Increased endoplasmic reticulum (ER) stress is known to be one of the causes of hypothalamic neuronal damage, as well as a cause of metabolic disorders such as obesity and diabetes. Recent evidence ...has suggested that Undaria pinnatifida (UP), an edible brown algae, has antioxidant activity. However, the neuroprotective effect of UP has yet to be examined. In this study, to investigate the neuroprotective effect of UP on ER stress-induced neuronal damage in mouse hypothalamic neurons, mice immortal hypothalamic neurons (GT1-7) were incubated with extract of UP. ER stress was induced by treating with tunicamycin. Tunicamycin induced apoptotic cell death was compared with the vehicle treatment through excessive ER stress. However UP protected GT1-7 cells from cell death, occurring after treatment with tunicamycin by reducing ER stress. Treatment with UP resulted in reduced increment of ATF6 and CHOP, and recovered the decrease of phosphorylation of Akt/mTOR by tunicamycin and the increment of autophagy. These results show that UP protects GT1-7 cells from ER stress induced cell death through the Akt/mTOR pathway. The current study suggests that UP may have a beneficial effect on cerebral neuronal degeneration in metabolic diseases with elevated ER stress.
Increased oxidative stress and impaired antioxidant defense are important mechanisms in the pathogenesis of diabetic myopathy. Alpha-lipoic acid (ALA) has been indicated as a weight-loss treatment in ...rodents and humans, but studies are limited. In the present study, we aimed to determine the influence of ALA, a potent biological antioxidant, on metabolic and growth processes in diabetic rat skeletal muscle.
Male 25-week-old type 2 diabetic rats (OLETF) were randomly divided into two groups, a control group (OLETF-C) and an ALA-treated group (OLETF-ALA) supplemented with 100 mg/kg ALA for 8 weeks. Age-matched, healthy, nondiabetic LETO (LETO-C) rats were used as controls.
At 32 weeks of age, body weight was decreased by 6.8%, and the areas under the curve of IP-GTT, fasting glucose, and insulin were less in OLETF-ALA rats compared with OLETF-C rats. ALA significantly preserved muscle mass and enhanced muscle fiber cross-sectional area and fiber frequency percentage in the skeletal muscle of OLETF rats. Although the activation of myoD, myogenin, and myostatin in gastrocnemius muscle was significantly inhibited in OLETF-ALA rats relative to OLETF-C rats, there were no differences in the expression levels of muscle atrogin-1 and MuRF1 between the two groups. ALA treatment significantly increased the levels of phosphorylated 5'-AMPK, SIRT1, and PGC-1α, as well as the levels of phosphorylated AKT, mTOR, and p70S6 kinase in OLETF-ALA rats compared with OLETF-C rats. In contrast, the levels of phosphorylated p38 MAPK, IRS-1, and FOXO1 were decreased in OLETF-ALA rats compared with OLETF-C rats.
ALA treatment preserved mass in the gastrocnemius muscles of OLETF rats. ALA significantly upregulated the AMPK/SIRT1/PGC-1α and AKT/mTOR/p70S6K signaling pathways in OLETF rat skeletal muscle. Therefore, ALA may be a potential therapeutic intervention for skeletal muscle loss in animal models of insulin resistance.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The prevalence of obesity and related comorbidities is increasing worldwide, including in Korea. The Korean Society for the Study of Obesity released the Obesity Fact Sheet 2017 to address this ...problem in the Korean population.
Data from the National Health Insurance Service Health Checkup database from 2006 to 2015 were standardized by age and sex using the 2010 Census. The definition of obesity was a body mass index (BMI) ≥25 kg/m
, and that of abdominal obesity was a waist circumference ≥90 cm in men and ≥85 cm in women. Multivariate adjusted Cox regression analysis was conducted, and hazard ratios (HRs) with 95% confidence intervals were calculated for comorbidities.
From 2009 to 2015, the prevalence of obesity increased from 29.7% to 32.4%, and that of abdominal obesity increased from 18.4% to 20.8%. Obesity with abdominal obesity also increased from 15.1% to 17.7%. Between 2014 and 2015, the prevalence of obesity increased until 30-40 years of age, but decreased from 40-50 years of age in men. In women, it increased until the mid-70s, and decreased thereafter. Abdominal obesity increased from 20-30 years of age to 70-80 years of age, but decreased thereafter. The HRs for type 2 diabetes mellitus, hypertension, dyslipidemia, myocardial infarction, and ischemic stroke were elevated in subjects with abdominal obesity, and their incidence increased as the BMI increased, but slowed down at BMI ≥35 kg/m
.
Based on the Obesity Fact Sheet 2017, strategies for reducing the prevalence of obesity and abdominal obesity are essential.
This paper proposed an ANN (Artificial Neural Network) controller to damp out inter-area oscillation of a power system using BESS (Battery Energy Storage System). The conventional lead-lag ...controller-based PSSs (Power System Stabilizer) have been designed using linear models usually linearized at heavy load conditions. This paper proposes a non-linear ANN based BESS controller as the ANN can emulate nonlinear dynamics. To prove the performance of this nonlinear PSS, two linear PSS are introduced at first which are linearized at the heavy load and light load conditions, respectively. It is then verified that each controller can damp out inter-area oscillations at its own condition but not satisfactorily at the other condition. Finally, an ANN controller, that learned the dynamics of these two controllers, is proposed. Case studies are performed using PSCAD/EMTDC and MATLAB. As a result, the proposed ANN PSS shows a promising robust nonlinear performance.
Human cytochrome P450 1B1 (CYP1B1)-mediated biotransformation of endobiotics and xenobiotics plays an important role in the progression of human breast cancer. In this study, we investigated the ...effects of WY-14643, a peroxisome proliferator-activated receptor α (PPARα) agonist, on CYP1B1 expression and the related mechanism in MCF7 breast cancer cells. We performed quantitative reverse transcription-polymerase chain reaction, transient transfection, and chromatin immunoprecipitation to evaluate the effects of PPARα on peroxisome proliferator response element (PPRE)-mediated transcription. WY-14643 increased the protein and mRNA levels of CYP1B1, as well as promoter activity, in MCF-7 cells. Moreover, WY-14643 plus GW6471, a PPARα antagonist, significantly inhibited the WY-14643-mediated increase in CYP1B1 expression. PPARα knockdown by a small interfering RNA markedly suppressed the induction of CYP1B1 expression by WY-14643, suggesting that WY-14643 induces CYP1B1 expression via a PPARα-dependent mechanism. Bioinformatics analysis identified putative PPREs (-833/-813) within the promoter region of the CYP1B1 gene. Inactivation of these putative PPREs by deletion mutagenesis suppressed the WY-14643-mediated induction of CYP1B1 promoter activation. Furthermore, WY-14643 induced PPARα to assume a form capable of binding specifically to the PPRE-binding site in the CYP1B1 promoter. Our findings suggest that WY-14643 induces the expression of CYP1B1 through activation of PPARα.
BACKGROUNDThis study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic ...acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN). METHODSThis study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS). RESULTSOf the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval CI) between the two groups was -0.65 (-1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ₁=0.51). For the TSS, the treatment difference was -0.05 (-1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ₂=0.054). There were no serious adverse events associated with the treatments. CONCLUSIONGLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.
In Korea, patients diagnosed with complex regional pain syndrome (CRPS) in the army are typically discharged from the army; however, the course of the disease after discharge is not known. The ...purpose of this study was to investigate the course of CRPS that occurred in the army and to identify the influences of various clinical and psychosocial factors immediately before discharge on the disease course.
Clinical profiles and psychosocial status were collected from the medical records of 16 patients with CRPS type 1 who were discharged during the period between March 2017 and April 2018. The degree of improvement after discharge was assessed by follow-up evaluation through telephone contact. Cox proportional hazards regression was performed to identify clinical and psychosocial predictors for the rate of recovery.
The median time to recovery after discharge was 39 weeks (95% confidence interval CI = 8.8-69.2 weeks). The sole predictor for time to recovery after discharge was the time period from the onset of pain to discharge. Each one-week increase in the duration of pain experienced in the military was associated with a 18.2% (95% CI = 5.3%-29.5%) reduction in the rate of recovery after discharge (P = 0.007).
Patients who experienced a short period of pain in the military demonstrated a relatively good prognosis after discharge. This may show how prolonged pain in the army could affect the experience of pain from a social point of view, in that it shows the disease course after a change in the social environment.
Highlights • We investigated protective efficacy of FAdV-4 vaccine against other serotypes. • To test that efficacy we conducted serological study and animal challenge study. • That vaccine provided ...broad cross-protection efficacy to vaccinated bird and progenies.
Atmospheric particulate matter (PM) is an important cause of skin damage, and an increasing number of studies have been conducted to discover safe, natural materials that can alleviate the oxidative ...stress and inflammation caused by PM. It has been previously shown that the extract of Ecklonia cava Kjellman, a perennial brown macroalga, can alleviate oxidative stress in epidermal keratinocytes exposed to PM less than 10 microns in diameter (PM10). The present study was undertaken to further examine the anti-inflammatory effects of E. cava extract and its major polyphenolic constituent, dieckol. HaCaT keratinocytes were exposed to PM10 in the presence or absence of E. cava extract or dieckol and analyzed for their viability, prostaglandin E2 (PGE2) release, and gene expression of cyclooxygenase (COX)-1, COX-2, microsomal prostaglandin E2 synthase (mPGES)-1, mPGES-2, and cytosolic prostaglandin E2 synthase (cPGES). PM10 treatment decreased cell viability and increased the production of PGE2, and these changes were partially abrogated by E. cava extract. E. cava extract also attenuated the expression of COX-1, COX-2, and mPGES-2 stimulated by PM10. Dieckol attenuated PGE2 production and the gene expression of COX-1, COX-2, and mPGES-1 stimulated by PM10. This study demonstrates that E. cava extract and dieckol alleviate airborne PM10-induced PGE2 production in keratinocytes through the inhibition of gene expression of COX-1, COX-2, mPGES-1, and/or mPGES-2. Thus, E. cava extract and dieckol are potentially useful natural cosmetic ingredients for counteracting the pro-inflammatory effects of airborne PM.
Objectives
Pulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). The survival rates and mortality‐predictive factors of a nationwide registry of ...Korean patients with CTD‐PH measured by echocardiography were determined.
Methods
Patients with CTD‐PH were enrolled between April 2008 and December 2012. Hemodynamic parameters and clinical data (WHO‐functional class FC, organ involvement, laboratory tests and treatment agents) were recorded. Survival rates were calculated by using the Kaplan–Meier method. Mortality‐associated factors were examined by Cox proportional hazards regression analysis.
Results
In total, 174 incident PH cases (61 with systemic lupus erythematosus, 50 with systemic sclerosis, 10 with mixed CTD, 22 with rheumatoid arthritis (RA) and 31 with other CTDs) were diagnosed by Doppler echocardiography. Of these, 25 (14%) died during the 3.8 ± 2.7 year follow‐up period after PH diagnosis. The 1‐ and 3‐year survival rates were 90.7% and 87.3%, respectively. Compared to the other CTD‐PHs, RA‐PH had the lowest survival rates (56% 3 year survival; P = 0.022). Multiple regression analysis revealed that low diffusion capacity of carbon monoxide (DLCO), pleural effusion and diabetes mellitus were poor prognostic factors (P = 0.008, 0.04 and 0.009, respectively). Anti‐UI‐RNP (ribonucleoprotein) antibody positivity was protective (P = 0.022). In patients with WHO‐FC III/IV, patients who received vasodilators had lower mortality than those who did not (P = 0.038).
Conclusions
In Korean patients with CTD‐PH, the 3‐year survival rate was 87%. Low diffusion capacity of carbon monoxide (DLCO), pleural effusion and diabetes mellitus were independent poor prognostic factors. Anti‐UI‐RNP antibody was protective. Prompt PAH‐specific vasodilator therapy may improve the survival of patients with severe CTD‐PH.
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