课程文献中心 更多>>

关键词： Autoimmune myocarditis   CD4(+)T cell   Hydrogen   Necroptosis   TNF/TNFR1 signalling  

摘要： Autoimmune myocarditis refers to the inflammation of myocardial tissue caused by innate and adaptive immune responses, characterized by elevated levels of tumour necrosis factor-α (TNF-α), a classic pro-inflammatory factor. Although hydrogen exhibits anti-inflammatory and antioxidant properties, its therapeutic effects in autoimmune myocarditis have not been evaluated. Therefore, the present study aimed to explore whether hydrogen can alleviate autoimmune myocarditis via TNF-α. An experimental autoimmune myocarditis (EAM) model was established in BALB/c mice via subcutaneous injection of pig-derived myocardial myoglobin emulsified with complete Freund's adjuvant. The treatment group received 2 % hydrogen inhalation twice a day (3 h each time) for 21 days. CD4+ T cell expression was higher in the EAM group than in the Control group, and this increase was attenuated following treatment with hydrogen. Additionally, the levels of TNF-α and related inflammatory factors were substantially higher in the EAM group than in the Control group, and these changes were reversed following hydrogen treatment. Echocardiography assessments demonstrated a significant improvement in heart function following treatment with hydrogen compared to that in the EAM group. Pathological results revealed significant inflammatory cell infiltration and fibrosis in the hearts of the untreated EAM group. Tissue immunofluorescence and protein immunoblotting indicated elevated necroptosis markers in the EAM group, which were downregulated after treatment with hydrogen. This study demonstrates that hydrogen effectively ameliorated autoimmune myocarditis by modulating necroptosis via the TNF/TNFR1 signalling pathway, making it a promising novel therapeutic strategy for myocarditis.

关键词： 嵌合抗原受体T细胞   基因转导   扩增   冻存   生产工艺  

摘要： CAR-T细胞疗法正处于高速发展阶段,作为恶性血液肿瘤的重要治疗手段,其临床应用范围正逐步向实体瘤和自身免疫性疾病领域扩展,这对生产工艺提出了更高的要求。CAR-T细胞产品的生产工艺特殊且复杂,不仅与产品质量息息相关,更与临床治疗费用直接挂钩,生产工艺的自动化和优化是增强产品临床应用可及性的关键。本文聚焦自体CAR-T细胞产品,对其生产工艺的研究进展进行了综述,旨在为该类品种优化生产工艺、缩短生产周期、降低生产成本提供参考和借鉴。

摘要： Leukemia stem cells (LSCs) are a small yet powerful subset of leukemic cells that possess the ability to self-renew and have a long-term tumorigenic capacity, playing a crucial role in both leukemia development and therapy resistance. These LSCs are influenced by external and internal factors within the bone marrow niche. By delving into the intricate interplay between LSCs and their immune environment, we can pave the way for innovative immunotherapies that target both the malignant stem cells and the suppressive immune microenvironment, addressing both the “seed” and the “soil” simultaneously. Through the analysis of public datasets and patient samples, we show that elevated IL1RL1 expression correlates with poor prognosis and therapy resistance in acute myeloid leukemia (AML). At the core of this process, stem cell leukemogenesis initiation and maintenance signals are driven by a stress-induced IL-33/IL1RL1 autocrine loop. This LSC-induced IL-33/IL1RL1 signaling fosters an immune regulatory microenvironment. Therefore, IL1RL1 emerges as a promising therapeutic target, with IL1RL1-specific T cell-engaging bispecific antibodies holding great potential as cutting-edge immunotherapeutics for AML. © The Author(s) 2025.

关键词： 造血干细胞   造血干细胞移植   造血干细胞动员   细胞因子   血小板生成素   CXCR4拮抗剂   整合素拮抗剂   化疗   动员效能  

摘要： 背景:造血干细胞移植是一种广泛应用于血液系统恶性和非恶性疾病的重要治疗手段,动员和收集足够的造血干细胞是保证患者移植后快速、持续造血功能重建的前提,但最常用的粒细胞集落刺激因子联合或不联合化疗的经典方案仍有10%-40%的动员失败率。目的:综述近年来造血干细胞动员现状,分析不同方案的优缺点,展望未来动员新方案。方法:以“造血干细胞,造血干细胞移植,造血干细胞动员,细胞因子,血小板生成素,CXCR4拮抗剂,整合素拮抗剂,化疗,动员效能”为中文关键词,以“hematopoietic stem cell,hematopoietic stem cell transplantation,hematopoietic stem cell mobilization,cytokines,thrombopoietin,CXCR4 antagonists,integrin antagonist,chemotherapy,mobilization efficiency”为英文关键词,在CNKI、PubMed、万方数据库进行检索,文献语种限制为中文、英文,检索年限为1990-2024年,共检索到300多篇文献,最终纳入68篇文献进行分析。结果与结论:越来越多的研究发现粒细胞集落刺激因子联合普乐沙福、白细胞介素、血小板生成素及整合素拮抗剂等能够更加有效地动员造血干细胞,联合使用可以减少粒细胞集落刺激因子的使用剂量,减少相关不良反应。一些新药如可溶性重组flt3-配体(简称CDX-301)、双重α9β1/α4β1整合素抑制剂BOP等可与粒细胞集落刺激因子联合,促进造血干细胞动员。此外还发现一些潜在的动员靶点如前列腺素E2受体及1-磷酸鞘氨醇等,尚在研究阶段。除固有的患者特征、治疗特征外,开发纳入生物标志物的预测模型,有助于有效预测造血干细胞动员失败,提升干细胞动员技术。

关键词： Precision nutrition   Obesity   Gut microbiota   Omics technologies, Weight loss, Prevention   AI   artificial intelligence   AMPK   AMP-activated protein kinase   BCFAs   branched-chain fatty acids   BMI   body mass index   DCA   deoxycholic acid   EWL   excess weight loss   FMT   fecal microbiota transplantation   FXR   farnesoid X receptor   GLP-1   glucagon-like peptide 1   HDAC7   histone deacetylase 7A   HDACs   histone deacetylases   HDL   high-density lipoproteins   IGF2BP2   insulin like growth factor 2 MRNA binding protein 2   IL   interleukin   LDL   low-density lipoproteins   LPS   lipopolysaccharides   ML   machine learning   NF-κB   nuclear factor-kappa B   NGS   next-generation sequencing   PPARγ   peroxisome proliferator-activated receptor gamma   PUFAs   polyunsaturated fatty acids   PYY   insulin, leptin, and peptide YY   SAM   S-adenosyl methionine   SCFAs   short-chain fatty acids   TET   Ten-Eleven Translocation   T2DM   type 2 diabetes mellitus   TGR5   G-protein coupled receptor 1   TLR4   Toll-like receptor 4   TMA   trimethylamine   TMAO   trimethylamine N-oxide   TNF-α   as tumor necrosis factor  

摘要： Obesity is a complex and multifactorial condition strongly associated with metabolic burdens and cardiovascular diseases. This review focuses on precision nutrition as a strategy for obesity management, exploring how personalized interventions can modulate the composition and functionality of the gut microbiome to promote weight loss and improve metabolic health. A growing body of evidence suggests that imbalances in gut microbiota composition directly impact lipid metabolism, immune and inflammatory pathways, and appetite regulation mechanisms. Furthermore, the review discusses the relationship between gut microbiota and dietary factors, highlighting how certain types of diets (such as the Mediterranean diet and fiber-rich diets) can promote the production of short-chain fatty acids (SCFAs) and the growth of beneficial bacteria associated with weight regulation and reduced inflammation. While diet is the primary factor modulating the gut microbiota, factors such as genetics and epigenetic characteristics, body composition, maternal nutritional, type of birth delivery, physical activity and even drug use also play significant roles in this modulation. Although the use of precision nutrition approaches still faces challenges, such as cost and variability in individual response, the integration of omics technologies, artificial intelligence, and machine learning appear to offer great potential as tools to identify specific microbial and genetic profiles that allow for the personalization of nutritional interventions. These technologies enable large-scale analysis of dietary, genomic, and microbial factors to create dietary strategies to prevent or treat obesity that meet the specific metabolic needs of each individual. Thus, the application of these tools in clinical settings could transform obesity management, creating data-driven interventions that enhance treatment effectiveness.

关键词： Anti-inflammatory   Biological activity   In silico screening   Signaling transduction pathway   Small molecules   TNF-α  

摘要： TNF-α is a key cytokine, plays a critical role in the pathogenesis of autoimmune and inflammatory diseases such as rheumatoid arthritis and psoriasis. As a result, TNF-α has emerged as a pivotal therapeutic target. Currently, monoclonal antibodies and decoy receptors targeting TNF-α are widely used, yet they face limitations such as administration challenges. These drawbacks have driven the exploration of small molecule inhibitors as alternative therapeutic agents due to their oral bioavailability, ability to cross biological barriers, and cost-effective production. Significant efforts have been directed toward developing small-molecule TNF-α inhibitors, which function either by disrupting the TNF trimer or by blocking TNF-αTNFR interactions. Several candidates have progressed to clinical trials, demonstrating their potential as therapeutic agents. This review provides a comprehensive overview of TNF-α small-molecule inhibitors, covering their discovery, design strategies, structure-activity relationships, and biological evaluation. Additionally, it discusses current clinical outcomes and outlook to guide researchers in the drug design and development of more potent inhibitors.

关键词： Asthma   Cytokines   Epithelial-mesenchymal transition   Macrophage extracellular traps   Metrnl  

摘要： Macrophage extracellular traps (METs) are crucial for initiating airway inflammation and modulating the immune microenvironment of asthmatic airways. Metrnl/IL-41 is a negative regulator of airway inflammatory responses. However, the role of Metrnl/IL-41 in the cross-talk between METs and airway epithelial cells, as well as its effect on the pathophysiology of asthma airway remodeling, are still unclear. We aimed to elucidate the role of METs and Metrnl/IL-41 in airway epithelial cells and chronic asthma. Immunofluorescence and scanning electron microscopy were used to visualize METs formation. The effects of Metrnl/IL-41 on the proliferation, epithelial‒mesenchymal transition (EMT), and migration of METs-treated 16-HBE cells were determined. The role of Metrnl/IL-41 in macrophage polarization was analyzed. A chronic asthmatic murine model was established to explore the effects of rm-Metrnl/IL-41 and budesonide on lung histopathology changes, airway hyperresponsiveness, and airway inflammation and airway remodeling. Exposure to house dust mite (HDM) induced METs production in macrophages. Metrnl/IL-41 partially abrogated METs-mediated migration and EMT in 16-HBE cells by inhibiting the nuclear factor-κB (NF-κB) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways. Rm-Metrnl/IL-41 reduced airway inflammation, airway hyperresponsiveness, mucus secretion, collagen deposition, transforming growth factor-β1 (TGF-β1) levels, and EMT-related protein levels in asthmatic mice. Additionally, Metrnl/IL-41 significantly reduced neutrophils, M1 macrophages, and Th17 cells numbers in the lungs of asthmatic mice. METs play critical roles in EMT and airway remodeling, inhibiting METs formation may constitute a prospective therapeutic approach for asthma. Metrnl/IL-41 is a crucial protective cytokine against airway inflammation, indicating its potential as a therapeutic target in asthma.

关键词： Ankylosing spondylitis   Bone erosion   CD14(+)CD11c(+)HLA-II(+) monocyte   CD14(+)CD11c(+)HLA-II(−) monocyte   CSF-1  

摘要： Abnormal monocytes are involved in the pathogenesis of ankylosing spondylitis (AS). We investigated the association between an imbalance of monocyte subpopulations and bone destruction in AS. Compared to controls, AS patients exhibited increased CD14 + CD11c + HLA-II − monocytes and decreased CD14 + CD11c + HLA-II + monocytes in peripheral blood. LPS stimulation promoted a shift from CD14 + CD11c + HLA-II − monocytes toward CD14 + CD11c + HLA-II + monocytes, enhancing the former's capacity to promote CD4 + T cell proliferation. Micro RNA-seq analysis indicated that AS CD14 + CD11c + HLA-II − monocytes were involved in osteoclast differentiation and overproduced soluble osteoclastogenic cytokine CSF-1. In 40 AS patients, evaluated CD14 + CD11c + HLA-II − monocytes correlated positively with Spondyloarthritis Research Consortium of Canada (SPARCC) MRI inflammation score ( r  = 0.336, P  = 0.034) and bone erosion score ( r  = 0.423, P  = 0.007), but inversely with ankylosis score ( r  = −0.346, P  = 0.029). Conversely, CD14 + CD11c + HLA-II + monocytes showed the opposite correlation. Our findings demonstrate that expansion of CD14 + CD11c + HLA-II − monocytes contribute to bone erosion in AS, potentially mediated through CSF-1-driven osteoclast differentiation.

关键词： Traumatic brain injury   Hemorrhage   Pain   Secondary injury   Anesthesia   Morphine   ANOVA   analysis of variance   ANCOVA   analysis of covariance   BBB   blood-brain barrier   BSCB   blood spinal cord barrier   CCI   controlled cortical impact   FITC   fluorescein Isothiocyanate   GABA   amma-aminobutyric acid   H&E   hematoxylin and eosin   HMGB1   high mobility group box 1   IL   interleukin   LPS   lipopolysaccharide   NMDA   N   methyl-D-aspartic acid   SCI   spinal cord injury   T   thoracic   TBI   traumatic brain injury   TRPV1   transient receptor potential vanilloid 1  

摘要： Traumatic brain injury (TBI) is a major cause of death and disability in the United States. In many cases, TBI is accompanied by additional tissue damage (polytrauma) that will engage pain (nociceptive) sensory fibers. Prior work using an animal model (rats) has shown that nociceptive stimulation after a spinal cord injury (SCI) fosters hemorrhage at the site of injury and amplifies secondary tissue loss. The current study explores whether noxious stimulation fosters hemorrhage after a TBI. Anesthetized rats were given a cortical impact of the frontal region. Nociceptive fibers that express the transient receptor potential vanilloid 1 (TRPV1) receptor were engaged by applying capsaicin to one hind paw a day after injury. Brain tissue was collected three hours later. Capsaicin applied contralateral, but not ipsilateral, to injury increased the area of hemorrhage in both male and female animals. Noxious stimulation fostered capillary fragmentation in the area of injury and increased infiltration of Evan's blue, implying a breakdown of the blood-brain barrier. Inducing a coma-like state with pentobarbital blocked capsaicin-induced hemorrhage after TBI. Systemic morphine also had a protective effect. Engaging pain fibers with electrical stimulation applied to the tail increased the area of hemorrhage and this effect too was blocked by systemic morphine. The results suggest that pain after TBI fosters hemorrhage, which increases the area of secondary tissue loss.

关键词： Cytotoxicity   Gene expression   Inflammation   Mercuric chloride   Oxidative stress   Pyroptosis  

摘要： An in vitro model using human peripheral blood mononuclear cells (PBMCs) was established to investigate the cytotoxic, oxidative and inflammatory effects and changes in purinergic system parameters caused by mercuric chloride (HgCl 2 ). Cells were exposed to concentrations of HgCl 2 (0.05, 0.5, 5, and 50 μM) for 24, 48 and 72 h. Cell viability was measured by trypan blue and MTT assays, and IC 50 ; apoptosis and cell death were assessed by flow cytometry. Oxidative stress was evaluated by reactive species (RS) generation, determination of Mercury (ICP-MS), Nitric Oxide (NO), and lipid peroxidation. Increased levels of HgCl₂ induced RS generation, NO, lipid peroxidation, apoptosis, and altered the cell cycle, reducing DNA synthesis and cell division of PBMCs. Flow cytometry confirmed decreased viability and increased late apoptosis. HgCl₂ accumulation in PBMCs was confirmed by ICP-MS. HgCl₂ altered purinergic system components, inhibiting NTPDase and increasing ADA activity. At 5 μM, it increased gene expression of purinergic receptors and both anti-inflammatory (IL-10) and pro-inflammatory markers (IL-1β, IL-6, TNF-α, NLRP3, CASP-1, NF-κB). Overexpression of the P2X7/NLRP3/CASP-1/IL-1β axis triggered cell death by pyroptosis. These findings provide compelling evidence HgCl 2 induces cytotoxic and inflammatory effects in PBMCs.