1,637 research outputs found

    Acetyl-CoA-mediated autoacetylation of fatty acid synthase as a metabolic switch of de novo lipogenesis in Drosophila

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    De novo lipogenesis is a highly regulated metabolic process, which is known to be activated through transcriptional regulation of lipogenic genes, including fatty acid synthase (FASN). Unexpectedly, we find that the expression of FASN protein remains unchanged durin

    Apoptosis Induction in Primary Human Colorectal Cancer Cell Lines and Retarded Tumor Growth in SCID Mice by Sulforaphane

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    We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 μM) and subG1 (SFN 12.5 and 25 μM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential (ΔΨm). Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer

    A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait.

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    In humans, the connection between sleep and mood has long been recognized, although direct molecular evidence is lacking. We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and seasonality scores. hPER3-P415A/H417R transgenic mice showed an altered circadian period under constant light and exhibited phase shifts of the sleep-wake cycle in a short light period (photoperiod) paradigm. Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize PERIOD1/2 proteins, which play critical roles in circadian timing. Although hPER3-P415A/H417R-Tg mice showed a mild depression-like phenotype, Per3 knockout mice demonstrated consistent depression-like behavior, particularly when studied under a short photoperiod, supporting a possible role for PER3 in mood regulation. These findings suggest that PER3 may be a nexus for sleep and mood regulation while fine-tuning these processes to adapt to seasonal changes

    Risk Analysis of Cargos Damages for Aquatic Products of Refrigerated Containers: Shipping Operators’ Perspective in Taiwan

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    As the development of refrigerated container, transportation of aquatic products is growing rapidly in recent years. It is very important to avoid cargos damages for aquatic products of refrigerated containers, while the shipping operators are running this scope of business. Hence, the risk issue of adopting various improvement strategies would be important for the container shipping operators. In the light of this, the main purpose of this paper is to analyze the risks of cargos damages for aquatic products of refrigerated containers based on the container shipping operators’ perspective in Taiwan. We use four risk assessment procedures - risk identification, risk analysis and evaluation, risk strategies, and risk treatment - as the research method in this paper. The risk factors are generated from literature review and experts interviewing. Then, three dimensions with nineteen risk factors are preliminary identified. We used these risk factors to proceed with the empirical study via questionnaires. Three points of empirical results are presented. At first, the top factor of perceived risk as well as of risk severity is ‘container data setting errors.’ Secondly, the top factor of risk frequency is ‘lack of the goods’ pre-cooling themselves.’ Thirdly, three risk factors are classified into the low-risk area, whereas sixteen risk factors are placed on the medium-risk area. There is no risk factor fix on the high-risk area. Furthermore, three risk strategies - risk prevention, risk reduction, and risk transfer - are suggested to adopt by different risk factors

    “I can’t see an end in sight.” How the COVID-19 pandemic may influence suicide risk: a qualitative study

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    <jats:p> Zusammenfassung: Theoretischer Hintergrund: Das Ziel der vorliegenden Studie war es, eine deutschsprachige Adaptation der Bergen Study Addiction Scale (BStAS), einer Skala zur Erfassung von exzessivem Studierverhalten, zu entwickeln und zu validieren. Methode: Die Daten von 615 Studierenden wurden analysiert. Die Dimensionalität der BStAS wurde mittels konfirmatorischer Faktorenanalyse überprüft. Außerdem wurden Korrelations- und hierarchische Regressionsanalysen durchgeführt, um Zusammenhänge von exzessivem Studierverhalten mit Persönlichkeit und Gesundheit zu untersuchen. Ergebnisse: Der Vergleich mit Dynamic Fit Index Cutoffs deutete auf eine moderate Missspezifikation des einfaktoriellen Modells hin. Wie erwartet war exzessives Studierverhalten positiv mit wöchentlichen Lernstunden, Neurotizismus, wahrgenommenem Stress, psychosomatischen Beschwerden und Schlafproblemen assoziiert und hing negativ mit Lebenszufriedenheit zusammen. Schlussfolgerung: Es ist fraglich, ob alle Items der BStAS Aspekte einer Verhaltenssucht erfassen. Die Ergebnisse legen dennoch nahe, dass die BStAS ein Studierverhalten misst, das in Bezug auf physische und psychische Gesundheit von Relevanz ist. </jats:p&gt

    Trajectory of low-density lipoprotein cholesterol in patients with chronic kidney disease and its association with cardiovascular disease

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    BackgroundThe role of longitudinal temporal trends in LDL-C in cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) and diabetes is unclear. This study categorized the long-term LDL-C trajectory and determined its association with the incidence of atherosclerotic CVD in patients with CKD according to diabetes status and estimated glomerular filtration rate (eGFR).MethodsThe risk of atherosclerotic CVD was estimated in 137,127 Taiwanese patients with CKD using six LDL-C trajectory classes determined by the latent class mixed model as optimal, near optimal, above optimal, borderline, sustained high, and declined high over 5 years.ResultsThe risk of CVD was higher in the sustained high LDL-C [>160 mg/dL over time; adjusted hazard ratio (aHR) = 1.68, 95% CI = 1.45–1.94], declined high LDL-C (>160 to <100 mg/dL; aHR = 1.23, 95% CI = 1.11–1.38), and borderline LDL-C (approximately 140 mg/dL over time; aHR = 1.16, 95% CI = 1.07–1.26) groups than in the optimal LDL-C group (<100 mg/dL over time). There was no such association in patients with an eGFR <15 mL/min/1.73 m2. Persistent diabetes was associated with a 1.15–2.47-fold increase in CVD in patients with high LDL-C (>120 mg/dL).ConclusionThe LDL-C trajectory pattern was associated with the phenotype of CVD risk. The degree of risk varied according to eGFR and diabetes status. A stable low LDL-C over time was potentially beneficial for prevention of CVD. Intensive lipid management and periodic assessment of LDL-C is essential to reduce the risk of CVD in patients with CKD and diabetes

    Preoperative Proteinuria Is Associated with Long-Term Progression to Chronic Dialysis and Mortality after Coronary Artery Bypass Grafting Surgery

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    AIMS: Preoperative proteinuria is associated with post-operative acute kidney injury (AKI), but whether it is also associated with increased long-term mortality and end-stage renal disease (ESRD) is unknown. METHODS AND RESULTS: We studied 925 consecutive patients undergoing CABG. Demographic and clinical data were collected prospectively, and patients were followed for a median of 4.71 years after surgery. Proteinuria, according to dipstick tests, was defined as mild (trace to 1+) or heavy (2+ to 4+) according to the results of the dipstick test. A total of 276 (29.8%) patients had mild proteinuria before surgery and 119 (12.9%) patients had heavy proteinuria. During the follow-up, the Cox proportional hazards model demonstrated that heavy proteinuria (hazard ratio [HR], 27.17) was an independent predictor of long-term ESRD. There was a progressive increased risk for mild proteinuria ([HR], 1.88) and heavy proteinuria ([HR], 2.28) to predict all-cause mortality compared to no proteinuria. Mild ([HR], 2.57) and heavy proteinuria ([HR], 2.70) exhibited a stepwise increased ratio compared to patients without proteinuria for long-term composite catastrophic outcomes (mortality and ESRD), which were independent of the baseline GFR and postoperative acute kidney injury (AKI). CONCLUSION: Our study demonstrated that proteinuria is a powerful independent risk factor of long-term all-cause mortality and ESRD after CABG in addition to preoperative GFR and postoperative AKI. Our study demonstrated that proteinuria should be integrated into clinical risk prediction models for long-term outcomes after CABG. These results provide a high priority for future renal protective strategies and methods for post-operative CABG patients
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