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关键词： Artificial Intelligence   Biomarkers   biological DMARD  

关键词： Caspase-43   GBM   IL32   NF-κB  

摘要： Background & objectives Glioblastoma multiforme (GBM) is the most aggressive form of brain tumour, characterised by rapid progression, high recurrence, and poor prognosis. The immunosuppressive tumour microenvironment (TME) of GBM poses a major barrier to effective therapy. Interleukin (IL)-32, a pro-inflammatory cytokine, has been implicated in cancer progression, but its specific role in GBM remains unclear. This study aimed to investigate the immunoregulatory functions of IL-32 in GBM, particularly its impact on monocyte differentiation and macrophage polarisation. Methods Transcriptomic data from TCGA-GBM and GEO-GSE156902 were analysed to identify differentially expressed genes (DEGs), with a focus on IL-32. Functional enrichment analyses (GO and Kyoto Encyclopaedia of Genes and Genomes- KEGG) and protein-protein interaction (PPI) network construction were conducted using R software and Cytoscape. IL-32 expression was validated by qPCR and Western blot (WB) in GBM cell lines. Single-cell RNA sequencing data were integrated to determine IL-32 expression across brain cell types. Additionally, correlations between IL-32 and RNA modification genes (m6A, m5C, m1A) were analysed. Results IL-32 was significantly upregulated in GBM tissues and particularly enriched in microglial cells. Functional studies revealed that IL-32 promotes caspase-43-mediated monocyte differentiation into macrophages. Moreover, IL-32 induced a phenotypic shift from M1 to M2 macrophages via NF-κB pathway activation. PPI analysis confirmed IL-32 as a hub gene involved in immune regulation. RNA modification analysis showed positive correlations between IL-32 and METTL3, and a negative correlation with TET2, indicating epigenetic modulation of IL-32-related immune functions. Interpretation & conclusions IL-32 plays a pivotal immunoregulatory role in the GBM microenvironment by driving macrophage differentiation and M2 polarisation, contributing to tumour immune evasion. These findings highlight I

关键词： biological DMARD   Observational studies/ registry  

关键词： Allergic asthma   interferons   mast cells   respiratory virus   IL-5  

摘要： Background: Mast cells are important sentinel cells in defense against mucosal infection. Exacerbations of allergic asthma and asthma deaths have been associated with respiratory viral infections. Elevated levels of IL-5 have been associated with the pathogenesis of severe atopic diseases, many of which respond to IL-5 blockade. Objective: We sought to examine the impact of IL-5 signaling on mast cells infected with respiratory viruses. Methods: Cord blood-derived human mast cells were treated with IL-5 or left untreated and infected with human coronavirus OC43, respiratory syncytial virus (RSV), or oncolytic reovirus. Mast cell expression of interferons and of interferon-stimulated genes was evaluated. Total RNA sequencing was performed to determine the impact of IL-5 on the transcriptome of human mast cells, and related functional assays were performed. Results: IL-5-treated mast cells produced significantly more type I and III interferons than did controls not treated with IL-5. Mechanistically, IL-5 treatment led to greater expression of the prosurvival factor B-cell lymphoma 2 (BCL2) and endothelial PAS domain protein 1 (EPAS1) and protected mast cells from apoptosis-induced stress. IL-5 blockade was associated with a decrease in EPAS1 expression in the peripheral blood of asthmatic patients, as shown by transcriptomic data from clinical trials of mepolizumab and benralizumab. Conclusions: IL-5 signaling selectively promotes interferon responses in mast cells and maintains mast cell populations during mucosal viral infection via a novel IL-5/EPAS1 axis. (J Allergy Clin Immunol 2025;155:1968-80.)

关键词： comorbidity   dendritic cells   inflammation mediators   psoriasis   psychological stress  

摘要： BackgroundPsychological stress often accompanies psoriasis, and both conditions involve an overactive IL-23/Th17 inflammatory axis. However, the mechanism behind the comorbidity of psoriasis and psychological stress remains unclear. This study established a mouse model of comorbid psoriasis and psychological stress to investigate the impact on skin inflammation and the IL-23/Th17 axis. Chronic restraint stress and imiquimod cream were used to induce psychological stress and psoriasis. Behavioural tests included the open-field test and elevated plus maze, while psoriasis severity was assessed using the Psoriasis Severity Index and histopathology. Flow cytometry measured cDC2 populations in the lesion and spleen, and ELISA quantified levels of key inflammatory factors in serum and lesions. Mice with psoriasis alone showed anxiety symptoms, which were significantly exacerbated in the comorbid group. The comorbid group exhibited more severe lesions, with elevated levels of IL-23 and IL-17A in both serum and lesions compared to the psoriasis-only group. The number of CD11c+ cDCs in the dermis and the proportion of cDC2s in the lesion and spleen were also significantly higher in the comorbid group. Psychological stress intensifies anxiety symptoms and exacerbates the inflammatory response in the skin and systemic tissues of mice with comorbid psoriasis and psychological stress. This occurs via the overactivation of the IL-23/Th17 inflammatory axis, leading to increased mobilisation of cDC2s and higher levels of inflammatory mediators like IL-23 and IL-17A, thus chronicling inflammation. These findings enhance our understanding of the mechanisms linking psoriasis and psychological disorders, paving the way for identifying potential therapeutic targets.

关键词： Cerebellar motor disorders   Lead toxicity   Cucumis sativus   Caspase-3   TNF-alpha  

摘要： Cerebellar Motor Disorders (CMDs) are characterized by unsteady gait and uncoordinated movements. Reports indicate that CMDs are caused by congenital malformations, hereditary ataxia, and heavy metal exposure, such as Lead. The antioxidant-rich nature of plants, such as Cucumis sativus (Cucumber), has been well-documented. Accordingly, this study investigated the protective activity of aqueous Cucumis sativus fruit extract (CS) in a lead acetate (Pb) rat model of CMD. Forty Wistar rats (n = 8) were randomly assigned into five groups and treated for twenty-eight days as follows: Group A served as control;Group B received 100 mg/kg body weight (bw) of Pb;Group C received 500 mg/kg bw of CS and Pb;Group D received 1000 mg/kg bw of CS and Pb;Group E received 200 mg/kg bw of Vitamin-E and Pb. Thereafter, neurobehavioral activities, antioxidant enzymes, lipid peroxidation, nitric oxide, Pb concentration, Caspase-3, TNF-alpha, and cerebella histology were evaluated. Findings revealed that Pb-exposed rats demonstrated significant (p < 0.05) weight loss, impaired motor functions, dysregulated antioxidant enzymes activity, increased lipid peroxidation, elevated cerebellar nitric oxide and Pb concentration, as well as degenerating Purkinje cells and vacuolations in the cerebellum. Also, a significant upregulation (p < 0.05) of Caspase-3 and TNF-alpha was observed in the cerebella of Pb-exposed rats. However, pretreatment with CS mitigated (p < 0.05) these adverse effects induced by Pb. Taken together, this study offers novel insights into the role of CS as a promising neuroprotective agent and provides translational research evidence demonstrating that CS can be further developed into drugs useful against CMDs.

关键词： Keloid   Pruritus   Superficial dermis   IL-31   IL-31 receptor   M2 macrophages  

摘要： BackgroundThe exact pathogenesis of keloid (KD) associated pruritus is still unknown and responds poorly to current antipruritic therapies. Pruritogenic role of interleukin-31 (IL-31) has been studied extensively and was proven in a variety of pruritus associated diseases, while its role in KD is still rather *** aim of this study is to explore the pathophysiological mechanism of KD-associated pruritus by detecting the correlation between the severity of pruritus and the expression of pruritogenic cytokines IL -31 and its receptor complex components, IL-31 receptor alpha (IL-31RA) and Onstostatin M receptor beta (OSMR beta), and the number of their source *** total of 46 keloid tissue samples were included in this study and clinical data were recorded, of which 24 were available with both lesional and clinically adjacent uninvolved perilesional skin ( AUPS, taken at least 0.5 cm away from the keloid edge ), and 22 were available with lesional skin only. In this study, immunofluorescence detection was used to detect and compare the expression differences of IL-31 and its receptors (IL-31RA and OSMR beta) in different layers (epidermis, superficial dermis, and deep dermis) between keloid lesions and AUPS and the correlation between the IL-31 expression level and the severity of KD-associated pruritus was explored. In addition, immunofluorescence co-localization was used to explore the cell source of IL-31, and the correlation between the number of source cells and the severity of KD-associated pruritus was explored. The fluorescence intensity in epidermis and number of infiltrating cells in the dermis was quantified and normalized by ImageJ *** this study, the KD and AUPS groups were matched for age and gender, which were not statistically different and, there was no significant difference in the sample causes and distribution between two groups. Compared with the AUPS, the number of IL-31(+) cells in the superficial and deep d

关键词： Systemic lupus erythematosus (SLE)   Lupus nephritis (LN)   Granzyme B   Cytotoxicity   PI3K  

摘要： Objective: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which is affected by the environmental, genetic factors as well as the immune system. Previous reports have implicated IFN-alpha in the pathogenesis of SLE. Up to date, however, no research has ever investigated the effect of IFN-alpha on CD8+T cells, which might be implicated in the pathogenesis of SLE. In the present study, we aimed to explore the pathologic role of IFN-alpha in regard to dysfunction of CD8+T cells in SLE. Methods: Serum level of IFN-alpha was detected in SLE and healthy controls (HC). Surface expression of lysosomeassociated membrane protein 1 (LAMP-1;CD107a) and secretion of granzyme B of CD8+T cells was measured in SLE and HC with or without IFN-alpha co-stimulation/PI3K inhibitor. Results: Our results demonstrated that there was increased surface expression of CD107a of CD8+T cells in SLE patients compared with healthy controls (HC), indicating enhanced cytotoxicity of CD8+T cells in SLE patients. Meanwhile, increased secretion of granzyme B was also detected in CD8+T cells of SLE compared with HC, which correlated with the disease activity (SLEDAI). Furthermore, elevated serum level of IFN-alpha in SLE was confirmed in our study. In vitro study, granzyme B secretion by CD8+T cells was upregulated upon IFN-alpha costimulation, which was consistent with enhanced cytotoxicity of CD8+T cells upon IFN-alpha costimulation, as reflected by elevated surface expression of CD107a. PI3K inhibitor reversed increased granzyme B synthesis upon IFN-alpha costimulation in a dose-dependent manner. Conclusion: In summary, elevated serum level of IFN-alpha was responsible for increased secretion of granzyme B and enhanced cytotoxicity of CD8+T cells in SLE and this process may be related to PI3K pathway. Relevant molecules and mechanism remains to be explored in the future.