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关键词： CETP   HDL   IL-1β   LPS   SR-B1  

摘要： Sepsis is the dysregulated immune response to an infection and is a leading cause of mortality. Low levels of high-density lipoprotein (HDL) cholesterol are associated with increased risk of death from sepsis, and increasing levels of HDL by inhibition of cholesteryl ester transfer protein (CETP) has been shown to decrease mortality in mouse models of sepsis. The objective of this study was to investigate the cellular mechanisms by which CETP inhibition and HDL lead to improved survival during sepsis. We found that HDL inhibits lipopolysaccharide (LPS)-induced activation of IL-1 beta in a mouse model of sepsis. The activation of IL-1 beta was dependent on the activity of scavenger receptor class B type 1 (SR-B1), and knockdown of SR-B1 significantly attenuated LPS-induced production of IL-1 beta in macrophages. Additionally, we found that LPSinduced SR-B1 internalization occurs through the endosome-lysosome pathway, which is also likely responsible for LPS degradation in the macrophages. Furthermore, we revealed that raising HDL by CETP inhibition markedly enhanced HDL-mediated antiinflammatory effects in response to LPS stimulation, and these effects were not due to CETP itself but rather were HDL-dependent. Finally, we show that pharmacological inhibition of CETP significantly improved endotoxemia-induced mortality by inhibiting IL-1 beta production in the liver and circulation after LPS injection. Pathologically, CETP inhibition attenuated LPS-induced diffuse alveolar damage and hepatocyte necrosis, which may contribute to the improved mortality in mice treated with the CETP inhibitor anacetrapib. Taken together, our findings uncover a cellular mechanism by which HDL attenuates LPS-induced pro-inflammatory response via SR-B1-mediated LPS degradation.

关键词： IL-8 gene   Rs4073   Polymorphism   Oral mucositis  

摘要： Objectives The aim of this study was to investigate the association between Interleukin-8 (IL-8) rs4073 polymorphism and oral mucositis (OM). Design A prospective randomized controlled design was employed in this study. The investigation encompassed 107 patients diagnosed with OM following radiotherapy and 153 patients who did not develop OM post-radiotherapy. The study period spanned from the initiation of radiotherapy to six weeks post-treatment. All participants were diagnosed with head and neck cancer and were undergoing radiation therapy. Patient ages ranged from 33 to 75 years. This single-center study was conducted at Southern Hospital. The Visual Analogue Scale (VAS) and the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) were utilized to evaluate OM. Additionally, genotyped using Sanger sequencing, and serum IL-8 expression levels were quantified by ELISA. Results Individuals carrying the A allele (OR=1.470, 95 %CI= (1.028-2.101)) and AA genotype (OR=2.165, 95 %CI=(1.044-4.489)) may face a significantly higher risk of OM (P < 0.05). Notably, the concentration of IL-8 in serum samples from patients with OM was markedly elevated compared to that observed in the control group (P < 0.001). The A allele and AA genotype of the polymorphic site rs4073 of IL-8 were significantly correlated with the severity (A vs. T: OR=1.983, 95 %CI= (1.136-3.460);AA vs. TT: OR= 3.545, 95 %CI= (1.135-11.075)) and intensity of pain (A vs. T: OR=1.889, 95 %CI=(1.095-3.260);AA vs. TT: OR= 3.438, 95 %CI= (1.133-10.425)) in OM (P < 0.05). Conclusion The IL-8 rs4073 polymorphism may exert a significant influence on the susceptibility to OM after radiation therapy.

关键词： DMT-naive multiple sclerosis   Interleukin-10   Chitinase-3-like protein-1   Motor disability   Cognition   Quality of life  

摘要： Background: Multiple sclerosis (MS) is a chronic neuroinflammatory disease with heterogeneous clinical presentations and progression rates that pose challenges to its management. Identifying prognostic biomarkers is crucial for individualized treatment approaches. Interleukin-10 (IL-10) has emerged as a key anti-inflammatory cytokine with neuroprotective effects, while Chitinase-3-like protein 1 (CHI3L1) reflects the pathogenic glial activation and neurodegeneration. Objective: This study aimed to assess baseline serum IL-10 and CHI3L1 levels as biomarkers of disease burden and their correlation with clinical, cognitive, and quality-of-life (QoL) parameters in disease-modifying therapy (DMT)-naive MS patients. Methods: A cross-sectional, case-control study was conducted on 115 DMT-naive MS patients and 15 healthy controls. Only 73 RRMS and 29 CIS confirmed MS participated in the study analysis. Serum IL-10 and CHI3L1 levels were measured using sandwich ELISA kits and were correlated with various demographic, clinical, motor, cognitive, and quality of life (QOL) parameters. Results: Serum levels of IL-10 and CHI3L1 were significantly higher among MS patients compared to the healthy controls (P = 0.0001 for each one) and were negatively correlated with each other (r =-0.529 and P < 0.001). Second finding IL-10 levels negatively correlated with duration of disease (r =-0.389, P < 0.001), total number of relapse (r =-0.445, P < 0.001), motor disability (EDSS), Timed 25-Foot walk test (25-FWT), and depression scores (r =-0.398, P = 0.003, r =-0.340, P = 0.002 and r =-0.288, P = 0.008 respectively). It's positively correlated with most domains of QoL. CHI3L1 correlated positively with the total number of relapses (r = 0.253, P = 0.021), and EDSS (r = 0.346, P = 0.001), while negatively correlated with vitality, social, physical function, and general health domains of QoL (P = 0.009, 0.03, 0.001, and 0.013, respectively) Conclusion: IL-10 serves as a potential biomarker fo

关键词： antibody test | Han population | human leukocyte antigen | polymorphism | Treponema pallidum  

摘要： Some associations between Treponema pallidum (TP) susceptibility and human leukocyte antigen (HLA) loci at low resolution have been reported. However, the data for TP infection and HLA alleles at high resolution are limited. The purpose of this study was to perform a high-resolution screen for HLA alleles that confer susceptibility to TP infection in the Chinese Han population. A total of 184 individuals with TP infection were included in the study, and 254 unrelated healthy blood donors were included in the control group. The samples were genotyped for the HLA-A, -C, -B, -DRB1, -DQB1 and -DPB1 loci using next-generation sequencing (NGS) technology. The correlations between TP infection and the alleles and haplotypes of HLA loci were determined by statistical analysis. Five HLA alleles, including HLA-A*32:01 (0.00% vs. 1.57%, p = 0.024), -B*52:01 (1.36% vs. 4.13%, p = 0.025), -C*01:02 (22.55% vs. 16.54%, p = 0.029), -C*04:03 (1.63% vs. 0.2%, p = 0.046) and -DQB1*05:03 (1.63% vs. 4.13%, p = 0.046), are potentially associated with TP infection. However, no significant difference was detected after p value correction. The frequency of the HLA-A*33:03-C*03:02-B*58:01-DRB1*03:01-DQB1*02:01-DPB1*05:01 haplotype in the control group was greater than that in the TP infection group (p = 0.002). In contrast, the frequency of the HLA-A*02:07-C*01:02-B*46:01-DRB1*08:03-DQB1*06:01-DPB1*02:01, HLA-A*11:01-C*03:04-B*13:01-DRB1*09:01-DQB1*03:03-DPB1*05:01, HLA-A*11:01-C*07:02-B*40:01-DRB1*08:03-DQB1*06:01-DPB1*02:01 and HLA-A*30:01-C*06:02-B*13:02-DRB1*07:01-DQB1*02:02-DPB1*02:01 haplotypes were lower in the control group than in the TP infection group (p < 0.05). HLA-C*01:02 and -C*04:03 may confer susceptibility to TP infection, whereas A*32:01, -B*52:01 and -DQB1*05:03 may protect against TP infection. These data are helpful in preventing and controlling TP transmission.

关键词： Certolizumab pegol   Rheumatoid arthritis   Rheumatoid factor   Tumor necrosis factor inhibitor  

摘要： IntroductionAlthough the efficacy of tumor necrosis factor inhibitors (TNFi) is reduced in patients with rheumatoid factor (RF)-high rheumatoid arthritis (RA), certolizumab pegol (CZP), lacking the Fc portion, may not be affected. This study aimed to compare CZP with Fc-containing TNFi and investigate whether RF levels affect the efficacy of CZP in patients with *** multicenter retrospective study involved patients with RA (n = 1010) who received TNFi with concomitant methotrexate (MTX). Patients were categorized by baseline RF quartiles. The primary endpoint was the Simplified Disease Activity Index (SDAI) remission rates at 26 weeks for patients treated with CZP and those receiving Fc-containing TNFi. The secondary endpoint compared the efficacy of CZP and adalimumab (ADA) in each RF quartile using propensity score-based inverse probability of treatment weighting (PS-IPTW).ResultsIn the overall cohort, the SDAI remission rate was the lowest in Q4 (RF >= 136.45 IU/mL). In Q4, multivariable logistic regression analysis showed that only the introduction of CZP was significantly associated with remission at 26 weeks. The Fc-containing TNFi group had significantly lower SDAI remission rates in Q4 compared with Q1-Q3. Conversely, the SDAI remission rates were similar between the two groups treated with CZP. After PS-IPTW adjustment in Q4, CZP-treated patients showed a significantly lower SDAI and higher remission rate (36.6%) compared with the ADA-treated patients (24.5%) (p = 0.0172). No significant differences in SDAI remission rates were observed between the two groups in *** may be more effective than Fc-containing TNFi in patients with RA and high RF levels.

摘要： Background and Aims: Interleukin 21 receptor (IL-21R) serves as the exclusive signalling receptor for interleukin 21 (IL-21). Although IL-21 has been linked to various immunological disorders, its involvement in atherosclerosis remains poorly unde...

摘要： Whether one or two agents added to post-transplant cyclophosphamide (PTCy) are needed in HLA-matched allogeneic hematopoietic stem cell transplantation (allo-HSCT) with peripheral blood stem cells (PBSC) is debated. We retrospectively compared PTCy in association with a calcineurin inhibitor (PTCy+CNI) or with a CNI plus mycophenolate mofetil (PTCy+CNI+MMF) in adult patients transplanted for acute myeloid leukemia in first complete remission and receiving PBSC in the period from 2010 to 2020. Propensity score matching was performed using exact matching for donor type (related or unrelated) and the nearest neighbor for other variables (i.e. age, adverse cytogenetics, Karnofsky performance status, patient and donor cytomegalovirus serology, conditioning intensity). Each group comprised 146 patients, with 63% in total undergoing matched unrelated-allo-HSCT. Median follow up was longer for PTCy+CNI (36 [IQR 31-39] months versus 25 [IQR 19-30] months for PTCy+CNI+MMF, p < 0.01). At 2 years, PTCy+CNI was associated with a higher incidence of extensive chronic GVHD (16% [95% CI 10-22] versus 6% [95% CI 3-12] for PTCy+CNI+MMF, p < 0.03) while no differences were observed for all the other transplant outcomes. Addition of MMF to PTCy and CNI may help to prevent extensive chronic GVHD in HLA-matched allo-HSCT with PBSC.

关键词： effector B cells   psoriasis   regulatory B cells  

摘要： Psoriasis is a chronic inflammatory skin disease driven by immune dysregulation. This study explores the role of B cells, particularly cytokine-producing subsets, in psoriasis pathogenesis. Although T cells, particularly Th17, have been well documented in psoriasis, recent evidence suggests that B cells contribute to the disease process. Flow cytometry analysis of 50 psoriasis patients and 20 healthy controls revealed a significant increase in IL-6-producing effector B cells (Beffs) and a decrease in IL-10-producing regulatory B cells (Bregs) in psoriasis patients. As IL-6 is pro-inflammatory and IL-10 is anti-inflammatory, this imbalance likely exacerbates inflammation in psoriasis. The study also examined the effects of guselkumab, an IL-23 inhibitor, on cytokine-producing B cells. The frequency of IL-6-producing Beffs in the blood was significantly (p < 0.05) elevated in patients with psoriasis compared with that in healthy controls. In contrast, the frequency of IL-10-producing Bregs in the blood was significantly (p < 0.05) decreased in patients with psoriasis compared with that in healthy controls. In 10 biologic-na & iuml;ve psoriasis patients, guselkumab significantly reduced IL-6-producing Beffs 4 weeks posttreatment, corresponding with a marked decrease in the Psoriasis Area and Severity Index (PASI). However, IL-10-producing Bregs showed no significant change over this period, suggesting that regulatory B cell recovery may require a longer timeframe or additional stimuli. These findings highlight the potential of B cells as biomarkers for disease activity and therapeutic response in psoriasis. The observed cytokine imbalance suggests that targeting B cell-mediated inflammation could be a novel therapeutic avenue. Further research is needed to assess long-term Breg dynamics and their role in maintaining immune homeostasis in psoriasis. This study reinforces the importance of both effector and regulatory B cells in psoriasis and suggests that monitoring the

关键词： Chicken interleukin-17   Infectious bursal disease virus   DNA vaccine   Adjuvant  

摘要： Infectious bursal disease virus (IBDV) is an important immunosuppressive virus in chickens, which caused an acute and highly contagious infectious disease and resulted in considerable economic losses in the world poultry industry. Although IBDV VP2 DNA vaccine has been extensively proved only partial protection, the efficacy of DNA vaccines against IBDV can be augmented by choosing potential molecular adjuvants. To investigate whether chicken IL-17 (chIL-17) is qualified for the molecular adjuvant, we constructed chIL-17 gene vector, coimmunized chickens with chIL-17 gene vector and IBDV VP2 DNA vector, and analyzed the effect of IL-17 gene on the immunogenicity of VP2 DNA vaccine. Results showed that co-administrated chIL-17 gene and VP2 DNA vaccine significantly increased IBDV-specific serum antibody titer, and promoted lymphocyte proliferation and interference-gamma (IFN-gamma) production. Mechanically, chIL-17 reduced virus titer in bursa of fabricius tissue and mortality of IBDV-infected chicken. More importantly, chIL-17 gene significantly enhanced the protection induced by the VP2 gene against virulent IBDV *** data show that chIL-17 is a promising immunoadjuvant to facilitate humoral as well as cellular immunity in a vaccine setting against IBDV, and suggest that it should be evaluated as a new DNA vaccine adjuvant in strategies for other poultry diseases.

摘要： Background and Aims: Epitranscriptomics, particularly N6-Methyladenosine (m 6A), which is the most common in mammals, represents a new therapeutic target for inflammatory conditions, such as cardiovascular diseases. Despite this, our understanding...