Dengue virus (DENV) envelope [E] protein is the major surface protein of the virions that indued neutralizing antibodies. The domain III of envelope protein (EDIII) is an immunogenic region that holds potential for the development of vaccines; however, the epitopes of DENV EDIII, especially neutralizing B-cell linear epitopes, have not been comprehensively mapped. We mapped neutralizing B-cell linear epitopes on DENV-1 EDIII using 27 monoclonal antibodies against DENV-1 EDIII proteins from mice immunized with the DENV-1 EDIII. Epitope recognition analysis was performed using two set of sequential overlapping peptides (16m and 12m) that spanned the entire EDIII protein from DENV-1, respectively. This strategy identified a DENV-1 type- specific and a group-specific neutralizing epitope, which were highly conserved among isolates of DENV-1 and the four DENV serotypes and located at two regions from DENV-1 E, namely amino acid residues 309-320 and 381-392(aa 309-320 and 381-392), respectively. aa310 -319(310KEVAETQHGT319)was similar among the four DENV serotypes and contact residues on aa 309 -320 from E protein were defined and found that substitution of residues E309 , V312, A313 and V320 in DENV-2, -3, -4 isolates were antigenically silent. We also identified a DENV-1 type-specific strain-restricted neutralizing epitope, which was located at the region from DENV-1 E, namely amino acid residues 329-348 . These novel type- and group-specific B-cell epitopes of DENV EDIII may aid help us elucidate the dengue pathogenesis and accelerate vaccine design.
Amino Acid Sequence ; Animals ; Antibodies, Neutralizing ; immunology ; Dengue ; virology ; Dengue Virus ; chemistry ; genetics ; immunology ; Epitope Mapping ; Epitopes, B-Lymphocyte ; chemistry ; genetics ; immunology ; Humans ; Mice ; Molecular Sequence Data ; Viral Envelope Proteins ; chemistry ; genetics ; immunology

Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and beta-cyclodextrin (beta-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of beta-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s(-1). Then, the synergetic drug delivery systems were prepared with the ratio of 6.74 : 1 (w/w) for beta-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in beta-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, beta-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems approximately lipid microspheres < beta-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and beta-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by beta-CD through hydrogen bonds.
Acetaminophen ; administration & dosage ; chemistry ; Administration, Oral ; Drug Delivery Systems ; Electrical Equipment and Supplies ; Electrochemical Techniques ; instrumentation ; methods ; Hydrogen Bonding ; Kinetics ; Lipids ; chemistry ; Microspheres ; Solubility ; Taste ; drug effects ; beta-Cyclodextrins ; chemistry

A series of cycloberberine derivatives were designed, synthesized and evaluated for their anti-cancer activities in vitro. Among these analogs, compounds 6c, 6e and 6g showed strong inhibition on human HepG2 cells. They afforded a potent effect against DOX-resistant MCF-7 breast cells as well. The primary mechanism showed that cell cycle was blocked at G2/M phase of HepG2 cells treated with 6g using flow cytometry assay. It significantly inhibited the activity of DNA Top I at the concentration of 0.1 mg mL-1. Our results provided a basis for the development of this kind of compounds as novel anti-cancer agents.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Berberine ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; DNA Topoisomerases, Type I ; metabolism ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Hep G2 Cells ; Humans ; MCF-7 Cells ; Molecular Structure ; Structure-Activity Relationship

Head and Neck Neoplasms ; surgery ; Hemangioma, Cavernous ; surgery ; Humans ; Infant ; Thoracic Neoplasms ; surgery

OBJECTIVETo study the effects of flavonoids of Rhizoma Drynariae on gene level of rats without ovaries (OP) by technology of cDNA array.

METHODThe models of rats without ovaries were made After. 24 weeks of treatment, put them to death and sampled 6 ml blood from the abdominal aorta and 4cm spinal cord. Take out the total RNA, then separate the mRNA to check.

RESULTThere is 70 genes difference between the blank control group and model group, 9 genes difference between the blank control group and flavonoids of Rhizoma Drynariae group. The genes over expression of OP rats models regain normal after the models were fed on flavonoids of Rhizoma Drynariae. There are no differences in the spinal cords genes in the cDNA array analysis of this trail.

CONCLUSIONThe genes over expression of OP rats models regain normal after the models were fed on flavonoids of Rhizoma Drynariae for 6 months. The result shows that the flavonoids of Rhizoma Drynariae does have certain effects on the gene expression of rats without ovaries.

Animals ; Female ; Flavonoids ; isolation & purification ; pharmacology ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Oligonucleotide Array Sequence Analysis ; Ovariectomy ; Plants, Medicinal ; chemistry ; Polypodiaceae ; chemistry ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo study the anti-angiogenic effect of ginsenoside Rg3 (Rg3 in abbreviation) in human nasopharyngeal carcinoma HNE-1 cells in vitro.

METHODSThe tube-like structure (TLS) formation of HNE-1 cells, cultured in medium with different concentrations of Rg3, was determined by in vitro anti-angiogenic test based on preliminary experiment observing the TLSs formed by HNE-1 cells on Matrigel and their structural characteristics. The VEGF expression level in HNE-1 cells was determined by immunohistochemistry (IHC) and Western-blot test after 48-hour cultured in medium with different concentrations of Rg3.

RESULTSHNE-1 cells could form TLSs and mosaic vessels when mix-cultured with CRL-2480 on Matrigel. Rg3 could inhibit the TLS formation of HNE-1 cells. After 24-hour culture in medium with Rg3 at concentrations of 0, 50, 100 and 200 µg/ml, the number of TLSs were 75.50 ± 6.86, 55.00 ± 11.92, 39.75 ± 7.93 and 24.50 ± 6.25, respectively, which were negatively correlated with the concentrations of Rg3 (r = -0.928; P < 0.01). After 48 hours of culture, the expressions of VEGF significantly declined by IHC test with results as 0.19 ± 0.03, 0.13 ± 0.02, 0.11 ± 0.01, and 0.08 ± 0.01, respectively, which were negatively correlated with the concentrations of Rg3 (r = -0.911; P < 0.01). The expressions of VEGF also gradually decreased as revealed by Western blot test, with corresponding results as 119.49, 111.51, 86.45, and 38.29. All of the tests showed significantly declined results in the group at the concentration of 200 µg/ml Rg3.

CONCLUSIONRg3 can inhibit the vasculogenic mimicry of HNE-1 cells, and the possible mechanism might be associated with the down-regulation of VEGF protein expression in HNE-1 cells.

Angiogenesis Inhibitors ; administration & dosage ; pharmacology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Line ; Cell Line, Tumor ; Coculture Techniques ; Dose-Response Relationship, Drug ; Down-Regulation ; Endothelial Cells ; cytology ; Ginsenosides ; administration & dosage ; pharmacology ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neovascularization, Pathologic ; prevention & control ; Umbilical Veins ; cytology ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo understand the receiving sensibility of the points on the hand's six channels for music sound wave in the healthy persons, so as to provide experimental basis for exploring the mechanism of music treatment.

METHODSBy the radiating and receiving sound wave system, the total receiving music sound (RMS) power of the music sound wave were measured at the points of the hand's six channels and non-acupuncture in 34 healthy undergraduates.

RESULTSThere was the specific receiving sensibility at Taiyuan (LU 9). The total RMS power of the music sound wave at Daling (PC 7) and Shaohai (HT 3) in the female was stronger than that in the male.

CONCLUSIONThere is the difference in the receiving sensibility of the music sound wave at the different acupoints of different channels.

Acupuncture Points ; Female ; Hand ; Humans ; Male ; Meridians ; Music Therapy ; Vibration

OBJECTIVETo investigate the cell biological mechanism of koumine-induced apoptosis of human colonic adenocarcinoma cells.

METHODSThe effects of LoVo cell koumine on the membrane potential, mitochondrial membrane potential, concentration of cytosolic free calcium, reactive oxygen species (ROS) and gap junctional intercellular communication was observed by laser scanning confocal microscopy.

RESULTS AND CONCLUSIONKoumine lowered the membrane potential and mitochondrial membrane potential of LoVo cells and decreased the concentration of free cytosolic calcium, which was increased to a level higher than the basal one after addition of EDTA. Koumine also increased the reactive oxygen species and enhanced the gap junctional intercellular communication of LoVo cells. These findings may explain the possible mechanisms of koumine-induced LoVo cell apoptosis.

Adenocarcinoma ; metabolism ; pathology ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Calcium ; metabolism ; Cell Communication ; drug effects ; Cell Line, Tumor ; Colonic Neoplasms ; metabolism ; pathology ; Gap Junctions ; drug effects ; metabolism ; Humans ; Indole Alkaloids ; pharmacology ; Membrane Potential, Mitochondrial ; drug effects ; Microscopy, Confocal ; Reactive Oxygen Species ; metabolism

OBJECTIVETo investigate the effects of low-intensity pulsed ultrasound in repairing injured articular cartilage.

METHODSTen adult New Zealand rabbits with bilateral full-thickness osteochondral defects on the cartilage surface of intercondylar fossas were used in this study. The wounds in the left knees were treated with low-intensity pulsed ultrasound as the experimental group. The right knees received no treatment as the control group. All the animals were killed at 8 weeks after injury and the tissues in the wounds were collected for gross appearance grading, histological grading and proteoglycan quantity.

RESULTSThe scores of the gross appearance grades, histological grades and the optical density of toluidine blue of the tissues in the experimental group were significantly higher than those of the controls at 8 weeks after injury (P < 0.05).

CONCLUSIONSLow-intensity pulsed ultrasound can accelerate the repair of injured articular cartilage.

Animals ; Biopsy, Needle ; Cartilage, Articular ; injuries ; pathology ; Disease Models, Animal ; Female ; Immunohistochemistry ; Knee Injuries ; pathology ; therapy ; Male ; Rabbits ; Sensitivity and Specificity ; Ultrasonic Therapy ; methods ; Wound Healing ; physiology

OBJECTIVETo explore the clinical phenotype and genotype in a Chinese family affected with early-onset familial Alzheimer's disease (EOFAD).

METHODSPotential mutation of beta-amyloid precursor protein (APP) gene, presenilin 1 (PSEN1) gene and apolipoprotein E (APOE) gene was detected with polymerase chain reaction (PCR) and direct sequencing.

RESULTSHomozygous APOE ε 2 allele and no gene mutation of APP gene were detected in the proband (III1). A 488A>G mutation (His163Arg) of the PSEN1 gene was found in the proband and other 4 family members (IV1, IV12, IV21, V2).

CONCLUSIONA mutation (c.488A>G, p.His163Arg) of PSEN1 gene was found in a Chinese family affected with EOFAD.

Adult ; Age of Onset ; Aged ; Alzheimer Disease ; genetics ; Child ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Presenilin-1 ; genetics