藏红花素保护溃疡性结肠炎模型大鼠的作用及相关机制

文题释义：溃疡性结肠炎：一种非特异性结直肠炎性病变,病变部位多位于乙状结肠和直肠,可蔓延至降结肠,甚至整个结肠,病变多局限于黏膜和黏膜下层,以血性腹泻为常见症状,病情反复,病程漫长。藏红花素：是提取自番红花的单糖基或二糖基多烯酯,属于水溶性类胡萝卜素化合物。背景：藏红花素具有抗炎、抗氧化应激等作用,但对于溃疡性结肠炎治疗作用及相关机制研究仍不明确。目的：探讨藏红花素对溃疡性结肠炎大鼠的保护作用及相关机制。方法：将SD大鼠30只随机分为5组,正常组、模型组、藏红花素低剂量组、藏红花素高剂量组、阳性对照组。采用葡聚糖硫酸钠诱导法构建溃疡性结肠炎大鼠模型,并采用藏红花素0.05,0.1 g/kg灌胃干预。阳性对照组给予柳氮磺嘧啶灌胃。结果与结论：①形态学评估：干预1周后,与模型组大鼠相比,藏红花素干预的各组大鼠灌胃后结肠组织损伤评分、大鼠结肠疾病活动指数评分显著降低(P < 0.05);②氧化应激水平检测显示,与模型组相比,藏红花素干预的各组大鼠结肠组织丙二醛含量及髓过氧化物酶活性降低(P < 0.05),超氧化物歧化酶活性升高(P < 0.05);③免疫组织化学染色显示,与模型组相比,藏红花素干预的各组大鼠1周后肿瘤坏死因子α和白细胞介素23蛋白免疫反应下降(P < 0.05);④免疫印迹蛋白检测显示,与模型组相比,藏红花素干预的各组大鼠肠组织总蛋白Bax、Caspase-3、Toll样受体4及MyD88的表达水平蛋白表达下调(P < 0.05),Bcl-2蛋白表达上调(P < 0.05);⑤结果说明藏红花素对溃疡性结肠炎大鼠有一定的治疗作用,其机制可能与下调Toll样受体4/MyD88信号通路及抑制结肠的氧化应激、炎症反应及细胞凋亡有关。ORCID: 0000-0002-1941-1235(杨敏杰)中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

天麻总酚抗大鼠脑缺血再灌注损伤的转录组学分析及实验验证

目的 通过转录组测序技术(RNA sequencing,RNA-seq)分析天麻总酚(total polyphenols of Gastrodia elata,TPGE) 抗大鼠脑缺血再灌注损伤(cerebral ischemic reperfusion injury,CIRI)的转录组学特征,并采用定量聚合酶链反应(...     

Molecular and genetic biomarkers implemented from next-generation sequencing provide treatment insights in clinical practice for Waldenström macroglobulinemia

Waldenström macroglobulinemia (WM) is a distinct type of indolent lymphoplasmacytic lymphoma (LPL) with a high frequency of MYD88^L265P mutation. Treatment for WM/LPL is highly variable in clinic and ibrutinib (a Bruton tyrosine kinase inhibitor, BTKi) has become a new treatment option for WM. To investigate the clinical impact of genetic alterations in WM, we assembled a large cohort of 219 WMs and 12 LPLs dividing into two subcohorts: a training cohort, patients sequenced by a same targeted 29-gene next-generation sequencing (NGS) panel, and a validation cohort, patients sequenced by allele specific-PCR or other targeted NGS panels. In both training and validation subcohorts, MYD88^L265P and TP53 mutations showed favorable and adverse prognostic effects, respectively. CXCR4 nonsense/missense mutations (CXCR4^NS/MS), cytogenetic complex karyotypes, and a family history of lymphoma/leukemia in first-degree relatives were associated with significantly worse clinical outcomes only or more in the validation subcohort. We further investigated the efficacy of various treatments and interaction with genetic factors in the entire cohort. Upfront dexamethasone usage was associated with poorer clinical outcomes in patients who received non-proteasome-containing chemotherapy as first-line treatment independent of genetic factors. Maintenance rituximab was associated with better survival. Ibrutinib/BTKi showed potential benefit in relapsed/refractory patients and patients without CXCR4^NS/MS including those with TP53 mutations. In conclusion, genetic testing for MYD88^L265P, TP53, and CXCR4 mutations and cytogenetic analysis provide important information for prognosis prediction and therapy selection. The findings in these study are valuable for improving treatment decisions on therapies available for WM/LPL patients with integration of NGS in clinic.     

The roles of toll like receptor 3, 7 and 8 in allergic rhinitis pathogenesis

Allergic rhinitis, as an allergic and nasal hypersensitivity disease, is associated with the inflammation of nasal mucosa. It appears that innate immune receptors are the important risk factors in the pathogenesis of the inflammatory disease. Toll-like receptors (TLRs) are the most important receptors of innate immunity; their crucial roles in the recognition of allergens and subsequently pathogenesis of allergic diseases have been evaluated recently. TLR3, 7 and 8 are the intracellular members of the innate immune receptors and recognize intracellular single and double strand RNAs. This review article collected the investigations regarding the roles of TLR3, 7 and 8 in the allergic rhinitis pathogenesis.     

Flow cytometry-based diagnosis of primary immunodeficiency diseases

Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited diseases of the immune system. The definite diagnosis of PID is ascertained by genetic analysis; however, this takes time and is costly. Flow cytometry provides a rapid and highly sensitive tool for diagnosis of PIDs.Flow cytometry can evaluate specific cell populations and subpopulations, cell surface, intracellular and intranuclear proteins, biologic effects associated with specific immune defects, and certain functional immune characteristics, each being useful for the diagnosis and evaluation of PIDs. Flow cytometry effectively identifies major forms of PIDs, including severe combined immunodeficiency, X-linked agammaglobulinemia, hyper IgM syndromes, Wiskott-Aldrich syndrome, X-linked lymphoproliferative syndrome, familial hemophagocytic lymphohistiocytosis, autoimmune lymphoproliferative syndrome, IPEX syndrome, CTLA 4 haploinsufficiency and LRBA deficiency, IRAK4 and MyD88 deficiencies, Mendelian susceptibility to mycobacterial disease, chronic mucocuneous candidiasis, and chronic granulomatous disease. While genetic analysis is the definitive approach to establish specific diagnoses of PIDs, flow cytometry provides a tool to effectively evaluate patients with PIDs at relatively low cost.     

TLR4及MyD88在大鼠局灶性脑缺血耐受过程中的作用

目的本实验拟探究经脑缺血预处理后Toll样受体4（TLR4）及其下游髓样分化因子88（MyD88）蛋白在脑缺血耐受中的作用。方法采用改进的大鼠大脑中动脉线栓法构造大鼠脑缺血预处理模型,取大鼠脑组织后应用2,3,5-氯化三苯基四氮唑（Trc）染色观察鼠脑梗死面积变化,干湿法探究脑水肿程度改变,并通过Westernblot横向对比各组TLR4及MyD88蛋白表达情况。结果缺血处理后大鼠当其再次面临缺血再灌注损伤时,TLR4蛋白和MyD88蛋白表达在各观察时间点均呈现了不同程度的降低,且梗死面积及脑水肿程度也有所降低。结论经脑缺血预处理后脑组织可产生对致死性再灌注损伤的耐受,这种耐受是通过TLR4及MyD88蛋白的下调表达实现的并具有一定的时效性。