课程文献中心 更多>>

关键词： DNA methylation   IL6   Methotrexate   Propolis   Epigenetic   Leukemia   COVID-19   Epidrugs  

摘要： BackgroundThe natural active ingredient propolis, which is used to support the treatment of inflammatory diseases, and the drug methotrexate (MTX), which is used to treat tumor diseases, have already shown that they are able to change the DNA methylation *** aim of the study was to evaluate the ability of propolis oral spray and intravenous methotrexate to modulate the DNA methylation profile of the interleukin-6 (IL6) gene, which encodes an inflammatory cytokine that is important in both inflammatory and tumor *** propolis intervention was tested in adults affected by COVID-19 (n = 114) and the methotrexate intervention was tested in children and adolescents with leukemia (n = 64). DNA methylation in the IL6 gene promoter was analyzed using the methylation-specific PCR (MSP) technique using DNA extracted from oral mucosa or *** fully methylated profile in blood cells of adults with COVID-19 was observed in 100% of the samples both before and after the propolis intervention. The methylated profile was also observed in buccal cells from pediatric patients with leukemia in 100% of the samples regardless of MTX *** is concluded that the methylated profile in the IL6 gene promoter is a common profile for adult blood cells and pediatric oral cells and is not modulated by the use of propolis or methotrexate.

关键词： Systemic sclerosis   Interleukin 40   Biomarkers  

摘要： BackgroundInterleukin 40 (IL-40) is a cytokine implicated in malignancies and rheumatic disorders. Its association with fibrotic mediators has been previously described. Since inflammation and fibrosis are hallmarks of systemic sclerosis (SSc), we aimed to analyze the role of IL-40 in SSc. MethodsIL-40 levels were analyzed in the serum of 90 SSc patients and 75 healthy controls (HCs). IL-40 expression in dermal biopsies from 5 SSc patients and 5 HCs was assessed via immunohistochemistry. IL-40 was analyzed in 39 SSc patients with interstitial lung disease treated with cyclophosphamide (CPA) and in 24 SSc patients with active progressive disease treated with rituximab (RTX). SSc activity was assessed by the European Scleroderma Study Group (ESSG) index. The effect of recombinant IL-40 on peripheral blood mononuclear cells (PBMCs) from 10 SSc patients was determined in vitro. IL-40 was analyzed in 24 individuals at risk of developing SSc (VEDOSS), who were categorized as progressors (n = 11) and nonprogressors (n = 13). ResultsIL-40 expression was elevated in the skin of SSc patients compared to HCs, particularly in fibroblasts and immune infiltrates. Serum IL-40 was increased in SSc compared to HCs (p < 0.0001) and was associated with ESSG (r = 0.372, p = 0.0005) and gastrointestinal involvement (p < 0.05). IL-40 correlated with serum IL-8 (r = 0.270, p = 0.019) and TGF-beta 1 (r = 0.301, p = 0.024) levels. In the CPA and RTX cohort, no significant changes in the serum IL-40 were observed upon treatment. Baseline and changes in IL-40 levels were associated with changes in several clinical parameters. IL-40 was elevated in patients at risk of SSc compared to HCs (p = 0.0003). No significant changes were observed in progressors vs. nonprogressors;however, IL-40 was associated with capillaroscopy findings (p < 0.05). IL-40 induced the upregulation of IL-6 (p = 0.002), MCP-1 (p = 0.002) and IL-10 (p = 0.002) in PBMCs from SSc patients in vitro. ConclusionsIL-40 was upreg

关键词： Lung carcinoma   Molecular pathogenesis   HLA-A   HLA-B   HLA-DR  

摘要： According to GLOBOCAN 2022 estimates, lung cancer is the leading cause of cancer morbidity and mortality in 2022. 5 year survival rate is dismal for the disease, despite advances in therapeutic modalities. Current research into lung cancer therapy is largely focused on molecular advancements. Our study was focused on finding association between the HLA expression in lung carcinoma patients, in northern region of India. It contributes data for basic molecular understanding of pathogenesis in lung cancer patients. This study was conducted in the Department of Pathology and Department of Pulmonary critical care and sleep medicine, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi. A total of 35 lung cancer cases and 35 healthy controls were taken over a period of 18 months and results were compared. In our study the mean age of presentation for lung carcinoma patients was 52.29 years HLA-A11 (p value = 0.028) and HLA-B51 (p value = 0.035), were under expressed in the patients as compared to control group, and HLA-DRB1*15 (p value = 0.037) was over expressed in the patients as compared to control group. However, no statistically significant result was seen in co-relation to the clinical staging. The results of this small sample study provide data for a completely new population and might help to guide in understanding the role of HLA in lung carcinoma patients for future studies.

关键词： Hypobaric hypoxia   HAPE   NKT cells   IL-10   curcumin  

摘要： Background: There are environment-dependent pro-inflammatory and anti-inflammatory pathways during exposure to high altitudes. Although inhibiting the inflammatory pathway can alleviate high altitude pulmonary edema (HAPE), it is currently unclear whether inflammation is the cause of edema or the result of edema in HAPE-afflicted patients. Natural killer T (NKT) cells are a subset of T cells that play an important role in a variety of lung diseases. However, its specific role in HAPE remains unclear. Methods: HAPE rat model was established under hypobaric hypoxia condition. To investigate the role of NKT cells in HAPE, phenotypic and functional changes of NKT cells and their subpopulations were analyzed by flow cytometry. To further investigate the effect of TNF-alpha on NKT cells, rats were given intraperitoneal injection of TNF-alpha, and then, NKT cells were characterized by flow cytometry. Subsequently, the levels of TNF-alpha in the lungs and spleens of rats were detected by ELISA, and HAPE rats were treated with curcumin. Results: Compared with normal control, the ratio of TNF-alpha and IL-10 secreted by lung NKT cells was decreased in HAPE rats induced by hypoxia. Further analysis showed that the mean fluorescence intensity (MFI) of TNF-alpha in NKT cells did not change significantly, but the MFI of IL-10 increased significantly. Moreover, the MFI of IL-10 produced by TNF-alpha-treated rat lung NKT cells was higher, which was completely different from spleen NKT cells. ELISA experiments indicated that TNF-alpha was enriched in the lung tissue of rats regardless of hypoxia, and the level of TNF-alpha in lung tissue was upregulated after hypoxia. Furthermore, when HAPE rats were treated with curcumin, the MFI of IL-10 in the NKT cell subsets decreased. Conclusions: NKT cells produce high levels of IL-10, which inhibits the production of lung inflammation in HAPE rats. With the increase of TNF-alpha level, the inhibitory effect of lung NKT cells on inflammation

关键词： chronic lymphocytic leukemia   IL-10   MYC   statins   Toll-like receptors  

摘要： The cytokine-signaling inhibitor ruxolitinib causes disease flares of chronic lymphocytic leukemia (CLL). This tumor-promoting activity correlates with its ability to inhibit interleukin (IL)-10 production by CLL B cells that have been activated with IL-2 and the Toll-like receptor 7 (TLR7) agonist resiquimod (called 2S cells) in vitro. In TLR-activated normal human B cells, IL-10 production is regulated by cholesterol biosynthesis and can be inhibited by statins. The goal of this study was to determine if statins affect IL-10 production by 2S cells. Lipophilic statins decreased IL-10 production from 2S CLL cells by inhibiting activation of MYC along with secondary signaling events that amplify and maintain IL10 transcription. IL-10 production was restored when the prenylation defect imposed by statins was corrected by adding geranylgeranyl pyrophosphate. CLL cells activated by ruxolitinib in vivo were enriched with genes associated with prenylation inhibition in TLR-activated human B cells in vitro. These findings suggest IL-10 production by 2S-activated CLL cells is regulated by cholesterol biosynthesis in part through geranylgeranyl pyrophosphate production and substrate prenylation. If IL-10 production in the 2S model constitutes a surrogate test for drug responses in vivo, realization of the potential clinical benefits of statins in CLL may require coadministration of other agents.

关键词： Adult-onset Still's disease   Mass cytometry   Tocilizumab  

摘要： BackgroundEarly administration of IL-6R blockade is effective in adult-onset Still's disease (AOSD), but the underlying immune alterations during combined immunotherapy remain *** employed high-dimensional single-cell mass cytometry and an unbiased bioinformatics pipeline to characterize the immune landscape in treatment-na & iuml;ve AOSD patients, stable AOSD patients after 24 weeks of IL-6R blockade plus methotrexate and prednisone, and matched healthy controls. Cytokine profiling was conducted using a high-throughput cytometric bead array, and potential regulatory networks were identified using the PerformanceAnalytics package. Validation was performed via flow cytometry and mRNA *** identified 22 peripheral immune cell populations and characterized their composition and phenotypic markers. Treatment-na & iuml;ve AOSD patients exhibited significant depletion of CD4+ T cells and B cells, along with excessive activation of CD8+ T cells and a previously unreported CD45+CD3-CD19-CD10-CD66a+ population, findings that were validated in an independent AOSD cohort. mRNA sequencing revealed the proinflammatory role of CD8+ T cells. Notably, these dysregulated immune profiles were markedly restored following immunotherapy. IL-18, IL-21, and IFN-gamma demonstrated strong associations with adaptive immune cells and AOSD clinical *** IL-6R blockade effectively modulates immune dysregulation in refractory AOSD, reversing key pathological immune alterations and highlighting its therapeutic potential.

关键词： alpha-olefins   Fischer-Tropsch synthesis   green separation technology   ionic liquids   microwave-assisted extraction  

摘要： The actual applications of extraction methods for alpha-olefins separation are limited by their long time and high energy consumption. Hence, this study employs microwave technology to intensify the extraction process using Ag-based ionic liquid (Ag-IL), where the influence of microwave irradiation and the mechanism of microwave-assisted ionic liquid extraction (MAILE) are investigated, along with a comprehensive techno-economic analysis of process feasibility. The results of COSMO-RS and DFT simulations demonstrate the dominant role of pi-complexation in identifying Ag-IL with high selectivity, indicating the possible enhancement caused by microwave irradiation. The subsequent kinetic experiments show that compared with conventional routes, the MAILE accelerated the extraction process by approximately 89.72%. As a result, the total annual cost of unit product of the overall process is reduced by 6.43% according to techno-economic analysis by Aspen Plus, indicating that MAILE is a cost-effective, scalable, and sustainable approach to alpha-olefin separation, offering process efficiency and environmental sustainability.

关键词： polysaccharides   black mulberry   colitis   Weissella   TNF   tight junctionprotein  

摘要： Colitis is characterized by immune dysregulation and gut microbiota imbalance. This study investigates the therapeutic effects of polysaccharides from black mulberry (PBM) on dextran sulfate sodium-induced colitis in mice. PBM administration significantly alleviated colitis symptoms, including body weight loss, histological damage, and inflammation, while enhancing antioxidant capacity and strengthening tight junction protein expression. PBM modulated gut microbiota composition, notably increasing Weissella spp., which correlated with elevated short-chain fatty acids (SCFAs) and decreased pro-inflammatory markers. Colonic RNA sequencing revealed the role of PBM in attenuating colitis via the TNF-alpha/NF-kappa B/ICAM-1 signaling pathway. Fecal microbiota transplantation (FMT) from PBM-treated mice confirmed that microbiota modulation from PBM contributed to these therapeutic effects. These findings suggest PBM as a natural therapeutic agent for colitis, offering a multifaceted approach to restoring gut homeostasis through microbiota modulation and inflammatory pathway regulation. This study provides new insights into dietary polysaccharides as potential adjunctive therapies for colitis.

关键词： IL-6   apathy   brain–body   cancer cachexia   metabolism   neuroimmune circuit  

摘要： Neuropsychiatric complications of cancer cachexia include apathy. Zhu et al. identified a brain circuit sensitive to tumor-driven interleukin-6 (IL-6) signaling that directly reduces motivation by suppressing dopaminergic activity. Targeted circuit-based and pharmacologic interventions, including systemic anti-IL-6 antibodies, reversed motivational deficits and point to new therapeutic avenues for apathy.