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关键词： 哮喘   丹龙定喘汤   炎症   辅助性T细胞17   调节性T细胞  

摘要： 目的：探讨丹龙定喘汤对白蛋白（OVA）所致的支气管哮喘小鼠炎症的作用及改善机制。方法：60只SPF级BALB/c雌性小鼠，随机分为正常对照组、模型对照组、地塞米松0.63 mg/kg组、丹龙定喘汤13、27、53 g/kg组，每组10只。除正常对照组外，其他组小鼠于第1、14d腹腔注射0.2mLOVA溶液致敏，在第28d，将1%OVA生理盐水溶液超声雾化并以最大雾量吸入激发，1次/d，30 min/次，连续5d。第35d开始雾化吸入1%OVA溶液激发哮喘，每周雾化3次，同时各药物组灌胃给予相应药物，1次/d，共6w。末次给药1 h后，小鼠进行气道反应性高低的检测；检测结束后取材，摘眼球取血，全血测定血常规观察炎症细胞变化；检测血清检测白介素10（IL-10）、白介素17（IL-17）的含量；取肺泡灌洗液检测辅助性T细胞17（Th17细胞）、调节性T细胞（Treg细胞）的水平；多聚甲醛固定右肺上叶后包埋切片进行苏木精-伊红染色（HE染色）和马松染色（Masson染色）。结果：与正常对照组相比，模型对照组小鼠经不同浓度的乙酰甲胆碱刺激后Penh值显著升高，全血中白细胞和粒细胞比例显著增加，支气管周围炎症浸润与胶原沉积明显，肺泡灌洗液中Th17细胞占比、血清中IL-17含量显著增加，Treg细胞占比、血清IL-10含量明显降低（P＜0.05或P＜0.01）；与模型对照组相比，丹龙定喘汤penh值、全血中白细胞和粒细胞比例显著降低，支气管周围炎症浸润与胶原沉积情况显著改善，肺泡灌洗液中Th17细胞占比、血清IL-17含量显著降低，Treg细胞占比、血清IL-10的含量明显升高（P＜0.05或P＜0.01）。结论：丹龙定喘汤能够有效改善OVA所致的哮喘模型小鼠的气道炎症反应，其机制可能与调节Th17/Treg间细胞免疫平衡进而影响炎症反应相关。

关键词： interleukin-6   platelets   hyper-responsiveness   thrombo-inflammation   thrombosis  

摘要： Interleukin-6 (IL-6) is a pleiotropic cytokine with critical roles in immune regulation, inflammation, and haematopoiesis. While its functions in host defence and tissue repair are well established, accumulating evidence suggests that IL-6 also can directly and indirectly modulate megakaryocyte and platelet biology. This review examines the mechanistic basis supporting IL-6-mediated platelet hyper-responsiveness, in addition to its effect on megakaryopoiesis and thrombopoiesis in thromboinflammatory disease states. We discuss how IL-6-mediated trans-signalling may sensitizes platelets to activation, and that this may be exclusive to glycoprotein VI (GPVI) stimulation due to Janus kinase (JAK)-signal transducer 2 crosstalk, in addition to other mechanisms that may contribute to priming platelets. We further highlight clinical evidence linking IL-6 to thrombotic complications in cardiovascular disease and infection (e.g., COVID-19 and sepsis). Given the emerging interest in IL-6-targeting therapies as anti-inflammatory and anti-thrombotic agents, a thorough understanding of how IL-6 can drive platelet responsiveness is crucial.

摘要： Chronic granulomatous disease (CGD) is an inborn error of immunity characterized by defective NAD phosphate oxidase function, leading to impaired microbial killing, recurrent infections, and granulomatous inflammation. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for CGD, particularly effective when a fully HLA-matched donor is available. However, the place of HLA-haploidentical HSCT remains less established. This retrospective multicenter study analyzed outcomes of 64 patients with CGD (53 males;46 with X-linked CGD) who underwent a first HSCT with HLAhaploidentical family donors, with either in vitro T-cell receptor (TCR)alpha beta/CD19 depletion or in vivo depletion using posttransplant cyclophosphamide (PTCY). The mean age at transplant was 5.8 years (range, 0-33). Patients exhibited a high disease burden before HSCT, with 45% experiencing infections in the 6 months before HSCT and 67% exhibiting inflammation. Outcomes in the entire cohort showed a 3-year overall survival, event-free survival (EFS), and grade 3 to 4 graft-versus-host disease (GVHD)-free EFS of 75.9%, 70.2%, and 56.1%, respectively, and were not affected by the type of depletion or age. The cumulative incidence (CI) of primary graft failure (PGF) was 20.6%. The CI of grade 2 to 4 acute GVHD was higher in the PTCY group (P = .04), whereas the CI of grade 3 to 4 GVHD was not. These results indicate that HLAhaploidentical HSCT is a feasible transplant option for patients with CGD lacking HLA-matched donors. Further refinement of transplant protocols is necessary to mitigate graft failure and acute GVHD, ultimately improving access and outcomes for this life-saving therapy.

关键词： Major histocompatibility complex   MHC   Genetics   Adaptation   Disease ecology  

摘要： Sea turtles are one taxon of high conservation concern that encounter many pathogens, but their disease ecology is understudied, hindering our ability to predict impacts of disease on population viability. Fibropapillomatosis (FP) is a neoplastic tumor-forming disease that has been documented in all sea turtle species, with an especially high prevalence in green turtles Chelonia mydas. Here, we use Hawaiian green turtles (honu) as a study system to examine the roles of immunogenetic diversity and transcriptional modulation in sea turtle disease responses. Specifically, we quantified gene expression profiles associated with FP and characterized host diversity of major histocompatibility complex class I (MHCI) immune loci. We found 65 genes differentially expressed in blood between clinically healthy (n = 5) and FP-afflicted turtles (n = 5) with enriched biological processes of the innate immune system, aligned with expectations of reptilian immune systems and active disease resistance. Our results also suggest a role for disease tolerance in response to FP, as evidenced by enriched biological processes related to regulation of immune and metabolic homeostasis, increase in cellular detoxification, and increased tissue repair mechanisms. Honu (n = 89) had 23 unique MHCI alleles belonging to 3 distinct functional supertypes, but none were significantly associated with FP;this could be a result of intrinsic demographic properties of the population or reflect a lesser/differing role of the reptilian adaptive immune system. Our study advances the understanding of reptilian disease response and evolutionary mechanisms underlying immunogenetic diversity, both of which are important for promoting the adaptive potential of species vulnerable to extinction.

关键词： Hypoxia-inducible factor-1 alpha   Periodontitis   Saliva   SuPAR   Tumor necrosis factor alpha  

摘要： Background The aim of the study is to evaluate saliva levels of Soluble urokinase plasminogen activator receptor (suPAR), Hypoxia-inducible factor-1 alpha (HIF-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) in stage III grade A, grade B, grade C periodontitis and periodontal health and to understand the roles of these molecules in periodontal inflammation process and also to compare the three biomarkers' discriminative efficacy in periodontal disease. Methods A total of 80 individuals, 20 with stage III grade A periodontitis (group A), 20 with stage III grade B periodontitis (group B), 20 with stage III grade C periodontitis (group C) and 20 with healthy periodontium (group H) were recruited for this study. Full-mouth clinical periodontal measurements were recorded in periodontal charts. Whole saliva samples were collected to determine the levels of suPAR, HIF-1 alpha and TNF-alpha in study groups using enzyme-linked immunosorbent assay (ELISA) method. Results The saliva concentration of suPAR, HIF-1 alpha, and TNF alpha was significantly higher in group A, group B, and group C compared with group H (p < .05). Additionally, salivary suPAR concentration was significantly higher in group C than in groups A and B (p < .05). Positive statistically significant correlations were observed between three biomarkers and all clinical parameters (p < .05). Conclusions Increased levels of saliva suPAR, HIF-1 alpha, and TNF alpha suggest that these molecules may play a role in periodontitis. In addition, the higher salivary suPAR levels in grade C periodontitis compared to other grades suggest that suPAR may be one of the potential molecules that can be used to predict disease progression and periodontal disease classification.

关键词： 纳米乳佐剂   单磷酰脂质A   QS-21   复合佐剂   免疫原性  

摘要： 目的 制备基于纳米乳（nano-emulsion,NE）佐剂的不同复合佐剂，探讨其用于流感疫苗的免疫效果。方法 将NE佐剂分别与单磷酰脂质A(monophosphoryl lipid A,MPLA)、QS-21联用制备复合佐剂后，与流感疫苗配伍，于第0和28天经肌内注射免疫雌性BALB/c小鼠，初免后第28及42天，采用血凝抑制（hemagglutination inhibition,HI）、ELISA试验及流式细胞术评价免疫效果；加强免疫后第14天，用10 LD50H1N1流感病毒毒株A/Victoria/2570/2019(IVR-215)(H1N1)鼻内感染雌性BALB/c小鼠，评价攻毒保护效果。结果 复合佐剂组小鼠均能产生高水平的特异性IgG抗体以及功能性HI抗体；两种复合佐剂的加入均能提高小鼠脾脏CD3+CD4+、CD3+CD8+T细胞水平。复合佐剂组小鼠攻毒后存活率达100%，体质量下降率低于10%。结论 免疫辅以复合佐剂的流感疫苗，较单独佐剂疫苗具有更高的免疫原性，本研究为流感疫苗佐剂的开发以及佐剂复合化研发奠定了基础。

关键词： ischemic stroke   neuronal injury   Formononetin   molecular mechanisms   protective effects  

摘要： Backgrounds: Inflammation plays a pivotal role in the advancement of ischemic stroke, and Formononetin has been recognized for its potential benefits due to its anti-inflammatory effects. Although Formononetin shows promise for reducing cerebral ischemic injury, its precise effectiveness and the underlying molecular mechanisms still need to be thoroughly explored. The research aimed to investigate Formononetin's impact and mechanisms on ischemic brain damage. Methods: In this study, both the ischemia/reperfusion (I/R) mouse model and the oxygen-glucose deprivation/reperfusion (OGD/R) cell model were used. The I/R mouse model was prepared using the middle cerebral artery occlusion (MCAO) method, while the OGD/R SH-SY5Y cell model was established using the oxygen-glucose OGD/R method. Hematoxylin and Eosin (H&E) staining, Tunnel fluorescence staining, and Nissl staining were employed to observe the effects of Formononetin on neuronal damage, apoptosis, and survival in I/R mouse brain tissue. Additionally, the effects of Formononetin on the levels of pro-inflammatory factors in I/R mice and OGD/R cells were detected using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and Enzyme-Linked Immunosorbent Assay (ELISA) methods. The c-Fos/Interleukin-10 (IL-10)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in I/R mice and OGD/R cells was examined using RT-qPCR and Western Blot (WB). Furthermore, rescue validation was performed using targeted interventions of IL-10 and c-Fos, confirming that the c-Fos/IL-10/STAT3 signaling pathway is a key target of Formononetin. Results: Our findings reveal that Formononetin notably decreased infarct size and neuronal damage in vivo (p < 0.001). Additionally, Formononetin decreased inflammation and lowered levels of pro-inflammatory cytokines (p < 0.05). In cell models, Formononetin effectively suppressed neuronal injury induced by OGD/R and the related inflammatory markers (p < 0.001). Mechanistic s

关键词： MIR3142HG   IL-6   STAT3   Trx-1   CRC  

摘要： BackgroundColorectal cancer (CRC) is a prevalent and highly malignant neoplasm on a global scale, ranking as the second most widespread cause of cancer-associated death. Long noncoding RNAs (lncRNAs) control tumorigenic processes in CRC by modulating inflammatory signals. However, the precise mechanisms remain *** regulated by thioredoxin-1 (Trx-1) and interleukin (IL)-6 were identified by RNA sequencing (RNA-seq). The effect of MIR3142HG on CRC growth, migration, and invasion was assessed through methods of cell counting kit-8 (CCK-8), colony formation assay, Transwell assay, and animal experimentation, respectively. The regulation of signal transducer and activator of transcription 3 (STAT3) on the MIR3142HG promoter was verified using chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. The interaction of MIR3142HG with Trx-1 and STAT3 proteins was validated with RNA-binding protein immunoprecipitation (RIP) and RNA-pulldown experiments. Bioinformatics analysis and tissue microarray were utilized for evaluating the clinical value of MIR3142HG in *** identified a lncRNA, MIR3142HG, regulated by Trx-1 knockdown and IL-6 treatment. Overexpression of MIR3142HG enhanced CRC cell proliferation, migration, and invasion, while its knockdown impaired these processes. STAT3 bound to the MIR3142HG promoter and activated its transcription. Upregulated MIR3142HG acted as a scaffold for the Trx-1/STAT3 complex to inhibit the degradation of Trx-1 and phosphorylated STAT3 (p-STAT3). In situ hybridization (ISH) results of CRC tissues indicated that MIR3142HG expression was significantly elevated during the early stages of CRC. Moreover, consistent with the Cancer Genome Atlas (TCGA) dataset, high MIR3142HG expression predicted better *** study identified a novel lncRNA MIR3142HG, which interacts with STAT3 and Trx-1 to promote CRC progression, providing a possible diagnostic target for CRC.

摘要： Background: 3-acetyl-11-keto-beta-boswellic acid (AKBA) is a monomer extracted from the traditional Chinese herbs of Boswellia that has antitumor effects. However, the therapeutic effects and mechanisms of AKBA in prostate cancer (PCa) are unclear. Objective: To predict the target of AKBA treatment of PCa using network pharmacology methods and validate the predicted targets through CCK-8, flow cytometry, cell scratch test, Transwell chamber assay, and proteomics. Methods: The protein-protein interaction (PPI) network was established. Further analysis was performed by gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes for biological functionality and pathway enrichment. CCK-8 assay, flow cytometry, wound healing assay, and Transwell chamber assay were used to detect cell proliferation, apoptosis, invasion, and metastasis, respectively. Transcriptomics was used to detect the effects of AKBA on protein levels in PCa cells. Results: 120 potential targets for the AKBA treatment of PCa were obtained. GO enrichment analysis revealed that the biological processes of AKBA treatment of PCa include the steroid metabolic process, drug response, and fatty acid metabolic process. The results of KEGG enrichment revealed that the IL-17 signaling pathway is the key pathway for the AKBA treatment of PCa. In addition, experimental results demonstrate that AKBA inhibits the proliferation of PCa cells, induces cell apoptosis, and suppresses cell invasion and metastasis. Proteomics identified 119 differentially expressed proteins, which were primarily enriched in pathways closely related to the phogosome, pathways in cancer, IL-17 signaling pathway, spliceosome, PPAR signaling pathway, and HIF-1 signaling pathway. Conclusion: Through the methodologies of network pharmacology and transcriptomics, AKBA may exert its therapeutic effects on PCa by modulating the expression of the IL-17 signaling pathway.

关键词： 宫颈癌   桂枝茯苓汤加味   放化疗   疗效   T淋巴细胞亚群  

摘要： 目的 分析桂枝茯苓汤加味对宫颈癌术后放化疗增效作用及对T淋巴细胞亚群水平的影响。方法 回顾性分析2017年1月至2020年5月医院收治的106例宫颈癌患者的资料，所有患者均行宫颈癌根治术，根据术后治疗方式分为研究组（54例，术后放化疗联合桂枝茯苓汤加味治疗）、对照组（52例，术后放化疗治疗），两组术后随访3年。对比两组中医证候评分、肿瘤标志物、T淋巴细胞亚群、免疫球蛋白免疫球蛋白（Immunoglobulin，Ig）、补体及不良反应情况及抗肿瘤效果。结果 两组治疗后主症、次症中医证候评分均低于治疗前（P＜0.05），研究组治疗后更低（P＜0.05）。两组治疗后（Carcinoembryonic Antigen，CEA）、糖类抗原125（Carbohydrate Antigen 125，CA125）、鳞状细胞癌抗原（Squamous Cell Carcinoma Antigen，SCCA）均低于治疗前（P＜0.05），研究组治疗后更低（P<0.05）。研究组治疗前后的Th1/Th2、Th17/Treg、CD4＋/CD8＋对比差异均无统计学意义（P＞0.05）；对照组治疗后的Th1/Th2、Th17/Treg均高于治疗前，CD4＋/CD8＋均低于治疗前（P＜0.05）；研究组治疗后Th1/Th2、Th17/Treg低于对照组，CD4＋/CD8＋高于对照组（P＜0.05）。研究组治疗前后的IgG、IgM、C3、C4对比差异均无统计学意义（P＞0.05），对照组治疗后的IgG、IgM、C3、C4均低于治疗前（P＜0.05），研究组治疗后的IgG、IgM、C3、C4均高于对照组（P＜0.05）。研究组的皮肤反应、放射性膀胱炎发生率低于对照组（P＜0.05）。研究组的3年无病生存曲线优于对照组（P＜0.05）。结论 桂枝茯苓汤加味治疗用于宫颈癌术后放化疗患者可增强抗肿瘤效果，降低肿瘤标志物，维持机免疫功能稳定，减轻毒副反应。