Fbx4蛋白质及其研究进展

泛素介导的蛋白降解途径参与了许多生物学过程.SCF复合体是一种非常重要的E3 泛素连接酶,F-box蛋白是SCF复合体的一个亚基,Fbx4蛋白是众多F-box蛋白中的一种,是底物特异性识别SCF Fbx4/αβ-crystallin酶的重要组成部分,Fbx4蛋白失活或表达水平改变影响SCFFbx4/αβ-crystallin酶活性,从而影响细胞周期蛋白D1的表达水平.同时Fbx4蛋白还是端粒长度调节的一个重要调控因子.     

Hippo pathway monomerizes STAT3 to regulate prostate cancer growth

Prostate cancer ranks among the most commonly diagnosed malignancies for men and has become a non‐negligible threat for public health. Interplay between inflammatory factors and cancer cells renders inflammatory tissue environment as a predisposing condition for cancer development. The Hippo pathway is a conserved signaling pathway across multiple species during evolution that regulates tissue homeostasis and organ development. Nevertheless, whether Hippo pathway regulates cancer‐related inflammatory factors remains elusive. Here, we show that high cell density–mediated activation of the Hippo pathway blunts STAT3 activity in prostate cancer cells. Hippo pathway component MST2 kinase phosphorylates STAT3 at T622, which is located in the SH2 domain of STAT3. This phosphorylation blocks the SH2 domain in one STAT3 molecule to bind with the phosphorylated Y705 site in another STAT3 molecule, which further counteracts IL6‐induced STAT3 dimerization and activation. Expression of a nonphosphorylatable STAT3 T622A mutant enhances STAT3 activity and IL6 expression at high cell density and promotes tumor growth in a mice xenograft model. Our findings demonstrate that STAT3 is a novel phosphorylation substrate for MST2 and thereby highlight a regulatory cascade underlying the crosstalk between inflammation and the Hippo pathway in prostate cancer cells.     

IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells

Neurokinin 2 receptor (NK2R), a G protein‐coupled receptor for neurokinin A (NKA), a tachykinin family member, regulates various physiological functions including pain response, relaxation of smooth muscle, dilation of blood vessels, and vascular permeability. However, the precise role and regulation of NK2R expression in cancer cells have not been fully elucidated. In this study, we found that high NK2R gene expression was correlated with the poor survival of colorectal cancer patients, and Interferon (IFN‐α/β) stimulation significantly enhanced NK2R gene expression level of colon cancer cells in a Janus kinas 1/2 (JAK 1/2)‐dependent manner. NKA stimulation augmented viability/proliferation and phosphorylation of Extracellular‐signal‐regulated kinase 1/2 (ERK1/2) levels of IFN‐α/β‐treated colon cancer cells and NK2R blockade by using a selective antagonist reduced the proliferation in vitro. Administration of an NK2R antagonist alone or combined with polyinosinic‐polycytidylic acid, a synthetic analog of double‐stranded RNA, to CT26‐bearing mice significantly suppressed tumorigenesis. NK2R‐overexpressing CT26 cells showed enhanced tumorigenesis and metastatic colonization in both lung and liver after the inoculation into mice. These findings indicate that IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells, suggesting that NK2R blockade may be a promising strategy for colon cancers.     

蒙药砂蓝刺头定性与定量质量控制方法研究

目的建立砂蓝刺头Echinops gmelini的质量控制方法。方法采用薄层色谱法,以三氯甲烷-醋酸乙酯-甲醇-甲酸(6∶1∶1∶0.8)为展开剂对砂蓝刺头花中1-甲基-4-甲氧基-8-(β-D-葡萄吡喃型糖苷)-2(1H)-喹啉酮(MMQ)进行定性鉴别;建立砂蓝刺头HPLC指纹图谱,并对MMQ的含量测定方法进行研究。结果建立的TLC方法对照品斑点清晰,分离度好;建立的指纹图谱分析方法能够区分砂蓝刺头与近源植物,标定了8个特征峰,并指认出其中4个成分。定量方法测定结果显示MMQ在2.024~151.800μg/mL呈良好线性关系,平均加样回收率为101.54%,RSD为1.46%。7批样品中MMQ的质量分数为0.13%~0.53%。结论建立的质量控制方法科学、可靠,可为砂蓝刺头质量标准的建立提供实验依据。     

当归红芪超滤膜提取物对阿霉素致心肌细胞凋亡的影响

目的:研究当归红芪超滤膜提取物(UFE-AH)对阿霉素所致心肌细胞凋亡的影响.方法:取新生1～2d的Wistar乳鼠,用差速贴壁法原代提取心肌细胞,调整细胞密度1×106/mL,于37℃5％ CO2培养箱中密闭培养48 h.用2.5 mg·L-1阿霉素作用于心肌细胞24 h成功建立心肌细胞凋亡模型.实验分5组:正常对照组、阿霉素组(2.5 mg·L-1)、UFE-AH低、中、高剂量干预组(阿霉素造模前2h预先分别给予3.75,7.5,15 g·L-1当归红芪超滤膜提取物).四氮唑蓝(MTT)法检测各组细胞生长抑制率,单细胞凝胶电泳检测DNA损伤,Western blot(蛋白印迹法)检测B淋巴细胞瘤-2蛋白(Bel-2),Bel-2相关X蛋白(Bax)表达水平.结果:与正常组相比,阿霉素组心肌细胞生长抑制率明显增加,且头部DNA含量占总含量的百分数(HDNA％),尾部DNA含量占总含量的百分数(TDNA％),尾长(TL),尾短(TM),尾距(OTM)均明显升高,Bcl-2蛋白表达水平下降、Bax表达水平升高,均有统计学意义(P＜0.01);UFE-AH干预组的心肌细胞生长抑制率明显降低,且HDNA％,TDNA％,TL,TM,OTM数值均降低,Bcl-2蛋白表达水平上调,Bax表达水平下调,有显著性差异(P＜0.01).结论:UFE-AH可减轻阿霉素对心肌细胞DNA的损伤,上调Bcl-2/Bax而抑制心肌细胞的凋亡,具有抗心肌细胞凋亡的保护作用.     

黄芪注射液对2型糖尿病患者血管功能及微循环状态的影响

目的:探讨黄芪注射液对2型糖尿病患者血管功能及微循环状态的影响。方法:将2型糖尿病患者70例根据随机分配方式分为对照组(常规西药治疗组)和观察组(常规西药治疗加黄芪注射液组)各35例,观察2组患者治疗前及治疗后1个疗程、2个疗程的脉搏波传导速度、血清ET-1、血液黏度及血小板活化指标变化情况。结果:观察组治疗后1个疗程、2个疗程的脉搏波传导速度、血清ET-1、血液黏度及血小板活化指标均低于对照组(P0.05)。结论:黄芪注射液对2型糖尿病患者的脉搏波传导速度、血清ET-1、血液黏度及血小板活化状态影响较大,因此对患者血管功能及微循环状态的改善发挥着积极作用。     

针刺对实验性2型糖尿病作用机理的研究进展

对2型糖尿病机理的研究越来越受到人们的关注.本文就针刺对实验性2型糖尿病作用机理的进展情况从胰岛素抵抗、阿片肽、胰岛组织形态学、机体内环境四个方面进行了综述,并指出不足之处和提出了该领域的研究方向.     

基质金属蛋白酶-9与结直肠癌

基质金属蛋白酶（MMP）能够降解细胞外基质,对肿瘤生长、侵袭和扩散至关重要。作为MMP 家族中相对分子质量最大的,MMP-9参与结直肠癌的生成和进展。研究显示 MMP-9可用于结直肠癌患者的早期诊断,组织和血浆中 MMP-9表达水平与结直肠癌患者术后预后呈负相关。另外,针对MMP-9在结直肠癌组织中表达增加这一特点可设计相关的靶向治疗药物。