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BACKGROUND: Evaluating the activities of daily living (ADL) is an important factor for diagnosing dementia. The Everyday Cognition (ECog) scale was developed to measure ADL changes that were correlated with specific neuropsychological impairments. A short form of the ECog (ECog-12) was also developed, consisting of 12 items, two from each of the six cognitive domains of the ECog. The Korean full version of ECog (K-ECog) has recently been standardized, but the need for a shortened version has been raised in clinical practice. The purpose of this study was to develop a Korean version of ECog-12 (K-ECog-12) and to verify its reliability and validity by comparing those to the full version of K-ECog. METHODS: The participants were 267 cognitively normal older adults (CN), 183 patients with mild cognitive impairment (MCI), and 89 patients with dementia. The Korean-Mini Mental State Examination (K-MMSE), Korean-Montreal Cognitive Assessment (K-MoCA), and Short form of Geriatric Depression Scale (SGDS) were administered to all participants. The K-ECog and Korean-Instrumental Activities of Daily Living (K-IADL) were rated by the informants of patients. RESULTS: K-ECog-12 was newly constructed by replacing one item for the visuospatial function in the original ECog-12 with another one through an item response theory analysis on Korean data. The internal consistencies (Cronbach's α) of K-ECog-12 and K-ECog were 0.95 and 0.99, respectively. The test-retest reliabilities (Pearson's r) were 0.67 for K-ECog-12 and 0.73 for K-ECog. The K-ECog-12 was significantly correlated with K-ECog as well as K-IADL, K-MMSE, and K-MoCA. The K-ECog-12 scores differed significantly between the CN, MCI, and dementia groups, as did the K-ECog scores. Receiver operating characteristic curve analyses showed that K-ECog-12, like K-ECog, could differentiate MCI and dementia patients from CN as well. CONCLUSION: The K-ECog-12 is as reliable and valid as the K-ECog in assessing ADL. Therefore, K-ECog-12 can be used as an alternative to the K-ECog in clinical and community settings in Korea.
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Disfunción Cognitiva , Demencia , Humanos , Anciano , Demencia/diagnóstico , Actividades Cotidianas/psicología , Reproducibilidad de los Resultados , Pruebas Neuropsicológicas , Disfunción Cognitiva/diagnóstico , Cognición , República de CoreaRESUMEN
DNA-reactive compounds are harnessed for cancer chemotherapy. Their genotoxic effects are considered to be the main mechanism for the cytotoxicity to date. Because this mechanism preferentially affects actively proliferating cells, it is postulated that the cytotoxicity is specific to cancer cells. Nonetheless, they do harm normal quiescent cells, suggesting that there are other cytotoxic mechanisms to be uncovered. By employing doxorubicin as a representative DNA-reactive compound, we have discovered a cytotoxic mechanism that involves a cellular noncoding RNA (ncRNA) nc886 and protein kinase R (PKR) that is a proapoptotic protein. nc886 is transcribed by RNA polymerase III (Pol III), binds to PKR, and prevents it from aberrant activation in most normal cells. We have shown here that doxorubicin evicts Pol III from DNA and, thereby, shuts down nc886 transcription. Consequently, the instantaneous depletion of nc886 provokes PKR and leads to apoptosis. In a short-pulse treatment of doxorubicin, these events are the main cause of cytotoxicity preceding the DNA damage response in a 3D culture system as well as the monolayer cultures. By identifying nc886 as a molecular signal for PKR to sense doxorubicin, we have provided an explanation for the conundrum why DNA-damaging drugs can be cytotoxic to quiescent cells that have the competent nc886/PKR pathway.
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Apoptosis/efectos de los fármacos , ADN/metabolismo , MicroARNs/metabolismo , ARN no Traducido , Línea Celular , Doxorrubicina/farmacología , Humanos , MicroARNs/genética , ARN Polimerasa III/metabolismo , ARN no Traducido/genética , ARN no Traducido/metabolismo , Transducción de Señal/efectos de los fármacos , eIF-2 Quinasa/metabolismoRESUMEN
BACKGROUND: In the early diagnosis of dementia, an important factor is the evaluation of activities of daily living. The Everyday Cognition (ECog) scale was developed to measure functional changes that are the everyday correlates of specific neuropsychological impairments. This study aimed to examine the validity of the Korean version of Everyday Cognition (K-ECog). METHODS: The participants were 268 cognitively normal older adults (NA), 151 amnestic mild cognitive impairment (aMCI), and 77 dementia of the Alzheimer's type (DAT). The Korean-Mini Mental State Examination (K-MMSE), Korean-Montreal Cognitive Assessment (K-MoCA), and Short form of the Geriatric Depression Scale (SGDS) were administered to all the participants. The K-ECog and Korean-Instrumental Activities of Daily Living (K-IADL) were rated by their informants. RESULTS: Internal consistency (Cronbach's α) of K-ECog global function was 0.93, and its test-retest reliability (Pearson's r) was 0.73. K-ECog was significantly correlated with K-IADL (0.66), K-MMSE (-0.38), and K-MoCA (-0.26). Confirmatory factor analysis of K-ECog yielded seven factor model that the original ECog proposed. K-ECog global score and six domain scores were significantly different across the NA, aMCI, and DAT groups. Receiver operating characteristic curve analyses showed that K-ECog effectively differentiated aMCI and DAT patients from NA, suggesting that K-ECog is as sensitive for detecting functional impairments as K-IADL. The proposed optimal cut-off score to differentiate aMCI from NA was 1.41. CONCLUSION: K-ECog is proven reliable and valid for clinical use. K-ECog can be used to distinguish very early stages of impaired ADL and cognitive impairment in the community.
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Disfunción Cognitiva/diagnóstico , Demencia/diagnóstico , Pruebas Neuropsicológicas , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Reproducibilidad de los Resultados , República de CoreaRESUMEN
IL-21, a pleiotropic cytokine strongly linked with autoimmunity and inflammation, regulates diverse immune responses. IL-21 can be potently induced in CD4(+) T cells by IL-6; however, very little is known about the mechanisms underlying the transcriptional regulation of the Il21 gene at the chromatin level. In this study, we demonstrated that a conserved noncoding sequence located 49 kb upstream of the Il21 gene contains an enhancer element that can upregulate Il21 gene expression in a STAT3- and NFAT-dependent manner. Additionally, we identified enhancer-blocking insulator elements in the Il21 locus, which constitutively bind CTCF and cohesin. In naive CD4(+) T cells, these upstream and downstream CTCF binding sites interact with each other to make a DNA loop; however, the Il21 promoter does not interact with any cis-elements in the Il21 locus. In contrast, stimulation of CD4(+) T cells with IL-6 leads to recruitment of STAT3 to the promoter and novel distal enhancer region. This induces dynamic changes in chromatin configuration, bringing the promoter and the regulatory elements in close spatial proximity. The long-range interaction between the promoter and distal enhancer region was dependent on IL-6/STAT3 signaling pathway but was disrupted in regulatory T cells, where IL-21 expression was repressed. Thus, our work uncovers a novel topological chromatin framework underlying proper transcriptional regulation of the Il21 gene.
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Linfocitos T CD4-Positivos/metabolismo , Cromatina/genética , Proteínas de Unión al ADN/genética , Interleucinas/genética , Animales , Secuencia de Bases , Factor de Unión a CCCTC , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Secuencia Conservada , Elementos de Facilitación Genéticos , Regulación de la Expresión Génica , Humanos , Interleucina-6/farmacología , Ratones , Ratones Endogámicos C57BL , Factores de Transcripción NFATC/metabolismo , Regiones Promotoras Genéticas , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , CohesinasRESUMEN
Type 2 diabetes mellitus (T2DM) is a chronic disease manifested by hyperglycemia. It is essential to effectively control hyperglycemia to prevent complications of T2DM. Here, we hypothesize that repression of transcriptional activity of forkhead box O1 (FoxO1) via histone deacetylase inhibitors (HDACi) ameliorates hyperglycemia in T2DM rats. METHODS: Male Long-Evans Tokushima Otsuka (LETO) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats aged 14 weeks were administered sodium valproate (VPA, 0.71% w/v) dissolved in water for 20 weeks. Electrophoretic mobility shift assay (EMSA) and luciferase assay were performed for elucidation of transcriptional regulation through acetylation of FoxO1 by HDACi. RESULTS: VPA attenuated blood glucose levels in accordance with a decrease in the expression of gluconeogenic genes in hyperglycemic OLETF rats. It has been shown that HDAC class I-specific and HDAC class IIa-specific inhibitors, as well as pan-HDAC inhibitors decrease FoxO1 enrichment at the cis-element of target gene promoters. Mutations in FoxO1 prevent its acetylation, thereby increasing its transcriptional activity. HDAC3 and HDAC4 interact with FoxO1, and knockdown of HDAC3, HDAC4, or their combination increases FoxO1 acetylation, thereby decreasing the expression of gluconeogenic genes. CONCLUSIONS: These results indicate that HDACi attenuates the transcriptional activity of FoxO1 by impeding deacetylation, thereby ameliorating hyperglycemia in T2DM rats.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Proteína Forkhead Box O1/genética , Inhibidores de Histona Desacetilasas/uso terapéutico , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/genética , Transcripción Genética , Acetilación , Animales , Diabetes Mellitus Experimental/genética , Proteína Forkhead Box O1/metabolismo , Gluconeogénesis/efectos de los fármacos , Gluconeogénesis/genética , Glucosa/toxicidad , Glucosa-6-Fosfato/metabolismo , Células Hep G2 , Histona Desacetilasas/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Fosfoenolpiruvato Carboxiquinasa (GTP)/genética , Fosfoenolpiruvato Carboxiquinasa (GTP)/metabolismo , Ratas Endogámicas OLETF , Proteínas Represoras , Transcripción Genética/efectos de los fármacos , Ácido Valproico/administración & dosificación , Ácido Valproico/farmacología , Ácido Valproico/uso terapéuticoAsunto(s)
Proteínas de Unión al GTP/genética , Polimorfismo de Nucleótido Simple , Sus scrofa/genética , Sus scrofa/inmunología , Adiposidad , Animales , Peso Corporal , Haplotipos , Desequilibrio de Ligamiento , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Sus scrofa/fisiologíaRESUMEN
BACKGROUND: Langerhans cells (LCs) are skin-resident dendritic cells (DCs) that orchestrate skin immunity. CCCTC-binding factor (CTCF) is a highly conserved DNA-binding protein that regulates higher-order chromatin organization and is involved in various gene regulation processes. OBJECTIVE: We sought to clarify a possible role for CTCF in LC homeostasis and function in vivo. METHODS: We used a conditional gene deletion mouse system to generate DC- and LC-specific CTCF-ablated mice. Short hairpin RNA-mediated RNA interference was used to silence CTCF expression in human monocyte-derived Langerhans cells. DC populations were assessed by using flow cytometry and immunofluorescence. Gene expression arrays were performed to identify genes regulated by CTCF in LCs. Contact hypersensitivity and epicutaneous sensitization responses were measured to examine the functional significance of CTCF ablation. RESULTS: DC-specific CTCF deletion led to a reduced pool of systemic DCs, with LCs most severely affected. Decreases in epidermal LC numbers were specifically associated with self-turnover defects. Interestingly, CTCF-deficient LCs demonstrated impaired migration out of the epidermis. Whole-transcriptome analyses revealed that genes that promoted cell adhesion were highly expressed, but CCR7 was downregulated in CTCF-depleted LCs. Hapten-induced contact hypersensitivity responses were more sustained in LC-specific CTCF-deficient mice, whereas epicutaneous sensitization to protein antigen was attenuated, indicating that CTCF-dependent LC homeostasis is required for optimal immune function of LCs in a context-dependent manner. CONCLUSION: Our results show that CTCF positively regulates the homeostatic pool and the efficient emigration of LCs, which are required for modulating the functional immune network of the skin.
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Dermatitis por Contacto/genética , Homeostasis/genética , Células de Langerhans/metabolismo , Proteínas Represoras/genética , Animales , Factor de Unión a CCCTC , Adhesión Celular , Movimiento Celular/genética , Movimiento Celular/inmunología , Dermatitis por Contacto/inmunología , Dermatitis por Contacto/patología , Epidermis/inmunología , Epidermis/metabolismo , Epidermis/patología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Haptenos , Homeostasis/inmunología , Humanos , Células de Langerhans/inmunología , Células de Langerhans/patología , Ratones , Ratones Noqueados , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/inmunología , Receptores CCR7/genética , Receptores CCR7/inmunología , Proteínas Represoras/antagonistas & inhibidores , Proteínas Represoras/deficiencia , Proteínas Represoras/inmunología , Transducción de SeñalRESUMEN
CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.
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Inhibition of histone deacetylases (HDACs) by valproic acid (VPA) attenuates inflammatory, hypertrophic, and fibrotic responses in the hearts of spontaneously hypertensive rats (SHRs); however, the molecular mechanism is still unclear. We hypothesized that HDAC inhibition (HDACi) attenuates cardiac hypertrophy and fibrosis through acetylation of mineralocorticoid receptor (MR) in SHRs. Seven-week-old SHRs and Wistar-Kyoto rats were treated with an HDAC class I inhibitor (0.71% w/v in drinking water; VPA) for 11 weeks. Sections of heart were visualized after trichrome stain as well as H&E stain. Histone modifications, such as acetylation (H3Ac [acetylated histone 3]) and fourth lysine trimethylation (H3K4me3) of histone 3, and recruitment of MR and RNA polymerase II (Pol II) into promoters of target genes were measured by quantitative real-time polymerase chain reaction after chromatin immunoprecipitation assay. MR acetylation was determined by Western blot with anti-acetyl-lysine antibody after immunoprecipitation with anti-MR antibody. Treatment with VPA attenuated cardiac hypertrophy and fibrosis. Although treatment with VPA increased H3Ac and H3K4me3 on promoter regions of MR target genes, expression of MR target genes as well as recruitment of MR and Pol II on promoters of target genes were decreased. Although HDACi did not affect MR expression, it increased MR acetylation. These results indicate that HDACi attenuates cardiac hypertrophy and fibrosis through acetylation of MR in spontaneously hypertensive rats.
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Acetilación/efectos de los fármacos , Cardiomegalia/tratamiento farmacológico , Fibrosis/tratamiento farmacológico , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Receptores de Mineralocorticoides/metabolismo , Animales , Cardiomegalia/genética , Cardiomegalia/metabolismo , Inmunoprecipitación de Cromatina/métodos , Fibrosis/genética , Fibrosis/metabolismo , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Histona Desacetilasas/genética , Histonas/genética , Histonas/metabolismo , Masculino , Regiones Promotoras Genéticas/efectos de los fármacos , Regiones Promotoras Genéticas/genética , ARN Polimerasa II/genética , ARN Polimerasa II/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptores de Mineralocorticoides/genéticaRESUMEN
Acetylation of the mineralocorticoid receptor (MR) by inhibition of lysine deacetylases attenuates MR's transcriptional activity. However, the specific lysine acetyltransferases that are responsible for acetylation of the MR remain unknown. We hypothesized that the acetyltransferases cyclic adenosine monophosphate response element-binding binding protein (CBP) and acetyltransferase p300 (p300) attenuate transcriptional activity of the MR through its acetylation. Expression of MR target genes was measured by quantitative real-time polymerase chain reaction. Recruitment of MR and RNA polymerase II (Pol II) on promoters of target genes was analysed by chromatin immunoprecipitation. Acetylation of the MR was determined by western blot with an anti-acetyl-lysine antibody after immunoprecipitation with an anti-MR antibody. In human embryonic kidney (HEK) 293 cells, overexpression of CBP or p300, but not p300/CBP-associated factor, increased MR acetylation and decreased expression of MR target genes. The downregulation of target genes coincided with a decrease in the recruitment of MR and Pol II to specific hormone response elements. These results demonstrate that overexpression of CBP or p300 attenuates the transcriptional activity of the MR through its acetylation in HEK 293 cells. Our data provide strong evidence identifying CBP and p300 as lysine acetyltransferases responsible for the regulation of MR that may provide new therapeutic targets for the treatment of hypertension.
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Acetiltransferasas/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Receptores de Mineralocorticoides/genética , Receptores de Mineralocorticoides/metabolismo , Transcripción Genética , Factores de Transcripción p300-CBP/metabolismo , Acetilación/efectos de los fármacos , Aldosterona/farmacología , Secuencia de Bases , Células HEK293 , Humanos , Regiones Promotoras Genéticas/efectos de los fármacos , Regiones Promotoras Genéticas/genética , ARN Polimerasa II/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transcripción Genética/efectos de los fármacosRESUMEN
Rice wine, in which γ-aminobutyric acid is present, is beneficial to human health and is one of the three most well-known fermented wines in the world, and is very popular in China. The rapid detection of γ-aminobutyric acid was studied in rice wine using near infrared spectroscopy with an optical fibre probe. Through the selection of detection conditions, including a waveband range of 12500-4000 cm(-1), a scanning duration of 16 scans and a resolution of 8 cm(-1), the near infrared spectrum of rice wine was acquired three times, for every wine sample, with an optical fibre probe. The resulting average value of the spectrum was obtained and the corresponding data were analysed via normalization. By adopting a multivariate calibration partial least squares method (PLS) and establishing a calibration model, the highest precision for γ-aminobutyric acid in rice wine was predicted when the factor coefficient was 17. The overall results demonstrating the content of γ-aminobutyric acid in rice wine was predicted to be between 157.6696-317.5813 mg/L, with a relative standard deviation of prediction between 0.01-5 %, as well as the fact that the single sample measuring time was less than 20 s, prove that near infrared spectroscopy is a rapid, accurate and effective method to adopt for detecting the content of γ-aminobutyric acid in rice wine.
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In this study we investigated the effects of luteolin supplementation (0.05% w/w) on mammary tumor growth in C3H mice, a strain of mouse mammary tumor virus negative, fed either high-fat (45% fat of energy) or low-fat diet (15% fat of energy). Animals (n = 12/group) were allocated into 4 experimental groups (low-fat diet, low-fat diet + luteolin supplementation, high-fat diet, high-fat diet + luteolin supplementation). Experimental diet were fed for 13 wk and 7,12-dimethylbenz[a]anthracene was administered once a week for 6 wk starting at Week 1 to induce mammary tumors. Study results showed that animals on low-fat diet supplemented with luteolin exhibited longer tumor latency and lower tumor weights and sizes compared to the other groups. Animals fed high-fat diet showed increased serum IGF-1 levels and the elevated mammary tissue expression of Ki-67, IRS-1, pp38, Cdk4, and Cdk6. Luteolin inhibited IRS-1, Cdk4, and Cdk6 expression in high-fat fed animals. The expression of pp38, cyclinD1, and Bcl-xL was suppressed by luteolin supplementation both in the low-fat and high-fat diet groups. These results suggest that excess energy supply increases the risk of mammary tumor formation and luteolin suppresses tumor formation regardless of dietary fat content through its cell cycle regulatory and proapoptotic activity.
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Luteolina/farmacología , Neoplasias Mamarias Experimentales/dietoterapia , Animales , Apoptosis/efectos de los fármacos , Dieta Alta en Grasa , Suplementos Dietéticos , Ingestión de Energía/efectos de los fármacos , Femenino , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/metabolismo , Neoplasias Mamarias Experimentales/metabolismo , Ratones Endogámicos C3H , Transducción de Señal/efectos de los fármacos , Aumento de Peso/efectos de los fármacosRESUMEN
In response to escalating environmental concerns and the urgent need for sustainable drug delivery systems, this study introduces biodegradable pH-responsive microcapsules synthesized from a blend of gelatin, alginate, and hyaluronic acid. Employing the coacervation process, capsules were created with a spherical shape, multicore structure, and small sizes ranging from 10 to 20 µm, which exhibit outstanding vitamin E encapsulation efficiency. With substantial incorporation of hyaluronic acid, a pH-responsive component, the resulting microcapsules displayed noteworthy swelling behavior, facilitating proficient core ingredient release at pH 5.5 and 7.4. Notably, these capsules can effectively deliver active substances to the dermal layer under specific skin conditions, revealing promising applications in topical medications and cosmetics. Furthermore, the readily biodegradable nature of the designed capsules was demonstrated through Biochemical Oxygen Demand (BOD) testing, with over 80 % of microcapsules being degraded by microorganisms after one week of incubation. This research contributes to the development of responsive microcapsules and aligns with broader environmental initiatives, offering a promising pathway to mitigate the impact of microplastics while advancing various applications.
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Alginatos , Cápsulas , Preparaciones de Acción Retardada , Liberación de Fármacos , Gelatina , Ácido Hialurónico , Ácido Hialurónico/química , Alginatos/química , Gelatina/química , Concentración de Iones de Hidrógeno , Preparaciones de Acción Retardada/química , Portadores de Fármacos/química , Vitamina E/químicaRESUMEN
Keratoconus is a complex and multifactorial disease and its exact aetiology remains unknown. This current study examined the important environmental risk factors and their association with keratoconus. This study was registered in the PROSPERO International Prospective Register of systematic reviews under registration number CRD42021256792 in 2021. Scopus, Web of Science, PubMed, and Cochrane CENTRAL databases were searched for all relevant articles published from 1 January 1900 to 31 July 2021. National Institutes of Health Quality Assessment Tool was used to assess the methodological quality of the studies. The assessment for statistical heterogeneity was assessed using the Z-statistics on RevMan v5.4. P-value of <0.05 was considered as statistically significant and I2 < 25% as homogenous. Thirty studies were included in this meta-analysis. Pooled odds ratio was calculated with 95% CI. The pooled odds ratio (OR) of eye rubbing, atopy, asthma, and eczema was 3.64 (95% CI, 2.02, 6.57), 1.90 (95% CI, 1.22, 2.94), 1.36 (95% CI, 1.15, 1.61) and 1.90 (95% CI, 1.22, 2.94), respectively. The OR for diabetes was 0.86 (95% CI 0.73, 1.02), and use of sunglasses, contact lens, allergic conjunctivitis, side sleep position and prone sleep position was 0.40 (95% CI, 0.16, 0.99), 1.68 (0.70, 4.00), 2.24 (95% CI, 0.68, 7.36), 3.81 (95% CI, 0.31, 46.23), 12.76 (95% CI, 0.27, 598.58), respectively. Twenty studies were considered to be of high quality, nine to be moderate and one to be low. Environmental risk factors have been identified to play a role in the susceptibility of keratoconus. However, further large-scale longitudinal studies are needed to understand the mechanisms between environmental risk factors and keratoconus.
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Conjuntivitis Alérgica , Queratocono , Humanos , Queratocono/diagnóstico , Queratocono/epidemiología , Queratocono/etiología , Revisiones Sistemáticas como Asunto , Factores de Riesgo , Oportunidad RelativaRESUMEN
BACKGROUND: Articulation disorder decreases the clarity of language and causes a decrease in children's learning and social ability. The demand for non-face-to-face treatment is increasing owing to the limited number of therapists and geographical or economic constraints. Non-face-to-face speech therapy programs using serious games have been proposed as an alternative. OBJECTIVE: The aim of this study is to investigate the efficacy of home therapy on logopedic and phoniatric abilities in children with articulation disorder using the Smart Speech game interface. METHODS: This study is a prospective single-arm clinical trial. Children with articulation disorders, whose Urimal Test of Articulation and Phonology (U-TAP) was -2 SDs or less and the Receptive and Expressive Vocabulary Test score was -1 SD or more, were enrolled. A preliminary evaluation (E0) was conducted to check whether the children had articulation disorders, and for the next 4 weeks, they lived their usual lifestyle without other treatments. Prior to the beginning of the training, a pre-evaluation (E1) was performed, and the children trained at home for ≥30 minutes per day, ≥5 times a week, over 4 weeks (a total of 20 sessions). The Smart Speech program comprised oral exercise training, breathing training, and speech training; the difficulty and type of the training were configured differently according to the participants' articulation error, exercise, and vocal ability. After the training, postevaluation (E2) was performed using the same method. Finally, 8 weeks later, postevaluation (E3) was performed as a follow-up. A voice evaluation included parameters such as maximum phonation time (MPT), fundamental frequency (F0), jitter, peak air pressure (relative average perturbation), pitch, intensity, and voice onset time. Articulation parameters included a percentage of correct consonants (PCC; U-TAP word-unit PCC, U-TAP sentence-unit PCC, and three-position articulation test) and alternate motion evaluation (diadochokinesis, DDK). Data obtained during each evaluation (E1-E2-E3) were compared. RESULTS: A total of 13 children with articulation disorders aged 4-10 years were enrolled in the study. In voice parameters, MPT, jitter, and pitch showed significant changes in repeated-measures ANOVA. However, only MPT showed significant changes during E1-E2 (P=.007) and E1-E3 (P=.004) in post hoc tests. Other voice parameters did not show significant changes. In articulation parameters, U-TAP, three-position articulation test (TA), and DDK showed significant changes in repeated-measures ANOVA. In post hoc tests, U-TAP (word, sentence) and TA showed significant changes during E1-E2 (P=.003, .04, and .01) and E1-E3 (P=.001, .03, and .003), and DDK showed significant changes during E1-E2 only (P=.03). CONCLUSIONS: Home-based serious games can be considered an alternative treatment method to improve language function. TRIAL REGISTRATION: Clinical Research Information Service KCT0006448; https://cris.nih.go.kr/cris/search/detailSearch.do/20119.
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BACKGROUND/AIM: The abnormal growth of vascular smooth muscle cells (VSMCs) induced by reactive oxygen species (ROS) is considered a major pathogenic process in vascular diseases. Interleukin (IL)-24 specifically inhibits cancer cell growth through the induction of cell cycle arrest and apoptosis. However, the role of IL-24 in ROS-induced VSMC growth has not yet been investigated. METHODS: An MTT assay, gene expression analysis, flow cytometry and a scratch wound healing assay were performed to determine the anti-growth effects of IL-24 in H(2)O(2)-treated mouse vascular aortic smooth muscle (MOVAS) cells. To elucidate the effect of IL-24 on ROS-induced signaling, Western blot analysis was employed. RESULTS: IL-24 inhibited the growth of normal MOVAS cells treated with H(2)O(2) by inducing a cell cycle arrest at the G(0)/G(1) phase through the regulation of p21 and cyclin D1. Furthermore, IL-24 suppressed mRNA expression of vascular endothelial growth factor and platelet-derived growth factor and subsequently decreased the level of cell migration in response to H(2)O(2). Interestingly, IL-24 attenuated the H(2)O(2)-induced ROS production by reducing the mitochondrial H(2)O(2) production and enhancing the expression of antioxidant enzymes. We also showed that the ability of H(2)O(2) to induce the PI3K/Akt and Erk signaling pathways was blocked by IL-24. CONCLUSION: These findings suggest a novel mechanism in which IL-24 suppresses the growth of normal VSMCs by inhibiting H(2)O(2)-induced ROS production through the regulation of mitochondrial ROS production and expression of antioxidant enzymes.
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Interleucinas/fisiología , Miocitos del Músculo Liso/fisiología , Especies Reactivas de Oxígeno/metabolismo , Animales , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ratones , Mitocondrias/metabolismo , Músculo Liso Vascular/citología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
This review discusses the current practices, attitudes, and trends in diagnosing and managing keratoconus (KC) in adults and children by optometrists and ophthalmologists in order to highlight the differences on a global scale. Two independent reviewers searched the electronic databases and grey literature for all potential articles published from 1 January 2000 to 1 June 2022 on management of KC. Keywords used in searches included "keratoconus", "diagnosis", "management", "treatment", "attitude", "practices", "opinion", "optometrist", "ophthalmologist", "consensus", and "protocol". A total of 19 articles was included in this review-12 from the database search and seven from the grey literature. Although a common stepwise approach of non-surgical management was noted, there were differences in the rates of prescribing rigid gas permeable lenses. Furthermore, while clinicians agreed on the need for early diagnosis, the timeline and type of referral varied significantly. A similar discordance was found in the milestones for surgical intervention and preferred surgical techniques. Practice patterns in keratoconus diagnosis and management vary throughout the world. Multiple recommendations and suggestions to minimise the differences have been provided in the literature, with the main themes being improvement in education, interdisciplinary patient care, and further research to reach consensus.
RESUMEN
â¢VKH is an idiopathic autoimmune disease presenting with uveomeningeal syndrome.â¢Granulomatous uveitis and serious retinal detachments are the most common findings of VKH.â¢VKH can masquerade as IIH by presenting with severe headache and optic disc edema.â¢The characteristic retinal finding of VKH can be easily missed by direct funduscopy.
RESUMEN
OBJECTIVE: The study of Hanwoo (Korean native cattle) has mainly been focused on meat quality and productivity. Recently the field of microbiome research has increased dramatically. However, the information on the microbiome in Hanwoo is still insufficient, especially relationship between vagina and feces. Therefore, the purpose of this study is to examine the microbial community characteristics by analyzing the 16S rRNA sequencing data of Hanwoo vagina and feces, as well as to confirm the difference and correlation between vaginal and fecal microorganisms. As a result, the goal is to investigate if fecal microbiome can be used to predict vaginal microbiome. METHODS: A total of 31 clinically healthy Hanwoo that delivered healthy calves more than once in Cheongju, South Korea were enrolled in this study. During the breeding season, we collected vaginal and fecal samples and sequenced the microbial 16S rRNA genes V3-V4 hypervariable regions from microbial DNA of samples. RESULTS: The results revealed that the phylum-level microorganisms with the largest relative distribution were Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria in the vagina, and Firmicutes, Bacteroidetes, and Spirochaetes in the feces, respectively. In the analysis of alpha, beta diversity, and effect size measurements (LefSe), the results showed significant differences between the vaginal and fecal samples. We also identified the function of these differentially abundant microorganisms by functional annotation analyses. But there is no significant correlation between vaginal and fecal microbiome. CONCLUSION: There is a significant difference between vaginal and fecal microbiome, but no significant correlation. Therefore, it is difficult to interrelate vaginal microbiome as fecal microbiome in Hanwoo. In a further study, it will be necessary to identify the genetic relationship of the entire microorganism between vagina and feces through the whole metagenome sequencing analysis and meta-transcriptome analysis to figure out their relationship.
RESUMEN
Gut microbiomes are well recognized to serve a variety of roles in health and disease, even though their functions are not yet completely understood. Previous studies have demonstrated that the microbiomes of juvenile and adult dogs have significantly different compositions and characteristics. However, there is still a scarcity of basic microbiome research in dogs. In this study, we aimed to advance our understanding by confirming the difference in fecal microbiome between young and adult dogs by analyzing the feces of 4-month and 16-month-old Jindo dogs, a domestic Korean breed. Microbiome data were generated and examined for the two age groups using 16S rRNA analysis. Comparison results revealed that the 16-month-old group presented a relatively high distribution of Bacteroides, whereas the 4-month-old group presented a comparatively high distribution of the Lactobacillus genus. Microbial function prediction analyses confirmed the relative abundance of lipid metabolism in 4-month-old dogs. In 16-month-old dogs, glucose metabolism was determined using microbial function prediction analyses. This implies that the functional microbiome changes similarly to the latter in adults compared with childhood. Overall, we discovered compositional and functional variations between genes of the gut microbial population in juveniles and adults. These microbial community profiles can be used as references for future research on the microbiome associated with health and development in the canine population.