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摘要： Background and ObjectivesMultiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS characterized by a heterogeneous disease trajectory, highlighting the need for biomarkers to predict disease activity. Current disease-monitoring tools primarily reflect existing disease damage rather than impending activity. Peripheral blood mononuclear cells (PBMCs) are an ideal source of potential biomarkers due to their accessibility and their known role in MS pathology. Among PBMCs, myeloid cells are key players in MS pathogenic processes, yet they have not been as extensively studied than lymphocytes. The objective of our study was to identify indicators of MS disease activity through immune *** analyzed PBMCs using high-dimensional flow cytometry with a panel focusing on myeloid cells. We performed unsupervised clustering analyses to define a comprehensive immune landscape at a single-cell resolution. Supervised machine learning methods were used to extract immune features indicative of MS *** analyzed PBMCs from 135 individuals with MS with retrospective longitudinal follow-up and 44 healthy controls (HCs). Among the individuals with MS, 53 were untreated and were compared with HCs. Using an elastic-net model, 20 immune features were identified as contributors to the classification of MS and HCs (receiver operating characteristic-AUC 0.8881). To explore associations between immune features and disease activity, we focused on individuals with relapsing-remitting MS (n = 106). We identified a subpopulation of classical monocytes (CMs) with high expression of human leukocyte antigen - DR isotype (HLA-DR) and positive for CD141 (HLA-DRhiCD141+) as a predictor of impending relapses over 2 years (hazard ratio [HR] 2.8, 95% CI 1.6-4.7) and disability worsening in patients with higher relapse activity. HLA-DRhiCD141+ CMs could be retrieved by manual gating using 9 parameters and were similarly indicative of 2-year relapse risk (HR 1.

关键词： Nibea albiflora   The receptors of Interleukin 10   Vibrio parahaemolyticus   Vibrio alginolyticus   Poly (I C)  

摘要： The transmembrane receptor complex of Interleukin-10 (IL-10), comprising the IL-10R alpha subunit and IL-10R beta subunits, belong to the class II cytokine receptor family. In the present study, IL-10R alpha and IL-10R beta were characterized in Nibea albiflora (referred to as NaIL-10R alpha (MZ620685.1) and NaIL-10R beta (OK149228.1)), whose fulllength cDNA sequences were 2745bp (NaIL-10R alpha) containing an ORF of 1755 bp that encoded a protein of 584 aa, and 1570bp (NaIL-10R beta) with an ORF 975 bp encoding a protein of 324 aa, respectively. Both receptor subunits contained two extracellular fibronectin type III (FNIII) domains, an intracellular domain and a transmembrane part, which are typical features of class II cytokine receptor family. Real-time PCR analysis showed that NaIL-10R alpha and NaIL-10R beta were widely expressed in various healthy tissues, with a relatively high expression in immune-related organs (head kidney, spleen, kidney, liver and gill). Their expressions were significantly up-regulated after infection against Poly I:C, Vibrio parahaemolyticus and Vibrio alginolyticus. As a typical membrane receptor, NaIL-10R alpha was located on the cell membrane and co-located with NaIL-10 and NaIL10R beta on the membrane of HEK293T cells, suggesting the potential interaction between those components. After successful isolation.

关键词： Osteoclast   TNF alpha   Chemokine   Microenvironment   Rheumatoid arthritis  

摘要： The balance between bone formation by osteoblasts and bone resorption by osteoclasts is a critical step in maintaining bone homeostasis. Excessive activation of osteoclasts is important in the bone destruction seen in diseases such as osteoporosis and rheumatoid arthritis. The microenvironment around bone marrow cells regulates osteoclastogenesis through cytokine expression. Tumor necrosis factor-alpha (TNF alpha) is a proinflammatory cytokine that plays an important role in bone loss in rheumatoid arthritis. Therefore, this study investigated the effect of TNF alpha on osteoclastogenesis via chemokines produced by microenvironmental cells. In in vitro culture of mouse bone marrow cells, TNF alpha added simultaneously with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) from the initiation of culture significantly inhibited osteoclast formation. By contrast, TNF alpha stimulation from 7 days after prior stimulation with RANKL and M-CSF significantly promoted osteoclastogenesis. This late-stage promotional effect was associated with the upregulation in non-adherent bone marrow cells of C-X3-C motif chemokine ligand 1 (CX3CL1) and C-X-C motif ligand 7 (CXCL7), which are potent chemoattractant and adhesion molecules. Neutralizing antibodies against TNF receptor 1 (TNFR1) and TNFR2 markedly suppressed osteoclastogenesis in the presence of TNF alpha. Additionally, these antibodies significantly reduced CX3CL1-but not CXCL7-mRNA expression levels in non-adherent bone marrow cells. In conclusion, our results suggest that TNF alpha treatment in the late stage promotes osteoclast formation and increases the expression of CX3CL1 in non-adherent bone marrow cells. These findings highlight the time-dependent role of TNF alpha in osteoclastogenesis relative to non-adherent bone marrow cells.

关键词： chondrocyte   interleukin‑1β   isorhamnetin   nuclear factor‑κB   osteoarthritis  

摘要： Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the western blot data shown in Fig. 3B on p. 4256 were strikingly similar to data that had already appeared in a paper written by different authors at different research institutes that had already been published in the journal . In view of the fact that the abovementioned data had already apparently been published prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 4253‑4258, 2017; DOI: 10.3892/mmr.2017.7041].

关键词： Dengue infection   Tumor necrosis factor   Severe dengue   Immunoglobulin   Immune markers  

摘要： Dengue fever (Dengue Virus, Arbovirus) results in severe illness with mortality and morbidity, caused by any of four Dengue serotypes which results in a range of clinical manifestations. The sequence of infections can be an important cause of dengue severity. Early prediction of the high risk of complications in Dengue is dynamic and important to avoid hospital overcrowding during dengue epidemics. Multiple immune markers play a vital role in disease progression Primarily, TNF stimulates the production of reactive oxygen species resulting in cell death. The present study has an ideal design for identifying the risk factors of severity in dengue. Seven different biomarkers namely, TNF-alpha, TNFRSF7/CD27, TNFRSF9/CD137, TRAIL/TNFSF10, TNFRSF6B/DcR3, TNFSF6/Fas ligand and Fas/TNFRSF6/CD95, were evaluated in this study. Significantly, the level of TNFRSF7/CD27 in the dengue groups dengue without warning signs (D-W), dengue with warning signs (D + W), and severe dengue (SD) was higher than in the control group. Moreover, significant changes in the biomarker levels of TNFRS9/ CD137, TRAIL/TNFSF10, and TNFRSF6B/DcR3 were observed in the DI and SD groups as compared to healthy control group. In addition, the TNF alpha marker levels were significantly greater in the D-W group than in the healthy control group. However, biomarkers such as TNFRSF6/CD95, and TNFSF6/Fas ligand were markedly elevated in all the dengue (D-W, D + W, and SD) groups as compared to healthy control. The present study identifies these biomarkers that are differently expressed among D-W, D + W and subsequently augmented in SD.

关键词： IMQ   dendritic cells   T helper cells   NF-kappa B pathway   T cell polarization  

摘要： Although imiquimod (IMQ) is widely used to induce psoriasis-like inflammation in mouse models, its direct effects on dendritic cells (DCs) and their capacity to drive T cell polarization remain poorly defined. The systemic complexity of in vivo models hinders the ability to delineate the direct, cell-intrinsic effects of IMQ. To address this gap, an in vitro DC-CD4+ T cell co-culture system was established using bone marrow-derived DCs and na & iuml;ve CD4+ T cells isolated from OT-II mice, enabling precise evaluation of the direct immunomodulatory effects of IMQ. IMQ treatment markedly upregulated maturation markers (CD40, CD80, CD86 and major histocompatibility complex class II), and increased IL-12 and IL-6 secretion in a dose-dependent manner. These effects were significantly attenuated by NF-kappa B inhibitors (caffeic acid phenethyl ester and Bay 11-7082), indicating a critical role for NF-kappa B signaling in DC activation. When co-cultured with na & iuml;ve CD4+ T cells, IMQ-treated DCs promoted robust differentiation toward T helper (Th)1 and Th17 subsets. Neutralization of IL-12 and IL-6 in the co-culture system significantly reduced the frequencies of Th1 and Th17 cells and their cytokine output, confirming that these responses were mediated by DC-derived cytokines. Collectively, the present findings demonstrated that IMQ directly activated DCs via NF-kappa B signaling and induced pathogenic Th cell responses through IL-12 and IL-6 production. By eliminating confounding in vivo factors, the present study provided evidence for the DC-intrinsic effects of IMQ and offered mechanistic insights into the cellular pathways linking innate immune sensing to adaptive T cell responses in psoriasis.

关键词： HLA   Desensitization   Antibodies   Waitlist   Infectious complications  

摘要： HLA antibodies remain a barrier to lung transplantation due to the risk of antibody-mediated rejection (AMR). Desensitization is an option to lower antibody levels and increase access to transplant by reducing risk of AMR. However, concerns remain regarding the efficacy, durability, and risks of administering this treatment while waiting for deceased donor offers. We performed longitudinal antibody assessments for 15 highly sensitized lung candidates undergoing desensitization with plasmapheresis-based treatment protocols. Of the 14 patients transplanted, a significant decrease in overall antibody level was observed in the 2 of 4 patients transplanted within 15 days of the end of their first treatment. Conversely, of the 10 who were transplanted more than 15 days after first treatment, 7 patients rebounded to pre-treatment levels or higher within 3-4 weeks. For the 3 patients in this group who showed a durable decrease, this effect did not manifest until months following treatment. When comparing outcomes for the desensitization cohort against a control group that received treatment post-transplant, no significant differences in survival or acute rejection were observed. These results demonstrate that while plasmapheresis-based waitlist desensitization can effectively remove or reduce the level of HLA antibodies, rebound limits its effectiveness for most patients. To promote successful outcomes, pre-transplant therapy should be targeted to candidates with high lung composite allocation scores likely to be transplanted within the first week after treatment, while aggressive post-transplant immunosuppression may be a safer approach for most highly sensitized patients.