Prehospital factors associated with out-of-hospital cardiac arrest outcomes in a metropolitan city: a 4-year multicenter study.

BACKGROUND: Prehospital factors play a vital role in out-of-hospital cardiac arrest (OHCA) survivability, and they vary between countries and regions. We investigated the prehospital factors associated with OHCA outcomes in a single metropolitan city in the Republic of Korea. METHODS: This study included adult medical OHCA patients enrolled prospectively, using data from the citywide OHCA registry for patients registered between 2018 and 2021. The primary outcome was survival to hospital discharge. Multivariable logistic regression analysis was conducted to determine the factors associated with the study population's clinical outcomes, adjusting for covariates. We performed a sensitivity analysis for clinical outcomes only for patients without prehospital return of spontaneous circulation prior to emergency medical service departure from the scene. RESULTS: In multivariable logistic regression analysis, older age (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.95-0.97), endotracheal intubation (adjusted odds ratio [aOR] 0.29; 95% [CIs] 0.17-0.51), supraglottic airway (aOR 0.29; 95% CI 0.17-0.51), prehospital mechanical chest compression device use (OR 0.13; 95% CI 0.08-0.18), and longer scene time interval (OR 0.96; 95% CI 0.93-1.00) were negatively associated with survival. Shockable rhythm (OR 24.54; 95% CI 12.99-42.00), pulseless electrical activity (OR 3.11; 95% CI 1.74-5.67), and witnessed cardiac arrest (OR 1.59; 95% CI 1.07-2.38) were positively associated with survival. In the sensitivity analysis, endotracheal intubation, supraglottic airway, prehospital mechanical chest compression device use, and longer scene time intervals were associated with significantly lower survival to hospital discharge. CONCLUSIONS: Regional resuscitation protocol should be revised based on the results of this study, and modifiable prehospital factors associated with lower survival of OHCA should be improved.

Perfluorinated compounds in adults and their association with fasting glucose and incident diabetes: a prospective cohort study.

BACKGROUND: The endocrine disruption of perfluorinated compounds is an emerging issue. We aimed to examine the association of serum perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels with incident diabetes and fasting serum glucose concentration. METHODS: This prospective cohort study was based on an urban-based cohort subpopulation from the Korean Genome and Epidemiology Study. Serum samples (600 µL) were received from 100 participants in the normoglycemic baseline survey (2004-2013), and concentrations of PFOA and PFOS were measured using mass spectrometry. The incidence of diabetes was tracked in the follow-up survey (2012-2016). RESULTS: The mean age was 56.4 years (men, 59%). The median serum PFOA and PFOS concentrations were 4.29 ng/mL and 9.44 ng/mL, respectively. PFOA and PFOS concentrations differed according to age, sex, and residential area. After 60 months, 23 patients had diabetes. Log-transformed PFOA (lnPFOA) and log-transformed PFOS (lnPFOS) were significantly higher in those who transitioned to diabetes than in those who did not (both p < 0.05). After multivariate adjustment, lnPFOA (coefficient = 6.98, 95% CI -0.04-14, p = 0.054) and lnPFOS (coefficient = 7.06, 95% CI -0.96-15.08, p = 0.088) predicted increased fasting glucose without statistical significance. In addition, lnPFOA, but not lnPFOS, significantly predicted incident diabetes (HR = 3.98, 95% CI 1.42-11.1, p < 0.01). CONCLUSION: Exposure to PFOA and PFOS may have a potential dysglycemic effect. In particular, exposure to PFOA increased the risk of diabetes. Further research with larger sample size is warranted.

Ameliorative Effects of Lactobacillus plantarum HAC01 Lysate on 3T3-L1 Adipocyte Differentiation via AMPK Activation and MAPK Inhibition.

Lactobacillus plantarum HAC01 has been shown to effectively treat metabolic diseases. However, the precise pharmacological effects and molecular mechanisms of L. plantarum HAC01 remain unclear. In this study, we investigate the anti-adipogenic effects of L. plantarum HAC01 lysate and its associated mechanism of action. To induce lipid accumulation, 3T3-L1 cells were incubated in differentiation media with or without L. plantarum HAC01 lysate. Our results show that L. plantarum HAC01 lysate treatment not only reduced lipid accumulation during the differentiation of 3T3-L1 cells, but also decreased the expression of adipogenic and lipogenic genes involved in lipid metabolism in a dose-dependent manner. Additionally, L. plantarum HAC01 lysate inhibited CCAAT/enhancer-binding protein (C/EBP) beta within 4 h of differentiation induction and inhibited peroxisome proliferator-activated receptor gamma, C/EBP alpha, and sterol regulatory element-binding proteins within 2 d. Moreover, treatment with L. plantarum HAC01 lysate increased the phosphorylation of adenosine monophosphate-activated protein kinase, an important regulator of energy metabolism, and decreased the phosphorylation of mitogen-activated protein kinase. These results indicate that L. plantarum HAC01 lysate may have anti-adipogenic effects and support its potential as a useful agent for the treatment of obesity.

Honeysuckle Berry (Lonicera caerulea L.) Inhibits Lipase Activity and Modulates the Gut Microbiota in High-Fat Diet-Fed Mice.

Honeysuckle berry (HB, Lonicera caerulea L.) is an oriental herbal medicine reported to have beneficial effects on metabolic disorders, such as obesity and non-alcoholic fatty liver disease. The fruit part of HB is rich in anthocyanin, a type of polyphenol. Most studies credit the antioxidant and anti-inflammatory properties of HB as the mechanisms of its effectiveness. This study investigated the inhibitory effects of HB on lipase using an in vitro assay and the modulatory effect of HB on gut microbiota in high-fat diet (HFD)-fed mice. HB inhibited pancreatic lipase activity with IC50 values of approximately 0.47 mg/mL. The fecal triglyceride (TG) levels were higher from the HFD of the HB-fed mice than they were for the control mice. Moreover, the fecal microbiota from the HFD of the HB-fed mice had relatively lower Firmicutes and higher Bacteroidetes than that from the HFD-only mice. These results suggest that HB modulates gut microbiota composition, which may contribute to body fat reduction. Hence, HB could present a useful agent for treating metabolic diseases through lower TG uptake and the regulation of gut microflora.

Lithium enhances exercise-induced glycogen breakdown and insulin-induced AKT activation to facilitate glucose uptake in rodent skeletal muscle.

The purpose of this study was to investigate the effect of lithium on glucose disposal in a high-fat diet-induced type 2 diabetes mellitus (T2DM) and streptozotocin-induced type 1 diabetes mellitus (T1DM) animal model along with low-volume exercise and low-dose insulin. Lithium decreased body weight, fasting plasma glucose, and insulin levels when to treat with low-volume exercise training; however, there were no adaptive responses like an increase in GLUT4 content and translocation factor levels. We discovered that lithium enhanced glucose uptake by acute low-volume exercise-induced glycogen breakdown, which was facilitated by the dephosphorylation of serine 473-AKT (Ser473-AKT) and serine 9-GSK3ß. In streptozotocin-induced T1DM mice, Li/low-dose insulin facilitates glucose uptake through increase the level of exocyst complex component 7 (Exoc7) and Ser473-AKT. Thus, lithium enhances acute exercise-induced glycogen breakdown and insulin-induced AKT activation and could serve as a candidate therapeutic target to regulate glucose level of DM patients.

Clinical Characteristics and Outcomes of COVID-19 Cohort Patients in Daegu Metropolitan City Outbreak in 2020.

BACKGROUND: A coronavirus disease 2019 (COVID-19) outbreak started in February 2020 and was controlled at the end of March 2020 in Daegu, the epicenter of the coronavirus outbreak in Korea. The aim of this study was to describe the clinical course and outcomes of patients with COVID-19 in Daegu. METHODS: In collaboration with Daegu Metropolitan City and Korean Center for Diseases Control, we conducted a retrospective, multicenter cohort study. Demographic, clinical, treatment, and laboratory data, including viral RNA detection, were obtained from the electronic medical records and cohort database and compared between survivors and non-survivors. We used univariate and multi-variable logistic regression methods and Cox regression model and performed Kaplan-Meier analysis to determine the risk factors associated with the 28-day mortality and release from isolation among the patients. RESULTS: In this study, 7,057 laboratory-confirmed patients with COVID-19 (total cohort) who had been diagnosed from February 18 to July 10, 2020 were included. Of the total cohort, 5,467 were asymptomatic to mild patients (77.4%) (asymptomatic 30.6% and mild 46.8%), 985 moderate (14.0%), 380 severe (5.4%), and 225 critical (3.2%). The mortality of the patients was 2.5% (179/7,057). The Cox regression hazard model for the patients with available clinical information (core cohort) (n = 2,254) showed the risk factors for 28-day mortality: age > 70 (hazard ratio [HR], 4.219, P = 0.002), need for O2 supply at admission (HR, 2.995; P = 0.001), fever (> 37.5°C) (HR, 2.808; P = 0.001), diabetes (HR, 2.119; P = 0.008), cancer (HR, 3.043; P = 0.011), dementia (HR, 5.252; P = 0.008), neurological disease (HR, 2.084; P = 0.039), heart failure (HR, 3.234; P = 0.012), and hypertension (HR, 2.160; P = 0.017). The median duration for release from isolation was 33 days (interquartile range, 24.0-46.0) in survivors. The Cox proportional hazard model for the long duration of isolation included severity, age > 70, and dementia. CONCLUSION: Overall, asymptomatic to mild patients were approximately 77% of the total cohort (asymptomatic, 30.6%). The case fatality rate was 2.5%. Risk factors, including older age, need for O2 supply, dementia, and neurological disorder at admission, could help clinicians to identify COVID-19 patients with poor prognosis at an early stage.

New Simple 3-Dimensional Computed Tomogram Classification Leading to Successful Conservative Treatment in 51 Atlanto-Axial Rotatory Fixation Children.

OBJECTIVE: to present a new and easy classification of atlanto-axial rotatory fixation (AARF) and to investigate the efficiency of conservative treatment of AARF. BACKGROUND: Although there is a precise definition and diagnostic classification of AARF, there is still significant difficulty in measuring the atlas and axis angles because all of the atlas or axis cannot be seen in a certain 2-dimensional computed tomogram image. In addition, some recent case reports showed that long-term conservative treatment can reduce pediatric AARFs, even that are severe or chronic. METHODS: Fifty-one children with AARF were analyzed retrospectively with new 3-dimensional computed tomogram (3DCT)-based AARF classification; the mean age was 72.7 ± 35.2 months (19-139 months). In the new AARF classification, type 1 was defined as that when the C1C2 angle is not 0° on midline and type 2 as that when the C1C2 angle is 0° on the midline. RESULTS: All 7 children with AARF type 1 were treated successfully only with Halter tractions. Twenty among 44 children with type 2 did not show any difference in improvement compared with not-treated 24 children with type 2. CONCLUSION: The first new AARF classification based on 3DCT appears to be easy to use and even the most severe children with AARF may be managed only with conservative treatment such as long-term Halter traction.

QRS complex characteristics and patient outcomes in out-of-hospital pulseless electrical activity cardiac arrest.

BACKGROUND: Pulseless electrical activity (PEA) is increasingly observed in out-of-hospital cardiac arrest (OHCA), but outcomes are still poor. We aimed to assess the relationship between QRS characteristics and outcomes of patients with OHCA with initial PEA (OHCA-P). METHODS: This prospective observational study included patients aged at least 18 years who developed OHCA-P between 1 January 2016 and 31 December 2018, and were enrolled in the Daegu Emergency Medical Services registry, South Korea. We performed multivariable logistic regression analyses to identify the associations between QRS characteristics and OHCA-P outcomes, in which QRS complexes were considered separately (model 1) and simultaneously (model 2). The primary outcome was survival to hospital discharge and the secondary outcome was a favourable neurological outcome. RESULTS: Of the 3659 patients with OHCA, 576 were enrolled (median age 73 years; 334 men). A higher QRS amplitude was associated with survival to hospital discharge and a favourable neurological outcome in model 1 (adjusted OR (aOR) 1.077 and 1.106, respectively; 95% CI 1.021 to 0.136 and 1.029 to 1.190, respectively) and model 2 (aOR 1.084 and 1.123, respectively; 95% CI 1.026 to 1.145 and 1.036 to 1.216, respectively). A QRS width of <120 ms was associated with survival to hospital discharge and a favourable neurological outcome in model 1 (aOR 3.371 and 4.634, respectively; 95% CI 1.633 to 6.960 and 1.562 to 13.144, respectively) and model 2 (aOR 3.213 and 5.103, respectively; 95% CI 1.568 to 6.584 and 1.682 to 15.482, respectively). Survival to hospital discharge and neurological outcome were not associated with QRS frequency. CONCLUSION: OHCA-P outcomes were better when the initial QRS complex showed a higher amplitude or narrower width.

Role of PGC-1α in the Mitochondrial NAD+ Pool in Metabolic Diseases.

Mitochondria play vital roles, including ATP generation, regulation of cellular metabolism, and cell survival. Mitochondria contain the majority of cellular nicotinamide adenine dinucleotide (NAD+), which an essential cofactor that regulates metabolic function. A decrease in both mitochondria biogenesis and NAD+ is a characteristic of metabolic diseases, and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) orchestrates mitochondrial biogenesis and is involved in mitochondrial NAD+ pool. Here we discuss how PGC-1α is involved in the NAD+ synthesis pathway and metabolism, as well as the strategy for increasing the NAD+ pool in the metabolic disease state.

Lactiplantibacillusplantarum ATG-K2 Exerts an Anti-Obesity Effect in High-Fat Diet-Induced Obese Mice by Modulating the Gut Microbiome.

Obesity is a major health problem. Compelling evidence supports the beneficial effects of probiotics on obesity. However, the anti-obesity effect of probiotics remains unknown. In this study, we investigated the anti-obesity effects and potential mechanisms of Lactiplantibacillus plantarum ATG-K2 using 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese mice. 3T3-L1 cells were incubated to determine the effect of lipid accumulation with lysate of L. plantarum ATG-K2. Mice were fed a normal fat diet or HFD with L. plantarum ATG-K2 and Orlistat for 8 weeks. L. plantarum ATG-K2 inhibited lipid accumulation in 3T3-L1 adipocytes, and reduced body weight gain, WAT weight, and adipocyte size in HFD-induced obese mice, concurrently with the downregulation of PPARγ, SREBP1c, and FAS and upregulation of PPARα, CTP1, UCP1, Prdm16, and ND5. Moreover, L. plantarum ATG-K2 decreased TG, T-CHO, leptin, and TNF-α levels in the serum, with corresponding gene expression levels in the intestine. L. plantarum ATG-K2 modulated the gut microbiome by increasing the abundance of the Lactobacillaceae family, which increased SCFA levels and branched SCFAs in the feces. L. plantarum ATG-K2 exhibited an anti-obesity effect and anti-hyperlipidemic effect in 3T3-L1 adipocytes and HFD-induced obese mice by alleviating the inflammatory response and regulating lipid metabolism, which may be influenced by modulation of the gut microbiome and its metabolites. Therefore, L. plantarum ATG-K2 can be a preventive and therapeutic agent for obesity.

A Brief Telephone Severity Scoring System and Therapeutic Living Centers Solved Acute Hospital-Bed Shortage during the COVID-19 Outbreak in Daegu, Korea.

With the epidemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2, the number of infected patients was rapidly increasing in Daegu, Korea. With a maximum of 741 new patients per day in the city as of February 29, 2020, hospital-bed shortage was a great challenge to the local healthcare system. We developed and applied a remote brief severity scoring system, administered by telephone for assigning priority for hospitalization and arranging for facility isolation ("therapeutic living centers") for the patients starting on February 29, 2020. Fifteen centers were operated for the 3,033 admissions to the COVID-19 therapeutic living centers. Only 81 cases (2.67%) were transferred to hospitals after facility isolation. We think that this brief severity scoring system for COVID-19 worked safely to solve the hospital-bed shortage. Telephone scoring of the severity of disease and therapeutic living centers could be very useful in overcoming the shortage of hospital-beds that occurs during outbreaks of infectious diseases.

Selenoprotein W deficiency does not affect oxidative stress and insulin sensitivity in the skeletal muscle of high-fat diet-fed obese mice.

Selenoprotein W (SelW) is a selenium-containing protein with a redox motif found abundantly in the skeletal muscle of rodents. Previous in vitro studies suggest that SelW plays an antioxidant role; however, relatively few in vivo studies have addressed the antioxidant role of SelW. Since oxidative stress is a causative factor for the development of insulin resistance in obese subjects, we hypothesized that if SelW plays a role as an antioxidant, SelW deficiency could aggravate the oxidative stress and insulin resistance caused by a high-fat diet. SelW deficiency did not affect insulin sensitivity and H2O2 levels in the skeletal muscle of control diet-fed mice. SelW levels in the skeletal muscle were decreased by high-fat diet feeding for 12 wk. High-fat diet induced obesity and insulin resistance and increased the levels of H2O2 and oxidative stress makers, which were not affected by SelW deficiency. High-fat diet feeding increased the expression of antioxidant enzymes; however, SelW deficiency did not affect the expression levels of antioxidants. These results suggest that SelW does not play a protective role against oxidative stress and insulin resistance in the skeletal muscle of high-fat diet-fed obese mice.

Application of a Dual-Dispatch System for Out-of-Hospital Cardiac Arrest Patients: Will More Hands Save More Lives?

BACKGROUND: Recovery after out-of-hospital cardiac arrest (OHCA) is difficult, and emergency medical services (EMS) systems apply various strategies to improve outcomes. Multi-dispatch is one means of providing high-quality cardiopulmonary resuscitation (CPR), but no definitive best-operation guidelines are available. We assessed the effects of a basic life support (BLS)-based dual-dispatch system for OHCA. METHODS: This prospective observational study of 898 enrolled OHCA patients, conducted in Daegu, Korea from March 1, 2015 to June 30, 2016, involved patients > 18 years old with suspected cardiac etiology OHCA. In Daegu, EMS started a BLS-based dual-dispatch system in March 2015, for cases of cardiac arrest recognition by a dispatch center. We assessed the association between dual-dispatch and OHCA outcomes using multivariate logistic regressions. We also analyzed the effect of dual-dispatch according to the stratified on-scene time. RESULTS: Of 898 OHCA patients (median, 69.0 years; 65.5% men), dual-dispatch was applied in 480 (53.5%) patients. There was no difference between the single-dispatch group (SDG) and the dual-dispatch group (DDG) in survival at discharge and neurological outcomes (survival discharge, P = 0.176; neurological outcomes, P = 0.345). In the case of less than 10 minutes of on-scene time, the adjusted odds ratio was 1.749 (95% confidence interval [CI], 0.490-6.246) for survival discharge and 6.058 (95% CI, 1.346-27.277) for favorable neurological outcomes in the DDG compared with the SDG. CONCLUSION: Dual-dispatch was not associated with better OHCA outcomes for the entire study population, but showed favorable neurological outcomes when the on-scene time was less than 10 minutes.

Effects of feeding ethanol on growth performances, carcass characteristics, and lipid metabolism of finishing Korean cattle (Hanwoo) steers.

OBJECTIVE: The purpose of this study was to determine the effects of feeding ethanol on growth performances, carcass characteristics, and lipid metabolism of finishing Korean cattle (Hanwoo) steers. METHODS: Thirty (30) Hanwoo steers (average 25.1 months of age, body weight 660.1 kg) were assigned to three treatments: control (0% ethanol), E-3 (1.44% ethanol for 3 months), or E-5 (0.72% ethanol for 2 months followed by 1.44% ethanol for 3 months). The animals were allotted by treatment group into six pens and fed concentrate and perennial ryegrass. Ethanol (30%, v/v) was supplemented into drinking water twice a day to meet final concentrations based on average water consumption of finishing Hanwoo steers. RESULTS: There were no statistical differences among the groups in final body weight, average daily gain, or carcass yield grade indices such as cold carcass weight, fat thickness, and loin area. The marbling score tended (p = 0.228) to increase with the highest score (6.7) in the E-5 group followed by 6.3 and 6.0 in E-3 and control groups, respectively. The appearance frequencies of quality grades of 1++ (the best), 1+, 1, and 2, were; 30%, 50%, 0%, and 20% for control, 10%, 80%, 10%, and 0% for E-3, and 10%, 80%, 0%, and 10% for E-5 groups, respectively, indicating improvements of quality grades by feeding ethanol. Concentrations of serum glucose tended to decrease whereas those of insulin and non-esterified fatty acid to increase by feeding ethanol (E-3 and E-5; p>0.05). CONCLUSION: Feeding ethanol directly into drinking water of finishing Hanwoo steers stimulated lipogenesis in intramuscular adipose tissue (marbling) and thereby improved carcass quality grade. The serum metabolites results supported the hypothesis of lipolysis of existing adipose tissue, such as abdominal fats, and lipogenesis in intramuscular adipocytes.

Nutritional regulation of renal lipogenic factor expression in mice: comparison to regulation in the liver and skeletal muscle.

Regulation of lipogenesis by pathophysiological factors in the liver and skeletal muscle is well understood; however, regulation in the kidney is still unclear. To elucidate nutritional regulation of lipogenic factors in the kidney, we measured the renal expression of lipogenic transcriptional factors and enzymes during fasting and refeeding in chow-fed and high-fat-fed mice. We also examined the regulatory effect of the liver X receptor (LXR) on the expression of lipogenic factors. The renal gene expression of sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS) was reduced by fasting for 48 h and restored by refeeding, whereas the mRNA levels of forkhead box O (FOXO)1/3 were increased by fasting and restored by refeeding. Accordingly, protein levels of SREBP-1, FAS, and phosphorylated FOXO1/3 were reduced by fasting and restored by refeeding. The patterns of lipogenic factors expression in the kidney were similar to those in the liver and skeletal muscle. However, this phasic regulation of renal lipogenic gene expression was blunted in diet-induced obese mice. LXR agonist TO901317 increased the lipogenic gene expression and the protein levels of SREBP-1 precursor and FAS but not nuclear SREBP-1. Moreover, increases in insulin-induced gene mRNA and nuclear carbohydrate-responsive element binding protein (ChREBP) levels were observed in the TO901317-treated mice. These results suggest that the kidney shows flexible suppression and restoration of lipogenic factors following fasting and refeeding in lean mice, but this is blunted in obese mice. LXR is involved in the renal expression of lipogenic enzymes, and ChREBP may mediate the response.

New Intervention Model of Regional Transfer Network System to Alleviate Crowding of Regional Emergency Medical Center.

Emergency department (ED) crowding is a serious problem in most tertiary hospitals in Korea. Although several intervention models have been established to alleviate ED crowding, they are limited to a single hospital-based approach. This study was conducted to determine whether the new regional intervention model could alleviate ED crowding in a regional emergency medical center. This study was designed as a "before and after study" and included patients who visited the tertiary hospital ED from November 2011 to October 2013. One tertiary hospital and 32 secondary hospitals were included in the study. A transfer coordinator conducted inter-hospital transfers from a tertiary hospital to a secondary hospital for suitable patients. A total of 1,607 and 2,591 patients transferred from a tertiary hospital before and after the study, respectively (P < 0.001). We found that the median ED length of stay (LOS) decreased significantly from 3.68 hours (interquartile range [IQR], 1.85 to 9.73) to 3.20 hours (IQR, 1.62 to 8.33) in the patient group after implementation of the Regional Transfer Network System (RTNS) (P < 0.001). The results of multivariate analysis showed a negative association between implementation of the RTNS and ED LOS (beta coefficient -0.743; 95% confidence interval -0.914 to -0.572; P < 0.001). In conclusion, the ED LOS in the tertiary hospital decreased after implementation of the RTNS.

TLR2 deficiency attenuates skeletal muscle atrophy in mice.

Oxidative stress and inflammation are associated with skeletal muscle atrophy. Because the activation of toll-like receptor (TLR) 2 induces oxidative stress and inflammation, TLR2 may be directly linked to skeletal muscle atrophy. This study examined the role of TLR2 in skeletal muscle atrophy in wild-type (WT) and TLR2 knockout (KO) mice. Immobilization for 2 weeks increased the expression of cytokine genes and the levels of carbonylated proteins and nitrotyrosine in the skeletal muscle, but these increases were lower in the TLR2 KO mice. Muscle weight loss and a reduction in treadmill running times induced by immobilization were also attenuated in TLR2 KO mice. Furthermore, immobilization increased the protein levels of forkhead box O 1/3, atrogin-1 and muscle ring finger 1 in the WT mice, which was attenuated in TLR2 KO mice. In addition, immobilization-associated increases in ubiquitinated protein levels were lower in the TLR2 KO mice. Immobilization increased the phosphorylation of Akt and p70S6K similarly in WT and KO mice. Furthermore, cardiotoxin injection into the skeletal muscle increased the protein levels of atrogin-1, interleukin-6, and nitrotyrosine and increased the levels of ubiquitinated proteins, although these levels were increased to a lesser extent in TLR2 KO mice. These results suggest that TLR2 is involved in skeletal muscle atrophy, and the inhibition of TLR2 offers a potential target for preventing skeletal muscle atrophy.

Hemin improves insulin sensitivity in skeletal muscle in high fat-fed mice.

The present study examined whether hemin could prevent the development of high-fat diet-induced insulin resistance in the liver and skeletal muscle using a hyperinsulinemic-euglycemic clamp. A four-week high-fat feeding to mice increased the body weight, fat mass, and plasma levels of insulin and lipid, which were reduced by hemin. High-fat diet reduced whole body glucose uptake, which were increased by hemin. Insulin-stimulated hepatic glucose production (HGP) was increased by high-fat diet, but hemin had no significant effect on HGP. Skeletal muscle glucose uptake was reduced by high-fat diet, and hemin normalized the glucose uptake. High-fat diet increased triglyceride levels and mRNA levels of lipogenic enzymes, and decreased mRNA levels of enzymes involved in lipid ß-oxidation, which was reversed by hemin. Phosphorylated AMP-activated protein kinase levels were increased in the skeletal muscle of high fat-fed hemin-injected mice. High-fat diet reduced mRNA levels of antioxidant enzymes and increased mRNA levels of inflammatory cytokines and nitrotyrosine levels, which was normalized by hemin in the skeletal muscle. However, hemin had no significant effect on these factors in the liver. These results suggest that hemin prevents the development of high-fat diet-induced insulin resistance by increased insulin sensitivity in the skeletal muscle.

Comparative study on estrogen receptor alpha dimerization and transcriptional activity of parabens.

Parabens are used as preservatives in various household products, including oral products, cosmetics, and hair/body washes. In recent years, the widespread use of parabens has raised concerns due to the potential health risks associated with their estrogenic effects. In the present study, we evaluated and compared the estrogenic activity of parabens using two cell-based in vitro tests: (1) bioluminescence resonance energy transfer (BRET)-based estrogen receptor alpha (ERα) dimerization using HEK293 cells that were stably transfected with ERα-fused NanoLuc luciferase (Nluc) and HaloTag (HT) expression vector, and (2) stably transfected transcriptional activation (STTA) assays using ERα-HeLa9903 cells. The following parabens were tested using the BRET-based ERα dimerization assay and showed estrogenic activity (PC20 values): methyl paraben (MP, 5.98 × 10-5 M), ethyl paraben (EP, 3.29 × 10-5 M), propylparaben (PP, 3.09 × 10-5 M), butyl paraben (BP, 2.58 × 10-5 M), isopropyl paraben (IsoPP, 1.37 × 10-5 M), and isobutyl paraben (IsoBP, 1.43 × 10-5 M). Except MP, all other parabens tested using the STTA assay also showed estrogenic activity: EP, 7.57 × 10-6 M; PP, 1.18 × 10-6 M; BP, 3.02 × 10-7 M; IsoPP, 3.58 × 10-7 M; and IsoBP, 1.80 × 10-7 M. Overall, EP, PP, BP, IsoPP, and IsoBP tested positive for estrogenic activity using both assays. These findings demonstrate that most parabens, albeit not all, induce ERα dimerization and possess estrogenic activity.

The obesogen bisphenol A promotes adipogenesis in canine adipose-derived stem cells: Potential implication in dog obesity.

The growing number of companion dogs has contributed to a rapidly growing market for pet products, including dog toys. However, little is known about the hazardous substances released from dog toys. This study aims to examine the potential presence of obesogens, a subset of endocrine-disrupting chemicals (EDCs) that are widely utilized as raw materials in the manufacture of dog toy components, and their effects on dog health. To achieve this, we adapted and employed a migration method typically used for children's products to simulate obesogen exposure in dogs through sucking or chewing toys. We demonstrated that out of various obesogens, bisphenol A (BPA) was released from dog toys into synthetic saliva, whereas phthalates and azo dyes were not detected in any of the leachates. Additionally, we found that BPA induced adipogenic differentiation in canine adipose-derived stem cells (cADSCs). Our RNA sequencing experiments revealed that BPA alters the adipogenesis-related gene signature in cADSCs by elevating the expression levels of ADIPOQ, PLIN1, PCK1, CIDEC, and FABP4. The associated transcriptional changes are involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which may contribute to the promotion of adipogenesis by BPA. Our findings suggest that companion dogs are at risk of BPA exposure, which may contribute to obesity in dogs. Therefore, the implementation of precautionary measures is crucial.