HIV and AIDS remain as the crucial global health concern, therefore, research and development of novel anti-HIV-1 chemical therapeutics is still of paramount significance, which may be illuminated by cases of successful marketed drugs. Herein, we document the discovery and biological profile of new anti-HIV-1 drugs approved by FDA between 2005 and 2008 and some drug candidates are also discussed.

Animals ; Enterovirus A, Human ; genetics ; Enterovirus Infections ; virology ; Humans ; Reverse Genetics ; methods

AlM:To investigate the protective effect of astaxanthin (AST) on human retinal pigment epithelial (RPE) cells against oxidative damage induced by hydrogen peroxide (H2O2).METHODS:Human RPE cells were subcultured, cell activity was detected by MTT, rate of apoptosis was detected by flow cytometry and cell ultrastructure changes were observed under transmission electron microscope. RESULTS: MTT results showed that cell activity elevated to ( 53. 66%± 3. 25% and 70. 43%± 2. 38% after 10-8 mol/L and 10-4 mol/L AST treated. The difference had statistically significant (P<0. 05) compared with oxidative injury group (38. 76%± 3. 74%). Flow cytometry results showed that the apoptosis rate of RPE cells decreased to 30. 23%± 1. 91% and 12. 58%± 2. 12% in AST pretreated group, the difference was significant (P<0. 05) compared with oxidative injury group ( 42. 50%± 1. 94%); Electron microscopy showed that the morphology of cells gradually improved accompanied with the concentration of AST elevated.CONCLUSlON:AST may inhibit hydrogen peroxide-induced apoptosis of RPE cells, it can provide reliable evidence for pursue effective medicine to prevent and treat retina injury.

1H NMR-based metabolomic approach combined with multivariate statistical analysis was used to evaluate the quality of 21 Farfarae Flos (FF) samples from different growth regions. Principal component analysis showed that wild and cultivated FF could be separated clearly, suggesting a big chemical difference existed between them. Supervised PLS-DA analysis indicated that the wild samples showed higher levels of secondary metabolites, such as bauer-7-ene-3β, 16α-diol, chlorogenic acid, rutin, 7-(3'-ethylcrotonoyloxy)-1α-(2'-methyl-butyryloxy)-3, 14-dehydro-Z-notonipetranone (EMDNT), tussilagone, β-sitosterol and sitosterone. This is consistent with traditional experience that the quality of wild samples are better than that of cultivated ones. The content of pyrrolizidine alkaloids senkirkine also differed greatly among samples from different habitats. The Pearson correlation analysis showed that senkirkine is positively correlated with 4, 5-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 3,4-O-dicaffeoylquinic acid, rutin, kampferol analogues, to a statistically significant extent. The correlation between the toxic compounds and the bioactive components in FF should be further studied.
Chlorogenic Acid ; Drugs, Chinese Herbal ; chemistry ; Flowers ; chemistry ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Metabolomics ; Quinic Acid ; analogs & derivatives ; Rutin ; Sitosterols ; Tussilago ; chemistry

ObjectiveTo evaluate the clinical effectiveness of posterolateral autograft bone graft fusion transpedicular screw system internal fixation and anterior debridement in the treatment of dorsal and lumber spinal tuberculosis. MethodsFrom March 1996 to July 2000,posterolateral autograft bone graft fusion transpedicular screw system internal fixation and anterior debridement procedures were used in 62 patients suffering from dorsal and lumber spinal tuberculosis in our department,48 of them were involved in a longitudinal study follow-up for a mean of 3.6(1.5-5.5)years postoperatively. ResultsAll patients showed successful posterolateral bone graft fusion. Among 38 cases of Pott's paraplegia, 30 were completely recovered,5 were partly recovered,the rate of recovery was 92.1%. The average immediate postoperative correction of kyphosis angle was 29.1°,the average loss of correction was only 3.2°at final follow-up.ConclusionsPosterolateral autograft bone graft fusion transpedicular screw system internal fixation and anterior debridement procedure were found helpful in strengthening the stability of the spine in dorsal and lumber spinal tuberculosis, providing successful interbody fusion and recovery of Pott's paraplegia, correcting the kyphosis, and preventing progression of kyphosis.

RIG-I-like receptors (RLRs) belong to pattern recognition receptors, which perform significant roles in antiviral responses. RLRs can initiate a cascade of signaling transduction that induces the production of type I interferon and activates the interferon signaling pathway, ultimately resulting in antiviral responses. In the course of evolution, viruses have been constantly counteracting host immune systems to facilitate their own survival and replication, and have developed a set of antagonistic strategies. These mainly comprise elusion, disguise and attack strategies to eliminate the activation of RLRs. In virus-infected cells, RLRs recognize viral RNA and then induce antiviral responses. A better understanding of viral antagonistic strategies against RLRs will provide insights into the development of new antiviral medicines. This mini-review concludes that there are three main antagonistic strategies by which RNA viruses can counteract the activation of the RLRs pathway. It aims to provide references and insights for similar studies on viral antagonism in an array of RNA viruses.
DEAD Box Protein 58 ; DEAD-box RNA Helicases ; genetics ; immunology ; Host-Pathogen Interactions ; Humans ; RNA Viruses ; genetics ; immunology ; physiology ; RNA, Double-Stranded ; genetics ; immunology ; RNA, Viral ; genetics ; immunology ; Virus Diseases ; genetics ; immunology ; virology

Objective To investigate the effects of toll-like receptor 9 (TLR9) agonist CpG ODN2216 on the sensitivity of pancreatic cancer cell line PANC1's to gemcitabine.Methods The immunofluorescence staining method and Western blot method were used to examine the expression of TLR9 protein in PANC1 cells.The changes of sensitivity to gemcitabine after CpG ODN2216 treatment were examined by MTT assay.Results The TLR9 protein was highly expressed in PANC1 cells and the median inhibition concentration of gemcitabine against PANC1 cells was reduced from (1.23 ± 0.14) mg/L to (0.28 ± 0.13) mg/L after CpG ODN2216 treatment,and the difference between the two groups was statistically significant (P ＜0.01).After 0.01,0.10,1.00,10.00 mg/L gemcitabine treatment with CpG 0DN2216,the inhibition rates of PANC1 were (34.4 ±1.3)％,(43.5 ± 2.7)％,(76.3 ± 2.5)％,(95.3 ± 2.2)％ ; and without CpG ODN2216,the inhibition rates of PANC1 were (14.5 ± 0.9) ％,(23.5 ± 1.1) ％,(44.8 ± 1.4) ％,(63.6 ± 1.8) ％,and the difference between the two groups was statistically significant (P ＜ 0.01).Conclusions The sensitivity of PANC1 cells to gemcitabine can be enhanced by CpG ODN2216.

Objective To evaluate the safety of surgical procedures for patients after heart valve prosthesis implantation.Methods Clinical data of 12 cases with heart valve prosthesis implantation undergone other surgical treatment from November 1996 to December 2005 were retrospectively analyzed.All the cases had routine oral warfarin with prothrombin time (PT) of 20.0—28.3 s averaged 23.5 s, international normalized ratio (INR) for prothrombin of 1.79—2.23 averaged 1.95 and heart functional class Ⅰ—Ⅲ.Among them,appendectomy was performed in three cases with acute appendicitis,reposition and repair in one with inguinal hernia,radical gastrectomy in two with gastric carcinoma,left hemicolectomy in one,cholecystectomy in three,left femoral head replacement in one,and bilateral high ligation and ablation of great saphenous vein in one.Elective surgical operation was performed in seven cases,and emergency operation in five.In those with elective surgery,warfarin was stopped 2—3 days before operation,while 5—10 mg vitamin K_1 was injected intramuscularly 6—8 hours before emergency surgery with preoperative median PT of 15.1 and 15.3 s and median INR of 1.24 and 1.30,respectively.In operation,5—10 mg vitamin K_1 were injected intravenously into the patients by drip depending on their bleeding on the surface of wound.ECG,blood pressure,hemoglobin and oxygen saturation were routinely monitored for all the cases intraoperatively and postoperatively.For the cases with heart function above class Ⅱ,fluid infusion was adjusted based on intubated central venous pressure,and for those with general anesthesia,analyses of blood gases and electrolyte were monitored routinely in operation.Results OPeration time averaged 20—160 rain in all the 12 patients,with blood loss 5—280 ml in average and without complications of massive hemorrhage,thrombosis and heart failure.Conclusions Surgical operation was safe for patients with heart valve prosthesis implantation,if preoperative PT and INR were adjusted to about 15 s and 1.30,respectively by cessation of warfarin or application of vitamin K_1,combined with careful manipulation and strengthened perioperative management.

OBJECTIVETo investigate the effects of the quinoline derivative PQ1 combined with cisplatin on the proliferation and gap junction communication of prostate cancer PC3 cells.

METHODSWe cultured in vitro prostate cancer PC3 cells and divided them into DMSO blank control, cisplatin control, and cisplatin (10 mg/ml) plus PQ1 (1, 2, 5, 10, and 15 μmol/L) groups. We measured the proliferation of the prostate cancer PC3 cells, determined the expressions of the connexin 43 (Cx43) mRNA and protein by RT-PCR and Western blot, and compared the indexes among different groups.

RESULTSCisplatin combined with PQl at 1 - 10 μmol/L significantly inhibited the proliferation of the PC3 cells and the inhibition rate rose in a concentration- and time-dependent manner, from (48.72 ± 0.98)% vs (50.33 ± 0.62)% at 0 μmol/L to (77.38 ± 1.12)% vs (83.50 ± 1.05)% at 15 μmol/L at 24 and 48 hours (P < 0.05). Compared with the cisplatin control, cisplatin combined with PQ1 at 1, 2, 5, 10, and 15 μmol/L increased the expression of Cx43 mRNA from 0.379 ± 0.113 to 0.669 ± 0.031, 0.831 ± 0. 127, 0.769 ± 0.100, 0.532 ± 0.086, and 0.475 ± 0.134, respectively (P < 0.05), and cisplatin combined with PQ1 at 1, 2, 5, and 10 μmol/L elevated that of Cx43 protein from 0.138 ± 0.146 to 0.263 ± 0.111, 0.306 ± 0.152, 0.415 ± 0.280, and 0.643 ± 0.310, respectively (P < 0.05).

CONCLUSIONThe quinoline derivative PQ1 can promote the gap junction communication of prostate cancer PC3 cells and enhance the killing effect of cisplatin on PC3 cells by upregulating the expressions of Cx43 mRNA and protein.

Aminoquinolines ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Connexin 43 ; genetics ; metabolism ; Dose-Response Relationship, Drug ; Gap Junctions ; drug effects ; physiology ; Humans ; Male ; Prostatic Neoplasms ; metabolism ; pathology ; physiopathology ; RNA, Messenger ; metabolism ; Time Factors