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关键词： 葛根素   类风湿关节炎   疗效   AKT   FOXO1  

摘要： 目的 基于蛋白激酶B(AKT)/磷酸化叉头框蛋白O1(FOXO1)-白介素（IL）-9（AKT-FOXO1-IL-9）信号通路，探究葛根素治疗类风湿关节炎（RA）大鼠的疗效机制。方法 将36只大鼠随机分为空白组，模型组，阳性对照组，葛根素低、中、高剂量组，除空白组外，其余组采用Ⅱ型胶原诱导建立RA大鼠模型。造模成功后，给予不同剂量葛根素和甲氨蝶呤治疗，检测大鼠体质量和足趾厚度，采用生化方法检测大鼠血液流变学指标，采用X光观察大鼠关节形态变化，采用番红固绿染色和阿利新蓝染色观察大鼠关节组织的病理学，ELISA法检测大鼠血清中IL-9及类风湿因子水平及Western blot检测蛋白AKT、FOXO1的变化。结果 与空白组相比，模型组大鼠足趾厚度最厚，X线光片显示关节狭窄比较明显，边缘性骨侵袭较重；番红固绿染色显示关节边缘出现毛刺样改变，伴有炎症细胞的渗出，软骨细胞增殖分泌加剧；炎症因子IL-9及类风湿因子水平表达最高，AKT、FOXO1蛋白表达量最高（P＜0.05）。与模型组相比，不同剂量葛根素治疗组大鼠足趾厚度降低；X光片显示，葛根素治疗组大鼠脚掌关节狭窄及边缘性骨侵袭有改善；番红固绿染色结果显示，不同剂量的葛根素治疗后，炎症细胞渗出减少，炎症因子IL-9及类风湿因子、AKT、FOXO1蛋白表达水平降低且差异均有统计学意义(P＜0.05)，其中高剂量葛根素组最明显。与高剂量的葛根素组相比，阳性对照组以上结果均降低且差异均有统计学意义(P＜0.05)。结论 葛根素通过抑制AKT-FOXO1-IL-9通路对RA大鼠具有良好的疗效，其中葛根素高剂量组（60 mg/kg）的疗效最好且存在剂量反应关系。

关键词： Oral commensal bacteria   beta-Defensin   IL-17 signaling pathway   OPC   Safety evaluation  

摘要： Oropharyngeal candidiasis (OPC) commonly occurs in immunocompromised individuals, and enhancing endogenous antimicrobial defenses with probiotics has emerged as an effective prevention strategy. Given the critical role of human beta-defensin-2 (HBD-2) in combating Candida albicans infection in the oral cavity, this study aimed to identify oral commensal bacteria promoting HBD-2 production in the host. Thirty-five Streptococcus salivarius strains were screened using the HOK-16B cell line, and two were identified as significantly promoting HBD-2 secretion. These strains were further validated in a murine OPC model. The results indicated that oral intervention with S. salivarius CCFM1416 activated the IL-17/IKB zeta signaling pathway in the host (IKB zeta from 67.73 to 122.27 pg/mg), upregulating the expression of beta-defensin (from 13.64 to 25.21 pg/mg). Consequently, C. albicans colonization and adhesion in the oral cavity were markedly reduced. Finally, a 14-day oral toxicity study demonstrated that oral administration of S. salivarius CCFM1416 is safe in vivo. In summary, the research results indicated that S. salivarius CCFM1416 can effectively prevent the occurrence of OPC and is an excellent probiotic candidate for the prevention of oral mucosal infections.

摘要： MHC-E is a highly conserved, non-polymorphic MHC protein that engages inhibitory and activating receptors on natural killer (NK) cells and T cells and can also present antigens to T cell receptors. NK cell responses driven by activating receptor interactions with MHC-E are implicated in controlling chronic viral infections and cancer. Immunotherapeutic targeting of interactions between MHC-E and inhibitory receptors to increase the activation of NK cells and T cells shows promise in improving antitumour immune responses. Furthermore, MHC-E-restricted CD8+ T cells elicited by cytomegalovirus-based vaccines might, for certain infections and cancers, be more effective than CD8+ T cells restricted by classical MHC class I or class II molecules. The ability of MHC-E to regulate or mediate both innate and adaptive immune responses independently of the MHC haplotype of an individual raises the possibility of new, universally effective vaccines and immunotherapies for infectious disease and cancer. Although the therapeutic exploitation of MHC-E is still in its infancy, recent advances in the understanding of MHC-E biology show enormous potential, as described in this Review.

关键词： Psoriasis   Spleen   Neutrophil   Granulopoiesis   IL-6  

摘要： BackgroundPsoriasis is an immune-mediated chronic inflammatory condition characterized by significant neutrophil infiltration in the skin. Given that the spleen is the largest peripheral immune organ in the body, it is important to investigate whether it has any impact on skin inflammation in *** investigate this mechanism, a psoriatic mouse model was established by IMQ application. Flow cytometry and immunohistochemistry analyses were performed to determine the percentage of various immune cells in the spleen. The role of neutrophils was specifically assessed using the anti-Gr-1 antibody. Splenic granulopoiesis was evaluated using EdU labeling. To understand the spleen's role in skin inflammation, splenectomy was performed on the experimental mice. IL-6 levels were measured by ELISA, and P-STAT3 in neutrophils was detected via immunofluorescence. Further examination of IL-6's effects on neutrophil formation involved treating mice with IL-6 antibody. The severity of psoriasis was evaluated through histological staining and PASI *** study revealed that the spleens of psoriatic mice were enlarged compared to those of vehicle mice. Among immune cell populations, neutrophils showed the most significant changes, with marked increases in both spleen and skin of psoriatic mice and patients, contributing to disease progression. Post-splenectomy, neutrophil infiltration in the skin was reduced by approximately 60% in psoriatic mice. This indicates that the neutrophils in the skin were primarily derived from the spleen. Additionally, the spleen showed a notable capacity for granulopoiesis with elevated neutrophils. Moreover, we found elevated IL-6 levels in the skin, blood, and spleen in the model, which was decreased after splenectomy. Treatment with an IL-6 antibody reduced neutrophil formation in both the spleen and skin, which alleviated skin inflammation in psoriatic mice. Additionally, P-STAT3 signaling was decreased following IL-6 antibod

关键词： Epilepsy   Saikosaponin a   Ferroptosis   Akt/ERK   IL-1  

摘要： Saikosaponin A (SSa), a triterpenoid saponin isolated from Astragalus membranaceus, possesses multiple pharmacological properties, including anticonvulsant, antiepileptic, and anti-inflammatory activities. This study aimed to elucidate the molecular mechanisms by which SSa exerts therapeutic effects in temporal lobe epilepsy (TLE), with a particular focus on the involvement of ferroptosis pathways. In a kainic acid-induced TLE mouse model, electroencephalography (EEG) was used to monitor seizure frequency. Behavioral tests were employed to evaluate cognitive, learning, and memory functions. Additionally, molecular biology techniques were used to investigate the neuroprotective mechanisms of SSa. EEG recordings showed that SSa treatment significantly reduced seizure frequency and severity. Behavioral assessments indicated improvements in cognition, learning, and memory. Histological analysis revealed decreased neuronal death in the hippocampus. Transmission electron microscopy and Golgi-Cox staining demonstrated a marked increase in hippocampal neuron density following SSa treatment. At the cellular level, SSa significantly downregulated the expression of IL-17, phosphorylated Akt (p-Akt), and phosphorylated ERK (p-ERK) in Erastin-induced ferroptotic hippocampal neurons. Notably, the inhibitory effect of SSa on ferroptosis was reversed by IL-17 agonist treatment, suggesting that IL-17 plays a pivotal role in this pathway. In conclusion, SSa alleviates seizures and improves cognitive function in TLE by inhibiting IL-17/Akt/ERK-mediated ferroptosis in hippocampal neurons.

关键词： Biomarker   Diagnostic accuracy   Interleukin-6   IL-6   Late-onset neonatal sepsis  

摘要： Late-onset neonatal sepsis (LONS) remains a leading cause of morbidity and mortality in neonates, particularly among preterm and low birth weight infants. Interleukin-6 (IL-6) has emerged as a promising biomarker for early detection of LONS, yet the diagnostic performance of IL-6 remains inconsistent across studies. This meta-analysis aimed to evaluate the overall diagnostic accuracy of IL-6 in detecting LONS and to assess the certainty of evidence using the GRADE approach. A comprehensive search of five databases was conducted up to July 15, 2025. Twenty-two studies were eligible for inclusion, of which 20 (n = 3527 neonates) were included in the meta-analysis. A bivariate random-effects model was used to estimate pooled sensitivity and specificity, and the area under the SROC curve was used to assess overall diagnostic accuracy. Pooled sensitivity and specificity were 85.2% (95% CI: 80.0-89.3%) and 84.1% (95% CI: 77.5-89.0%), respectively. The positive and negative likelihood ratios were 5.43 and 0.18, with a diagnostic odds ratio of 31.4. The AUC was 0.91, indicating excellent diagnostic accuracy. Subgroup and sensitivity analyses confirmed the robustness of the findings, and no significant threshold effect was detected. However, suspected publication bias was noted. The GRADE assessment rated the certainty of evidence as moderate. Conclusion: IL-6 demonstrates high diagnostic accuracy for LONS and may serve as a valuable tool for early identification, though standardization of cutoff thresholds and further validation studies are warranted. What is Known:center dot IL-6 is an early-rising biomarker for late-onset neonatal sepsis (LONS), but its diagnostic accuracy varies across *** is New:center dot This meta-analysis used a bivariate model to estimate IL-6 performance, yielding high pooled sensitivity (85.2%) and specificity (84.1%).

关键词： EBV   tonsil   children   CD4+T cell   CD8+T cells  

摘要： Introduction Epstein-Barr virus (EBV) infects B lymphocytes and establishes lifelong persistence in the B cells. While systemic T-cell responses have been well characterized, the local immune response at the site of viral entry in children from undeveloped countries remains poorly *** Tonsillar CD4 and CD8 T cells in 32 pediatric patients undergoing tonsillectomy were classified as primary infected (PI), EBV carriers (EC), and non-infected children by serology. T-cell subsets were assessed by flow cytometry, whereas LMP1 and EBNA2 viral proteins were evaluated by *** A higher percentage of activated HLA-DR+ CD8 T cells in PI patients was demonstrated. Notably, PD-1 expression was increased in both PI and EC, in particular in activated HLA-DR+ CD8 T cells. Positive correlations of EBNA2 with follicular helper T cells and Th1 cells, as well as a negative correlation between EBNA2 and activated CD8 T cells, were *** These findings suggest that, during asymptomatic primary infection by EBV, activated CD8 T cells are observed, but they may be cells that may exhibit features of exhaustion, which probably explains the absence of symptoms. PD-1 expression in CD8 T cells remains in EC. Additionally, Tfh, Th1, and CD8 T cells may influence the expression of EBNA2 and LMP1 latent viral antigens in tonsils.

关键词： Kidney organoid   Kidney transplantation   Allograft rejection   HiPSC  

摘要： The aim of this study is to establish an in vitro co-culture system to model allograft rejection using kidney organoids system derived from human induced pluripotent stem cells (hiPSCs). We co-cultured kidney organoids derived from wild-type hiPSCs with HLA-mismatched peripheral blood mononuclear cells (PBMCs) from healthy controls (HC) for 24 h. To assess allogeneic rejection modeling, we measured the expression of HLA molecules, (HLA-ABC and HLA-DR), and evaluated cellular damage in the kidney organoids. Additionally, we analyzed the distribution of T cells and their subsets within the co-cultured PBMCs. The immunosuppressive effect of tacrolimus was also evaluated in this co-culture system. Transcriptomic analysis, conducted using RNA sequencing, identified molecules associated with allogeneic rejection. When kidney organoids were co-cultured with alloreactive PBMCs for 24 h, HLA-ABC and HLA-DR expression significantly increased in kidney organoid cells. Additionally, kidney organoids showed reduced cell viability and increased apoptosis compared to syngeneic controls, as assessed by flow cytometry and Annexin V/PI staining. However, treatment with tacrolimus reduced HLA expression in a dose-dependent manner, highlighting the diminished alloimmune responses. Further analysis of PBMC subsets revealed shifts in T helper (TH) and cytotoxic T cell (TC) populations under allogeneic conditions, including increased effector TH and TC cells. Transcriptomic analysis through RNA sequencing identified 256 differentially expressed genes (DEGs), with notable immune-related pathways such as NF-kappa B and TNF signaling involved in allograft rejection. These results provide evidence that a co-culture system with allogeneic kidney organoids and PBMCs can potentially model transplant rejection in vitro.

关键词： Copyrights  

摘要： Ulcerative colitis is a chronic nonspecific intestinal inflammatory disease, which usually occurs in the rectal and colonic mucosa and submucosa. Ligustilide, a major component derived from Angelica sinensis (Oliv.) Diels, exerts anti-inflammation effect. However, its impact and molecular mechanism on colitis remain obscure. In this study, in vivo and in vitro experiments verified that ligustilide protected against colitis by suppressing macrophage-mediated inflammation and repairing intestinal barrier. Of note, we utilized a thermal proteome profiling strategy to preliminarily find early growth response factor 1 (EGR1) as a target of ligustilide. Cellular thermal shift assay, drug affinity responsive target stability, and surface plasmon resonance analysis revealed that ligustilide directly targeted His386 to bind to EGR1. Furthermore, RNA-sequencing, dual luciferase reporter gene assay, and rescue experiments illustrated that ligustilide disturbed the nuclear translocation of EGR1 and broke its combination with a disintegrin and metalloproteinase 17 (ADAM17) promoter, thereby inhibiting ADAM17 transcription and downstream tumor necrosis factor-alpha (TNF-alpha) production, as well as expression of inflammatory proteins cyclooxygenase 2 and inducible nitric oxide synthase. Finally, the in vivo experiment with EGR1 overexpression proved that EGR1 was essential for the protective effects of ligustilide on colitis mice. Taken together, our study demonstrates that ligustilide targets EGR1 to inhibit the EGR1-ADAM17-TNF alpha pathway, thus alleviating macrophage-mediated intestinal inflammation and restoring gut barrier.