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关键词： BoAHV   IFN   SH-SY5Y   TLR3   interference RNA   pro-inflammatory cytokines   replication  

摘要： Varicellovirus bovinealpha (BoAHV) 1 and 5 are alphaherpesviruses that differ in their neuropathogenic potential. While BoAHV-5 causes necrotizing meningoencephalitis in calves, neurological cases associated with BoAHV-1 are less frequent. In this study we used differentiated the human neuroblastoma cell line (SH-SY5Y) to evaluate the mRNA expression of Toll-like receptor 3 (TLR3), its adaptor molecule TRIF and the production of interferons and pro-inflammatory cytokines during infection with both alphaherpesviruses. TLR3 was activated with polyinosinic acid: polycytidylic acid (Poly I:C) and it was genetically silenced using TLR3-targeted siRNA. BoAHV infection induced an initial upregulation of TLR3, followed by a notable decrease, particularly in BoAHV-5-infected cells. TLR3 knockdown was effective for 72 hours in uninfected cells although it was reversed shortly after BoAHV infection. In the presence of activated TLR3, virus titers remained high, indicating limited antiviral activity of TLR3 signaling. TRIF was downregulated early after infection, implying viral interference with the innate immune response. In contrast, Poly I:C upregulated TLR3 and TRIF. IFN-β was upregulated following infection and IFN-α/β, TNF-α and IL-6 were induced even in TLR3-silenced cells, implicating the involvement of alternative signaling pathways. These findings demonstrate how bovine alphaherpesviruses modulate the innate immune mechanisms, highlighting differential viral strategies to evade the immune response which may contribute to neuropathogenesis.

关键词： ACE   AT1   CRP   FMD   IL   LDL   PBMC   PWV   TNF-α   Tregs   angiotensin 1   angiotensin-converting enzyme   antihypertensive agents   blood pressure   c-reactive protein   cardiovascular diseases   flow-mediated dilatation   hypertension   inflammation   interleukin   low-density lipoprotein   peripheral blood mononuclear cell   pulse wave velocity   regulatory T-cells   tumor necrosis factor alpha  

摘要： BACKGROUND:The short-chain fatty acid propionate has been shown to attenuate atherosclerosis, for example by modulating intestinal cholesterol metabolism. Beyond cholesterol metabolism, data from rodent models suggest a potential additional effect on blood pressure reduction. MATERIAL AND METHODS:We conducted a prospective uncontrolled, exploratory, and observational study on 58 individuals receiving propionate supplementation (500 mg twice daily) without preexisting atherosclerotic cardiovascular disease, assessing peripheral and central blood pressure, arterial stiffness, and endothelial function. All parameters were measured at baseline and follow-up after 3 months. RESULTS:Propionate supplementation was associated with a significant reduction in peripheral systolic (-2.4 mmHg, P = 0.0181, Cohen's d = 0.17) and diastolic (-2.5 mmHg, P = 0.0155, Cohen's d = 0.27) blood pressure, as well as central DBP (-2.4mmHg, P = 0.0198, Cohen's d = 0.26). Regulatory T-cell frequency increased significantly (P = 0.0036). No changes were observed in pulse wave velocity, flow-mediated dilatation, and cytokine concentrations. CONCLUSION:Propionate supplementation is associated with a mild reduction in blood pressure in a rather normotensive population of individuals without preexisting atherosclerotic disease.

关键词： axial spondyloarthritis   leptin   adiponectin   TNF-alpha   IL17-A   biomarkers   disease activity   radiographic progression   syndesmophytes   personalized medicine  

摘要： Background/Objectives: Axial spondyloarthritis (axSpA) is a chronic immune-mediated inflammatory disorder affecting the spine and sacroiliac joints, with variable clinical expression. This study assessed serum levels of inflammatory (TNF-alpha, IL-17A) and metabolic (leptin, adiponectin) biomarkers and their associations with disease activity, inflammation, structural damage, and comorbidities. Methods: This prospective cross-sectional study assessed 89 axSpA patients using clinical, laboratory, and radiological evaluations. Disease activity was measured using ASDAS-CRP and BASDAI scores. Radiographic damage was quantified using the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Serum concentrations of TNF-alpha, IL-17A, leptin, and adiponectin were quantified by enzyme-linked immunosorbent assay (ELISA). Clinical and imaging correlations were analyzed. Results: Serum leptin levels correlated significantly with higher disease activity scores, inflammatory markers (CRP, ESR), radiographic progression (syndesmophyte formation, mSASSS), and arterial hypertension. Adiponectin levels were inversely associated with disease activity, structural damage, and arterial hypertension, suggesting anti-inflammatory, bone- and cardio-protective properties. TNF-alpha levels showed an association with inflammatory markers and were higher in patients with peripheral enthesitis. IL-17A levels were weakly correlated with disease activity and structural severity and were significantly lower in patients with a history of anterior uveitis. Conclusions: Leptin and adiponectin may serve as complementary biomarkers in axSpA, reflecting both inflammatory burden and structural damage. While TNF-alpha and IL-17A remain key therapeutic targets, their correlation with structural changes appears limited. Biomarker profiling could support personalized disease monitoring. Longitudinal studies are needed to validate prognostic implications.

关键词： APOE epsilon 4   Interleukin-1 beta   Neuroinflammation   autophagy  

摘要： Introduction: Here we consider the collision of a genetic factor and an essential instigator in Alzheimer's neuropathogenesis: (i) the Alzheimer's gene (APOE epsilon 4), which downregulates lysosomal autophagy and induces synthesis of (ii) the instigator, interleukin-1 beta (IL-1 beta), which drives synthesis of beta APP for A beta plaques and of MAPKp38 for phosphorylation of tau for formation of neurofibrillary tangles (NFTs), the two cardinal features of AD. Methods: RT-PCR, immunoblotting and immunohistochemistry techniques were used to assess the levels of IL-1 beta and its signaling cascade in AD epsilon 4,4, epsilon 3,3, and age-matched controls (AMC3,3) in hippocampal regions of the brain. Results: IL-1 beta and its downstream signaling proteins TLR-2, MyD88, NF kappa B, COX-1, and COX-2 were greater in tissues from AD epsilon 4,4 than AD epsilon 3,3 or AMC3,3. Cathepsin B, D, and L levels, which play a pivotal role and are necessary for lysosomal autophagy, were lower in AD epsilon 4,4 than in AD epsilon 3,3 or AMC epsilon 3,3. IL-1 beta and its downstream signaling cascade TLR-2, MyD88, NF kappa B, COX-1, and COX-2 expression levels were high in SH-SY5Y and T98G cells transfected with APO epsilon E4. Conclusions: APOE epsilon 4 causes Alzheimer's by downregulating autophagy, thus inducing IL-1 beta for A beta plaque and neurofibrillary tangle formation.

关键词： 血清免疫球蛋白G型   类风湿因子   类风湿关节炎   检验   诊断  

摘要： 探讨血清免疫球蛋白G型类风湿因子(IgG-RF)在类风湿关节炎(RA)患者中的诊断价值,为临床鉴别不同类型类风湿疾病提供参考依据。方法 采用便利抽样法选取2024年1月至2024年12月就诊的30例RA患者(观察组)及30例其他风湿性疾病患者(对照组),检测两组的IgG-RF、ESR、FDP与DD水平并进行对症干预。结果 观察组与对照组在干预前后的FDP、DD水平存在显著差异(P<0.05);ESR及RF异常率差异不明显(P>0.05);干预后,观察组VAS评分显著高于对照组(5.32±0.85分vs.1.76±0.59分);晨僵时间长于对照组(79.28±11.94分钟VS.31.54±3.39分钟);关节压痛数多于对照组(12.25±1.17个vs.3.34±0.62个)。结论 IgG-RF检测显著提高了RA的早期诊断率,尤其在血清阴性患者中具有重要应用前景。未来需开展多中心大样本研究,进一步验证其在不同人群中的诊断阈值及与关节影像学进展的相关性。

关键词： atherosclerosis   macrophages   molecular dynamics   tigogenin   Tribulus terrestris L  

摘要： Atherosclerosis (AS) is a major contributor to cardiovascular disease. In traditional Chinese medicine, Tribulus terrestris L., or Baijili (BJL), has shown therapeutic effects on inflammation and cardiovascular issues. Our prior research indicated that BJL inhibited LPS-induced inflammatory factor expression in macrophages, but this does not confirm its anti-atherosclerotic effects. To model AS, ApoE-/- mice were fed a high-fat diet (HFD) and treated with Lipitor or BJL (50, 100, or 200 mg/kg/day). Assessments included aortic plaque area, serum lipid profiles, and serum cytokine levels. Bioinformatics, WGCNA, and machine learning were used to identify macrophage-associated AS key functional genes (ASKFGs). Molecular docking and dynamics simulations assessed interactions of BJL's components, Hecogenin (Heco) and Tigogenin (Tigo), with proteins like MMP-9 and TNF-alpha. In vitro, LPS-stimulated RAW264.7 macrophages were used to evaluate the effects of BJL, Heco, and Tigo on inflammatory gene and protein expression via RT-qPCR and Western blot. Results showed that BJL administration, particularly at 50 mg/kg/day, significantly reduced aortic plaque area, decreased serum TC and LDL-C levels, and lowered inflammatory cytokines in HFD-fed ApoE-/- mice. Computational analyses identified 202 macrophage-related AS disease genes, with TNF, MMP-9, CXCR2, and CD36 validated as key targets. Molecular modeling showed both Heco and Tigo have favorable ADMET properties and stable interactions with MMP-9 and TNF-alpha. Tigo demonstrated potent binding activity with a peak energy of approximately -26 kcal/mol for TNF-alpha and -20 kcal/mol for MMP-9. In vitro, Tigo markedly inhibited LPS-induced expression of TNF-alpha, MMP-9, and CXCR2 in macrophages. Mechanistically, Tigo suppressed inflammation by inhibiting the TNF-alpha/NF-kappa B signaling pathway, as evidenced by the reduced phosphorylation of p65 and I kappa B alpha. In conclusion, BJL alleviates atherosclerosis in ApoE-/- mi

关键词： T淋巴细胞亚群   IL-6   胃癌   预后   相关性  

摘要： 探讨胃癌患者外周血T淋巴细胞亚群(CD3+、CD4+、CD8+)及白细胞介素-6(IL-6)表达水平与预后的相关性。方法 选取2023年6月至2024年10月我院收治的70例胃癌患者为研究组,同期选取70例健康体检者为对照组。体检当天对所有对象分别采用流式细胞术检测T淋巴细胞亚群,ELISA法检测IL-6水平,并开展组间对比。对于研究组随访半年,根据生存状态分为不良组(20例)与良好组(50例),对比两组各指标值,并通过Logistic回归分析预后的相关性。结果 研究组CD3+(54.32±7.89)%、CD4+(25.17±9.34)%显著低于对照组(68.15±6.23)%、(37.21±5.12)%(P<0.05),CD8+(34.56±6.11)%、IL-6(7.12±3.45)ng/L显著高于对照组(24.32±3.58)%、(3.54±1.12)ng/L(P<0.05)。不良组CD3+(44.21±10.23)%、CD4+(19.87±10.56)%低于良好组(56.78±7.01)%、(27.34±9.65)%(P<0.05),CD8+(41.23±6.23)%、IL-6(9.89±3.21)ng/L显著高于预后良好组(32.45±5.34)%、(6.32±3.12)ng/L(P<0.05)。Logistic回归显示,肿瘤分期(OR=0.166,95%CI:0.053-0.524)、CD3+(OR=0.662,95%CI:0.500-0.875)、CD8+(OR=2.044,95%CI:1.269-3.309)、IL-6(OR=1.472,95%CI:1.197-1.803)是独立预后因素(P<0.05)。结论 胃癌患者存在T淋巴细胞亚群失衡及IL-6异常高表达,CD3+、CD8+、IL-6可作为评估预后的有效生物标志物。

关键词： 脓毒症   连续性肾脏替代治疗(CRRT)   护理干预   炎性因子   肾功能恢复  

摘要： 探讨连续性肾脏替代治疗(CRRT)联合护理配合对脓毒症患者的临床疗效以及血清炎性因子清除率和肾功能改善的影响。方法 收集我院2022年1月至2022年12月收治的53例脓毒症患者,并随机分为观察组(n=27)和对照组(n=26)。对照组采用常规护理配合CRRT治疗,观察组则实施优化护理干预,包括心理支持、感染监控、营养支持及早期活动措施等,以配合CRRT治疗。分别对两组患者治疗前后的血清炎性因子水平(PCT、TNFα、IL6、VCAM1),ICU住院时间及尿量恢复时间进行比较,同时评估其疗效和肾功能水平。结果 两组患者治疗前的基线资料(性别、年龄)差异无统计学意义(P>0.05)。治疗后观察组PCT、TNFα、IL6及VCAM1水平较治疗前显著降低,且低于对照组(P<0.05)。观察组的总有效率显著高于对照组(92.59% vs 69.23%,P=0.031)。观察组ICU住院时间及尿量恢复时间明显短于对照组(P=0.001)。治疗后观察组BUN及Scr水平降低幅度显著优于对照组,两组间差异具有统计学意义(P=0.001)。结论 通过优化护理干预配合CRRT治疗,可显著提升脓毒症患者的疗效,加速肾功能恢复,改善患者血清炎性因子水平,并缩短住院时间,有助于提升患者预后及生存质量,值得临床推广应用。

关键词： B-cell lymphoma   HLA class II   lymphoma-associated molecules   dendritic cells   immune escape   CD4+T cells   immunotherapy  

摘要： B-cell lymphomas, including Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL), evade CD4+ T-cell immunity through novel HLA class II-associated immunosuppressive mechanisms. Despite expressing surface HLA-DR, these tumors fail to activate antigen-specific CD4+ T cells, independent of co-stimulation or PD-L1 checkpoint inhibition. We identified lymphoma-secreted factors that broadly disrupt HLA class II-mediated antigen presentation in both malignant B cells and dendritic cells (DCs), silencing T-cell responses. This inhibition is allele-independent (affecting DR1, DR4, DR7) but spares HLA class I-mediated CD8+ T-cell recognition, indicating a targeted immune evasion strategy. Biochemical and mass spectrometry (MALDI-MS) analyses revealed unique low-molecular-weight peptides (693-790 Da) in BL cells, absent in normal B cells, which may mediate this suppression. Functional fractionation confirmed bioactive inhibitory fractions in lymphoma lysates, further implicating tumor-intrinsic molecules in immune escape. These findings highlight a previously unrecognized axis of B-cell lymphoma immune evasion, where secreted factors disable HLA class II function across antigen-presenting cells. Therapeutically, neutralizing these immunosuppressive molecules could restore CD4+ T-cell surveillance and enhance immunotherapies in B-cell malignancies. This work underscores the importance of HLA class II dysfunction in lymphoma progression and identifies candidate targets for reversing immune suppression.

关键词： 多发性骨髓瘤   补体   免疫球蛋白   淋巴细胞亚群  

摘要： 探索不同分期的多发性骨髓瘤患者(Multiple Myeloma,MM)补体、免疫球蛋白和淋巴细胞亚群的临床意义。方法 选取2023年3月至2025年3月某院收治的90例MM患者,根据ISS分期将患者分为Ⅰ期、Ⅱ期、Ⅲ期。检测四组外周血补体(C3/C4)、免疫球蛋白(IgG/IgA/IgM)、淋巴细胞亚群。比较各期补体、免疫球蛋白及淋巴细胞亚群水平差异。结果 通过分析不同分期MM患者的患者的补体(C3/C4)、免疫球蛋白(IgG/IgA/IgM)、淋巴细胞亚群水平。发现Ⅲ期的C4、IgG/IgA、CD3+T/CD56+NK水平均高于Ⅰ期与Ⅱ期,C3低于Ⅰ期但高于Ⅱ期,IgM低于Ⅰ期和Ⅱ期,CD19低于Ⅱ期但高于Ⅰ期,差异均有统计学意义(P<0.05);结论 MM患者补体C4、免疫球蛋白IgG/IgA增高程度与疾病严重性密切相关,而IgM随疾病严重程度降低,淋巴细胞亚群无明显变化,建议在诊疗过程中监测C4和免疫球蛋白的变化,为病情检测和治疗方案优化提供客观依据。