Bone marrow-derived mesenchymal stromal cells (MSCs) have been reported to be beneficial for the treatment of liver fibrosis. Here, we investigated the use of genetically engineered MSCs that overexpress hepatocyte growth factor (HGF) as a means to improve their therapeutic effect in liver fibrosis. Liver fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. HGF-secreting MSCs (MSCs/HGF) were prepared by transducing MSCs with an adenovirus carrying HGF-encoding cDNA. MSCs or MSCs/HGF were injected directly into the spleen of fibrotic rats. Tissue fibrosis was assessed by histological analysis 12 days after stem cell injection. Although treatment with MSCs reduced fibrosis, treatment with MSCs/HGF produced a more significant reduction and was associated with elevated HGF levels in the portal vein. Collagen levels in the liver extract were decreased after MSC/HGF therapy, suggesting recovery from fibrosis. Furthermore, liver function was improved in animals receiving MSCs/HGF, indicating that MSC/HGF therapy resulted not only in reduction of liver fibrosis but also in improvement of hepatocyte function. Assessment of cell and biochemical parameters revealed that mRNA levels of the fibrogenic cytokines PDGF-bb and TGF-β1 were significantly decreased after MSC/HGF therapy. Subsequent to the decrease in collagen, expression of matrix metalloprotease-9 (MMP-9), MMP-13, MMP-14 and urokinase-type plasminogen activator was augmented following MSC/HGF, whereas tissue inhibitor of metalloprotease-1 (TIMP-1) expression was reduced. In conclusion, therapy with MSCs/HGF resulted in an improved therapeutic effect compared with MSCs alone, probably because of the anti-fibrotic activity of HGF. Thus, MSC/HGF represents a promising approach toward a cell therapy for liver fibrosis.

In three groups of healthy young subjects (n = 33; mean ages 6.4, 13.5, 17.1 years), muscle enzyme activities (creatine kinase, hexose phosphate isomerase, aldolase, pyruvate kinase, lactate dehydrogenase, citrate synthase, fumarase) of the vastus lateralis muscle were investigated to show age-dependent variations. A significant age-dependent increase in aldolase (P less than 0.05) and pyruvate kinase (P less than 0.01) activity and a decrease in fumarase activity (P less than 0.01) were computed. In relation to the age-dependent variation, maximum LDH activities could be measured at an age of 12-14 years; significantly decreased activities of the glycolytic enzymes could only be found in the youngest group.

Objective: To propose a new and practical MRI grading method for cervical neural foraminal stenosis and to evaluate its reproducibility. Methods:We evaluated 50 patients (37 males and 13 females, mean age 49 years) who visited our institution and underwent oblique sagittal MRI of the cervical spine. A total of 300 foramina and corresponding nerve roots in 50 patients were qualitatively analysed from C4-5 to C6-7. We assessed the grade of cervical foraminal stenosis at the maximal narrowing point according to the new grading system based on T 2 weighted oblique sagittal images. The incidence of each of the neural foraminal stenosis grades according to the cervical level was analysed by x 2 tests. Intra-and interobserver agreements between two radiologists were analysed using kappa statistics. Kappa value interpretations were poor (k,0.1), slight (0.1#k#0.2), fair (0.2,k#0.4), moderate (0.4,k#0.6), substantial (0.6,k#0.8) and almost perfect (0.8,k#1.0).Results: Significant stenoses (Grades 2 and 3) were rarely found at the C4-5 level. The incidence of Grade 3 at the C5-6 level was higher than that at other levels, a difference that was statistically significant. The overall intraobserver agreement according to the cervical level was almost perfect. The agreement at each level was almost perfect, except for only substantial agreement at the right C6-7 by Reader 2. No statistically significant differences were seen according to the cervical level.Overall kappa values of interobserver agreement according to the cervical level were almost perfect. In addition, the agreement of each level was almost perfect. Overall intra-and interobserver agreement for the presence of foraminal stenosis (Grade 0 vs Grades 1, 2 and 3) and for significant stenosis (Grades 0 and 1 vs Grades 2 and 3) showed similar results and

Cyclophilins (Cyps) belong to a group of proteins that have peptidyl-prolyl cis-trans isomerase (PPIase) and molecular chaperone activities. Originally, Cyps were identified as the intracellular receptors for the immunosuppressive drug cyclosporin A. Cyps are found in all prokaryotes and eukaryotes, and have been structurally conserved throughout evolution, implying their importance in cellular function. There are seven major Cyp isoforms in humans. CypA is up-regulated in many human cancers, and there is a strong correlation between over-expression of the CYPA gene and malignant transformation in some cancers. Moreover, CypA is directly under the transcriptional control of two critical transcription factors for cancer development: p53 and hypoxia inducible factor-1a. This review discusses the general biological functions of Cyps under a variety of stress conditions, and the importance and diverse roles of overexpression of CYP genes in human cancers, with a particular emphasis on CYPA. These oncogenic properties suggest that CypA is a promising target for cancer therapy.

Faith-based organizations (FBOs) (e.g., churches, mosques, and gurdwaras) can play a vital role in health promotion. The Racial and Ethnic Approaches to Community Health for Asian Americans (REACH FAR) Project is implementing a multi-level and evidence-based health promotion and hypertension (HTN) control program in faith-based organizations serving Asian American (AA) communities (Bangladeshi, Filipino, Korean, Asian Indian) across multiple denominations (Christian, Muslim, and Sikh) in New York/New Jersey (NY/NJ). This paper presents baseline results and describes the cultural adaptation and implementation process of the REACH FAR program across diverse FBOs and religious denominations serving AA subgroups. Working with 12 FBOs, informed by implementation research and guided by a cultural adaptation framework and community-engaged approaches, REACH FAR strategies included (1) implementing healthy food policies for communal meals and (2) delivering a culturally-linguistically adapted HTN management coaching program. Using the Ecological Validity Model (EVM), the program was culturally adapted across congregation and faith settings. Baseline measures include (i) Congregant surveys assessing social norms and diet (n = 946), (ii) HTN participant program surveys (n = 725), (iii) FBO environmental strategy checklists (n = 13), and (iv) community partner in-depth interviews assessing project feasibility (n = 5). We describe the adaptation process and baseline assessments of FBOs. In year 1, we reached 3790 (nutritional strategies) and 725 (HTN program) via AA FBO sites. Most AA FBOs lack nutrition policies and present prime opportunities for evidence-based multi-level interventions. REACH FAR presents a promising health promotion implementation program that may result in significant community reach.