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1.
BMC Nephrol ; 24(1): 64, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949396

RESUMO

BACKGROUND: Chronic kidney disease (CKD) has a significant impact on global health. Studies have shown that subclinical thyroid dysfunction may be related to CKD, but the association between subclinical thyroid dysfunction and CKD in the general population is unclear. We aimed to evaluate the risk of CKD according to thyroid function status in a large cohort. METHODS: We analyzed data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 3,257 participants aged ≥ 19 years who underwent thyroid and kidney function assessments were included in this study. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 and/or urine albumin-creatinine ratio ≥ 30 mg/g. The risk of CKD according to thyroid function status was assessed using logistic regression, adjusted for potential confounders. RESULTS: Overall, 6.7% of the participants had CKD. There were no significant differences in thyroid-stimulating hormone and free thyroxine levels between the groups with and without CKD. The proportion of participants with CKD was significantly different among the thyroid function status groups (p = 0.012) and tended to increase significantly in the following order: subclinical hyperthyroidism (1.5%), euthyroidism (6.6%), and subclinical hypothyroidism (12.6%) (p for trend < 0.001). Subclinical hypothyroidism was a significant risk factor for CKD, even after adjusting for sex, age, household income, education, smoking, alcohol consumption, walking activity, abdominal obesity, hypertension, low high-density lipoprotein cholesterol, elevated triglycerides, hyperglycemia, free thyroxine, and thyroid-peroxidase anibody (odds ratio 2.161, 95% confidence interval 1.032-4.527, p = 0.041). CONCLUSION: Subclinical hypothyroidism is an independent predictor of CKD in the general population.


Assuntos
Hipotireoidismo , Insuficiência Renal Crônica , Glândula Tireoide , Humanos , Estudos Transversais , Hipotireoidismo/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Tiroxina , Glândula Tireoide/fisiopatologia
2.
Endocr J ; 70(4): 393-401, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-36567075

RESUMO

Metabolic syndrome (MetS) is considered very important because of the increased risk for cardiovascular diseases. Identifying modifiable factors may help prevent MetS. We aimed to investigate the relationship between iodine intake as a dietary factor and MetS in euthyroid adult in an iodine-replete area. A total of 4,277 adult aged ≥19 years from the Korea National Health and Nutrition Examination Survey VI (2013-2015) with urinary iodine concentration (UIC) results and normal thyroid function were included. Participants were grouped according to their iodine nutrition status based on the WHO recommendations and modifications: insufficient (<100 µg/L), adequate (100-299 µg/L), and excessive (≥300 µg/L) iodine intake. We estimated the odds ratios (ORs) for MetS according to the UIC groups using logistic regression models. Of the study participants, 27.2% men and 23.9% women had MetS. Men with excessive iodine intake had a significantly lower risk of elevated triglycerides [OR 0.733, 95% confidence interval (CI) 0.603-0.890, p = 0.010], as compared to those with adequate iodine intake. Women with insufficient iodine intake had a significantly greater risk of elevated blood glucose (OR 1.519, 95% CI 1.011-2.282, p = 0.044), as compared to those with adequate iodine intake. In women, insufficient iodine intake was a significant risk factor for MetS compared to adequate iodine intake, even after adjusting for confounding variables including age, smoking, alcohol consumption, walking activity, serum thyroid-stimulating hormone, free thyroxine, and anti-thyroid peroxidase antibody (OR 1.544, 95% CI 1.031-2.311, p = 0.035). There was no association between iodine intake and risk of MetS in men. In conclusion, insufficient iodine intake was associated with an increased risk of MetS only in euthyroid adult women. Our data support that sex differences may influence the relationship between iodine intake as a dietary pattern and MetS.


Assuntos
Bócio Nodular , Iodo , Síndrome Metabólica , Iodo/administração & dosagem , Síndrome Metabólica/epidemiologia , Estado Nutricional , Fatores de Risco , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Adulto , Bócio Nodular/epidemiologia , República da Coreia/epidemiologia , Prevalência , Pessoa de Meia-Idade
3.
Allergol Int ; 72(3): 466-476, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36586745

RESUMO

BACKGROUND: Platelets play a modulatory role in inflammatory response by secreting a vast array of granules and disintegrating into membrane-bound microparticles upon activation. The interplay between eosinophils and platelets is postulated to be implicated in the pathology of allergic airway inflammation. In this study, we investigated whether activated platelets can induce eosinophil extracellular trap (EET) formation, a cellular process by which activated eosinophils release net-like DNA fibers. METHODS: Platelets were stimulated with the calcium ionophore, A23187, and the platelet agonists, thrombin and adenosine diphosphate (ADP). Platelet cultures were fractionated into conditioned medium (CM) and pellet, which were then overlaid on eosinophils to examine EET formation. RESULTS: The CM and pellet from A23187-activated platelets stimulated eosinophils to generate EET, whereas those from thrombin- or ADP-activated platelets failed to induce such generation. The EET-inducing activity of the A23187-activated platelet culture was linearly proportional to the number of activated platelets. Interestingly, while EET formation induced by the direct stimulation of eosinophils with A23187 was NADPH oxidase (NOX)-dependent, EET formation induced by A23187-activated platelets was NOX-independent and significantly inhibited by necroptosis pathway inhibitors. CONCLUSIONS: Activated platelets and their products may induce EET formation, thereby potentiating their role in eosinophilic airway inflammation.


Assuntos
Plaquetas , Armadilhas Extracelulares , Humanos , Plaquetas/metabolismo , Trombina/farmacologia , Trombina/metabolismo , Ionóforos de Cálcio/metabolismo , Calcimicina/farmacologia , Calcimicina/metabolismo , Armadilhas Extracelulares/metabolismo , Inflamação/metabolismo , Difosfato de Adenosina/metabolismo , Cálcio/metabolismo
4.
PLoS One ; 17(12): e0279494, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36584082

RESUMO

BACKGROUND: Recent studies have indicated that the triglyceride-glucose (TyG) index or subclinical thyroid dysfunction is associated with carotid plaques, a predictor of cardiovascular disease risk. However, evidence for this association is limited and inconsistent. This study aimed to evaluate the risk of carotid plaques according to TyG index and thyroid function status in the general population. METHODS: A total of 2,931 individuals who underwent carotid ultrasound as part of a comprehensive health examination at the Health Promotion Center of Soonchunhyang University Hospital were retrospectively reviewed. Based on the TyG index and thyroid function status, the participants were divided into six groups: LoTyG-SHyper (low TyG index with subclinical hyperthyroidism), LoTyG-Eu (low TyG index with euthyroidism), LoTyG-SHypo (low TyG index with subclinical hypothyroidism), HiTyG-SHyper (high TyG index with subclinical hyperthyroidism), HiTyG-Eu (high TyG index with euthyroidism), and HiTyG-SHypo (high TyG index with subclinical hypothyroidism). A multivariate logistic regression analysis was conducted to determine the risk of carotid plaques. RESULTS: The proportion of participants with significant carotid plaques was significantly different among the six groups (p<0.001, p for trend<0.001). The odds ratio (OR) and 95% confidence interval (CI) for significant carotid plaques were significantly higher in the HiTyG-SHypo group than in the LoTyG-Eu group, even after adjusting for confounding variables including sex, age, smoking, obesity, hypertension and diabetes mellitus (OR 1.506, 95% CI 1.045-2.170, p = 0.028). The OR of significant carotid plaques was higher in the HiTyG-Eu group than in the LoTyG-Eu group; however no associations were observed after additional adjustment for confounding variables. CONCLUSION: The TyG index and thyroid function status are important predictors of the risk of carotid plaques in healthy individuals. Early evaluation of carotid plaques may be necessary for subjects with high insulin resistance and subclinical hypothyroidism.


Assuntos
Hipertireoidismo , Hipotireoidismo , Humanos , Glucose , Estudos Transversais , Estudos Retrospectivos , Triglicerídeos , Hipotireoidismo/complicações , Hipertireoidismo/complicações , Hipertireoidismo/epidemiologia , Fatores de Risco , Glicemia , Biomarcadores
5.
J Gastroenterol Hepatol ; 37(8): 1617-1623, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35434848

RESUMO

BACKGROUND AND AIM: The association between thyroid autoimmunity and nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we aimed to investigate the relationship between thyroid autoimmunity and NAFLD in a large cohort of euthyroid subjects. METHODS: We analyzed clinical and biochemical data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 1589 middle-aged participants aged 45-65 years, with normal thyroid function, were included in this study. NAFLD was defined as a hepatic steatosis index of > 36. We estimated the odds ratios (ORs) for NAFLD according to anti-thyroid peroxidase antibody (TPOAb) positivity by using logistic regression models, and adjusted for potential confounders. RESULTS: Overall, 24% (n = 378) of the subjects had NAFLD. Subjects with NAFLD showed a higher positivity for TPOAb (11% vs 7%, P = 0.014) compared with those without NAFLD. TPOAb positivity was a significant risk factor for NAFLD [OR 1.668, 95% confidence interval (CI) 1.019-2.730, P = 0.042] even after adjusting for confounding variables, including age, sex, household income, education, smoking, alcohol consumption, walking activity, abdominal obesity, elevated blood pressure, dyslipidemia and hyperglycemia. In addition, TPOAb positivity predicted the risk of advanced liver fibrosis (OR 3.112, 95% CI 1.256-7.713, P = 0.014) in subjects with NAFLD, independent of the confounding variables. CONCLUSION: In euthyroid subjects, thyroid autoimmunity is associated with NAFLD and advanced liver fibrosis, independent of known metabolic risk factors. Large longitudinal studies in the future will help clarify the causality.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Autoimunidade , Estudos Transversais , Humanos , Cirrose Hepática/complicações , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Fatores de Risco , Glândula Tireoide/metabolismo
6.
Int J Mol Sci ; 23(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35409225

RESUMO

Lysophosphatidylserine (LysoPS) is an amphipathic lysophospholipid that mediates a broad spectrum of inflammatory responses through a poorly characterized mechanism. Because LysoPS levels can rise in a variety of pathological conditions, we sought to investigate LysoPS's potential role in airway epithelial cells that actively participate in lung homeostasis. Here, we report a previously unappreciated function of LysoPS in production of a mucin component, MUC5AC, in the airway epithelial cells. LysoPS stimulated lung epithelial cells to produce MUC5AC via signaling pathways involving TACE, EGFR, and ERK. Specifically, LysoPS- dependent biphasic activation of ERK resulted in TGF-α secretion and strong EGFR phosphorylation leading to MUC5AC production. Collectively, LysoPS induces the expression of MUC5AC via a feedback loop composed of proligand synthesis and its proteolysis by TACE and following autocrine EGFR activation. To our surprise, we were not able to find a role of GPCRs and TLR2, known LyoPS receptors in LysoPS-induced MUC5AC production in airway epithelial cells, suggesting a potential receptor-independent action of LysoPS during inflammation. This study provides new insight into the potential function and mechanism of LysoPS as an emerging lipid mediator in airway inflammation.


Assuntos
Receptores ErbB , Sistema de Sinalização das MAP Quinases , Células Epiteliais/metabolismo , Receptores ErbB/metabolismo , Humanos , Inflamação/metabolismo , Lisofosfolipídeos/metabolismo , Lisofosfolipídeos/farmacologia , Mucina-5AC/metabolismo , Mucosa Respiratória/metabolismo
7.
J Endocr Soc ; 5(11): bvab154, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34703960

RESUMO

BACKGROUND: Fine needle aspiration is the gold standard for differential diagnosis of thyroid nodules; however, the malignancy rate for indeterminate cytology is 20% to 50%. OBJECTIVE: We evaluated the efficacy of shear wave elastography added to ultrasonography for differential diagnosis of thyroid nodules. METHODS: We retrospectively reviewed the medical records of 258 consecutive patients. Thyroid nodules were divided into 4 categories according to maximum elasticity (EMax) and nodule depth/width (D/W) ratio: Category 1 (EMax ≥ 42.6 kPa; D/W < 0.9); Category 2 (EMax < 42.6 kPa; D/W < 0.9); Category 3 (EMax ≥ 42.6 kPa; D/W ≥ 0.9); and Category 4 (EMax < 42.6 kPa; D/W ≥ 0.9). The EMax cutoff value was set using receiver operating characteristic (ROC) curve analysis to predict nodular hyperplasia (NH) vs follicular neoplasm (FN). Cutoff value for nodule D/W ratio was set using ROC curve analysis for malignancy. RESULTS: NH was the most prevalent pathology group in Category 1, FN in Category 2, and papillary thyroid carcinoma in Category 3. Category 3 demonstrated the highest rate of malignancy (81.8%) and had 55.4% sensitivity and 90% specificity for predicting malignancy. When assessing the benign pathology of NH in follicular patterned lesion, Category 1 demonstrated the highest NH prevalence of 88.9% (34/37) and had 73.9% sensitivity and 85.0% specificity. CONCLUSION: The performance for malignancy was highest in Category 3 and predictive ability for benign pathology of NH in follicular lesion was highest in Category 1. The information of EMax and nodule D/W ratio was useful to predict the pathology of thyroid nodules.

8.
Eur J Endocrinol ; 185(5): 707-715, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34519275

RESUMO

OBJECTIVE: Recent studies have reported that thyroid hormone levels are associated with metabolic syndrome (MetS) even in euthyroid subjects. However, the association between thyroid autoimmunity and MetS is uncertain. This study aimed to investigate the relationship between thyroid autoimmunity and MetS in a large cohort study of euthyroid subjects. METHODS: A total of 4775 participants aged ≥19 years from the Korea National Health and Nutrition Examination Survey VI (2013-2015) with anti-thyroid peroxidase antibody (TPOAb) results and normal thyroid functions were included in this study. Subjects were grouped according to thyroid autoimmunity (positivity of TPOAb). We estimated the odds ratios (ORs) for MetS according to TPOAb positivity using logistic regression models, adjusted for potential confounders. RESULTS: Of the study subjects, 25% (n = 1206) were diagnosed with MetS. Subjects with MetS showed higher median TPOAb levels (6.3 vs 6.8 IU/mL, P < 0.001) and higher positivity of TPOAb (5 vs 7%, P = 0.002) than those without MetS. There was a significant difference in prevalence of MetS depending on the TPOAb positivity (25% vs 33%, P = 0.002). Subjects with TPOAb positive had a significantly greater risk of abdominal obesity (OR 1.675, 95% CI: 1.302-2.154, P < 0.001), low high-density lipoprotein cholesterol (OR: 1.603, 95% CI: 1.244-2.066, P < 0.001) and elevated blood pressure (OR: 1.418, 95% CI: 1.099-1.829, P = 0.007) as compared to those with TPOAb negative. Positivity of TPOAb was a significant risk factor for MetS even after adjusting for confounding variables including age, sex, household income, education, smoking, alcohol consumption, walking activity, thyroid-stimulating hormone and free thyroxine (OR: 1.389, 95% CI: 1.048-1.841, P = 0.022). CONCLUSION: In euthyroid subjects, thyroid autoimmunity is associated with MetS. Further large longitudinal studies are needed to clarify causality.


Assuntos
Síndrome Metabólica/epidemiologia , Tireoidite Autoimune/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria , Pressão Sanguínea , HDL-Colesterol/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Razão de Chances , População , República da Coreia/epidemiologia , Fatores de Risco , Fatores Socioeconômicos , Tireoidite Autoimune/complicações , Adulto Jovem
9.
Theranostics ; 11(2): 958-973, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391515

RESUMO

Rationale: Aberrant androgen receptor (AR) signaling via full-length AR (AR-FL) and constitutively active AR variant 7 (AR-V7) plays a key role in the development of castration-resistant prostate cancer (CRPC) and resistance to hormone therapies. Simultaneous targeting of AR-FL and AR-V7 may be a promising strategy to overcome resistance to hormone therapy. This study aimed to identify novel drug candidates co-targeting AR-FL and AR-V7 activities and elucidate their molecular mechanism of anti-CRPC activities. Methods: Using a CRPC cell-based reporter assay system, we screened a small library of antimalarial agents to explore the possibility of repositioning them for CRPC treatment and identified bruceantin (BCT) as a potent anti-CRPC drug candidate. A series of cell-based, molecular, biochemical, and in vivo approaches were performed to evaluate the therapeutic potential and molecular mechanism of BCT in CRPC. These approaches include reporter gene assays, cell proliferation, RNA-seq, qRT-PCR, mouse xenografts, co-immunoprecipitation, GST pull-down, immobilized BCT pull-down, molecular modeling, and bioinformatic analyses. Results: We identified BCT as a highly potent inhibitor co-targeting AR-FL and AR-V7 activity. BCT inhibits the transcriptional activity of AR-FL/AR-V7 and downregulates their target genes in CRPC cells. In addition, BCT efficiently suppresses tumor growth and metastasis of CRPC cells. Mechanistically, BCT disrupts the interaction of HSP90 with AR-FL/AR-V7 by directly binding to HSP90 and inhibits HSP90 chaperone function, leading to degradation of AR-FL/AR-V7 through the ubiquitin-proteasome system. Clinically, HSP90 expression is upregulated and correlated with AR/AR-V7 levels in CRPC. Conclusion: Our findings suggest that BCT could serve as a promising therapeutic candidate against CRPC and highlight the potential benefit of targeting AR-FL/AR-V7-HSP90 axis to overcome resistance caused by aberrant AR-FL/AR-V7 signaling.


Assuntos
Antagonistas de Receptores de Andrógenos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Quassinas/farmacologia , Receptores Androgênicos/química , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Diabetes ; 70(1): 182-195, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33046512

RESUMO

Becn1/Beclin-1 is a core component of the class III phosphatidylinositol 3-kinase required for autophagosome formation and vesicular trafficking. Although Becn1 has been implicated in numerous diseases such as cancer, aging, and neurodegenerative disease, the role of Becn1 in white adipose tissue and related metabolic diseases remains elusive. In this study, we show that adipocyte-specific Becn1 knockout mice develop severe lipodystrophy, leading to adipose tissue inflammation, hepatic steatosis, and insulin resistance. Ablation of Becn1 in adipocytes stimulates programmed cell death in a cell-autonomous manner, accompanied by elevated endoplasmic reticulum (ER) stress gene expression. Furthermore, we observed that Becn1 depletion sensitized mature adipocytes to ER stress, leading to accelerated cell death. Taken together, these data suggest that adipocyte Becn1 would serve as a crucial player for adipocyte survival and adipose tissue homeostasis.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo Branco/metabolismo , Proteína Beclina-1/metabolismo , Resistência à Insulina/genética , Lipodistrofia/metabolismo , Doenças Metabólicas/metabolismo , Animais , Proteína Beclina-1/genética , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Homeostase/genética , Inflamação/genética , Inflamação/metabolismo , Lipodistrofia/genética , Doenças Metabólicas/genética , Camundongos , Camundongos Knockout
11.
Artigo em Inglês | MEDLINE | ID: mdl-33020132

RESUMO

INTRODUCTION: Recent studies have suggested that extracellular circulating and urinary mitochondrial DNA (mtDNA) are associated with mitochondrial dysfunction in obesity and type 2 diabetes mellitus (T2DM). However, the changes to cell-free serum and urinary mtDNA after bariatric surgery in patients with obesity with T2DM have not been investigated to date. RESEARCH DESIGN AND METHODS: We prospectively recruited patients with obesity (n=18), and with obesity and T2DM (n=14) who underwent bariatric surgery, along with healthy volunteers (HV) as a control group (n=22). Serum and urinary mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) copy numbers were measured using quantitative PCR (qPCR). The mtDNA copy numbers of patients with obesity (with and without T2DM) were followed up 6 months after surgery. RESULTS: The copy numbers of urinary mtND-1 and mtCOX-3 in patients with obesity, with or without T2DM, were higher than those in the HVs. Moreover, urinary mtCOX-3 copy number increased in patients with obesity with T2DM compared with patients with obesity without T2DM (p=0.018). Meanwhile, serum mtCOX-3 copy numbers in HV were higher in both obesity patient groups (p=0.040). Bariatric surgery reduced urinary mtND-1 and mtCOX-3 copy numbers, as well as serum mtCOX-3 copy numbers only in patients with obesity with T2DM. CONCLUSION: These results suggest that T2DM induces greater kidney mitochondrial dysfunction in patients with obesity, which can be effectively restored with bariatric surgery.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Humanos , Mitocôndrias , Obesidade/complicações , Obesidade/genética , Obesidade/cirurgia
12.
PLoS One ; 15(8): e0236881, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745107

RESUMO

PIERCE1, p53 induced expression 1 in Rb null cells, is a novel p53 target involved in the DNA damage response and cell cycle in mice. These facts prompted us to study the function of PIERCE1 with respect to p53-associated pathophysiology of cancer in humans. Unexpectedly, PIERCE1 did not respond to overexpression and activation of p53 in humans. In this study, we swapped p53 protein expression in human and mouse cells to find the clue of this difference between species. Human p53 expression in mouse cells upregulated PIERCE1 expression, suggesting that p53-responsive elements on the PIERCE1 promoter are crucial, but not the p53 protein itself. Indeed, in silico analyses of PIERCE1 promoters revealed that p53-responsive elements identified in mice are not conserved in humans. Consistently, chromatin immunoprecipitation-sequencing (ChIP-seq) analyses confirmed p53 enrichment against the PIERCE1 promoter region in mice, not in human cells. To complement the p53 study in mice, further promoter analyses suggested that the human PIERCE1 promoter is more similar to guinea pigs, lemurs, and dogs than to rodents. Taken together, our results confirm the differential responsiveness of PIERCE1 expression to p53 due to species differences in PIERCE1 promoters. The results also show partial dissimilarity after p53 induction between mice and humans.


Assuntos
Proteínas de Ciclo Celular , Elementos de Resposta/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Dano ao DNA/genética , Humanos , Camundongos , Regiões Promotoras Genéticas , Transcrição Gênica/fisiologia
13.
Oncogene ; 39(36): 5876-5887, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32728173

RESUMO

KRAS-mutant non-small cell lung cancer (NSCLC) is a major lung cancer subtype that leads to many cancer-related deaths worldwide. Although numerous studies on KRAS-mutant type NSCLC have been conducted, new oncogenic or tumor suppressive genes need to be detected because a large proportion of NSCLC patients does not respond to currently used therapeutics. Here, we show the tumor-promoting function of a cell cycle-related protein, PIERCE1, in KRAS-mutant NSCLC. Mechanistically, PIERCE1 depletion inhibits cell growth and AKT phosphorylation (pAKT) at S473, which is particularly observed in KRAS-mutant lung cancers. Analyses of AKT-related genes using microarray, immunoblotting, and real-time quantitative PCR indicated that PIERCE1 negatively regulates the gene expression of the AKT suppressor, TRIB3, through the CHOP pathway, which is a key regulatory pathway for TRIB3 expression. Similarly, in vivo analyses of PIERCE1 depletion in the KRAS mutation-related lung cancer mouse models revealed the suppressive effect of PIERCE1 knockout in urethane- and KRASG12D-induced lung tumorigenesis with decreased pAKT levels observed in the tumors. Tissue microarrays of human lung cancers indicated the expression of PIERCE1 in 83% of lung cancers and its correlation with pAKT expression. Thus, we illustrate how PIERCE1 depletion may serve as a therapeutic strategy against KRAS-mutant NSCLC and propose the clinical benefit of PIERCE1.


Assuntos
Proteínas de Ciclo Celular/deficiência , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Mutação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Transdução de Sinais , Animais , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Knockout , Modelos Biológicos , Prognóstico
14.
Exp Anim ; 69(4): 414-422, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-32581195

RESUMO

Colorectal cancer is the second most lethal cancer type across all ages and sexes, the many mechanisms of which are still currently being further elucidated. PIERCE1 has been known to be involved in the cell cycle and proliferation, the expression of which is regulated by stress conditions in a p53-dependent manner. Through a database search, we found that PIERCE1 was significantly augmented in patients with colorectal carcinoma compared to normal samples, suggesting its possible role in tumor regulation. Recently, PIERCE1 has also been reported to increase proliferation of a liver cancer cell line, indicating its possible role as an oncogene. To examine its relevance to tumorigenesis, such as whether it has either oncogenic or tumor suppressive function, PIERCE1 was knocked down and overexpressed in several colorectal cancer cell lines and mice, respectively. To evaluate the roles of Pierce1 in vivo, we established a Pierce1 transgenic (TG) mouse model and then administered azoxymethane with dextran sodium sulfate (DSS) to induce colorectal carcinogenesis via promoting mutations in Apc and Kras. Nonetheless, PIERCE1 depletion in these cell lines showed no significant change in cell growth. AOM/DSS-treated Pierce1 TG mice were comparable with respect to colon lengths, the number of polyps, and tumor sizes to those of the control mice. These results implicate that PIERCE1 does not play an oncogenic or tumor suppressive role in AOM/DSS-induced colorectal cancer.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Neoplasias Colorretais/genética , Expressão Gênica , Animais , Azoximetano/efeitos adversos , Ciclo Celular/genética , Proteínas de Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/patologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos Transgênicos , Proteína Supressora de Tumor p53/fisiologia
15.
J Neurosci Nurs ; 52(5): 234-238, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32568810

RESUMO

PURPOSE: The aim of this study was to evaluate the effectiveness of evidence-based guidelines for fever management of critically ill adult patients with brain injury. METHODS: We used a pretest-posttest design with 48 patients 19 years or older admitted to an intensive care unit after surgery for brain injury. We applied evidence-based guidelines only to an experimental group of 24 patients and compared with 24 control patients who did not receive evidence-based guidelines. Experimental and control groups were matched 1:1 using the Acute Physiology and Chronic Health Evaluation II score. Data included the proportion of patients with reduced fever and time to normalized temperature. RESULTS: The proportion of patients whose temperature fell to normal after fever was 4.5 times higher in the experimental group than in the control group. The time it took the patients' highest fever to fall to normal during their intensive care unit stay was 4.84 times faster in the experimental group than in the control group (hazard ratio, 4.84; 95% confidence interval, 1.79-13.11; P = .002). CONCLUSION: Evidence-based guidelines for fever management in patients with a brain injury can be used in nursing practice with rapid response, improving healthcare efficiency and contributing to better outcomes for critically ill patients.


Assuntos
Lesões Encefálicas/complicações , Estado Terminal , Medicina Baseada em Evidências , Febre , Guias como Assunto , Lesões Encefálicas/cirurgia , Feminino , Febre/enfermagem , Febre/terapia , Mortalidade Hospitalar , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
16.
Acta Radiol ; 61(12): 1628-1635, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32138522

RESUMO

BACKGROUND: Although uncommon, intra-parotid lymph node (IPLN) metastasis should be considered in the differential diagnosis of parotid masses in patients with head and neck cancers. PURPOSE: To compare the clinical and imaging features of IPLN metastases from head and neck cancers and simultaneous parotid primary tumors. MATERIAL AND METHODS: A retrospective review of 2199 patients with non-parotid head and neck cancers revealed 63 patients who also underwent parotidectomy during curative resection of head and neck cancer. After exclusion of direct extension to the parotid gland from adjacent primary tumors (n = 12) and IPLN metastases from skin cancer (n = 5), the final study group was composed of 46 patients, including 26 (1.2%) with 33 IPLN metastases and 20 (0.9%) with 24 simultaneous parotid primary tumors. We compared clinical features of patients (sex, age, site of primary tumor, histologic type, history of prior treatment for malignancy, TNM stages, side of parotid lesion, multiplicity, and metastasis in ipsilateral cervical LNs) and the CT (location in parotid gland, maximum dimension, margins, and central necrosis or cystic change) and 18F-FDG PET/CT (maximum standardized uptake value) findings. RESULTS: Ipsilateral level II LN metastasis was more frequent in the IPLN metastasis group than in the simultaneous parotid primary tumor group (73.1% vs. 35.0%, P < 0.05). Imaging features such as location in parotid gland, maximum dimension, margins, central necrosis or cystic change, and maximum standardized uptake value showed no significant differences between the two groups. CONCLUSION: CT and PET/CT findings of IPLN metastasis are indistinguishable from simultaneous parotid primary tumor in patients with head and neck cancers.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Neoplasias Parotídeas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/cirurgia , Compostos Radiofarmacêuticos , Estudos Retrospectivos
17.
BMC Cancer ; 20(1): 118, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32050941

RESUMO

BACKGROUND: Although shear wave elastography (SWE) is reported to be useful in detecting malignant thyroid nodules, it shows a wide range of cut-off values of elasticity index (EI) in detecting malignant nodules. The cause of discrepancy remains unclear. Fibrosis of the tumors is known to increase the EI in SWE, and matching of SWE and surgical histopathology has not been fully illustrated in thyroid cancer. We aimed to evaluate the reproducibility of the new total nodular region of interest (ROI) method excluding the subjective features of focal circular ROI placement and to determine the lesion that causes the elevation of EI on SWE and on histopathology. METHODS: A total of 29 thyroid cancers from 28 patients were included. We evaluated the reproducibility of EI in the new total nodular ROI using Q-Box Trace program and compared the EI in focal nodular ROI using a 3-mm circular area. We analyzed the correlation between fibrosis and EI. RESULT: The coefficient of variation (CV) of the intrarater assay was significantly lower in total nodular ROI than in focal nodular ROI within the image in rater 1 (1.7% vs. 13.4%, p < 0.001) and in rater 2 (1.4% vs. 16.9%, p < 0.001) and in different images in rater 1 (7.6% vs. 12.3%, p = 0.040) and in rater 2 (7.5% vs. 19.8%, p = 0.004). Moreover, CV of the interrater assay showed similar results (14.9% vs. 19%, p = 0.030). Interrater intraclass correlation coefficient showed better agreement in total nodular ROI than in focal nodular ROI (0.863 vs. 0.783). The degree of fibrosis on histopathology showed significant correlations with EI (EMean, p < 0.001; EMax, p = 0.027), and the location of fibrosis was concordant with the high EI area on SWE. CONCLUSION: Our study revealed that the new total nodular ROI method showed higher reproducibility and better agreement in intra- and interrater assay than the focal nodular ROI method, suggesting a valuable and standardized method in clinical practice. Moreover, our results showed that fibrosis in the histopathology increased EI on SWE and might lead to the discrepancy of the cut-off values in detecting thyroid cancer.


Assuntos
Técnicas de Imagem por Elasticidade , Elasticidade , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico , Biópsia , Técnicas de Imagem por Elasticidade/métodos , Técnicas de Imagem por Elasticidade/normas , Feminino , Fibrose , Humanos , Masculino , Reprodutibilidade dos Testes , Ultrassonografia
18.
Eur Radiol ; 30(4): 2152-2160, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31844961

RESUMO

OBJECTIVE: To assess the diagnostic accuracy of 256-row multislice computed tomographic angiography (CTA) compared with three-dimensional rotational angiography (3DRA) in the postoperative evaluation of cerebral aneurysms treated with titanium clips. METHODS: A total of 128 patients (42 men, 86 women; mean age, 57.6 years) with 143 cerebral aneurysms treated using titanium clips underwent both CTA and 3DRA. Two reviewers retrospectively evaluated the following parameters on CTA and 3DRA: (1) residual/recurrent aneurysm (absent or present), (2) patency of parent artery (patent or occluded/severe stenotic (> 70%)), and (3) patency of adjacent branch (patent or occluded/absent). RESULTS: A total of 24 residual/recurrent aneurysms were detected by 3DRA. The sensitivity, specificity, and accuracy of CTA for the detection of residual/recurrent aneurysms were 83.3%, 100%, and 97.2% for reviewer 1 and 79.2%, 100%, and 96.5% for reviewer 2, respectively. The sensitivity, specificity, and accuracy of CTA for the evaluation of patency of parent artery were 100%, 100%, and 100%, respectively, for both reviewers. The sensitivity, specificity, and accuracy of CTA for evaluation of the patency of adjacent branch were 85.1%, 100%, and 92.3% for reviewer 1 and 82.4%, 100%, and 90.9% for reviewer 2, respectively. CONCLUSION: A 256-row multislice CTA is a valuable non-invasive tool for assessment of cerebral aneurysms treated with titanium clips. KEY POINTS: • A 256-row multislice CTA is an accurate imaging technique for the postoperative assessment of cerebral aneurysms treated with titanium clips. • Sensitivity of CTA for the detection of residual/recurrent aneurysms was 79-83% compared with 3DRA. • CTA is still limited in detecting residual/recurrent aneurysms of < 2 mm and small adjacent branches.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento Tridimensional/métodos , Aneurisma Intracraniano/diagnóstico , Tomografia Computadorizada Multidetectores/métodos , Titânio , Procedimentos Cirúrgicos Vasculares/instrumentação , Adulto , Angiografia Cerebral/métodos , Feminino , Humanos , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório , Reprodutibilidade dos Testes , Estudos Retrospectivos , Instrumentos Cirúrgicos
19.
Korean J Intern Med ; 34(4): 850-857, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29466846

RESUMO

BACKGROUND/AIMS: The aim of this study was to address the role of the elasticity index as a possible predictive marker for detecting papillary thyroid carcinoma (PTC) and quantitatively assess shear wave elastography (SWE) as a tool for differentiating PTC from benign thyroid nodules. METHODS: One hundred and nineteen patients with thyroid nodules undergoing SWE before ultrasound-guided fine needle aspiration and core needle biopsy were analyzed. The mean (EMean), minimum (EMin), maximum (EMax), and standard deviation (ESD) of SWE elasticity indices were measured. RESULTS: Among 105 nodules, 14 were PTC and 91 were benign. The EMean, EMin, and EMax values were significantly higher in PTCs than benign nodules (EMean 37.4 in PTC vs. 23.7 in benign nodules, p = 0.005; EMin 27.9 vs. 17.8, p = 0.034; EMax 46.7 vs. 31.5, p < 0.001). The EMean, EMin, and EMax were significantly associated with PTC with diagnostic odds ratios varying from 6.74 to 9.91, high specificities (86.4%, 86.4%, and 88.1%, respectively), and positive likelihood ratios (4.21, 3.69, and 4.82, respectively). The ESD values were significantly higher in PTC than in benign nodules (6.3 vs. 2.6, p < 0.001). ESD had the highest specificity (96.6%) when applied with a cut-off value of 6.5 kPa. It had a positive likelihood ratio of 14.75 and a diagnostic odds ratio of 28.50. CONCLUSION: The shear elasticity index of ESD, with higher likelihood ratios for PTC, will probably identify nodules that have a high potential for malignancy. It may help to identify and select malignant nodules, while reducing unnecessary fine needle aspiration and core needle biopsies of benign nodules.


Assuntos
Técnicas de Imagem por Elasticidade , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Adulto , Idoso , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia
20.
J Neurointerv Surg ; 11(5): 528-532, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30538146

RESUMO

BACKGROUND AND PURPOSE: Alternative metrics (altmetrics), based on mentions in online media, is a new tool that can help to identify the most influential articles to diverse public audiences. This article aimed to determine the 100 most mentioned articles in the field of neurointervention and to analyze their characteristics. MATERIALS AND METHODS: We selected the 808 journals that were considered journals potentially publishing articles on neurointervention. We also selected articles using keywords. Using the Altmetric.com search tool, we identified the 101 most mentioned neurointervention articles based on the highest altmetric attention scores (AASs) within selected journals and articles. Each article was evaluated for several characteristics including AAS, number of citations, journal title, journal category, impact factor of the journal, year of publication, authorship, country, type of document, and topic. RESULTS: The AASs for the top 101 articles ranged from 1586 to 39. Stroke published the largest number of articles (19.8%) followed by the New England Journal of Medicine (17.8%). The majority of articles were published in multidisciplinary journals (38.6%), were published in 2017-2018 (43.6%), originated from the USA (54.5%), were original articles (66.3%), and dealt with intra-arterial thrombolysis or thrombectomy for acute ischemic stroke (58.4%). Tudor G Jovin was the most prolific author, authoring 18 of the most mentioned neurointervention articles CONCLUSIONS: This study presents a detailed list of the 101 most mentioned neurointervention articles in online media, thus providing useful information on the dissemination of neurointervention research to the general public.


Assuntos
Bibliometria , Neurocirurgia/estatística & dados numéricos , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Embolização Terapêutica , Internet , Fator de Impacto de Revistas , Publicações Periódicas como Assunto , Trombectomia
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