Eleven compounds were isolated from the culture of Streptomyces sp. CPCC 202950 by a combination of various chromatographic techniques including column chromatography over macroporous resin HP-20, MCI, and reversed-phase HPLC. Their structures were identified as 1H-pyrrole-2-carboxamide(1),5'-deoxy-5'-methylthioinosine(2), vanillamide(3), trans-3-methylthioacrylamide(4), 1,2,3,4-Tetraydro-1H-pyrido[3,4-b]indole-3-carboxylic acid(5), cyclo(L-pro-L-tyr) (6), N-[2-(4-hydroxyphenyl)]ethylacetamide(7), benzamide (8), cyclo ('L-leucyl-trans-4-hydroxy-L-proline)(9), cyclo-(Phe-Gly) (10), and tryptophan (11). Among them, compounds 1 and 2 were new natural products. In the preliminary assays, none of the compounds exhibited obvious inhibition of HIV-1 protease activity (IC50 > 10 micromol x L(-1)).
Culture Media ; chemistry ; metabolism ; HIV Protease ; analysis ; HIV Protease Inhibitors ; chemistry ; isolation & purification ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization ; Streptomyces ; chemistry ; metabolism

Objective To observe the effect of 5-aza-2'-deoxycytidine(5-aza-CdR)on the normal epithelial specific-1 gene(NES1)and the growth of human gastric cancer xenografts in nude mice,and to explore the possible anti-tumor mechanisms and search for new treatment for gastric cancer.Methods Human gastric caner xenograft model in nude mice was established and treated with 5-aza-CdR.The growth of xenografts in nude mice was observed,and the status of methylation and protein expression of NES1 gene were detected by MSP and immunohistochemistry respectirely.Results After treatment with 5-aza-CdR,the growth of the xenografts in nude mice was greatly inhibited(P

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Diarrhea ; virology ; Female ; Humans ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; methods ; Young Adult

Accidents, Occupational ; Adolescent ; Adult ; Arsenic Poisoning ; Child ; Female ; Humans ; Male ; Middle Aged ; Water Pollution, Chemical

OBJECTIVE: To explore the effect of ulinastain on the expression of hemeoxy genase-1 (HO-1) in oil acid-induced acute lung injury in rats. METHODS: The animal model of acute lung injury was established by oil acid. Thirty SD rats were randomly divided into 3 groups: the blank control group (A), the acute lung injury group (B) and the acute lung injury group (C) followed by injecting 100 mL/kg ulinastatin. Each group consisted of 10 rats. Group A were given 0.2 mL/kg natural solution through the trial vein; Group B and C were given 0.2 mL/kg oil-acid through trial vein, while group C were injected 100mL/kg ulinastatin by the peritoneal cavity after injecting oil acid. After 4 hours, the rates of respiration were counted and blood samples were cramped out through the heart puncture for blood gas analysis. The expressions of hemeoxygenase-1 and the pathologic construction changes were determined by HE staining in the lower right lung of rats in the 3 groups. RESULTS: The respiration dysfunction caused by oil acid could be prominently improved by ulinastain. There was only a little expression of hemeoxygenase-1 in the lung of Group A, but the expression increased in Group B and significatively increased in Group C. CONCLUSION Ulinastatin may protect the rats from acute lung injury through increasing the expression of HO-1.
Acute Lung Injury ; chemically induced ; metabolism ; Animals ; Glycoproteins ; pharmacology ; Heme Oxygenase (Decyclizing) ; metabolism ; Lung ; drug effects ; metabolism ; Male ; Oleic Acid ; adverse effects ; Rats ; Rats, Sprague-Dawley

Objective:To investigate the effect of alogliptin on bone loss in ovariectomized(OVX)mice.Methods:For animal experiments, thirty 8-week-old C57BL/6J female mice were divided into Sham group, OVX group, and OVX+ alogliptin group. OVX+ alogliptin group were administered with alogliptin in a dosage of 20 mg·kg -1·d -1 by gavage, Sham and OVX groups with equivalent saline. After 12 weeks intervention, serum bone anabolism indicators were detected, and Micro CT and HE staining were used to observe and analyze the bone trabecular structure of femur and tibia in mice. For in vitro experiments, bone marrow mesenchymal stem cells(BMSCs)were incubated with 100 μmol/L alogliptin for osteoblast differentiation. Alkaline phosphatase(ALP)and alizarin red S staining were used to determine the ALP activity and mineralization after osteogenic induction and culture. Real-time fluorescence quantitative PCR and Western blot were used to detect mRNA and protein expressions of osteoblast related genes. Results:Alogliptin intervention improved the biochemical indexes of bone anabolism and protected against bone microstructure deterioration to alleviate bone loss in OVX mice. Alogliptin stimulated osteoblast differentiation and elevated expression levels of Runt-related transcription factor 2(Runx2), ALP, osteocalcin, and osterix in in vitro experiments. Conclusion:Alogliptin can alleviate bone loss in OVX mice.

Objective:To investigate the clinical characteristics and treatment of patients with CD4+CD8-T-cell large granular lymphocytic leukemia(T-LGLL).Methods:The clinical manifestations,diagnosis and treatment of 1 case of CD4+CD8-T-LGLL patient were reported,and relevant literatures were reviewed.Results:The patient was a 70-year-old woman with slow clinical progress,mainly manifested by thrombocytopenia and myelodysplasia.The blood smear was mainly composed of large granular lymphocytes.Immunotyping and T-cell receptor gene rearrangement analysis showed that it was in line with T-LGLL.Partial remission(PR)was achieved through the treatment of cyclophosphamide(50 mg/d)combined with prednisone(gradually reduced and stopped later).Conclusion:CD4+CD8-T-LGLL is very rare in clinical practice,and its clinical manifestations are different from those of CD4-CD8+T-LGLL.

OBJECTIVETo construct lentivector carrying Tie2-Small interfering RNA (SiRNA), so as to study its influence on malignant melanoma cells.

METHODSRecombinant plasmid pSilencer 1.0-U6-Tie2-siRNA and plasmid pNL-EGFP were digested with XbaI, ligated a target lentiviral transfer plasmid of pNL-EGFP-U6-Tie2-I or pNL-EGFP-U6-Tie2-II, and then the electrophoresis clones was sequenced. Plasmids of pNL-EGFP-U6-Tie2-I and pNL-EGFP-U6-Tie2-II were constructed and combined with pVSVG and pHelper, respectively, to constitute lentiviral vector system of three plasmids. The Lentiviral vector system was transfected into 293T cell to produce pNL-EGFP-U6-Tie2- I and pNL-EGFP-U6-Tie2-II lentivirus. Then the supernatant was collected to determine the titer. Malignant melanoma cells were infected by both lentiviruses and identified by Realtime RT-PCR to assess inhibitory efficiency.

RESULTSThe recombinant lentiviral vectors of Tie2-RNAi were constructed successfully which were analyzed with restriction enzyme digestion and identified by sequencing. And the titer of lentiviral vector was 8.8 x 10(3)/ml, which was determined by 293T cell. The results of Realtime RT-PCR demonstrated that the lentiviral vectors of Tie2-RNAi could infect malignant melanoma cells and inhibit the expression of Tie2 genes in malignant melanoma cells (P<0.01). There was no significant difference in the expression level (P>0.05) between the two lentiviral vectors of Tie2-RNAi.

CONCLUSIONSLentivector carrying Tie2-SiRNA can be constructed successfully and inhibit the expression of Tie2 gene in vitro significantly. The study will supply the theory basis for the further research on the inhibition of tumor growth in vivo.

Cell Line, Tumor ; Genetic Vectors ; Humans ; Lentivirus ; genetics ; Melanoma ; genetics ; Plasmids ; RNA Interference ; RNA, Small Interfering ; genetics ; Receptor, TIE-2 ; genetics ; Transfection

OBJECTIVETo evaluate the fast serum pepsinogen level of the healthy adults among local population in areas with high incidence of gastric cancer and to study the suitable cut-off values of serum pepsinogen abnormality for the screen of chronic atrophic gastritis (CAG) and gastric carcinoma (GC) in China.

METHODSSerum PG I and PG II levels were detected with time resolved fluorescence immunoassay (TRFIA). The fast serum PG I and PG I level as well as PG I/PG II ratio of 606 healthy adult residents among local population in Zanhuang county, Hebei province were detected and the normal distribution ranges determined. The relationship between different cut-off values of serum PG I level, PG I/PG II ratio and corresponding pathological changes in gastric mucosae were comparatively analyzed with serum PG detection, endoscopic biopsy and pathological observation in 720 cases of local residents receiving endoscopic examination in the high incidence area of gastric cancer. The efficacy, sensitivity and specificity of different PG I, PG II abnormality cut-off values in the screen p rogram of CAG and GC were statistically analyzed.

RESULTSThe serum PG I, PG II and PG I/PG II ratio levels of healthy adults from a local natural population in the high incidence area of gastric cancer were all skewed from normal distribution. The median level of PG I, PG II and PG I/PG II were 161 microg/L, 14.8 microg/L and 10.5 respectively. Data from comparative studies on serum PG level and pathological changes of gastric mucosae showed that within the serum PG I range from 40 microg/L to 80 microg/L and PG I/PG II ratio range from 3 to 8, sensitivity of the screening program for CAG and GC increased while the specificity decreased along with the increase of cutoff values of serum PG I and PG I/PG II ratio. Results from statistical receiver operator characteristic curve (ROC) analysis suggested that the best cut-off value of PG I and PG I/PG II abnormality for the screening of CAG and GC being PG I < or =60 microg/L,PG I/PG II < or =6 respectively.

CONCLUSIONThe serum PC I, PG II and PG I/PG II ratio levels of healthy adults from a local natural population in the high incidence area of gastric cancer were all skewed from normal distribution. Serum PG I < or =60 microg/L and PG I/PG II ratio < or =6 as abnormal cut-off value for the screen of CAG and GC could result relatively good sensitivity and specificity.

China ; Chronic Disease ; Gastritis, Atrophic ; blood ; diagnosis ; Humans ; Mass Screening ; Pepsinogen A ; blood ; Reference Values ; Sensitivity and Specificity ; Stomach Neoplasms ; blood ; diagnosis

OBJECTIVETo study the correlation between serum pepsinogen (PG) level and gastric mucosal changes of the residents who live in the high incidence area of gastric cancer, and investigate the value of serum PG level in screening for chronic atrophic gastritis (CAG) and gastric cancer (GC).

METHODSSerum PG level was detected with time resolved fluorescence immunoassay (TRFIA). The correlation between serum PG level and gastric mucosal changes was analyzed through endoscopic biopsy and pathological examination in 720 adult residents.

RESULTSThe median serum PG I, PG II level and PG I / PG II ratio in 30 healthy residents with normal gastric mucosa was 172.0 microg/L, 9.6 microg/L and 17.5, respectively. The median serum PG I level of GC patients was significantly lower than that of chronic gastritis patients, gastric ulcer (GU) patients and local healthy residents (P < 0.05). The median PG I level of GU patients was significantly higher than that of the healthy resident group and the other groups (P <0.05). Serum PG II level in CAG, GC and GU groups were all significantly higher than that in CSG and healthy resident group (P <0.05). The PG I/PG II ratio in CAG or GC patients was significantly lower than that in the other groups (P < 0.05). The sensitivity and specificity of serum PG I < or = 60 microg/L for screening CAG or GC was 19.7% and 95.5% respectively, which were 34.7%, 89.3% for PG I/PG II < or =6, and 14.1%, 97.3% for PG I < or =60 microg/L + PG I /PG II < or =6. None in GU group was found to have serum PG I < or =60 microg/L. The median serum PG I level and PG I /PG II ratio in chronic gastritis (including CSG and CAG) with intestinal metaplasia were significantly lower than that of healthy resident group (P < 0.05). The sensitivity and specificity for screening of intestinal metaplasia were 16.6% and 92.9% by PG I < or =60 microg/L; 25.6% and 80.4% by PG I/PG II < or =6; 11.9% and 93.9% by PG I < or =60 microg/L + PG I/ PG II < or = 6.

CONCLUSIONSerum pepsinogen level of the residents in the high incidence area of gastric cancer is closely correlated with the pathological changes of gastric mucosa. Though the sensitivity of serum pepsinogen level is relatively lower in the screening for chronic gastritis, gastric cancer and intestinal metaplasia, the specificity was quite high. PG I < or = 60 microg/L may be usful in differential diagnosis of gastric cancer from gastric ulcer.

Diagnosis, Differential ; Gastric Mucosa ; pathology ; Gastritis, Atrophic ; blood ; diagnosis ; pathology ; Humans ; Metaplasia ; Pepsinogen A ; blood ; Pepsinogen C ; blood ; Sensitivity and Specificity ; Stomach Neoplasms ; blood ; diagnosis ; pathology ; Stomach Ulcer ; blood ; diagnosis ; pathology