The over-expression of Polo-like kinase 1(Plk1)is critical in the producing and progressing of multi-ple human tumors and is recognized as an effective target for the development of novel anti-cancer drugs.Currently a variety of small molecules targeting ATP or substrates binding sites have entered different stages of clinical trials.Polo-box domain(PBD)is a unique domain of Plks which plays an important role in the sub-cellular location of Plks and also in the recognition of their substrates,therefore it has become an attractive target for the development of novel target-directed Plk1 inhibitors.In this paper,PBD function of Plk1 was intro-duced,the progress of small molecule and phosphoserine /phosphothreonine contained short peptide Plk1 inhibi-tors targeting PBD was summarized.Further development of this kind of inhibitors was also proposed.

AIM: To investigate the binding characteristics of cholecystokinin receptors in rat pulmonary interstitial macrophages (PIMs). METHODS: The PIMs were isolated from rat lung tissues, purified using the collagenase digestion method combined with alveolar lavage and pulmonary vessel perfusion. The PIM membrane was obtained by supercentrifuge. Receptors for CCK in PIMs were examined using [~3H] labeled CCK-8S as ligand. The specificity of [~3H]-CCK-8S binding to PIMs membrane and the subtypes of CCK receptors were determined by competitive inhibition experiments with CCK-8S, CCK-A and CCK-B receptors selective antagonists (CR1409 and CR2945). The effects of time and incubation temperature on the specific binding were also observed. RESULTS: The specific binding of [~3H]-CCK-8S was not detected in normal rat PIMs, but was detected in the rat administrated with LPS for 48 h. The capacity of ligand-receptor binding was dependent on the incubation temperature and time. Scatchard analysis of the saturation curves suggested that the presence of CCK receptors with high affinity [Kd=(0.68?0.28)mmol/L] and low binding capacity [Bmax=(32.50?2.70) pmol?g~(-1) protein] in PIMs. By means of competitive inhibition studies, the specific binding of [~3H]-CCK-8S to rat PIMs was inhibited by unlabelled CCK-8S [IC_(50)=(3.20?1.13) nmol/L], CCK-AR specific antagonist CR 1 409 [IC_(50)=(0.19?0.06)?mol/L] and CCK-BR specific antagonist CR 2945[IC_(50)=(2.30?0.80)nmol/L]. CONCLUSION: These results suggest the presence of two subtypes of CCK-AR and CCK-BR and provide a structural basis for CCK to play a pivotal role in PIMs.

OBJECTIVETo study the correlation between the expression levels of phagocytic NADPH oxidase p22phox subunit and left ventricular mass index (LVMI) in patients with non-valvular chronic heart failure and explore the role of oxidative stress caused by NADPH oxidase p22phox subunit in left ventricular remodeling.

METHODSSemi-quantitative RT-PCR was used to examine the expression levels of phagocytic NADPH oxidase p22phox in 59 patients with non-valvular chronic heart failure and 20 control subjects. All the subjects underwent ultrasonic cardiography to record their IVST, LVPWT, LVEDd, LVEDs, and EF. Based on the calculated LVMI, the patients were divided into heart failure without LV hypertrophy (LVH) group and heart failure with LVH group.

RESULTSThe patients with heart failure showed significantly higher expression of phagocytic NADPH oxidase p22phox than the control subjects (0.91∓0.37 vs 0.68∓0.33, P=0.039), and the patients with LVH had significantly higher p22phox expression than those without LVH (1.58∓0.20 vs 0.71∓0.24, P=0.026). LVMI showed a positive correlation with the expression of p22phox in these patients (r=0.508, P<0.05).

CONCLUSIONNADPH oxidase p22phox expression level is positively correlated with LVMI and can be indicative of the level of left ventricular remodeling in patients with non-valvular chronic heart failure.

Adult ; Aged ; Case-Control Studies ; Female ; Heart Failure ; metabolism ; physiopathology ; Humans ; Hypertrophy, Left Ventricular ; metabolism ; physiopathology ; Male ; Middle Aged ; NADPH Oxidases ; metabolism ; Ventricular Remodeling

OBJECTIVETo explore beryllium oxide induced oxidative lung injury and the protective effects of LBP.

METHODSIntoxication of animals were induced by once intratracheal injection and LBP intervention by intragastric administration. The content of HIF-1, VEGF and HO-1 of lung tissues were measured by kits. The pathological changes of lung tissue were showed by pathological section. The changes of lung ultrastructure were observed by electron microscope.

RESULTSPathological changes of the lung tissue in beryllium oxide exposure group rats were in line with the characteristics of beryllium disease in human. Compared with the control group, HO-1 was increased in beryllium oxide exposure 40 d group and low doses of LBP group, compared with the control group, HO-1 was increased in beryllium oxide exposure 80d group and LBP treatment groups (P < 0.05 or P < 0.01). Compared with the control group, HIF-1 was increased in beryllium oxide exposure 40 d group, LBP treatment groups, beryllium oxide exposure 60 d and 80 d groups (P < 0.05 or P < 0.01). Compared with the control group, VEGF was increased of all phases, especially in beryllium oxide exposure 40d and 80 groups, LBP treatment groups and beryllium oxide exposure 60 d (P < 0.05 or P < 0.01). The content of HO-1 of beryllium oxide exposure group was higher than the LBP treatment for 40d group but below LBP treatment for 80 d group (P < 0.05). The content of HIF1 of beryllium oxide exposure group was higher than high dose of LBP treatment for 60d group and LBP treatment for 80 d group (P < 0.01). The content of VEGF of beryllium oxide exposure group was higher than LBP treatment for 40 d group and high dose of LBP treatment for 60 d (P < 0.05 or P < 0.01).

CONCLUSIONSBeO can cause abnormal expression of related genes of lung tissue in rats, LBP has protective effects on BeO caused lung injury.

Acute Lung Injury ; chemically induced ; physiopathology ; Acute-Phase Proteins ; pharmacology ; Animals ; Beryllium ; toxicity ; Carrier Proteins ; pharmacology ; Heme Oxygenase (Decyclizing) ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Lung ; drug effects ; pathology ; Membrane Glycoproteins ; pharmacology ; Oxidative Stress ; Protective Agents ; pharmacology ; Rats ; Vascular Endothelial Growth Factor A ; metabolism