Objective To investigate the role of the p38 MAPK pathway in the formation of cytoplasmic vacuoles .Methods Af-ter treated with Anisomycin ,SB203580 or SP600125 ,images of HepG2 ,LM3 ,QBC939 ,Hela and A549 cells were recorded by light microscopy and taken at a magnification of 400 × .The effects of anisomycin ,SB203580 and SP600125 on the activity of p38 and JNK were measured by Western blot .LM3 and A549 cells were stained with the ER-tracker red and the lyso-tracker red and subjec-ted to confocal microscopy analysis .Results (1)Anisomycin could abolish cytoplasmic vacuolization of HepG2 cells .(2)p38 MAPK activation was responsible for anisomycin-induced cytoplasmic vacuolization abolishment .(3)p38 MAPK blocking initiated cytoplas-mic vacuoles formation in various cancer cell lines .(4)p38 MAPK blocking-induced cytoplasmic vacuoles disrupted the integrity of endoplasmic reticulum .(5)p38 MAPK blocking reversibly induced cytoplasmic vacuoles formation .Conclusion These observations provide direct evidence for a role of p38 MAPK signaling in regulating the formation of cytoplasmic vacuoles .

Abstract: Large-scale clinical trial is an important measure of clinical evaluation on drugs. This paper introduces the concept and features of large-scale clinical trial, the possibility and necessity of large-scale clinical trial of traditional Chinese medicine, as well as its administration and quality control, with Myocardial Infarction Secondary Prevention Study in Traditional Chinese Medicine (MISPS-TCM), a National Program Subject, as an example.

In order to investigate the changes in the expression of extracellular signal-regulated kinase (ERK1/ERK2) and angiotensin-converting enzyme (ACE) in the patients with atrial fibrillation (AF), 52 patients with rheumatic heart diseases were examined. Nineteen patients had chronic persistent AF (AF > or = 6 months, CAF), 12 patients had paroxymal AF (PAF) and 21 patients had no history of AF. The ERK expression was detected at the mRNA level by reverse transcription polymerase chain reaction, at the protein level by Western blotting and at atrial tissue level by immunohistochemistry. ERK-activating kinases (MEK1/2) and ACE were determined by Western blotting techniques. The expression of ERK2-mRNA was increased in the patients with CAF (74 +/- 19 U vs sinus rhythm: 32 +/- 24 U, P < 0.05). Activated ERK1/ERK2 and MEK1/2 were increased to more than 150% in the patients with AF compared to those with sinus rhythm. No significant difference between CAF and PAF was found. The expression of ACE was three-fold increased in the patients with CAF compared to those with sinus rhythm. Patients with AF showed an increased expression of ERK1/ERK2 in atrial interstitial cells and marked atrial fibrosis. An ACE-dependent increase in the amounts of activated ERK1/ERK2 in atrial interstitial cells may be one of molecular mechanisms for the development of atrial fibrosis in the patients with AF. These findings may have important impact on the treatment of AF.
Adult ; Aged ; Atrial Fibrillation ; enzymology ; etiology ; Female ; Gene Expression ; Heart Atria ; enzymology ; Humans ; Male ; Middle Aged ; Mitogen-Activated Protein Kinase 1 ; genetics ; metabolism ; Mitogen-Activated Protein Kinase 3 ; genetics ; metabolism ; Peptidyl-Dipeptidase A ; genetics ; metabolism ; Rheumatic Heart Disease ; complications

Objective To study the association of single nucleotide polymorphism (SNP) of the protein tyrosine phosphatase-1B (PTP-1B) gene with type 2 diabetes mellitus and obesity in Chinese. Methods SNPs in the PTP-1B gene were detected by direct sequencing to PCR products, and the detected SNPs were genotyped in case-spouse samples with the technique of fluorescence real-time PCR. Results Totally 6 SNPs were found in PTP-1B gene. Three SNPs (I5/37 C→A,I6/82 A→G, I7/301 C→T) were in the intron regions and the other 3 (E8/45 C→T, E9/35 G→A, E10/372 G→A)in the exon regions. Among them, E9/35 G→A was a newly found mutation site. The A allele frequency of I5/37 C→A, T allele frequency of I7/301 C→T and G allele frequency of I6/82 A→G in type 2 diabetes were significantly higher than those in the normal spouse group (P