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关键词： Atherosclerotic plaque stability   CHIP   Fibroblast-like cells   IL-1β inhibition   Prg4  

摘要： Targeting interleukin-1 beta (IL-1β) to mitigate inflammation is known to stabilize atherosclerotic plaques, thereby lowering the risk of acute cardiovascular events. The precise mechanisms are not yet known. Fideler et al. examined the effects of IL-1β on exaggerated atherosclerosis following clonal hematopoiesis of indeterminate potential (CHIP). Unexpectedly, they showed an effect of IL-1β blockage on fibroblast-like cells and their role in the progression of atherosclerosis in the presence of CHIP. Here, we discuss these findings and place them in context of current insights on plaque fibroblast identity and function. While single cell sequencing studies had observed the presence of plaque fibroblasts in atherosclerotic plaques, their function has yet to be unraveled. By focusing on both in vitro and ex vivo models, the research explored how IL-1β stimulation drives functional and molecular changes in fibroblast-like cells, such as increased cytokine production and enhanced matrix degradation, which replicate the inflammatory microenvironment commonly seen in atherosclerotic lesions. Furthermore, the study suggests that inhibiting IL-1β might encourage the accumulation of fibroblast-like cells within the fibrous cap, a process that could improve plaque stability by reducing inflammatory activity and strengthening the structural integrity of the plaque. Depletion of proteoglycan 4 (Prg4) -positive cells, that represent fibroblasts amongst other cell types, reduced cap thickness in atherosclerosis with clonal hematopoiesis of indeterminate potential. The findings suggest that IL-1β not only plays a critical role in promoting inflammation, but also in altering the phenotype of fibroblast-like cells, contributing to the destabilization of atherosclerotic plaques. This study is the first to show a function of plaque fibroblast-like cells in exaggerated atherosclerosis following clonal hematopoiesis of indeterminate potential. Future studies should confirm this effect

关键词： 硫辛酸   加巴喷丁   糖尿病性神经痛   疼痛症状   超敏-C反应蛋白  

摘要： 目的:探究硫辛酸联合加巴喷丁对糖尿病性神经痛(PDN)患者疼痛症状及血清肿瘤坏死因子-α(TNF-α)、超敏-C反应蛋白(hs-CRP)水平的影响。方法:选取2021年10月至2023年9月于南阳市第二人民医院院诊疗的PDN患者62例,根据治疗方案不同分为对照组、观察组。其中予以硫辛酸的31例为对照组,予以加巴喷丁+硫辛酸的31例为观察组。比较两组临床疗效、不良反应发生率、治疗前后疼痛症状、神经传导速度[腓总神经、正中神经的感觉神经传导速度(SCV)和运动神经传导速度(MCV)]、相关血清因子[TNF-α、缺氧诱导因子(HIF)-1α、hs-CRP、内皮生长因子(VEGF)]水平。结果:两组临床总有效率比较差异显著(P<0.05);观察组治疗后临床症状积分低于对照组(P<0.05);观察组治疗后相关血清因子水平低于对照组(P<0.05);观察组治疗后神经传导速度高于对照组(P<0.05);两组不良反应发生率比较无显著差异(P>0.05)。结论:硫辛酸联合加巴喷丁治疗PDN疗效显著,不仅可改善临床症状,调节神经传导速度,还可抑制体内炎症反应,且安全可靠。

关键词： Alarmins   IL-33   Interleukin 33   Neuroinflammation   Schizophrenia   Soluble interleukin 33 receptor   sST2  

摘要： Schizophrenia is a multi-aetiologic disease. Inflammation have recently been involved in its pathophysiology. Recent research suggests that inflammation may be a key factor in its pathophysiology. Alarmins, interleukin-33 (IL-33), its soluble receptor sST2 and the ratio IL-33/sST2, have been investigated as neuroinflammation biomarkers. However, data on alarmins in schizophrenia remain scarce and conflicting, with findings varying across studies. The aim of this systematic review consists of analysing the relationships between IL-33, its sST2 and the ratio IL-33/sST2 in schizophrenia. The authors follow the PRISMA recommendations. The keywords IL-33 OR interleukin-33 OR sST2 OR soluble ST2 OR IL-33/sST2 were intersected with the Boolean operator AND with the key words schizophrenia OR psychosis OR psychotic disorder. The search was carried out in PubMed/MEDLINE, EMBASE, PsycInfo, Scopus and Web of Science. Despite the initial search yielding 115 publications, only five studies met inclusion criteria, comprising 107 healthy controls (HC) and 267 patients, highlighting the limited data available. IL-33 and its sST2 were significantly increased in patients with an acute relapse compared to HC, while patients in clinical remission had levels comparable to those of HC. No consistent relationship was found between antipsychotic treatment and IL-33 or sST2 levels, raising questions about the influence of medication on these markers. The quality of evidence was low to moderate (10 ± 1, with an evidence level of 3 ± 0, according to the Oxford Centre for Evidence-Based Medicine criteria). This systematic review highlights the possibility that IL-33 and sST2 play a role in the pathophysiology of schizophrenia, particularly in relation to neuroinflammation and neuronal dysfunction. However, the controversial and inconsistent findings suggest the need for larger, well-controlled studies. Additionally, the lack of mechanistic insight into how these alarmins contribute to schizoph

关键词： 射频消融   硬化剂   剥脱术   下肢静脉曲张   治疗效果   缓激肽  

摘要： 目的:射频消融(RFA)联合泡沫硬化剂注射(FS)与传统剥脱术对下肢静脉曲张患者围术期指标及血清相关细胞因子水平的影响。方法:选取2021年1月至2023年12月郑州四六〇医院收治的87例下肢静脉曲张患者临床资料,做回顾性研究。将患者按治疗方案分为两组,其中予以RFA联合FS治疗的44例为研究组,予以传统剥脱术治疗的43例为对照组。对比两组围术期指标、治疗效果、疾病相关评分[静脉临床严重程度评分(VCSS)、阿伯丁静脉曲张问卷(AVVQ)、慢性静脉功能不全生活质量问卷-14(CIVIQ-14)]、血清相关细胞因子水平[缓激肽、P物质、肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)]、并发症。结果:对比对照组,研究组手术时间、术中出血量、术后1 d疼痛评分、术后早期下床时间、住院时间均较少(P<0.05);研究组治疗效果优于对照组(P<0.05);术后1个月研究组VCSS、CIVIQ-14、AVVQ评分低于对照组(P<0.05);术后1个月研究组缓激肽、P物质、TNF-α、IL-6低于对照组(P<0.05);研究组并发症发生率低于对照组(P<0.05)。结论:RFA联合FS治疗下肢静脉曲张效果显著,其创伤小、疼痛轻、恢复快,可降低术后并发症,提高患者生活质量。

关键词： Cervical stromal cells   IL-1β   Labor onset   Myometrium cells   Prostaglandin  

摘要： Inflammatory cytokines such as IL-1β and prostaglandins (PGs) are pivotal in the initiation of labor. Nevertheless, the synergistic interaction between PGs and IL-1β remains to be fully elucidated. Labor is defined as regular and gradually increasing uterine contractions accompanied by progressive dilation of the cervix, and descent of the fetal. This study employed Luminex to monitor alterations in inflammatory cytokine levels within myometrial tissue (n = 10) during labor compared to non-labor (n = 10) conditions. And the synergistic relationship between PGs and IL-1β by investigating the primary myometrium cells and cervical stromal cells culture. The results showed that the inflammatory cytokines of IL-1β, IL-6, IL-8 and TNF-α in the myometrium tissue were increased in labor group. In myometrium cells, PGF2α and IL-1β synergistically up-regulated COX-2 mRNA, upregulated the transcription of PRA and PRB, PGF2α alleviated that IL-1β up-regulated IL-8 mRNA. In cervical stromal cells, IL-1β up-regulated the COX-2 and PRB protein expression. PGE2 abated that IL-1β up-regulated IL-8 mRNA. PGE increased the expression of PRs, which is more pronounced with the prolonged duration. Ratio of PRA/PRB show an increased trend with IL-1β and PGE2 co-regulated. This study further clarified the synergistic regulatory mechanism of IL-1β and PGs, offering a theoretical foundation for the development of strategies aimed at labor induction and the prevention and treatment of preterm birth. © 2025

关键词： AZD3839   BACE1   gp130   Interleukin-6   Long-term potentiation   Neuronal activity   Verubecestat  

摘要： The pleiotropic cytokine IL-6 regulates numerous processes in the body, including neuronal functions. IL-6 either binds to membrane-bound receptor (mIL-6R) and triggers signaling via heteromerization with the signal transducer gp130 (classical signaling), or binds to its soluble form (sIL-6R) to act on cells that do not express mIL-6R (trans-signaling). The ß-secretase BACE1 can cleave gp130 as well as IL-6R and we hypothesized that BACE1 may alter neuron activity and synaptic transmission via modulation of IL-6 signaling. We used multielectrode array (MEA) recordings to monitor electrical activity of neuronal networks in acute cerebellar slices as well as long-term potentiation (LTP) induced by high-frequency stimulation in the hippocampus and to assess how exposure to IL-6 affects these processes. A pharmacological approach was applied to elucidate the contribution of trans-signaling involving BACE1. Spontaneous neuronal activity in cerebellar slices significantly decreased upon perfusion with IL-6 but not LIF and recovered during wash out. BACE1 inhibitors verubecestat or AZD3839 abolished the inhibitory effects of IL-6. Furthermore, IL-6 and LIF reversibly inhibited LTP in hippocampal slices, and in contrast to cerebellar neurons, BACE1 inhibitors verubecestat or AZD3839 did not abolish the inhibitory effect of IL-6 on LTP. Interestingly, a dramatic rebound effect on excitatory postsynaptic potentials was observed with BACE1 inhibitor AZD3839 but not verubecestat during wash out. Our results support relevant and differential roles of IL-6, LIF and BACE1 in pathways modulating neuronal discharge activity in the cerebellum and the synaptic plasticity in the hippocampus, and a possible involvement of this interaction in deficits of memory and learning. © 2025 Elsevier Ltd

关键词： Ankylosing spondylitis   Anti-IL-17A   Multiple sclerosis   Psoriasis   Psoriatic arthritis  

摘要： Anti-IL-17A antibodies are used in rheumatological conditions. While not approved for multiple sclerosis (MS), anti-IL-17As reduce new gadolinium-enhancing lesions. Optimal treatment for those with MS and comorbid rheumatological conditions remains unclear. We report safety and efficacy outcomes for anti-IL-17A treatment with and without concurrent MS disease modifying therapy (DMT). Patients with MS and anti-IL-17A use were identified using electronic medical records. Primary outcomes were severe infections and markers of immunosuppression. Secondary outcomes were MS relapses and new MRI lesions. Six patients (median age: 50.1) without recent MS disease activity had anti-IL-17A monotherapy exposures (17.4 total patient-years);seven (median age: 48.2) had concurrent MS DMT use (8.8 patient-years), including anti-CD20 treatment in three patients. One patient on anti-IL-17A monotherapy had a serious infection. No patients had new or worsening lymphopenia. Four of six patients on anti-IL-17A monotherapy had new MS disease activity. No relapses or new MRI lesions occurred during concurrent MS DMT use. No significant safety concerns were identified with anti-IL-17A and MS DMT combination therapy, although exposure duration was limited. More MS disease activity was seen with anti-IL-17A monotherapy. Dual therapy with an MS DMT may be reasonable for MS patients who require anti-IL-17A treatment. © 2025 Elsevier Ltd

关键词： Renal fibrosis   Sodium butyrate (NaB)   M2 macrophage polarization   IL-4/STAT6 signaling pathway   LKB1  

摘要： Background: Renal fibrosis is a critical pathological characteristic of chronic kidney disease, and current anti- fibrotic therapies has limited efficacy. Sodium butyrate (NaB) has been shown to be highly effective in mitigating bleomycin-induced pulmonary fibrosis;however, its specific impact on renal fibrosis and the underlying mechanisms remain unclear. This study aims to elucidate the role and mechanism of NaB in renal fibrosis by using a mouse model of renal fibrosis induced through Unilateral Ureteral Obstruction (UUO) and folic acid (FA) administration. Results: NaB significantly decreased the distribution of collagen fibers in renal tissues and mitigated fibrosis in a dose-dependent manner. Further analysis indicated that NaB inhibited M2 macrophage polarization in the renal tissues of UUO model mice by blocking the phosphorylation of STAT6, hence reducing renal fibrosis. Additionally, in vitro experiments demonstrated that NaB inhibited fibroblast activation induced by M2 macrophages. Mechanistic studies revealed that NaB attenuates fibroblast activation and M2 macrophage polarization by upregulating LKB1 and inhibiting the activation of the STAT6 signaling pathway. Conclusion: NaB may exert its effects by inhibiting the activation of the IL-4/STAT6 signaling pathway through the upregulation of LKB1, which suppress the polarization of M2 macrophages and consequently reduce renal fibrosis. These findings establish a theoretical foundation for NaB as a novel drug candidate for renal fibrosis and indicate its potential applicability in clinical treatments for this condition.

关键词： Brucella   Goat   InDel   PTPRT   TNF  

摘要： Brucella, an intracellular facultative coccidia, causes brucellosis, which poses a significant threat to livestock farming and public health, and screening for candidate genes associated with resistance to brucellosis is considered an effective strategy for controlling the transmission and infection of this disease. In this context, we detected InDel genetic variants of the tumor necrosis factor (TNF) and protein tyrosine phosphatase receptor T (PTPRT) genes in the Shaanbei White Cashmere (SWBC) goat and analyzed the correlation between their polymorphisms and the risk of brucellosis infection in goats. The results indicated that the TNF rs669191919 and PTPRT rs639317914 loci were polymorphic in the examined goat populations. Both loci exhibited a 13 bp InDel deletion and resulted in three genotypes: insertion/insertion (II), insertion/deletion (ID), and deletion/deletion (DD), with II genotypes and I alleles occurring at higher frequencies. The polymorphism information content (PIC) values suggested that both InDel variant loci were moderately polymorphic (0.25 < PIC <0.50). Furthermore, association analysis revealed that none of the four established genetic models codominant, dominant, recessive, and allele showed an association between the polymorphisms at the rs669191919 and rs639317914 loci and the risk of brucellosis in goats (P > 0.05). Bioinformatics analyses indicated that the rs669191919 and rs639317914 loci specifically bind to the transcription factors upstream transcription factor 1 (USF1) and nescient helix-loop-helix 1 (NHLH1), respectively. In summary, our findings suggest that polymorphisms at the TNF rs669191919 and PTPRT rs639317914 loci do not influence resistance to brucellosis in goats. However, investigations into the specific binding of these polymorphic loci to transcription factors may represent a novel avenue for exploring the mechanisms underlying resistance to brucellosis in livestock. © 2025

关键词： 结核性胸腔积液   恶性胸腔积液   白细胞介素-27   腺苷脱氨酶   诊断  

摘要： 目的:探讨白细胞介素-27(IL-27)、腺苷脱氨酶(ADA)在结核性胸腔积液(TPE)中的诊断价值。方法:选取义乌市中心医院2021年10月至2024年2月收治的150例胸腔积液患者为研究对象,其中82例患者确诊为TPE,纳入TPE组,68例为恶性胸腔积液,纳入非TPE组,比较两组胸腔积液IL-27、ADA水平,绘制受试者工作特征(ROC)曲线,分析IL-27、ADA单独及联合诊断TPE的价值,并分析IL-27与ADA水平的相关性。结果:TPE组胸腔积液IL-27、ADA水平均高于非TPE组(P<0.05);ROC曲线显示,胸腔积液IL-27、ADA水平诊断TPE的最佳截断值分别为337.46 ng/L、36.14 U/L,联合检测诊断TPE的ROC曲线下面积(AUC)为0.976,敏感度、特异度分别为97.60%、85.30%;Pearson相关性分析显示,胸腔积液IL-27与ADA水平呈正相关性(r=0.366,P<0.05)。结论:胸腔积液IL-27、ADA水平可作为TPE与恶性胸腔积液的鉴别诊断指标,联合检测具有较高的诊断效能。