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关键词： Vascular calcification   Moscatilin   Dendrophenol   WNT3   beta-catenin   IL13R Alpha 2   STAT3  

摘要： Introduction: Vascular calcification, a devastating vascular complication accompanying atherosclerotic cardiovascular disease and chronic kidney disease, increases the incidence of adverse cardiovascular events and compromises the efficacy of vascular interventions. However, effective therapeutic drugs and treatments to delay or prevent vascular calcification are lacking. Objectives: This study was designed to test the therapeutic effects and mechanism of Moscatilin (also known as dendrophenol) from Dendrobium huoshanense (an eminent traditional Chinese medicine) in suppressing vascular calcification in vitro, ex vivo and in vivo. Methods: Male C57BL/6J mice (25-week-old) were subjected to nicotine and vitamin D3 (VD3) treatment to induce vascular calcification. In vitro, we established the cellular model of osteogenesis of human aortic smooth muscle cells (HASMCs) under phosphate conditions. Results: By utilizing an in-house drug screening strategy, we identified Moscatilin as a new naturally- occurring chemical entity to reduce HASMC calcium accumulation. The protective effects of Moscatilin against vascular calcification were verified in cultured HASMCs. Unbiased transcriptional profiling analysis and cellular thermal shift assay suggested that Moscatilin suppresses vascular calcification via binding to interleukin 13 receptor subunit A2 (IL13RA2) and augmenting its expression. Furthermore, IL13RA2 was reduced during HASMC osteogenesis, thus promoting the secretion of inflammatory factors via STAT3. We further validated the participation of Moscatilin-inhibited vascular calcification by the classical WNT/(3-catenin pathway, among which WNT3 played a key role in this process. Moscatilin mitigated the crosstalk between WNT3/(3-catenin and IL13RA2/STAT3 to reduce osteogenic differentiation of HASMCs. Conclusion: This study supports the potential of Moscatilin as a new naturally-occurring candidate drug for treating vascular calcification via regulating the IL13RA2/S

关键词： IL-9   TH9 cells   ILC2s   Allergic airway inflammation   Asthma   Type 2 inflammation   Cancer  

摘要： While much is known about the functional effects of type 2 cytokines interleukin (IL)-4, IL-5 and IL-13 in homeostasis and disease, we still poorly understand the functions of IL-9. Chronic inflammation seen in allergic diseases, autoimmunity and cancer is however frequently accompanied by overproduction of this elusive type 2 cytokine. Initially identified as a T cell and mast cell growth factor, and later as the hallmark cytokine defining TH9 cells, we now know that IL-9 is produced by multiple innate and adaptive immune cells. Recent evidence suggests that IL-9 controls discrete aspects of the allergic cascade, cellular responses of immune and stromal cells, cancer progression, tolerance and immune escape. Despite functioning as a pleiotropic cytokine in mucosal environments, like the lungs, the direct and indirect cellular targets of IL-9 are still not well characterized. Here, we discuss IL-9 ' s cellular senders and receivers, focusing on asthma and cancer. Moreover, we review current research directions and the outlook of targeted therapy centered around the biology of IL-9.

关键词： Canine   Bone mesenchymal stem cells   Chondrocyte   Inflammation   Exosome  

摘要： Osteoarthritis is a degenerative disease of cartilage, and exosome derived from mesenchymal stem cells (MSCs) are considered promising for treating inflammatory musculoskeletal disorders, although their mechanisms are not fully understood. This study aimed to investigate the effects of exosomes derived from canine bone marrow mesenchymal stem cells (cBMSCs-Exos) on the expression of inflammatory factors and genes related cartilage matrix metabolism in IL-1 beta-induced canine chondrocytes. Canine BMSCs were isolated and characterized for surface markers and trilineage differentiation. Exosomes were then extracted and performed surface labeling detection. Canine chondrocytes were exposed to IL-1 beta to mimic osteoarthritis in vitro. Subsequently, the chondrocytes were treated with exosomes from BMSCs, and the expression levels of related genes and IL-6 protein were assessed. The mesenchymal stem cells isolated from bone marrow and cultured exhibited positive CD44 and CD90, negative expression of CD45 and HLA, and demonstrated potential to differentiate into adipocytes, osteoblasts and chondrocytes. Exosomes from BMSCs exhibited positivity expression of CD9, CD63 and CD81. Treatment with exosomes significantly reduced IL-6 and TNF-alpha mRNA levels induced by IL-1 beta, as well as IL-6 protein expression. Additionally, a significant decrease was observed in the mRNA levels catabolic marker genes MMP-13, ADAMTS-5, and COX2. Conversely, there was a significant increase in the mRNA levels of anti-inflammatory cytokines IL-4, IL-10, and anabolic marker genes, such as COL2A1, ACAN, and SOX9. cBMSCs-Exos play a vital role in cartilage protection by suppressing the expression of pro-inflammatory and anabolic genes while simultaneously enhancing the expression of genes involved in synthesis metabolism.

关键词： Stevens-Johnson syndrome (SJS)   (TEN)   SJS/TEN pathogenesis   severe cutaneous adverse reactions (SCARs)   IL-1 beta   IL-6   RIPK3   cytokines in SJS/TEN   immune response in skin disorders   inflammatory pathways in SJS/TEN  

摘要： Background/Objectives: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are rare but severe skin conditions, often triggered by medications, that can be life-threatening. These conditions frequently affect the eyes, causing ocular surface disease, which can result in visual impairment or blindness. Although the exact mechanisms behind SJS/TEN remain unclear, key inflammatory mediators such as IL-1 beta, IL-6, and RIPK3 are believed to play critical roles in inflammation, necroptosis, and regulatory processes. Investigating these factors offers new insights into the disease's underlying mechanisms and potential targets for treatment. This study aims to determine the roles of IL-1 beta, IL-6, and RIPK3 in the pathogenesis of SJS/TEN. Methods: The study examined the expression levels of IL-1 beta, IL-6, and RIPK3 in skin biopsies from patients with biopsy-confirmed SJS/TEN, using lichen planus as a positive control and normal skin as a baseline control. Immunohistochemistry was employed for this analysis. Additionally, the impact of SJS/TEN patient plasma on mitochondrial function was assessed in platelets and human corneal epithelial (H-CET) cells. Using a fluorescent plate reader, mitochondrial activity and superoxide ion levels were measured, comparing plasma from SJS/TEN patients to normal human plasma. Results: Skin biopsies from SJS/TEN patients showed a significantly higher expression of IL-1 beta, IL-6, and RIPK3 compared to both lichen planus and normal controls. Furthermore, plasma from SJS/TEN patients significantly reduced platelet viability and increased mitochondrial and total cellular superoxide ions, as demonstrated by elevated levels of MitoSOX Red and CellROX Red. Conclusions: These findings suggest that IL-1 beta, IL-6, and RIPK3 may contribute to the pathogenesis of SJS/TEN and highlight their potential as targets for therapeutic intervention.

关键词： bipolar disorder   Galectin-3   cytokines   inflammation  

摘要： Objectives: This study aimed to assess serum Galectin-3 (Gal-3) and IL-6 levels, along with other inflammatory markers, in type-1 bipolar disorder (BD) patients and explore their relationship with clinical features, metabolic parameters, and symptom severity. Background: The study included 38 manic, 35 euthymic BD patients, and 40 healthy controls. Sociodemographic data, such as age, gender, alcohol and smoking habits, and body mass index (BMI), were recorded. Methods: The Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D) were administered to patients. Biochemical measurements included Gal-3, IL-6, CRP, neutrophil, lymphocyte, platelet counts, and inflammatory indices like NLR, PLR, SII, and SIRI. Results: Gal-3 levels significantly differed among the groups (F = 52.251, p < 0.001), with the highest levels in euthymic patients. IL-6 levels were elevated in both manic and euthymic patients compared to controls (F = 7.379, p = 0.001). Manic patients had significantly higher levels of neutrophils, monocytes, CRP, NLR, PLR, SII, and SIRI. A positive correlation was found between Gal-3 levels, the total number of episodes, and YMRS scores in manic patients. In euthymic patients, Gal-3 levels correlated positively with disease duration and episode count. Conclusions: Elevated Gal-3 levels, particularly in the euthymic phase, may serve as a biomarker for BD and indicate ongoing inflammation. These findings suggest Gal-3 could help identify BD and differentiate the euthymic phase.

关键词： HLA   HLA-DQA1*01:67:02   novel allele   sequencing-based typing  

摘要： HLA-DQA1*01:67:02 differs from HLA-DQA1*01:67:01 by one nucleotide substitution in codon 229 in exon 4.

关键词： hemodialysis   dialysis   arteriovenous fistula   allograft   risk assessment   immunization  

摘要： Objectives: The aim of this study was to assess the HLA alloreactivity of cold-stored saphenous vein allografts (CSVAs) by identifying the production of HLA donor-specific antibodies (DSAs) in the recipient. The secondary objective was to evaluate CSVA rejection-related complications, such as CSVA thrombosis and/or aneurysmal degeneration in the recipient. Methods: This was a single-center, prospective, experimental before-and-after study which included participants undergoing CSVA placement, either to create a vascular access (VA) for hemodialysis or to create a lower limb arterial bypass. On Day 1, before CSVA placement, total blood samples were taken for HLA typing by sequence-specific primers (SSPs) and anti-HLA antibody detection using a Luminex assay. One month after CSVA placement, a second blood sample was taken to assess the appearance of donor-specific antibodies or an increase in the level of anti-HLA antibodies. Patency of the CSVA and potential aneurysmal degeneration were evaluated at 3 and 6 months with a Doppler ultrasound checkup. Results: From September 2022 to November 2023, 45 patients were included (30 men, 67%;mean age: 71 +/- 12 years). One month after CSVA placement, no appearance of de novo anti-HLA antibody was detected in anti-HLA antibody-negative patients at inclusion (n = 28). Among the patients who already had anti-HLA antibodies at inclusion (n = 17), no increase in anti-HLA antibody levels or appearance of de novo anti-HLA antibodies was detected. Conclusions: This prospective study evaluating the immunogenicity of CSVAs through the appearance of anti-HLA antibodies one month after placement demonstrates that they do not seem to induce any HLA alloreactivity. Therefore, they may be used without the risk of HLA immunization in patients awaiting organ transplantation.

关键词： Keywords   Diabetic cardiomyopathy   Interleukin-1   Inflammation   Cytokines  

摘要： Diabetic cardiomyopathy (DCM) is the primary cause of heart failure in patients with diabetes and is characterised by contractile dysfunction and left ventricular hypertrophy. The complex pathological and physiological mechanisms underlying DCM have contributed to a limited number of available treatment options. A substantial body of evidence has established that DCM is a low-grade inflammatory cardiovascular disorder, with the interleukin-1 (IL-1) family of cytokines playing crucial roles in initiating inflammatory responses and shaping innate and adaptive immunity. In this review, we aim to provide an overview of the underlying mechanisms of the IL-1 family and their relevance in DCM of various aetiologies. Furthermore, we highlighted potential therapeutic targets within the IL-1 family for the management of DCM.

关键词： Seizures   Autoimmune associated epilepsy   Human leukocyte antigen   Anti-glutamic acid decarboxylase 65 (GAD65)   antibody  

摘要： Objective: Anti-GAD65 antibodies have been identified in people with epilepsy for many years, but their pathophysiological relevance is still debated. Susceptibility to autoimmune disease has been associated with Human Leukocyte Antigen (HLA) subtypes. Therefore, this study aimed to determine if there are common HLA types in anti-GAD65 antibody associated epilepsy cases compared to epilepsy controls. Methods: People with anti-GAD65 associated epilepsy and epilepsy controls were recruited from three Brisbane Hospitals from 2021 to 2023. Cases had high titre anti-GAD65 antibodies confirmed in CSF. High resolution genotyping for class I and II HLA to 3 fields was performed using next generation sequencing. Results: 10 anti-GAD65 cases (8 with epilepsy and 2 with post-encephalitic epilepsy) and 45 controls were included. 6 cases (all female) had co-morbid autoimmune disease. A single class II association was found for DPB1*02 (Padj = 0.0109), which was identified in 7 of the cases (70 % vs 7.7 % controls). Significant association was preserved at high resolution for HLA-DPB1*02:02:01. Conclusion: HLA association in anti-GAD65 antibody associated epilepsy might provide preliminary evidence to implicate an immune aetiology. DPB1*02 may confer a susceptibility to anti-GAD65 associated epilepsy and this class II association suggests a role for T cells in the pathophysiology.