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South Korea has faced many social issues due to long working hours, lack of rest areas, and poor rest facility environments for cleaners, security guards, department store workers, etc. Discussions have been ongoing about mandating the installation of rest facilities. From August 18, 2022, Article 128-2 of the Occupational Safety and Health Act, concerning the installation of rest facilities, was enforced. Consequently, employers in all industries are required to install rest facilities, and laws have been established to ensure these facilities meet certain standards. Accordingly, this study investigated the current status of rest facility installations and the awareness of the law's enactment in Korean industrial sites. The results, analyzed by gender, age, managerial status, industry, and size of the business, indicated that younger people were less satisfied with the rest facilities. Managers were more knowledgeable about the legal regulations than workers. In the service industry, compared to other industries, smaller businesses were less likely to have rest facilities and were less aware of the legal regulations. The results of this study are expected to be used as basic data to help establish the rest facility installation laws in Korea.
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Salud Laboral , República de Corea , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Salud Laboral/legislación & jurisprudencia , Lugar de Trabajo/legislación & jurisprudencia , Concienciación , Encuestas y Cuestionarios , Industrias/legislación & jurisprudenciaRESUMEN
Previous studies have investigated the health hazards caused by exposure to the noise of heavy equipment used at construction sites. Korea's Ministry of Land, Infrastructure, and Transport operates a registration system for construction machinery, and regular safety inspections are mandatory. Although workers inspecting construction machinery vehicles are exposed to unwanted noise, no noise exposure assessment has been made regarding these workers in Korea. The time-weighted average (TWA) daily average noise exposure level among construction machinery inspectors at 18 inspection centers was 75.3 dB(A). Among the inspection steps, the exhaust gas inspection step was found to exhibit the highest noise exposure level, up to 100 dB(A). In Korea, if the noise level of a workplace exceeds 85 dB(A) as a TWA, workers are required to undergo special medical examinations. This study found that special medical examinations were required for two of the 18 target inspection centers (approximately 115 workers) as the 8-hour TWA noise level exceeded 85 dB(A). Therefore, regular noise exposure assessment and special medical examinations for noise are required to prevent inspectors from developing hearing disorders due to noise exposure.
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Industria de la Construcción , Ruido en el Ambiente de Trabajo , Exposición Profesional , Humanos , República de Corea , Ruido en el Ambiente de Trabajo/efectos adversos , Exposición Profesional/análisis , Adulto , Monitoreo del Ambiente/métodos , Monitoreo del Ambiente/normas , Pérdida Auditiva Provocada por Ruido/etiología , Pérdida Auditiva Provocada por Ruido/prevención & control , MasculinoRESUMEN
PURPOSE: Dyslipidemia is a major health issue worldwide. There is growing interest in understanding the potential role of kimchi consumption on serum lipid profiles. However, there are limited epidemiological studies available on this topic. Therefore, this study aims to investigate the association between kimchi intake and serum lipid profiles. METHODS: We conducted an epidemiological study on participants (aged 40-69 years old) selected from the Health Examinees (HEXA) cohort study (n = 61,761). Four types of kimchi, including Baechu kimchi (cabbage kimchi), Kkakdugi (radish kimchi), Nabak kimchi/Dongchimi (a type of water kimchi made with fermented vegetables), and other kimchi, were assessed by a 106-food item semi-quantitative validated food frequency questionnaire (FFQ). Each kimchi intake is the average value calculated from the FFQ of the baseline and follow-up surveys. Fasting blood data were obtained at baseline and follow-up visits. Linear regression was used to examine the relationship between the intake of kimchi and the change in serum lipid profiles. RESULTS: The mean years between the baseline survey and a follow-up survey was 4.97 years. In this study, compared to the lowest category (< 1 serving/day), Baechu kimchi intake (2- < 3 servings/day) had more negative correlations with the change in values of total cholesterol (ß: -1.600, 95% confidence interval [CI, -2.744, -0.456]), triglycerides (ß: -3.372, 95% CI [-5.414, -1.330]), and low-density lipoprotein cholesterol (ß: -1.155, 95% CI [-2.214, -0.095]) in women. In men, Baechu kimchi intake (2- < 3 servings/day) had a more positive correlation associated with the changes in values of high-density lipoprotein cholesterol (ß: 0.049, 95% CI [0.031, 0.907]) compared to the lowest intake category (< 1 serving/day). CONCLUSIONS: Among Korean adults, consumption of kimchi, particularly Baechu kimchi, was found to be associated with improvements in serum lipid profiles. Further studies are required to conduct additional interventions to confirm the association between kimchi and serum lipid profiles.
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Feed has a great influence on the composition of swine manure, which is the principal cause of odor. Therefore, the purpose of this study is to simply change the shape of pig feed and control calories to find a suitable feed form for reducing the smell of swine manure. The experiment was conducted on 15 pigs from July to August 2021, and a total of three measurements were done. Three types of feed were evaluated in this study. The analysis items related to odor of swine manure are complex odor, ammonia, sulfur-based odors, and volatile organic compounds (VOCs). In the case of complex odor, dilution multiples tended to decrease over time, except for type A feed. The concentration of ammonia in all types of feed decreased over time. Most sulfur-based odorous substances except hydrogen sulfide at the first measurement were not detected. Representatively, Decane, 2,6-Dimethylnonane, and 1-Methyl-3-propylcycolhexane were detected in VOCs generated from swine manure. The major odorous substansces in swine manure have changed from ammonia and sulfur compounds to VOCs. In order to reduce the odor caused by swine manure, it is ad-vantageous to use low-calorie feed consisting of pellet-type.
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In a widespread social turmoil such as the Pandemic, job groups with high turnover rates and high job stress, such as the construction industry, will have a greater adverse impact than the general job group. This is to be used as basic data in preparing management plans by identifying the factors that hinder job stress and job satisfaction of construction workers. In this study, during the Pandemic period (1 September 2021 to 31 December 2021), a survey was conducted on job stress and job satisfaction among safety and health managers working at construction sites. The overall job satisfaction of workers in the construction industry was grasped by analyzing the level of correlation and the mutual influence on job stress, job satisfaction, general characteristics, and work-related characteristics. As a result, in terms of work characteristics, it was found that the smaller the working period in the current position, the more positive the job satisfaction was (p < 0.01). In addition, it was found that job satisfaction increased significantly when there was a promotion opportunity (p < 0.001). The construction industry is a job group with high basic job stress and low job satisfaction. In addition, it was evaluated that job stress increased during the pandemic.
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Industria de la Construcción , Estrés Laboral , Humanos , Satisfacción en el Trabajo , Estrés Laboral/epidemiología , Pandemias , Reorganización del PersonalRESUMEN
AIM: To investigate the effectiveness and safety of teneligliptin over placebo in patients with type 2 diabetes (T2D) inadequately controlled by triple therapy. MATERIALS AND METHODS: This trial was a prospective, multicentre, randomized, double-blind, placebo-controlled study. The 12-week double-blind period was followed by a 12-week, open-label clinical trial. One hundred patients with T2D who failed to achieve the glycaemic target (7.1% ≤ HbA1c ≤ 9.0%) with conventional triple oral antidiabetic drugs (OADs) of metformin, sulphonylurea, and sodium-glucose co-transporter-2 inhibitor were assigned randomly 1:1 into teneligliptin and placebo-teneligliptin groups. The primary endpoint was mean change in HbA1c level from baseline in each group at 12 weeks. RESULTS: For a total of 99 patients (n = 51 for the teneligliptin group, and n = 48 for the placebo-teneligliptin group), the mean age and duration of diabetes were 60.7 and 13.6 years, respectively, and HbA1c was 7.8% at baseline. At 12 weeks, the teneligliptin group achieved a significant reduction in HbA1c from baseline (-0.9% ± 0.6%, P < .001), with an intergroup difference of -0.75% compared with the placebo group (95% CI [-0.99%, -0.51%], P < .001). At the end of the 24-week treatment period, both groups showed significant reductions in HbA1c level from baseline (placebo-teneligliptin group, -0.8% ± 0.6% [P < .001], teneligliptin group, -0.9% ± 0.6% [P < .001]), without significant intergroup difference (-0.17%, 95% CI [-0.41%, 0.07%], P = .156). There was no significant difference between the groups in the rate of adverse events (placebo-teneligliptin group, n = 3 [6.3%]; teneligliptin group, n = 11 [11.1%]; P = .550), and the safety profiles were favourable in both groups. CONCLUSIONS: The current study shows that teneligliptin could be a valid option as a fourth OAD for the treatment of patients with T2D inadequately controlled with a triple combination of OADs.
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Diabetes Mellitus Tipo 2 , Metformina , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Diabetes Mellitus Tipo 2/terapia , Método Doble Ciego , Quimioterapia Combinada , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/efectos adversos , Metformina/efectos adversos , Estudios Prospectivos , Pirazoles , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Tiazolidinas , Resultado del TratamientoRESUMEN
Diabetes mellitus is characterized by hyperglycemia. Low-grade bacterial infection with hyperglycemia in patients with diabetes is associated with atherosclerosis development. Therefore, this study hypothesized that macrophages lead to more severe diabetic complications under combined conditions of high glucose and lipopolysaccharide (LPS)-induced inflammation than under normoglycemic conditions. Zerumbone is the main component of Zingiber zerumbet Smith essential oil, a type of wild ginger. It possesses various biomedical activities, including antibacterial, antioxidant, anti-inflammatory, and anticancer activities; however, the precise mechanism of its anti-inflammatory and epigenetic effects is not fully understood. In this study, the effects of zerumbone on the secretion of proinflammatory cytokines and its underlying regulatory mechanism were investigated in THP-1-derived macrophages exposed to high glucose and LPS. THP-1-derived macrophages were cultured under normoglycemic (5.5 mmol/L glucose) or hyperglycemic (25 mmol/L glucose) conditions in the absence or presence of zerumbone (5-50 µM) for 48 hours and then treated with 100 ng/mL LPS for 6 hours. Zerumbone (25 and 50 µM) suppressed the production of tumor necrosis factor-α and interleukin-6 and the activation of cyclooxygenase-2, nuclear factor-κB, histone deacetylases 3 proteins, and Toll-like receptor messenger RNA (mRNA) and increased the transcription of the sirtuin 1 (SIRT1), SIRT3, and SIRT6 mRNAs. Taken together, our results suggest that zerumbone may exert beneficial effects on diabetes and its complications.
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FN-kappa B , Sirtuinas , Glucosa/farmacología , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Lipopolisacáridos/farmacología , Macrófagos , FN-kappa B/metabolismo , Sesquiterpenos , Transducción de Señal , Sirtuinas/metabolismo , Sirtuinas/farmacologíaRESUMEN
Cell-matrix interactions govern cell behavior and tissue function by facilitating transduction of biomechanical cues. Engineered tissues often incorporate these interactions by employing cell-adhesive materials. However, using constitutively active cell-adhesive materials impedes control over cell fate and elicits inflammatory responses upon implantation. Here, an alternative cell-material interaction strategy that provides mechanotransducive properties via discrete inducible on-cell crosslinking (DOCKING) of materials, including those that are inherently non-cell-adhesive, is introduced. Specifically, tyramine-functionalized materials are tethered to tyrosines that are naturally present in extracellular protein domains via enzyme-mediated oxidative crosslinking. Temporal control over the stiffness of on-cell tethered 3D microniches reveals that DOCKING uniquely enables lineage programming of stem cells by targeting adhesome-related mechanotransduction pathways acting independently of cell volume changes and spreading. In short, DOCKING represents a bioinspired and cytocompatible cell-tethering strategy that offers new routes to study and engineer cell-material interactions, thereby advancing applications ranging from drug delivery, to cell-based therapy, and cultured meat.
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Materiales Biocompatibles/química , Mecanotransducción Celular , Animales , Materiales Biocompatibles/metabolismo , Materiales Biocompatibles/farmacología , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Linaje de la Célula , Dextranos/química , Peroxidasa de Rábano Silvestre/metabolismo , Humanos , Hidrogeles/química , Integrinas/metabolismo , Mecanotransducción Celular/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos C57BL , Oligopéptidos/química , Oxidación-Reducción , Tiramina/químicaRESUMEN
Methyl-CpG-binding protein (MeCP2) is highly expressed in neurons. It plays an important role in the development of synapses and the formation of circuits in the central nervous system (CNS). Mutations in MECP2 cause neurodevelopmental disorders and mental retardation in humans. Therefore, it has become important to determine the distribution and function of MeCP2 in vivo. The retina consists of three nuclear cell layers and two layers of synapses; neurons in each layer are connected to form fine circuits necessary for visual signal transduction. Using immunohistochemical analysis, we found that MeCP2 was expressed in all nuclear cell layers, with differences in the levels of MeCP2 expression observed among the layers. To understand the structural defects in the retina due to the loss of MeCP2, we sought to elucidate the organization of the retinal structure in the Mecp2 knockout (KO) mouse. Overall, we found a normal retinal structure in Mecp2 KO mice. However, because Mecp2 mutations have a highly variable effect on neuronal architecture, we analyzed morphological changes in a subset of retinal ganglion cells of Mecp2 KO mice. In Thy1-GFP mice crossed with Mecp2 mutant mice, Sholl intersections analyses showed a subtle increase in number of intersections due to increased branching proximal to the soma in Mecp2 KO mice. Our results demonstrate that the expression of MeCP2 and the effects of Mecp2 mutations are highly specific to tissue and cell types.
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MeCP2 plays a multifaceted role in gene expression regulation and chromatin organization. Interaction between MeCP2 and methylated DNA in the regulation of gene expression is well established. However, the widespread distribution of MeCP2 suggests it has additional interactions with chromatin. Here we demonstrate, by both biochemical and genomic analyses, that MeCP2 directly interacts with nucleosomes and its genomic distribution correlates with that of H3K27me3. In particular, the methyl-CpG-binding domain of MeCP2 shows preferential interactions with H3K27me3. We further observe that the impact of MeCP2 on transcriptional changes correlates with histone post-translational modification patterns. Our findings indicate that MeCP2 interacts with genomic loci via binding to DNA as well as histones, and that interaction between MeCP2 and histone proteins plays a key role in gene expression regulation.
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Regulación de la Expresión Génica/fisiología , Histonas/metabolismo , Proteína 2 de Unión a Metil-CpG/metabolismo , Transcripción Genética/fisiología , Animales , Secuenciación de Inmunoprecipitación de Cromatina , ADN/genética , ADN/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/genética , ADN (Citosina-5-)-Metiltransferasas/genética , Metilación de ADN/fisiología , Técnicas de Inactivación de Genes , Sitios Genéticos , Células HCT116 , Células HEK293 , Histonas/genética , Humanos , Proteína 2 de Unión a Metil-CpG/genética , Ratones , Ratones Noqueados , Nucleosomas/genética , Nucleosomas/metabolismo , Procesamiento Proteico-Postraduccional/fisiología , Sitio de Iniciación de la Transcripción/fisiología , ADN Metiltransferasa 3BRESUMEN
Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10-94; GT: OR = 15.87, p = 2.62 × 10-9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10-108; GT: OR = 12.63, p = 3.44 × 10-64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.
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Mammalian cells release extracellular vesicles (EVs) into their microenvironment that travel the entire body along the stream of bodily fluids. EVs contain a wide range of biomolecules. The transported cargo varies depending on the EV origin. Knowledge of the origin and chemical composition of EVs can potentially be used as a biomarker to detect, stage, and monitor diseases. In this paper, we demonstrate the potential of EVs as a prostate cancer biomarker. A Raman optical tweezer was employed to obtain Raman signatures from four types of EV samples, which were red blood cell- and platelet-derived EVs of healthy donors and the prostate cancer cell lines- (PC3 and LNCaP) derived EVs. EVs' Raman spectra could be clearly separated/classified into distinct groups using principal component analysis (PCA) which permits the discrimination of the investigated EV subtypes. These findings may provide new methodology to detect and monitor early stage cancer.
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Vesículas Extracelulares/metabolismo , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Espectrometría Raman/métodos , Plaquetas/patología , Eritrocitos/patología , Humanos , MasculinoRESUMEN
BACKGROUND/OBJECTIVE: Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. MATERIALS/METHODS: Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. RESULTS: Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. CONCLUSIONS: The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes.
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Delphinidin possesses strong anti-oxidant, anti-inflammatory, and anti-cancer properties. Suppression of the Wnt/ß-catenin signaling pathway is a potential strategy for chemoprevention and therapy. As aberrant activation of the ß-catenin signaling pathway contributes to prostate cancer progression, we evaluated the effect of delphinidin on this pathway in human PC3 prostate cancer cells. An MTT assay showed that treatment with delphinidin (15-180 µM, 72 hours) resulted in a dose-dependent growth inhibition of cells. Treatment with delphinidin increased the phosphorylation of serine or threonine residues on ß-catenin and decreased the levels of cytoplasmic ß-catenin. Moreover, treatment with delphinidin inhibited the nuclear translocation of ß-catenin and the expression of ß-catenin target genes such as cyclin D1, c-myc, Axin-2, and T cell factor-1. Delphinidin also induced the phosphorylation of glycogen synthase kinase 3ß and the expression of adenomatous polyposis coli and Axin proteins. Our results indicate that inhibition of cell growth by delphinidin is mediated, at least in part, through modulation of the ß-catenin signaling pathway. We suggest that delphinidin is a potent inhibitor of Wnt/ß-catenin signaling in prostate cancer cells.
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Methyl-CpG binding protein 2 (MeCP2) is critical for proper brain development and expressed at near-histone levels in neurons, but the mechanism of its genomic localization remains poorly understood. Using high-resolution MeCP2-binding data, we show that DNA sequence features alone can predict binding with 88% accuracy. Integrating MeCP2 binding and DNA methylation in a probabilistic graphical model, we demonstrate that previously reported genome-wide association with methylation is in part due to MeCP2's affinity to GC-rich chromatin, a result replicated using published data. Furthermore, MeCP2 co-localizes with nucleosomes. Finally, MeCP2 binding downstream of promoters correlates with increased expression in Mecp2-deficient neurons.
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Cromatina/metabolismo , Metilación de ADN/genética , Regulación del Desarrollo de la Expresión Génica/genética , Proteína 2 de Unión a Metil-CpG/genética , Mucosa Olfatoria/metabolismo , Animales , Secuencia de Bases , Sitios de Unión , Inmunoprecipitación de Cromatina , Secuencia Rica en GC , Proteína 2 de Unión a Metil-CpG/metabolismo , Ratones , Neuronas , Nucleosomas/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Análisis de Secuencia de ADN , Análisis de Secuencia de ARNRESUMEN
Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA-target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6). Here, by substituting nucleotide in pivot with abasic spacers, which prevent base pairing and alleviate steric hindrance, we eliminate miRNA-like off-target repression while preserving on-target activity at â¼ 80-100%. Specifically, miR-124 containing dSpacer pivot substitution (6pi) loses seed-mediated transcriptome-wide target interactions, repression activity and biological function, whereas other conventional modifications are ineffective. Application of 6pi allows PCSK9 siRNA to efficiently lower plasma cholesterol concentration in vivo, and abolish potentially deleterious off-target phenotypes. The smallest spacer, C3, also shows the same improvement in target specificity. Abasic pivot substitution serves as a general means to harness the specificity of siRNA experiments and therapeutic applications.
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Emparejamiento Base , Marcación de Gen/métodos , MicroARNs/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , Animales , Proteínas Argonautas/metabolismo , Northern Blotting , Línea Celular , Línea Celular Tumoral , Células HeLa , Células Hep G2 , Humanos , Immunoblotting , Ratones , Proproteína Convertasa 9 , Proproteína Convertasas/genética , Tratamiento con ARN de Interferencia/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serina Endopeptidasas/genéticaRESUMEN
Hyperglycemia contributes to diabetes and several diabetes-related complications. Gallic acid is a polyhydroxy phenolic compound found in various natural products. In this study, we investigated the effects and mechanism of gallic acid on proinflammatory cytokine secretion in high glucose-induced human monocytes (THP-1 cells). THP-1 cells were cultured under normoglycemic or hyperglycemic conditions, in the absence or presence of gallic acid. Hyperglycemic conditions significantly induced histone acetylation, nuclear factor-κB (NF-κB) activation, and proinflammatory cytokine release from THP-1 cells, whereas gallic acid suppressed NF-κB activity and cytokine release. It also significantly reduced CREB-binding protein/p300 (CBP/p300, a NF-κB coactivator) gene expression, acetylation levels, and CBP/p300 histone acetyltransferase (HAT) activity. In addition, histone deacetylase 2 (HDAC2) expression was significantly induced. These results suggest that gallic acid inhibits hyperglycemic-induced cytokine production in monocytes through epigenetic changes involving NF-κB. Therefore, gallic acid may have potential for the treatment and prevention of diabetes and its complications.
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Citocinas/metabolismo , Ácido Gálico/farmacología , Glucosa/farmacología , Histona Acetiltransferasas/metabolismo , Histona Desacetilasas/metabolismo , Monocitos/efectos de los fármacos , Acetilación , Proteína de Unión a CREB/genética , Proteína de Unión a CREB/metabolismo , Línea Celular , Epigénesis Genética , Expresión Génica/efectos de los fármacos , Humanos , Hiperglucemia , Inflamación , Monocitos/fisiología , FN-kappa B/antagonistas & inhibidores , Factores de Transcripción p300-CBP/genética , Factores de Transcripción p300-CBP/metabolismoRESUMEN
During postnatal development, neuronal activity controls the remodeling of initially imprecise neuronal connections through the regulation of gene expression. MeCP2 binds to methylated DNA and modulates gene expression during neuronal development and MECP2 mutation causes the autistic disorder Rett syndrome. To investigate a role for MeCP2 in neuronal circuit refinement and to identify activity-dependent MeCP2 transcription regulations, we leveraged the precise organization and accessibility of olfactory sensory axons to manipulation of neuronal activity through odorant exposure in vivo. We demonstrate that olfactory sensory axons failed to develop complete convergence when Mecp2 is deficient in olfactory sensory neurons (OSNs) in an otherwise wild-type animal. Furthermore, we demonstrate that expression of selected adhesion genes was elevated in Mecp2-deficient glomeruli, while acute odor stimulation in control mice resulted in significantly reduced MeCP2 binding to these gene loci, correlating with increased expression. Thus, MeCP2 is required for both circuitry refinement and activity-dependent transcriptional responses in OSNs.
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Proteína 2 de Unión a Metil-CpG/metabolismo , Bulbo Olfatorio/metabolismo , Células Receptoras Sensoriales/metabolismo , Animales , Axones/metabolismo , Axones/ultraestructura , Cadherinas/metabolismo , Proteína 2 de Unión a Metil-CpG/genética , Ratones , Ratones Transgénicos , Proteínas del Tejido Nervioso/metabolismo , Odorantes , Bulbo Olfatorio/citología , Protocadherinas , Células Receptoras Sensoriales/ultraestructura , Transcripción GenéticaRESUMEN
Hyperglycemia is a key feature in diabetes. Hyperglycemia has been implicated as a major contributor to several complications of diabetes. High glucose levels induce the release of proinflammatory cytokines. Luteolin is a flavone isolated from celery, green pepper, perilla leaf, and chamomile tea. Luteolin has been reported to possess antimutagenic, antitumorigenic, antioxidant, and anti-inflammatory properties. In this study, we investigated the effects of luteolin on proinflammatory cytokine secretion and its underlying epigenetic regulation in high-glucose-induced human monocytes. Human monocytic (THP-1) cells were cultured under controlled (14.5 mM mannitol), normoglycemic (NG, 5.5 mM glucose), or hyperglycemic (HG, 20 mM glucose) conditions, in the absence or presence of luteolin. Luteolin (3-10 µM) was added for 48 h. While hyperglycemic conditions significantly induced histone acetylation, NF-κB activation, and proinflammatory cytokine (IL-6 and TNF-α) release from THP-1 cells, luteolin suppressed NF-κB activity and cytokine release. Luteolin also significantly reduced CREB-binding protein/p300 (CBP/p300) gene expression, as well as the levels of acetylation and histone acetyltransferase (HAT) activity of the CBP/p300 protein, which is a known NF-κB coactivator. These results suggest that luteolin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF-κB. We therefore suggest that luteolin may be a potential candidate for the treatment and prevention of diabetes and its complications.
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Epigénesis Genética/efectos de los fármacos , Glucosa/química , Luteolina/farmacología , Monocitos/efectos de los fármacos , Acetilación , Línea Celular , Medios de Cultivo/química , Proteína p300 Asociada a E1A/metabolismo , Histona Acetiltransferasas/metabolismo , Histonas/metabolismo , Humanos , Hiperglucemia/metabolismo , Hipoglucemiantes/farmacología , Interleucina-6/metabolismo , FN-kappa B/metabolismo , Regiones Promotoras Genéticas , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Kidney function is critical in homocysteine clearance, and plasma homocysteine level is frequently increased in patients with renal failure. On the other hand, recent studies in animals have shown that hyperhomocysteinemia induces renal injury. In this study, we determined whether hyperhomocysteinemia can be a risk factor for the development of microalbuminuria in patients with type 2 diabetes. METHODS: A nested case-control study. Of 887 patients with type 2 diabetes who did not have microalbuminuria at baseline, 76 developed microalbuminuria during follow-up (mean, 36.0 +/- 11.7 months; range, 18 to 76 months). The control group consisted of 152 age- and sex-matched subjects who did not develop microalbuminuria. Baseline plasma homocysteine concentrations were measured in stored samples. RESULTS: Baseline plasma homocysteine concentrations and mean HbA1C levels during follow-up were significantly higher in patients who developed microalbuminuria than in those who remained normoalbuminuric. Multivariate logistic regression analysis showed that baseline plasma homocysteine level and mean HbA1C were independent predictors of microalbuminuria in type 2 diabetes. CONCLUSION: Hyperhomocysteinemia was associated with increased risk of microalbuminuria in patients with type 2 diabetes supporting the concept that hyperhomocysteinemia has an etiologic role in the pathogenesis of diabetic nephropathy.