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关键词： 抗原修复   免疫组织化学   FFPE   Tris   EDTA  

摘要： 目的 探究一种新型抗原修复液增强石蜡切片免疫组织化学染色效果。方法 分别用三种不同的抗原修复液（即常规使用的柠檬酸修复液、EDTA修复液，及新配方修复液）对30例不同组织的石蜡组织切片进行加热高压抗原修复，然后选择30个在细胞不同表达部位（细胞膜、浆及核）的抗体完成免疫组织化学染色，观察和统计比较用不同抗原修复液的染色效果（阳性染色染色深浅及阳性细胞数量）。结果 使用柠檬酸修复液组染色+为30.0%(9/30)、++为66.6%(20/30)、+++为3.3%(1/30)，EDTA修复液组+为10.0%(3/30)、++为83.3%(25/30)、+++为6.66%(2/30)，新型修复液组+为3.3%(1/30)、++为60.0%(18/30)、+++为36.6%(11/30)。结论 新型抗原修复液在多种石蜡组织样本中表现出较好的修复效果，可以缩短抗原修复时间，为组织抗原修复提供了一种新的选择，具有实用价值。

关键词： cytokine   HLA   IFNE   immunity   interferon   MHC   ovarian cancer   tumor grade   tumor stage  

摘要： Problem Interferon-epsilon (IFN epsilon), which is highly abundant in the epithelium of the female reproductive tract (FRT), is a recently identified tumor suppressor for ovarian cancer. IFN epsilon induces the expression of certain HLA class I family members in HGSOC (high-grade serous ovarian cancer), and its expression is lost during ovarian tumorigenesis. However, tumor stage-dependent expression of HLA class I family members in ovarian cancer has not been previously *** of Study Data analysis and visualization were performed using various gene expression and transcriptomics datasets in the R statistical programming *** We found that the expression of HLA-A, -B, -C, -E, -F, -G, and -J is lower in late stage ovarian tumors compared to early-stage tumors. The total expression of HLA class I family members decreases with age in ovarian cancer. Furthermore, we showed that the expression of some IFN-regulated genes, which were shown to be upregulated by IFN epsilon, decreases from early to late stage in ovarian cancer, in parallel to the loss of IFN epsilon expression in ovarian tumorigenesis and possibly in tumor progression. We also found that breast tumors (another hormonally driven cancer) with positive progesterone receptor status have lower IFN epsilon mRNA expression compared to those with negative PR status. Besides, we reported that breast tumors with positive estrogen receptor (ER) status have lower expression of IFN epsilon compared to those with negative ER *** Combined, this study points that the decrease in the expression of IFN epsilon, HLAs, or some other IFN epsilon-regulated genes during ovarian cancer progression might contribute to worse prognosis in advanced disease.

关键词： Preeclampsia   Hypoxia inducible factor 1 subunit alpha   Endothelial dysfunction   Vascular regeneration   Pregnancy complications  

摘要： Pre-eclampsia (PE) is a common pregnancy complication, closely associated with endothelial dysfunction and inhibition of angiogenesis. This study aims to explore the pathological mechanisms causing endothelial dysfunction and suppressed angiogenesis in PE, with the aim of identifying potential drug targets. Human umbilical vein endothelial cells (HUVECs) were exposed to angiotensin II (Ang-II) to mimic PE-related endothelial dysfunction. Angiogenic capacity was evaluated using tube formation assay, scratch assay, flow cytometry, and CCK-8 assay. A Reduced Uterine Perfusion Pressure (RUPP) mouse model was established to recapitulate PE. Expression profiles of hypoxia-inducible factor-1 alpha (HIF-1 alpha), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sENG), and tumor necrosis factor-alpha (TNF-alpha) were quantified via Western blot and RT-qPCR. Biochemical assessments included levels of malondialdehyde, superoxide dismutase, glutathione, and the urine protein/creatinine (UP/cr) ratio. Systolic blood pressure was measured while placental histopathology was examined using hematoxylin and eosin (HE) staining. In HUVECs exhibiting endothelial dysfunction, ICAM-1 and VCAM-1 were markedly upregulated, whereas HIF-1 alpha expression was significantly reduced. Overexpression of HIF-1 alpha boosted HUVEC proliferation and migration, attenuated apoptosis and oxidative stress, enhanced expression of VEGF and PlGF, and suppressed expression of sFlt-1, sENG, and TNF-alpha, thereby promoting angiogenesis. In the RUPP-modeled PE mouse model, diminished HIF-1 alpha expression coincided with elevated ICAM-1 and VCAM-1, leading to endothelial dysfunction, elevated systolic blood pressure, and increased UP/cr ratio. Conversely, HIF-1 alpha overexpression ameliorated placental tissue damage and oxidative str

关键词： DRB3*03:85   HLA-DRB3   Korean   massively parallel sequencing   new allele  

摘要： DRB3*03:85 is distinguished from HLA-DRB3*03:01:01:01 by a single nonsynonymous substitution at codon 122 in exon 3.

关键词： 呼吸道合胞病毒   单克隆抗体   被动免疫   临床试验   F蛋白   呼吸道感染   抗病毒药   预防  

摘要： 呼吸道合胞病毒（respiratory syncytial virus， RSV）作为全球公共卫生的重要威胁，其引发的下呼吸道感染（如毛细支气管炎、肺炎）是导致婴幼儿和老年人住院的首要原因。?值得注意的是，尽管该病毒造成的疾病负担持续加重，当前防治手段的迭代速度却未能匹配其临床需求的迫切性。究其根本，现行防治体系仍面临双重瓶颈：一方面，传统疫苗因中和抗体效价不足导致免疫应答滞后；另一方面，抗病毒药物（如利巴韦林）则受限于耐药性，难以形成持续保护。在此背景下，基于RSV F蛋白融合前构象状态（prefusion fusion protein， preF）的高分辨结构解析及抗体工程技术的突破性发展，靶向preF抗原表位的高效中和性单克隆抗体（monoclonal antibody， mAb）应运而生。特别值得关注的是，这类抗体凭借高特异性和长效保护成为研究热点。现基于RSV结构生物学的深入解析，系统综述RSV单克隆抗体的研发进展与临床转化潜力。首先，通过对比分析已上市药物与在研抗体的作用机制差异，揭示其相较于传统疗法的被动免疫优势；其次，结合临床试验数据，探讨其面临的挑战；最后，从联合疗法、新型给药途径等维度提出未来研究方向。

关键词： IL-6 family   metabolic-associated fatty liver disease   lipid metabolism   insulin resistance   inflammation  

摘要： As lifestyle patterns change, the rates of type 2 diabetes and obesity are increasing together, leading to an increase in metabolic-associated fatty liver disease (MAFLD), now recognized as the most frequently occurring liver disease globally. MAFLD presents a significant threat to public health and imposes a substantial socioeconomic burden. This condition encompasses a spectrum of hepatic manifestations, beginning with excessive fat accumulation and hepatic steatosis, and possibly progressing to non-alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and liver cancer. The pathogenesis of MAFLD is intricately linked to lipid accumulation, oxidative stress, and lipotoxicity. Notably, the interleukin-6 (IL-6) cytokine family plays a complex role in the onset and development of MAFLD, primarily through the modulation of lipid metabolism, insulin resistance, inflammatory responses, and liver fibrosis. This review examines the impact of the IL-6 family on the progression of MAFLD. It explores targeting the IL-6 family as a potential future therapy for MAFLD.

关键词： Acetic acid   caspase-1   febuxostat   IL-1 beta   NLRP3   ulcerative colitis  

摘要： BackgroundUlcerative colitis (UC) is a persistent inflammation of the mucous membrane of the large intestine, mostly impacting the colon and rectum. Lack of secure and efficient medical treatments motivates the search for new therapeutic agents to efficiently manage UC and its associated outcomes. The objective of this study was to investigate the preventive effect of febuxostat in rats with UC caused by acetic acid (AA).MethodsAA (2 ml, 3% v/v) was administered intrarectally to induce UC. Preceding the administration of AA, febuxostat (10 mg/kg/day) was orally administered for two *** suppressed AA-induced UC by ameliorating colonic histological alterations, including inflammation, glandular hyperplasia, goblet cell loss, and mucosal ulcerations, while simultaneously reducing colon weight, malondialdhyde, and interleukin-18 contents. Febuxostat successfully rectified the metabolic imbalance between oxidants and antioxidants induced by AA. Furthermore, febuxostat decreased the levels of caspase-1 and NOD-LRR and pyrin domain containing protein 3 and increased colon length, catalase activity, and zonula occludens-1 *** mitigated AA-induced UC in rats by influencing the NLRP3/caspase-1/IL-1 beta signaling pathway, controlling the equilibrium between oxidants and antioxidants, and improving the integrity of the barrier of the colon.

关键词： tocilizumab   canine   IL-6R   autoimmune   monoclonal antibody  

摘要： Introduction Tocilizumab (TCZ) is an immunosuppressive drug approved for the treatment of rheumatoid arthritis in humans. Molecularly, it is a humanized monoclonal antibody (mAb) that binds to the interleukin-6 receptor (IL-6R), blocking its inflammatory pathway with the IL-6 protein. A previous study has looked at the safety of topical TCZ as eye drops in dogs, however, no studies have tested its potential use in canine diseases based on species antibody *** and methods (1) To assess the biological inhibitory effect of TCZ on canine macrophages in vitro (n = 3), the median fluorescence intensity of phospho-STAT3 (Y705) was determined using flow cytometry and compared to the inhibitory effect of human macrophages (n = 2). (2) To try and characterize the receptor region of interest in the canine IL-6R, homology modeling was performed using the MODELLER 10.4 software. (3) To investigate the real-time ligand-binding affinity and kinetic parameters for canine IL-6R with TCZ, surface plasmon resonance (SPR) spectroscopy was used, and results were compared to the human IL-6R interaction with *** Our results confirm binding of TCZ with canine IL-6R. In comparison, canine IL-6R binds two orders of magnitude less than human IL-6R in its dissociation constant. Canine cell culture required a higher concentration of TCZ compared to human cell culture to produce a similar inhibitory *** and clinical significance The binding of TCZ to canine IL-6R resulting in a biological response is a specific example of the new possibilities to harness humanized mAb for canine diseases. TCZ may not be a feasible treatment due to the binding affinity and the high concentrations needed. However, future studies should explore potential suitable human mAb for treating canine autoimmune diseases.

关键词： allergic contact dermatitis   atopic dermatitis   cytokine signatures   irritant contact dermatitis   translational study