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1.
Int J Mol Sci ; 21(22)2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33207561

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a complex disease that is affected by genetic predisposition and epigenetic modification. Deregulation of epigenetic pathways is now recognized as a frequent event in NAFLD, and understanding the mechanistic roles of these epigenetic factors may lead to new strategies for NAFLD treatment. Enhancer of zeste homolog 2 (EZH2) catalyzes methylation on Lys 27 of histone H3, which leads to chromatin compaction and gene silencing. EZH2 regulates embryonic development and cell lineage determination and is related to many human diseases. Recent studies show that EZH2 has critical roles in liver development, homeostasis, and regeneration. Moreover, aberrant activation of EZH2 promotes NAFLD progression. Several EZH2 inhibitors have been developed and studied both in vitro and in clinical trials. In this review, we summarize our current understanding of the role of EZH2 in NAFLD and highlight its potential as a novel therapeutic target for NAFLD treatment.


Assuntos
Sistemas de Liberação de Medicamentos , Proteína Potenciadora do Homólogo 2 de Zeste , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo
2.
J Toxicol Environ Health A ; 81(11): 397-407, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29557720

RESUMO

The objective of this study was to elucidate the effect of hepatic damage on cisplatin (CDDP)-induced acute kidney injury (AKI). Thioacetamide (TAA, 150 mg/kg), a hepatotoxicant, was intraperitoneally (i.p.) injected to male Sprague-Dawley rats for 3 d prior to CDDP (5 mg/kg, i.p.) injection. All animals were sacrificed 5 d after CDDP treatment, and urine or blood was obtained to measure various parameters. No significant changes in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity were observed after CDDP treatment. However, pretreatment with TAA significantly elevated ALT and AST activity. Serum blood urea nitrogen and creatinine levels significantly increased in CDDP-treated group compared to control. In addition, urinary excretion of novel protein-based biomarkers such as neutrophil gelatinase-associated lipocalin, vascular endothelial growth factor, kidney injury molecule-1, and tissue inhibitor of metalloproteinase-1 rose markedly in the CDDP-treated group. In particular, pretreatment with TAA markedly elevated CDDP-induced urinary excretion of protein-based nephrotoxic biomarkers compared with CDDP alone. Hematoxylin and eosin staining demonstrated that pretreatment with TAA following CDDP injection led to more severe tubular damage and apoptosis in rats compared with CDDP alone. Antioxidant status was significantly reduced in kidneys following pretreatment with TAA prior to CDDP. These findings indicate that liver injury enhanced the vulnerability of kidney to CDDP-induced AKI and this phenomenon may be associated with severe apoptotic damage.


Assuntos
Injúria Renal Aguda/fisiopatologia , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Fígado/fisiopatologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/urina , Carcinógenos/toxicidade , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Tioacetamida/toxicidade
3.
Lasers Med Sci ; 33(5): 1055-1064, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29502159

RESUMO

The etiology of intervertebral disc (IVD) degeneration accompanied by low back pain (LBP) is largely unknown, and there are no curative therapies. Painful IVD degeneration is associated with infiltrated macrophage-mediated inflammatory response of human nucleus pulposus (NP) cells. The present study aimed to address the hypothesis that pro-inflammatory cytokines derived from macrophages lead to the altered molecular phenotype of human NP cells and to investigate the effects of phototherapy (630, 525, 465 nm with 16, 32, 64 J/cm2) on pain-related cytokine interleukin (IL)-6 and chemokine IL-8 under inflammatory conditions in human NP cells. Human NP cells were treated with soluble factors derived from macrophages in an inflammatory microenvironment, similar to that found in degenerative IVD. Human NP cells were also treated with phototherapy (630, 525, 465 nm with 16, 32, 64 J/cm2), and their cytokine and chemokine levels were detected. The soluble factors caused modulated expression of IL-6, IL-8, and matrix metalloproteinases (MMPs) at the gene and protein levels, causing a shift toward matrix catabolism through the expression of MMPs and increased pain-related factors via preferential activation of the nuclear factor-kappa B (NF-κB) p50 protein. Importantly, phototherapy attenuated the protein and gene expression of pain-related factor IL-6 at all doses and wavelengths. Interestingly, phototherapy also modulated the protein and gene expression of IL-8, which is responsible for the anabolic response, at a wavelength of 465 nm at all doses, in human NP cells. These findings suggested that phototherapy, at an optimal dose and wavelength, might be a useful therapeutic tool to treat IVD degeneration.


Assuntos
Degeneração do Disco Intervertebral/terapia , Núcleo Pulposo/patologia , Fototerapia , Linhagem Celular , Citocinas/metabolismo , Feminino , Expressão Gênica/efeitos da radiação , Humanos , Inflamação/metabolismo , Dor Lombar/metabolismo , Dor Lombar/terapia , Macrófagos/metabolismo , Masculino , NF-kappa B/metabolismo , Núcleo Pulposo/imunologia , Núcleo Pulposo/metabolismo
4.
Asian-Australas J Anim Sci ; 27(1): 115-22, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25049933

RESUMO

This study investigated on the effects of adding mechanically deboned chicken meat (MDCM) hydrolysates on the quality properties of imitation fish paste (IFP) during storage. IFP was prepared from Alaska Pollack, spent laying hens surimi and protein hydrolysates which were enzymatically extracted from MDCM. The study was designed as a 3×4 factorial design with three MDCM hydrolysate content groups (0%, 0.4%, and 0.8%) and four storage times (0, 2, 4, and 6 weeks). Addition of MDCM hydrolysates increased crude fat content but lowered water content (p<0.05). The breaking force of IFP, an indicator of gel formation, increased in treated groups compared to control (p<0.05). Angiotensin I-converting enzyme (ACE) activity was inhibited and free radical scavenging activity increased with increasing MDCM hydrolysate content (p<0.05). In conclusion, the addition of MDCM to IFP improves gel characteristics. Additionally, protein hydrolysates from MDCM serve as a potential source of ACE inhibiting peptides.

5.
ACS Omega ; 8(7): 6538-6549, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36844518

RESUMO

Aglycone- and glycoside-derived forms of flavonoids exist broadly in plants and foods such as fruits, vegetables, and peanuts. However, most studies focus on the bioavailability of flavonoid aglycone rather than its glycosylated form. Kaempferol-3-O-ß-d-glucuronate (K3G) is a natural flavonoid glycoside obtained from various plants that have several biological activities, including antioxidant and anti-inflammatory effects. However, the molecular mechanism related to the antioxidant and antineuroinflammatory activity of K3G has not yet been demonstrated. The present study was designed to demonstrate the antioxidant and antineuroinflammatory effect of K3G against lipopolysaccharide (LPS)-stimulated BV2 microglial cells and to evaluate the underlying mechanism. Cell viability was determined by MTT assay. The inhibition rate of reactive oxygen species (ROS) and the production of pro-inflammatory mediators and cytokines were measured by DCF-DA assay, Griess assay, enzyme-linked immunosorbent assay (ELISA), and western blotting. K3G inhibited the LPS-induced release of nitric oxide, interleukin (IL)-6, and tumor necrosis factor-α (TNF-α) as well as the expression of prostaglandin E synthase 2. Additionally, K3G reduced the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB) related proteins. Mechanistic studies found that K3G downregulated phosphorylated mitogen-activated protein kinases (MAPKs) and upregulated the Nrf2/HO-1 signaling cascade. In this study, we demonstrated the effects of K3G on antineuroinflammation by inactivating phosphorylation of MPAKs and on antioxidants by upregulating the Nrf2/HO-1 signaling pathway through decreasing ROS in LPS-stimulated BV2 cells.

6.
Obes Res Clin Pract ; 17(4): 335-342, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37336708

RESUMO

INTRODUCTION: We aimed to evaluate the relationships between hepatic steatosis and various indices of obesity, and to identify the most useful index for the prediction of hepatic steatosis in children and adolescents with obesity. METHODS: A total of 226 children and adolescents with a mean body mass index (BMI) z-score of 2.65 and a mean age of 11.4 years were subjected to anthropometric and body composition measurements, laboratory testing, abdominal fat mass assessment, and hepatic fat accumulation by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF). The participants were divided into quartiles according to the severity of their hepatic steatosis, and the presence of hepatic steatosis was defined using an MRI-PDFF ≥ 5%. RESULTS: The multivariate ordinal regression analysis showed that the severity of hepatic steatosis was positively associated with BMI, waist circumference, waist-to-hip ratio, waist-to-height ratio, fat mass, fat-free mass, visceral adiposity, and abdominal subcutaneous adiposity. Higher activities of liver enzymes and higher concentrations of triglyceride, C-reactive protein, fasting insulin, and leptin were associated with more severe hepatic steatosis, whereas high-density lipoprotein-cholesterol and adiponectin were negatively associated with hepatic steatosis. The indices of obesity with areas under the receiver operating characteristic curves (AUCs) > 0.8 for the prediction of hepatic steatosis were liver enzymes, visceral adipose tissue area, waist-to-hip ratio, and waist-to-height ratio. CONCLUSION: The severity of hepatic steatosis significantly correlated with various indices of obesity and cardiometabolic markers in children and adolescents with obesity. The indices of abdominal obesity would be the most useful for the prediction of hepatic steatosis.


Assuntos
Fígado Gorduroso , Obesidade Infantil , Adolescente , Humanos , Criança , Estudos Transversais , Obesidade Infantil/complicações , Obesidade Infantil/diagnóstico por imagem , Fígado Gorduroso/diagnóstico por imagem , Índice de Massa Corporal , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico por imagem , Imageamento por Ressonância Magnética
7.
Exp Dermatol ; 21(10): 796-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22913469

RESUMO

Sebaceous glands are known to affect hair growth. Nevus sebaceus, a sebaceous gland hamartomas, presents as hairless patches. In this study, cultures of nevus sebaceus sebocytes (NSS) and normal scalp hair follicle sebocytes (NS) were used in performance of microarray, RT-PCR, western blot assay and immunofluorescence staining. NSS- and NS-conditioned media were also added to the culture of outer root sheath cells (ORSCs), dermal papilla cells (DPCs) or normal scalp hair follicle sebocytes. Results of this study showed a decrease in the survival rate of ORSCs and DPCs and hair growth in the NSS-conditioned medium-treated group, compared with the control and NS-conditioned medium-treated groups. An increase in expression of fibroblast growth factor (FGF)-5, Dickkopf-1 and inflammatory cytokines and a decrease in expression of Wnt10b and Lef1 were observed. In conclusion, NSS showed an increase in expression of hair growth-suppressing bioactive factors, including FGF-5, and a decrease in expression of hair growth-stimulating factors.


Assuntos
Cabelo/crescimento & desenvolvimento , Nevo Pigmentado/patologia , Neoplasias das Glândulas Sebáceas/patologia , Glândulas Sebáceas/patologia , Neoplasias Cutâneas/patologia , Meios de Cultivo Condicionados , Fator 5 de Crescimento de Fibroblastos/genética , Expressão Gênica , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Humanos , Nevo , Nevo Pigmentado/metabolismo , Neoplasias das Glândulas Sebáceas/metabolismo , Glândulas Sebáceas/metabolismo , Neoplasias Cutâneas/metabolismo , Células Tumorais Cultivadas
8.
Ann Allergy Asthma Immunol ; 109(6): 448-53, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23176886

RESUMO

BACKGROUND: We previously found that skin-colonizing Staphylococcus aureus in early childhood atopic dermatitis (AD) originates predominantly from the patient's nose, whereas maternal transmission did not contribute substantially to colonization. OBJECTIVE: To investigate the transmission route and definitive source of skin-colonizing S aureus in early childhood AD. METHODS: A total of 527 children and 32 healthy teachers from 2 kindergartens and 1 elementary school were included in the study. Children were screened for AD and categorized into 3 groups (AD, borderline, and healthy). Samples were collected from 5 to 6 different body sites, including the skin, subungual spaces, and anterior nares. The identity of colonies apparent on mannitol salt agar plates was confirmed by polymerase chain reaction amplification of the nuc gene. The genotypic composition of cultured isolates was examined by pulsed-field gel electrophoresis and analyzed with a dendrogram. RESULTS: The total colonization rate was higher in the AD group (34.6%) than in the borderline (21.1%) and healthy groups (25.4%). In the AD group, S aureus was more frequently cultured from the subungual areas (30.8%) than the anterior nares (19.2%). To assess self-contamination or recolonization, dendrogram analysis revealed that most isolate pairs (22/23) had the same pulsed-field gel electrophoresis pattern. CONCLUSION: As with the anterior nares, the subungual spaces are important reservoir of skin-colonizing S aureus in early childhood AD. The transmission route for self-contamination or recolonization of S aureus appears to be from children's anterior nares to the skin through their own fingers. Child-to-child and/or teacher-to-child transmission in a classroom do not seem to be definite routes of S aureus transmission.


Assuntos
Dermatite Atópica/microbiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/transmissão , Staphylococcus aureus/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Criança , Pré-Escolar , Eletroforese em Gel de Campo Pulsado/métodos , Docentes , Humanos , Nuclease do Micrococo/genética , Nariz/microbiologia , Staphylococcus aureus/genética
9.
Nutr Neurosci ; 15(1): 25-30, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22305650

RESUMO

OBJECTIVE: The purpose of this study was to assess the association between cerebral infarction (CI), nutritional status, and depression. METHODS: Subjects with and without CI (n = 146; 73 CI vs. 73 non-CI) were recruited from Kyung Hee University Medical Center (Seoul, Korea) and were matched according to age and gender. The subjects' medical histories, health-related behavioral habits, food intake, nutritional assessment, and depression status were analyzed. RESULTS: The prevalence of hypertension or diabetes were much higher in subjects in the CI group than in the non-CI group (P < 0.001). Subjects with CI registered lower dietary intakes of potassium, dietary fiber, fish, fruits, and vegetables than non-CI subjects (P < 0.05). By the mini-nutritional assessment (MNA) classification, malnutrition affected 57.5% of subjects in the CI group, but none of the subjects in the non-CI group (P < 0.001). The average Beck depression inventory (BDI) score was 43.6 ± 7.7 points in the CI group and 20.6 ± 13.1 points in the non-CI group (P < 0.001). Higher MNA scores (well-nourished status) were inversely associated with CI prevalence (odds ratio (OR) = 0.23; 95% CI: 0.07, 0.79) after controlling for age, gender, medical history, and health-related factors, whereas BDI was not associated with CI prevalence (OR = 1.32; 95% CI: 0.90, 1.94). DISCUSSION: CI patients had several comorbidities, inappropriate health-related behavioral habits, malnourished status, and severe depression prior to CI onset. Indices of well-nourished status were inversely associated with CI. Accordingly, it would be desirable to develop a protocol for medical nutrition therapy in CI patients to improve nutritional status.


Assuntos
Infarto Cerebral/epidemiologia , Depressão/epidemiologia , Depressão/fisiopatologia , Desnutrição/epidemiologia , Estado Nutricional , Idoso , Estudos de Casos e Controles , Infarto Cerebral/complicações , Depressão/complicações , Depressão/psicologia , Feminino , Avaliação Geriátrica , Humanos , Hipertensão , Entrevistas como Assunto , Masculino , Desnutrição/complicações , Desnutrição/fisiopatologia , Pessoa de Meia-Idade , Avaliação Nutricional , Prevalência , República da Coreia , Fatores de Risco , Inquéritos e Questionários
10.
Arch Toxicol ; 86(12): 1885-97, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22885791

RESUMO

Melamine-induced renal toxicity is associated with crystal formation in the kidney following exposure to melamine and cyanuric acid. However, metabolomic profiling of intact kidney tissue after chronic intake of melamine and cyanuric acid (M + CA) mixtures has rarely been studied. The present study investigated the melamine-induced renal toxicity by determining metabolites in the kidney through [(1)H]nuclear magnetic resonance. Melamine (63 mg/kg) and cyanuric acid (6.3 mg/kg) were co-administered to rats via oral gavage for 30 days. The mixture of M + CA (63/6.3 mg/kg) induced nephrotoxicity, as determined by increased blood urea nitrogen (BUN) and creatinine levels. The kidney weights were significantly increased in the animals treated with M + CA (63/6.3 mg/kg). The histological analysis revealed epithelial degeneration and necrotic cell death in the proximal and distal tubules. Furthermore, various metabolites were altered in both renal medullar and cortical tissues. In the medullar tissues, asparagine, choline, creatinine, cysteine, ethanolamine, glucose, isoleucine, glutamine, and myo-inositol levels were elevated, but glucitol, phenylalanine, tyrosine, and sn-glycero-3-levels were reduced. In the cortex, ethanolamine, hypoxanthine, isoleucine and o-phosphoethanolamine levels were increased, whereas formate, glucose, glutathione, threonine, and myo-inositol levels were decreased, suggesting the M + CA-induced renal cell injury. These data suggest that a mixture of M + CA-induced metabolites may be useful biomarkers for the detection of kidney injury.


Assuntos
Biomarcadores/sangue , Biomarcadores/urina , Nefropatias/induzido quimicamente , Nefropatias/patologia , Metabolômica/métodos , Triazinas/toxicidade , Animais , Análise Química do Sangue , Western Blotting , Peso Corporal/efeitos dos fármacos , Imuno-Histoquímica , Rim/patologia , Espectroscopia de Ressonância Magnética , Masculino , Análise Multivariada , Tamanho do Órgão/efeitos dos fármacos , Análise de Componente Principal , Ratos , Ratos Sprague-Dawley , Urinálise
11.
Prev Nutr Food Sci ; 27(1): 99-107, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35465112

RESUMO

Edible insects are commonly consumed across the world because of their size, availability, and nutritional benefits. They have also been recommended as a potential solution to food shortage because of their high nutritional value. In this study, we demonstrated the immunological effects of Gryllus bimaculatus on RAW 264.7 cells and splenocytes obtained from mouse. This is the first study to evaluate the immunological effects of G. bimaculatus water extract. Innate and adaptive immunity were evaluated and measured in RAW 264.7 cells and/or mouse splenocytes using a cell viability assay; changes in cytokine abundance, nitric oxide production, and cell surface molecule abundance were determined using flow cytometry; and western blotting analysis was performed for various immune signaling pathways. G. bimaculatus water extract showed no cytotoxicity in cells, and the results suggest that treatment with G. bimaculatus water extract can induce macrophage activation through mitogen-activated protein kinase and nuclear factor-κB signaling, induction of proinflammatory cytokines [interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α] and activation of the expression of cell surface molecules [cluster of differentiation (CD)80, CD86, major histocompatibility complex (MHC) class I, and MHC class II]. Treatment with G. bimaculatus water extract increased the production of cytokines (IL-2, IL-4, and interferon-γ) in splenocytes. The results indicate that G. bimaculatus water extract can regulate innate and adaptive immunity via modulation macrophages and splenocytes activation and can serve as an immunological agent. We inferred that G. bimaculatus is a safe and efficient natural material that enhances immunological activity.

12.
J Clin Med ; 11(12)2022 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-35743590

RESUMO

BACKGROUND: Childhood obesity is linked to adverse cardiovascular outcomes in adulthood. This study aimed to assess the impact of childhood obesity on the vasculature and to investigate whether vascular alteration precedes arterial wall thickening in childhood. METHODS: A total of 295 overweight (body mass index [BMI] 85th to 95th percentile, n = 30) and obese (BMI ≥ 95th percentile, n = 234) children aged 7-17 years and 31 normal-weight controls with similar age and gender were prospectively recruited. We assessed anthropometric data and laboratory findings, and measured the carotid intima-media thickness (IMT), carotid artery (CA) diameter, M-mode-derived arterial stiffness indices, and velocity vector imaging parameters, including the CA area, fractional area change, circumferential strain, and circumferential strain rate (SR). RESULTS: The mean ± standard deviation age of the participants was 10.8 ± 2.1 years; 172 (58%) children were male. Regarding structural properties, there was no difference in the IMT between the three groups. The CA diameter was significantly increased in obese children, whereas the CA area showed a significant increase beginning in the overweight stage. Regarding functional properties, contrary to ß stiffness and Young's elastic modulus, which were not different between the three groups, the circumferential SR showed a significant decrease beginning in the overweight stage and was independently associated with BMI z-scores after adjusting for covariates. CONCLUSION: We have demonstrated that arterial stiffening and arterial enlargement precede arterial wall thickening, and that these vascular alterations begin at the overweight stage in middle childhood or early adolescence.

13.
Heliyon ; 8(10): e11008, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36247133

RESUMO

Background: Since January 2022, the Omicron variant has become the dominant strain in South Korea, and COVID-19 cases among hospitalized patients and their guardians or caregivers have increased. We evaluated the usefulness of universal periodic screening for SARS-CoV-2 in patients and resident caregivers in a South Korean tertiary care hospital. Methods: We evaluated the reason for testing in COVID-19 confirmed patients and resident caregivers during their hospitalization from March 3 to 31, 2022. The rate of positive PCR universal testing in hospital (or residency) (HD) on days 3 and 7 in asymptomatic patients and caregivers were evaluated. The test for SARS-CoV-2 was done by RT-PCR. Results: During the study period, 677 patients were diagnosed with COVID-19. The reasons for testing were the symptoms (226 (33%)), pre-admission test (183 (27%)), exposure to COVID-19 (124 (18%)), universal testing on HD 3 (94 (14%)), and that on HD 7 (34 (5%)). Caregivers (n = 340) were tested during their residency due to exposure to COVID-19 cases, 103 (30%); universal testing on HD 3, 90 (26%); symptom development, 46 (14%); pre-stay, 39 (11%); and universal testing on HD 7, 29 (9%). The positive test rates of inpatients and caregivers on HD 3 and HD 7 were as follows: 1.4% (93/6553) and 2.1% (55/2646) in inpatients, and 1.3% (79/5989) and 1.7% (35/2106) in caregivers, respectively. Conclusions: Universal testing, regardless of symptom or epidemiologic link, is useful for detecting pre-symptomatic and asymptomatic COVID-19 cases among hospitalized patients and caregivers and preventing a nosocomial outbreak during the Omicron era.

14.
Exp Mol Med ; 54(8): 1236-1249, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35999456

RESUMO

Acquired resistance to inhibitors of anaplastic lymphoma kinase (ALK) is a major clinical challenge for ALK fusion-positive non-small-cell lung cancer (NSCLC). In the absence of secondary ALK mutations, epigenetic reprogramming is one of the main mechanisms of drug resistance, as it leads to phenotype switching that occurs during the epithelial-to-mesenchymal transition (EMT). Although drug-induced epigenetic reprogramming is believed to alter the sensitivity of cancer cells to anticancer treatments, there is still much to learn about overcoming drug resistance. In this study, we used an in vitro model of ceritinib-resistant NSCLC and employed genome-wide DNA methylation analysis in combination with single-cell (sc) RNA-seq to identify cytidine deaminase (CDA), a pyrimidine salvage pathway enzyme, as a candidate drug target. CDA was hypomethylated and upregulated in ceritinib-resistant cells. CDA-overexpressing cells were rarely but definitively detected in the naïve cell population by scRNA-seq, and their abundance was increased in the acquired-resistance population. Knockdown of CDA had antiproliferative effects on resistant cells and reversed the EMT phenotype. Treatment with epigenome-related nucleosides such as 5-formyl-2'-deoxycytidine selectively ablated CDA-overexpressing resistant cells via accumulation of DNA damage. Collectively, our data suggest that targeting CDA metabolism using epigenome-related nucleosides represents a potential new therapeutic strategy for overcoming ALK inhibitor resistance in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Citidina Desaminase/genética , Citidina Desaminase/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Epigenoma , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/farmacologia , Receptores Proteína Tirosina Quinases/metabolismo , Análise de Célula Única
15.
Ann Allergy Asthma Immunol ; 106(4): 323-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21457881

RESUMO

BACKGROUND: Colonization of Staphylococcus aureus is well known to be an aggravating factor for the flare-up of atopic dermatitis (AD), yet few studies have been done on its spread in families with childhood AD. OBJECTIVE: To evaluate the characteristic features of skin-colonizing S aureus and to identify the source of S aureus in early childhood AD. METHODS: Forty-four subjects with AD, 51 borderline (BD) subjects, and 36 normal controls (NC) aged 3-6 years and their mothers were recruited from four different kindergartens. After comparing the positive culture rate of S aureus in three different groups of children and their mothers, we determined if there is a possibility of intrafamilial transmission between the children with AD and their mothers using polymerase chain reaction and pulsed-field gel electrophoresis. RESULTS: A high prevalence (72.7%) of S aureus colonization was found in the AD group compared with the BD and NC groups. However, the prevalence rate of S aureus in the mothers who had children with AD was not significantly higher than in the mothers from the BD and NC groups. Based on the pulsed-field gel electrophoresis results, the cutaneous re-colonization of S aureus in childhood AD appears to have been primarily originating from the patients' noses, and maternal origin does not appear to substantially contribute to S aureus transmission in early childhood AD. CONCLUSIONS: Since the cutaneous colonization of S aureus in early childhood AD predominantly originated from the patients' own noses, the maternal transmission route does not appear to contribute substantially to the colonization of S aureus in early childhood AD.


Assuntos
Dermatite Atópica/microbiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/crescimento & desenvolvimento , Distribuição de Qui-Quadrado , Pré-Escolar , Contagem de Colônia Microbiana , Estudos Transversais , DNA Bacteriano/química , DNA Bacteriano/genética , Dermatite Atópica/epidemiologia , Eletroforese em Gel de Campo Pulsado , Feminino , Humanos , Mães , Reação em Cadeia da Polimerase , Prevalência , República da Coreia/epidemiologia , Instituições Acadêmicas , Infecções Cutâneas Estafilocócicas/epidemiologia , Staphylococcus aureus/genética
16.
Prev Nutr Food Sci ; 26(4): 453-458, 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35047442

RESUMO

Gryllus bimaculatus, traditionally used in oriental medicine, demonstrates functional and pharmacological potential through demonstrating immunomodulatory, hepato-protective properties, anti-inflammatory, antioxidant, and neuroprotective effects. In this study, we examined the effect of G. bimaculatus on cell proliferation and apoptosis in lung cancer cells. This is the first study to examine the anti-cancer effects of G. bimaculatus extracts on non-small cell lung cancer. Frozen G. bimaculatus was obtained, homogenized, and dissolved in distilled water. Using a freeze dryer, samples were concentrated until almost all the water was removed, and extracts were diluted in solutions of phosphate buffered saline. Anti-cancer effects of extracts on human non-small cancer lung cells were estimated based on cell cytotoxicity, western blot, and flow cytometry, using lipopolysaccharides as a positive control. H460 and A549 human non-small cell cancer lung cells were treated with G. bimaculatus water extracts of various concentrations, with lipopolysaccharide used as a pos-itive control. The results showed that treatment with the extract for 24 or 48 h inhibited H460 proliferation, demonstrated by reduced cell numbers with morphological changes. Furthermore, flow cytometry analysis demonstrated that the extracts induced cell death on H460. However, extracts did not show cytotoxic effects on A549 cells. In conclusion, the extract induced apoptosis of lung cancer cells, possibly via caspase, Bcl-2 family signaling pathways. Therefore, G. bimaculatus water extracts are safe and efficient natural materials that may have great potential in the treatment of lung cancer.

17.
J Microbiol Biotechnol ; 30(12): 1793-1800, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33144551

RESUMO

Bifidobacterium strains can provide several health benefits, such as antimicrobial and immunomodulatory effects. Some strains inhibit growth or cell adhesion of pathogenic bacteria, including multidrug-resistant bacteria, and their antibacterial activity can be intensified when combined with certain antibiotics. In addition, some strains of bifidobacteria reduce viral infectivity, leading to less epithelial damage of intestinal tissue, lowering the virus shedding titer, and controlling the release of antiviral substances. Furthermore, bifidobacteria can modulate the immune system by increasing immunoglobulins, and inducing or reducing pro- or antiinflammatory cytokines, respectively. In particular, these anti-inflammatory effects are helpful in the treatment of patients who are already suffering from infection or inflammatory diseases. This review summarizes the antimicrobial effects and mechanisms, and immunomodulatory effects of Bifidobacterium strains, suggesting the potential of bifidobacteria as an alternative or complementary treatment option.


Assuntos
Antibacterianos/farmacologia , Bifidobacterium/imunologia , Imunomodulação , Probióticos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antibiose , Antivirais/farmacologia , Bactérias , Citocinas , Farmacorresistência Bacteriana Múltipla , Células Epiteliais/microbiologia , Trato Gastrointestinal/microbiologia , Humanos , Intestinos/microbiologia
18.
Obes Res Clin Pract ; 14(6): 566-572, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33004301

RESUMO

BACKGROUND: Significant dropout rates remain a serious concern in pediatric weight control program, but few studies have identified predictors of dropout. AIMS: The objective of the study is to identify factors associated with dropout from a pediatric lifestyle modification weight control program at different phases. METHODS: Data on overweight and obese participants (n = 242) aged 11-18 years in the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition (ICAAN) study were collected at baseline, 6-months, and 24-months through self-report and a laboratory test. Logistic regression analysis was performed for those who dropped out during the first 6-months, and multivariate generalized estimating equation analysis identified longitudinal factors associated with those who dropped out after 24 months. RESULTS: Lower family functioning (OR = 2.30, 95% CI [1.18-4.46]), exercise group (OR = 0.36, 95% CI [0.15-0.86]), lower initial attendance rate (OR = 6.09, 95% CI [2.94-12.6]), and non-self -referral pathways (OR = 2.35, 95% CI [1.05-5.27]) were significantly associated with 6-month dropouts. For late dropout, lower family functioning (OR = 1.71, 95% CI [1.06-2.77]) and lower initial attendance rates (OR = 2.06, 95% CI [1.12-3.81]) remained significant. CONCLUSION: Family function and initial attendance rate were associated with lower dropout rates. Developing a supportive family environment and focusing on the early-stage factors at the intervention's outset may reduce overall dropout rates in obesity prevention intervention.


Assuntos
Estilo de Vida , Obesidade Infantil , Adolescente , Terapia Comportamental , Criança , Humanos , Sobrepeso , Pacientes Desistentes do Tratamento
19.
Ann Dermatol ; 32(1): 31-37, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33911706

RESUMO

BACKGROUND: Based on clinical and genetic differences, atopic dermatitis (AD) and psoriasis have been classified in two different diseases, but recently, some authors regarded them as in one spectrum. The histological similarities including epidermal hyperplasia between chronic stages of AD and psoriasis supports the presence of two diseases in one spectrum. OBJECTIVE: We investigated clinical and immunohistopathological characteristics of adult Korean patients with AD showing psoriasiform chronic dermatitis on histopathology. METHODS: In total, 59 Korean patients with chronic AD were enrolled. Clinical, laboratory, and histopathological features were compared between AD patients with psoriasiform features and those with non-psoriasiform chronic dermatitis features on histology. In addition, immunohistopathological characteristics were analyzed using antibodies for key regulatory and effector cytokines in psoriasis. RESULTS: Fifteen patients (25.4%) showed a more "psoriasiform" histological appearance. The lesions in patients with psoriasiform features often showed clearer boundaries and noticeable scaling. The interleukin (IL)-23 expression in the psoriasiform chronic dermatitis group was not different from that in the psoriasis group, but the IL-17 expression was less than that in the psoriasis group. In the case of IL-12, multiple dermal inflammatory cells with dendrites were stained in the psoriasiform chronic dermatitis group compared with the 2 other non-psoriasiform subgroups. CONCLUSION: The results suggest that IL-12 secreted from dermal inflammatory cells might be one of the important factors associated with the formation of psoriasiform features in chronic AD. However, further studies are required to better define the specific role of IL-12.

20.
Clin Exp Otorhinolaryngol ; 12(1): 72-78, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30189718

RESUMO

OBJECTIVES: To develop a simple algorithm for prescreening of obstructive sleep apnea (OSA) on the basis of respiratory sounds recorded during polysomnography during all sleep stages between sleep onset and offset. METHODS: Patients who underwent attended, in-laboratory, full-night polysomnography were included. For all patients, audio recordings were performed with an air-conduction microphone during polysomnography. Analyses included all sleep stages (i.e., N1, N2, N3, rapid eye movement, and waking). After noise reduction preprocessing, data were segmented into 5-s windows and sound features were extracted. Prediction models were established and validated with 10-fold cross-validation by using simple logistic regression. Binary classifications were separately conducted for three different threshold criteria at apnea hypopnea index (AHI) of 5, 15, or 30. Prediction model characteristics, including accuracy, sensitivity, specificity, positive predictive value (precision), negative predictive value, and area under the curve (AUC) of the receiver operating characteristic were computed. RESULTS: A total of 116 subjects were included; their mean age, body mass index, and AHI were 50.4 years, 25.5 kg/m2 , and 23.0/hr, respectively. A total of 508 sound features were extracted from respiratory sounds recorded throughout sleep. Accuracies of binary classifiers at AHIs of 5, 15, and 30 were 82.7%, 84.4%, and 85.3%, respectively. Prediction performances for the classifiers at AHIs of 5, 15, and 30 were AUC, 0.83, 0.901, and 0.91; sensitivity, 87.5%, 81.6%, and 60%; and specificity, 67.8%, 87.5%, and 94.1%. Respective precision values of the classifiers were 89.5%, 87.5%, and 78.2% for AHIs of 5, 15, and 30. CONCLUSION: This study showed that our binary classifier predicted patients with AHI of ≥15 with sensitivity and specificity of >80% by using respiratory sounds during sleep. Since our prediction model included all sleep stage data, algorithms based on respiratory sounds may have a high value for prescreening OSA with mobile devices.

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