干扰素通路调控与自身免疫疾病

干扰素信号通路是细胞抵抗病原微生物侵染的重要防线。通过识别病源相关模式分子、激活下游通路,干扰素的表达被显著上调并分泌于细胞外,作用于自身和周围细胞,引发众多下游基因的转录激活。这些基因产物直接参与抗侵染过程或调控机体免疫反应。干扰素信号通路需要被正确调控,其异常激活会导致炎症和自身免疫疾病的发生。正确地识别“自己”和“非己”分子是首要的一步。鉴于干扰素通路所抵抗的微生物侵染中,核酸分子是重要的免疫原性分子,内源性核酸分子的代谢调控显得尤为重要。细胞编码一系列参与核酸代谢的酶,这些蛋白质功能的发挥对保持细胞核酸稳态至关重要。以单基因突变引发的自身免疫疾病Aicardi-Goutières综合征为例,目前发现9种基因可突变致病,均来自DNA代谢相关的和RNA代谢相关的基因。尽管这9种基因突变都导致干扰素通路的异常激活,但中间所依赖的参与蛋白并不相同。可见,同样症状的疾病,其致病机理也可能不同,这也将影响有效治疗方案的确定,凸显基因检测在诊治自身免疫疾病中的必要性。本综述通过阐述细胞内环境稳态对干扰素通路正确识别“自己”和“非己”的重要作用,帮助理解自身免疫疾病的发病机理。     

长时间左心辅助循环成功经验探讨

目的：对长时间左心辅助循环成功经验进行探讨。方法：于2002年7月9日对一例冠状动脉搭桥术加二尖瓣置换术后出现严重低心排的患者施行左心辅助,共23小时40分,抢救成功。结论：左心辅助作为一种安全有效和可信的救治衰竭心脏的方法,其成功应用有以下4要素：应用时机和病人选择、装置的选择及其表现、操作左心辅助医生对左心辅助理论的理解和对临床情况的判断力、左心辅助并发症的防治。     

木犀草素通过调节凝血活性物质及凝血因子含量维持机体血液循环功能的稳定

目的 探讨木犀草素通过调节凝血活性物质及凝血因子含量维持机体血液循环功能的作用机制。 方法 采用试剂盒和试管法测定木犀草素作用后的凝血酶原时间和血浆复钙时间;采用酶联免疫吸附法检测木犀草素对血液凝血活性物质血栓素(TXB2)、纤维酶原激活物抑制剂(PAI 1)、促红细胞生成素(EPO)和凝血因子Ⅶ(FⅦ)、凝血因子Ⅸ(FⅨ)含量的影响;采用PCR法测定木犀草素对凝血因子Ⅶ、Ⅸ的基因表达情况。 结果 木犀草素能缩短凝血酶原时间和血浆复钙时间,与对照组相比,40 mg/kg的木犀草素使凝血酶原时间和血浆复钙时间分别降低62.89%和64.05%(t=8.713 6、6.218 1,均P结论 木犀草素具有维持机体血液循环功能稳定的作用,其作用机制是通过提高凝血活性物质的含量,调节凝血因子的基因表达量,提高凝血因子的含量,以及抑制纤维酶原的激活和增加血液的黏度等多方面综合作用来实现的。     

叶表面角质层在贝母属植物叶鉴定中的意义

叶表面角质层在贝母属植物叶鉴定中的意义李萍，濮祖茂，蒋鑫，刘惠娟，徐国钧（中国药科大学生药学教研室；分析中心电镜室南京２１０００９）ＴｈｅｄｉａｇｎｏｓｔｉｃｖａｌｕｅｏｆｔｈｅｃｕｔｉｃｌｅｉｎｔｈｅｌｅａｖｅｓｆｒｏｍｇｅｎｕｓＦｒｉｔｉｌｌａｒ...     

Triptolide prevents bone loss via suppressing osteoclastogenesis through inhibiting PI3K-AKT-NFATc1 pathway

Bone loss (osteopenia) is a common complication in human solid tumour. In addition, after surgical treatment of gynaecological tumour, osteoporosis often occurs due to the withdrawal of oestrogen. The major characteristic of osteoporosis is the low bone mass with micro-architectural deteriorated bone tissue. And the main cause is the overactivation of osteoclastogenesis, which is one of the most important therapeutic targets. Inflammation could induce the interaction of RANKL/RANK, which is the promoter of osteoclastogenesis. Triptolide is derived from the traditional Chinese herb lei gong teng, presented multiple biological effects, including anti-cancer, anti-inflammation and immunosuppression. We hypothesized that triptolide could inhibits osteoclastogenesis by suppressing inflammation activation. In this study, we confirmed that triptolide could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells (BMMCs) and RAW264.7 cells and inhibited the osteoclast bone resorption functions. PI3K-AKT-NFATc1 pathway is one of the most important downstream pathways of RANKL-induced osteogenesis. The experiments in vitro indicated that triptolide suppresses the activation of PI3K-AKT-NFATc1 pathway and the target point located at the upstream of AKT because both NFATc1 overexpression and AKT phosphorylation could ameliorate the triptolide suppression effects. The expression of MDM2 was elevated, which demonstrated the MDM-p53-induced cell death might contribute to the osteoclastogenesis suppression. Ovariectomy-induced bone loss and inflammation activation were also found to be ameliorated in the experiments in vivo. In summary, the new effect of anti-cancer drug triptolide was demonstrated to be anti-osteoclastogenesis, and we demonstrated triptolide might be a promising therapy for bone loss caused by tumour.     

A disintegrin and metalloproteinase 8 induced epithelial‐mesenchymal transition to promote the invasion of colon cancer cells via TGF‐β/Smad2/3 signalling pathway

A disintegrin and metalloproteinase 8 (ADAM8) protein is a multi‐domain transmembrane glycoprotein which involves in extracellular matrix remodelling, cell adhesion, invasion and migration. ADAM8 and epithelial‐mesenchymal transition (EMT) play an important role in tumour invasion has been well established. However, the interaction between ADAM8 and EMT has remained unclear. The data of colon cancer patients obtained from TCGA (The Cancer Genome Atlas) and GTEx (Genotype‐Tissue Expression Project) were analysed by the bioinformatics research method. The expression of ADAM8 in colon cancer cells was up‐regulated and down‐regulated by transfecting with the expression plasmid and small interfering RNA, respectively. Transwell invasion assay, immunohistochemistry, immunocytochemistry, Western blotting and qRT‐PCR were utilized to study the effect of ADAM8 on colon cancer cell''s EMT and its related mechanisms. Analysis of TCGA and GTEx data revealed that ADAM8 was linked to poor overall survival in colon cancer patients. Besides, ADAM8 was correlated with multiple EMT biomarkers (E‐cadherin, N‐cadherin, Vimentin, Snail2 and ZEB2). In vitro, we also proved that the up‐regulation of ADAM8 could promote EMT effect and enhance the invasive ability of colon cancer cells. On the contrary, the down‐regulation of ADAM8 in colon cancer cells attenuated these effects above. Further studies suggested that ADAM8 modulated EMT on colon cancer cells through TGF‐β/Smad2/3 signalling pathway. Our research suggested that ADAM8 could be a potential biomarker for the prognosis of colon cancer and induced EMT to promote the invasion of colon cancer cells via activating TGF‐β/Smad2/3 signalling pathway.     

Activity Characteristics and Tyrosinase Inhibition Mechanism of a Silk Fibroin Oligopeptide and Cordyceps Polysaccharide Composite

International Journal of Peptide Research and Therapeutics - Silk fibroin is an excellent raw material for medical products as it shows remarkable biocompatibility, water-based processing, and...