37 research outputs found

    The Molecular Mechanisms of Thymidine Phosphorylase in Survival of Monocytic Leukemia Cell

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    Thymidine phosphorylase (TP; EC 2.4.2.4), catalyzing the reversible reaction of thymidine to thymine and 2-deoxy-α-D-ribose-1-phosphate, plays roles not only in dTTP metabolism but also angiogenesis and anti-apoptosis. Previously, our laboratory found that depletion of TP in monocytic leukemia cell line U937 and THP-1 cell lines by lentiviral-based small hairpin RNA (shRNA) leads to apoptosis. Interestingly, expression of catalytic dead TP was able to rescue these cells, but not addition of TP catabolites to the culture medium. These results indicate that TP provides a survival signal independent of the catalytic function. In this study, I further dissect the mechanism of TP-mediated cell survival. Several signal cascades involved in cell survival, such as ERK1/2 and Akt, were found to be reduced by TP depletion. In addition, perturbation of mitochondrial membrane potential is accompanied by a decrease in Bcl-2 expression in cells depleted of TP. Contrarily, STAT3, one of the signals in JAK/STAT cascade involved in cell survival, stayed more active in these cells with the increased levels of COX2, SOCS3 and GM-CSF transcription. In order to understand the mechanism, I performed yeast two-hybrid screening to search for TP interacting proteins. Despite several proteins were identified capable of interacting with TP in yeast, co-expression of each of these proteins with TP did not form complex in human. Therefore, it remains to learn how TP exerts its biological function in influencing cell survival signal in monocytic leukemia cells

    The Relationship between Metabolically Healthy Obesity and the Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis

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    Cardiovascular disease (CVD) risk in individuals with metabolically healthy obesity (MHO) is unclear. We searched databases from inception to May 2019. Data were pooled using a random effects model. Newcastle-Ottawa Scale assessment was performed. Primary and secondary outcomes were CVD risk and all-cause mortality. Forty-three studies involving 4,822,205 cases were included. The median percentage of females, age and duration of follow-up was 52%, 49.9 years and 10.6 years, respectively. The mean Newcastle-Ottawa Scale score of the articles was 7.9 ± 1.0. Compared to individuals with a metabolically healthy normal weight, individuals with MHO had higher adjusted risk of CVD and all-cause mortality. We identified a significant linear dose-response relationship between body mass index (BMI) and CVD risk among metabolically healthy individuals (p < 0.001); every unit increase in BMI increased the CVD risk. Multivariate meta-regression analysis showed that an increased proportion of women and age resulted in the risk of CVD affected by MHO reduction (p = 0.014, p = 0.030, respectively). Age and sex explained the observed heterogeneity and reported the adjusted R2. MHO resulted in a significantly increased risk for CVD; therefore, long-term weight loss should be encouraged

    Tongue Pressure Sensing Array Integrated with a System-on-Chip Embedded in a Mandibular Advancement Splint

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    Obstructive sleep apnea (OSA), which is caused by obstructions of the upper airway, is a syndrome with rising prevalence. Mandibular advancement splints (MAS) are oral appliances for potential treatment of OSA. This work proposes a highly-sensitive pressure sensing array integrated with a system-on-chip (SoC) embedded in a MAS. The device aims to measure tongue pressure distribution in order to determine the efficacy of the MAS for treating OSA. The flexible sensing array consists of an interdigital electrode pair array assembled with conductive polymer films and an SoC capable of retrieving/storing data during sleep, and transmitting data for analysis after sleep monitoring. The surfaces of the conductive polymer films were patterned with microdomed structures, which effectively increased the sensitivity and reduced the pressure sensing response time. The measured results also show that the crosstalk effect between the sensing elements of the array was negligible. The sensitivity of the sensing array changed minimally after the device was submerged in water for up to 100 h

    Association of metabolically healthy obesity and elevated risk of coronary artery calcification: a systematic review and meta-analysis

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    Background Metabolically healthy obesity (MHO) is defined as obesity with less than two parameters of metabolic abnormalities. Some studies report that MHO individuals show similar risk of cardiovascular disease (CVD) compared with metabolically healthy non-obese (MHNO) individuals, but the results are conflicting. Coronary artery calcium (CAC) reflects the extent of coronary atherosclerosis and is a useful tool to predict future risk of CVD. The objective of this meta-analysis was to investigate whether MHO is associated with elevated risk of CAC. Method We searched Cochrane, PubMed, and Embase up to April 19, 2019. Prospective cohort and cross-sectional studies examining the association between MHO subjects and CAC were included with MHNO as the reference. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effect models. Subgroup analysis and meta-regression were applied to define possible sources of heterogeneity. We conducted this research following a pre-established protocol registered on PROSPERO (CRD 42019135006). Results A total of nine studies were included in this review and six studies with 23,543 participants were eligible for the meta-analysis. Compared with MHNO subjects, MHO had a higher odds of CAC (OR 1.36, 95% CI [1.11 to 1.66]; I2 = 39%). In the subgroup analysis, the risk associated with MHO participants was significant in cohort studies (OR = 1.47, 95% CI [1.15,1.87], I2 = 0%), and borderline significant in cross-sectional studies. The risk of CAC was also significant in MHO participants defined by Adult Treatment Panel III (ATP III) (OR = 1.55, 95% CI [1.25,1.93], I2 = 0%). The univariate meta-regression model showed that age and smoking status were possible effect modifiers for MHO and CAC risk. Conclusion Our meta-analysis showed that MHO phenotypes were associated with elevated risk of CAC compared with MHNO, which reflects the extent of coronary atherosclerosis. People with obesity should strive to achieve normal weight even when only one metabolic abnormality is present

    Laparoendoscopic single-site retroperitoneoscopic adrenalectomy compared with conventional laparoscopy and open surgery

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    Objective: Laparoendoscopic single-site surgery (LESS) is a new laparoscopy development that avoids the use of multiple ports and minimizes morbidity. Combined with retroperitoneoscopy, LESS is suitable for adrenalectomy. We compared open, conventional laparoscopic, and LESS-retroperitoneoscopic adrenalectomy (LESS-RA) surgeries for adrenal tumor removal. Furthermore, we analyzed the conventional retroperitoneoscopic adrenalectomy (CRA) and LESS-RA outcomes. Materials and Methods: We examined 178 patients who underwent adrenalectomy: 43 by open surgery, 72 by conventional laparoscopy, and 63 by LESS-RA. We analyzed the outcomes of operative time, estimated blood loss (EBL), complications, postoperative convalescence, time to resuming oral intake, analgesics on demand, and hospital stay. Results: We found that the open surgery group had a significantly greater mean EBL than the conventional laparoscopy or LESS-RA group (353.1±313.6 mL vs. 62.3±76.9 mL vs. 60.9±64.3 mL, respectively; p<0.0001). Open surgery was lengthier than LESS-RA. Both hospital stay and time to resuming oral intake were shortest in the LESS-RA group, followed by conventional laparoscopy and open surgery. CRA and LESS-RA did not differ significantly in mean tumor size, operation time, or EBL. However, there were significant differences in postoperative hospital stay length (6.4±3.4 days vs. 3.6±1.3 days, respectively; p<0.0001), time to resuming oral intake (1.2±0.5 days vs. 0.4±0.5 days, respectively; p<0.0001), and number of on-demand intravenous or intramuscular analgesics needed (0.5±0.8 ampoules/vial vs. 0.3±0.6 ampoules/vial, respectively; p=0.0484). Conclusion: The standard approach to adrenalectomy recently improved from open to laparoscopic surgery, transperitoneal to retroperitoneal access, and multiple ports to a single port. Here we found that laparoscopic surgery had better intra- and postoperative outcomes than open surgery. Furthermore, patients treated with LESS-RA required less postoperative recovery time and less analgesic use than those treated with CRA

    Obesity phenotypes and their relationships with atrial fibrillation

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    Background This study assessed the associations of metabolic obesity phenotypes with the risk of atrial fibrillation (Afib). Methods This prospective cohort study categorized Taiwanese adults according to their body mass index (BMI) and metabolic health status at baseline. We assigned the participants to the underweight (BMI < 18.5 kg/m2), normal weight (BMI = 18.5–23.9 kg/m2), and overweight/obesity groups (BMI ≥ 24 kg/m2). Metabolically healthy was defined as absence of hypertension, diabetes, and hyperlipidemia and the presence of healthy metabolic profiles. Results In total, 5,742 adults were included. During a median follow-up of 13.7 years, 148 patients developed Afib. Compared to the metabolically healthy normal weight group, the risk of Afib was significantly higher than those in the metabolically unhealthy overweight/obesity (hazard ratio = 2.20, 95% confidence interval [1.12–4.33]) and metabolically unhealthy normal weight groups (HR = 2.64, 95% CI [1.34–5.17]). Additionally, the point estimate suggested a 1.97-fold greater risk among the metabolically healthy overweight/obesity group, although this difference was not significant given the wide confidence interval (HR = 1.97, 95% CI [0.80–4.86]). Conclusion Our results demonstrated the relationships of metabolic health and weight regarding the risk of Afib in Taiwanese adults. The Afib risk among metabolic and obesity phenotypes is associated with a metabolically unhealthy status. A trend toward a higher Afib risk with obesity among metabolically healthy subjects was observed. However, the result was not robust and it still suggested further study
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