课程文献中心 更多>>

关键词： IL-33   Endometriosis   Pain   Macrophages   Inflammation  

摘要： Endometriosis, a persistent inflammatory disease, is associated with pelvic or abdominal pain. The immune system and sensory nervous system show a synergistic effect on regulation of pain. In particular, Interleukin-33 (IL-33) is released as a danger signal and drives key hallmarks of severe endometriosis. To explore the mechanistic involvement of IL-33 in pain associated with endometriosis, both an in vivo murine endometriosis model and in vitro experiments with RAW 264.7 cells and dorsal root ganglion (DRG) neurons were utilized. In vivo, we demonstrated that IL-33 significantly exacerbated endometriosis and induced hyperalgesia in mice. By interacting with the ST2 receptor in macrophages, IL-33 enhanced the release of tumor necrosis factor alpha (TNF-alpha) and Interleukin 1 beta (IL-1 beta). This process set off an inflammatory cascade, which further facilitated macrophages recruitment and neurogenesis in ectopic lesions. As an ion channel expressed by nociceptors, transient receptor potential vanilloid 1 (TRPV1) expression was significantly increased in DRG in the presence of IL-33. In vitro, we confirmed that IL-33 elevated the release of TNF-alpha in macrophages. Ultimately, macrophage-derived TNF-alpha increased TRPV1 protein level in DRG neuronal cells through the TNFR1/p38 MAPK signaling pathway. Overall, these results revealed an inductive role of IL-33 in pain associated with endometriosis, and highlighted the interaction between macrophages and sensory neurons.

关键词： IL-6   Post-transplantation cyclophosphamide   Anti-thymocyte globulin   GVHD   Hematopoietic stem cell transplantation  

摘要： BackgroundPost-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common prophylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD. MethodThe clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from January 2019 to February 2023. ResultsForty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 +/- 10.55 vs. 117.65 +/- 127.67;p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II-IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II-IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%;p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%;p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%;p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%;p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038). ConclusionSerum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II-IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms o

关键词： Sepsis   Acute respiratory distress syndrome (ARDS)   IL-27   Nrf2/HO1   Ferroptosis  

摘要： ObjectivesAcute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by high morbidity and mortality rates. Sepsis-induced ARDS involves excessive inflammatory responses, which are modulated by macrophages. This study aimed to elucidate the effect of Recombinant Mouse IL-27 Protein on macrophage ferroptosis and polarization, as well as its impact on sepsis-induced *** cecal ligation and puncture (CLP)-induced sepsis model was established using wild-type (WT) or IL27R-/- mice. Then, the mice were randomly divided into 4 groups: a control group, a CLP group, an IL-27 + CLP combination group, and an IL-27, CLP, and Oltipraz combination group. RAW 264.7 cells and BMDMs were used to further determine the role and mechanism of IL-27 in *** vitro, IL-27 alone did not alter the expression of proteins linked to the ferroptosis pathway or macrophage polarization. Contrastingly, the combination of IL-27 with LPS further amplified LPS-induced alterations in the ferroptosis pathway, thereby promoting macrophage M1 polarization and inhibiting M2 polarization. Additionally, IL-27 + LPS increased ROS levels in macrophages. A sepsis-induced ARDS mouse model was then established via CLP. In vivo, IL-27 exacerbated CLP-induced lung injury in WT mice. Additionally, it decreased the expression levels of ferroptosis-related proteins (Nrf2, HO-1, GPX4) and increased those of Ptgs2 in the lung tissue of septic mice. Besides, GSH and SOD levels in lung tissue were also reduced. Moreover, IL-27 also promoted M1 polarization and inhibited M2 polarization in macrophages. In IL27R-/- mice, the effects of IL-27 were abrogated. Oltipraz inhibited IL-27-induced changes by up-regulating Nrf2 expression. Overall, this present study demonstrated that the combination of IL-27 and LPS-induced macrophage ferroptosis, promoted macrophage M1 polarization, and inhibited M2 polarization by inhibiting the Nrf2/HO-1 *** may alleviate ARDS-relat

关键词： 盐酸青藤碱   急性T淋巴细胞白血病   CEM细胞   细胞凋亡   RNA-seq测序   增殖抑制   工程化细胞  

摘要： 背景:盐酸青藤碱有抗多种肿瘤的作用,但目前尚不清楚盐酸青藤碱对急性T淋巴细胞白血病的作用。目的:探讨盐酸青藤碱对急性T淋巴细胞白血病CEM细胞的抑制作用。方法:应用不同浓度(0.5,1,2,4 mmol/L)盐酸青藤碱处理CEM细胞,CCK-8检测细胞增殖抑制率并计算IC50;倒置显微镜和吉姆萨染色观察CEM细胞形态变化;利用RNA-Seq测序分析差异基因表达并进行生物信息学分析。结合转录组测序结果,流式细胞术检测不同浓度(1,2,4 mmol/L)盐酸青藤碱作用后CEM细胞凋亡率;Western blot检测不同浓度(1,2,4 mmol/L)盐酸青藤碱作用后CEM细胞中Bcl-2、Bax、Caspase-9蛋白的表达。结果与结论:①盐酸青藤碱呈剂量和时间依赖性地抑制CEM细胞生长;②盐酸青藤碱干预后CEM细胞数量下降,核固缩;③RNA-seq测序筛出53个异常表达基因,基因本体分析主要富集在细胞过程、细胞解剖实体与粘连关系等,信号通路分析与肿瘤相关的是细胞凋亡;④盐酸青藤碱呈剂量依赖性地促进CEM细胞凋亡;⑤盐酸青藤碱上调CEM细胞中Bax、Caspase-9蛋白表达,下调Bcl-2蛋白表达。由此可见,盐酸青藤碱可诱导CEM细胞凋亡从而抑制细胞增殖,可能与其上调Bax和Caspase-9蛋白表达,以及下调Bcl-2蛋白表达有关。

关键词： Hydroxychloroquine   IgA nephropathy   network pharmacology   TNF   toll-like receptor signaling pathway  

摘要： Background IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally and has a high propensity to develop into end-stage renal disease (ESRD). Hydroxychloroquine has been proven to reduce proteinuria in IgAN patients, but the precise mechanism remains unclear. Therefore, network pharmacology was used to investigate the *** PubChem and SwissADME databases were utilized to acquire the structure of hydroxychloroquine. The SwissTargetPrediction, PharmMapper, DrugBank, TargetNet, and BATMAN-TCM databases were then utilized to obtain the targets. The target genes related to IgAN were then gathered from the databases, which included GeneCards, PHARMGKB, DrugBank, OMIM, and DisGeNET. Common targets were obtained by UniProt. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to define the main molecular mechanisms and pathways. Furthermore, a protein-protein interaction (PPI) network was constructed using the STRING tool, and the core targets were obtained by Cytoscape. Finally, molecular docking between the core targets and hydroxychloroquine was *** 167 common target genes were acquired by overlapping. The core targets were TNF, ALB, IL1B, JUN, FOS, SRC, and MMP9. The GO and KEGG results showed the targets to be related to the production of inflammatory cytokines and chemokines and were engaged in the toll-like receptor (TLR) signaling pathway. At the same time, the molecular docking results showed that the core targets all combined with hydroxychloroquine *** This study proved that hydroxychloroquine may treat IgAN through the TLR signaling pathway, and the restraint of TNF, TLR, IL1B, and JUN may be essential for the treatment.

关键词： Optical biosensor   Multi-resonance analysis   IL-6   IL-8   OSCC   Point-of-care diagnostics   Semi-distributed interferometer   Biomarker detection   Surface functionalization  

摘要： Biomarker-based diagnostics offer a promising approach for early cancer detection, while simultaneous analysis of multiple biomarkers can further improve disease diagnosis by enhancing sensitivity and specificity of the detection. This work presents a multi-resonance analysis strategy for the simultaneous detection of oral cancer biomarkers interleukin-6 and interleukin-8 in artificial saliva with a Fiber-Bragg grating-assisted semi-distributed interferometer-based probe. The analysis of the sensor response takes advantage of the entire spectral feature, which enhances the robustness and reliability of the detection results. Unlike single-feature approaches, multi-resonance analysis ensures greater resilience to spectral distortions, since the spectral features of the proposed sensor exhibit varying sensitivity to biomolecular interactions. The sensor demonstrated a limit of detection (LoD) of 480 aM for IL-6 and 23.4 fM for IL-8 in artificial saliva with high specificity to target proteins.

关键词： Atherosclerosis   C1q/TNF-related protein-1   Mendelian randomization   Coronary artery disease   Ischemic stroke   Multivariate  

摘要： Aims: To investigate the causal relationship between C1q/TNF-related protein-1 (CTRP1) and atherosclerosis across various vascular sites, informed by studies connecting CTRP1 to coronary artery disease. Methods: Summary statistics of CTRP1 from the available genome-wide association studies and atherosclerosis in classic vascular sites (including cerebral, coronary, and other arteries) from the FinnGen biobank were extracted for a primary MR analysis, and the analysis was replicated using Ischemic Stroke cohort (large artery atherosclerosis) for validation. The inverse variance-weighted method was used for primary assessment. Sensitivity analysis was performed by Cochrane's Q test and leave-one-out analysis. Potential pleiotropic effects were assessed by MR-Egger intercept and MR-PRESSO global test. Additionally, multivariable MR (MVMR) analysis was performed to investigate the independent effect of CTRP1 on atherosclerosis after removing confounding factors. Results: Reliable causal evidence was found for CTRP1 involvement in three atherosclerosis endpoints: causal effects of CTRP1 on cerebral atherosclerosis (OR =1.31, CI:1.04-1.66;FDR_P=0.0222)], coronary atherosclerosis (OR=1.13, CI: 1.08-1.19;FDR_P=2.86e-07), and atherosclerosis at other sites (OR=1.06, CI:1.02-1.11;FDR_P=0.0125). The validation cohort further confirmed its causal effect on large-artery atherosclerosis (OR=1.10, CI:1.03-1.18;FDR_P=0.0115). The reverse MR analysis did not support the causal effect of atherosclerosis on CTRP1. Moreover, the MVMR analysis, adjusting for confounders (CTRP3, CTRP5, and CTRP9A), highlighted a significant independent causal effect of CTRP1 remaining on atherosclerosis. Conclusion: CTRP1 may represent a promising target for preventing and treating systemic atherosclerosis.

关键词： Neuroimmunology   Pediatric Demyelinating Disease   Early Stage Investigator  

关键词： 创伤性脑损伤   骨痂   骨折愈合   炎症反应   细胞因子   激素   神经肽   基因   干细胞  

摘要： 背景:骨折延迟愈合和不愈合是常见的临床问题。在临床观察中,常见到合并创伤性脑损伤的四肢骨折患者的骨折愈合速度明显快于无脑损伤的患者。这一现象背后的可能机制已成为当前研究的重要焦点。近年来的研究表明,创伤性脑损伤通过调控细胞因子、激素、神经信号以及干细胞等机制,显著加速了骨痂形成和骨折愈合过程。目的:总结创伤性脑损伤促进骨痂形成及骨折愈合机制的最新研究进展,为临床应用提供理论依据。方法:文章第一作者通过检索中国知网、万方、维普、PubMed、Embase、Web of Science及Cochrane Library数据库2013年1月至2024年10月相关文献,个别文献追溯至20年前。检索词为“创伤性脑损伤,骨痂,骨折愈合,炎症反应,细胞因子,激素,神经肽,基因,干细胞”“traumatic brain injury,callus,fracture healing,inflammatory response,cytokines,hormones,neuropeptides,genes,stem cells”,最终选取符合纳入标准的文献共计83篇。结果与结论:创伤性脑损伤对骨痂形成及骨折愈合的促进作用机制极其复杂,涉及细胞因子、激素、神经系统和干细胞等多个调节环节。然而,目前关于创伤性脑损伤促进骨痂形成及骨折愈合的具体机制尚未得到全面、清晰的理解,仍需进一步深入研究。现有研究表明,创伤性脑损伤主要通过促进细胞因子(如胰岛素样生长因子1)和激素(如生长激素及瘦素)的释放,调控神经系统,促进干细胞的增殖与分化等机制来加速骨痂形成和骨组织再生。此外,创伤性脑损伤会引发一系列免疫反应,包括炎症因子的释放和免疫细胞的激活,这些反应能够调节骨折修复的过程。具体而言,免疫反应通过增强局部血流、促进细胞迁移和激活成纤维细胞,从而支持骨愈合的不同阶段。同时,创伤性脑损伤诱发的干细胞活化也在骨折修复中发挥了关键作用。活化的干细胞能够分化为骨细胞、软骨细胞和脂肪细胞,促进骨组织再生和修复。因此,创伤性脑损伤诱发的免疫反应与干细胞的活化共同作用,为骨折愈合提供了必要的支持。这些机制能够加速骨愈合过程,显著缩短愈合时间,提升骨折患者的预后。综上所述,创伤性脑损伤通过多重机制促进骨痂形成和骨折愈合,展现其在骨修复中的重要性。未来研究应聚焦创伤性脑损伤影响骨愈合的信号通路及调控因子,深入理解其作用机制,这将为开发靶向治疗、干细胞及神经调控疗法提供理论基础,具有缩短愈合时间、优化康复方案、改善预后的临床价值。因此,探索创伤性脑损伤引发的生物效应将为骨折治疗开辟新途径。

关键词： HSP90   ADAM33   IL-lβ   支气管哮喘   治疗效果  

摘要： 目的:探讨血清热休克蛋白90(HSP90)、解整合素-金属蛋白酶33(ADAM33)、白细胞介素-1β(IL-1β)水平联合检测对支气管哮喘(简称哮喘)患儿治疗效果的评估价值。方法:选取2022年1月至2024年3月周口市中心医院177例哮喘患儿为研究对象,依据病情程度分为重度组(n=44)、中度组(n=61)、轻度组(n=72),另选取同期177例健康体检儿童为对照组。对比4组入院时血清HSP90、ADAM33、IL-lβ水平并分析其相关性,采用Logistic回归分析影响患儿治疗效果的单因素及多因素,并分析各指标水平联合检测对患儿治疗效果的预测价值。结果:4组入院时血清HSP90、ADAM33、IL-lβ水平比较,对照组<轻度组<中度组<重度组(P<0.05);入院时血清HSP90、ADAM33、IL-lβ水平均与患儿病情程度呈正相关(P<0.05);未有效控制患儿入院时动脉血二氧化碳分压(PaCO_(2))、HSP90、ADAM33、IL-lβ均高于有效控制、动脉血氧分压(PaO_(2))均低于有效控制患儿(P<0.05);PaCO_(2)、HSP90、ADAM33、IL-lβ水平为哮喘患儿未有效控制的危险因素,PaO_(2)为哮喘患儿未有效控制的保护因素(P<0.05);入院时血清HSP90、ADAM33、IL-lβ水平联合预测患儿未有效控制的效能为0.927,均高于各指标单独预测(P<0.05)。结论:哮喘患儿血清HSP90、ADAM33、IL-lβ水平与病情程度有关,其联合检测可有效预测患儿治疗效果,为早期临床合理治疗提供参考。