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关键词： Cerebral alveolar echinococcosis   TNF-alpha   VEGF-A   Microvessel density   Brain edema  

摘要： Alveolar echinococcosis (AE) is an infrequent zoonosis caused by Echinococcus multilocularis with a high degree of disability and mortality. Metastatic cerebral alveolar echinococcosis (CAE) is very rare and the lesions could lead to severe perilesional brain edema (PLBE) and subsequent uncontrollable intracranial hypertension. In this study, we sought to determine the expression of edema-associated factors in CAE lesions and their associations with PLBE. We retrospectively evaluated the clinical data of 18 CAE patients who received craniotomy. Severity of PLBE was described by edema index (EI). Archived specimens were processed for immunohistochemistry to detect tumor necrosis factor alpha (TNF-alpha), vascular endothelial growth factor A (VEGF-A) and microvessel density (MVD) in CAE lesions. Expression intensity of CAE lesions was quantified by integral optical density (IOD) or count and was compared to the control group. The results showed TNF-alpha and VEGF-A were significantly expressed in CAE lesions (p < 0.001), their levels were positively correlated with PLBE (TNF-alpha: r = 0.701, p = 0.001;VEGF-A: r = 0.803, p < 0.001). The MVD of CAE lesions had a similar expression with normal brain tissue, and it was positively correlated with PLBE and VEGF-A (PLBE: r = 0.849, p < 0.001;VEGF-A: r = 0.687, p = 0.002). In conclusion, we speculated the upregulation of TNF-alpha and VEGF-A induced the formation of PLBE. Besides, though there was no extra increase of MVD, it was still regulated by VEGF-A and provided a better anatomical basis for the formation of PLBE and further promoted it.

关键词： HLA-DQB1*02:01:01:27   new allele   third-generation sequencing  

摘要： HLA-DQB1*02:01:01:27 differs from HLA-DQB1*02:01:01:01 by the deletion of a single Thymine nucleotide in intron 2.

关键词： T cells   Macrophages   Glycolysis   Mitochondria   ATP   Aspartate   Citrate   Acetyl-CoA   RFX5   Cathepsin   Cytokines   TNF  

摘要： Background: Rheumatoid Arthritis is a systemic autoimmune disease affecting 0.5-1 % of the population. Despite a growing therapeutic armamentarium, RA remains incurable, and many patients suffer significant morbidity over time. The strongest genetic risk derives from HLA class II polymorphisms, implicating T cells as pathogenic drivers. Innate immune cells, e.g. monocytes and macrophages (MD) contribute to chronic tissue inflammation through an array of pro-inflammatory functions but also present antigen to autoreactive T cells. Differentiation, survival, and effector functions of both T cells and MD are ultimately controlled by their bioenergetic and biosynthetic programs, identifying cellular metabolism as a critical disease mechanism in RA. Objectives: Summarize current knowledge about metabolic conditions in the RA joint and disease-relevant metabolic circuits shaping the effector repertoire of RA T cells and MD. Results: The rheumatoid joint is a glucose deplete tissue environment, selecting for invading immune cells that can survive on non-glucose fuel sources. Inflamed synovium instead offers the amino acid glutamine and RA CD4+ T cells and RA MD rely on glutamine and glutamate to support their pathogenic functions. The metabolic hallmark of RA T cells is their low mitochondrial performance, resulting in low ATP production, low generation of reactive oxygen species (ROS) and low availability of tricarboxylic acid (TCA) cycle intermediates, all shifting RA T cells towards autoreactivity. The underlying defect stems from insufficient repair of mitochondrial DNA (mtDNA). Functional consequences include reversal of the TCA cycle, accumulation of citrate and lack of malate production. Excessive citrate promotes cytoskeletal hyperacetylation, creating hypermigratory and tissueinvasive T cells. Surplus acetyl-CoA supports lipid droplet formation and lipotoxicity. Lack of malate production disrupts the malate-aspartate shuttle, restricts recovery of cytosolic NAD and

关键词： cytokine   end-stage renal disease   heart failure   IL-2R alpha   inflammation  

摘要： Aims: Heart failure (HF) is a leading cause of mortality in patients with end-stage renal disease (ESRD) undergoing haemodialysis. Identifying novel predictors of HF is essential for improving diagnostic precision and enhancing patient outcomes. Methods: This study included 68 participants from the Haemodialysis Centre at the Second Hospital of Tianjin Medical University. Clinical characteristics and echocardiographic data were collected and analysed. We measured the plasma of 44 cytokines to investigate their correlation with cardiac function and their potential as HF biomarkers. Results: In the HF with reduced ejection fraction (HFrEF) group, the levels of several cytokines, including stem cell growth factor-beta (SCGF-beta), C-X-C motif chemokine 10 (CXCL10), interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-16 (IL-16), interleukin-1 receptor antagonist protein (IL-1Ra), interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), leukaemia inhibitory factor (LIF), C-C motif chemokine 3 (CCL3), interleukin-10 (IL-10), interleukin-2 receptor subunit alpha (IL-2R alpha), tumour necrosis factor ligand superfamily member 10 (TNFSF10), macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF), were significantly increased, while C-C motif chemokine 11 (CCL11)/eotaxin levels were decreased compared with those in the control group (P < 0.05). Receiver operating characteristic (ROC) curve analysis highlighted TNF-alpha [area under the ROC curve (AUC) = 0.85, odds ratio (OR) = 1.080, 95% confidence interval (CI): 1.033-1.128, P = 0.001], IFN-gamma (AUC = 0.84, OR = 1.836, 95% CI: 1.289-2.615, P = 0.003) and IL-2R alpha (AUC = 0.82, OR = 1.022, 95% CI: 1.009-1.035, P = 0.001) as excellent predictors for HFrEF in haemodialysis patients with ESRD, and they outperformed soluble suppression of tumourigenicity-2 (sST2) but slightly underperformed N-terminal pro-brain

关键词： cardiometabolic risk   obesity phenotypes   adipokines   biomarkers  

摘要： Up to 30% of individuals with obesity may exhibit normal insulin sensitivity, a favorable lipid profile, and no signs of hypertension. This prompts the exploration of factors distinguishing cardiometabolically healthy individuals from those developing complications. This cross-sectional study included 116 individuals categorized into four groups by combining abdominal obesity and cardiometabolic health statuses. We compared circulating adipokines and gut microbiota composition between these groups. Individuals with abdominal obesity had higher levels of hs-CRP, TNF-alpha, MCP-1, IL-18, chemerin, and leptin, and a less favorable gut microbiota composition, including higher levels of potentially harmful bacteria (CAG-Pathogen) and lower levels of beneficial bacteria (CAG-Ruminococcaceae and CAG-Akkermansia), compared to those with adequate waist circumference. Those with obesity but cardiometabolically healthy displayed similar adipokine levels and microbiota composition to those with adequate waist. In contrast, individuals with abdominal obesity cardiometabolically abnormal exhibited significantly higher levels of hs-CRP, IL-18, chemerin, and leptin, and lower levels of adiponectin and CAG-Ruminococcaceae compared to those with abdominal obesity cardiometabolically healthy and adequate waist. Additionally, they differed in hs-CRP and adiponectin/leptin ratio from individuals with obesity cardiometabolically healthy. These findings suggest that altered adipokine profiles and gut microbiota may contribute to the development or persistence of cardiometabolic complications in obesity.

关键词： HLA   HLA-DRB3*02:213   next-generation sequencing   novel allele  

摘要： HLA-DRB3* 02:213 differs from DRB3* 02:02 by one nucleotide substitution in codon 6 in exon 2.

关键词： traumatic brain injury   astrogliosis   microglia   agathisflavone   neuroprotection   NRLP3   IL-1 beta  

摘要： Traumatic brain injury (TBI) has a complex and multifactorial pathology and is a major cause of death and disability for humans. Immediately after TBI, astrocytes and microglia react with complex morphological and functional changes known as reactive gliosis to form a glial scar in the area immediately adjacent to the lesion, which is the major barrier to neuronal regeneration. The flavonoid agathisflavone (bis-apigenin), present in Poincianella pyramidalis leaves, has been shown to have neuroprotective, neurogenic, and anti-inflammatory effects, demonstrated in vitro models of glutamate-induced toxicity, neuroinflammation, and demyelination. In this study, we evaluated the effect and mechanisms of agathisflavone in neuronal integrity and in the modulation of gliosis in an ex vivo model of TBI. For this, microdissections from the encephalon of Wistar rats (P6-8) were prepared and subjected to mechanical injury (MI) and treated or not with daily agathisflavone (5 mu M) for 3 days. Astrocyte reactivity was investigated by measuring mRNA and expression of GFAP protein in the lesioned area by immunofluorescence and Western blot. The proportion of microglia was determined by immunofluorescence for Iba-1;mRNA expression for inflammasome NRPL3 and interleukin-1 beta (IL-1 beta) was determined by RT-qPCR. It was observed that lesions in the cortical tissue induced astrocytes overexpressing GFAP in the typical glial scar formed and that agathisflavone modulated GFAP expression at the transcriptional and post-transcriptional levels, which was associated with a reduction of the glial scar. MI induced an increase in the proportion of microglia (Iba-1+), which was not observed in agathisflavone-treated cultures. Moreover, the flavonoid modulated negatively both the NRLP3 and IL-1 beta mRNA expression that was increased in the lesioned area of the tissue. These findings support the regulatory properties of agathisflavone in the control of the inflammatory response in glial cells,

关键词： ESKAPE   HLA   Hypothetical proteins   Multi-epitope   P. aeruginosa  

摘要： ObjectivesPseudomonas aeruginosa, identified as an ESKAPE pathogen, contributes to severe clinical diseases worldwide and despite its prevalence an effective vaccine or treatment remains elusive. Numerous computational methods are being employed to target hypothetical proteins (HPs). Presently, no studies have predicted multi-epitope vaccines for these ***, 877 HPs from P. aeruginosa were included in the study and the data showcased here illustrate a methodical approach to prioritize the proteome by employing diverse comparative proteomics. The study employed physicochemical property assessment and conserved domain analysis to identify stable and immunologically pertinent proteins for epitope prediction. The VaxiJen2.0 antigenicity assessment aided in epitope selection, contributing to the foundational steps in vaccine development by predicting T-cell and B-cell epitopes. Potential T and B cell epitopes with high antigenicity, non-toxic categorization, and robust binding affinities were identified in the investigation. The periplasmic HP WP_132813935.1 was predicted as conserved, stable, and soluble. The T-cell peptide RTSMRALAY and the B-cell peptide MPVYLYLM were predicted to be probable non-allergen and demonstrated strong binding with MHC class I allele HLA-C*03:*** research provides a comprehensive approach to predict T and B cell epitopes for conditions associated with P. aeruginosa, offering a candidate pool for tailored vaccine development. However, the efficacy of these epitopes in vaccine development necessitates clinical validation and testing for confirmation.

关键词： lymphedema   CD4(+) T cell   IL-33   fibroblast   ST2  

摘要： Lymphedema is an intractable disease most commonly associated with lymph node dissection for cancer treatment and can lead to a decreased quality of life. Type 2 T helper (Th2) lymphocytes have been shown to be important in the progression of lymphedema. The activation of IL-33 and its receptor, the suppression of tumorigenicity 2 (ST2) signaling pathway, induces the differentiation of Th2 cells, but its involvement in lymphedema remains unclear. In the present study, we analyzed the dynamics of immune cell infiltration, including the IL-33/ST2 axis, in a mouse tail lymphedema model. Neutrophil infiltration was first detected in the lymphedema tissue on postoperative day (POD) 2. Macrophage infiltration increased from POD 2 to 5. The number of CD4+ T cells, including 50% Tregs, gradually increased from POD 14. The mRNA expression of ll13 and Ifng increased on POD 21. The expression of IL-33 was induced in fibroblast nuclei within dermal and subcutaneous tissues from POD 2, and the expression of the Il1rl1 gene encoding ST2 increased from POD 7. We demonstrated the infiltration process from innate to acquired immune cells through the development of a mouse tail lymphedema. The IL-33/ST2 axis was found to be induced during the transition from innate to acquired immunity.

摘要： Donor lymphocyte infusion (DLI) prevents acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) relapses following hematopoietic stem cell transplantation. Given the life-threatening toxicities such as graft versus host disease (GVHD), the identification of variables associated with response without toxicities is warranted. We hypothesized that HLA evolutionary divergence (HED), defined by the diversity between two given alleles of the same HLA gene, may be such a factor. A retrospective multicenter case-control study was conducted to evaluate the outcomes of pre-emptive (preDLI) and prophylactic DLI (proDLI) regarding their HED score, in AML or MDS patients. DLI-treated patients were matched with controls (1:2 matched) from French transplantation centers according to hospital, hemopathy, donor type, and risk classification. In total, 201 patients were included (N = 147 in the preDLI group, N = 54 in the proDLI group). Relapse-free survival was significantly better in the preDLI group (hazard ratio [HR] = 0.23, 95% confidence interval [CI]: 0.14-0.55, p < 0.001) than in controls. However, this benefit was offset by a higher incidence of severe GVHD (HR = 4.88, 95% CI: 2.30-10.32, p < 0.001). HED A, B, C, DQA1, DQB1, DPB1, and DRB1 were calculated for 65 DLI-treated patients. High-class II HED was significantly associated with higher GVHD and relapse-free survival (GRFS, HR = 0.33, 95% CI: 0.20-0.77, p = 0.005). Specific DQAB associations directly improved GRFS (HR = 0.23, 95% CI: 0.09-0.58, p = 0.004). In conclusion, screening the class II HED score identifies patients eligible for DLI treatment who will benefit the most from this strategy.