心肌的基质金属蛋白酶表达对房颤心肌重构的影响

心肌细胞在房颤期间发生了结构的改变,细胞外基质(ECM)保证心肌细胞的正常定位和心肌组织的完整性,而胶原是其主要组成成分.基质金属蛋白酶(MMPs)介导胶原降解,影响心肌细胞结构的改变.是重构过程中心脏基质降解的主要因素.细胞外基质的降解也同时取决于基质金属蛋白酶与其抑制剂TIMPs的平衡.     

安徽省流行性脑脊髓膜炎流行病学分析及防制对策

目的了解安徽省流行性脑脊髓膜炎(流脑)流行病学特征,为做好流脑防制工作提供科学依据。方法采用流行病学调查及临床、实验室检测。结果安徽省自2003年起流脑发病增多,2004~2005年度全省报告流脑235例,发病率0.37/10万,病死率8.09%;分布在全省60.0%的县,主要集中在皖南和江淮地区;有明显的冬春季发病高峰,1~4月病例数占总病例数的84.3%;13~18岁、7~12岁病例数分别占总病例数的42.6%和16.6%;全省有6个市发生7起聚集性流脑疫情,其中6起发生在学校;流行菌群发生变迁,以C群脑膜炎奈瑟菌为主。结论应采取以接种脑膜炎球菌多糖疫苗为主的综合性预防措施,同时开展流脑病例监测、流脑带菌率监测和流脑抗体水平监测。     

Inhibiting collagen I production and tumor cell colonization in the lung via miR-29a-3p loading of exosome-/liposome-based nanovesicles

The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients’ outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol–miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.     

Cutaneous Neurofibroma Heterogeneity: Factors that Influence Tumor Burden in Neurofibromatosis Type 1

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金茵利胆胶囊对四氯化碳诱导大鼠肝纤维化的保护作用

目的 探讨金茵利胆胶囊对四氯化碳(CCl₄)诱导大鼠肝纤维化的保护作用。方法 将SD大鼠随机分为空白对照组、模型组、水飞蓟素(阳性药)组、金茵利胆胶囊低剂量组和高剂量组,每组8只。除空白对照组外,其余各组大鼠采用CCl₄腹腔注射,每周2次,连续6周诱导大鼠肝纤维化模型,造模期间连续灌胃给药6周。实验结束后计算肝脏、脾脏脏器指数；观察肝脏组织的病理变化和纤维化程度；检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆汁酸(TBA)等生化指标含量；SOD试剂盒检测大鼠血清抗氧化能力；采用ELISA法检测大鼠血清中IL-6、IL-1β和TNF-α炎症指标水平；免疫组化法检测大鼠肝脏中α-平滑肌肌动蛋白(α-SMA)的表达情况；实时荧光定量PCR法检测Col-Ⅰ、Col-Ⅲ、Col-Ⅳ、NF-κB、MMP2、TIMP1和TGF-β1等基因的相对表达量。结果 与模型组比较,金茵利胆胶囊能显著降低肝脏指数(P < 0.01)；降低血清中ALT、AST和TBA水平(P < 0.05)；改善肝组织纤维化程度；增加了SOD的含量(P < 0.01)；降低IL-6、IL-1β和TNF-α炎症指标水平(P < 0.05)；降低α-SMA的表达水平；降低肝脏Col-Ⅰ、Col-Ⅲ、Col-Ⅳ、NF-κB、MMP2、TIMP1和TGF-β1等基因的相对表达量(P < 0.05)。结论 金茵利胆胶囊对CCl₄诱导的大鼠肝纤维化有保护作用,其作用机制可能与抑制肝细胞外基质沉积和肝星状细胞活化有关。     

Lipoid proteinosis: Novel ECM1 pathogenic variants and intrafamilial variability in four unrelated Arab families

Background/objectives

Lipoid proteinosis (LP) is a rare autosomal recessive multisystem disorder that is caused by loss-of-function pathogenic variants in the extracellular matrix protein-1 (ECM1) gene. The typical clinical manifestations of LP include hoarseness of voice, beaded papules on the eyelids, infiltration and scarring of the skin and mucosa, as well as neuropsychological abnormalities. Currently, more than 70 pathogenic variants have been reported, including nonsense, missense, splice site, deletion and insertion pathogenic variants, and more than half of them occurred in exons 6 and 7.

Methods

Clinical evaluation and Sanger sequencing were performed on eight patients from four unrelated Arab families.

Results

We identified two novel ECM1 variants, one nonsense pathogenic variant in exon 6 (c.579G>A, p.Trp193*) and a deletion of three nucleotides (c.1390_1392del, p.Glu464del) in exon 9, and two previously reported frameshift variants; c.692_693delAG, in exon 6 and c.11dupC in exon 1.

Conclusions

Although all patients had characteristic manifestations of lipoid proteinosis, we observed intrafamilial phenotypic variability. Our data expand the pathogenic variant spectrum of ECM1 and also supports the fact that exon 6 is one of the most common hot spots of pathological variants in ECM1.