ANTRODIA CINNAMOMEA EXTRACT ATTENUATES CARBON TETRACHLORIDE-INDUCED CHRONIC LIVER FIBROSIS IN SPRAGUE-DAWLEY RATS

Background: Antrodia cinnamomea (AC) mycelia have been traditionally used by majority of the indigenous populace in Taiwan for symptoms including treating alcohol intoxication. Other beneficial effects have been studied at some point. The present study evaluated the hepato-protection effects in Sprague-Dawley rats. Methods: The model used carbon tetrachloride (CCl4) to induce a chronic liver injury in male rats. Animals were treated with silymarin 200 mg/kg and AC mycelia at doses of 206, 619 and 1,032 mg/kg. The effects of AC on hepatic enzyme markers alanine and aspartate aminotransferase (ALT and AST) and other biochemical parameters were measured in the CCl4 -induced rats. Results: AC demonstrated a hepato-protective effect by decreasing ALT and AST levels and increasing albumin levels in CCl4 treated rats. The effects of AC on the activity of antioxidant enzymes were evaluated. AC administration restored the activities of catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GrD). The degree of liver fibrosis was significantly reduced by AC administration in CCl4 -treated rats. Conclusion: These results suggest that AC could protect the hepatocytes from CCl4 -induced liver injury likely via an antioxidant mechanism

Diabetes and Health Outcomes Among Older Taiwanese with Hip Fracture

Abstract Objective: Hip fracture tremendously impacts functional abilities for the elderly with high morbidity and mortality; recovery is compromised by co-morbidities. Diabetes mellitus is a common co-morbidity for the aging population, but little is known about the influence of diabetes on outcomes of the Asian elderly with hip fracture. Research Design and Methods: This study was a secondary analysis of data on 242 community-dwelling elders with hip fracture from three previous longitudinal studies. Sixty-one cases (25.2%) had diabetes. Outcomes were measured by the Chinese Barthel Index, Medical Outcomes Study Short Form-36 Taiwan version, and analyzed by the generalized estimating equation approach to examine how diabetes influenced hip-fractured elders' mortality, service utilization, mobility, daily activities, and health-related quality of life during the first 12 months after postsurgical discharge in Taiwan. Results: Hip-fractured elderly with diabetes had a significantly higher mortality rate (22.6% vs. 10.3%, p=0.03) during the first year following discharge, and significantly higher readmission rate (10.0% vs. 2.5%, p=0.04) from the first to third month following discharge than those without diabetes. After controlling for covariates, elderly participants without diabetes had an overall 2.2 times (confidence interval [CI]=1.15?4.21) greater odds of recovery in walking ability and better reported general health (?=9.33; p=0.01) and physical functioning (?=7.26; p=0.02) than those with diabetes during the first year after discharge. Conclusions: Diabetes negatively influenced outcomes of elderly patients with hip fracture. The results may provide a reference for developing interventions for hip-fractured elders with diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98472/1/rej%2E2011%2E1308.pd

Chondroprotective effects and mechanisms of resveratrol in advanced glycation end products-stimulated chondrocytes

[[abstract]]INTRODUCTION: Accumulation of advanced glycation end products (AGEs) in joints contributes to the pathogenesis of cartilage damage in osteoarthritis (OA). We aim to explore the potential chondroprotective effects of resveratrol on AGEs-stimulated porcine chondrocytes and cartilage explants. METHODS: Chondrocytes were isolated from pig joints. Activation of the IkappaB kinase (IKK)-IkappaBalpha-nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)-activator protein-1 (AP-1) pathways was assessed by electrophoretic mobility shift assay (EMSA), Western blot and transfection assay. The levels of inducible nitric oxide synthase (iNOS)-NO and cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) were measured by Western blot, Griess reaction or ELISA. The expression and enzyme activity of matrix metalloproteinase-13 (MMP-13) were determined by real time RT/PCR and gelatin zymography, respectively. RESULTS: We show that AGEs-induced expression of iNOS and COX-2 and production of NO and PGE2 were suppressed by resveratrol. Such effects of resveratrol were likely mediated through inhibiting IKK-IkappaBalpha-NF-kappaB and JNK/ERK-AP-1 signaling pathways induced by AGEs. By targeting these critical signaling pathways, resveratrol decreased AGEs-stimulated expression and activity of MMP-13 and prevented AGEs-mediated destruction of collagen II. Histochemistry analysis further confirms that resveratrol could prevent AGEs-induced degradation of proteoglycan and aggrecan in cartilage explants. CONCLUSIONS: The present study reveals not only the effects and mechanisms regarding how resveratrol may protect cartilage from AGEs-mediated damage but also the potential therapeutic benefit of resveratrol in the treatment of OA

Cytochrome P450 Metabolism of Betel Quid-Derived Compounds: Implications for the Development of Prevention Strategies for Oral and Pharyngeal Cancers

Betel quid (BQ) products, with or without tobacco, have been classified by the International Agency for Research on Cancer (IARC) as group I human carcinogens that are associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. There are estimated 600 million BQ users worldwide. In Taiwan alone there are 2 million habitual users (approximately 10% of the population). Oral and pharyngeal cancers result from interactions between genes and environmental factors (BQ exposure). Cytochrome p450 (CYP) families are implicated in the metabolic activation of BQ- and areca nut-specific nitrosamines. In this review, we summarize the current knowledge base regarding CYP genetic variants and related oral disorders. In clinical applications, we focus on cancers of the oral cavity and pharynx and OPMDs associated with CYP gene polymorphisms, including CYP1A1, CYP2A6, CYP2E1, and CYP26B1. Our discussion of CYP polymorphisms provides insight into the importance of screening tests in OPMDs patients for the prevention of oral and pharyngeal cancers. Future studies will establish a strong foundation for the development of chemoprevention strategies, polymorphism-based clinical diagnostic tools (e.g., specific single-nucleotide polymorphism (SNP) “barcodes”), and effective treatments for BQ-related oral disorders

Effects of and satisfaction with short message service reminders for patient medication adherence: a randomized controlled study

BACKGROUND: Medication adherence is critical for patient treatment. This study involved evaluating how implementing Short Message Service (SMS) reminders affected patient medication adherence and related factors. METHODS: We used a structured questionnaire to survey outpatients at three medical centers. Patients aged 20 years and older who were prescribed more than 7 days of a prescription medication were randomized into SMS intervention or control groups. The intervention group received daily messages reminding them of aspects regarding taking their medication; the control group received no messages. A phone follow-up was performed to assess outcomes after 8 days. Data were collected from 763 participants in the intervention group and 435 participants in the control group. RESULTS: After participants in the intervention group received SMS reminders to take medication or those in the control group received no messages, incidences of delayed doses were decreased by 46.4 and 78.8% for those in the control and intervention groups, respectively. The rate of missed doses was decreased by 90.1% for participants in the intervention group and 61.1% for those in the control group. We applied logistic regression analysis and determined that participants in the intervention group had a 3.2-fold higher probability of having a decrease in delayed doses compared with participants in the control group. Participants in the intervention group also showed a 2.2-fold higher probability of having a decrease in missed doses compared with participants in the control group. CONCLUSIONS: Use of SMS significantly affected the rates of taking medicine on schedule. Therefore, daily SMS could be useful for reminding patients to take their medicine on schedule

Enhanced Differentiation of Three-Gene-Reprogrammed Induced Pluripotent Stem Cells into Adipocytes via Adenoviral-Mediated PGC-1α Overexpression

Induced pluripotent stem cells formed by the introduction of only three factors, Oct4/Sox2/Klf4 (3-gene iPSCs), may provide a safer option for stem cell-based therapy than iPSCs conventionally introduced with four-gene iPSCs. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) plays an important role during brown fat development. However, the potential roles of PGC-1α in regulating mitochondrial biogenesis and the differentiation of iPSCs are still unclear. Here, we investigated the effects of adenovirus-mediated PGC-1α overexpression in 3-gene iPSCs. PGC-1α overexpression resulted in increased mitochondrial mass, reactive oxygen species production, and oxygen consumption. Microarray-based bioinformatics showed that the gene expression pattern of PGC-1α-overexpressing 3-gene iPSCs resembled the expression pattern observed in adipocytes. Furthermore, PGC-1α overexpression enhanced adipogenic differentiation and the expression of several brown fat markers, including uncoupling protein-1, cytochrome C, and nuclear respiratory factor-1, whereas it inhibited the expression of the white fat marker uncoupling protein-2. Furthermore, PGC-1α overexpression significantly suppressed osteogenic differentiation. These data demonstrate that PGC-1α directs the differentiation of 3-gene iPSCs into adipocyte-like cells with features of brown fat cells. This may provide a therapeutic strategy for the treatment of mitochondrial disorders and obesity

Nuclear Export Signal Mutation of Epidermal Growth Factor Receptor Enhances Malignant Phenotypes of Cancer Cells

Nuclear epidermal growth factor receptor (EGFR) has been shown to be correlated with drug resistance and a poor prognosis in patients with cancer. Previously, we have identified a tripartite nuclear localization signal (NLS) within EGFR. To comprehensively determine the functions and underlying mechanism of nuclear EGFR and its clinical implications, we aimed to explore the nuclear export signal (NES) sequence of EGFR that is responsible for interacting with the exportins. We combined in silico prediction with site-directed mutagenesis approaches and identified a putative NES motif of EGFR, which is located in amino acid residues 736-749. Mutation at leucine 747 (L747) in the EGFR NES led to increased nuclear accumulation of the protein via a less efficient release of the exportin CRM1. Interestingly, L747 with serine (L747S) and with proline (L747P) mutations were found in both tyrosine kinase inhibitor (TKI)-treated and -naïve patients with lung cancer who had acquired or de novo TKI resistance and a poor outcome. Reconstituted expression of the single NES mutant EGF

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Down-Regulation of NDRG1 Promotes Migration of Cancer Cells during Reoxygenation

One characteristic of tumor microenvironment is oxygen fluctuation, which results from hyper-proliferation and abnormal metabolism of tumor cells as well as disorganized neo-vasculature. Reoxygenation of tumors can induce oxidative stress, which leads to DNA damage and genomic instability. Although the cellular responses to hypoxia are well known, little is known about the dynamic response upon reoxygenation. In order to investigate the transcriptional responses of tumor adaptation to reoxygenation, breast cancer MCF-7 cells were cultured under 0.5% oxygen for 24 h followed by 24 h of reoxygenation in normoxia. Cells were harvested at 0, 1, 4, 8, 12, and 24 h during reoxygenation. The transcriptional profile of MCF-7 cells upon reoxygenation was examined using Illumina Human-6 v3 BeadChips. We identified 127 differentially expressed genes, of which 53.1% were up-regulated and 46.9% were down-regulated upon reoxygenation. Pathway analysis revealed that the HIF-1-alpha transcription factor network and validated targets of C-MYC transcriptional activation were significantly enriched in these differentially expressed genes. Among these genes, a subset of interest genes was further validated by quantitative reverse-transcription PCR. In particular, human N-MYC down-regulated gene 1 (NDRG1) was highly suppressed upon reoxygenation. NDRG1 is associated with a variety of stress and cell growth-regulatory conditions. To determine whether NDRG1 plays a role in reoxygenation, NDRG1 protein was overexpressed in MCF-7 cells. Upon reoxygenation, overexpression of NDRG1 significantly inhibited cell migration. Our results revealed the dynamic nature of gene expression in MCF-7 cells upon reoxygenation and demonstrated that NDRG1 is involved in tumor adaptation to reoxygenation

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis