课程文献中心 更多>>

关键词： 清热化痰活血汤   孟鲁司特纳   小儿支原体肺炎   淋巴细胞   C反应蛋白  

摘要： 目的:探究清热化痰活血汤治疗小儿肺炎支原体肺炎(MPP)的疗效及对免疫及淋巴细胞与C反应蛋白比值(LCR)的影响.方法:选用 2023 年 1 月～12 月在本院接受治疗的支原体肺炎患儿 198 例,按照信封随机法均分为联合组(清热化痰活血汤联合孟鲁司特钠治疗,n=99 例)和对照组(孟鲁司特钠治疗,n=99 例),比较两组疗效及治疗前后主、次症评分,症状缓解时间,免疫功能[C反应蛋白(CRP)、白细胞介素-6(IL-6)、LCR、免疫球蛋白(IgM)]、肺功能[第 1s用力呼气量(FEV1)、最大呼吸峰流速(PEF)、1s用力呼气量占用力肺活量比值(FEV1/FVC)].结果:联合组治疗后总有效 41 例,总有效率 96.97%,较对照组的 84.85%高(P＜0.05);联合组主症、次症各项评分均低于对照组(P＜0.05);联合组症状缓解时间均短于对照组(P＜0.05);联合组血清治疗后 CRP、IL-6 明显低于对照组(P＜0.05),LCR、IgM高于对照组(P＜0.05).两组患儿治疗后FEV1、PEF、FEV1/FVC水平均明显升高,且联合组高于对照组(P＜0.05).结论:清热化痰活血汤治疗MPP,临床效果显著,可改善发热、咳嗽等临床症状,提升免疫功能,降低炎症因子水平,改善肺功能,促进疾病的康复和预后.

关键词： Aurapten   IL-17   Rheumatoid arthritis   TNF-α   Umblliprenine  

摘要： Objective: To compare the anti-arthritic potential of orally administered auraptene (AUR) and umbellliprenin (UMB) in chronic inflammation by exploring the differential effect on regulating TNF-α and IL-17. Methods & materials: Sixty male rats were divided into ten groups, and after confirming chronic inflammation, the treatment groups received AUR or UMB orally for 9 days. On day 16, histopathological changes were evaluated. Altered serum levels of the inflammatory cytokines TNF-α and IL-17 were examined as the underlying mechanisms. Results: Administering AUR orally at 16 mM/kg caused a significant increase in body weight gain compared to the baseline (p < 0.05), while UMB at a dose of 64 mM/kg significantly reduced edema size (p < 0.01). TNF-α levels were significantly lower in all doses of AUR and UMB treatments compared to the arthritis control group (p < 0.05). Treatment with AUR at all relative doses resulted in a significant decrease in IL-17 levels compared to the arthritis control group (p < 0.05), whereas UMB treatment did not show a significant effect on IL-17 levels. Conclusion: AUR and UMB regulate TNF-α and IL-17 differently;AUR inhibits both, showing broad therapeutic potential, while UMB specifically targets TNF-α, showing a specialized role. © 2024 The Authors

关键词： asthma   biologics   biomarkers  

摘要： BackgroundIn patients with severe asthma, treatment with anti-interleukin-5 (IL-5) biologics can lead to a reduction in fractional exhaled nitric oxide (FeNO) in some patients. The clinical implications of varying FeNO responses to anti-IL-5 biologics remain unclear. This study aims to categorise patients based on their FeNO response to anti-IL-5 biologics and evaluate the association of these categories with clinical *** used the Danish Severe Asthma Register (DSAR) to identify the early FeNO response profiles in patients receiving anti-IL5 biologics. We defined FeNO responders as patients with elevated FeNO levels at baseline and a decrease corresponding to the minimal clinically important difference (MCID) at 4 months of follow-up and FeNO non-responders as those who did not experience a *** identified 403 patients on anti-IL5 treatment in DSAR, and 265 (66%) had elevated FeNO levels at baseline. After 4 months of treatment, 151 (57%) patients showed a significant decrease in FeNO levels, and 114 (43%) did not. FeNO responders were more likely to achieve clinical remission of asthma (34% vs. 19%, p = 0.01, OR 2.11, CI 1.04, 5.18, p = 0.03) than FeNO non-responders after 12 months of treatment. The higher remission rates in FeNO responders mainly reflected a higher rate of normalisation of lung *** levels were reduced after anti-IL5 treatment in a significant proportion of patients treated with anti-IL5, and this was associated with clinical remission. Early FeNO response to anti-IL5 could potentially be used as a biomarker to guide management decisions with biologics towards remission of disease in severe asthma.

关键词： Atopic dermatitis   Pruritus   Human leukocyte antigens   Alleles  

关键词： Interleukin 17   biomarkers   cancer   carcinogenesis   cytokines   prognosis   therapy  

摘要： Interleukin 17 (IL17) is a cytokine involved in immune regulation and has been increasingly recognized for its role in cancer progression. This systematic review aims to integrate data on IL17's role in various tumors to better understand its implications for cancer prognosis and treatment. The review included 105 studies (27.6% experimental and 72.4% clinical). Clinical studies involved 9,266 patients: 31.2% males, 60.0% females, and 8.8% with undefined gender. IL17A and IL17 were the most studied subtypes (36.2% and 33.3%, respectively). Breast cancer (26.7%), colorectal carcinoma (13.3%), and hematologic malignancies (10.5%) were the most researched neoplasms. IL17A promoted tumor growth in breast cancer and correlated with poor outcomes in colorectal, breast, and lung cancers. IL17 also played a significant role in immune modulation in gliomas and other tumors. IL17A significantly influences tumor growth and prognosis across various cancers, with notable roles in immune modulation and poor outcomes in multiple cancer types.

关键词： Bis[monoacylglycerol]phosphates   Enzymology/Enzyme mechanisms   Glycerophospholipids   Inflammation   Lipotoxicity   Macrophage   Phospholipids/Phosphatidic acid  

摘要： Long-chain acyl-CoA synthetase 1 (ACSL1) catalyzes the conversion of long-chain fatty acids to acyl-CoAs. ACSL1 is required for β-oxidation in tissues that rely on fatty acids as fuel, but no consensus exists on why ACSL1 is induced by inflammatory mediators in immune cells. We used a comprehensive and unbiased approach to investigate the role of ACSL1 induction by interferon type I (IFN-I) in myeloid cells in vitro and in a mouse model of IFN-I overproduction. Our results show that IFN-I induces ACSL1 in macrophages via its interferon-α/β receptor, and consequently that expression of ACSL1 is increased in myeloid cells from individuals with systemic lupus erythematosus (SLE), an autoimmune condition characterized by increased IFN production. Taking advantage of a myeloid cell-targeted ACSL1-deficient mouse model and a series of lipidomics, proteomics, metabolomics and functional analyses, we show that IFN-I leverages induction of ACSL1 to increase accumulation of fully saturated phosphatidic acid species in macrophages. Conversely, ACSL1 induction is not needed for IFN-I's ability to induce the prototypical IFN-stimulated protein signature or to suppress proliferation or macrophage metabolism. Loss of ACSL1 in IFN-I stimulated myeloid cells enhances apoptosis and secondary necrosis in vitro, especially in the presence of increased saturated fatty acid load, and in a mouse model of atherosclerosis associated with IFN overproduction, resulting in larger lesion necrotic cores. We propose that ACSL1 induction is a mechanism used by IFN-I to increase phosphatidic acid saturation while protecting the cells from saturated fatty acid-induced cell death.

关键词： allergic asthma   interleukin-33   interleukin-9   macrophage polarization   macrophage subset  

摘要： BackgroundMacrophages, one of the most abundant immune cells in the lung, have drawn great attention in allergic asthma. Currently, most studies emphasize alternative activated (M2) polarization bias. However, macrophage function in allergic asthma is still controversial. Interleukin (IL)-9 contributes to the development and pathogenesis of allergic airway inflammation. We sought to investigate the IL-9-producing macrophage and its role in allergic *** model of ovalbumin (OVA)-induced allergic airway inflammation was employed to evaluate IL-9 production in macrophages of lung tissues. We used 22 cytokines or stimuli to screen for IL-9-producing mouse macrophage subset in vitro. Real-time PCR, flow cytometry, ELISA, and RNA-seq to explore the subset. Conditional IL-33 receptor knockout (Lyz-ST2KO) mice and cellular adoptive transfer experiment were used to characterize the potential roles of M(IL-33 + IL-2) in allergic *** identified a unique pathogenic IL-9-producing macrophage in OVA-induced allergic airway inflammation. We found that only IL-33 significantly induced IL-9 production in mouse macrophages, and IL-2 collaborated with IL-33 to promote IL-9 production, referred to as M(IL-33 + IL-2). Importantly, human monocyte-derived macrophages produced IL-9 after IL-33 and IL-2 stimulation. Using Lyz-ST2KO mice and adoptive transfer of M(IL-33 + IL-2), we found that M(IL-33 + IL-2) significantly promoted pathogenesis in OVA-induced allergic airway inflammation. M(IL-33 + IL-2) has a distinctive gene expression profile with high expression of IL-9, IL-5, and IL-13 and its polarization is dependent on JAK2-STAT3-IRF1 *** identification of M(IL-33 + IL-2) subset extends the diversity and heterogeneity of macrophage subsets and may offer novel therapeutic strategies for the treatment of allergic inflammation.

关键词： binding specificity   cytokine receptors   cytokines   gp130   interleukin-6 family   pleiotropy  

摘要： Historically, cytokines belonging to the gp130 family bind to specific ligand-binding receptors that stimulate cell signaling through a receptor complex comprising gp130 or gp130 together with another structurally related signaling receptor. However, recent findings increasingly dispel these stereotypes and suggest that the receptor specificity of gp130-activating cytokines is less strict than originally assumed. Weitz et al. now provide the latest example of this pleiotropy and report that human interleukin-6 can bind and stimulate signaling via the interleukin-11 receptor. Possible biological and therapeutic consequences of these findings are discussed.

关键词： Tripterygium wilfordii polyglycoside tablets   Hepatocellular carcinoma   therapeutic drug   IL-6   PI3K/MAPK/STAT3 signaling pathway  

摘要： Tripterygium wilfordii polyglycoside tablets (TWPT) have traditionally been used to treat certain inflammatory diseases. This study validated TWPT as a novel application in hepatocellular carcinoma treatment through multiple targets, thereby expanding its clinical medication scope. TWPT exhibited a low toxicity and a significantly antihepatoma effects in vitro and in vivo. Through network pharmacology analysis, we found TWPT attenuated the progression of hepatocellular carcinoma by multi-targeting, including IL-6, MMP9, TNF-alpha and VEGFA. Additionally, TWPT targeted IL-6 to regulate downstream pathways, including the PI3K/Akt, JAK2/STAT3, and MAPK signaling pathways. Thus, TWPT could be developed as a potential therapeutic drug for hepatocellular carcinoma.

关键词： Biomarker   CD8 T-cells   Computational pathology   MHC-I   Melanoma  

摘要： The success of immune checkpoint inhibitors (ICI) for melanoma therapy has catalyzed the introduction of ICI in increasingly early stages of disease. This exposes many patients with lower risk of relapse to the risk of protracted adverse events, highlighting the need for biomarkers guiding the use of ICI. Already many years ago, brisk infiltration of primary melanomas by lymphocytes has been linked to improved patient outcome, but controversial findings due to a high variability in classification systems have been described. CD8+ T-cells have been identified as a primary mediator of antitumor immunity in patients treated with ICI. As CD8+ T-cells require the presentation of antigen via MHC-I on target cells, downregulation and loss of MHC-I has been observed as resistance mechanisms to ICI. Here, we revisit the role of MHC-I expression and CD8+ T-cell infiltration in melanoma evolution using a cohort of advanced primary and matched metastatic melanomas by using an automated immunohistochemistry and digital pathology workflow. Our results show that downregulation of MHC-I expression is a frequent event in advanced primary melanomas that is associated with decreased CD8+ T cell infiltration and early metastatic spread to sentinel lymph nodes. Furthermore, MHC-I downregulation and decreased infiltration with CD8+ T-cells is also associated with resistance to ICI. Our results suggest that analyses of MHC-I expression and CD8+ T-cell infiltration patterns could serve as future biomarkers to guide the decision to treat patients in early stages of melanoma with ICI.