Cyclic AMP Response Element-Binding Protein ; DNA ; analysis ; genetics ; Female ; Humans ; Infant ; Male ; Muscular Atrophy, Spinal ; genetics ; Nerve Tissue Proteins ; genetics ; Polymerase Chain Reaction ; RNA-Binding Proteins ; SMN Complex Proteins

Acupuncture Therapy ; Adult ; Aged ; Diabetic Retinopathy ; therapy ; Female ; Humans ; Middle Aged ; Retinal Hemorrhage ; therapy

Objective To investigate the role of directly constitutive activation of p38 mitogen-activated protein kinases(p38MAPKs)signaling in ?-globin gene expression and fetal hemoglobin(HbF)induction,and provide direct data for the relationship between phosphorylation of p38 and erythroid differentiation of human K562 erythroleukemia cells.Methods The human K562 erythroleukemia cells were transfected with pCDNA 3.1-MKK3(Glu)and pCDNA 3.1-MKK3(Ala)recombinant plasmids by lipofectamineTM 2000.Then,the stable cell lines overexpressing constitutively active p38 and constitutively inhibitive p38 activation were established by the addition of G418 to select single cell G418-resistant clones and identification with reverse transcriptase-polymerase chain reaction(RT-RCR)and Western blot assays,named K562-MKK3(Glu)and K562-MKK3(Ala)cells,respectively.Furthermore,the direct effects of constitutively active p38 on the ?-globin gene expression and HbF induction were analyzed by RT-PCR and benzidine staining,respectively.Results The results of RT-PCR and Western blot showed that there were no evident changes in the mRNA and protein levels of p38 for various cell models,but compared with K562,K562-vect,and K562-MKK3(Ala)cells,the phosphorylation of p38 and expression of ?-globin levels in K562-MKK3(Glu)cells were significantly up-regulated.The results of benzidine staining displayed that the mean percentages of positive cells stained by benzidine in K562,K562-vect,K562-MKK3(Ala),K562-MKK3(Glu)cells,and K562-MKK3(Glu)cells treated with SB203580 were(3.2?1.4)%,(3.7?1.2)%,(2.8?0.9)%,(32.6?5.3)%,and(7.8? 2.3)%(q = 7.56 P

1)which represented 340 genes and 171 down-regulated(SLR

G protein-coupled receptor 119 (GPR119) has been a promising target for the treatment of type 2 diabetes. It can not only directly promote insulin secretion, but also indirectly increase insulin secretion by stimulating the release of glucose-dependent GIP/CLP-1 without causing hypoglycemia. The remarkable advantages of small molecule GPR119 agonists make it one of the research hotspots for the development of type 2 diabetes drugs. This article reviews the anti-diabetic small molecules based on the GPR119 target in the past five years.

Objective: To investigate the actualities of service in Outpatient Pharmacy and Emergency Pharmacy. Methods: With queuing theory of operational research and data statistics, the specialities and varities of service in both Pharmacies were investigated before and after the application of computer network. Results: (1)The distribution of the patients number arriving the Pharmacies was unequal.(2) The time of service was extended after using network.(3)The average individual time of service in Emergency Pharmacy was 74 s, and 48 s in Outpatient Pharmacy. The reasons for the average individual time of service in Emergency Pharmacy more than that in Outpatient Pharmacy was related to the formulation of drugs in 2 pharmacies and the number of drugs on prescriptions. (4)The number of windows for service should be increased in Emergency Pharmacy after using network. Conclusion: Operational research and data statistics will provide the data assisting the manager in making decisions. [

OBJECTIVETo explore the regulation of transdermal absorption of Secretio Bufonis (SB) and the effect of low frequency complex impulse current (LFCIC) on it.

METHODSBy modifying three-chamber flow diffusion pool to develop a prototype LFCIC device for transdermal delivery, using high performance liquid chromatograph (HPLC) to determine the quantitative transdermal absorption of the amount of ingredients of SB, including bufalin, cinobufagin and resibufogenin, etc. and the transdermal absorption velocity was calculated.

RESULTSThe chief ingredients of SB could be absorbed through skin, but the volume was low. Additional application of LFCIC could enhance the cumulative infiltration volume and velocity of transdermal diffusion. Difference appeared 2 hrs after and significant difference appeared 4 hrs after the application, and 13.8 Hz showed the optimal effect of transdermal delivery.

CONCLUSIONChief ingredients of SB could be absorbed through transdermal medication, and LFCIC can evidently enhance the amount and velocity of transdermal absorption of SB.

Animals ; Bufanolides ; chemistry ; pharmacokinetics ; Bufonidae ; Chromatography, High Pressure Liquid ; Electric Stimulation ; Iontophoresis ; Male ; Materia Medica ; Rabbits ; Skin Absorption

PBL(Problem-Based Learning, PBL) is a problem-oriented and effective supplementary teaching method. PBL is giving a great help to improve self-learning, communication and cooperation, thinking and problems solving abilities for the students. In the process of PBL teaching, attention should be paid to two important items. One item is the role transfer for the teacher. Teacher is only a guider in PBL teaching, teacher should avoid excessive interfere of the process for keeping the passion and enthusiasm of the students. Meanwhile, students should always be realized that they are the main part in PBL teaching, they should not depend on their teacher too much. Another important item is how to find and solve the frequently encountered problems, in order to avoid students wandering from the subject, and lead them toward the main goal to get effective teaching and learning.

Objective To explore the effect of the gene silencing of phosphatidic acid-preferring phospholipase A1 (PA-PLA1) on insulin secretion in mouse insulin-secreting cell line MIN6. Methods The siRNA expression vector of mouse PA-PLA1 gene targeting was constructed using mouse PA-PLA1 mRNA sequence available in GenBank, and MIN6 cells were transfected with the vector. Fluorescence quantitative PCR and Western-blotwere applied to screen efficient RNAi-vector. After transfection with obtained efficient RNAi-vectors for 48 hours, glucose-stimulated insulin secretion experiments were conducted, and the changes of insulin secretion were examined. Results Four siRNA expression vectors of mouse PA-PLA1 gene targeting were confirmed to be successfully constructed by the analyses of enzyme cleavage and sequencing. The results of fluorescence quantitative PCR and Western blot analyses indicated that the siRNA expression vectorpGPU6-PA-PLA1-1885was the most effective RNAi-vector in the four vectors. The expression levels of the PA-PLA1 mRNA and protein of the MIN6 cells transfectedwith pGPU6-PA-PLA1-1885 decreased to 46.3% and 33.9% of that of the control, respectively, and meanwhile the insulin secretion levels of the cells decreased to 65.0% of that of the control (P < 0.05). Conclusion The gene silencing of phosphatidic acid-preferring phospholipase A1 might decrease insulin secretion in MIN6 cells.

This paper is to report the study of the pharmacokinetics of a fusion protein TAT-haFGF(14-154) for human acidic fibroblast growth factor and transcriptional activator protein in rat plasma, and the investigation of their penetration across blood-brain barrier in mice and rats, in order to provide a basis for clinical development and treatment of Alzheimer's disease. Enzyme-linked immunosorbent assay (ELISA) was used to determine concentration of TAT-haFGF(14-154) in rat plasma and in mouse brain homogenate; and immunohistochemistry was used to analyze the distribution in brain. The concentration-time curve fitted two-compartment open model which was linear kinetics elimination after a single intravenous injection of TAT-haFGF(14-154) in rat at the dose of 300 microg x kg(-1). The half life time was 0.049 +/- 0.03 h for distribution phase and 0.55 +/- 0.05 h for elimination phase, and the weight was 1/C2. The result showed that TAT-haFGF(14-154) could be detected in the brain by ELISA and immunohistochemistry, the elimination of TAT-haFGF(14-154) in rat was swift, and TAT-haFGF(14-154) could penetrate across the blood-brain barrier, distribute in pallium and hippocampus and locate in the nucleus.