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关键词： atopic dermatitis   cytokines   IL36G   immune infiltration   monocytes  

摘要： Atopic dermatitis (ad) is a chronic inflammatory skin disease, with recent studies indicating that immune cells, such as monocytes and inflammatory cytokines, play a crucial role. By retrieving datasets from public databases and analysing immune cell infiltration in lesional skin using CIBERSORT, we found that monocytes and M2 macrophages were significantly upregulated in atopic dermatitis. Differentially expressed gene (DEG) functional enrichment analysis revealed that cytokine-cytokine receptor interaction was the most significantly enriched pathway. Further analysis of cytokines and their receptors, along with their correlation with infiltrating immune cells, identified IL36G-expressing monocytes as a key target in atopic dermatitis. We compared immune cell infiltration and cytokine-related targets in similar inflammatory skin diseases, such as psoriasis and urticaria, to evaluate similarities and differences among these three skin conditions. The analysis revealed that IL36G-expressing monocytes were also highly expressed in psoriasis but did not play a pivotal role in urticaria. Finally, we used molecular docking to predict and validate drugs targeting IL36G. Our study highlights IL36G-expressing monocytes as a common key target in atopic dermatitis and psoriasis, offering novel insights and therapeutic strategies for these related diseases.

关键词： Myocardial infarction   Responsive hydrogel   IL1(3   Nanobody  

摘要： The cardiac microenvironment profoundly restricts the efficacy of myocardial regeneration tactics for the treatment of myocardial infarction (MI). A prospective approach for MI therapeutics encompasses the combined strategy of scavenging reactive oxygen species (ROS) to alleviate oxidative stress injury and facilitating macrophage polarization towards the regenerative M2 phenotype. In this investigation, we fabricated a ROSsensitive hydrogel engineered to deliver our previously engineered IL-1(3-VHH for myocardial restoration. In mouse and rat models of myocardial infarction, the therapeutic gel was injected into the pericardial cavity, effectively disseminated over the heart surface, forming an in situ epicardial patch. The IL-1(3-VHH released from the hydrogel exhibited penetrative potential into the myocardium. Our results imply that this infarct-targeting gel can adhere to the damaged cardiac tissue and augment the quantity of anti-IL-1(3 antibodies. Moreover, the anti-IL-1(3 hydrogel safeguards cardiomyocytes from apoptosis by neutralizing IL-1(3 and inducing M2-type polarization within the myocardial infarction regions, thereby facilitating therapeutic cardiac repair. Our results emphasize the effectiveness of this synergistic comprehensive treatment modality in the management of MI and showcase its considerable potential for promoting recovery in infarcted hearts.

摘要： The polarization of the monocyte/macrophage compartment toward an anti-inflammatory profile is considered detrimental in tuberculosis (TB), but the factors controlling M2 polarization in this context are still poorly understood. Here, we found that B cells promote the differentiation of human monocytes toward an M2-like activation program through a process primarily dependent on IL-6 and the activation of STAT3 signaling in monocytes. This confers monocytes with immunomodulatory properties characterized by a reduced ability to produce proinflammatory cytokines and to stimulate IFN gamma secretion by allogeneic T cells. Our findings were validated using B cells from TB patients, which constitutively produce high levels of IL-6, underscoring the clinical relevance of our experimental observations. Collectively, our results indicate that human B-cell-derived IL-6 might impair TB immunity by driving monocyte polarization toward an anti-inflammatory phenotype.

关键词： early life   fetal   gammadelta   microbiota   probiotics  

摘要： The early life period is increasingly being recognized as a window of opportunity to shape immunity, where microbiota and related probiotics have an important impact. Innate gamma delta T cells are the first T cells generated in utero, populating epithelial tissues such as the lung and contributing to tissue protection through, for example, IL17 production. Here, we studied the influence of maternal microbiota and probiotic supplementation during pregnancy on innate gamma delta T cells in the lung and thymus of newborn mice. Detailed time-kinetic experiments showed that at birth, the murine lung T cell population was specifically dominated by IL17-committed gamma delta T cells expressing an invariant V gamma 6V delta 1 TCR. Single-cell RNA-sequencing showed that the biased IL17-commitment of perinatal lung gamma delta T cells is highly conserved between mice and humans. While maternal microbiota depletion with antibiotics tended to decrease the frequency of the lung V gamma 6 T cells of the offspring at birth, the maternal administration of Lacticaseibacillus rhamnosus (***.), but not of Bifidobacterium animalis subsp. lactis (***.), increased significantly their frequency, resulting in the augmentation of the IL17-commitment of the mouse lung T cell compartment. Altogether, our data indicate that the maternal microbiota contributes to the shaping of IL17-committed gamma delta T cells in the lungs of newborns and that maternal administration of specific probiotic strains can enhance this process.

关键词： Whole-body CT scanning radiation   Low-dose radiation   IFN   Tumor microenvironment  

摘要： Objective: This study aims to elucidate the impact of repeated whole-body computed tomography (CT) scans on systemic immunity, the tumor immune microenvironment, and tumor control. This inquiry was prompted by clinical observations indicating a decrease in the levels of IFN-(3 and IFN-gamma in patients' blood following wholebody CT scans. Methods: A Lewis lung carcinoma (LLC) mouse model was established and divided into two groups: a control group and a group subjected to multiple whole-body CT scanning radiation (WBCTSs). The study monitored tumor growth trends across both groups and employed a comprehensive set of analytical techniques-including enzyme-linked immunosorbent assay (ELISA), flow cytometry analysis, immunohistochemistry, RNA sequencing, and single-cell sequencing-to assess differences in cytokine profiles (IFN-(3 and IFN-gamma), proportions of key immune cells, and gene expression variations between the groups. Results: Repeated CT scan radiation does not promote tumor progression. In tumor tissues subjected to multiple CT scans, an increase in the proportion of CD8+ T cells, elevated interferon levels, and up-regulation of genes associated with killing in CD8+ T cells and genes associated with Ifnb in macrophages were observed. In contrast, radiation from multiple whole-body CT scans resulted in a decrease in the proportion of CD8+ T cells in the blood and spleen, a decrease in serum interferon levels, and down-regulation of killing-related genes in CD8+ T cells. Conclusion: Our results suggest that repeated whole-body CT scanning radiation induces systemic immunosuppression and immune activation in tumor tissues. Multiple repeated CT scans do not promote tumor progression.

关键词： osteomyelitis   etanercept   tumor necrosis factor inhibitors   adalimumab   acquired hyperostosis syndrome  

摘要： Objectives Primary chronic non-bacterial osteomyelitis of the mandible (CNOM) is a rare auto-inflammatory disease of unknown aetiology that bears pathophysiological resemblance to both SAPHO syndrome in adults and chronic recurrent multifocal osteomyelitis (CRMO) in children. Both SAPHO and CRMO respond to TNF-alpha blockade. Previously reported treatment regimens in CNOM including NSAIDs, corticosteroids, antibiotics, anti-resorptive therapy and surgery all bear disappointing results. TNF-alpha blockade is suggested as a treatment option by some experts but this is not backed by any clinical data. We sought to retrospectively and exhaustively report our experience of anti-TNF-alpha therapy in refractory *** Fifteen patients with refractory CNOM and high disease burden were referred to our centre. TNF-alpha blockade was attempted in 10 cases, given its efficacy in neighbouring diseases, its good tolerance profile and failure of previous treatment strategies. We herein retrospectively report detailed outcomes for all patients having received anti-TNF-alpha therapy for this indication in our *** TNF-alpha-targeting therapy resulted in a rapid and sustained remission in a majority of patients with CNOM, without serious adverse events. Treatment was tapered and stopped without relapse in some patients despite a refractory course of several years. Male sex seems to be associated with a poorer *** Our results suggest that blocking TNF-alpha is efficient and safe in CNOM.

关键词： EPA   DHA   Insulin resistance   Muscle IL-6   IL-6/AMPK  

摘要： Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported to improve insulin resistance (IR), but the mechanisms and differences remain unclear. Our results showed that EPA and DHA activated muscle IL-6 and improved IR in high-fat diet-fed mice. After knocking out muscle IL-6, the effect of EPA on improving systemic IR was abolished, but the effect of DHA was restored;however, neither EPA nor DHA improved muscle IR through activating AMPK. Furthermore, EPA and DHA activated IL-6 and improved palmitic acid-induced IR in C2C12 myotube cells. After silencing IL-6, neither EPA nor DHA improved IR through activating AMPK in myotube cells. Once AMPK was inhibited, the effect of EPA and DHA on improving IR was both abolished. Additionally, IL-6 activated AMPK and improved IR in myotube cells. In conclusion, EPA but not DHA improves systemic IR mainly due to attenuating muscle IR through IL-6/AMPK signaling pathway.

关键词： experimental validation   Ganoderma lucidum (Leyss.Ex Fr.) karst   Ganodermanontriol   network pharmacology   pneumonia  

摘要： Ganoderma lucidum (Leyss. ex Fr.) Karst, commonly known as Lingzhi, has long been employed in traditional Chinese medicine for its medicinal properties, particularly in alleviating respiratory issues like cough and asthma. Recognized both as a therapeutic agent and an edible supplement, Lingzhi is celebrated for its health-promoting benefits. Despite its widespread use, the effectiveness of G. lucidum in treating pneumonia has not been extensively studied, highlighting the need for further research. This research aimed to evaluate the potential of G. lucidum in pneumonia treatment and to uncover the mechanisms behind its effects, specifically examining how its active constituents influence inflammatory pathways. The study utilized approaches such as network pharmacology, bioinformatics, molecular docking, and in vivo experiments. High-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) analyses revealed eight triterpenoids in G. lucidum, with ganodermanontriol being the most prominent. Molecular docking studies anticipated the interactions between these compounds and target proteins, while in vivo experiments on pneumonia-induced rat models assessed the efficacy of ganodermanontriol. Additionally, HPLC and LC-MS confirmed the presence of eight triterpenoids in the ethanol extract of G. lucidum, predominantly ganodermanontriol. Network pharmacology and molecular docking identified key genes-including TNF, EGFR, ESR1, HIF1A, HSP90AA1, and SRC-that played significant roles in the regulation of inflammatory pathways. In vivo results demonstrated that ganodermanontriol treatment mitigated lung tissue damage in rats with experimentally induced pneumonia by reducing the release of inflammatory mediators. Further mechanistic studies showed that ganodermanontriol downregulated TNF-alpha and inhibited the NF-kappa B/MAPKs signaling pathways. These findings suggested that ganodermanontriol holds promising potential as an anti-inflammato