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There are few studies on the connection between food components and circular RNA (circRNA), a type of noncoding RNA that is significant for living organisms. (-)-Epigallocatechin-3-O-gallate (EGCG) has been reported to have various biological effects, and elucidation of the molecular mechanism is important for clarifying the functionality of EGCG. In the current study, we looked at how EGCG regulates the expression of circRNA in the liver, which expresses a lot of circRNAs. Mice were given EGCG (10 mg/kg b.w.) orally for one week before circRNA microarray testing was done on their livers. The microarray analysis revealed that mice treated with EGCG had altered expression of 35 circRNAs in their livers. To clarify the function of mmu_circRNA_011775, one of the circRNAs upregulated by EGCG, mouse liver cells after the mmu_circRNA_011775 expression vector was transfected into NMuLi cells, next-generation sequencing (NGS) was used to analyze the gene expression. NGS analysis shows that the expression of the genes responsible for liver fibrosis and inflammation. Gene ontology (GO) analysis showed that mmu_circRNA_011775 changed the meaning of GO terms associated with the cardiovascular system. In the microarray, EGCG altered 35 genes expression. Among them, pre-ribosomal RNA-derived circRNA mmu_circRNA_011775 regulated the expression of various genes related to liver fibrosis and cardiovascular system.
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Catequina/análogos & derivados , MicroARNs , ARN Circular , Animales , Ratones , ARN Circular/genética , ARN Circular/metabolismo , ARN/genética , ARN/metabolismo , MicroARNs/genética , Cirrosis Hepática , Perfilación de la Expresión GénicaRESUMEN
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as novel cardioprotective agents. However, their direct impact on cardiomyocyte injury is yet to be studied. In this work, we investigate the underlying molecular mechanisms of empagliflozin (EMPA), an SGLT2 inhibitor, in mitigating palmitate (PA)-induced cardiomyocyte injury in H9c2 cells. We found that EMPA significantly attenuated PA-induced impairments in insulin sensitivity, ER stress, inflammatory cytokine gene expression, and cellular apoptosis. Additionally, EMPA elevated AMP levels, activated the AMPK pathway, and increased carnitine palmitoyl transferase1 (CPT1) gene expression, which collectively enhanced fatty acid oxidation and reduced stress signals. This study reveals a novel mechanism of EMPA's protective effects against PA-induced cardiomyocyte injury, providing new therapeutic insights into EMPA as a cardioprotective agent.
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BACKGROUND: Oolonghomobisflavans are unique polyphenols found in oolong teas. Oolonghomobisflavan B (OHBFB), a dimer of (-)-epigallocatechin-3-O-gallate (EGCG), is an active compound found in green tea. PURPOSE: OHBFB has been reported to exert an inhibitory effect on lipase enzyme activity. However, little is known regarding its intercellular signaling induction effect. Further, there are no reports describing the anti-cancer effects of OHBFB. METHODS: The effect of OFBFB on B16 melanoma cells was evaluated by cell counting, and its mechanisms were determined by western blot analysis with or without protein phosphatase 2A (PP2A) inhibitor treatment. Intracellular cyclic adenosine monophosphate (cAMP) levels were evaluated by time-resolved fluorescence resonance energy transfer analysis. Quartz crystal microbalance (QCM) analysis was performed to assess the binding of OHBFB to 67LR. RESULTS: Cell growth assay and western blot analyses showed that OHBFB inhibited melanoma cell growth, followed by myosin phosphatase target subunit 1 (MYPT1) and myosin regulatory light chain (MRLC) dephosphorylation via protein phosphatase 2A (PP2A)-dependent mechanisms. These effects are mediated by intracellular cAMP- and protein kinase A (PKA) A-dependent mechanisms. QCM analysis identified the 67-kDa laminin receptor (67LR) as an OHBFB receptor with a Kd of 3.7 µM. We also demonstrated for the first time that OHBFB intake suppresses tumor growth in vivo. CONCLUSIONS: Taken together, these results indicate that the cAMP/PKA/PP2A/MYPT1/MRLC pathway is a key mediator of melanoma cell growth inhibition following OHBFB binding to 67LR and that OHBFB suppresses tumor growth in vivo.
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Catequina , Melanoma Experimental , Animales , Humanos , Proteína Fosfatasa 2/metabolismo , Polifenoles/farmacología , Catequina/farmacología , Ciclo Celular , Melanoma Experimental/tratamiento farmacológico , Receptores de Laminina/química , Receptores de Laminina/metabolismoRESUMEN
INTRODUCTION: Epidemiological studies indicated that inflammatory bowel disease (IBD), with Crohn's disease and ulcerative colitis as its two main types, is associated with dementia. However, little is known about how adolescents with IBD will affect their cognitive ability as adults. The hippocampus, which is crucial for memory and adult neurogenesis, is closely associated with modulation of cognitive processes. Using a low kDa dextran sulfate sodium (DSS, 5 kDa)-induced chronic colitis (mild chronic colitis) mice model in adolescent mice, we investigated the effects of mild chronic colitis on cognitive functions and hippocampal neurogenesis from adolescent mice to adult mice. METHODS: We induced DSS-induced mild chronic colitis in C57BL/6J male mice by multiple-cycle administration of 1%-2% DSS in autoclaved drinking water. Mice were subjected to novel-object recognition and Y-maze tests. Neurogenesis markers and neuroinflammation-related proteins in the hippocampus of mice were measured. Tight junction proteins in the colon of mice were measured. RESULTS: Mild chronic colitis induced cognitive impairment and decreased adult neurogenesis. Notably, we found a positive correlation with the protein levels between tight junction protein, ZO-1, in the colon and mature neuron marker, NeuN, in the hippocampus. Moreover, mild chronic colitis leads to hippocampal neuroinflammation in adolescent mice. CONCLUSION: Our findings provide new evidence of the association between IBD and dementia risk.
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Disfunción Cognitiva , Colitis , Demencia , Enfermedades Inflamatorias del Intestino , Masculino , Animales , Ratones , Sulfato de Dextran , Enfermedades Neuroinflamatorias , Ratones Endogámicos C57BL , Colitis/inducido químicamente , Colitis/complicaciones , Colitis/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Colon/metabolismo , Modelos Animales de Enfermedad , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/metabolismo , NeurogénesisRESUMEN
BACKGRUOUND: Post-transplant diabetes mellitus (PTDM) is a risk factor for poor outcomes after kidney transplantation (KT). However, the outcomes of KT have improved recently. Therefore, we investigated whether PTDM is still a risk factor for mortality, major atherosclerotic cardiovascular events (MACEs), and graft failure in KT recipients. METHODS: We studied a retrospective cohort of KT recipients (between 1994 and 2017) at a single tertiary center, and compared the rates of death, MACEs, overall graft failure, and death-censored graft failure after KT between patients with and without PTDM using Kaplan-Meier analysis and a Cox proportional hazard model. RESULTS: Of 571 KT recipients, 153 (26.8%) were diagnosed with PTDM. The mean follow-up duration was 9.6 years. In the Kaplan- Meier analysis, the PTDM group did not have a significantly increased risk of death or four-point MACE compared with the non-diabetes mellitus group (log-rank test, P=0.957 and P=0.079, respectively). Multivariate Cox proportional hazard models showed that PTDM did not have a negative impact on death or four-point MACE (P=0.137 and P=0.181, respectively). In addition, PTDM was not significantly associated with overall or death-censored graft failure. However, patients with a long duration of PTDM had a higher incidence of four-point MACE. CONCLUSION: Patient survival and MACEs were comparable between groups with and without PTDM. However, PTDM patients with long duration diabetes were at higher risk of cardiovascular disease.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Diabetes Mellitus/etiología , Factores de Riesgo , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/complicacionesRESUMEN
Epigallocatechin 3-O-gallate (EGCG) is a predominant component in green tea with various health benefits. The 67 kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that is overexpressed in various types of cancer; 67LR was identified a cell surface EGCG target that plays a pivotal role in tumor growth, metastasis, and resistance to chemotherapy. However, the plasma concentration of EGCG is limited, and its molecular mechanisms remain unelucidated in colon cancer. In this study, we found that the phosphodiesterase 5 (PDE5) inhibitor, vardenafil (VDN), potentiates EGCG-induced apoptotic cell death in colon cancer cells. The combination of EGCG and VDN induced apoptosis via activation of the endothelial nitric oxide synthase/cyclic guanosine monophosphate/protein kinase Cδ signaling pathway. In conclusion, the PDE5 inhibitor, VDN, may reduce the intracellular PDE5 enzyme activity that potentiates EGCG-induced apoptotic cell death in Caco-2 cells. These results suggest that PDE5 inhibitors can be used to elevate cGMP levels to induce 67LR-mediated, cancer-specific cell death. Therefore, EGCG may be employed as a therapeutic candidate for colon cancer.
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BACKGROUND: The internet has become a major source of health information, and obtaining appropriate information requires various abilities and skills, labeled as electronic health literacy (eHealth literacy). The existing instruments for measuring eHealth literacy are outdated because they were developed during the Web 1.0 era, or not sufficiently sensitive for people with a specific condition or disease because they were designed to assess eHealth literacy over a broad range for a general population. Approximately one in ten adults worldwide live with diabetes. Health professionals have a responsibility to identify patients with low eHealth literacy to prevent them from obtaining misleading internet diabetes information. AIMS: The aims were to develop a condition-specific eHealth literacy scale for diabetes and to evaluate its psychometric properties among people with type 2 diabetes. METHODS: An instrument development design was used. This study recruited 453 people diagnosed with type 2 diabetes at the outpatient clinics of hospitals in 2021. Psychometric properties (internal consistency, measurement invariance, and content, structural, convergent, and known-groups validities) were analyzed. RESULTS: An expert panel assessed content validity. Exploratory factor analysis, exploratory graph analysis, and confirmatory factor analysis (CFA) for structural validity yielded a two-factor solution (CFI = 0.977, SRMR = 0.029, RMSEA = 0.077). Cronbach's alpha and omega values were excellent for each factor (0.87-0.94). Multigroup CFA yielded configural and metric measurement invariance across the gender, age, and glycemic control status groups. Convergent validity with a comparator instrument to measure health literacy was supported by a moderate correlation, and known-groups validity determined using groups with different internet-use frequencies was satisfied with a high effect size. CONCLUSION: A new condition-specific eHealth literacy scale for people with type 2 diabetes was developed, comprising 10 items. The scale exhibited good psychometric properties; however, test-retest reliability must be determined for the stability of the scale and cross-cultural validity is required among different languages. The brief scale has the merits of being feasible to use in busy clinical practice and being less burdensome to respondents. The scale can be applied in clinical trials of internet-based diabetes interventions for assessing the eHealth literacy of respondents.
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Hepatic fibrosis is the excessive production and deposition of the extracellular matrix, resulting in the activation of the fibrogenic phenotype of hepatic stellate cells (HSCs). The Hippo/Yes-associated protein (YAP) signalling pathway is a highly conserved kinase cascade that is critical in regulating cell proliferation, differentiation, and survival, and controls stellate cell activation. Empagliflozin, a sodium-glucose cotransporter type-2 inhibitor, is an antidiabetic drug that may prevent fibrotic progression by reducing hepatic steatosis and inflammation. However, little is known about its mechanism of action in liver fibrosis. In this study, we used male C57 BL/6 J mice fed a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) as a model for hepatic fibrosis. For 5 weeks, the mice received either a vehicle or empagliflozin based on their assigned group. Empagliflozin attenuated CDAHFD-induced liver fibrosis. Thereafter, we identified the Hippo pathway, along with its effector, YAP, as a key pathway in the mouse liver. Hippo signalling is inactivated in the fibrotic liver, but empagliflozin treatment activated Hippo signalling and decreased YAP activity. In addition, empagliflozin downregulated the expression of pro-fibrogenic genes and activated Hippo signalling in HSCs. We identified a mechanism by which empagliflozin ameliorates liver fibrosis.
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OBJECTIVE: This study investigated whether a new sustained-release (SR) pregabalin formulation is noninferior to immediate-release (IR) pregabalin in alleviating peripheral neuropathic pain in Korean patients. MATERIALS AND METHODS: This was a randomized, double-blind, active-controlled phase 3 study of patients with diabetic peripheral neuropathy or postherpetic neuralgia from 41 sites in South Korea in 2017-2018. Eligible patients were randomized (1:1) to receive once-daily SR pregabalin or twice-daily IR pregabalin (150 to 600 mg/d) in a double-dummy manner for 12 weeks according to a stratified permuted block randomization scheme. The primary endpoint was the Daily Pain Rating Scale score at the end of treatment, averaged from the last 7 available scores. RESULTS: A total of 319 of 371 (86.0%) randomized patients completed the 12-week treatment (SR pregabalin: n=154; IR pregabalin: n=165; per-protocol set: n=296). The least square mean difference between both groups for the primary endpoint was 0.06 (SE 0.19); (95% confidence interval -0.31 to 0.42), with the lower limit of the confidence interval above the pre-specified margin (-0.78; Pnoninferiority<0.0001). Drug-related treatment-emergent adverse events (TEAEs) were comparable between both groups. The incidence of drug-related TEAEs leading to treatment discontinuation was low (SR pregabalin: 2.7%; IR pregabalin: 1.1%). No serious drug-related TEAEs or deaths occurred. DISCUSSION: The results demonstrate that the new once-daily SR pregabalin formulation is noninferior to twice-daily IR pregabalin in reducing peripheral neuropathic pain and is well tolerated in Korean patients with diabetic peripheral neuropathy or postherpetic neuralgia after 12 weeks of treatment.
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Neuropatías Diabéticas , Neuralgia Posherpética , Neuralgia , Analgésicos , Preparaciones de Acción Retardada/uso terapéutico , Neuropatías Diabéticas/tratamiento farmacológico , Método Doble Ciego , Humanos , Neuralgia/inducido químicamente , Neuralgia/tratamiento farmacológico , Neuralgia Posherpética/tratamiento farmacológico , Dimensión del Dolor , Pregabalina , Resultado del TratamientoRESUMEN
OBJECTIVE: The natural course of diabetes of the exocrine pancreas (DEP) is not well established. We aimed to compare the risk of insulin initiation, diabetic complications, and mortality between DEP and type 2 diabetes. RESEARCH DESIGN AND METHODS: Using the Korean National Health Insurance Service-Health Screening Cohort between 2012 and 2017, we divided patients with diabetes into those with diabetes without prior pancreatic disease (indicated type 2 diabetes, n = 153,894) and diabetes with a prior diagnosis of pancreatic disease (indicated DEP, n = 3,629). ICD-10 codes and pharmacy prescription information were used to define type 2 diabetes, DEP, and acute and chronic diabetes complications. Kaplan-Meier curves were produced to compare insulin use over time between groups. We created logistic regression models for odds of progression to diabetic complications and mortality. RESULTS: DEP was associated with a higher risk of insulin use than type 2 diabetes (adjusted hazard ratio 1.38 at 5 years [95% CI 1.30-1.47], P < 0.0001). Individuals with DEP showed higher risks of hypoglycemia (odds ratio 1.85 [1.54-2.21], P < 0.0001), diabetic neuropathy (1.38 [1.28-1.49], P < 0.0001), nephropathy (1.38 [1.27-1.50], P < 0.0001), retinopathy (1.10 [1.01-1.20], P = 0.0347), coronary heart disease (1.59 [1.48-1.70], P < 0.0001), cerebrovascular disease (1.38 [1.28-1.49], P < 0.0001), and peripheral arterial disease (1.34 [1.25-1.44], P < 0.0001). All-cause mortality was higher in those with DEP (1.74 [1.57-1.93], P < 0.0001) than in those with type 2 diabetes. CONCLUSIONS: DEP is more likely to require insulin therapy than type 2 diabetes. Hypoglycemia, micro- and macrovascular complications, and all-cause mortality events are higher in DEP compared with type 2 diabetes.
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Complicaciones de la Diabetes , Diabetes Mellitus Tipo 2 , Hipoglucemia , Páncreas Exocrino , Enfermedades Pancreáticas , Estudios de Cohortes , Complicaciones de la Diabetes/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Hipoglucemia/complicaciones , Insulina/uso terapéutico , Enfermedades Pancreáticas/complicaciones , Factores de RiesgoRESUMEN
Health literacy is considered to be an emerging determinant of health behaviors and outcomes. The underlying mechanisms linking health literacy to diabetes self-management are currently unclear. This study assessed a mediation model consisting of a direct pathway between health literacy and self-management, and indirect pathways via social isolation only, self-efficacy only, and social isolation and self-efficacy serially in people with type 2 diabetes. A cross-sectional design was employed, and a total of 524 participants were recruited from outpatient clinics of multi-institutions from June 2020 to February 2021. The mediation model was analyzed using the PROCESS macro on SPSS with bootstrap bias-corrected 95% confidence intervals (CIs) with 10,000 bootstrapping iterations. Health literacy positively affected self-management. The estimated indirect effect of health literacy on self-management via social isolation was significant, at 0.018 (95% CI = 0.004-0.036). The indirect effect via self-efficacy was estimated at 0.214 (95% CI = 0.165-0.266). The indirect effect via social isolation and self-efficacy serially was 0.013 (95% CI = 0.006-0.023). The findings of this study suggest that clinical practice can be improved through more comprehensive diabetes self-management interventions that promote all of the components of health literacy, social contacts/networks, and self-efficacy in particular.
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The increasing use and distribution of chemicals are causing serious chemical accidents such as fires, explosions, and leaks during manufacturing and handling. In most cases, all risks caused by chemicals are classified as accidents due to defects in process facilities, human errors, and multi-cause accidents. Among chemical accidents caused by human errors, accurate analysis of accidents caused by the complex action of various types of human failures is required. Based on the accident investigation reports that occurred in South Korea from 2010 to 2017, chemical accidents caused by human failure were analyzed, and the fundamental causes were derived by classifying them into human error and violation. Human failure was analyzed according to the classification criteria for human failure of health and safety executive (HSE). As a result of the analysis, several types of human failure acted in combination to be a more significant cause of chemical accidents; incorrect application of process rules and procedures, inappropriate chemical information, lack of education, and defects in the current safety regulation were analyzed as the main causes. In addition, the cause of human errors was presented through case studies of chemical accidents in South Korea.
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Liberación de Peligros Químicos , Incendios , Accidentes , Accidentes de Trabajo , Humanos , República de Corea/epidemiologíaRESUMEN
Animal and clinical studies have revealed that (-)-epigallocatechin-3-O-gallate (EGCG), one of the major bioactive polyphenols in green tea, showed several pharmacological effects including anti-obesity effect and anti-inflammatory effect. We previously reported that the second messenger cyclic guanosine monophosphate (cGMP) mediates its anti-inflammatory and anti-cancer properties. Here we demonstrated that glucosyl-hesperidin, enhances the cGMP-inducing effects of green tea extract in vivo. Moreover, glucosyl-hesperidin intake potentiated the green tea-elicited upregulation of the anti-inflammatory factor, toll-interacting protein.
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Catequina , Hesperidina , Animales , Catequina/análogos & derivados , Catequina/farmacología , Guanosina Monofosfato , Polifenoles/farmacología , TéRESUMEN
PURPOSE: The aims of this study were to develop a new instrument for measuring self-management with a hierarchical structure [the Diabetes Self-Management Scale (DSMS)] in patients with type 2 diabetes, and evaluate its psychometric properties. METHOD: The DSMS instrument was developed in three phases: (1) conceptualization and item generation; (2) content validity and pilot testing; and (3) field testing of its psychometric properties. A convenience sample of 473 participants was recruited in three university hospitals and one regional health center, South Korea. RESULTS: Exploratory and confirmatory factor analyses yielded two second-order component models explaining the common variance among six first-order factors. Principal axis factoring with a varimax rotation accounted for 60.88% of the variance. Confirmatory factor analysis of the hierarchical structure revealed the following fit indices: χ2/df = 1.373, standardized root-mean-square residual = .050, goodness-of-fit index = .935, incremental fit index = .975, comparative fit index = .974, and root-mean-square error of approximation = .039. All Cronbach' α values for internal consistency exceeded the criterion of .70. All of the intraclass correlation coefficients for test-retest reliability exceeded .70 except that for the taking-medication subscale. The components of the DSMS were moderately correlated with the comparator measures of self-efficacy and health literacy administered for convergent validity. CONCLUSION: The DSMS is a new instrument for measuring the complex nature of self-management in patients with type 2 diabetes, comprising 17 items scored on a five-point Likert scale. The DSMS exhibits satisfactory psychometric properties for five reliability and validity metrics, and so is a suitable instrument to apply in both research and clinical practices.
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Diabetes Mellitus Tipo 2/enfermería , Medición de Resultados Informados por el Paciente , Psicometría/instrumentación , Autoeficacia , Automanejo/métodos , Automanejo/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , República de Corea , Encuestas y CuestionariosRESUMEN
BACKGROUND: The prevalence of obesity has rapidly increased in countries across the world in recent decades. The 2019 Obesity Fact Sheet released by the Korean Society for the Study of Obesity addressed the prevalence of obesity and abdominal obesity during the period of 2009 to 2018 and obesity-related social factors. METHODS: Data from the Korean National Health Insurance Service health checkup database between 2009 and 2018 and the Korea National Health and Nutrition Examination Survey between 2010 and 2017 were analyzed. The prevalence of obesity and abdominal obesity was calculated after standardizing for age and sex based on the 2010 population and housing census. RESULTS: From 2009 to 2018, the prevalence of obesity and abdominal obesity increased to 35.7% and 23.8%, respectively, in 2018. Upward trends in the prevalence of obesity and abdominal obesity was observed among both sexes and nearly all age groups. The prevalence of obesity and abdominal obesity was higher among individuals with lower education and household income levels. Among occupations, managers exhibited the highest prevalence of obesity and abdominal obesity. Further, the prevalence of obesity and abdominal obesity became higher among individuals working longer hours and split and night shift workers. CONCLUSION: The 2019 Obesity Fact Sheet provides information on changes in obesity dynamics during the past decade and obesity-related social factors in the Korean adult population. This report might constitute a cornerstone by which to establish targets for future interventions for reversing the rise in the prevalence of obesity and reducing the burden of obesity in Korea.
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ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonicus A. Berger (O. japonicus), so-called Wa-song in Korea, a traditional food and medicine that grows on mountain rocks and roof tiles. Wa-song containing various phenolic compounds have been reported as a medicinal plant for prevention of fibrosis, cancer, inflammation, and oxidative damage. AIM OF THE STUDY: The present study was designed to examine the anti-angiogenic effects of cultivated Orostachys japonicus 70% ethanol extract (CE) in vascular endothelial growth factor (VEGF)-stimulated human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: CE was prepared with 70% ethanol. HUVECs, rat aortic rings, and matrigel plug in mice were treated with CE (10-20 µg/mL) and VEGF (20-50 ng/mL), and the anti-angiogenic activities of CE were analyzed by SRB, wound healing, trans-well invasion, capillary-like tubule formation, rat aortas, Western blot, and matrigel plug assay. Phenolic compounds in CE were analyzed using a high-performance liquid chromatography (HPLC)-PDA system. RESULTS: Treatment of CE (10-20 µg/mL) markedly suppressed proliferation of HUVECs in the presence (from 136.5% to 112.2%) or absence of VEGF (from 100.0% to 92.1%). The proliferation inhibitory effect of CE was caused by G0/G1 cell cycle arrest, and the decrease of CDK-2, CDK-4, Cyclin D1 and Cyclin E1. Furthermore, CE treatment showed significant angiogenesis inhibitory effects on motility, invasion and micro-vessel formation of HUVECs, rat aortic rings and subcutaneous matrigels under VEGF-stimulation condition. In HUVECs, CE-induced anti-angiogenic effect was regulated by inhibition of the PI3K/AKT/mTOR, MAPK/p38, MAPK/ERK, FAK-Src, and VEGF-VEGFR2 signaling pathways. CONCLUSION: This study demonstrated that CE might be used as a potential natural substance, multi-targeted angiogenesis inhibitor, functional food material.
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Inhibidores de la Angiogénesis/farmacología , Crassulaceae/química , Neovascularización Patológica/tratamiento farmacológico , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Inductores de la Angiogénesis/farmacología , Animales , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Colágeno/efectos de los fármacos , Colágeno/metabolismo , Combinación de Medicamentos , Fase G1/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Laminina/efectos de los fármacos , Laminina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neovascularización Patológica/metabolismo , Proteoglicanos/efectos de los fármacos , Proteoglicanos/metabolismo , Ratas , Ratas Sprague-Dawley , Fase de Descanso del Ciclo Celular/efectos de los fármacosRESUMEN
PURPOSE: Patients with diabetes frequently need to perform certain numeric tasks such as interpreting blood glucose levels. However, there is no psychometrically sound instrument for objectively measuring diabetes-specific health numeracy. This study aimed to develop a new objective diabetes health numeracy test (DHNT) and evaluate its psychometric properties in adult patients with type 2 diabetes. METHODS: An instrument development study was conducted. Initial items were evaluated by six experts for content validity. After a pilot test, a convenience sample of 257 participants with type 2 diabetes was recruited at 2 university hospitals from May to September 2018. The structural, convergent, and criteria validity, and internal consistency of the DHNT with binary item responses were evaluated. Data were analyzed using exploratory factor analysis, Rasch analysis, tetrachoric correlation, Spearman's correlation, and the Kuder-Richardson-20 formula. RESULTS: Exploratory factor analysis yielded a single-factor solution comprising seven items. Rasch analysis confirmed that no item did not fit with the single factor and identified that the item difficulty parameters had moderate values. The convergent and criterion validity of the instrument were demonstrated, with diabetes knowledge and subjective diabetes numeracy, respectively, as was its acceptable internal consistency, by a Kuder-Richardson-20 coefficient of .81. CONCLUSION: The DHNT demonstrated satisfactory psychometric properties. The instrument with moderate levels of item difficulty may have a lower cognitive burden. The developed instrument can be applied in practice to tailor the education of diabetes self-management as per the levels of health numeracy of specific patients.
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Diabetes Mellitus Tipo 2/psicología , Evaluación Educacional , Alfabetización en Salud , Matemática , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/análisis , Diabetes Mellitus Tipo 2/terapia , Evaluación Educacional/métodos , Análisis Factorial , Femenino , Alfabetización en Salud/normas , Humanos , Masculino , Matemática/normas , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Automanejo/psicologíaRESUMEN
The present study investigated whether glucagon like peptide1 (GLP1) improves glucose uptake through glucose transporter type 4 (GLUT4), mediated by the activation of sirtuin 1 (SIRT1), in skeletal muscle cells with palmitate inducedinsulin resistance. The levels of glucose uptake, GLUT4, protein kinase A (PKA), and cyclic adenosine monophosphate (cAMP) were determined in human skeletal muscle myotubes (HSMMs) exposed to palmitate and GLP1. Then, to determine whether PKA/cAMP were downstream signals of GLP1, a PKA inhibitor was used. To determine whether SIRT1 contributes to GLP1 action in HSMMs with palmitateinduced insulin resistance, the levels of peroxisome proliferatoractivated receptor γ coactivator 1α (PGC1α) deacetylation and SIRT1 activity were assessed using a SIRT1 inhibitor and small interfering RNA (siRNA). The phosphorylation levels of protein kinase B (Akt) and insulin receptor substrate 1 (IRS1) as insulin signaling pathways, were assessed in GLP1treated HSMMs exposed to palmitate. The influence of SIRT1 on the GLP1induced activation of insulin signaling pathway was determined using a SIRT1 inhibitor. GLP1 restored the palmitateinduced reductions in the levels of glucose uptake, GLUT4 mRNA, GLUT4 promoter activity, and GLUT4 protein in HSMMs. PKA and cAMP, as GLP1 downstream signals, played a role in this process. GLP1 increased the deacetylation levels of PGC1α, and stimulated SIRT1 in HSMMs. Moreover, the SIRT1 inhibitor and siRNA of SIRT1 suppressed the effect of GLP1 on GLUT4 expression in HSMMs exposed to palmitate. The SIRT1 inhibitor also prevented the GLP1induced phosphorylation of IRS1 and Akt in palmitatetreated HSMMs. The present findings suggest that in palmitateinduced insulinresistant HSMM, GLP1 activates SIRT1 through the PKA/cAMP pathway, which in turn enhances glucose uptake through GLUT4 and the insulin signaling pathway.
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Péptido 1 Similar al Glucagón/farmacología , Resistencia a la Insulina , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Ácido Palmítico/farmacología , Sirtuina 1/metabolismo , Acetilación , Activación Enzimática , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Humanos , Modelos Biológicos , Fosforilación , Proteínas Recombinantes/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
We performed an infrared spectroscopic study on a single crystal of Sr2VO3FeAs grown by a self-flux method. This layered material system consists of two alternative layers of [SrVO3]-1 and [SrFeAs]+1. Since the typical size of single crystalline Sr2VO3FeAs samples is 200 [Formula: see text] 200 [Formula: see text] 10 [Formula: see text]m3 an optical study on this material is challenging. We observed an additional interband transition around 1000 cm-1, which is absent in other doped Ba-122 Fe-pnictides. The origin of this additional transition is not clearly known yet. We also observed a hidden Fermi liquid behavior. Interestingly, we observed a Fano line-shaped phonon which appears near 555 cm-1 below 200 K and shows a strong blue-shift when the temperature is lowered. The amplitude, width, and asymmetric Fano parameter of this phonon show anomalies at 150 K, which are probably related to an electronic phase observed below 155 K recently by an NMR study (Ok et al 2017 Nat. Commun. 8 2167). Our finding may help to understand the electronic phase observed previously in the same material.
RESUMEN
Orostachys japonicus has traditionally been used as a food product and a fork medicine in Asia to treat various diseases. Angiogenesis is a critical process that contributes to various chronic diseases via excessive delivery of oxygen and nutrients. Common anti-angiogenic drugs have serious problems related to high costs and side effects; thus, natural products with low costs and no cytotoxicity have garnered increasing interest. In this study, we evaluated and compared the anti-angiogenic effects and phenolic compound contents between wild (WOEs) and cultivated O. japonicus extracts (COEs) prepared under various extract conditions. WOEs and COEs suppressed cell proliferation of human umbilical vein endothelial cells (HUVECs) and inhibited vascular endothelial growth factor-induced chemotactic migration, invasion, and capillary-like tube formation in HUVECs. Among COEs, that prepared by 70% EtOH (70% CE) showed the most effective anti-angiogenic activity in HUVECs. When compared to WOEs, total polyphenol and total flavonoid contents were 1.28 to 4.38 times higher in COEs, and 70% CE contained the greatest flavonoid contents (28.28 ± 0.93 mg%), as well as the highest levels of major phenolic compounds including gallic acid (21.84 µg/mL), epicatechin-gallate (6.58 µg/mL), kaempferol (6.32 µg/mL), and quercetin (8.55 µg/mL). Although further studies are required to identify the molecular mechanisms behind these anti-angiogenic effects, 70% CE could be used as an herbal medicine, functional food ingredient, and potent angiogenesis inhibitor. PRACTICAL APPLICATION: Environmental factors such as altitude, nutrients, exposure to sunlight, and temperature can influence the type and quantity of bioactive components in plants. The advantage of cultivated plants is that the above-mentioned factors can be artificially adjusted compared to wild plants. Based on economic efficiency, productivity, and consistent quality, anti-angiogenesis activity of cultivated O. japonicus is of greater commercial value as a functional food than wild O. japonicus.