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Pan W.-H.,Institute of Population Health science | Pan W.-H.,Academia Sinica, Taiwan | Pan W.-H.,National Taiwan University | Chang Y.-P.,Chia Nan University of Pharmacy and Science | And 8 more authors.
Journal of Geriatric Psychiatry and Neurology | Year: 2012

Although nutrient deficiencies are thought to play roles in the development of depression, observational studies have yielded inconsistent results. This study aimed to investigate whether multiple marginal nutrient deficiencies are associated with symptoms of depression in community-dwelling older Taiwanese. Data from 1371 elderly adults recruited from the Elderly Nutrition and Health Survey in Taiwan was used in this study. Depressive symptom scores on depressed mood and emotions affecting daily life were derived from the Medical Outcomes Study Short Form-36 (SF-36). Hemoglobin, serum ferritin, plasma vitamins B6, B12, and folate concentration, and erythrocyte transketolase and glutathione reductase activation coefficients were measured. After adjusting for age, gender, cognitive function, physical activity, disease history, and medication in the multivariate analysis, anemia, and marginal B6 deficiency were significantly associated with the presence of depression symptoms, respectively. In addition, co-occurrence of vitamin B6 with low folate level and co-occurrence of anemia either with low vitamin B6 or with folate level were all associated with the depressive mood and with depressive emotions defined by SF-36 (odds ratios [OR] in the range of 2.32?7.13, all P values ?.05). The magnitude of the ORs is larger when the number of deficiencies increased. Elderly people with coexisting marginal deficiencies of nutrients involved in the S-adenosylmethionine and hemoglobin production were more likely to experience depressed mood and emotion that affect daily activity. Examining status of these nutrients is worthy of consideration for older adults with depressed symptoms. © The Author(s) 2012. Source

Chern J.-H.,National Health Research Institute | Hsu P.-C.,National Yang Ming University | Wang L.-W.,National Health Research Institute | Tsay H.-J.,National Yang Ming University | And 2 more authors.
Chemico-Biological Interactions | Year: 2010

Increasing evidence indicates that microglial activation plays an important role in the pathogenesis of Alzheimer's disease (AD). In AD, activated microglia may facilitate the clearance of β-amyloid (Aβ), a neurotoxic component in AD pathogenesis. However, microglial activation comes at the cost of triggering neuro-inflammation, which contributes to cerebral dysfunction. Thus, pharmacological approaches that can achieve a favorable combination of a reduced microglia-mediated neuro-inflammation, and an enhanced Aβ clearance may be beneficial for preventing the progression of the disease. Here, we show that some newly synthesized compounds may exert such a combination of functions. Using mouse primary microglia and RAW264.7 cells, we found that some thiourea derivatives significantly enhanced microglial Aβ phagocytosis and suppressed microglial immune responses, as evidenced by the reduced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2). Of note, some commercially available inhibitors for iNOS and/or COX-2, such as ibuprofen, dextromethorphan, and NG-methyl-l-arginine (l-NMA), show negligible effects on microglial Aβ phagocytosis. Among the thiourea derivatives, our data show that a lead compound, designated as compound #326, (1-Naphthalen-1-yl-3-[5-(3-thioureido-phenoxy)-pentyl]-thiourea) appears to be the most potent in promoting Aβ phagocytosis and in inhibiting the LPS-induced expression of iNOS and COX-2 (when used at concentrations in the low μM range). The potency of compound #326 may have beneficial effects on modulating microglial activation in AD. The structure-activity relationship indicates that the thiourea group, alkyl linker, and the hydrophobic aryl group largely influence the dual functions of the compounds. These findings may indicate a structural basis for the improved design of future drug therapies for AD. © 2010 Elsevier Ireland Ltd. Source

Wu M.-J.,Taichung Veterans General Hospital | Wu M.-J.,National Yang Ming University | Wu M.-J.,Chung Shan Medical University | Wu M.-J.,National Chung Hsing University | And 9 more authors.
Journal of the Chinese Medical Association | Year: 2010

Background: The objective of this study was to determine the risk of renal failure in patients with under-recognized chronic kidney disease (CKD) in the self-pay standard medical screening program of health management centers. Methods: The abbreviated Modification of Diet in Renal Disease equation was used to calculate the estimated glomerular filtration rate (eGFR) of study subjects. Study subjects with eGFR less than 60 mL/min/1.73m2 but with normal results of routine assessment, including serum creatinine, blood urea nitrogen, urinalysis and kidney ultrasound, were defined as having under-recognized CKD. Episodes of renal failure requiring dialysis within 2 years in subjects with stage 3 to stage 5 CKD were evaluated. Results: A total of 15,817 subjects were recruited and 28.4% of subjects were identified by routine assessments as having a kidney problem. The prevalences of CKD 3A, 3B, 4 and 5 were 8.3%, 1.9%, 0.3% and 0.2%, respectively. All subjects with stages 4 and 5 CKD had abnormal serum creatinine levels, but 48.7% of 1,507 subjects with stage 3 CKD (stage 3A, n = 713; stage 3B, n = 21) had normal routine assessments. Subjects with under-recognized stage 3B CKD had the highest risk (20%) of developing renal failure compared to subjects with stages 3-5 CKD and abnormal results of routine assessments. Conclusion: Identifying subjects with CKD stage 3 by the eGFR equation, especially in stage 3B, is advantageous in detecting the risk of renal failure over the routine clinical assessment that is currently carried out by health management institutions in Taiwan. © 2010 Elsevier. Source

Chuang S.-Y.,Institute of Population Health science | Yu Y.,National Health Research Institute | Yu Y.,Zhejiang University | Huey-Herng Sheu W.,Taichung Veterans General Hospital | And 8 more authors.
Stroke | Year: 2015

Background and Purpose-Limited studies have investigated the risk of cerebrovascular events associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in subjects at high risk. We examined the short-term (defined as 30-day period) effect of selective and nonselective NSAIDs use on the risk of ischemic and hemorrhagic stroke in patients with hypertension. Methods-We conducted a case-crossover study using the National Health Insurance Research Database in Taiwan. We identified 1653 hypertensive subjects with stroke (defined as International Classification of Diseases-Ninth Revision-CM-codes: 433.x, 434.x, and 436.x for ischemic stroke; 430 and 431 for hemorrhagic stroke) in 2010. We investigated the transient effect of NSAIDs use on stroke using conditional logistic regressions with the adjustment of potential confounders. Results-The results suggested that NSAIDs use during the 30 days before stroke was associated with a 1.57-fold increased risk of ischemic stroke, but not of hemorrhagic stroke (adjusted odds ratio, 1.57; 95% confidence interval, 1.26-1.97 for ischemic stroke; and adjusted odds ratio, 1.38; 95% confidence interval, 0.79-2.40 for hemorrhagic stroke). When classifying NSAIDs into selective and nonselective groups, nonselective NSAIDs use significantly increased the risk of ischemic stroke (adjusted odds ratio, 1.55; 95% confidence interval, 1.24-1.94), but not of hemorrhagic stroke (adjusted odds ratio, 1.56; 95% confidence interval, 0.90-2.73). Conclusions-The results demonstrate an increased risk of stroke, specifically ischemic stroke among hypertensive subjects with NSAIDs use. It would be important to closely monitor the transient effect of initial NSAIDs treatment, particularly in patients with hypertension. © 2015 American Heart Association, Inc. Source

Fang W.-T.,National Health Research Institute | Fan C.-C.,Mackay Memorial Hospital | Fan C.-C.,Yuanpei University | Li S.-M.,National Health Research Institute | And 24 more authors.
International Journal of Cancer | Year: 2014

SOX2 is a transcription factor essential for self-renewal and pluripotency of embryonic stem cells. Recently, SOX2 was found overexpressed in the majority of the lung squamous cell carcinoma (SQC), in which it acts as a lineage-survival oncogene. However, downstream targets/pathways of SOX2 in lung SQC cells remain to be identified. Here, we show that BMP4 is a downstream target of SOX2 in lung SQC. We found that SOX2-silencing-mediated inhibition of cell growth was accompanied by upregulation of BMP4 mRNA and its protein expression. Meta-analysis with 293 samples and qRT-PCR validation with 73 clinical samples revealed an inversely correlated relationship between levels of SOX2 and BMP4 mRNA, and significantly lower mRNA levels in tumor than in adjacent normal tissues. This was corroborated by immunohistochemistry analysis of 35 lung SQC samples showing lower BMP4 protein expression in tumor tissues. Cell-based experiments including siRNA transfection, growth assay and flow cytometry assay, further combined with a xenograft tumor model in mice, revealed that reactivation of BMP4 signaling could partially account for growth inhibition and cell cycle arrest in lung SQC cells upon silencing SOX2. Finally, chromatin immunoprecipitation analysis and luciferase reporter assay revealed that SOX2 could negatively regulate BMP4 promoter activity, possibly through binding to the promoter located in the first intron region of BMP4. Collectively, our findings suggest that BMP4 could act as a tumor suppressor and its downregulation by elevated SOX2 resulting in enhanced growth of lung SQC cells. © 2014 UICC. Source

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