课程文献中心 更多>>

关键词： HLA-DPB1*1156:01:02   next-generation sequencing   novel allele  

摘要： HLA-DPB1*1156:01:02 differs from HLA-DPB1*1156:01:01 by a single nucleotide substitution at position 262 C>A.

关键词： Oncology   Anti-Inflammatory Agents   Non-Steroidal   Cytokines and Chemokines   Biomarkers  

摘要： Background: Immune-related adverse events (irAEs) represent a distinct category of drug toxicity that affects up to 50% of cancer patients treated with immune checkpoint inhibitor (ICI) therapy within the first year of treatment [1]. Among the many biomarkers associated with irAEs, interleukin-6 (IL-6) has gained increasing prominence [2]. It remains unclear whether high or low levels of IL-6 predispose patients treated with ICIs to the development of irAEs. Objectives: To analyze the association between IL-6 levels measured in the peripheral blood of patients with cancer before and after starting ICI therapy and the risk of developing irAEs. Methods: This is a preliminary analysis of the AUTENTIC project, a multicenter, observational, prospective cohort designed to identify factors potentially predictive of irAEs. Informed consent was obtained from all participants before their consecutive enrollment. Inclusion criteria were: (1) initiation of treatment with one ICI or a combination of ICIs; and (2) ICI-naïve status. Exclusion criteria were: (1) life expectancy <3 months from initiation of ICI therapy; (2) any contraindication to ICIs, such as active severe autoimmune disease or poor performance status (ECOG score ≥3); (3) concurrent treatment with chemotherapy, or other specific cancer therapy; or (4) active immunosuppressive treatment, including prednisone at doses >10 mg/day. We obtained a baseline sample before the first ICI cycle (pre-ICI) and a follow-up sample just before the second ICI cycle (post-ICI). The IL-6 levels in both pre- and post-ICI samples were measured using an IL-6 Enzyme Linked Immunosorbent Assay (ELISA) kit. Patients were censored if they experienced an irAE, cancer progression or death. The primary endpoint was defined as the cumulative incidence of a first irAE of any grade during the follow-up. Quantitative and categorical variables were expressed as means with standard deviations or medians with ranges, and frequencies with percentages

关键词： Inflammatory bowel diseases   Anti-TNF treatment   Antiphospholipid syndrome  

摘要： Introduction: Ant-iTNF treatment has been broadly linked with autoantibodies and autoimmune disorders development. After the clinical observation of aPTT (activated partial thromboplastin clotting time) prolongation in our cohort of IBD patients treated with anti-TNF, we sought to determine the presence of antiphospolipid antibodies in our population, along with antiphospholipid syndrome (APS) occurrence. Methods: We included in the study 289 patients treated with anti-TNFa antibodies. Results: Twenty four of 289 patients presented a prolonged aPPT (8.3%) after starting anti-TNF treatment. We found antiphospholipid antibodies in 70.8% (17/24) of patients with aPTT prolongation. No major thrombotic events were reported although one patient met criteria for APS because of persistent antiphospolipid antibodies and two miscarriages. Another patient was diagnosed with lupus-like syndrome. Conclusion: Anti-TNF treatment is associated with the induction of various antibodies, among them, antiphospholipid antibodies. However, a very low number of patients develop APS. Testing for antiphospholipid antibodies patients with prolonged aPPT could identify those at risk and lead to individualized treatment. Additional prospective studies are necessary to acquire more information. (c) 2024 Elsevier Espana, S.L.U. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

关键词： Observational studies/registry   Biomarkers   Epitranscriptomics   epigenetics   and genetics   biological DMARD  

关键词： Innate immunity   Plasmacytoid dendritic cells   Interferons   Sex differences   DDX3  

摘要： During the course of viral infections, IFN-I producing pDCs are fundamental in establishing antiviral defense. However, little is known about the molecular mechanisms by which biological sex contributes to differences in IFN-I production by pDCs. Here, we aimed to identify X-chromosome-encoded proteins as a source of sex differences in IFN-I responses by pDCs. We identified the host-cell factor DDX3 as a key mediator for the sex dimorphism in the IFN alpha response. DDX3 was significantly higher expressed in female pDCs and was translocated together with IRF7 to the nucleus to orchestrate IFN-I transcription. DDX3 as driver of sex differences in the initial and chronic IFN-I response might serve as a novel target to limit IFN-I-mediated hyperactivation of immune cells.

关键词： Amyotrophic lateral sclerosis   MiR-223   Interleukin-1 beta   Inflammasome  

摘要： Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease identified by progressive motor neuron loss. NLRP3 inflammasomes induce inflammation and pyroptosis, which can lead to neurodegeneration, muscle atrophy, and respiratory decline. miR-223 targets NLRP3 and suppresses inflammasome formation. Here, miR-223, NLRP3 and IL-1 beta levels were evaluated as plasma biomarkers in the incidence and progression of ALS. Methods 32 ALS patients and 32 healthy subjects were assessed. In all patients, the functional disability was determined by Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and the respiratory dysfunction was assessed by the percent predicted forced vital capacity (ppFVC) index in spirometry examination. Plasma levels of miR-223, NLRP3 and IL-1 beta were assessed in ALS and control groups. Results Compared to the healthy controls, ALS patients showed decreased miR-223 expression (P < 0.0001), increased NLRP3 expression (P = 0.0002) and increased IL-1 beta level (P = 0.0003). The areas under the ROC curves for miR-223, NLRP3 and IL-1 beta were 0.82, 0.76 and 0.75 respectively. The ALSFRS-R and ppFVC values were positively correlated with miR-223 and negatively correlated with NLRP3 and IL-1 beta levels. Conclusion Our results indicated that changes in miR-223, NLRP3 and IL-1 beta levels may correlate with the occurrence and functional progression of ALS. Additionally, therapeutic approaches based on miR-223 and inflammatory mediators can be proposed as effective strategies against disease progression.

关键词： Safety   Clinical Trial   Remission  

关键词： HLA   HLA-DQB1*06:03:56   next-generation sequencing   novel allele  

摘要： HLA-DQB1*06:03:56 differs from HLA-DQB1*06:03:01 by one nucleotide substitution in codon 130 in exon 3.

关键词： CAR-T cell   hepatocellular carcinoma   immunoactivation   tumor microenvironment   vitality backpacks  

摘要： Chimeric antigen receptor (CAR)-T-cell therapy achieves considerable success in the treatment of malignant tumors, but clinical relapse due to the tumor microenvironment (TME) is very common. The TME of solid tumors is characterized by weak acidity, hypoxia, and elevated reactive oxygen species (ROS) levels, which collectively impair the function and persistence of infiltrating CAR-T cells. In this study, acid-sensitive responsive CaMnCO3 nanoparticles (CMC NPs), are developed that simultaneously mitigate TME acidosis and hypoxia. IL-21 is encapsulated within CMC NPs (denoted as CMC-21), which are then surface-conjugated to CAR-T cells as functional 'vitality backpacks' to enhance cellular activity. The CMC-21 backpack enables sustained release of IL-21, persistently enhancing CAR-T cell antitumor immunity across both low- and high-dose infusion regimens. Furthermore, CMC NPs exert dual modulatory effects on the TME by: 1) consuming protons to neutralize acidic conditions, and 2) catalytically converting endogenous H2O2 to O2 to relieve hypoxia. This multimodal remodeling of the immunosuppressive TME significantly enhances the infiltration and activity of adoptively transferred CAR-T cells while simultaneously boosting endogenous T cell and NK cell recruitment in vivo. These findings establish a novel CAR-T cell enhancement strategy through sustained IL-21 release from CMC-21 backpacks, offering new possibilities for solid tumor immunotherapy.

关键词： Serpin A3   TNF-alpha   Retinoic acid   Vitamin B6   In vitro adipogenesis  

摘要： SERPINA3G participates in the antiadipogenesis and insulin resistance induced by TNF-alpha in 3T3-F442A murine cells. Here, we show that the human orthologue SERPINA3 is expressed in human subcutaneous and visceral adipose depots of normal-weight individuals and that TNF-alpha and RA induced the overexpression of SERPINA3 mRNA in cultured human subcutaneous and visceral adipocytes, although only TNF-alpha induced the expression of serpin A3 protein. We also demonstrate that vitamin B6 abrogated the expression of the SERPINA3 gene and diminished the anti-adipogenic effects of TNF-alpha on mature adipocytes. Our results indicate that SERPINA3 is expressed in human adipose tissues and modulates the antiadipogenic effects of TNF-alpha, and suggest serpin A3 could be a promissory target in the inflammatory processes linked to obesity and other adipose dysfunctions.