靶向结直肠癌Wnt信号通路的药物研究进展

结直肠癌是胃肠道中常见的恶性肿瘤,临床上具有发病率高和死亡率高的特点.在结直肠癌细胞的胞浆、胞核内常伴有Wnt信号通路中β-catenin等信号分子的异常表达.不同种类的靶向苗头化合物可作用于Wnt信号通路或其上下游相关信号分子,从而抑制或减缓结直肠癌的发生和发展.本文通过对Wnt信号通路成分及Wnt信号通路与结直肠癌...     

Discovery of Cellular RhoA Functions by the Integrated Application of Gene Set Enrichment Analysis

The small GTPase RhoA has been studied extensively for its role in actin dynamics. In this study, multiple bioinformatics tools were applied cooperatively to the microarray dataset {"type":"entrez-geo","attrs":{"text":"GSE64714","term_id":"64714"}}GSE64714 to explore previously unidentified functions of RhoA. Comparative gene expression analysis revealed 545 differentially expressed genes in RhoA-null cells versus controls. Gene set enrichment analysis (GSEA) was conducted with three gene set collections: (1) the hallmark, (2) the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and (3) the Gene Ontology Biological Process. GSEA results showed that RhoA is related strongly to diverse pathways: cell cycle/growth, DNA repair, metabolism, keratinization, response to fungus, and vesicular transport. These functions were verified by heatmap analysis, KEGG pathway diagramming, and direct acyclic graphing. The use of multiple gene set collections restricted the leakage of information extracted. However, gene sets from individual collections are heterogenous in gene element composition, number, and the contextual meaning embraced in names. Indeed, there was a limit to deriving functions with high accuracy and reliability simply from gene set names. The comparison of multiple gene set collections showed that although the gene sets had similar names, the gene elements were extremely heterogeneous. Thus, the type of collection chosen and the analytical context influence the interpretation of GSEA results. Nonetheless, the analyses of multiple collections made it possible to derive robust and consistent function identifications. This study confirmed several well-described roles of RhoA and revealed less explored functions, suggesting future research directions.     

银杏叶提取物对青春期乏运动大鼠行为学的影响

目的 探讨银杏叶提取物对青春期乏运动大鼠行为学的影响及其可能机制.方法 将24只4周龄SD雄鼠随机分为正常对照组(NC)、乏运动组(AS)以及银杏叶提取物处理组(GBE),干预性饲养至8周龄,进行旷场实验及高架十字迷宫实验检测行为学改变.比色法检测脑组织匀浆丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性.Weste...     

Suchilactone inhibits the growth of acute myeloid leukaemia by inactivating SHP2

ContextSuchilactone, a lignan compound extracted from Monsonia angustifolia E.Mey. ex A.Rich. (Geraniaceae), has little research on pharmacological activity; whether suchilactone has inhibitory effect on acute myeloid leukaemia (AML) is unclear.ObjectiveTo investigate the antitumor effect of suchilactone and its mechanism in AML.Materials and methodsThe effects of suchilactone on cell growth were detected by CCK-8 and flow cytometry. Network pharmacology was conducted to explore target of suchilactone. Gene expression was detected by western blot and RT-PCR. SHI-1 cells (1 × 10⁶ cell per mouse) were subcutaneously inoculated into the female SCID mice. Suchilactone (15 and 30 mg/kg) was dissolved in PBS with 0.5% carboxymethylcellulose sodium and administered (i.g.) to mice once a day for 19 days, while the control group received PBS with 0.5% carboxymethylcellulose sodium. Tumour tissues were stained with Ki-67 and TUNEL.ResultsSuchilactone exerted an effective inhibition on the growth of SHI-1 cells with IC₅₀ of 17.01 μM. Then, we found that suchilactone binds to the SHP2 protein and inhibits its activation, and suchilactone interacted with SHP2 to inhibit cell proliferation and promote cell apoptosis via blocking the activation of SHP2. Moreover, Suchilaction inhibited tumour growth of AML xenografts in mice, as the tumour weight decreased from 0.618 g (control) to 0.35 g (15 mg/kg) and 0.258 g (30 mg/kg). Suchilactone inhibited Ki-67 expression and increased TUNEL expression in tumour tissue.Discussion and conclusionsOur study is the first to demonstrate suchilactone inhibits AML growth, suggesting that suchilactone is a candidate drug for the treatment of AML.     

炎症微环境作用下BMPs-ERK5信号通路对牙周膜干细胞成骨分化的影响

目的 探讨炎症微环境作用下骨形态发生蛋白-细胞外信号调节激酶5(Bone morphogenetic proteins-extracellular signal-regulated kinase 5,BMPs-ERK5)信号通路对人牙周膜干细胞(Human periodontal ligament stem cells...     

AT1 receptor downregulation: A mechanism for improving glucose homeostasis

There is a pathophysiological correlation between arterial hypertension and diabetes mellitus, established since the pre-diabetic state in the entity known as insulin resistance. It is known that high concentrations of angiotensin-Ⅱ enable chronic activation of the AT1 receptor, promoting sustained vasoconstriction and the consequent development of high blood pressure. Furthermore, the chronic activation of the AT1 receptor has been associated with the development of insulin resistance. From a m...     

Prediction of return of spontaneous circulation in out-of-hospital cardiac arrest with non-shockable initial rhythm using point-of-care testing: a retrospective observational study

BACKGROUND:Out-of-hospital cardiac arrest(OHCA) is a public health concern, and many studies have been conducted on return of spontaneous circulation(ROSC) and its prognostic factors.Rotational thromboelastometry(ROTEM^?), a point-of-care testing(POCT) method, has been useful for predicting ROSC in patients with OHCA, but very few studies have focused on patients with non-shockable rhythm. We examined whether the parameters of POCT could predict ROSC in patients with OHCA and accompany...     

Tetramethylpyrazine inhibits the proliferation,invasiveness and migration of cervical cancer C33A cells by retarding the Hedgehog signaling pathway

Cervical carcinoma (CC) ranks among the top four most common cancers in women worldwide. Over the last 10 years, several studies have confirmed the inhibitory effects of tetramethylpyrazine (TMP) on numerous types of cancer. To investigate the inhibitory effect of TMP on the CC C33A cell line, MTT and colony formation assays were performed to determine how TMP affects C33A cell survival and proliferation. Proliferation-, migration- and hedgehog (Hh) signaling pathway-related protein expression levels were analyzed via western blotting. Wound-healing and Transwell assays were used to detect the migration and invasion abilities of C33A cells, respectively. The results indicated that TMP markedly reduced the C33A cell survival rate compared with the cervical epithelial Ect1 cell line, which was unaffected by TMP treatment. C33A cell proliferation was downregulated by TMP treatment in a dose-dependent manner. TMP treatment also significantly inhibited C33A cell migration and invasiveness in a dose-dependent manner. Furthermore, TMP inhibited the Hh signaling pathway, as demonstrated by a dose-dependent reduction in Hh-related protein expression levels following TMP treatment. Subsequently, treatment with smoothened agonist increased the proliferation, invasiveness and migration abilities of TMP-treated C33A cells. In conclusion, TMP inhibited the proliferation, migration and invasiveness of CC cells via inhibition of the Hh signaling pathway.