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BACKGROUND: With the widespread outbreak of monkeypox, it is crucial to enhance awareness and understanding of the disease, especially among high-risk individuals. This study aimed to investigate the knowledge levels of individuals seeking preexposure vaccination in Taiwan. METHODS: This descriptive cross-sectional questionnaire survey was conducted online, and included a nationwide sample of high-risk adults receiving preexposure vaccination. The questionnaire comprised 30 items with six aspects and explanatory variables. A multivariate logistic regression model was used to identify the factors that influenced participants' knowledge of human monkeypox. RESULTS: Among 2,604 participants, 97.3 % were male, 76.4 % identified as homosexual, and 24.4 % had a history of HIV infection. Approximately half of the participants displayed inadequate knowledge of human monkeypox, with weaker performance in diagnosis and treatment aspects. Using a multivariate logistic model, we found that those with a medical background or higher education level had a better understanding after adjustment for potential confounding factors. Among those with an educational level of college or below, men who had sex with men (MSM) without HIV displayed significantly lower knowledge levels (OR: 0.68; 95 % CI 0.51-0.91). CONCLUSIONS: The existence of a knowledge gap within subgroups of MSM highlights the necessity for targeted educational interventions.
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Background and Objectives: Peripheral arterial stiffness (PAS), assessed by brachial-ankle pulse wave velocity (baPWV), is an independent biomarker of cardiovascular diseases (CVD) in patients on maintenance hemodialysis (HD). Malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidative stress marker, has been linked to atherosclerosis and CVD. However, the association between serum MDA-LDL and PAS among HD patients has not been fully elucidated. This study aimed to examine the association of serum MDA-LDL with PAS in HD patients and to identify the optimal cutoff value of serum MDA-LDL for predicting PAS. Materials and Methods: A cross-sectional study was conducted in 100 HD patients. Serum MDA-LDL was quantified using an enzyme-linked immunosorbent assay (ELISA), and baPWV was measured using a volume plethysmographic device. Patients were divided into the PAS group (baPWV > 18.0 m/s) and the non-PAS group (baPWV ≤ 18.0 m/s). The associations of baPWV and other clinical and biochemical parameters with serum MDA-LDL were assessed by multivariable logistic regression analyses. A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff value of serum MDA-LDL for predicting PAS. Results: In multivariable logistic regression analysis, higher serum MDA-LDL, older age, and higher serum C-reactive protein [odds ratios (ORs) and 95% confidence intervals: 1.014 (1.004-1.025), 1.044 (1.004-1.085) and 3.697 (1.149-11.893)] were significantly associated with PAS. In the ROC curve analysis, the optimal cutoff value of MDA-LDL for predicting PAS was 80.91 mg/dL, with a sensitivity of 79.25% and a specificity of 59.57%. Conclusions: Greater serum MDA-LDL levels, particularly ≥80.91 mg/dL, were independently associated with PAS in HD patients. The findings suggest that oxidative stress plays a crucial role in the pathogenesis of PAS, and targeting MDA-LDL may be a potential therapeutic strategy for reducing cardiovascular risk in HD patients.
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Biomarcadores , Lipoproteínas LDL , Malondialdehído , Diálisis Renal , Rigidez Vascular , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice Tobillo Braquial , Biomarcadores/sangre , Estudios Transversales , Lipoproteínas LDL/sangre , Modelos Logísticos , Malondialdehído/sangre , Malondialdehído/metabolismo , Estrés Oxidativo/fisiología , Análisis de la Onda del Pulso , Diálisis Renal/efectos adversos , Factores de Riesgo , Curva ROC , Rigidez Vascular/fisiologíaRESUMEN
OBJECTIVE: Global prevalence of obesity has continued to rise and poses public health concerns. Current anti-obesity medications are mainly focused on suppressing appetite. Thermogenic fat cells that increase energy expenditure may be a promising alternative target to combat obesity. Our study aims to investigate the effects of aerobic, resistance, and high-intensity interval training on thermogenic gene expression in white adipose tissue in high fat diet induced obese mice. METHODS: Fifty 6-week-old male C57BL/6 mice were initially divided into control group and high fat diet group for obesity induction. After 8 weeks of obesity induction, obese mice were subdivided into sedentary, aerobic exercise, resistance exercise, and high intensity interval training groups. Trained obese mice were submitted to 8 weeks of exercise. RESULTS: Our results showed that all three exercises significantly decreased body weight, and improved metabolic profiles including glucose tolerance, total cholesterol, and low-density lipoprotein cholesterol. Moreover, aerobic exercise training increases serum irisin levels and thermogenic gene expressions such as Prdm16, Cidea, and Pgc-1α in epididymal white adipose tissue of obese mice. CONCLUSION: Our findings suggest that when it comes to the adaption of thermogenic fat cells, the modality of exercise should be taken into consideration. Aerobic exercise may induce a modest increase in the expression levels of certain thermogenic genes in epididymal white adipose tissue.
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Dieta Alta en Grasa , Entrenamiento de Intervalos de Alta Intensidad , Masculino , Ratones , Animales , Ratones Endogámicos C57BL , Dieta Alta en Grasa/efectos adversos , Ratones Obesos , Tejido Adiposo Blanco , LDL-Colesterol , Obesidad , Expresión GénicaRESUMEN
Objectives: Adiponectin has anti-inflammatory and antiatherogenic effects and is important in the pathogenesis of cardiovascular diseases. In this cross-sectional study, our objective was to study the potential correlation between serum adiponectin levels and endothelial function in participants with coronary artery disease (CAD). Materials and Methods: We collected serum specimens from 125 fasting participants with CAD. The endothelial function was measured using the vascular reactivity index (VRI) determined by digital thermal monitoring, and VRI values of >2.0, 1.0-1.9, and <1.0 indicated good, intermediate, and poor vascular reactivity, respectively. A commercially available enzyme immunoassay kit was used to measure serum adiponectin levels. Results: The cohort included 55, 57, and 13 patients with good, intermediate, and poor vascular reactivity, respectively. Poor vascular reactivity was shown to be associated with older age, higher levels of serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), C-reactive protein, and lower levels of serum albumin and adiponectin. The linear regression analysis with multivariable forward stepwise approach revealed that age (ß = -0.232), serum LDL-C (ß = -0.264), and serum adiponectin (ß = 0.574) were correlated with the VRI in CAD patients significantly. Conclusion: Fasting serum adiponectin levels were associated with good endothelial function determined using the VRI in patients with CAD.
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Vascular calcification (VC) is associated with increased cardiovascular risks in patients with chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors, such as empagliflozin, can improve cardiovascular and renal outcomes. We assessed the expression of Runt-related transcription factor 2 (Runx2), interleukin (IL)-1ß, IL-6, AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor (Nrf2), and heme oxygenase 1 (HO-1) in inorganic phosphate-induced VC in mouse vascular smooth muscle cells (VSMCs) to investigate the mechanisms underlying empagliflozin's therapeutic effects. We evaluated biochemical parameters, mean artery pressure (MAP), pulse wave velocity (PWV), transcutaneous glomerular filtration rate (GFR), and histology in an in vivo mouse model with VC induced by an oral high-phosphorus diet following a 5/6 nephrectomy in ApoE-/- mice. Compared to the control group, empagliflozin-treated mice showed significant reductions in blood glucose, MAP, PWV, and calcification, as well as increased calcium and GFR levels. Empagliflozin inhibited osteogenic trans-differentiation by decreasing inflammatory cytokine expression and increasing AMPK, Nrf2, and HO-1 levels. Empagliflozin mitigates high phosphate-induced calcification in mouse VSMCs through the Nrf2/HO-1 anti-inflammatory pathway by activating AMPK. Animal experiments suggested that empagliflozin reduces VC in CKD ApoE-/- mice on a high-phosphate diet.
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Insuficiencia Renal Crónica , Calcificación Vascular , Ratones , Animales , Proteínas Quinasas Activadas por AMP/metabolismo , Hemo-Oxigenasa 1/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Análisis de la Onda del Pulso , Calcificación Vascular/etiología , Calcificación Vascular/complicaciones , Insuficiencia Renal Crónica/metabolismo , Fosfatos/metabolismo , Antiinflamatorios/farmacología , Miocitos del Músculo Liso/metabolismoRESUMEN
INTRODUCTION: Impaired handgrip strength is an indication for sarcopenia and frailty screening, and is associated with increased osteoporotic risks and all-cause mortality. Osteocalcin, secreted by osteoblasts, is a versatile factor that participates in bone turnover and muscle adaptation. The role of osteocalcin in muscle strength has mainly been discussed in animal models and requires more human data. The study aimed to investigate the association between the serum osteocalcin level and handgrip strength in middle-aged individuals and older adults with diabetes. METHODS: Adult participants (aged 40 and above, N = 237) with diabetes were enrolled in a medical center in northern Taiwan. Subjects were divided into normal, low muscle mass without dynapenia, dynapenia without low muscle mass, and groups of low muscle mass with dynapenia according to their handgrip strength and muscle mass measurements. Physical performance, including handgrip strength, repeated sit-to-stand tests, walking speed, and short physical performance batteries, was documented. Body composition was measured by bioelectrical impedance analysis. RESULTS: The median serum osteocalcin level was highest in the dynapenic group without low muscle mass (median [Q1, Q3], 14.1 [11.2, 16.3] ng/mL). Multivariate logistic regression showed that a higher serum osteocalcin level was associated with worse handgrip strength (OR: 3.89, 95% CI: 1.66-9.10) after adjusting for body mass index (adiposity), skeletal muscle mass index (muscle), and medication with dipeptidyl peptidase-4 inhibitor. Further sex stratification revealed a more significant association between serum osteocalcin level and impaired handgrip strength in women but not in men. The female groups showed increases in the risk of impaired handgrip strength: 4.84-fold in the osteocalcin T2 group (11.4 ≤ osteocalcin <15.0 ng/mL) and 4.54-fold in the osteocalcin T3 group (osteocalcin ≥15.0 ng/mL). Moreover, after adjusting for various confounders, 8.41-fold and 8.03-fold increases in the risk of impaired handgrip strength were observed in the osteocalcin T2 group (11.4≤ osteocalcin <15.0 ng/mL) and osteocalcin T3 group (osteocalcin ≥14.5 ng/mL), respectively. CONCLUSION: Higher serum osteocalcin is associated with increased risks of impaired handgrip strength and impaired physical performance. Dose-dependent associations were found especially in postmenopausal women but not in men.
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Diabetes Mellitus , Sarcopenia , Femenino , Humanos , Masculino , Anciano , Persona de Mediana Edad , Fuerza de la Mano/fisiología , Osteocalcina , Caracteres Sexuales , Fuerza Muscular , Sarcopenia/diagnóstico , Músculo EsqueléticoRESUMEN
BACKGROUND: Bariatric surgery is associated with significant improvements in immunity in individuals with obesity, but the exact efficacy in reducing pneumonia and influenza infections is unclear. OBJECTIVE: To investigate the association between bariatric surgery and the risk of pneumonia and influenza infection. SETTING: Nondiabetic patients who underwent bariatric surgery and matched controls were identified from the National Health Insurance Research Database of Taiwan. METHODS: We identified 1648 nondiabetic patients who underwent bariatric surgery from the National Health Insurance Research Database of Taiwan in 2001-2009. These patients were matched by propensity score with 4881 nondiabetic patients with obesity who did not undergo bariatric surgery. We followed the surgical and control cohorts until death, any diagnosis of pneumonia or influenza, or December 31, 2012. The Cox proportional hazards regression model was used to calculate the relative risk of pneumonia and influenza infection in those who underwent bariatric surgery compared with those who did not. RESULTS: Overall, there was a .87-fold (95% CI, .78-.98) reduced risk of pneumonia and influenza infection in the surgical group versus the control group. Four years after bariatric surgery, a sustainable effect of the surgery was observed, and the risk of pneumonia and influenza infection was .83-fold reduced in the surgical group (95% CI, .73-.95). Individuals with obesity who underwent bariatric surgery had a reduced risk of pneumonia and influenza infection compared with matched control individuals. CONCLUSION: Individuals with obesity who underwent bariatric surgery had a reduced risk of pneumonia and influenza infection compared with matched control individuals.
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Cirugía Bariátrica , Gripe Humana , Obesidad Mórbida , Neumonía , Humanos , Estudios Retrospectivos , Taiwán/epidemiología , Gripe Humana/epidemiología , Obesidad/complicaciones , Obesidad/cirugía , Neumonía/epidemiología , Neumonía/etiología , Obesidad Mórbida/cirugíaRESUMEN
Obesity is associated with excessive fat accumulation in adipose tissue and other organs, such as skeletal muscle, whereas aerobic exercise (AE) plays an important role in managing obesity through profound protein regulation. Our study aimed to investigate the impact of AE on proteomic changes in both the skeletal muscle and the epididymal fat pad (EFP) of high-fat-diet-induced obese mice. Bioinformatic analyses were performed on differentially regulated proteins using gene ontology enrichment analysis and ingenuity pathway analysis. Eight weeks of AE significantly reduced body weight, increased the serum FNDC5 level, and improved the homeostatic model assessment of insulin resistance. A high-fat diet caused alterations in a subset of proteins involved in the sirtuin signaling pathway and the production of reactive oxygen species in both skeletal muscle and EFP, leading to insulin resistance, mitochondrial dysfunction, and inflammation. On the other hand, AE upregulated skeletal muscle proteins (NDUFB5, NDUFS2, NDUFS7, ETFD, FRDA, and MKNK1) that enhance mitochondrial function and insulin sensitivity. Additionally, the upregulation of LDHC and PRKACA and the downregulation of CTBP1 in EFP can promote the browning of white adipose tissue with the involvement of FNDC5/irisin in the canonical pathway. Our study provides insights into AE-induced molecular responses and may help further develop exercise-mimicking therapeutic targets.
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Dieta Alta en Grasa , Resistencia a la Insulina , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Ratones Obesos , Proteómica , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo/metabolismo , Obesidad/genética , Factores de Transcripción/metabolismo , Fibronectinas/metabolismo , Músculo Esquelético/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , NADH Deshidrogenasa/metabolismoRESUMEN
BACKGROUND: Lean Non-alcoholic Fatty Liver Disease (NAFLD) shares a similar disease burden to those of their overweight counterparts and should be detected early. We hypothesized that the adiponectin-leptin ratio (AL ratio) could be a good marker for early detection of lean NAFLD independent of insulin resistance. MATERIALS AND METHODS: A total of 575 adults without diabetes were enrolled in a community-based study. The subjects were stratified into the lean controls, lean NAFLD, simple overweight/obesity and overweight/obesity NAFLD groups according to body mass index (BMI) and ultrasonographic fatty liver indicators. Serum adiponectin and leptin levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD in relation to the tertiles of serum AL concentration after adjustment. Receiver operating characteristic (ROC) analyses were applied to evaluate the diagnostic performance of the AL ratio for NAFLD. RESULTS: The mean age of the participants was 42.8 ± 11.5 years. Comparing with the lean controls, the odds of having lean NAFLD for the highest versus the lowest tertile of AL ratio was 0.28(95%CI: 0.12-0.69) after adjustment. Putting AL ratio, BMI, triglyceride, AST/ALT ratio to the diagnosis performance of NAFLD, the ROC was 0.85 (95% CI: 0.82-0.88), 0.83 (95% CI 0.78-0.87) and 0.86 (95% CI 081-0.91) for all NAFLD, NAFLD in women and NAFLD in men, respectively. (p < .001). CONCLUSIONS: The study revealed that the AL ratio could be a good biomarker to early distinguish lean NAFLD patients from lean controls independent of insulin resistance. [AQ3]Key messagesThe prevalence of non-alcoholic fatty liver disease (NAFLD) increases globally and is related to liver diseases and metabolic dysfunctions. Lean subset of NAFLD shares a similar disease burden to those of their overweight counterparts and should be detected early.Adiponectin-leptin ratio were associated with the severity of steatosis and was a predictor of obese NAFLD better than each single adipokine. To date, there is no investigation that explores specifically for the relationship between lean NAFLD and AL ratio.Our study found that adiponectin-leptin ratio is a sole independent marker regardless of insulin resistance in lean NAFLD. Having lean NAFLD for the highest versus the lowest tertile of adiponectin-leptin ratio was 0.28(95%CI: 0.12-0.69) after adjustment of age, sex, current smoking, exercise habits, HOMA-IR and AST/ALT. ROC for the NAFLD performance is good for the early detection (0.85; 95% CI: 0.82-0.88). Further rigorous investigation is necessary and should be promptly performed.
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Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adiponectina , Índice de Masa Corporal , Leptina , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Obesidad , SobrepesoRESUMEN
BACKGROUND: Travel, especially international travel, has become one of the most popular leisure activities in the world. The risk of accidents and travel-related illnesses, including infectious and non-communicable diseases, should not be neglected. To provide a more comprehensive pre-travel consultation to international travelers, this study aimed to investigate the knowledge, attitude, and practice of travelers about travel health insurance. METHODS: This was a cross-sectional study. Anonymous structured questionnaires were distributed to 1000 visitors to the Taiwan International Travel Fair in May 2019. RESULTS: The top three important travel health insurances were accidental death and disablement insurance (92%), accidental medical reimbursement (90.4%), and 24-hour emergency assistance (89%). In addition to education level, travel-associated illness, and special activities during travel, a significant association was observed between the willingness to buy various travel health insurances and the willingness of pre-travel consultation. CONCLUSIONS: Most travelers would buy travel health insurance; however, disproportional respondents understood the content of travel health insurance. Most travelers considered travel clinics to be the most reliable information source regarding travel health insurance. Therefore, travel medicine specialists are encouraged to offer more information about travel health insurance during pre-travel consultation.
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Conocimientos, Actitudes y Práctica en Salud , Viaje , Humanos , Estudios Transversales , Enfermedad Relacionada con los Viajes , Seguro de Salud , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Sarcopenia and vertebral fracture affect a large number of older adults and can be debilitating. However, the correlation between sarcopenia and vertebral fracture has not been well studied. Thus, this study investigates the correlation between vertebral fragility fracture and the severity of sarcopenia. METHOD: This cross-sectional study included 300 community-dwelling older adults with risk higher than 10-year probability of 3% for a hip fracture and 20% for a major osteoporotic fracture by FRAX score. Sarcopenia was defined according to the Asian Working Group for Sarcopenia consensus. Bone mineral density (BMD) was classified into normal or abnormal groups (T score ≤ -1.0) according to WHO criteria. Vertebral fracture was graded mild, moderate, and severe by a standardized semi-quantitative method. The association between sarcopenia and vertebral fragility fracture was investigated using a logistic regression model adjusted for confounding factors. RESULTS: Compared with the normal BMD group, the abnormal BMD group had a significantly higher prevalence of sarcopenia (7.4 vs. 26.6%, p < 0.001), poorer muscle mass (p < 0.001), and poorer hand grip (p < 0.001). The prevalence of moderate-to-severe fracture was significantly different (p = 0.006) among severe sarcopenia (16.7%), sarcopenia (6.9%), and non-sarcopenia (3.7%) for thoracic vertebrae. In the logistical regression model adjusted for confounding factors, sarcopenia plus severe sarcopenia was identified as a risk factor for moderate-to-severe thoracic vertebral fragility fracture (odds ratio [OR] = 3.29, 95% CI: 1.23-8.78, p = 0.018). We further classified the participants into normal, sarcopenia, and severe sarcopenia and found that sarcopenia and severe sarcopenia had a dose-dependent association with prevalence of thoracic vertebral fragility fractures with ORs of 2.56 (95% CI: 0.66-9.91) and 4.04 (95% CI: 1.24-13.20), respectively; p for trend = 0.014. CONCLUSION: Sarcopenia is a potential risk factor for and has a dose-dependent association with moderate-to-severe thoracic fragility fracture in older adults at increased risk for fractures.
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Fracturas Osteoporóticas , Sarcopenia , Fracturas de la Columna Vertebral , Humanos , Anciano , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/epidemiología , Vértebras Torácicas , Estudios Transversales , Fuerza de la Mano/fisiología , Densidad Ósea/fisiología , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/complicaciones , Factores de Riesgo , Sarcopenia/complicaciones , Sarcopenia/epidemiología , Absorciometría de Fotón/efectos adversos , Absorciometría de Fotón/métodosRESUMEN
Septic shock can aggravate organ dysfunction and even lead to death. Juniperus communis (JCo) extract has been experimentally demonstrated to have anti-inflammatory and antioxidant effects. We investigated the anti-inflammatory and antioxidant mechanism of JCo extract in vivo and in vitro. In a lipopolysaccharide (LPS)-induced acute kidney injury rat model, JCo extract improved animal survival, reduced kidney injury scores, suppressed kidney injury molecule-1, and preserved E-cadherin expression from LPS damage, as demonstrated by the immunohistochemistry examinations of the rat kidneys. In LPS-stimulated NRK-52E cells, JCo extract inhibited nuclear factor-κB (NF-κB) and increased adenosine monophosphate-activated protein kinase (AMPK) expression, prompting the activation of the antioxidant nuclear factor erythroid 2-related factor-2/heme oxygenase-1 pathway against oxidative stress. JCo extract ameliorated LPS-induced acute kidney injury by suppressing NF-κB signaling and stimulating the release of tumor necrosis factor-α and interleukin-1ß through the AMPK pathway.
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Epigenetic modifications such as DNA methylation play an essential role in imprinting specific transcriptional patterns in cells. We performed genome-wide DNA methylation profiling of murine lymph node-derived ILCs, which led to the identification of differentially methylated regions (DMRs) and the definition of epigenetic marker regions in ILCs. Marker regions were located in genes with a described function for ILCs, such as Tbx21, Gata3, or Il23r, but also in genes that have not been related to ILC biology. Methylation levels of the marker regions and expression of the associated genes were strongly correlated, indicating their functional relevance. Comparison with T helper cell methylomes revealed clear lineage differences, despite partial similarities in the methylation of specific ILC marker regions. IL-33-mediated challenge affected methylation of ILC2 epigenetic marker regions in the liver, while remaining relatively stable in the lung. In our study, we identified a set of epigenetic markers that can serve as a tool to study phenotypic and functional properties of ILCs.
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Inmunidad Innata , Linfocitos , Animales , Biomarcadores , Metilación de ADN/genética , Epigénesis Genética , Estudio de Asociación del Genoma Completo , RatonesRESUMEN
CONTEXT: There is a medical need for effective insulin-independent antidiabetic drugs that can promote pancreatic ß-cell function and have a low risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients. R-form verapamil (R-Vera), which is able to enhance the survival of ß-cells and has higher cardiovascular safety margin compared with racemic verapamil, was developed as a novel approach for T2DM treatment. OBJECTIVE: This randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of 3 dosages of R-Vera added to ongoing metformin therapy in T2DM patients who had inadequate glycemic control on metformin alone. METHODS: Participants were randomly assigned in an equal ratio to receive R-Vera 450, 300, or 150 mg per day, or matching placebo, in combination with metformin. The primary endpoint was change in hemoglobin A1c (HbA1c) after 12 weeks of treatment. RESULTS: A total of 184 eligible participants were randomized to receive either R-Vera or placebo plus metformin. At week 12, significant reductions in HbA1c were observed for R-Vera 300 mg/day (-0.36, Pâ =â 0.0373) and 450 mg/day (-0.45, Pâ =â 0.0098) compared with placebo. The reduction in HbA1c correlated with decreasing fasting plasma glucose levels and improved HOMA2-ß score. Treatment with R-Vera was well tolerated with no hypoglycemic episodes occurring during the trial. CONCLUSION: Addition of R-Vera twice daily to ongoing metformin therapy significantly improved glycemic control in T2DM patients. The favorable efficacy and safety profile of R-Vera 300 mg/day can be considered as the appropriate dose for clinical practice.
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Diabetes Mellitus Tipo 2 , Hipoglucemia , Metformina , Glucemia , Método Doble Ciego , Quimioterapia Combinada , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Insulina/uso terapéutico , Resultado del Tratamiento , Verapamilo/uso terapéuticoRESUMEN
Basic processes of the fatty acid metabolism have an important impact on the function of intestinal epithelial cells (IEC). However, while the role of cellular fatty acid oxidation is well appreciated, it is not clear how de novo fatty acid synthesis (FAS) influences the biology of IECs. We report here that interfering with de novo FAS by deletion of the enzyme Acetyl-CoA-Carboxylase (ACC)1 in IECs results in the loss of epithelial crypt structures and a specific decline in Lgr5+ intestinal epithelial stem cells (ISC). Mechanistically, ACC1-mediated de novo FAS supports the formation of intestinal organoids and the differentiation of complex crypt structures by sustaining the nuclear accumulation of PPARδ/ß-catenin in ISCs. The dependency of ISCs on cellular de novo FAS is tuned by the availability of environmental lipids, as an excess delivery of external fatty acids is sufficient to rescue the defect in crypt formation. Finally, inhibition of ACC1 reduces the formation of tumors in colitis-associated colon cancer, together highlighting the importance of cellular lipogenesis for sustaining ISC function and providing a potential perspective to colon cancer therapy.
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Acetil-CoA Carboxilasa , Lipogénesis , Acetilcoenzima A/metabolismo , Acetil-CoA Carboxilasa/metabolismo , Ácidos Grasos/metabolismo , Lipogénesis/fisiología , Células Madre/metabolismoRESUMEN
Sepsis, which is a serious medical condition induced by infection, has been the most common cause of acute kidney injury (AKI) and is associated with high mortality and morbidity. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new oral antidiabetic drug that has greatly improved the cardiovascular and renal outcomes in patients with type 2 diabetes independent of its sugar lowering effect, possibly by attenuation of the inflammatory process. We investigated the effect of the SGLT2 inhibitor dapagliflozin on lipopolysaccharide (LPS)-induced endotoxic shock with AKI in streptozotocin-induced diabetic mice. Endotoxin shock with AKI was induced by intravenous injection of 10 mg/kg LPS in C57BL6 mice with streptozotocin-induced diabetic mellitus with or without dapagliflozin treatment. Observation was done for 48 hours thereafter. In addition, NRK-52E cells incubated with LPS or dapagliflozin were evaluated for the possible mechanism. Treatment with dapagliflozin attenuated LPS-induced endotoxic shock associated AKI and decreased the inflammatory cytokines in diabetic mice. In the in vitro study, dapagliflozin decreased the expression of inflammatory cytokines and reactive oxygen species and increased the expressions of AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor, and heme oxygenase 1. These results demonstrated that dapagliflozin can attenuate LPS-induced endotoxic shock associated with AKI; this was possibly mediated by activation of the AMPK pathway.
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Lesión Renal Aguda , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Proteínas Quinasas Activadas por AMP/metabolismo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/tratamiento farmacológico , Animales , Compuestos de Bencidrilo/efectos adversos , Citocinas , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos , Humanos , Lipopolisacáridos/toxicidad , Ratones , Ratones Endogámicos C57BL , EstreptozocinaRESUMEN
Postmenopausal women exhibit a higher prevalence of obesity due to decreased energy expenditure and increased food intake compared to their premenopausal counterparts. Brown adipose tissue (BAT) plays a key role in energy homeostasis, thus providing us with appealing therapeutic targets in obesity. However, how BAT proteomes are altered in response to low levels of estrogen remains unclear. To better understand the underlying mechanisms between the postmenopausal state and BAT proteomic changes, our study aimed to investigate the effect of ovariectomy on the BAT proteome. In this study, eight-week-old female Sprague Dawley rats were randomly allocated into bilateral ovariectomy (Ovx) and sham operation (Sham) groups. Mass spectrometry was used for proteomics assay and Ingenuity Pathway Analysis was applied to examine the differentially regulated proteins. Of the 1,412 identified proteins, 18 proteins were significantly upregulated, whereas 36 proteins were significantly downregulated in the Ovx group as compared to the Sham group. Our findings demonstrate that the proteins involved in BAT morphology, the browning of white adipose tissue, and metabolic substrates for thermogenesis were regulated by ovariectomy. The dysregulation of proteins by ovariectomy might be related to the disruption of BAT function in the postmenopausal status. Understanding how BAT proteomes are altered in response to ovariectomy may illuminate novel therapeutic strategies for the management of postmenopausal weight gain in the future.
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Tejido Adiposo Pardo , Proteoma , Tejido Adiposo Pardo/metabolismo , Animales , Femenino , Humanos , Ovariectomía/efectos adversos , Proteoma/metabolismo , Proteómica , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Coronavirus infectious disease 2019 (COVID-19) has had a great impact on global health, but with relatively few confirmed cases in Taiwan. People in Taiwan showed excellent cooperation with the government for disease prevention and faced social and behavioral changes during this period. This study aimed to investigate people's knowledge of COVID-19, attitudes and practices regarding vaccinations for influenza, pneumococcus and COVID-19. METHODS: We conducted a community-based, cross-sectional questionnaire survey from September 2020 to October 2020 among adults in northern Taiwan. The four-part questionnaire included questions on sociodemographic characteristics, knowledge, attitude, and practice toward COVID-19. RESULTS: Among a total of 410 respondents, 58.5% were categorized as having "good knowledge" responding to COVID-19. Among the total respondents, 86.6% were willing to receive influenza or pneumococcal vaccines, and 76% of them acted to receive COVID-19 immunization once the vaccine became available. Compared with the respondents with poor knowledge of COVID-19, those with good knowledge had a more positive attitude toward receiving influenza or pneumococcal immunization (OR 3.26, 95% CI = 1.74-6.12). CONCLUSIONS: Participants with good knowledge of COVID-19 had greater intent to receive immunization for influenza or pneumococcal vaccine. The promotion of correct knowledge of both COVID-19 and immunization preparations is necessary.
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Vacunas contra la COVID-19 , COVID-19 , Conocimientos, Actitudes y Práctica en Salud , Vacunas contra la Influenza , Vacunas Neumococicas , Adulto , Anciano , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/uso terapéutico , Estudios Transversales , Femenino , Humanos , Inmunización , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Encuestas y Cuestionarios , Taiwán/epidemiología , Negativa a la VacunaciónRESUMEN
Septic shock can increase pro-inflammatory cytokines, reactive oxygen species (ROS), and multiple organ dysfunction syndrome (MODs) and even lead to death. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been proven to exert potential antioxidant and anti-inflammatory effects. We investigated the effects of linagliptin on endotoxic shock and acute kidney injury (AKI) in animal and cell models. In the cell model, linagliptin attenuated ROS by activating the AMP-activated protein kinase (AMPK) pathway, restoring nuclear-factor-erythroid-2-related factor (Nrf2) and heme oxygenase 1 (HO-1) protein, and decreasing pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß)). In the animal model, 14-week-old conscious Wistar-Kyoto rats were randomly divided into three groups (n = 8 in each group). Endotoxin shock with MODs was induced by the intravenous injection of Klebsiella pneumoniae lipopolysaccharide (LPS, 20 mg/kg). Linagliptin improved animal survival without affecting hemodynamic profiles. In the histopathology and immunohistochemistry examinations of the rat kidneys, linagliptin (10 mg/kg) suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and inducible nitric oxide synthase (iNOS), decreased injury scores, and preserved E-cadherin expression from LPS damage. In conclusion, linagliptin ameliorated endotoxin-shock-induced AKI by reducing ROS via AMPK pathway activation and suppressing the release of TNF-α and IL-1ß in conscious rats.
Asunto(s)
Lesión Renal Aguda/prevención & control , Citocinas/metabolismo , Inflamación/prevención & control , Linagliptina/farmacología , Especies Reactivas de Oxígeno/metabolismo , Lesión Renal Aguda/inducido químicamente , Animales , Endotoxinas/toxicidad , Linagliptina/uso terapéutico , Masculino , FN-kappa B/metabolismo , Ratas , Ratas Endogámicas WKY , Transducción de SeñalRESUMEN
Patients with lean NAFLD make up an increasing subset of liver disease patients. The association between lean NAFLD and feutin-A, which serves as a hepatokine and adipokine, has never been examined. Our study aimed to explore the association of serum fetuin-A among lean and non-lean patients. The study comprised 606 adults from the community, stratified into lean or non-lean (BMI ≥ 24 kg/m2) and NAFLD or non-NAFLD (scoring of ultrasonographic fatty liver indicator, US-FLI ≥ 2/< 2). Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD among the tertiles of fetuin-A after adjustment. The least square means were computed by general linear models to estimate marginal means of the serum fetuin-A concentrations in relation to the NAFLD groups. The odds ratio (OR) of having NAFLD for the highest versus the lowest tertile of fetuin-A was 2.62 (95% CI: 1.72-3.98; p for trend < 0.001). Stratifying by BMI, the OR of having lean NAFLD for the highest versus the lowest tertile of fetuin-A was 2.09 (95% CI: 1.09-3.98; p for trend 0.026), while non-lean NAFLD had no significant association with the fetuin-A gradient after adjustments. Fetuin-A was positively associated with lean NAFLD after adjusting for central obesity and insulin resistance.