RESUMEN
The fungicide tebuconazole (TEB) poses risks to human and animal health via various exposure routes. It induces toxicity in multiple organs and disrupts reproductive health by affecting steroid hormone synthesis and fetal development. In this study, we investigated the impact of TEB on fetal testes using in vitro models, focusing on germ, Sertoli, and Leydig cells, and explored the mechanisms underlying cellular damage. The results revealed significant damage to germ cells and disruption of Leydig cell development. TEB exposure led to a decrease in germ cell numbers, as indicated by histological and immunostaining analyses. TEB induced the up- and down-regulation of the expression of fetal and adult Leydig cell markers, respectively. Additionally, TEB-treated fetal testes exhibited increased expression of oxidative-stress-related genes and proteins. However, co-treatment with the antioxidant N-acetylcysteine mitigated TEB-induced germ cell damage and prevented abnormal Leydig cell development. These findings suggest that administration of antioxidants can prevent the intratesticular damage typically caused by TEB exposure.
Asunto(s)
Células Intersticiales del Testículo , Técnicas de Cultivo de Órganos , Estrés Oxidativo , Especies Reactivas de Oxígeno , Testículo , Triazoles , Masculino , Animales , Testículo/efectos de los fármacos , Testículo/metabolismo , Triazoles/farmacología , Ratones , Especies Reactivas de Oxígeno/metabolismo , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Estrés Oxidativo/efectos de los fármacos , Técnicas de Cultivo de Órganos/métodos , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Antioxidantes/farmacología , Feto/efectos de los fármacos , Fungicidas Industriales/toxicidad , Células Germinativas/efectos de los fármacos , Células Germinativas/metabolismoRESUMEN
Treating female canine mammary gland tumors is crucial owing to their propensity for rapid progression and metastasis, significantly impacting the overall health and well-being of dogs. Mitoquinone (MitoQ), an antioxidant, has shown promise in inhibiting the migration, invasion, and clonogenicity of human breast cancer cells. Thus, we investigated MitoQ's potential anticancer properties against canine mammary gland tumor cells, CMT-U27 and CF41.Mg. MitoQ markedly suppressed the proliferation and migration of both CMT-U27 and CF41.Mg cells and induced apoptotic cell death in a dose-dependent manner. Furthermore, treatment with MitoQ led to increased levels of pro-apoptotic proteins, including cleaved-caspase3, BAX, and phospho-p53. Cell cycle analysis revealed that MitoQ hindered cell progression in the G1 and S phases in CMT-U27 and CF41.Mg cells. These findings were supported using western blot analysis, demonstrating elevated levels of cleaved caspase-3, a hallmark of apoptosis, and decreased expression of cyclin-dependent kinase (CDK) 2 and cyclin D4, pivotal regulators of the cell cycle. In conclusion, MitoQ exhibits in vitro antitumor effects by inducing apoptosis and arresting the cell cycle in canine mammary gland tumors, suggesting its potential as a preventive or therapeutic agent against canine mammary cancer.
Asunto(s)
Antineoplásicos , Apoptosis , Puntos de Control del Ciclo Celular , Proliferación Celular , Neoplasias Mamarias Animales , Compuestos Organofosforados , Ubiquinona , Animales , Perros , Apoptosis/efectos de los fármacos , Neoplasias Mamarias Animales/tratamiento farmacológico , Neoplasias Mamarias Animales/patología , Neoplasias Mamarias Animales/metabolismo , Femenino , Línea Celular Tumoral , Puntos de Control del Ciclo Celular/efectos de los fármacos , Antineoplásicos/farmacología , Ubiquinona/análogos & derivados , Ubiquinona/farmacología , Compuestos Organofosforados/farmacología , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacosRESUMEN
OBJECTIVES: The goal was to evaluate neonatal outcomes based on treatment strategies and time points for haemodynamically significant patent ductus arteriosus (hsPDA) in very-low-birth-weight preterm infants, with a particular focus on surgical closure. METHODS: This retrospective study included very-low-birth-weight infants born between 2014 and 2021 who received active treatment for hsPDA. Neonatal outcomes were compared between (i) primary surgical closure versus primary ibuprofen; (ii) early (<14th post-natal day) versus late primary surgical closure (≥14th post-natal day); and (iii) primary versus secondary surgical closure after ibuprofen failure. Further analysis using 1:1 propensity score matching was performed. Logistic regression was conducted to analyse the risk factors for post-ligation cardiac syndrome (PLCS) and/or acute kidney injury (AKI). RESULTS: A total of 145 infants with hsPDA underwent active treatment for closure. The in-hospital death rate and the incidence of severe bronchopulmonary dysplasia (BPD) were similar between the primary surgical closure group and the primary ibuprofen group in a 1:1 matched analysis. Severe BPD was significantly higher in the late surgical closure group than in the early primary surgical closure group with 1:1 propensity score matching (72.7% vs 40.9%, P=0.033). The secondary surgical closure group showed the mildest clinical condition; however, the probability of PLCS/AKI was highest (38.6%) compared to the early (15.2%) or the late primary surgical group (28.1%, P<0.001), especially in extremely premature infants (gestational age < 28 weeks). CONCLUSIONS: Surgical patent ductus arteriosus closure is not inferior to pharmacologic treatment. Considering the harmful effect of a prolonged patent ductus arteriosus shunt exposure, a timely decision and timely efforts should be made to minimize the risk of severe BPD and PLCS/AKI after surgical closure.
Asunto(s)
Conducto Arterioso Permeable , Ibuprofeno , Recién Nacido de muy Bajo Peso , Humanos , Conducto Arterioso Permeable/cirugía , Recién Nacido , Estudios Retrospectivos , Masculino , Femenino , Ibuprofeno/uso terapéutico , Ligadura/métodos , Recien Nacido Prematuro , Edad Gestacional , Puntaje de Propensión , Procedimientos Quirúrgicos Cardíacos/métodos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Resultado del Tratamiento , Factores de RiesgoRESUMEN
BACKGRUOUND: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. RESULTS: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. CONCLUSION: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
Asunto(s)
Atorvastatina , LDL-Colesterol , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Dislipidemias , Hemoglobina Glucada , Hipoglucemiantes , Metformina , Humanos , Atorvastatina/uso terapéutico , Atorvastatina/administración & dosificación , Metformina/uso terapéutico , Metformina/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Masculino , Femenino , Método Doble Ciego , Persona de Mediana Edad , Dislipidemias/tratamiento farmacológico , Dislipidemias/sangre , Hemoglobina Glucada/análisis , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Anciano , LDL-Colesterol/sangre , Resultado del Tratamiento , AdultoRESUMEN
Dragon fruit peel, often discarded, is a valuable source of commercial pectin. This study investigates different extraction methods, including cold-water (CW), hot-water (HW), ultrasound (US), and novel enzyme extraction (xylanase: EZX), to extract pectins from dragon fruit peel and compare their characteristics. The pectin yield ranged from 10.93% to 20.22%, with significant variations in physicochemical properties across methods (p < 0.05). FTIR analysis revealed that extraction methods did not alter the primary structural configuration of the pectins. However, molecular weights (Mws) varied significantly, from 0.84 to 1.21 × 103 kDa, and the degree of esterification varied from 46.82% to 51.79% (p < 0.05). Monosaccharide analysis identified both homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) pectic configurations in all pectins, predominantly comprising galacturonic acid (77.21-83.12 %mol) and rhamnose (8.11-9.51 %mol), alongside minor side-chain sugars. These properties significantly influenced pectin functionalities. In the aqueous state, a higher Mw impacted viscosity and emulsification performance, while a lower Mw enhanced antioxidant activities and promoted the prebiotic function of pectin (Lactis brevies growth). This study highlights the impact of extraction methods on dragon fruit peel pectin functionalities and their structure-function relationship, providing valuable insights into predicting dragon fruit peel's potential as a food-grade ingredient in various products.
RESUMEN
This study focuses on developing a biodegradable film using a novel hybrid citrus peel pectin. A bilayer approach with PLA was proposed and optimized using Response Surface Methodology (RSM) to complement pectin films' mechanical and barrier property limitations. The optimized film composition (2.90 g PLA and 1.96 g pectin) showed enhanced mechanical strength with a tensile strength (TS) of 7.04 MPa and an elongation at break (EAB) of 462.63%. In addition, it demonstrated lower water vapor (1.45 × 10-10 g/msPa), oxygen (2.79 × 10-7 g/ms) permeability, and solubility (23.53%). Compared to single-layer pectin films, the optimized bilayer film had a 25% increased thickness, significantly improved water barrier (3806 times lower) and oxygen barrier (3.68 times lower) properties, and 22.38 times higher stretchability, attributed to hydrogen bond formation, as confirmed by FTIR analysis. The bilayer film, effectively protected against UV and visible light, could be a barrier against light-induced lipid oxidation. Moreover, it demonstrated superior seal efficiency, ensuring secure sealing in practical applications. The bilayer pouch containing mustard dressing exhibited stable sealing with no leakage after immersion in hot water and ethanol, making it suitable for secure food pouch packaging.
RESUMEN
BACKGRUOUND: The association between low-density lipoprotein (LDL-C) levels and cardiovascular disease (CVD) risk in different age groups within the diabetes mellitus (DM) population remains unclear. The cohort study was conducted to investigate this relationship. METHODS: We assessed the 2009 to 2012 Korean National Health Screening and National Health Insurance Service records, with follow-up to the primary outcome (myocardial infarction [MI] or stroke) or December 2018. After excluding the participants with a history of MI or stroke, 2,227,394 participants with DM were included and categorized according to baseline LDL-C levels and age. Cox proportional hazards modeling was conducted. The CVD risk of age <40 years and LDL-C <70 mg/dL was set as the reference. In each age group, LDL-C <70 mg/dL was used as a reference for the subgroup analysis. RESULTS: The cut-off LDL-C value for increased MI risk in each age group varied (<40 years old, LDL-C ≥160 mg/dL: hazard ratios [HR], 2.03; 95% confidence interval [CI], 1.644 to 2.506) (40-49-year-old, LDL-C <115 mg/dL: HR, 1.245; 95% CI, 1.04 to 1.489) (50-59-year-old, LDL-C <115 mg/dL: HR, 1.21; 95% CI, 1.014 to 1.445) (60-69-year-old, LDL-C <145 mg/dL: HR, 1.229; 95% CI, 1.022 to 1.479) (≥70 years old group, LDL-C <100 mg/dL: HR, 1.238; 95% CI, 1.018 to 1.504). The cut-off LDL-C values for increased stroke risk varied in each age subgroup (<40 years old, LDL-C ≥160 mg/dL: HR, 1.395; 95% CI, 1.094 to 1.779) (40-49-year-old, LDL-C <145 mg/dL: HR, 1.13; 95% CI, 1.019 to 1.253) (50-59-year-old, LDL-C <160 mg/dL: HR, 1.079; 95% CI, 1.008 to 1.154) (60-69-year-old, LDL-C <130 mg/dL: HR, 1.07; 95% CI, 1.022 to 1.119) (≥70 years old, LDL-C <115 mg/dL: HR, 1.064; 95% CI, 1.019 to 1.112). CONCLUSION: The effect of LDL-C on the risk of CVD differs depending on the age of the population with DM.
Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Adulto , Anciano , Persona de Mediana Edad , Estudios de Cohortes , Enfermedades Cardiovasculares/epidemiología , LDL-Colesterol , Infarto del Miocardio/epidemiología , Diabetes Mellitus/epidemiología , Accidente Cerebrovascular/epidemiología , República de Corea/epidemiologíaRESUMEN
Background: This study investigated the real-world efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in Korean adults with type 2 diabetes mellitus (T2DM), whose insulin treatment was switched to IDegAsp. Methods: This was a multicenter, retrospective, observational study comprising two 26-week treatment periods, before and after switching to IDegAsp, respectively. Korean adults with uncontrolled T2DM treated with basal or premix insulin (±oral antidiabetic drugs) were enrolled. The primary objective was to compare the degree of glycosylated hemoglobin (HbA1c) change in each 26-week observation period. The analyses included changes in HbA1c, fasting plasma glucose (FPG), body weight, proportion of participants achieving HbA1c <7.0%, hypoglycemic events, and total daily insulin dose (ClinicalTrials.gov, number NCT04656106). Results: In total, 196 adults (mean age, 65.95 years; mean T2DM duration, 18.99 years) were analyzed. The change in both HbA1c and FPG were significantly different between the pre-switching and the post-switching period (0.28% vs. -0.51%, P<0.001; 5.21 mg/dL vs. -23.10 mg/dL, P=0.005), respectively. After switching, the rate of achieving HbA1c <7.0% was significantly improved (5.10% at baseline vs. 11.22% with IDegAsp, P=0.012). No significant differences (before vs. after switching) were observed in body weight change, and total daily insulin dose. The rates of overall and severe hypoglycemia were similar in the two periods. Conclusion: In real-world clinical practice in Korea, the change of insulin regimen to IDegAsp was associated with an improvement in glycemic control without increase of hypoglycemia, supporting the use of IDegAsp for patients with T2DM uncontrolled with basal or premix insulin.
RESUMEN
It has been generally accepted that insulin resistance (IR) and reduced insulin secretory capacity are the basic pathogenesis of type 2 diabetes mellitus (T2DM). In addition to genetic factors, the persistence of systemic inflammation caused by obesity and the associated threat of lipotoxicity increase the risk of T2DM. In particular, the main cause of IR is obesity and subjects with T2DM have a higher body mass index (BMI) than normal subjects according to recent studies. The prevalence of T2DM with IR has increased with increasing BMI during the past three decades. According to recent studies, homeostatic model assessment of IR was increased compared to that of the 1990s. Rising prevalence of obesity in Korea have contributed to the development of IR, non-alcoholic fatty liver disease and T2DM and cutting this vicious cycle is important. My colleagues and I have investigated this pathogenic mechanism on this theme through clinical and experimental studies over 20 years and herein, I would like to summarize some of our studies with deep gratitude for receiving the prestigious 2023 Sulwon Award.
Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Obesidad , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Diabetes Mellitus Tipo 2/epidemiología , Obesidad/epidemiología , Obesidad/complicaciones , Índice de Masa Corporal , Animales , República de Corea/epidemiología , PrevalenciaRESUMEN
BACKGROUND: The risk of heart failure (HF) in underweight diabetes mellitus (DM) patients has rarely been studied. We conducted a cohort study to investigate the association between underweight (BMI < 18.5 kg/m2) and BMI change over time and the risk of HF in patients with type 2 DM. METHODS: We utilized the health screening data from the National Health Insurance Service and the Korean National Health Screening database from 2009 to 2012, with follow-up until December 2018. Participants with DM were categorized into four groups based on their BMI at 4 years before study inclusion and BMI at the study entry: (1) Always Normal Weight (BMI at 4 years ago/BMI at study entry ≥18.5/≥18.5 kg/m2, reference group); (2) Transitioned to Underweight (≥18.5/<18.5 kg/m2); (3) Transitioned to Normal Weight (<18.5/≥18.5 kg/m2) and (4) Always Underweight (<18.5/<18.5 kg/m2). Participants were followed until the development of HF or at the end of the follow-up. Initial screening data included participants with DM who had the health screening during the study period (n = 2,746,079). Participants aged <20 years (n = 390), those who did not undergo health examination 4 years prior (n = 1,306,520), and those with missing data (n = 77,410) were excluded. Participants diagnosed with HF before study participation (n = 81,645) and within 1 year of study enrolment (n = 11,731) were excluded. After applying exclusion criteria, 1,268,383 participants were finally included in the analysis. The primary outcome was the development of HF. We employed Cox proportional hazards models, adjusting for various confounding factors, to assess the risk of developing HF. RESULTS: Median follow-up duration was 6.88 years and men were 63.16%. The mean ages of each groups were as follows: Always Normal Weight (57.92 ± 11.64 years), Transitioned to Underweight (62 ± 13.5 years), Transitioned to Normal Weight (56.6 ± 15.29 years) and Always Underweight (57.76 ± 15.35 years). In comparison with the Always Normal Weight group (n = 1,245,381, HF = 76,360), Transitioned to Underweight group (≥18.5/<18.5 kg/m2, n = 9304, HF = 880, adjusted Hazard Ratio (aHR)1.389, 95% confidence interval (CI) 1.3-1.485) or Transitioned to Normal Weight (<18.5/≥18.5 kg/m2, n = 6024, HF = 478, aHR 1.385, 95% CI 1.266-1.515) exhibited an increased risk of HF. The highest risk was observed in the Always Underweight group (<18.5/<18.5 kg/m2, n = 7674, HF = 665, aHR 1.612, 95% CI 1.493-1.740). CONCLUSIONS: Underweight was significantly associated with the risk of HF in the DM population. Active surveillance for HF in an underweight DM population is needed.
Asunto(s)
Diabetes Mellitus , Insuficiencia Cardíaca , Masculino , Humanos , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Obesidad/complicaciones , Delgadez/complicaciones , Delgadez/epidemiología , Factores de Riesgo , Índice de Masa Corporal , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/complicaciones , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologíaRESUMEN
BACKGRUOUND: Polyunsaturated fatty acids (PUFAs) reportedly have protective effects on pancreatic ß-cells; however, the underlying mechanisms are unknown. METHODS: To investigate the cellular mechanism of PUFA-induced cell protection, mouse insulinoma 6 (MIN6) cells were cultured with palmitic acid (PA) and/or docosahexaenoic acid (DHA), and alterations in cellular signaling and apoptosis were examined. RESULTS: DHA treatment remarkably repressed caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL)-positive red dot signals in PA-treated MIN6 cells, with upregulation of autophagy, an increase in microtubule- associated protein 1-light chain 3 (LC3)-II, autophagy-related 5 (Atg5), and decreased p62. Upstream factors involved in autophagy regulation (Beclin-1, unc51 like autophagy activating kinase 1 [ULK1], phosphorylated mammalian target of rapamycin [mTOR], and protein kinase B) were also altered by DHA treatment. DHA specifically induced phosphorylation on S2448 in mTOR; however, phosphorylation on S2481 decreased. The role of G protein-coupled receptor 120 (GPR120) in the effect of DHA was demonstrated using a GPR120 agonist and antagonist. Additional treatment with AH7614, a GPR120 antagonist, significantly attenuated DHA-induced autophagy and protection. Taken together, DHA-induced autophagy activation with protection against PA-induced apoptosis mediated by the GPR120/mTOR axis. CONCLUSION: These findings indicate that DHA has therapeutic effects on PA-induced pancreatic ß-cells, and that the cellular mechanism of ß-cell protection by DHA may be a new research target with potential pharmacotherapeutic implications in ß-cell protection.
Asunto(s)
Autofagia , Ácidos Docosahexaenoicos , Células Secretoras de Insulina , Transducción de Señal , Animales , Ratones , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Ácidos Docosahexaenoicos/farmacología , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Palmitatos/farmacología , Ácido Palmítico/farmacología , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGRUOUND: Inconsistent results have been reported regarding the association between the use of antidiabetic drugs and the clinical outcomes of coronavirus disease 2019 (COVID-19). This study aimed to investigate the effect of antidiabetic drugs on COVID-19 outcomes in patients with diabetes using data from the National Health Insurance Service (NHIS) in South Korea. METHODS: We analyzed the NHIS data of patients aged ≥20 years who tested positive for COVID-19 and were taking antidiabetic drugs between December 2019 and June 2020. Multiple logistic regression analysis was performed to analyze the clinical outcomes of COVID-19 based on the use of antidiabetic drugs. RESULTS: A total of 556 patients taking antidiabetic drugs tested positive for COVID-19, including 271 male (48.7%), most of whom were in their sixties. Of all patients, 433 (77.9%) were hospitalized, 119 (21.4%) received oxygen treatment, 87 (15.6%) were admitted to the intensive care unit, 31 (5.6%) required mechanical ventilation, and 61 (11.0%) died. Metformin was significantly associated with the lower risks of mechanical ventilation (odds ratio [OR], 0.281; 95% confidence interval [CI], 0.109 to 0.720; P=0.008), and death (OR, 0.395; 95% CI, 0.182 to 0.854; P=0.018). Dipeptidylpeptidase-4 inhibitor (DPP-4i) were significantly associated with the lower risks of oxygen treatment (OR, 0.565; 95% CI, 0.356 to 0.895; P=0.015) and death (OR, 0.454; 95% CI, 0.217 to 0.949; P=0.036). Sulfonylurea was significantly associated with the higher risk of mechanical ventilation (OR, 2.579; 95% CI, 1.004 to 6.626; P=0.049). CONCLUSION: In patients with diabetes and COVID-19, metformin exhibited reduced risks of mechanical ventilation and death, DPP- 4i was linked with lower risks of oxygen treatment and death, while sulfonylurea was related to the increased risk of mechanical ventilation.
Asunto(s)
COVID-19 , Hipoglucemiantes , Humanos , Masculino , Hipoglucemiantes/uso terapéutico , Femenino , Persona de Mediana Edad , COVID-19/epidemiología , COVID-19/mortalidad , República de Corea/epidemiología , Anciano , Adulto , Respiración Artificial/estadística & datos numéricos , SARS-CoV-2 , Metformina/uso terapéutico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/tratamiento farmacológico , Tratamiento Farmacológico de COVID-19 , Hospitalización/estadística & datos numéricos , Resultado del Tratamiento , Adulto Joven , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéuticoRESUMEN
BACKGRUOUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA), which is a therapeutic agent for the treatment of type 2 diabetes mellitus, has a beneficial effect on the cardiovascular system. METHODS: To examine the protective effects of GLP-1RAs on proliferation and migration of vascular smooth muscle cells (VSMCs), A-10 cells exposed to angiotensin II (Ang II) were treated with either exendin-4, liraglutide, or dulaglutide. To examine the effects of GLP-1RAs on vascular calcification, cells exposed to high concentration of inorganic phosphate (Pi) were treated with exendin-4, liraglutide, or dulaglutide. RESULTS: Ang II increased proliferation and migration of VSMCs, gene expression levels of Ang II receptors AT1 and AT2, proliferation marker of proliferation Ki-67 (Mki-67), proliferating cell nuclear antigen (Pcna), and cyclin D1 (Ccnd1), and the protein expression levels of phospho-extracellular signal-regulated kinase (p-Erk), phospho-c-JUN N-terminal kinase (p-JNK), and phospho-phosphatidylinositol 3-kinase (p-Pi3k). Exendin-4, liraglutide, and dulaglutide significantly decreased the proliferation and migration of VSMCs, the gene expression levels of Pcna, and the protein expression levels of p-Erk and p-JNK in the Ang II-treated VSMCs. Erk inhibitor PD98059 and JNK inhibitor SP600125 decreased the protein expression levels of Pcna and Ccnd1 and proliferation of VSMCs. Inhibition of GLP-1R by siRNA reversed the reduction of the protein expression levels of p-Erk and p-JNK by exendin-4, liraglutide, and dulaglutide in the Ang II-treated VSMCs. Moreover, GLP-1 (9-36) amide also decreased the proliferation and migration of the Ang II-treated VSMCs. In addition, these GLP-1RAs decreased calcium deposition by inhibiting activating transcription factor 4 (Atf4) in Pi-treated VSMCs. CONCLUSION: These data show that GLP-1RAs ameliorate aberrant proliferation and migration in VSMCs through both GLP-1Rdependent and independent pathways and inhibit Pi-induced vascular calcification.
Asunto(s)
Diabetes Mellitus Tipo 2 , Calcificación Vascular , Humanos , Angiotensina II/farmacología , Angiotensina II/metabolismo , Exenatida/farmacología , Liraglutida/farmacología , Músculo Liso Vascular/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Antígeno Nuclear de Célula en Proliferación/farmacología , Receptores de Péptidos Similares al Glucagón , Diabetes Mellitus Tipo 2/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/farmacología , Fosfatos/metabolismo , Fosfatos/farmacología , Proliferación Celular , Calcificación Vascular/metabolismoRESUMEN
BACKGRUOUND: Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states. METHODS: Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco's modified Eagle's medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours. RESULTS: SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation. CONCLUSION: These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.
Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Proteínas Quinasas Activadas por AMP/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Gluconeogénesis/genética , Glucosa , Fosfoenolpiruvato Carboxiquinasa (ATP)/genética , Fosfoenolpiruvato Carboxiquinasa (ATP)/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/farmacología , Proteínas Proto-Oncogénicas c-akt/uso terapéutico , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/farmacología , Transducción de Señal , Sodio/metabolismo , Sodio/farmacología , Sodio/uso terapéutico , Transportador 2 de Sodio-Glucosa/metabolismo , Transportador 2 de Sodio-Glucosa/farmacología , Transportador 2 de Sodio-Glucosa/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Obesity and metabolic syndrome are known risk factors for thyroid cancer. OBJECTIVE: We investigated the association between NAFLD and thyroid cancer risk in young adults. METHODS: This nationwide cohort study included 1 135 967 participants aged 20 to 39 years who underwent 4 consecutive health screenings in South Korea. NAFLD was categorized using the fatty liver index (FLI), as follows: ≥60, 30 to 60, and <30. The cumulative FLI points were defined as the number of times participants had a FLI of ≥30 (0-4). RESULTS: During a median follow-up of 5.2 years, 4126 participants (0.36%) were newly diagnosed with thyroid cancer. Compared with the participants with an FLI of <30, those with an FLI of 30 to 60 (men: hazard ratio [HR] 1.36 [95% CI, 1.22-1.51] and women: HR 1.44 [1.21-1.70]) and those with an FLI of ≥60 (men: HR 1.71 [1.53-1.92] and women: HR 1.81 [1.46-2.25]) had a significantly higher risk of thyroid cancer. Participants with higher cumulative FLI points had a higher risk of thyroid cancer compared to those with a cumulative FLI point of 0 (P < .001). During the follow-up period, the participants with an increased FLI exhibited an increased risk of thyroid cancer. CONCLUSION: NAFLD was associated with an increased risk of thyroid cancer in young adults. Repeatedly elevated FLI and progression of NAFLD were associated with an increased risk of thyroid cancer in this study.
Asunto(s)
Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Neoplasias de la Tiroides , Masculino , Humanos , Femenino , Adulto Joven , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Síndrome Metabólico/complicaciones , Estudios de Cohortes , Factores de Riesgo , Neoplasias de la Tiroides/etiología , Neoplasias de la Tiroides/complicacionesRESUMEN
Diuron is a phenylurea herbicide widely used in the agricultural industry. In recent years, the risk of infertility and developmental defects has increased due to exposure to environmental pollutants. In this study, we investigated the toxicity of diuron in fetal mouse testes using three-dimensional organ cultures. Fetal testes derived from embryonic day (E) 14.5 were cultured with 200 µM diuron for 5 days. The results revealed that diuron did not impair fetal germ cell proliferation or the expression levels of germ cell markers such as Ddx4, Dazl, Oct 4, Nanog, Plzf, and TRA 98. Similarly, the gene or protein expression of the Sertoli cell markers Sox9 and Wt1 in diuron-exposed fetal testes did not change after 5 days of culture. In contrast, diuron increased fetal Leydig cell markers (FLC), Cyp11a1, Cyp17a1, Thbs2, and Pdgf α, and decreased adult Leydig cell (ALC) markers, Sult1e1, Hsd173, Ptgds, and Vcam1. However, 3-ßHSD, an FLC and ALC marker, was consistently maintained upon exposure to diuron in fetal testes compared to non-treated groups. In conclusion, our study demonstrates that diuron negatively impacts Fetal Leydig cell development, although it does not affect germ and Sertoli cells.
Asunto(s)
Células Intersticiales del Testículo , Testículo , Ratones , Masculino , Animales , Testículo/metabolismo , Células Intersticiales del Testículo/metabolismo , Diurona/metabolismo , Células de Sertoli/fisiología , Feto/metabolismoRESUMEN
BACKGRUOUND: The effect of obesity on the development of type 2 diabetes mellitus (DM) in different age groups remains unclear. We assessed the impact of obesity on the development of DM for two age groups (40-year-old, middle age; 66-year-old, older adults) in the Korean population. METHODS: We analyzed Korean National Health Insurance Service data of 4,145,321 Korean adults with 40- and 66-year-old age without DM, between 2009 and 2014. Participants were followed up until 2017 or until the diagnosis of DM. We assessed the risk of DM based on the body mass index and waist circumference of the participants. Multiple confounding factors were adjusted. RESULTS: The median follow-up duration was 5.6 years. The association of general and abdominal obesity with the risk of DM development was stronger in the 40-year-old group (general obesity: hazard ratio [HR], 3.566, 95% confidence interval [CI], 3.512 to 3.622; abdominal obesity: HR, 3.231; 95% CI, 3.184 to 3.278) than in the 66-year-old group (general obesity: HR, 1.739; 95% CI, 1.719 to 1.759; abdominal obesity: HR, 1.799; 95% CI, 1.778 to 1.820). In the 66-year-old group, abdominal obesity had a stronger association with the development of DM as compared to general obesity. In the 40-year-old group, general obesity had a stronger association with the risk of DM development than abdominal obesity. CONCLUSION: The influence of general and abdominal obesity on the development of DM differed according to age. In older adults, abdominal obesity had a stronger association with DM development than general obesity.
Asunto(s)
Diabetes Mellitus Tipo 2 , Persona de Mediana Edad , Humanos , Anciano , Adulto , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiología , Factores de Riesgo , Obesidad/complicaciones , Obesidad/epidemiología , Índice de Masa CorporalRESUMEN
Left aortic arch with right descending aorta associated with coarctation of the aorta is a rare congenital cardiac anomaly. Conventional aortic arch repair in this condition may cause airway compression by the abnormally coursing descending aorta. We present the case of a neonate with this anomaly who underwent successful descending aortic translocation to prevent postoperative left main bronchial stenosis.
Asunto(s)
Síndromes del Arco Aórtico , Coartación Aórtica , Cardiopatías Congénitas , Recién Nacido , Humanos , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Aorta Torácica/anomalías , Coartación Aórtica/diagnóstico por imagen , Coartación Aórtica/cirugía , Aorta/cirugía , Cardiopatías Congénitas/complicaciones , Síndromes del Arco Aórtico/congénito , Complicaciones PosoperatoriasRESUMEN
This study investigated the valorization of novel HG-type hybrid citrus pectins derived from three cultivars: Setoka (ST), Kanpei (KP), and Shiranui (SH), and their application as packaging materials. The physicochemical properties of these pectins and their corresponding films were evaluated and compared to commercial citrus pectin. Significant variations were observed in pectin yield (18.15-24.12 %) and other physicochemical characteristics, such as degree of esterification (DE), degree of methoxylation (DM), and monosaccharide composition, among the different cultivars. All hybrid citrus pectins were classified as high-methoxy pectin types (66.67-72.89 %) with typical structural configurations like commercial citrus pectin. However, hybrid citrus pectin films exhibited superior physical properties, including higher mechanical strength, flexibility, and lower water solubility than commercial citrus pectin film, while maintaining similar transparency and moisture content. Additionally, the films displayed smooth and uniform surface morphology, confirming their excellent film-forming properties. Correlation analysis revealed that DE positively influenced mechanical properties (r = 1.0). Furthermore, the monosaccharide composition of pectins showed strong relationships (r = 0.8-1.0) with the film's mechanical and barrier properties. These findings highlight the potential of hybrid citrus pectin as potential packaging material, and the knowledge of the structure-function relationship obtained in this study could be useful for the tailored modification of citrus pectin-based packages.