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 compare the difference of protein and lipid metabolism between patients with inflammatory bowel disease and healthy controls,and to investigate the association of these changes with disease activity and location of the lessions.Methods The retrospective cohort study was carried out.The data of protein and lipid metabolisms collected from 195 patients with ulcerative colitis,76patients with Crohn's disease and 97 healthy controls during 1995 to 2007 were analyzed.Disease activity were evaluated using simple clinieal colitis activity index and simple index of Crohn's disease activity.The erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP)were measured.Results Serum levels of ESR in patients with ulcerative colitis were negatively linear correlated with serum levels of albumin/globulin ratio(β=-0.521,P＜0.01)and positively linear correlated with serum levels of α2globulin(β=0.319,P＜0.01).Serum levels of globulin in patients with Crohn's disease were positively linear correlated with serum levels of ESR(β=0.558,P＜0.01)and CRP(β=0.424,P=0.01).In ulcerative colitis,serum levels of albumin/globulin ratio,albumin and total cholesterol were significantly higher in patients with proctosigmoiditis than those in patients with lesions at other locus(P=0.003,0.005,0.038,respectively).In Crohn's disease,serum level of globulin was significantly higher in patients with lesions only at colon than that in patients with lesions only at small bowel(P=0.029).Conclusions Serum levels of albumin/globulin ratio and α2-globulin can be predictors of inflammatory activity in patients with ulcerative colitis.The increasing serum globulin may predict the progression of disease activity in patients with Crohn's disease.The nutritional deficiency is more critical in patiens with small bowel involvement than those with colon involvement.

Objective To analyze clinical diagnosis and management of 5 patients with actinomycete keratitis.Design Retro- spective case series.Participants 5 patients (5 eyes) with actinomycete keratitis.Methods The clinical features and microbiologic da- ta of 5 culture-proven cases of actinomycete keratitis recorded between October 2004 to March 2006 were analyzed.Main Outcome Measures clinical characteristics,isolations identification,drug susceptibility test and treatments.Results All patients were males and farmers.Of the 5 cases presented in this study,4 cases were followed by minor trauma as a predominant risk factor,and were pre- sented by a chronic progressive corneal ulcer with a wreath pattern of infiltrate.The diagnosis of all cases was based on laboratory in- vestigations,by which 4 cases of nocardia and one case of streptomyce were identified.A variable drug sensitivities were presented in nocardia isolates,which including TMP-SMZ,amicasin,gentamicin and fluorine-quinolones.Conclusions Nocardia keratitis is mainly followed by a minor trauma.It is identified predominantly by laboratory investigations.Tropical and systemically sensitive biotic are the initial choice,while debridement and amnionic transplantation could be an effective alternative.

OBJECTIVETo investigate the recent emerged endemic region of tick-borne encephalitis (TBE) regarding its natural reserves, in Charles Hilary, northern Xinjiang and to isolate and characterize the viral geographic strain.

METHODSUsing indirect fluorescent assay to detect tick-borne encephalitis virus (TBEV) specific IgG antibodies from serum of local residents including 2 unconfirmed viral encephalitis patients in 2011 spring-summer. Viruses were isolated from tick samples by inoculating BALB/c mice and BHK-21 cells. For phylogenetic analysis. TBEV NS1 gene fragments were detected by RT-PCR and then subjected to sequence alignment.

RESULTS1760 ticks were captured from the fields to have found that Ixodes persulcatus were dominated among the tick population. Two viral encephalitis patients were diagnosed as TBEV infection. In addition, 35.4% (23/65) local residents were detected positive for presence of TBEV specific-IgG antibodies in serum. After inoculation, morbidity and mortality of BALB/c mice were 72.9% (70/96) and 55.7% (44/79), respectively. TBEV specific-fragments were amplified from brain tissue of dead mice and cells culture supernatant. NS1 sequence alignment showed that the viral isolates were clustered into TBEV far-eastern sub-type, phylogenetically, and were mostly close to the isolates from northeastern China (99%) and Russian strain (98%).

CONCLUSIONIn this study, a new endemic loci of TBE was firstly described in Charles Hilary natural reserve, northern Xinjiang. TBEV geographic isolates belonged to TBEV far-eastern subtype while Ixodes persulcatus and Dermacentor silvarum played crucial roles for disease transition.

Adult ; Animals ; China ; epidemiology ; Encephalitis Viruses, Tick-Borne ; genetics ; immunology ; isolation & purification ; Encephalitis, Tick-Borne ; epidemiology ; transmission ; virology ; Female ; Humans ; Male ; Mice ; RNA, Viral ; genetics

AIMTo identify a novel alternative transcript of the novel retinal pigment epithelial cell gene (NORPEG) expressed in the human testis.

METHODSA human testis cDNA microarray was established and hybridized with cDNA probes from human fetal testes, adult testes and human spermatozoa. Differentially expressed clones were sequenced and analyzed. One of these clones was a short transcript of NORPEG which we proceeded to analyze by RT-PCR.

RESULTSThe novel short alternative transcript of NORPEG was isolated and named sNORPEG. It was 3486 bp in length and contained a 2952-bp open reading frame, encoding a 110.4-kDa protein of 983 amino acids. Amino acid sequence analysis showed that the sNORPEG protein contains six ankyrin repeats and two coiled-coil domains. It shares a high homology with the NORPEG and ankycorbin proteins in both its sequence and motifs. Blasting the human genome database localized sNORPEG to human chromosome 5p13.2-13.3. Expression profiles showed that sNORPEG was expressed in human fetal testes, adult testes and spermatozoa. Moreover, sNORPEG was found to be ubiquitously expressed in human tissues.

CONCLUSIONsNORPEG is expressed in different developmental stages of the testis and encodes a protein that may have roles in human testis development and spermatogenesis.

Alternative Splicing ; Amino Acid Sequence ; Base Sequence ; Cytoskeletal Proteins ; genetics ; DNA, Complementary ; Gene Expression Profiling ; Humans ; Male ; Molecular Sequence Data ; Open Reading Frames ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Amino Acid ; Testis ; metabolism ; Transcription Factors ; genetics

OBJECTIVETo study whether antisense oligonucleotides and ultrasonic microbubble intensifier transfection combined with ultrasound irradiation is an effective and directional way in reversing multidrug resistance (MDR) in tumors.

METHODSMdr1, mrp, and lrp genes antisense oligonucleotides on the ultrasound microbubble intensifier were transfected for the human HepG2/ADM cell lines and then the cells were radiated with low intensity ultrasound. The effects of the reversion of carcinoma cells' MDR and the reduction of their malignancy and growth capability in vitro and in vivo were assessed using RT-PCR, Western blot and MTT.

RESULTSThe treatment restrained the multiplication of the human HepG2/AMD cell lines. The levels of their mRNA and protein of cells' mdr1 and mrp genes dropped significantly. Growth of the subcutaneous transplanted tumors in the nude mice decreased.

CONCLUSIONSTransfection of MDR genes antisense oligonucleotides on the ultrasonic microbubble intensifier combined with low intensity ultrasound radiation may serve as a new treatment method for hepatocellular carcinoma.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Animals ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Humans ; Liver Neoplasms ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Microbubbles ; Oligonucleotides, Antisense ; genetics ; Transfection ; Ultrasonics

OBJECTIVETo explore the possible pathophysiological process and mechanisms underlying the development and formation of high altitude pulmonary edema(HAPE) by observing the changes in contents of VEGF, TNF-alpha, IL-6 and NO in serum from the initiated and recovery of HAPE patients.

METHODSWe studied 10 HAPE patients in a Chinese population. The patients were divided into two groups including HAPE initiate group and the recovery group. Contents of VEGF, TNF-alpha, IL-6 and NO in serum of the two groups were determined to study the process of HAPE.

RESULTSVEGF levels in the HAPE initiate one and the recovery groups were (167.9 +/- 26.5 and 53.1 +/- 17.0 pg/ ml), respectively. There was a significant decrease of VEGF content in recovery one compared to the HAPE group. The same results for TNF-alpha were gained. The levels of TNF-alpha in recovery group was much lower than that in the HAPE initiate one. They were (29.2 +/- 6.8) pg/ml and (86.2 +/- 24.1) pg/ml, respectively. The contents of IL-6 in HAPE initiate group and the recovery group were (32.3 +/- 16.5) pg/ml and (12. 5 +/- 8.0) pg/ml, respectively. But no significance existed. The level of NO in HAPE initiate group was (33.8 +/- 3.3) micromol/L, and it remarkably increased to (74.1 +/- 6.2) micromol/L in recovery one.

CONCLUSIONVEGF, TNF-alpha, IL-6 and NO participated in the different aspects of the pathophysiological process and might have influence on HAPE.

Adult ; Altitude ; Altitude Sickness ; complications ; physiopathology ; Humans ; Interleukin-6 ; blood ; Male ; Nitric Oxide ; blood ; Pulmonary Edema ; blood ; etiology ; physiopathology ; Tumor Necrosis Factor-alpha ; blood ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVETo investigate the specific antitumor immune response induced by idiotype protein (Id)-pulsed dendritic cells (DC) in vitro.

METHODSDC was generated from peripheral blood monocytes of the multiple myeloma (MM) patients using GM-CSF, IL-4, and TNF-alpha. The DCs were pulsed with idiotypic fragment, the F(ab')2 fragment of M protein from MM patient at the immature stage. The morphologic characteristics of the cells were observed with light and electron microscopes. The phenotypic features were analyzed with FACS, MTT assay was employed to evaluate the proliferation of autologous T cells and the inhibition rate of MM cells.

RESULTSDC precursors in peripheral blood could be induced to typical mature DC in medium containing GM-CSF, IL-4 and TNF-alpha. Mature DC with Id could increase the proliferation of the autologous T cells and activate naive T cells to become tumor specialized cytotoxic T lymphocytes (CTL). The CTL at different doses showed significant inhibition on or killing ability to autologous MM cells in vitro.

CONCLUSIONSIn a suitable cytokine environment, the DC precursors from peripheral blood of MM patients could be induced to functional DC, and vaccination of Id-pulsed DC could induce active antitumor immune response.

Adult ; Aged ; Antibodies, Anti-Idiotypic ; immunology ; Cancer Vaccines ; immunology ; Cells, Cultured ; Dendritic Cells ; immunology ; Female ; Humans ; Immunotherapy, Active ; Male ; Middle Aged ; Multiple Myeloma ; immunology ; therapy ; T-Lymphocytes, Cytotoxic ; immunology

OBJECTIVETo establish and evaluate a molecular diagnostic method for routine monitoring of four types of diarrheagenic Escherichia (E.) coli (DEC)and to study the distribution of four types of DEC isolated from diarrheal patients in Shanghai.

METHODSDEC-PCR standard operation procedure(SOP)had been developed for DEC detection and isolation, using the Statens Serum Institute (SSI) DEC PCR kits with multiplex PCR technique after verification tests on reference strains. Diarrhea specimens from 3 clinical hospitals in Shanghai were tested from June to September, 2012.

RESULTSSpecificity of the PCR kit was 100% by verification on the 26 DEC reference strains. A total number of 218 DEC isolates, including 181 fermented lactose and 37 unfermented lactose were identified from the 1887 stool specimens of diarrhea patients, with positive rate as 11.6%. The most common pathogen(54.1%, 118/218)was enteropathogenic E. coli(EPEC), followed by enterotoxigenic E. coli(ETEC, 41.3%, 90/218), enteroinvasive E. coli (EIEC, 4.1%, 9/ 218) and Shigatoxin-producing E. coli(STEC, 0.5%, 1/218)in addition to 18 Shigella isolates. ETEC dominated in diarrhea patients with foreign residency, as well as 1/3 were perinatal stage of neonatal ETEC of all diarrhea cases under the age of 5, while EPEC dominated in the Chinese diarrhea patients especially among young kids under the age of 2.

CONCLUSIONData was reliable after assessment on this molecular diagnostics and seperation procedures used for the routine monitoring on four types of DEC, while the diagnosis and reference ability of DEC regarding the laboratories net-working on food-borne pathogens need to be built up and improved.

Adolescent ; Adult ; China ; epidemiology ; Diarrhea ; diagnosis ; epidemiology ; microbiology ; Escherichia coli ; genetics ; isolation & purification ; Escherichia coli Infections ; diagnosis ; epidemiology ; Female ; Humans ; Infant ; Male ; Middle Aged ; Pathology, Molecular ; Sentinel Surveillance

OBJECTIVETo explore reproductive health condition of college students in Shanghai and provide scientific basis for reproductive health education.

METHODSFrom July 2004 to March 2005, 1192 college students (majors including medicine, science and engineering, arts and culture; 618 medical students and 549 non-medical; 555 male and 612 female) from seven time-day colleges in Shanghai were investigated with a reproductive health questionnaire involving sex. The questionnaire was constituted by 72 topics, involving the need of education, sex attitude, sex videos, sex hygiene knowledge and sexually transmitted diseases (STDs), etc.

RESULTS39.33% (459/1167) students thought they had accepted formal sex education; 49.19% (574/1167) students chose lecture as the favorite way; 41.90% (489/1167) students thought the reproductive health education would not increase the incidence of premarital sexual behavior; 64.10% (748/1167) students thought it was necessary to give college students reproductive health instructions and knowledge. On the other hand, we found 45.05% (250/555) boys and 27.45% (168/612) girls could accept the premarital sexual behaviors; 35.32% (196/555) boys and 39.38% (241/612) girls could accept premarital pregnancy; 44.39% (518/1167) students could calculate the safe period accurately; 71.38% (833/1167) students knew emergency contraception measures; 57.67% (673/1167) students knew how to and when to use condoms; To our surprise, only 2.19% (12/549) non-medical students and 12.14% (75/618) medical students knew exactly the whole 4 sexually transmitted diseases that needed to be essentially prevented in China.

CONCLUSIONAt present, the reproductive health condition of college students in Shanghai is sophisticated. Much more education on sex safety, self-protection skills and acquired immunodeficiency syndrome (AIDS) knowledge, etc should be reinforced.

Acquired Immunodeficiency Syndrome ; prevention & control ; Adolescent ; Adult ; China ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Reproductive Medicine ; statistics & numerical data ; Sampling Studies ; Sex Education ; statistics & numerical data ; Sexually Transmitted Diseases ; prevention & control ; Students ; Surveys and Questionnaires