Neprilysin(NEP)is a type Ⅱ integral membrane glycoprotein of the M13 zinc metalloprotease family．As a neuropeptide degrading enzyme,NEP has been discovered to possess an increasing amount of organ-specific functions from central nervous system to peripheral tissues since it was fimfly identified in 1974．For example,NEP has been shown to have an anti-tumour effect by inhibition of cell migration and proliferation while induction of an programmed cell death dependent of both its enzymatic activity and direct protein-protein interactions with key molecules involved in signal transduction pathways:NEP Was also implicated to have neuropmtective effect by preventing the accumulation of the neurotoxic amyloid β-peptide (Aβ)in brain．Through investigating the progression of various human diseases,impaired NEP expression and activity were found to occur frequently．Based on these findings,modulation of NEP levels in pathological cells is considered to be therapeutically applicable as a strategy to recover normal cell functions and thereafter relieve symptoms of diseases．Great research effort is being contributed to the study of regulatory mechanisms involved in expression and activity of this enzyme,and a number of encouraging results have already been achieved．Besides androgens,well-recognised regulators of NEP transcription in prostate,the female hormone oestrogen,aqueous extract of willow herb,components of green tea and neuropeptides bombesin,somatostatin as well as the intracellular domain of amyloid precursor protein were all shown to have a stimulatory effect on NEP expression and／or its activity．

OBJECTIVETo explore the possible mechanism of curcumin in inducing the apoptosis of breast cancer cell MDA-MB-231.

METHODCurcumin of different concentrations at 0, 10 25, 50, 100, 150, 200 micromol x L(-1) were used to intervene breast cancer cells MDA-MB-231 for 24 hours. MTT was used to observe its effect on the proliferation of breast cancer cells. The flow cytometry was used to detect its effect on the cell apoptosis. The real-time quantitative PCR and Western blot was used to assess the expression levels of GRP78 and CHOP in breast cancer cells.

RESULTCurcumin could inhibit the proliferative ability of breast cancer cells by inducing them in a concentration-dependent manner. Curcumin could significantly increase the expression levels of GRP78 and CHOP in breast cancer cells.

CONCLUSIONCurcumin could induce the apoptosis of breast cancer cells MDA-MB-231 by activating endoplasmic reticulum stress.

Apoptosis ; drug effects ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Curcumin ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Endoplasmic Reticulum Stress ; drug effects ; Female ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Transcription Factor CHOP ; genetics ; metabolism

Diversity-oriented synthesis (DOS) aims to efficiently generate collections of small molecules with diverse appendages, functional groups, stereochemistry and skeletons, thus yielding diverse biological activities capable of modulating a wide variety of biological processes. In this review, we discussed the common strategies employed in DOS with specific examples from recent literature, including reagent-based approach, substrate-based approach, build-couple-pair strategy and privileged substructure-based DOS. The application of some DOS libraries in drug discovery is also presented.
Drug Design ; Drug Discovery ; Small Molecule Libraries

In order to quickly and accurately identify the onset and offset of the QRS complex in electrocardiogram (ECG) signal with different forms, a triple local transform method was employed in the present study to detect the suspected onset and offset points of QRS. The accurate onset and offset points of QRS complexes were selected according to the rules drawn by the trial process based on the characteristics of angle and amplitude constituted within these suspected points. The method makes full advantage of the angle and amplitude characteristics of the QRS complex, by which the results can be acquired with some simple arithmetic quickly, accurately and adaptively. The method was investigated with data from the MIT-BIH arrhythmia database and satisfactory results were obtained.
Algorithms ; Arrhythmias, Cardiac ; diagnosis ; Databases, Factual ; Electrocardiography ; Humans ; Signal Processing, Computer-Assisted

Embryonic Stem Cells ; Humans ; Myocardial Infarction ; therapy ; Stem Cell Transplantation

Arrhythmogenic Right Ventricular Dysplasia ; complications ; Autopsy ; Cardiomyopathy, Hypertrophic ; complications ; Cause of Death ; Coronary Disease ; complications ; Coronary Vessel Anomalies ; complications ; Death, Sudden, Cardiac ; etiology ; pathology ; Humans

BACKGROUND:Platelet-derived growth factor has the ability of wound repair, and relevant studies mainly focus on bone tissue repair. However, there are less studies about the effect of platelet-derived growth factors in skin wound healing. OBJECTIVE:To investigate the role of platelet-derived growth factor to promote wound healing by the regulation of bone marrow mesenchymal stem cels to the wound. METHODS:Bone marrow mesenchymal stem cels from rats were cultured. Immunofluorescence method was conducted to detect cel surface markers of CD34 and CD44 in bone marrow mesenchymal stem cels. Thirty healthy male SD rats were divided into five groups at random. Bone marrow mesenchymal stem cels labeled with PKH-26 were injected into the rat caudal vein in each group. The rats were anesthetized 1 week after injection. On the center of rat back, a 3-cm incision was made to establish a wound healing model. Different concentrations of platelet-derived growth factor were injectedvia multi-points on the skin wound after modeling, and the control group was treated with the same volume of normal saline. Skin wound tissues were taken for relevant parameter measurement at 14 days after injection. RESULTS AND CONCLUSION: Under the fluorescence microscope, platelet-derived growth factor could induce the migration and accumulation of bone marrow mesenchymal stem cels to the trauma in a dose-dependent manner and promote the wound healing. Masson staining showed that, with the concentration increase, platelet-derived growth factors could reduce inflammatory cel infiltration and increase the number of colagen fibers. Results from western blot assay showed that platelet-derived growth factor could inhibit the expression of matrix metaloproteinase-1, promote the expression of tissue inhibitor of matrix metaloproteinase 1 in the wound, and inhibit the colagen degradation, thereby promoting skin wound healing indirectly.

0.01). Conclusion: Occlusal reduction might diminish the rate of postoperative pain following endodontic instrumentation.

ObjectiveTo find out the prevalence of brucellosis in Baotou,and to provide a scientific basis for integrated control of brucellosis.MethodIn 2010,high-risk people 7 to 70 years of age engaged in livestock farming,grazing,slaughtering,processing and selling were investigated in 9 districts (banners,counties)of Baotou city.In accordance with the principle of informed consent,blood samples were collected,serum titer was tested using the rose bengal agglutination test and tube agglutination test(SAT),and serum titer of 1:100(+ +) was considered as positive brucellosis,and results were evaluated based on brucellosis monitoring standards(GB 16885-1997).ResultsA total of 5832 copy blood samples were collected,and 250 cases were tested positive,the positive rate was 4.25％.The number of new cases was 164,accounting for 2.81％ (164/5832).Age was mainly concentrated in the 40 to 60 years,accounting for 66.0％(165/250).Brucellosis infection in the livestock industry accounted for 80.87％ (4757/5882).From the regional distribution,DAMAOQI had the most detected cases,and the detection rate was 12.10％ (73/603).ConclusionsContinue to increase the brucellosis prevention knowledge propaganda,carry out brucellosis surveillance of high-risk people,quarantine,and strengthen immunity is the only measure of effective control of brucellosis epidemic.

Objective To understand the arsenic level in drinking water and the current situation in prevention and control of endemic arsenic poisoning in Tuyouqi,Baotou of Inner Mongolia.Methods Through door-to-door survey,we selected patients with arsenic poisoning in order to monitor the arsenic poisoning condition of seven villages(Gangfangying,Laohuyao,Shilaozhang,Youfangying,Wanglaosi,Dajing and Xiaojing) in Tuyouqi,Baotou in 2010,and the disease was diagnosed based on Standard of Diagnosis for Endemic Arsenism(WS/T 211-2001).We also investigated the operation of Salaqi Water Company,Maodai Water Company and the Laohuyao water improvement project.We collected two samples per place in both low water period and high water period to measure water arsenic with silver diethyldithiocarbamate spectrophotometry(WS/T 28-1996).Results Three water improving projects were operating in normal conditions.Water arsenic in Salaqi Water Company and Maodai Water Company was level less than 0.01 mg/L,which met the National Safety Standards of drinking water with arsenic.Water arsenic in Laohuyao improvement project was 0.053 mg/L,which was higher than the drinking water safety standards.The seven villages in Tuyouqi had improved their water conditions.Among them,the arsenic level in Laohuyao was 0.052 mg/L,and the remaining six villages were ＜ 0.05 mg/L.There were 6 suspected cases,14 mild cases,4 moderate cases and 10 severe cases of the 2095 people monitored and no new cases found.The age of patients with arsenic poisoning was in the range of 40 to 70.Conclusions The monitoring results show that drinking water arsenic level in some villages in Tuyouqi is still excessive,but no new arsenic poisoning patients in arsenic poisoning areas are found.