- (OVA-) induced allergic lung inflammation. To address this, we studied wild-type mice treated with 7P and a control peptide in an in vivo mouse model of OVA-induced allergic inflammation and an in vitro cell model of Th9 differentiation, using flow cytometry, cytokine assays, and quantitative PCR. The binding of 7P to CD81 on naïve CD4+ T cells during lung Th9 differentiation was determined using CD81 overexpression and siRNA knockdown analyses. Administration of 7P significantly reduced Th9 cell differentiation after OVA sensitization and exposure. 7P also inhibited Th9 cell differentiation from naïve and memory CD4+ T cells in vitro. Furthermore, 7P inhibited the differentiation of human Th9 cells with high CD81 expression from naïve CD4+ T cells by blocking CD81 signaling. CD81 siRNA significantly reduced Th9 cell differentiation from naïve CD4+ T cells in vitro. Interestingly, CD81 overexpression in human naïve CD4+ T cells also enhanced Th9 development in vitro. These data indicate that 7P may be a good candidate for reducing IL-9 production in asthma. Copyright © 2020 Wanzhou Zhao et al.Chronic hepatitis C virus infection leads to the activation of innate immunity, a key component in HCV fibrosis. In the past, the use of IFN-based treatment regimens did not permit an adequate evaluation of the impact of HCV clearance on immune cells, because of their antiviral and immunomodulatory properties. The recent development of direct-acting antiviral (DAA) therapy, which is associated with high rates of sustained virological response, enables a more accurate analysis of the immunological modifications following HCV eradication. We studied the dynamics of blood myeloid dendritic cells, monocytes, slan-DCs, and T lymphocytes during IFN-free and IFN-based regimens in hepatitis C virus infection. Copyright © 2020 Serena Vita et al.Background Tracking progression of diabetic peripheral polyneuropathy (DPN) is usually focused on sensory nerves and subjective testing methods. Recent studies have suggested that distal muscle atrophy may precede sensation loss. Methods to objectively measure distal muscle size and strength are needed to help understand how neuropathy affects muscle function. Purpose To evaluate individual intrinsic and extrinsic foot muscle sizes and functional foot strength in participants with DPN. Methods Thirty individuals participated in this cross-sectional study (15 DPN and 15 matched controls). Sizes of 10 separate muscles of the lower leg and foot were measured using ultrasound imaging. Functional foot strength was also quantified using custom great toe and lateral toe flexion tests along with a doming test. Muscle size and strength metrics were compared between groups using ANOVAs and paired t-tests (α = 0.05). Correlations between strength and relevant muscle sizes were also evaluated. Results The sizes of all fod in the doming test before a relationship can be established between this test and DPN foot function. Future studies should include muscle quality measurements to better understand characteristics of affected muscles. Copyright © 2020 Adrienne D. Henderson et al.20(S)-Ginsenoside Rg3 (20(S)-Rg3) has been shown to induce apoptosis by interfering with several signaling pathways. Furthermore, it has been reported to have anticancer and antidiabetic effects. In order to detect the protective effect of 20(S)-Rg3 on diabetic kidney disease (DKD), diabetic rat models which were established by administering high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), and age-matched wild-type (WT) rat were given 20(S)-Rg3 for 12 weeks, with three groups control group (normal adult rats with saline), diabetic group (diabetic rats with saline), and 20(S)-Rg3 treatment group (diabetic rats with 20(S)-Rg3 (10 mg/kg body weight/day)). The biochemical indicators and the changes in glomerular basement membrane and mesangial matrix were detected. TUNEL staining was used to detect glomerular and renal tubular cell apoptosis. Immunohistochemical staining was used to detect the expression of fibrosis factors and inflammation factors in rat kidney tissues. link3 Through periodic acid-Schiff staining, we observed that the change in renal histology was improved and renal tubular epithelial cell apoptosis decreased significantly by treatment with 20(S)-Rg3.