Worldwide, about 85% of human immunodeficiency virus (HIV) infections were acquired through sexual transmission. Control strategies have been focused on behavioral change through educational efforts and condom promotion, which had achieved certain success in several countries. The past decade witnessed the extraordinary advances in highly active antiretroviral therapy (HAART) and its effectiveness. HAART fundamentally alters the course of HIV-1 infection by decreasing the plasma viral load to the undetectable level and increasing the number of CD4 + T cells. However, problems including drug resistance and adverse events also exist in HAART. In the near future, the major challenges may include: determining the role and efficacy of new drugs and new therapies; addressing the coinfection of HIV/liver diseases/tuberculosis; improving the savage management; addressing the issues faced by the resource-limited countries; and achieving further success in HIV/AIDS prevention and treatment.
Antiretroviral Therapy, Highly Active ; CD4-Positive T-Lymphocytes ; immunology ; HIV Infections ; drug therapy ; immunology ; prevention & control ; Humans

A TCM preparation named Fortified Xiaoshifanshi Powder was given to the mouse model of immune hepatic injury, and the results showed that the preparation could obviously decrease the serum ALT and AST activity in the animals of the model group in a certain dose-effect manner, and inhibit the increase of IL-6 and TNF-α levels with a positive correlation between the effect and the size of the dose.

OBJECTIVETo observe the effect of bear bile powder (BBP) on the STAT3 pathway and its downstream target genes of nude mice hepatocellular carcinoma (HCC) xenograft, and to explore its mechanism for treating HCC.

METHODSThe subcutaneous xenograft model was established using HepG2 cells. When the subcutaneous transplanted tumor was formed, naked mice were randomly divided into two groups, the BBP group and the control group. Mice in the BBP group were administered with BBP by gastrogavage, once daily for 3 consecutive weeks, while mice in the control group were administered with normal saline by gastrogavage, once daily for 3 consecutive weeks. The body weight and the tumor volume were measured once per week. By the end of medication, the tumor weight was weighed and the tumor inhibition ratio calculated. The apoptosis of the tumor tissue was detected by TdT-mediated dUTP nick end labeling (TUNEL). The expression of Bcl2-associated X protein (Bax), B cell lymphoma/eukemina-2 (Bcl-2), cyclin-dependent protein kinase (CDK4), cyclinD1 were detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression levels of signal transducers and transcription activators 3 (p-STAT3), proliferating cell nuclear antigen (PCNA), Bax, Bcl-2, CDK4, and cyclinD1 were determined by immunohistochemistry.

RESULTSBBP could inhibit the tumor volume and tumor weight, showing statistical difference when compared with the control group (P < 0.01). Results of TUNEL showed that BBP could significantly induce the apoptosis of hepatoma carcinoma cells. Results of RT-PCR showed that BBP could up-regulate the expression of Bax and down-regulate mRNA expression of Bcl-2, CDK4, and cyclinD1. Immunohistochemical results showed that BBP could up-regulate the expression of Bax and inhibit the protein expression of p-STAT3, PCNA, Bcl-2, CDK4, and cyclinD1.

CONCLUSIONBBP could induce the apoptosis of hepatoma carcinoma cells and inhibit their proliferation by regulating STAT3 pathway.

Animals ; Bile ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Hep G2 Cells ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Ursidae ; Xenograft Model Antitumor Assays ; bcl-2-Associated X Protein ; metabolism

Adult ; Endoscopy ; Female ; Hemangioma, Cavernous ; surgery ; Humans ; Orbital Neoplasms ; surgery ; Otorhinolaryngologic Surgical Procedures ; methods

BACKGROUNDThe incidence of HIV-1-related infection diseases and the mortality of AIDS have dramatically decreased since highly active antiretroviral therapy began to be used clinically in China in 1999. And we initiated a second clinical trial using a combination of Efavirenz and Indinavir to observe the effects of the immunoreaction.

METHODSTwenty patients with laboratory-confirmed chronic HIV-1 infection were recruited. Blood samples were collected initially and during the weeks after initiation of treatment. Within 48 hours of blood sampling, peripheral blood plasma and mononuclear cells were separated using routine methods. HIV-1 viral load was measured in thawed plasma samples. Within 48 hours of peripheral blood sampling, CD4(+) and CD8(+) T cell subsets were enumerated.

RESULTSThe drug regimen was efficient in reducing HIV-1 plasma viral load and increasing total CD4(+) T cell counts. The percentage of CD4(+) and CD8(+) T cell subsets expressing CD38 and HLA-DR activation markers was positively correlated with plasma viral load and tended to normalize.

CONCLUSIONSThe combination of Efavirenz and Indinavir was generally well tolerated and efficient at reducing HIV-1 RNA. Furthermore, the treatment improved the immunological function.

ADP-ribosyl Cyclase ; blood ; ADP-ribosyl Cyclase 1 ; Adult ; Aged ; Anti-HIV Agents ; administration & dosage ; Antigens, CD ; blood ; Benzoxazines ; CD4-CD8 Ratio ; Chronic Disease ; Drug Therapy, Combination ; Female ; HIV Infections ; drug therapy ; immunology ; virology ; HIV Protease Inhibitors ; administration & dosage ; HIV-1 ; HLA-DR Antigens ; blood ; Humans ; Indinavir ; administration & dosage ; Male ; Membrane Glycoproteins ; Middle Aged ; Oxazines ; administration & dosage ; Viral Load

To explore the effect of a tyrosine-kinase inhibitor STI571 and P21(WAF) gene clone on the proliferation, cycle, apoptosis of leukemia cell line K562, P21(WAF) gene was obtained by RT-PCR, and its sequence was approved to be correct, then P21-pcDNA3.1 vector was constructed and transfected into K562 cell line. After selected with G418, P21-pcDNA3.1-K562 cell clone that stably expression P21(WAF) was isolated. P21(WAF) protein was identified by Western blot. The survival rate were tested by MTT. Cell cycle and apoptosis were tested by flow cytometry. The results showed that the expression of P21(WAF) protein could be detected by Western blot in P21-pcDNa3.1-K562 cells. A strong inhibition of cell proliferation was observed in P21-pcDNA3.1-K562 cells as compared with that of the control. The cells cycle were arrested in G(0)/G(1) phase. The percentage of apoptosis was declined slightly after P21-pcDNA3.1-K562 cells were combined with STI571, meanwhile its survival rate declined more slowly than that of K562 cell with STI571. In conclusion, P21(WAF) inhibits the proliferation of K562 cell, meanwhile slightly inhibits its apoptosis induced by STI571and decrease its sensitivity to STI571.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; genetics ; Base Sequence ; Benzamides ; Blotting, Western ; Cell Cycle ; drug effects ; genetics ; Cell Proliferation ; drug effects ; Cloning, Molecular ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; metabolism ; Humans ; Imatinib Mesylate ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; metabolism ; pathology ; Molecular Sequence Data ; Piperazines ; pharmacology ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; pharmacology ; Transfection

OBJECTIVETo investigate the feasibility of serum pharmacology in evaluating the antitumor effect of Chinese medicine (CM) of Fuzheng Guben (supporting the healthy energy and strengthening the body's resistance to pathogens), the effects of Fuzheng Yiliu Decoction (FYD), a typical prescription of Fuzheng Guben, on proliferation and apoptosis of hepatoma cells in vitro were observed by two methods with serum pharmacology and traditional pharmacology, respectively.

METHODSHepG2 cells were treated with FYD-containing serum or crude FYD extract in vitro. The proliferation rate was determined by methyl thiazolyl tetrazolium (MTT) assay. Cell cycle and apoptosis rate was performed by flow cytometry. And the levels of interleukin-2 (IL-2) and tumor necrosis factor α (TNF-α) in FYD-containing serum were detected by radioimmunoassay.

RESULTSFYD-containing serum remarkably inhibited proliferation and induced apoptosis of hepatoma cells at least by promoting the production of IL-2 and TNF-α in vivo. On the contrary, crude FYD extract promoted the proliferation and did not induce cell apoptosis.

CONCLUSIONThe results by serum pharmacology were accordant with those of our previous animal and clinical trials which indicates that serum pharmacology is a reasonable and feasible method for the evaluation of the antitumor effect of herbs of Fuzheng Guben.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Hep G2 Cells ; Humans ; Interleukin-2 ; metabolism ; Medicine, Chinese Traditional ; Plant Extracts ; pharmacology ; Radioimmunoassay ; Serum ; Tumor Necrosis Factor-alpha ; metabolism

The purpose of this work was to investigate the effects of niflumic acid (NFA), a chloride channel blocker, on the proliferation of human hepatoma cell line (HHCC). Cell proliferation was analyzed by cell count and MTT assay. Cell cycle analysis was carried out by flow cytometry. [Ca(2+)](i) was determined by laser scanning confocal system. It was found that NFA decreased significantly the cell number and the MTT optical density (OD) of HHCC cells, and that the OD value was reversed after washout of NFA. Compared with control, NFA blocked cell cycle progression in G(1) phase. Extracellular application of NFA (100 micromol/L) induced a rapid decrease in [Ca(2+)](i). These findings demonstrate that blockage of chloride channels by NFA induces growth arrest of HHCC in G(1) phase, which may be due to the inhibition of Ca(2+)/CaM-dependent signaling pathways.
Calcium ; metabolism ; Calmodulin ; metabolism ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chloride Channels ; antagonists & inhibitors ; Humans ; Liver Neoplasms ; pathology ; Niflumic Acid ; pharmacology

Danshen,an efficacious agent for cardiovascular diseases,has been found to play an essential role in kidney injury.In the present study,the effect of Danshen on cisplatin-induced renal dysfunction was investigated in a mouse model.Danshen was administered to mice at a dose of 3 g/kg 4 days before and 3 days after cisplatin treatment.A single intraperitoneal injection of 20 mg/kg cisplatin was used to induce nephrotoxicity.The mice were sacrificed 72 h after cisplatin intoxication.Biochemical parameters including serum creatinine and blood urea nitrogen were analyzed.Histopathological changes of kidney tissues were detected using HE staining.Antioxidant enzymes (GSH-Px and SOD) and peroxidative product (MDA) were detected.Protein expressions of Nrf2 and its target genes including HO-1 and NQO1 were measured by Western blotting.The results showed that pretreatment with Danshen significantly reduced serum creatinine and blood urea nitrogen in the cisplatin-treated mice.Histopathological examination showed that Danshen mitigated the renal damage induced by cisplatin.Moreover,Danshen restored the activities of antioxidant enzymes (GSH-Px and SOD) and normalized the MDA contents in renal tissues.Western blotting revealed that Danshen enhanced the expressions of Nrf2 and its target genes in cisplatin-exposed mice.It was suggested that Danshen protects against the cisplatin-induced renal impairment in the mice,which is potentially associated with the upregulation of Nrf2-mediated signaling pathway.

OBJECTIVE: The stability of ketamine in biological samples was studied under different storage temperature and time. METHODS: The rabbits were given intragastric administration of ketamine with a dose of 150 mg/kg and were sacrificed after 30 minutes. Blood, liver, kidney and brain of the rabbits were stored at room temperature (between 18 degrees C and 24 degrees C) and -20 degrees C. The specimens were analyzed at different times by GC-MS and GC-NPD. RESULTS: At -20 degrees C, the concentration of ketamine decreased in all of samples (P < 0.05) within 30 days. The concentration of ketamine increased in all of samples stored at room temperature after 5 days(P < 0.05). CONCLUSION The stability of ketamine in biological samples stored at -20 degrees C was better than that at room temperature. The samples suspected containing ketamine should be stored at -20 degrees C and should be tested as soon as possible.
Animals ; Brain/metabolism* ; Cryopreservation ; Disease Models, Animal ; Drug Stability ; Female ; Forensic Toxicology ; Gas Chromatography-Mass Spectrometry/methods* ; Hydrogen-Ion Concentration ; Ketamine/poisoning* ; Kidney/metabolism* ; Liver/metabolism* ; Male ; Rabbits ; Specimen Handling/methods* ; Temperature ; Time Factors