This paper is to report the study of the pharmacokinetics of a fusion protein TAT-haFGF(14-154) for human acidic fibroblast growth factor and transcriptional activator protein in rat plasma, and the investigation of their penetration across blood-brain barrier in mice and rats, in order to provide a basis for clinical development and treatment of Alzheimer's disease. Enzyme-linked immunosorbent assay (ELISA) was used to determine concentration of TAT-haFGF(14-154) in rat plasma and in mouse brain homogenate; and immunohistochemistry was used to analyze the distribution in brain. The concentration-time curve fitted two-compartment open model which was linear kinetics elimination after a single intravenous injection of TAT-haFGF(14-154) in rat at the dose of 300 microg x kg(-1). The half life time was 0.049 +/- 0.03 h for distribution phase and 0.55 +/- 0.05 h for elimination phase, and the weight was 1/C2. The result showed that TAT-haFGF(14-154) could be detected in the brain by ELISA and immunohistochemistry, the elimination of TAT-haFGF(14-154) in rat was swift, and TAT-haFGF(14-154) could penetrate across the blood-brain barrier, distribute in pallium and hippocampus and locate in the nucleus.

AIM: To observe the effects of the human acidic fibroblast growth factor mutant (mhaFGF), lacking 27 amino acids at N-terminal, on the proliferation and signal transduction of the hepatocarcinoma cells. METHODS: The hepatocarcinoma cells were treated with human acidic fibroblast growth factor (haFGF) and mhaFGF, respectively. The expression levels of the signal proteins, Grb2 and Erk1/2, in the hepatocarcinoma cells were detected by semi-quantitative Western-blotting after treated for 15 min. The mitogenic activity of both haFGF and mhaFGF was detected by MTT method and the cell cycle was analysed by flow cytometer (FCM) after treated for 48 h. RESULTS: The mitogenic activity and the ratio of G 1 and S phase cells in mhaFGF-treated cells were markedly lower than that of the haFGF, and close to that of the control group. The expression level of both Grb2 and Erk1/2 in the mhaFGF-treated cells were lower than those in the haFGF- treated cells. CONCLUSION: The decrease in the mitogenic activity of mhaFGF is probably associated to its down-regulating the expression of the signal molecular, MAPK-ERK1/2 and Grb2.

Background: Livin, survivin and Pak-1 are all related to the occurrence and development of gastric cancer. Livin and survivin play their roles by inhibiting the activity of caspase-7. Aims: To investigate the expressions and significance of livin, survivin, Pak-1 and caspase-7 in different gastric mucosal lesions. Methods: A total of 45 cases of gastric cancer and paracancerous tissue, 45 chronic atrophic gastritis with intestinal metaplasia, 45 chronic non-atrophic gastritis from Jan. 2015 to Dec. 2019 at the Second Affiliated Hospital of Baotou Medical College were collected. Immunohistochemistry was used to detect the expressions of livin, survivin, Pak-1 and caspase-7, and their correlations with clinicopathological features of gastric cancer patients were analyzed. Results: Compared with chronic non-atrophic gastritis group and paracancerous group, the positivity expression rates of livin, survivin and Pak-1 in intestinal metaplasia group were significantly increased (P<0.05), while caspase-7 was significantly decreased (P<0.05). Compared with intestinal metaplasia group, the positivity expression rates of livin, survivin and Pak-1 in gastric cancer group were significantly increased (P<0.05), while caspase-7 was significantly decreased (P<0.05). Expressions of livin, survivin, Pak-1 and caspase-7 were correlated with the differentiation degree, TNM stage, depth of infiltration and lymph node metastasis in patients with gastric cancer (P<0.05). Conclusions: Livin, survivin, Pak-1 and caspase-7 play important roles in the occurrence and development of gastric cancer.

G protein-coupled receptors (GPCRs) are a large family of membrane protein receptors, and Takeda G protein-coupled receptor 5 (TGR5) is a member of this family. As a membrane receptor, TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism, including the processes of energy consumption, weight loss and blood glucose homeostasis. Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver, obesity and diabetes. With the global obesity situation becoming more and more serious, a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed. In this review, we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target, and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands, which can effectively provide new ideas for ligand research and promote drug research.