Allostasis ; physiology ; Chronic Disease ; General Adaptation Syndrome ; physiopathology ; Humans ; Stress, Psychological ; physiopathology

Acupuncture Therapy ; Aged ; Feeding and Eating Disorders ; therapy ; Humans ; Male

Acupuncture Therapy ; Adult ; Female ; Humans ; Laryngitis ; therapy

As a tumor suppressor, p53 is activated by numerous cellular and environmental signals, and plays a criticalrole in the cell cycle regulation, cell apoptosis and senenscence. The murine double minute (MDM)2 and double minute mu?rine 4 (MDMX) are two important regulators. MDMX is a p53 binding protein with strong sequence homology to MDM2, but lacks ubiquitin ligase activity, and which is unable to target p53 for proteasomal degradation. MDMX regulates p53 activity through its binding with p53 and its postranscriptional modification. MDMX in the closed and open structure binds to p53 to regulate its activity. As the main partner of MDMX, casein kinase 1 alpha (CK1α) disrupts the intramolecular binding in MD?MX in the cooperation to regulate p53 activity. The process of MDMX and CK1αin the regulation of p53 is multi-step and complicated. In this paper the mechanism of MDMX and CK1αin the regulation of p53 protein was reviewed.

OBJECTIVETo investigate the effect of midazolam on human ether-a-go-go (hERG) K+ channels exogenously expressed in human embryonic kidney cells (HEK-293) and the underlying molecular mechanisms.

METHODSWhole-cell patch clamp technique was used to record WT, Y652A and F656C hERG K+ current expressed in HEK-293 cells.

RESULTSMidazolam inhibited hERG K+ current in a concentration-dependent manner, the half-maximum block concentrations (IC50) values were (1.31 ± 0.32) µmol/L. The half-activation voltage (V1/2) were (2.32 ± 0.38) mV for the control and (-1.96 ± 0.83) mV for 1.0 µmol/L midazolam. The half-inactivation voltage (V1/2) was slightly shifted towards negative voltages from (-49.25 ± 0.69) mV in control to (-57.53 ± 0.53) mV after 1.0 µmol/L midazolam (P < 0.05). Mutations in drug-binding sites (Y652A or F656C) of the hERG channel significantly attenuated the hERG current blockade by midazolam.

CONCLUSIONMidazolam can block hERG K+ channel and cause the speed of inactivation faster. Mutations in the drug-binding sites (Y652 or F656) of the hERG channel were found to attenuate hERG current blockage by midazolam.

Dose-Response Relationship, Drug ; Ether-A-Go-Go Potassium Channels ; drug effects ; HEK293 Cells ; Humans ; Midazolam ; pharmacology ; Mutation ; Patch-Clamp Techniques ; Potassium Channel Blockers ; pharmacology

Animals ; Cerebral Cortex ; metabolism ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred Strains ; Morphine Dependence ; metabolism ; Neurotrophin 3 ; metabolism ; Prosencephalon ; metabolism

By Silica gel, Sephadex LH-20 and other materials for isolation and purification and by physicochemical methods and spectral analysis for structural identification, 23 compounds were isolated and identified from ethyl acetate portion of alcohol extract solution of Osmanthus fragrans fruits. Their structures were identified as nicotinamide (1), D-allitol (2), 5-hydroxymethyl-2-furancarboxaldehyde (3), acetyloleanolic acid (4), benzoic acid (5), ergosta-7,22-dien-3-one (6), beta-sitosterol (7), borreriagenin (8), cerevistero (9), c-veratroylglycol (10), methyl-2-O-beta-glucopyranosylbenzoate (11), 3', 7-dihydroxy-4'-methoxyisoflavon (12), umbelliferone (13), caffeic acid methyl ester (14), oleanolic acid (15), (-) -chicanine (16), dillapiol (17), 3beta,5alpha, 9alpha-trihydroxyergosta-7-22-dien-6-one (18), 2alpha-hydroxy-oleanolic acid (19), betulinic acid (20), betulin (21), 3, 3'-bisdemethylpinoresinol (22), and lupeol (23). All compounds were isolated from the osmanthus fruit for the first time. Except for compounds 4, 7, 15, 19, 23, the rest ones were isolated from the this plant for the first time.
Drugs, Chinese Herbal ; chemistry ; Fruit ; chemistry ; Oleaceae ; chemistry

Acupuncture Points ; Acupuncture Therapy ; Adult ; Facial Pain ; therapy ; Female ; Headache ; therapy ; Humans ; Male ; Middle Aged ; Toes

Animals ; Electrical Synapses ; Male ; Membrane Potentials ; physiology ; Neurons ; physiology ; Parietal Lobe ; cytology ; Patch-Clamp Techniques ; Rats ; Rats, Wistar

Objective To investigate the effect of valsartan,an angiotensinⅡtype 1 receptor (AT1 R)blocker,on radiosensitivity,invasive potential and proliferation activity of nasopharyngeal carcinoma cells(CNE-2)in vitro. Methods Radiosensitization of valsartan on CNE-2 cells in vitro was investigated by colony forming assay.Effect of ATl R blocker combined with radiation on invasive potential of CNE-2 cells was evaluated using 24-well Matrigel invasion chambers(Transwell).Apoptosis-inducing effect of valsartan combined with radiation on apoptosis of CNE-2 was identified by flowcytometry(FCM). Resuits When valsartan was given at 10-9.10-8 and 10-7 mol/L combined with radiation,sensitivity enhancement ratios (SER)were 1.10,1.20 and 1.36.and the invasive inhibition rates were 8.11%,16.49%and 16.77%,respectively.The SER of valsartan on CNE-2 distinctly increased when the exposure time was increased.After 24 h exposure to 10-8 mol/L valsartan combined witIl radiation.the apoptosis rate was 1.89%±0.09%,which was higher than 1.62%±0.06%in radiation alone group(t=4.79.P＜0.05). Conclusions AT1 R blocker valsartan combined with radiation can significantly inhibit the proliferation activity of nasophar,cngeal carcinoma cells in vitro in a dose- and time-dependent manner.Valsartan combined with radiation can potently inhibit the invasive potential of CNE-2.which may be involved in the mechanism of valsartan treatment in vivo.