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.

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

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

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

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

BACKGROUND:Impaired balance between osteogenesis and adipogenesis of bone marrow mesenchymal stem cels is a crucial pathological mechanism of osteoporosis. Mechanical loads applied to bone tissue can increase bone formation and improve bone strength, and meanwhile lead to the release of extracelular nucleotides, such as adenosine triphosphate.
OBJECTIVE: To determine the effects of adenosine triphosphate on the osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cels and to investigate the underlying mechanisms.
METHODS:The effect of adenosine triphosphate (10, 50, 250 μmol/L) on differentiation of bone marrow mesenchymal stem cels were measured by osteogenic and adipogenic related genes expression, alizarin red staining and oil red O staining. The activation of ERK1/2 signaling pathway by adenosine triphosphate was tested using western blot assay.
RESULTS AND CONCLUSION: Incubation of bone marrow mesenchymal stem cels with adenosine triphosphate resulted in the dose-dependent increase of osteogenic genes expression and calcium deposition, and inhibition of adipogenic genes expression and lipid droplet formation, but had no effects on cel proliferation. Adenosine triphosphate activated ERK1/2 signaling pathway, and U0126 as an ERK1/2 inhibitor restrained the effect of adenosine triphosphate on the differentiation of bone marrow mesenchymal stem cels.

This article was aimed to study the factors associated with sleep quality of anger-out and anger-in population based on the frequent pattern-tree (FP-Tree) growing algorithm with data mining. The algorithm of structuring frequent model FP-tree and mining frequent itemsets were designed. The database information scanned was recorded by using FP-Tree growing algorithm through state-trees. The frequent itemsets met minimum support required was generated through reducing the search space of project sets and scanning database only one. The data mining of all factors associated with emotional diseases was actualized. The results showed that factors associated with sleep quality of anger-out and anger-in population were disturbance in respiration, cough or snoring, feeling cold, hot or nightmares. The total time for program analysis was 2 seconds. It was concluded that data mining algorithm based on FP-Tree frequent itemsets can effectively realize the useful information receiving from factors associated with emotional diseases.

BACKGROUND: Studies showed that both anterior cervical disc replacement and anterior cervical decompression and fusion can achieve good clinical result in cervical spondylosis. However, it is not conclusive about which kind of surgical method has an advantage in avoiding the adjacent segment degeneration. OBJECTIVE: To compare the effect on adjacent segment degeneration of single segment cervical disc herniation treated with anterior cervical decompression and fusion and anterior cervical disc replacement. METHODS: We col ected clinical data of 178 patients with cervical disc herniation and receiving anterior cervical disc replacement or anterior cervical decompression and fusion from January 2009 to December 2012. A retrospective analysis was performed. There were 116 cases in the anterior cervical decompression and fusion group and 62 cases in the anterior cervical disc replacement group. RESULTS AND CONCLUSION: (1) Evaluation: visual analogue scale score, Japanese Orthopaedic Association Scores and neck disability index were improved significantly in both groups during final fol ow-up compared with that pre-treatment (P < 0.05). (2) No significant difference in range of motion of operation segment, adjacent upper segment and adjacent lower segment was detected between final fol ow-up and pre-operation in the anterior cervical disc replacement group (P > 0.05). At 3 months after surgery, in the anterior cervical decompression and fusion group, surgical segment was confluent, and range of motion lost. During final fol ow-up, range of motion of adjacent upper segment and adjacent lower segment was significantly increased, and the increased range of motion in the upper segment was bigger than that of the lower segment (P < 0.05). (3) During final fol ow-up, X-ray films and MRI images revealed the number of degenerated adjacent segment was more in the anterior cervical decompression and fusion group than in the anterior cervical disc replacement group (P <0.05). The number of degenerated middle and upper segments was more than that of the lower segment in both groups (P < 0.05). (4) The findings confirmed that anterior cervical disc replacement or anterior cervical decompression and fusion for treating cervical disc herniation could effectively relieve nerve symptoms of patients. However, compared with the anterior cervical disc replacement, adjacent segment degeneration occurs more commonly after anterior cervical decompression and fusion.

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

Adult ; Aluminum Silicates ; toxicity ; Humans ; Middle Aged ; Mining ; Occupational Exposure ; Prevalence ; Silicosis ; epidemiology