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关键词： gfap   il-6   oxidative stress   s100β   traumatic brain injury  

摘要： Background Traumatic brain injury (TBI) is a leading cause of neurological morbidity and mortality worldwide. Secondary injury mechanisms such as neuroinflammation and oxidative stress play a pivotal role in the progression of neuronal damage. Biomarkers, including S100β, glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), and oxidative stress parameters, can reflect the severity and progression of TBI, and their evaluation may assist in clinical decision-making. Objective This study aims to evaluate the serum levels of S100β, GFAP, IL-6, and oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), and catalase) in patients with TBI compared to healthy controls. Methods This case-control study was conducted at The University of Lahore from July to December 2024. A total of 96 participants were enrolled, including 48 TBI patients and 48 age- and sex-matched healthy controls. Blood samples were collected within 24 hours of injury in TBI patients. Serum concentrations of S100β, GFAP, and IL-6 were measured using ELISA (enzyme-linked immunosorbent assay), while MDA, SOD, and catalase levels were assessed using standard biochemical assays. Data were analyzed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York). Independent sample t-tests were used for group comparisons, and Pearson's correlation was applied to examine biomarker relationships. Results TBI patients exhibited significantly higher serum levels of S100β (1.92 ± 0.46 vs. 0.61 ± 0.18 ng/mL), GFAP (3.45 ± 0.71 vs. 1.12 ± 0.33 ng/mL), IL-6 (82.6 ± 18.4 vs. 19.5 ± 7.6 pg/mL), and MDA (5.12 ± 1.03 vs. 2.23 ± 0.66 µmol/L) compared to controls (p < 0.001 for all). SOD and catalase activities were significantly reduced in TBI patients (p < 0.001). S100β and GFAP correlated positively with IL-6 and MDA and negatively with SOD and catalase. Conclusion TBI is associated with elevated neural injury, inflammation, and oxidative stress biomarkers. These

关键词： autoantibody dynamics   biologic therapy   bullous pemphigoid   IL-23p19 inhibitors   immunopathogenesis   psoriasis   psoriatic arthritis  

关键词： Myeloproliferative neoplasms   PEG-IFN alpha 2a   Shortage   Outcomes  

摘要： Between March to December 2024, we observed a PEG-IFN alpha 2a shortage in France for MPN patients. We identified and followed 90 patients from our center and observed 80% of difficulties obtaining the drug, and 61 patients among all (67.8%) did not receive their prescribed drug on time (impacted group). Twenty-one patients need to reduce the dosage of PEG-IFN alpha 2a and 27 stopped the drug. Ten clinical events were identified with nine in the impacted group (p=0.04). No hematological or only partial responses were more frequent in the impacted group (p=0.01). The allelic burden variations were also studied during this period;17 patients obtained a VAF <10%. Eight patients stopped the drug because of VAF <4% and remained with molecular response. Three-quarters of the patients experimented with psychological and financial impacts of shortage. This study is the first one to explore a shortage of cytoreductive drugs happened in MPN. Much informations will be helpful for clinicians.

关键词： eosinophilic chronic rhinosinusitis   epithelial cells   IL-13   nasal polyps   periostin  

摘要： Background: Periostin is an extracellular matrix protein that is highly expressed in nasal polyp (NP) tissues in patients with chronic rhinosinusitis (CRS). This study investigated the cellular source of periostin in sinonasal tissues and the mechanism of IL-13-induced periostin production in nasal epithelial cells. Methods: The amount and localization of the periostin protein and mRNA were examined via immunohistochemistry and in situ hybridization analysis in control subjects and subjects with eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS. The expression levels of periostin and type 2 inflammatory cytokines in the tissue were measured by protein and mRNA levels. Normal human nasal epithelial cells were cultured in the presence of IL-13, and the effect of the specific inhibitors, leflunomide, PD98059, or PS1145, on periostin production was evaluated. Results: Periostin was mainly deposited in the subepithelial region of NP tissues in ECRS and was more highly expressed than in non-ECRS (p < 0.01) and control subjects (p < 0.001). The number of periostin mRNA-positive basal epithelial cells was significantly increased in NP tissues in ECRS. The IL-13 concentration was strongly correlated with periostin expression in the tissues (p < 0.0001, r = 0.8802). Periostin production was much greater in differentiated cells under long-term stimulation with IL-13 than in ciliated cells, and this effect was attenuated by leflunomide and PD98059, but not by PS1145. Conclusion: NP tissues from ECRS patients exhibit increased type 2 inflammatory cytokines and periostin. Nasal epithelial cells, particularly basal cells, are an important source of periostin. Exposure to IL-13 is important for periostin production from nasal epithelial cells.

关键词： Leishmania mexicana   Skin lesion   UV-B radiation   Immunosuppression   Mast cells   CD4   CD8   IFN-gamma  

摘要： In mice, susceptibility or resistance to Leishmania spp. infection is associated with distinct CD4+ T-helper cell responses. A predominant Th2 response, characterized by chronic disease, contrasts with a Th1 response, which promotes healing and parasite clearance. Ultraviolet B (UVB) radiation induces local and systemic immunosuppression by impairing antigen-presenting cell function, stimulating IL-10 production, and skewing the Th1/ Th2 balance towards a Th2 phenotype dominated by IL-4 and IL-10. This study investigated disease progression and early local immune responses in UVB-immunosuppressed C57BL/6 mice infected with Leishmania mexicana. Mice were exposed to immunosuppressive doses of UVB radiation and subsequently infected with L. mexicana promastigotes. Lesion size, parasite load, histopathology, and the presence of IL-10+, IFN-gamma+, mast cells, macrophages (MOMA2+), CD4+, and CD8+ T cells at the lesion site were evaluated. UVB-exposed, L. mexicana-infected mice exhibited altered tissue architecture, increased numbers of both intact and degranulated mast cells, and elevated IL-10+ and MOMA2+ cell infiltration in skin lesions, compared to wild-type, L. mexicana-infected controls. Conversely, CD4+, CD8+, and IFN-gamma+ cells were decreased in the UVB-exposed group. These findings suggest that exposure to UVB radiation acts as a risk factor for cutaneous leishmaniasis (LCL), as these findings indicate it can exacerbate lesions and increase parasite load through the induction of an unfavorable immune microenvironment.

关键词： HLA-B27   season   uveitis  

关键词： B cells   Influenza   Inflammasomes   Lymphocytes   Bone marrow cells   Tonsils   Cell staining   Cell signaling  

摘要： Persistent germinal center (GC) responses show increased benefit in optimal responses to influenza infection. Follicular helper T (TFH) cells provide the essential signals and help for maintenance of GCs and require IL-1 beta signaling for establishment and maintenance. We observe a preferential upregulation of IL-1 beta within GC B cells and coexpression of NLRP3 and caspase-1 with IL-1 beta confirms that GC B cells process IL-1 beta using a canonical NLRP3/caspase-1 mechanism. Using B cell specific ablation of IL-1 beta production and IL-1 beta signaling we further confirm that, GC B cells are the primary source of vital IL-1 beta within the GC and that IL-1 beta processing by GC B cells post influenza infection is driven by NLRP3 inflammasomes. We observe significant reduction of GC B cells and TFH cells in the absence of B cell derived IL-1 beta and our analysis of human B cells suggests similar mechanisms in human GC B cells. Our data present GC B cells in two novel roles, the first in producing IL-1 beta, which is associated with innate functions, within the GC and the second is providing helper cytokine to the TFH cell. Our findings add to the known complexity of the GC providing a target to enhance GC function and persistence.

关键词： Subarachnoid hemorrhage   G -protein-coupled receptor 40   NLRP3 inflammasome   Neuroinflammation   IL-1 beta   Exosome  

摘要： Subarachnoid hemorrhage is one type of strokes with high mortality and disability and there exists several mechanisms in SAH pathology. G-protein-coupled receptor 40 (GPR40) is proven to exert anti-inflammatory effects in several central nervous system (CNS) diseases. However, the precise role of GPR40 in SAH pathogenesis remains largely unknown. In this study, both in vivo and in vitro SAH models were used to investigate the mechanism of GPR40 attenuating neuroinflammation after SAH onset. We found that GPR40 expression in microglia decreased, which promoted IL-1 beta secretion and aggravated neuronal death after SAH onset. The GPR40 agonist GW9508 attenuated neuronal damage and ameliorated neurological deficits in SAH-model mice. Mechanistically, GPR40 in microglia inhibited pyroptosis, and cytokine production via inhibiting NLRP3/caspase-1/IL-1 beta pathway. Then the level of IL-1 beta secreted by microglia and transported to neurons via exosome were decreased, which down-regulated glutaminase, counteracted glutamate accumulation, and facilitated neuronal survival. These results revealed that GPR40 is a novel regulator that inhibits microglia-mediated neuroinflammation and is a potential therapeutic target in SAH therapy.