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.

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

Objective:To screen for the pathogenesis-related genes of osteosarcoma and to assess their roles for the de- velopment of osteosareoma.Methods:Total RNA was extracted from 3 ATCC osteosarcoma cell lines and an osteoblastic cell line and was used to synthesize biotinylated cRNAs;the latter were hybridized to Affymetrix~(?)GeneChip~(?)U133A ar- rays and a gene with more than 2 folds of change was selected.Ten of the differentially expressed genes were chosen and the primers were designed and the synthesized.Then SYBR~(?)Green real-time PCR(RT-PCR)method was used to detect the expression of the 10 genes in 9 fresh osteosarcoma specimens.ABI Prism 7 000 system was used to analyze the differ- ent expression between osteosarcoma cell line and osteoblastic cell line.Results:We identified 58 up-regulated and 142 down-regulated genes in the 3 osteosareoma cell lines.Many of the genes were firstly reported to be related to the patho- genesis of osteosarcoma.These differentially expressed genes were mainly involved in energy and material metabolism,on- cogene,signal transduction gene,transcription- related genes,cell cycle-related genes,cell apoptosis-related gene,im- mune response gene,tumor suppressor genes,etc.The array results of 10 randomly selected genes were further verified by the RT-PCR in 9 fresh osteosarcoma specimens.Conclusion:Many genes are involved in the pathogenesis of osteosarcoma. Gene microarray can help to discover the genes related to the pathogenesis of osteosarcoma,which may lay a foundation for studying the molecular mechanism of osteosarcom.

AIM: To investigate the expression of cystic fibrosis transmembrane conductance regulator (CFTR) in acute myeloid leukemia (AML) and its effect on the biological function of human erythroleukemia cell line TF1, and to explore the underlying mechanism .METHODS: The abundance of CFTR in the bone marrow mononuclear cells of patients with AML was measured by real-time PCR.After TF1 cells were incubated with CFTR specific inhibitor CFTRinh-172, cell viability, cell cycle distribution and cell apoptosis were analyzed by CCK-8 assay and flow cytometry . The Wnt signaling pathway-related proteins were determined by Western blot .RESULTS: CFTR was highly expressed in both patients with AML and leukemia cell lines .After incubated with CFTRinh172, the viability of TF1 cells was de-creased, the proportion of the cells in G0/G1 phase was increased, while that in S phase declined (P<0.05).Further-more, the cells treated with CFTRinh-172 exhibited higher apoptotic rate , accompanied with lower protein expression of β-catenin, c-Myc and cyclin D1 (P<0.05).CONCLUSION:CFTR expression is dramatically increased in AML .Inhibi-tion of CFTR restrains the growth and promotes the apoptosis of TF 1 cells via classical Wnt signaling pathway .

Adenine ; analogs & derivatives ; pharmacology ; Drug Resistance, Viral ; Hepatitis B virus ; drug effects ; Humans ; Organophosphonates ; pharmacology

OBJECTIVETo study the clinical efficacy and adverse reaction of compound Duzhong Jiangu granule (CDJG) on knee joint osteoarthritis (KJO) of Gan-Shen deficiency with stasis in tendon and muscle syndrome.

METHODSThe randomized controlled method was adopted in this study, comparative study was conducted in 400 patients in the treated group treated with CDJG and 200 patients in the control group treated with Zhuanggu Guanjie pill (ZGP).

RESULTSThe total effective rate in the treated group was 92% and the curative-markedly effective rate was 47%, which were higher than those in the control group respectively. Moreover, CDJG showed superiority in improving symptoms and with shorter initiating time of action as compared with ZGP. However CDJG had the effect more favourable for patients of mild condition.

CONCLUSIONCDJG is a kind of effective and safe medicine for treatment of KJO.

Aged ; Diagnosis, Differential ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Osteoarthritis, Knee ; drug therapy ; Phytotherapy

Adult ; Basic Helix-Loop-Helix Transcription Factors ; metabolism ; Cerebral Ventricle Neoplasms ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Fourth Ventricle ; Ganglioglioma ; metabolism ; pathology ; surgery ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Magnetic Resonance Imaging ; Nerve Tissue Proteins ; metabolism ; Oligodendrocyte Transcription Factor 2 ; Rosette Formation ; Synaptophysin ; metabolism ; Young Adult

The shape and structure of granules are controlled by the granulation process, which is one of the main factors to determine the nature of the solid dosage forms. In this article, three kinds of granules of a traditional Chinese medicine for improving appetite and promoting digestion, namely, Jianwei Granules, were prepared using granulation technologies as pendular granulation, high speed stirring granulation, and fluidized bed granulation and the powder properties of them were investigated. Meanwhile, synchrotron radiation X-ray computed micro tomography (SR-µCT) was applied to quantitatively determine the irregular internal structures of the granules. The three-dimensional (3D) structure models were obtained by 3D reconstruction, which were more accurately to characterize the three-dimensional structures of the particles through the quantitative data. The models were also used to quantitatively compare the structural differences of granules prepared by different granulation processes with the same formula, so as to characterize how the production process plays a role in the pharmaceutical behaviors of the granules. To focus on the irregularity of the particle structure, the box counting method was used to calculate the fractal dimensions of the granules. The results showed that the fractal dimension is more sensitive to reflect the minor differences in the structure features than the conventional parameters, and capable to specifically distinct granules in structure. It is proved that the fractal dimension could quantitatively characterize the structural information of irregular granules. It is the first time suggested by our research that the fractal dimension difference (Df,c) between two fractal dimension parameters, namely, the volume matrix fractal dimension and the surface matrix fractal dimension, is a new index to characterize granules with irregular structures and evaluate the effects of production processes on the structures of granules as a new indicator for the granulating process control and optimization.
Drugs, Chinese Herbal ; analysis ; Fractals ; Medicine, Chinese Traditional ; Powders ; Quantitative Structure-Activity Relationship ; Synchrotrons ; Technology, Pharmaceutical ; Tomography, X-Ray Computed

OBJECTIVETo investigate the contents of lead, cadmium, zinc and manganese in the follicular fluid and semen of infertile couples that are not professionally exposed to the four heavy metallic elements.

METHODSIn vitro fertilization pre-embryo transfer (IVF-ET) was carried out in wives, and follicular fluid collected after routine oocyte retrieval. Semen was obtained from husbands by masturbation. The contents of zinc in the follicular fluid and semen were determined by the flame atom absorption method and those of lead, cadmium and manganese by graphite furnace atomic absorption spectrometry.

RESULTSThe average concentrations of lead, cad- mium, zinc and manganese were 151.06 microg/L, 2.02 microg/L, 0.54 mg/L and 28.54 microg/L in the follicular fluid, and 250.23 microg/L, 7.42 microg/L, 189.11 mg/L and 82.15 microg/L in the semen. The follicular fluid samples in which lead, cadmium, zinc or manganese was detected constituted 43.8% (21/48), 22.9% (11/48), 75.0% (36/48) and 50.0% (24/48), and the semen samples accounted for 70.2% (33/47), 31.9% (15/47), 100.0% (47/47) and 46.8% (22/47), respectively.

CONCLUSIONThe results suggest that the average contents of lead, cadmium, zinc and manganese are higher in the semen than in the follicular fluid in the non-professionally exposed infertile couples, and so is the percentage of the samples containing each of the elements, with the exception of manganese.

Adult ; Cadmium ; analysis ; Environmental Exposure ; analysis ; Female ; Follicular Fluid ; chemistry ; Humans ; Infertility, Female ; metabolism ; pathology ; Infertility, Male ; metabolism ; pathology ; Lead ; analysis ; Male ; Manganese ; analysis ; Metals, Heavy ; analysis ; Semen ; chemistry ; Spectrophotometry, Atomic ; Zinc ; analysis

OBJECTIVETo observe the effects of Jinshuibao Capsule (JC) combined losartan potassium on some indices of early renal damage of hypertension patients of yin and yang deficiency syndrome (YYDS), such as levels of serum cystatin C (Cys C), beta2-microglobulin (beta2-MG), hypersensitive C-reactive protein (hs-CRP), uric acid (UA), blood pressure, blood lipids, and fasting blood glucose (FBG), and to explore their protective effects on early renal damage of hypertension patients and on the metabolisms of blood lipids and blood glucose.

METHODSTotally 106 hypertension patients of YYDS were randomly assigned to two groups, 53 patients in the control group (treated by losartan potassium) and 53 patients in the treatment group (treated by JC + losartan potassium). The treatment lasted for 16 weeks. The serum changes of UA, Cys C, beta2-MG, hs-CRP, blood lipids [including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C)], and FBG levels were measured to evaluate the renal protective effects and to assess their effect on the metabolisms of blood lipids and blood glucose.

RESULTSCompared with before treatment in the same group, the systolic blood pressure (SBP) decreased in the two groups after treatment, showing statistical difference (P < 0.05, P < 0.01), but there was no statistical difference between the two groups (P > 0.05). The diastolic blood pressure (DBP) was not obviously declined in the two groups after treatment, showing no statistical difference. Compared with before treatment in the same group, the LDL-C level decreased obviously after treatment in the control group. But there was no obvious change in FBG, TC, HDL-C, and TG in the control group, showing no statistical difference when compared with before treatment (P < 0.05). The FBG, TC, and LDL-C obviously decreased in the treatment group more obviously after treatment than before treatment, showing statistical difference (P < 0.05, P < 0.01). There was no statistical difference when compared with the control group after treatment (P > 0.05). Compared with before treatment in the same group, the levels of UA, Cys C, beta2-MG, and hs-CRP all decreased in the two groups, showing statistical difference (P < 0.05, P < 0.01). The SCr level decreased in the treatment group more obviously after treatment than before treatment, showing statistical difference (P < 0.05). Compared with the control group after treatment, the levels of Cys C, beta2-MG, and hs-CRP decreased more obviously after treatment in the treatment group, showing statistical difference (P < 0.05).

CONCLUSIONSJC combined losartan potassium showed better effects in treating early renal damage of hypertension patients of YYDS. They could protect and stabilize the renal functions more effectively. JC could regulate blood lipids and blood glucose.

Aged ; Aged, 80 and over ; C-Reactive Protein ; metabolism ; Cystatin C ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Hypertension ; diagnosis ; drug therapy ; pathology ; Kidney ; pathology ; Losartan ; therapeutic use ; Male ; Middle Aged ; Phytotherapy ; Yang Deficiency ; drug therapy ; Yin Deficiency ; drug therapy ; beta 2-Microglobulin ; blood