Animals ; Antigens, CD ; metabolism ; Cell Movement ; Cell Proliferation ; Endoglin ; Genetic Therapy ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Neoplasms ; pathology ; therapy ; Receptors, Cell Surface ; metabolism ; Thy-1 Antigens ; metabolism ; Vascular Cell Adhesion Molecule-1 ; metabolism

Animals ; China ; epidemiology ; Enterovirus A, Human ; genetics ; physiology ; Enterovirus Infections ; epidemiology ; metabolism ; virology ; Humans ; Receptors, Virus ; genetics ; metabolism

This article proposes the "Efficacy Theory" hypothesis of the traditional Chinese medicines (TCMs): TCMs take effects and weaken toxicities through the additive effects of numerous effective forms (including their constituents or/and metabolites) on a same target, the synergistic effects based on the overall action of the additive effects on individual targets and their toxicities scattering effects. A TCM may include approximately 1000 constituents and each constituent may produce about 100 metabolites in vivo after oral administration. Numerous effective forms of incalculable constituents and their metabolites could work like a "army group" together. When the quantity of a specific target molecule is larger than the pharmaceutical molecules, the molecules of different kinds of effective forms could combine with the target molecules successively, to exert the additive effects. When the target molecules are mostly occupied ("target most spaces occupied"), this TCM begins to work. The additive effects maybe exert not only in concentration but also in a time order way, which gives a sustained efficacy of TCM. The additive effects and the toxicities scattering effects are resulted from the same effective groups and not identical toxic groups among different effective form molecules. The "toxicities scattering effect" can be used to explain the non-toxic TCMs, but not fit for toxic TCMs. The efficacy theory showed that the variety of constituents and metabolites may participate in the process of pharmacodynamic actions, including the additive effects, synergy effects and toxicities scattering effects, which may be useful for explaining and developing the characteristic advantage of the TCMs. The questions we need to study or confirm are as follows: What are the TCMs' pharmacodynamic substance basis and mechanism made up of Why are toxicities of most TCMs' smaller How is the TCMs' "Efficacy Theory" which reflects characteristic advantage of TCMs applied in the research and development of new drugs.
Animals ; Drug Therapy ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Medicine, Chinese Traditional ; Pharmaceutical Preparations ; chemistry

OBJECTIVETo evaluate the effect and safety of Nuanxin Capsule (NXC) in treating patients with chronic heart failure (CHF).

METHODSAdopting the randomized, positive controlled, double-blinded design, 150 CHF patients were assigned to the treatment group and the control group equally, they were treated with optimal western medical therapeutic scheme in combining respectively with NXC and placebo for 24 weeks. The indices for effectiveness and safety evaluation, such as Chinese medicine syndrome, grade of heart function, myocardial contraction, as well as the re-hospitalization rate and mortality, were observed.

RESULTSThe total effective rate on heart function in the treatment group and the control group was 78.87% and 64.38% respectively, that on Chinese medicine syndrome was 85.9% and 63.0% respectively, comparisons of the two indices between the two groups all showed significant difference (P < 0.05, P < 0.01). And a better efficacy for improving patients' cardiac contraction function and quality of life was shown in the treatment group (P < 0.05, P < 0.01). The re-hospitalization rates in them were 23.9% and 53.4% respectively (P < 0.05), and 22.54% and 42.5% of the re-hospitalized patients had attack of acute heart failure, a significant difference was found between the two groups (P < 0.05). The mortality in them was 2.90% and 8.95% respectively, showing no significant difference between groups (P > 0.05). No obvious adverse effect was found in both groups.

CONCLUSIONSNXC could improve the heart function of patients, it has obvious curative effect and good safety in treating chronic heart failure.

Aged ; Aged, 80 and over ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart Failure ; drug therapy ; Humans ; Male ; Middle Aged ; Phytotherapy ; Treatment Outcome

Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.
Antineoplastic Agents ; Benzamides ; chemistry ; DNA Repair ; Drug Design ; Humans ; Molecular Docking Simulation ; Poly(ADP-ribose) Polymerase Inhibitors ; chemical synthesis ; chemistry ; Poly(ADP-ribose) Polymerases

Child ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Objective To observe the status of oxidative stress and activity of alkaline phosphatase(ALP) in rats exposed to high fluoride for the different periods and to analyze the effect of fluoride on the activity of ALP and oxidative stress in fluorosis rats. Methods Twenty-four Wistar rats were divided into control and high-fluoride groups according to their body mass, 12 rats in each group. The control group drank tap water(sodium fluoride concentrations < 1 mg/L), and high-fluoride group drank tap water containing sodium fluoride(sodium fluoride concentrations 221 mg/L). On a standard diet and water available ad hbitum, each rat was measured body weight once a week in 1,4,8,12 week. The biochemical techniques were used to test the indicators of oxidative stress including malonaldehyde(MDA), superoxidedismutase(SOD), glutathione peroxidase(GPx), uric acid and activity of ALP in serum of fluorosis rats. Results There was a interaction between fluoride and time in the activity of ALP (F = 4.690,P < 0.05). The activity of ALP was obviously higher in rats exposed to fluoride for 1,12 week [ (19.29± 3.69), (15.72 ± 0.79)kU/L] compared to the control[ (14.08 ± 1.99),(12.91 ± 3.97)kU/L, all P< 0.05] ; the level of MDA was obviously higher in rats exposed to fluoride for 1,4 week [ ( 13.37 ± 4.38 ), ( 11.82 ± 2.08) μmol/L ] compared to the respective control[ (8.75 ± 3.24), (7.42 ± 2.62)μmol/L, all P < 0.05]; difference of SOD and GPx between control and high-fluoride groups was not statistically significant(all P > 0.05); the level of uric acid in serum was significantly higher in high-fluoride group for 1,4 week[ (89.53 ± 13.21 ), (88.47 ± 19.78 )μmol/L] compared to the control [ (77.79 ± 11.43 ), (65.42 ± i 3.42) μ mol/L, all P < 0.05 ], but the level of uric acid showed lower in high-fluoride group for 8,12 week [(67.21 ± 9.44), (73.95 ± 9.52)μmol/L] compared to the control [(77.79 ± 11.43), (65.42 ± 13.42)μmol/L]. Conclusions Effect of overdose fluoride on ALP is time-dependant. On the other hand,overdose fluoride stimulates the status of oxidative stress in a way unrelated to the exposure period.

Objective To investigate the changes of plasma adrenomedullin(ADM),endothelin-1(ET-1) in infants with severe pneumonia complicated by acute congestive heart failure,and its relationship with heart function.Methods Forty-seven bronchopneumonia patients in their acute phase were divided into three groups:group A1,severe pneumonia complicated by acute congestive heart failure without congenitive heart disease(CHD)(n=15);group B1,severe pneumonia complicated by acute congestive heart failure with CHD(n=12);group C1,mild bronchopneumonia(n=20).A2,B2 and C2 groups were the convalescence groups of A1,B1 and groups C1 respertively.Group D,20 healthy infants were used as control group.Plasma ADM,ET-1 levels of patients in acute phase(pre-treatment)and convalescent phase and controls were measured by specific radioimmunoassary.Results 1.The plasma ADM levels significantly increased in the acute phase of A1,B1 and C1 compared with healthy controls(Pa0.05).3.The plasma ADM,ET-1 levels in A2 and B2 groups significantly decreased compared with those in group A1 and B1(Pa0.05).Conclusions The ADM,ET-1 play very important roles in the pathophysiological processes of pneumonia and congestive heart failure in infants.ET-1 may play an important role in the pathogenesis of severe pneumonia in infants complicated with congestive heart fai-lure.The level of plasma ET-1 is related with the degree of congestive heart failure.

Objective To investigate the association between essential hypertension(EH)and nonalcoholic fatty liver(NAFL).Methods Four hundred and nine patients of EH underwent liver uhrasonographic examina- tion during 2006-2007 year were enrolled.Patients were categorized as MS(n=312)or non-MS(n=97)ac- cording to the criteria by CDA.Body mass index(BMI),blood pressure,the profiles of blood lipid,liver func- tion,renal function,plasma sugar were determined.Results 1)The prevalence of fatty liver in EH+MS group (66.0%)was significantly higher than that of EH without MS group(41.2%,P