心肌干细胞调控ANG Ⅱ/AT1R/TGF-β1/SMAD/CX43通路改进心电生理学稳定性和室颤阈值

BACKGROUND:Previous studies have demonstrated that the electrophysiological stability and ventricular fibrillation threshold after myocardial infarction in rats are significantly improved in the mid-term of cardiac stem cell transplantation, but relative regulatory mechanism and pathway remain unclear. OBJECTIVE:To explore the relative molecular regulatory mechanism of cardiac stem cells improving the electrophysiological stability and ventricular fibrillation threshold after myocardial infarction in rats.  METHODS:Myocardial infarction was induced in 20 Sprague-Dawley rats by ligation of the left anterior descending coronary, which were then randomized into two groups (n=10 per group) and were subjected to the injection of cardiac stem cells labeled with PKH26 in phosphate buffer solution (cardiac stem cell group) or the same amount of phosphate buffer solution (PBS) alone (PBS group) into the local infarct zone at 2 weeks after modeling, respectively. Six weeks later, relevant signaling molecules involved in the ANGII/AT1R/TGF-β1/SMAD/Cx43 pathway were all examined in myocardial tissues of the left ventricle and harvested blood samples. RESULTS AND CONCLUSION:Compared with the PBS group, expressions of connexin 43 in different zones of the left ventricle were significantly increased in the cardiac stem cell group (P < 0.01); there was a significant reduction of the angiotensin II level in plasma and different regions of the left ventricular (P < 0.05; P < 0.01). Furthermore, in the cardiac stem cell group, expressions of angiotensin II type I receptor, transforming growth factor-β1, SMAD2 and SMAD3 were significantly decreased (P < 0.01). Whereas SMAD7 was significantly elevated (P < 0.05) in different areas of the left ventricle compared with the phosphate buffer solution group. These findings suggest that the cardiac stem cell transplantation can improve the electrophysiological stability and ventricular fibrillation threshold after myocardial infarction by enhancing the expression of connexin 43 via ANGII/AT1R/TGF-beta1/SMAD/CX43 signaling pathway.     

Structure-function relationships for human antibodies to pneumococcal capsular polysaccharide from transgenic mice with human immunoglobulin Loci

To investigate the influence of antibody structure and specificity on antibody efficacy against Streptococcus pneumoniae, human monospecific antibodies (MAbs) to serotype 3 pneumococcal capsular polysaccharide (PPS-3) were generated from transgenic mice reconstituted with human immunoglobulin loci (XenoMouse mice) vaccinated with a PPS-3-tetanus toxoid conjugate and their molecular genetic structures, epitope specificities, and protective efficacies in normal and complement-deficient mice were determined. Nucleic acid sequence analysis of three MAbs (A7, 1A2, and 7C5) revealed that they use two different V(H)3 genes (A7 and 1A2 both use V3-15) and three different V(kappa) gene segments. The MAbs were found to have similar affinities for PPS-3 but different epitope specificities and CDR3 regions. Both A7 and 7C5 had a lysine at the V(H)-D junction, whereas 1A2 had a threonine. Challenge experiments with serotype 3 S. pneumoniae in BALB/c mice revealed that both 10- and 1- micro g doses of A7 and 7C5 were protective, while only a 10- micro g dose of 1A2 was protective. Both A7 and 7C5 were also protective in mice lacking either an intact alternative (FB(-/-)) or classical (C4(-/-)) complement pathway, but 1A2 was not protective in either strain. Our data suggest that PPS-3 consists of epitopes that can elicit both highly protective and less protective antibodies and that the superior efficacies of certain antibodies may be a function of their structures and/or specificities. Further investigation of relationships between structure, specificity, and efficacy for defined MAbs to PPS may identify antibody features that might be useful surrogates for antibody (and vaccine) efficacy.     

In situ study of partially crystallized Bioglass and hydroxylapatite in vitro bioactivity using atomic force microscopy

The present work investigates, in situ, the in vitro bioactivity of partially crystallized 45S5 Bioglass (BG) as a function of immersion time in a simulated body fluid (SBF) using atomic force microscopy (AFM). The results obtained for the crystallized BG were compared to those of hydroxyapatite c- and a-faces. The calcium phosphate layer grows on the crystallized 45S5 B by multiple two-dimensional nucleation and fusion of these two-dimensional islands, which is essentially the same mode as for the hydroxyapatite c-face. The surface of the crystallized 45S5 BG was almost fully covered with a dense and compact calcium phosphate layer after 24 h. The calcium phosphate formation on the crystallized BG arises from a low surface energy of the surface layer and/or an effect of the layer to lower the resistance when the growth units of calcium phosphate incorporate into the growing island. These results indicate that the crystallized 45S5 BG is suitable to be used as a filler for polymeric matrix bioactive composites, as it maintains a high bioactivity associated with a stiffer behavior (as compared to standard BG).     

Detection of human papillomavirus in esophageal carcinoma

The aim of the study was to assess the prevalence of human papillomavirus (HPV) in the esophagus in the coastal region of Eastern Guangdong, Southern China, an area with a high incidence of esophageal carcinoma. Fresh surgical resection esophageal specimens were obtained from 176 esophageal carcinoma patients admitted to the Tumor Hospital of Shantou University Medical College. The samples were subjected to polymerase chain reaction (PCR) to detect HPV infection using consensus and type-specific primers for HPV type 6, 11, 16, and 18. The incidence rate was 65.5%, 69.1%, and 60% in tissues of cancerous, paracancerous and normal mucosa, respectively. Further analysis of the distribution of HPV types in the three sections of tissues showed that the high-risk HPV types 16 and 18 were found mainly in the cancer cells (43.2%), whereas the low-risk HPV types 6 and 11 were seen mainly in the normal mucosa (52.3%). The total infection rate of the high-risk HPV types 16 and HPV 18 was the highest in cancerous tissues (54.5%), followed by paracancerous tissues (19.5%), and the lowest in normal mucosa (11.7%). There was high incidence of HPV infection in the esophageal epithelium in Eastern Guangdong, Southern China, where esophageal carcinoma is prevalent. HPV was seen in the normal, paracancerous and cancerous tissues, with the high-risk HPV type 16 and 18 more common in cancerous tissues. The results indicate that the high incidence of esophageal carcinoma in this area is associated with HPV infection.     

Diagnostic usefulness of aberrant CD22 expression in differentiating neoplastic cells of B-Cell chronic lymphoproliferative disorders from admixed benign B cells in four-color multiparameter flow cytometry

The diagnosis of B-cell chronic lymphoproliferative disorders is a great challenge when made in a background of polyclonal B cells. We studied the diagnostic usefulness of aberrant CD22 expression for differentiating neoplastic from benign B cells by 4-color flow cytometry. Of 56 cases of B-cell chronic lymphoproliferative disorders, we found that neoplastic cells showed aberrant CD22 expression in 39 (70%) of 56 cases, including chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, hairy cell leukemia, and follicular lymphoma. In 4 cases, monoclonality was detected definitively only by evaluating the immunoglobulin light chain restriction in B cells with aberrant CD22 expression because numerous polyclonal B cells were present. Aberrant CD22 expression is a useful marker for detection of monoclonal B cells admixed with numerous benign polyclonal B cells.     

Age-dependent and iron-independent expression of two mRNA isoforms of divalent metal transporter 1 in rat brain

The DMT1(Nramp2/DCT1) is a newly discovered proton-coupled metal-ion transport protein. The cellular localization and functional characterization of DMT1 suggest that it might play a role in physiological iron transport in the brain. In the study, we evaluated effects of dietary iron and age on iron content and DMT1 expression in four brain regions: cortex, hippocampus, striatum, substantia nigra. Total iron content in all regions was significantly lower in the low-iron diet rats and higher in the high-iron diet rats than that in the control animals, showing that dietary iron treatment for 6-weeks can alter brain iron levels. Contrary to our expectation, there was no significant alternation in DMT1(+IRE) and (-IRE) mRNA expression and protein content in all brain regions examined in spite of the existence of the altered iron levels in these regions after 6-weeks' diet treatment although TfR mRNA expression and protein level were affected significantly, as was expected. The data demonstrates that expression of DMT1(+IRE) and (-IRE) was not regulated by iron in these regions of adult rats. The lack of response of DMT1 to iron status in the brain suggests that the IRE of brain DMT1 mRNA might be not really iron-responsive and that DMT1-mediated iron transport might be not the rate-limiting step in brain iron uptake in adult rats. Our findings also showed that development can significantly affect brain iron and DMT1(+IRE) and (-IRE) expression but the effect varies in different brain regions, indicating a regionally specific regulation in the brain.     

Matrix metalloproteinase activity and osteoclasts in experimental prostate cancer bone metastasis tissue

Previously, we and others showed that broad spectrum pharmaceutical inhibition of matrix metalloproteinase (MMP) activity reduces intraosseous tumor burden and bone degradation in animal models of bone metastasis. Herein, we used specific assays to measure net enzymatic activities of individual MMPs during colonization of bone by prostate cancer cells. PC3 cells were injected into the marrow of human fetal femurs previously implanted in SCID mice. Net MMP-9 activity in bone tissues peaked 2 weeks after injection, coinciding with a wave of osteoclast recruitment. In contrast, MMP-2 and MT1-MMP activity did not change. In vitro, co-culture of PC3 cells with bone tissue led to activation of pro-MMP-9 and increases in secreted net MMP-9 activity. Activation of pro-MMP-9 was prevented by metalloprotease inhibitors but not by inhibitors of other classes of proteases. Ribozyme suppression of MMP-9 expression in PC3 cells did not affect pro-MMP-9 activation or net MMP-9 activity and did not affect the phenotype of bone tumors. siRNA targeting of MMP-9 expression in preosteoclasts in vitro demonstrated that tumor-induced preosteoclast motility was dependent on MMP-9 expression. These data suggest that osteoclast-derived MMP-9 may represent a potential therapeutic target in bone metastasis and provide a rationale for the development of MMP-9-specific inhibitors.     

生物阻抗技术概述

简要叙述了人体组织阻抗特性、生物阻抗技术的基本原理和测量方法,全面介绍了生物阻抗技术在细胞测量、体积测量、人体组织结构分析、组织监测、人体成分分析、生物阻抗成像等各方面的应用.