Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency disease syndrome (AIDS). After over 26 years of efforts, there is still not a therapeutic cure or an effective vaccine against HIV/AIDS. The clinical management of HIV-1 infected people largely relies on antiretroviral therapy (ART). Although highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients, the huge burden of ART in developing countries, together with the increasing incidence of drug resistant viruses among treated people, calls for continuous efforts for the development of anti-HIV-1 drugs. Currently, four classes of over 30 licensed antiretrovirals (ARVs) and combination regimens of these ARVs are in use clinically including: reverse transcriptase inhibitors (RTIs) (e.g. nucleoside reverse transcriptase inhibitors, NRTIs; and non-nucleoside reverse transcriptase inhibitors, NNRTIs), protease inhibitors (PIs), integrase inhibitors and entry inhibitors (e.g. fusion inhibitors and CCR5 antagonists). Here, we intend to provide updated information of currently available antiretroviral drugs for ART to promote the development of novel anti-HIV-1 drugs.
Acquired Immunodeficiency Syndrome ; drug therapy ; Anti-HIV Agents ; chemistry ; pharmacology ; therapeutic use ; HIV Fusion Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Infections ; drug therapy ; HIV Integrase Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Protease Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV-1 ; drug effects ; Humans ; Molecular Structure ; Reverse Transcriptase Inhibitors ; chemistry ; pharmacology ; therapeutic use

Objective To investigate the impact of prior cerebral infarction (PCI) on in-hospital mortality in patients with Acute Myocardial Infarction (AMI).MethodsA retrospective analysis of documents of a total of 3572 consecutive patients with AMI admitted to Xuanwu Hospital of Capital Medical University from 2002 Jan.1 to 2009 Dec.31 were performed.Results There were 564 patients ( 15.8% )with PCI.Compared with the group of without PC1,the group with PCI were substantially older[(69.4 ±9.9) vs (64.2 ± 12.9)years,P =0.000],and had a higher prevalence of hypertensive disease,diabetes mellitus,prior myocardial infarction (MI) and non-ST-segment elevation myocardial infarction(NSTEMI)( respectively,71.0% vs 57.3%; 41.0% vs 25.7%,12.9% vs 9.5%; 14.9% vs 10.7%,P ＜ 0.01 ),and a higher in-hospital mortality ( 16.5% vs 10.0%,P= 0.000).Univariate analysis demonstrated that in-hospital mortality associated with age,gender,extensive anterior MI,anterior MI,diabetes mellitus,prior cerebral infarction,prior myocardial infarction,coronary angiography and percutaneous coronary intervention.Logistic regression analysis found that risk factors were age,extensive anterior MI,anterior MI,diabetes mellitus and prior cerebral infarction,and protective factors were coronary angiography and percutanous coronary intervention.PCI was independently associated with in-hospital mortality,OR 1.368,95% CI 1.047-1.787,P = 0.022.Conclusion In patients with acute myocardial infarction,the presence of PCI increases the risk of worse in-hospital outcome.

The change of kirenol, darutigenol and darutoside in Siegesbeckia and its first to ninth processed products were studied, and the ten fingerprints were compared, which provided the experimental basis for the study of Siegesbeckia processing tech- nology. The samples were analysed by HPLC on a SunFire-C18 column (4.6 mm x 150 mm, 5 μm) with gradient elution of acetonitrile (0.1% formic acid)-water (0.1% formic acid) at a flow rate of 1.0 mL x min(-1). Column temperaturewas 30 °C and the detected wavelength was 215, 320 nm. The calibration curves of kirenol, darutigenol and darutoside were linear in the range of 2.180-26.16, 2.900-34.80, and 1.012-6.072 mg x L(-1), respectively, and the average recoveries were 96.4%, 97.2% and 96.3% wit RSD 2.2%, 1.7% and 2.4%. This method was simple, the result was stable and had good repeatability, recovery and precision. The re- sult was the basis of the chemical contents variation in the processing of Siegesbeckia Herbs and further clarifying the effect of the changing.
Asteraceae ; chemistry ; Chemistry, Pharmaceutical ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Temperature

Cytokines such as erythropoietin (EPO) and thrombopoitein (TPO) and so on, which stimulate hematopoiesis, can regulate self-renewal, proliferation, differentiation, maturation and programmed cell death of hematopoietic cells through specifically binding to surface receptors. Recently random phage display peptide libraries and other screening methods have been used to isolate mimetic including small peptides and non-peptides molecules, which can mimic the same effects as cytokines, such as EPO and TPO, and demonstrate the similar potency and activity as EPO and TPO in a panel of in vitro biological assays and in animal experiments. These approaches are critical to further research of interactive mechanisms between cytokine and receptor, receptor activation and rational design of other desired cytokine mimetic. This review concisely introduced recent advances in research on mimetic of EPO, TPO and other cytokines and future directions.
Animals ; Cytokines ; pharmacology ; Erythropoietin ; pharmacology ; Hematopoiesis ; drug effects ; physiology ; Humans ; Peptide Library ; Peptides ; pharmacology ; Thrombopoietin ; pharmacology

OBJECTIVETo investigate the effect of Rongshi granule on osteopontin(OPN) expression.

METHODThe urlisthiasis rats were induced by ethylene glycol (EG) and ammonium chloride, the control group rats were non-treated, and the Rongshi granule groups (low-dose group, middle-dose group and high-dose group) were administered Rongshi granule in addition to EG and ammonium chloride in 21 days. Pooled 24 h urine samples from each group were collected weekly with the use of metabolic cages, the concentration of uric calcium and oxalic acid were respectively measured by EDTA and photoelectric colorimetric method. Eight animals from each group were killed at 0, 7, 14, and 21 days, kidneys were histologic examinaed and immunohistochemical staining.

RESULTThe expression of kidney osteopontin in model group was obviously higher than that of control group (P <0.01), and was up to the highest at 21 days with 1.4 times (0.281 3/0.201 8) of the control group. The expression of kidney osteopontin in all of the Rongshi granule groups were lower than those of model group (P < 0.05), with an obvious dose-dependent manner. The degree of the kidney calcium oxalate crystal of the rats in all the Rongshi granule groups was much lower than that of model group, and the uric calcium and oxalic acid were much lower than those of model group (P < 0.01).

CONCLUSIONThe Rongshi granule could inhibit the expression of osteopontin in rat urolithiasis model.

Ammonium Chloride ; Animals ; Calcium ; urine ; Calcium Oxalate ; metabolism ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Ethylene Glycol ; Female ; Kidney ; metabolism ; Kidney Calculi ; chemically induced ; metabolism ; Male ; Osteopontin ; metabolism ; Oxalic Acid ; urine ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the expression of recombinant human SCF-TPO fusion protein and its biological function.

METHODSFour primers were designed according to known sequences of TPO and SCF. The functional amino acid domains of TPO and SCF were amplified by RT-PCR from fetus hepatocytes, respectively. The expression plasmid pET32a/SCF-TPO was constructed by VOE gene fusion technique and expressed in E. coli BL21(DE3) plysS as inclusion body after isopropyl-beta-D-1-thiogalactopyranoside (IPTG) induction. The fusion protein was tested by SDS-PAGE and Western blot. The biological functions of SCF-TPO fusion protein in MO7e cells was investigated by MTT method after purification with metal chelating chromatography.

RESULTSThe high expression SCF-TPO fusion protein was obtained, reaching up to 30% of the total cellular protein. Western blot verified the correct fusion expression and MTT results showed the growth promoting effect of the SCF-TPO fusion protein on MO7e cells, with a higher promoting activity at 100 ng/ml.

CONCLUSIONSExpressed SCF-TPO fusion protein after renaturation has biological activity in promoting the proliferation of MO7e cells.

Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; genetics ; physiology ; Cloning, Molecular ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli ; genetics ; Genetic Vectors ; Humans ; Recombinant Fusion Proteins ; genetics ; metabolism ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cell Factor ; genetics ; metabolism ; physiology ; Thrombopoietin ; genetics ; metabolism ; physiology

In order to confirm the reasonability of designed recombinant exotoxin B7-1-Linker-PE40 and B7-2-Linker-PE40, their molecular biology characteristics, such as flexibility, antigenicity, hydrophilicity, epitope and secondary structure, were predicted by using a computer software GOLDKEY. It had been found that the recombinant fusion exotoxin had kept the epitope characterstics of B7-1, B7-2 and PE40, and had not got new epitope, and the antigenicity in flexible linker was extxemely low. The linker inserted in the recombinant fusion exotoxin had low epitope, low antigenicity and high flexibility. Compared to B7-1, B7-2 and PE40, there are several amino acid residues changes in B7-1-Linker-PE40 and B7-2-Linker-PE40, respectively, which might have some effect on secondary structure of the recombinant fusion exotoxins. Western blot analysis revealed that both B7-1-Linker-PE40 and B7-2-Linker-PE40 could bind specifically with antibodies against B7-1, B7-2 and PE40, respectively. The result of Western blot was consistant with the computer prediction that the recombinant proteins retain the antigenicity and spacial structure of B7 and PE40. It is suggested that both fusion proteins designed and constructed were resonable and computer analysis would be helpful for us to study the biological activity of the recombinant fusion exotoxin B7-1-Linker-PE40 and B7-2-Linker-PE40 and construct other recombinant proteins further.

As one important member of B7/CD28/CTLA-4 costimulatory signal pathway, B7-2 molecule plays a critical role in regulating T-cell response. In order to further explore its effects on regulation of T cell activation, proliferation and associated signal pathways, the cDNA encoding extracellular region of human B7-2 was amplified via PCR and subcloned into some prokaryotic expression vectors to express target protein in host strains. The expressed protein was identified with Western blot and MTT. Results showed that after screening, the expression level of the protein of interest attained the yield of over 20% total bacterial protein by using pGEX-4T-2 vector and E. coli BL21 (DE3)-CodonPlus-RIL host cells. The recombinant protein could specially react with B7-2 McAb and could stimulate T-cell proliferation combined with anti-CD3 antibody. In conclusion, the recombinant protein was bioactive, therefore the study will make it possible for the research of relationship between B7-2 structure and its function.
Antigens, CD ; biosynthesis ; genetics ; pharmacology ; B7-2 Antigen ; Blotting, Western ; Cloning, Molecular ; DNA, Complementary ; analysis ; Humans ; Membrane Glycoproteins ; biosynthesis ; genetics ; pharmacology ; Recombinant Proteins ; biosynthesis ; isolation & purification ; pharmacology

OBJECTIVETo investigate the association between 8 polymorphisms in the catechol-O-methyl transferase gene (COMT) and schizophrenia in Yuedong-Chaoshan region of China.

METHODSEight single nucleotide polymorphism (SNPs), namely rs4680, rs4818, rs165599, rs737865, rs2075507, rs6267, rs6269 and rs4633, in the COMT gene were genotyped in 279 schizophrenia patients and 100 healthy controls.

RESULTSThere was no significant difference between any single SNP and schizophrenia. However, association might exist between haplotypes (G)-G-A-A [(rs4680)-rs165599-rs2075507-rs6269] and A-A-C-(G) [rs2075507-rs6269-rs4633-(rs6267)] and schizophrenia.

CONCLUSIONIn the population of Yuedong region of China, the eight SNPs (rs4680, rs4818, rs165599, rs737865, rs2075507, rs6267, rs6269 and rs4633) in the COMT gene are unlikely to play a major role in the susceptibility to schizophrenia. There might be protective haplotypes in the COMT gene against schizophrenia.

Adult ; Catechol O-Methyltransferase ; genetics ; China ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Polymorphism, Single Nucleotide ; Schizophrenia ; enzymology ; genetics ; Young Adult

In order to investigate the expression of heavy chain of HLA-B * 2705 in prokaryotic system and identify its activity, the extra-membrane gene fragment of HLA-B * 2705 was amplified from full-length HLA-B*2705 cDNA by PCR and cloned into pGEM-T vector. After identification by sequencing, the prokaryotic expressing vector pET32a (+)-B * 2705 was constructed. The antigenic activity of expressed protein was identified by Western blot and antibody blocking reaction. The results indicated that the fused HLA-B * 2705 protein expression with high efficiency was obtained. The expressed product was more than 50% of the total bacteria protein. The antigenic activity of expressed protein was confirmed by Western blot and antibody blocking reaction. It is concluded that HLA-B * 2705 fusion protein are obtained as basis for the further studies.
Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; genetics ; HLA-B27 Antigen ; classification ; genetics ; immunology ; metabolism ; Humans ; Immunoglobulin Heavy Chains ; genetics ; immunology ; metabolism