Objective: To observe the effect of Liuwei Dihuang decoction on brain development of intrauterine growth retardation rats,and to demonstrate the relationship between brain and kidney in TCM.Methods: Animals were divided into 4 groups at random: normal group,model group,Huangqi(HQ) and Liuwei Dihuang(LD) treated groups.The IUGR model was established by passive smoking.On the 19th day of pregnancy,all rats were killed;the total numbers of embryos,the lively,dead and absorbed embryos were counted.The body and brain weight of lively embryos were scaled respectively,then microstructure and apoptosis in brain were observed.Results: Passive smoking can result in the number of dead and absorbed embryos increases.Compared with normal group,the number of apoptotic cells of model group increased.Compared with model group,in Huangqi and Liuwei Dihuang treated groups,the number of dead and absorbed embryos decreased apparently,body and brain weight increased obviously,the number of apoptotic cells reduced significantly(P

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

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 ; Lung Diseases ; diagnosis ; etiology ; Male ; Radiography, Thoracic ; Tomography, X-Ray Computed

PARP [poly(ADP-ribose)polymerase] represents a novel potential target in cancer therapy. It is involved in a DNA repair process by catalyzing the transfer of ADP-ribose units from NAD to a number of its substrate proteins. In this work, a series of novel azaindole derivatives was designed and synthesized. Moreover, 16 target molecules were screened and 8 compounds displayed inhibitory activity against PARP-1. It has been demonstrated that these azaindoles bearing cycloamine substituents at 2-position were active to both PARP-1 and PARP-2.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Aza Compounds ; chemical synthesis ; chemistry ; pharmacology ; Indoles ; chemical synthesis ; chemistry ; pharmacology ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism

The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.

Objective To evaluate the safety and feasibility of sphincter-preserving transabdominal-anal excision of middle-lower rectal cancer by mucosa-mucosa coloanal anastomosis. Methods There were 169 cases undergoing this procedure including 107 males and 62 females. The low margins of the tumors located between 5~9 cm from the anal verge. Histopathological examination showed adenocarcinoma in 163 cases, mucinous adenocarcinoma in 6, and adenoma with canceration in 6.According to Dukes′ classification,61 belonged to Dukes′ A,101 Dukes′B, and 7 Dukes′C. Results Postoperative complications included stomal leak in 5 cases, stomal stenosis in 3, and defecation frequency increased to 6～12 times daily in all cases during the early stage and gradually back to normal 12～18 weeks postoperation. An average follow-up of 5.8 years was made in 154 cases(91.1%).Local recurrence was 5.8%.Hepatic metastasis was 13.7%.The five year survival rate was 66.9%. Conclusion This anal-sphincter preserving procedure while fulfilling radical resection for middle-lower rectal carcinoma is both safe and feasible alternative approach.

OBJECTIVETo make the emergency response to the diseases control and prevention with flooding more scientific ally-based and efficient.

METHODSHubei and Jiangxi province were chosen as the study fields and to establish a data management system of emergency response on flooding using remote sensing (RS) and geographical information system (GIS).

RESULTSSpatial and basic data together with data on flooding were linked to the code of location, and established on the platform of GIS. Through this system, information on flooding was able to be more rapidly and visually analysed.

CONCLUSIONUsing this system, the extent of flooding and the possible epidemic of some communicable diseases during flooding could be ascertained and predicted scientifically and the resource and capacity of emergency response to the disease control and prevention in flooding areas could also be evaluated.

China ; Databases, Factual ; Disaster Planning ; organization & administration ; Disasters ; Environmental Monitoring ; Female ; Geographic Information Systems ; organization & administration ; Humans ; Male ; Management Information Systems

Aged ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Carcinoma, Large Cell ; metabolism ; pathology ; Diagnosis, Differential ; Histiocytic Sarcoma ; metabolism ; pathology ; surgery ; Hodgkin Disease ; metabolism ; pathology ; Humans ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Male ; Melanoma ; metabolism ; pathology ; Receptors, Cell Surface ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; surgery

Yeast strains with improved ethanol yield are important for efficient bioconversion of lignocellulosic biomass for fuel ethanol.Candida shehatae CICC1766 was adapted to 4%(v/v)ethanol,and then subjected to UV mutagenesis.One respiration deficient mutant Rd-5 with improved xylose fermentation capability was selected.Protoplasts of Rd-5 were inactivated by UV treatment,followed by the PEG-mediated protoplast fusion with a Saccharomyces cerevisiae strain with good ethanol-fermenting capability.The xylose fermenting capability of the fusants was investigated,and the fusant F6 demonstrated good ethanol fermentation performance,producing 18.75g/L ethanol from 50g/L xylose with an ethanol yield of 0.375 or 73.4% of its theoretical value of 0.511.Comparing with its parent Candida shehatae strain,the ethanol yield of F6 was increased by 28%.