Osteoclasts secrete factors that may promote mesenchymal stem cell mineralization in vitro. Fibroblasts are the most common cells in connective tissue and are involved in the process of exotic ossification in many diseases such as ankylosing spondylitis. The purpose of this study was to investigate whether osteoclast-like cells would induce the osteogenic differentiation of fibroblasts in vitro. In the present study, osteoclast-like cells (OLCs) were generated by CD14+ cells from human peripheral blood. Fibroblasts were primarily cultured from spinal ligaments. After treatment with conditioned medium of OLCs, the level of alkaline phosphatase (ALP) and mineralization of fibroblasts increased significantly. cDNA microarray analysis identified a set of differentially expressed mRNA associated with signal transduction, cell differentiation, and bone formation, and microarray analysis of microRNA expression profiles revealed a group of microRNAs, including hsa-miR-20a, hsa-miR-300, hsa-miR-185, hsa-miR-30d, hsa-miR-320a, hsa-miR-130b, hsa-miR-33a, hsa-miR-155, and hsa-miR-222, that were significantly down-regulated. These microRNAs were predicted to have an inhibitory effect on genes associated with osteogenic differentiation, such as BMP2, Osteocalcin, and Runx2. The current results suggest that osteoclasts might induce the osteogenic differentiation of fibroblasts in vitro and that miRNA may play an important role in regulation of the cell-cell interaction between osteoclasts and fibroblasts.
c-Met, a type of receptor tyrosine kinase, may be significantly associated with the progression of hepatocellular carcinoma (HCC). In addition, des-γ-carboxyprothrombin (DCP) has been found to interact with c-Met and activate HCC cell growth. Therefore, the functional inhibition of c-Met expressed on HCC cells should arrest HCC cell growth. The present study found that the c-Met inhibitor SU11274 suppressed HCC cell growth by inhibiting the activation of c-Met. Furthermore, this inhibitor also neutralized the activation of HCC cell growth resulting from the addition of DCP. These results suggest that the functional inhibition of c-Met might be a target for the development of chemotherapeutic agents for HCC, and especially those that are positive for expression of DCP.
Steroid bolus therapy for acute rejection after liver transplantation for hepatitis C virus (HCV) cirrhosis often results in graft loss due to adverse effects. The efficacy and safety of basiliximab for the treatment of acute cellular rejection (ACR) in adult liver transplantation has not been adequately evaluated. Three patients received basiliximab as rescue therapy for acute rejection. The outcome and biochemical parameters were recorded before and after treatment with basiliximab. These results were compared to 11 patients who received steroid therapy for ACR. The median time from transplantation to the development of ACR was 19 days (range, 9-49 days). The degree of ACR was mild or moderate. Resolution of rejection was obtained in all patients and the median time from the onset to resolution of ACR was 16 days (range, 6-41 days). A steroid resistant reaction occurred in 2 of 11 patients and OKT3 was used, and the rejection eventually resolved in all patients. Five patients died within 2 to 22 months after transplantation and four of them died from graft failure. In the basiliximab group, there were no significant immediate adverse effects. One patient died from pneumonia 8 months after transplantation. In conclusion: Basiliximab can be safely used as rescue therapy for ACR without significant adverse effects in patients who underwent liver transplantation for HCV cirrhosis.
High-quality textbooks and learning materials are especially important for school children, but school textbooks may contain incorrect health information. The objective of this study was to review the findings of analytical studies about the contents of textbooks used in elementary, junior high, or high schools. Of 450 studies we screened, we reviewed 14 that met the inclusion criteria, and summarized information regarding: i) authors and publication year, ii) target country, iii) topics selected, iv) school level, v) textbook subject(s), vi) analytical methods, and vii) findings. Of the selected 14 studies, 9 were conducted in the United States and Spain. Health topics focused mainly on sexuality, HIV/AIDS, and nutrition. The reviewed studies were classified according to the amount of topic information they contained, the accuracy of the health information provided, and the health information priorities conveyed. The findings of reviewed studies can be summarized as follows: some current school textbooks provide insufficient content and contain inaccurate or out-of-date health information. This study found through health-related content analysis of the school textbooks that textbooks in the United States and Spain cover sexuality, sexually transmitted diseases, and nutrition more often than do textbooks in other countries. Content quality is sometimes inappropriate and requires improvement.
Information about medical students' choice of specialty can be helpful for planning health manpower. However, such information from medical students in Malaysian medical schools is lacking. We carried out a cross-sectional questionnaire survey among fourth- and fifth-year medical undergraduate students at Melaka-Manipal Medical College. A total of 425 students responded to the survey questionnaire. Nearly a quarter of the students indicated internal medicine as their choice of specialty. Other choices were general surgery (13.2%), pediatrics (11.3%), orthopedics (12.7%) and obstetrics & gynecology (Ob/Gyn) (12.1%). Female students (OR 1.91; 95% CI 1.18-3.08), fourth-year students (OR 1.9; 95% CI 1.15-3.12), and students who reported a higher self-rated knowledge of their subject of choice were more likely to choose internal medicine and allied specialties (OR 1.53; 95% CI 1.07-2.19). The influence of teaching faculty and consultants at the teaching hospitals (74.4%) and inspiration obtained during clinical postings (71.9%) were the factors which were rated by the most students as 'important' for choosing a specialty. About half of the students intended to pursue their postgraduate studies in Malaysia, most of the rest in the United Kingdom or Australia. While internal medicine and surgical subspecialties were preferred, students were not inclined towards primary care or diagnostic subspecialties. Incentives should be provided and other measures should be taken to make these branches more attractive.
Liver fibrosis (LF) caused by chronic liver damage has been considered as an irreversible disease. As alternative therapy for liver transplantation, there are high expectations for regenerative medicine of the liver. Bone marrow (BM)- or peripheral blood-derived stem cells, including endothelial progenitor cells (EPCs), have recently been used to treat liver cirrhosis. We investigated the biology of BM-derived EPC in a mouse model of LF. C57BL/6J mice were subcutaneously injected with carbon tetrachloride (CCl4) every 3 days for 90 days. Sacrificed 2 days after final injection, whole blood (WB) was collected for isolation of mononuclear cells (MNCs) and biochemical examination. Assessments of EPC in the peripheral blood and BM were performed by flow cytometry and EPC colony-forming assay, respectively, using purified MNCs and BM c-KIT+, Sca-1+, and Lin− (KSL) cells. Liver tissues underwent histological analysis with hematoxylin/eosin/Azan staining, and spleens were excised and weighed. CCl4-treated mice exhibited histologically bridging fibrosis, pseudolobular formation, and splenomegaly, indicating successful induction of LF. The frequency of definitive EPC-colony-forming-units (CFU) as well as total EPC-CFU at the equivalent cell number of 500 BM-KSL cells decreased significantly (p < 0.0001) in LF mice compared with control mice; no significant changes in primitive EPC-CFU occurred in LF mice. The frequency of WB-MNCs of definitive EPC-CFU decreased significantly (p < 0.01) in LF mice compared with control mice. Together, these findings indicated the existence of impaired EPC function and differentiation in BM-derived EPCs in LF mice and might be related to clinical LF.
Discoid lupus erythematosus (DLE) is a chronic connective tissue disease of unknown etiology, but immunologic factors may play an important role in the pathogenesis. We investigated the features of immunohistochemical characterization of the cellular infiltrate in DLE. Skin samples were obtained from 5 patients using a 6 mm punch biopsy. Samples were stained with monoclonal antibodies against CD1a, CD3, CD4, CD8, CD20, CD25, CD30, and CD57. The number of cells stained with each monoclonal antibody was calculated. The number of cells stained with each monoclonal antibody in the dermis infiltration in DLE was calculated and all were higher than those in the normal control. The numbers of CD3+, CD4+, CD8+, CD20+, CD25+, or CD57+ cells in DLE were statistically higher than those in normal skin (p < 0.05). The numbers of CD1a+ and CD30+ cells in DLE were appreciably increased but had no statistical significance compared with normal skin. In conclusion, this study revealed that T lymphocytes, B lymphocytes, and natural killer cells may play some roles in the pathogenesis of DLE.
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