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 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 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

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 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 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

Objective:To establish mesenchymal cell bicaudal-C (Bicc1) gene conditional knockout mice models and analyze their phenotypes.Methods:Bicc1 f/+ mice were crossed with Pdgfra promoter-driven Cre mice to obtain the offspring mice. Genomic DNA was extracted from the toe and tail tissues from 1-2 weeks old mice, amplified by PCR and detected at the DNA level by agarose gel electrophoresis. Three Bicc1 gene conditional knockout mice (experimental group) and three wild-type mice (control group) were selected after identification and grew to 3 weeks of age for follow-up experiments. The Bicc1 gene was knocked out by the induction of tamoxifen intraperitoneal injection. After 1 week, the kidney, skeletal muscle, skin and adipose tissue samples were collected. Real-time quantitative PCR (RT-qPCR) was performed to determine the expression levels of Bicc1 mRNA in the collected tissue samples. HE and Masson staining were performed with tissue samples fixed in 10% paraformaldehyde, and observed with a light microscope. The SPSS 28.0 software was used to analyze the data, t-test was used for comparison between groups, and P<0.05 was considered statistically significant. Results:Mesenchymal cell Bicc1 gene conditional knockout mice models were obtained by breeding, and the genotype was Bicc1 f/fCre +/-. The genotype of the wild-type mice was Bicc1 f/fCre -/-. RT-qPCR showed that the expression levels of Bicc1 mRNA in kidney, skeletal muscle, skin and adipose tissue of the experimental mice were significantly lower than those of the control group (all P<0.01). HE staining and Masson staining showed that compared with the control group, glomerular atrophy could be observed in the experimental group, renal capsules were irregular in shape, and some renal capsules disappeared. The arrangement of skeletal muscle fibers were loose and scattered, and the accumulation of muscle fibers was not dense. There were no significant differences between the skin and adipose tissue. Conclusion:Mesenchymal cell Bicc1 gene conditional knockout mice models were successfully established, which could provide models for studying the mechanisms of action of Bicc1 gene in different tissues and organs. Mesenchymal cell conditional Bicc1 gene knockout affected the phenotypes of kidney and skeletal muscle in mice.

Objective:To establish mesenchymal cell bicaudal-C (Bicc1) gene conditional knockout mice models and analyze their phenotypes.Methods:Bicc1 f/+ mice were crossed with Pdgfra promoter-driven Cre mice to obtain the offspring mice. Genomic DNA was extracted from the toe and tail tissues from 1-2 weeks old mice, amplified by PCR and detected at the DNA level by agarose gel electrophoresis. Three Bicc1 gene conditional knockout mice (experimental group) and three wild-type mice (control group) were selected after identification and grew to 3 weeks of age for follow-up experiments. The Bicc1 gene was knocked out by the induction of tamoxifen intraperitoneal injection. After 1 week, the kidney, skeletal muscle, skin and adipose tissue samples were collected. Real-time quantitative PCR (RT-qPCR) was performed to determine the expression levels of Bicc1 mRNA in the collected tissue samples. HE and Masson staining were performed with tissue samples fixed in 10% paraformaldehyde, and observed with a light microscope. The SPSS 28.0 software was used to analyze the data, t-test was used for comparison between groups, and P<0.05 was considered statistically significant. Results:Mesenchymal cell Bicc1 gene conditional knockout mice models were obtained by breeding, and the genotype was Bicc1 f/fCre +/-. The genotype of the wild-type mice was Bicc1 f/fCre -/-. RT-qPCR showed that the expression levels of Bicc1 mRNA in kidney, skeletal muscle, skin and adipose tissue of the experimental mice were significantly lower than those of the control group (all P<0.01). HE staining and Masson staining showed that compared with the control group, glomerular atrophy could be observed in the experimental group, renal capsules were irregular in shape, and some renal capsules disappeared. The arrangement of skeletal muscle fibers were loose and scattered, and the accumulation of muscle fibers was not dense. There were no significant differences between the skin and adipose tissue. Conclusion:Mesenchymal cell Bicc1 gene conditional knockout mice models were successfully established, which could provide models for studying the mechanisms of action of Bicc1 gene in different tissues and organs. Mesenchymal cell conditional Bicc1 gene knockout affected the phenotypes of kidney and skeletal muscle in mice.