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1.
Phytomedicine ; 69: 153198, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32151917

RESUMO

BACKGROUND: Induced pluripotent stem cells (iPSCs) are regarded as the best potential cell source for cell-based regenerative medicine. To develop a safe and efficient iPSC-based cell therapy, it is very important to avoid possible teratoma formation, which can arise from undifferentiated iPSCs (USCs) remaining among differentiated cell products. Dried bark of Magnolia officinalis (Magnolia cortex, MC) has long been used in traditional medicine to treat gastrointestinal ailments and allergic diseases, and has shown have various pharmacological activities, including anti-bacterial, anti-inflammatory, and anti-cancer effects. However, its effects on iPSCs have not yet been examined. PURPOSE: In this study, we investigated the selective cytotoxic effects of ethanol extract of MC (EEMC) on undifferentiated iPSCs and elucidated the underlying apoptotic mechanisms in detail. We also investigated the inhibitory effects of EEMC on teratoma formation via in ovo experiments. RESULTS: We found that EEMC greatly reduced cell growth and induced apoptotic cell death in USCs, but not in differentiated or normal cells. EEMC caused G2/M cell cycle arrest, mitochondrial damage, and caspase activation of USCs, accompanied by p53 accumulation. In p53KO human iPSCs, EEMC had no cytotoxicity, reinforcing that EEMC-mediated apoptosis of USCs is p53-dependent. EEMC did not cause DNA damage in iPSC-derived differentiated cells. In ovo teratoma formation assay revealed that EEMC treatment before injection efficiently eliminated USCs and prevented teratoma formation. CONCLUSIONS: These results collectively indicate that EEMC has potent anti-teratoma activity, and therefore can be used for the development of safe iPSC-based therapy.

2.
Nutrients ; 12(3)2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32182802

RESUMO

Induced pluripotent stem cells (iPSCs) have similar properties to embryonic stem cells in terms of indefinite self-renewal and differentiation capacity. After in vitro differentiation of iPSCs, undifferentiated iPSCs (USCs) may exist in cell therapy material and can form teratomas after in vivo transplantation. Selective elimination of residual USCs is, therefore, very important. Prunellae Spica (PS) is a traditional medicinal plant that has been shown to exert anti-cancer, antioxidant, and anti-inflammatory activities; however, its effects on iPSCs have not been previously characterized. In this study, we find that ethanol extract of PS (EPS) effectively induces apoptotic cell death of USCs through G2/M cell cycle arrest, generation of intracellular reactive oxygen species, alteration of mitochondrial membrane potentials, and caspase activation of USCs. In addition, EPS increases p53 accumulation and expression of its downstream targets. In p53 knockout (KO) iPSCs, the EPS did not induce apoptosis, indicating that EPS-mediated apoptosis of USCs was p53-dependent. In addition, EPS was not genotoxic towards iPSCs-derived differentiated cells. EPS treatment before injection efficiently prevented in ovo teratoma formation of p53 wild-type (WT) iPSCs but not p53KO iPSCs. Collectively, these results indicate that EPS has potent anti-teratoma activity and no genotoxicity to differentiated cells. It can, therefore, be used in the development of safe and efficient iPSC-based cell therapies.

3.
Endocrinol Metab (Seoul) ; 35(1): 188-191, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32207279

RESUMO

X-linked adrenoleukodystrophy (X-ALD) occurs due to mutations in the ABCD1 gene that encodes the peroxisomal membrane protein peroxisomal transporter ATP-binding cassette sub-family D member 1 (ABCD1). Degradation of very long-chain fatty acids in peroxisomes is impaired owing to ABCD dysfunction, subsequently leading to adrenomyeloneuropathy, cerebral adrenoleukodystrophy, and adrenal insufficiency. X-ALD frequently induces idiopathic Addison's disease in young male patients. Here, we confirmed the diagnosis of X-ALD in a young male patient with primary adrenal insufficiency, and identified a novel ABCD1 gene mutation (p.Trp664*, c.1991 G>A).

4.
PLoS One ; 15(1): e0227012, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929538

RESUMO

Temporal trends of the prevalence and incidence of hypertrophic cardiomyopathy (HCM) have not been well established in Asian populations. Using the Korean National Health Insurance Services database, we identified patients with a confirmed diagnosis of HCM between 2010 and 2016. The annual prevalence and incidence of HCM, and their clinical characteristics were investigated. The prevalence of HCM has increased from 0.016% (n = 6313) in 2010 to 0.031% (n = 13,035) in 2016. During a 7-year period, 13,229 patients were newly diagnosed with HCM. The incidence rate increased from 4.15 (per 100,000 person-years) in 2010 to 5.6 in 2016. The prevalence and incidence of HCM increased with age and peaked during the 70s, with male predominance in all age groups. Chest pain is the most frequent clinical presentation followed by shortness of breath and syncope. Hypertension and dyslipidemia were the two most common comorbidities. Heart failure and atrial fibrillation was diagnosed in about 1/3 and 1/4 of patients with HCM, respectively. The prevalence and incidence of HCM gradually increased from 2010 to 2016, possibly due to heightened recognition of the disease. Given the progressively high incidence of HCM with age and high prevalence of coexisting modifiable risk factors, continued efforts are required to increase awareness regarding HCM-related symptoms and potential complications.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31958303

RESUMO

OBJECTIVE: To compare the efficacy and safety of an initial triple therapy using metformin, a dipeptidyl peptidase-4 (DPP4) inhibitor, and thiazolidinedione with a stepwise approach using sulfonylurea and metformin in new-onset, drug-naïve patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Among drug-naïve patients with 9.0%-12.0% glycated hemoglobin (HbA1c) but no hyperglycemic symptoms, 100 subjects who started triple medications (metformin 1000 mg/day, sitagliptin 100 mg/day, and lobeglitazone 0.5 mg/day) were selected as an initial triple therapy group. Age and body mass index-matched subjects (n=100) who started glimepiride (≥2 mg/day with uptitration) and metformin (≥1000 mg/day with uptitration) were selected as a conventional therapy group. We investigated changes in HbA1c level, dynamic indexes for insulin sensitivity and ß-cell function, and hypoglycemia. RESULTS: After 12 months of treatment, HbA1c levels decreased significantly in both groups: from 10.7%±1.0% to 6.7%±1.3% in the triple group, and from 10.5%±1.0% to 7.3%±1.2% in the conventional therapy group. At 12 months, achievement of the HbA1c target (<7.0%) was higher in the triple group than in the conventional group (70% vs 52%, p<0.01). Dynamic indexes related to ß-cell function and insulin sensitivity improved, and albuminuria reduced significantly only in the triple group. Hypoglycemia was more common in the conventional group. CONCLUSIONS: Initial triple combination therapy with the DPP4 inhibitor, metformin, and thiazolidinedione showed a higher achievement of the target HbA1c goal with a lower risk of hypoglycemia, better restoration of ß-cell function, and multiple metabolic benefits, implying durable glycemic control. This strategy may be useful for patients presenting with type 2 diabetes and high HbA1c levels.

6.
J Neurol ; 267(2): 513-521, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31691020

RESUMO

BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a neurodegenerative disorder characterized by deposition of intraneural inclusion bodies in the brain as well as the enteric nervous system. Emerging concepts regarding the brain-gut axis have been proposed for neurological disorders. Thus, the present study investigated the associations between colectomy and developing PD. METHODS: We conducted a retrospective cohort study using National Health Insurance Service-National Sample Cohort of Korea. This study included patients who underwent colectomy during 2003-2009, and up to 10 individuals per patient, matched in terms of age and sex, who did not undergo colectomy. The colectomy group was subdivided by the causes and surgical methods of colectomy. The risk of PD occurrence was evaluated over a follow-up period of at least 6 years using Cox regression analyses. RESULTS: Colectomy was associated with a higher risk of developing PD (adjusted hazard ratio [HR]: 1.962; 95% confidence interval [CI] 1.002-3.840). There was no significant difference in the occurrence of PD among the subgroups classified by the causes or surgical methods of colectomy. CONCLUSIONS: Colectomy was associated with the development of PD, suggesting that colon issues play an important role in the pathophysiological mechanisms of PD.

7.
Epilepsy Behav ; 102: 106719, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31805508

RESUMO

PURPOSE: The purpose of this study was to evaluate differences in stigma, disclosure management of epilepsy, and knowledge about epilepsy between patients with epilepsy who recognized and did not recognize the new Korean term for epilepsy. METHODS: This was a cross-sectional, multicenter study. The Stigma Scale-Revised, the Disclosure Management Scale, the Patient Health Questionnaire-9, and a questionnaire assessing knowledge about epilepsy were used. The set of questionnaires had two versions, using either the old or new name for epilepsy. Multivariate logistic regression analyses were used. RESULTS: A total of 341 patients with epilepsy and 509 family members were recruited. Approximately 62% of patients felt some degree of epilepsy-related stigma. Mild stigma, severe concealment of epilepsy diagnosis, and increased knowledge about epilepsy were independently identified as factors associated with recognition of the new term in patients. Recognition of the new term was more prevalent in patients and family members with higher education, female family members, and family members having patients with younger age at seizure onset and shorter duration of epilepsy. There were no significant differences between the two types of questionnaires. About 81% of patients and 93% of family members had a positive attitude about renaming epilepsy. CONCLUSION: The use of the new Korean term for epilepsy (cerebroelectric disorder) increased knowledge about epilepsy but did not reduce stigma and concealment of epilepsy diagnosis in Korean adults with epilepsy. Higher education may be an important factor for knowing the new term in patients and family members.

8.
Sci Rep ; 9(1): 18055, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792292

RESUMO

Although chronic kidney disease is known to increase the risk of atrial fibrillation (AF), the impact of the variability of renal function on the risk of incident AF is unknown. We aimed to evaluate the association between variability of renal function and the risk of developing AF among the general population. We evaluated a total of 3,551,249 adults who had three annual health check-ups provided by the National Health Insurance Service. The variability of renal function was defined as GFR-VIM, which is variability independent of the mean (VIM) of creatinine-based estimated glomerular filtration rate (eGFR). The study population was divided into four groups (Q1-4) based on the quartiles of GFR-VIM, and the risks of incident AF by each group were compared. During a mean of 3.2 ± 0.5 years follow-up, incident AF occurred in 15,008 (0.42%) subjects. The incidence rates of AF increased from Q1 to Q4 (0.98, 1.42, 1.27, and 1.63 per 1,000 person-years, respectively). Adjusting with multiple variables, Q4 showed an increased risk of incident AF compared to Q1 (hazard ratio (HR) 1.125, 95% confidence interval (CI) 1.071-1.181). Variability of serum creatinine or other definitions of variability showed consistent results. On subgroup analyses, Q4 in males or those with a decreasing trend of eGFR had significantly increased risks of incident AF compared to Q1 (HR 1.127, 95% CI 1.082-1.175; and HR 1.115, 95% CI 1.059-1.173, respectively). High variability of eGFR was associated with an increased risk of incident AF, particularly in males or those with decreasing trends of eGFR during follow-up.

9.
Am J Cardiol ; 124(12): 1881-1888, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31668346

RESUMO

The relation of progression of type 2 diabetes and detailed fasting glucose level with risk of atrial fibrillation (AF) is not well known. A total of 6,199,629 subjects not diagnosed with AF who underwent health check-up in 2009 were included from the Korean National Health Insurance Service database. Risk of AF was compared among subjects with normal fasting glucose (NFG), subjects with impaired fasting glucose (IFG), patients with diabetes duration <5 years (early diabetes mellitus [DM]), and patients with diabetes duration ≥5 years (late DM). Next, risk of AF stratified by fasting glucose level per 10 mg/dL was assessed. During a mean follow-up of 7.2 years, the risk of AF significantly increased across the time course of type 2 diabetes (adjusted hazard ratio (aHR) 1.04, 95% confidence interval (CI) 1.02 to 1.05 for IFG; aHR 1.06, 95% CI 1.04 to 1.08 for early DM; aHR 1.09, 95% CI 1.07 to 1.11 for late DM). The risk of AF was significantly higher in subjects who progressed to type 2 diabetes in the IFG group. Risk of AF increased with a 10 mg/dL increment of fasting blood glucose (p-for-trend <0.0001). However, there was a U-shape relationship between fasting blood glucose and risk of AF in those who received antidiabetic medication. In conclusion, the risk of AF increased with the time course of type 2 diabetes. However, low blood glucose in antidiabetic medication user was associated with an increased risk of AF.

10.
Epilepsy Behav ; 101(Pt A): 106569, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31675602

RESUMO

PURPOSE: The aim of this study was to examine social anxiety in South Korean adults with epilepsy and to identify associated factors. METHOD: This was a cross-sectional, multicenter study in South Korea. Social anxiety was assessed using short forms of the Social Phobia Scale (SPS-6) and Social Interaction Anxiety Scale (SIAS-6). The SPS-6 scores ≥9 and SIAS-6 scores ≥12 were considered indicative of social phobia and social interaction anxiety, respectively. The Patient Health Questionnaire-9 (PHQ-9); Stigma Scale-Revised (SS-R); Disclosure Management Scale; Family Adaptation, Partnership, Growth, Affection, Resolve (F-APGAR) scale; and a questionnaire assessing knowledge about epilepsy were also used. RESULTS: Of a total of 219 patients with epilepsy, 21% and 11% had SPS-6 scores ≥9 and SIAS-6 scores ≥12, respectively. In logistic regression analysis, SPS-6 scores ≥9 were independently associated with SS-R scores of 4-9 (odds ratio [OR]: 8.626, 95% confidence interval [CI]: 2.515-29.587, p = .001), SS-R scores 1-3 (OR: 5.496, 95% CI: 1.757-17.197, p = .003), and PHQ-9 scores ≥10 (OR: 4.092, 95% CI: 1.823-9.185, p = .001). In contrast, SIAS-6 scores ≥12 were related only to PHQ-9 scores ≥10 (OR: 8.740, 95% CI: 3.237-23.599, p < .001). Belonging to a dysfunctional family and lack of knowledge about epilepsy tended to be associated with social phobia (p = .071) and social interaction anxiety (p = .090), respectively. Epilepsy-related variables were not related to social anxiety. CONCLUSION: Social anxiety is not rare in patients with epilepsy. In this study, social phobia was associated with perceived stigma and depressive symptoms, whereas social interaction anxiety was related only to depressive symptoms in patients with epilepsy.

11.
Stem Cell Res ; 41: 101649, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31731184

RESUMO

Mutations in leucine-rich repeat kinase 2 (LRRK2) gene (LRRK2 G2019S) is a representative autosomal dominant mutation that can cause Parkinson's disease (PD). A bacterial artificial chromosome-based homologous recombination (BAC-based HR) system was utilized for gene therapy of LRRK2 G2019S-mutant induced pluripotent stem cells (iPSCs) produced by reprogramming episomal vectors. The gene-corrected iPSCs retained typical pluripotency required for their spontaneous differentiation into differentiated cells. The iPSCs had a normal karyotype and were confirmed to have no off-target sites by melting curve analysis.

12.
J Cardiovasc Electrophysiol ; 30(12): 2782-2789, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31637795

RESUMO

INTRODUCTION: The left atrium (LA), including the pulmonary vein antrum, is the main target of catheter ablation for atrial fibrillation (AF). However, there is a lack of data on the effect of extensive LA ablation on LA stiffness. This study sought to investigate the impact of extensive LA ablation on LA stiffness and dyspnea after the restoration of sinus rhythm. METHODS: In total, 97 patients with AF (80 patients who only underwent pulmonary vein isolation [PVI] and 17 patients who underwent extensive LA ablation) were investigated. Extensive LA ablation was defined as PVI plus at least two sets of LA linear-line ablation. LA stiffness was estimated using the ratio of E/e' to global longitudinal LA strain, as measured by echocardiography. The clinical outcomes we evaluated were AF recurrence and composite dyspnea, which we defined as newly prescribed diuretics or hospitalization for heart failure. RESULTS: Patients were 59.3 ± 10.0 years old on average, and 68 (70.1%) were male. There were no significant differences in baseline characteristics or echocardiographic parameters before ablation between the two groups. After ablation, LA stiffness was higher in the extensive ablation group compared with that in the PVI group (0.9 ± 0.6 vs 0.5 ± 0.3, respectively, P = .017). Multivariable linear regression analysis showed that extensive ablation increased LA stiffness (ß = 0.363, P < .001). AF recurrence was similar in both groups; however, composite dyspnea outcomes were worse in the extensive ablation group (P = .003). CONCLUSION: Extensive LA ablation was associated with a worsening of LA stiffness. This might explain dyspnea despite the successful restoration of sinus rhythm.

14.
Int J Cardiol ; 293: 153-158, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31253527

RESUMO

BACKGROUND: This study examined the effects of variability of four metabolic parameters, namely systolic blood pressure (BP), body mass index (BMI), fasting blood glucose (FBG), and total cholesterol level (TC) on the risk of HF. The effects of metabolic parameter variability on the risk of heart failure (HF) remain unclear. METHODS: We studied individuals aged ≥40 years who had undergone ≥3 health check-ups under the Korean National Health Insurance Corporation during 2009 and 2012, and those who did not have hypertension, diabetes, or dyslipidemia. BP, BMI, FBG, and TC were measured at every visit. We defined the variability of each parameter using the variability independent of the mean (VIM) method. VIMs were categorized into four groups according to quartiles. The metabolic variability (MV) score for each subject was defined as the number of VIMs in the highest quartile. RESULTS: Among the 3,820,191 subjects, 17,253 (0.45%) had incident HF during a mean 5.3 ±â€¯1.1 years of follow-up. High variability of each parameter was associated with increased HF risk, which increased according to the MV score. After multivariable adjustment, compared to subjects with MV score = 0, subjects with MV score = 1-4 had an increased risk of HF (adjusted HR [95% CI], 1.15 [1.10-1.19] for MV score = 1, 1.33 [1.28-1.39] for MV score = 2, 1.48 [1.40-1.57] for MV score = 3, 1.74 [1.55-1.96] for MV score = 4 [p-for-trend ≪0.0001]). CONCLUSIONS: High variability of BP, BMI, FBG, and TC was synergistically associated with a higher incidence of new-onset HF.

15.
Cardiovasc Diabetol ; 18(1): 32, 2019 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-30876421

RESUMO

The authors have retracted this article [1] because they have identified serious errors in their data analysis which change the conclusions of their study. All authors agree with this retraction.

16.
PLoS One ; 14(3): e0211766, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30845196

RESUMO

BACKGROUND AND OBJECTIVE: Elderly patients with atrial fibrillation (AF) are known to have a high risk of stroke and bleeding. We investigated the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in octogenarian patients with non-valvular AF compared with warfarin. METHODS: A total of 687 octogenarian patients with AF who were administered NOACs (n = 403) or warfarin (n = 284) for stroke prevention between 2012 and 2016 were included. Thromboembolic (TE) events (stroke or systemic embolism), major bleeding events, and all-cause death were analyzed. RESULTS: The NOACs group (age 83.4±3.2 years, women 52.4%, CHA2DS2-VASc score 5.0±1.8) comprised 141 dabigatran, 158 rivaroxaban, and 104 apixaban users. Most patients from the NOACs group had been prescribed a reduced dose of medication (85.6%). During 14±18 months of follow-up periods, there were 19 TE events and 18 major bleeding events. Patients with NOAC showed a lower risk of TE (1.84 vs. 2.71 per 100 person-years, hazard ration [HR] 0.134, 95% confidence interval [CI] 0.038-0.479, P = 0.002), major bleeding (1.48 vs. 2.72 per 100 person-years, HR 0.110, 95% CI 0.024-0.493, P = 0.001), and all-cause death (2.57 vs. 3.50 per 100 person-years, HR 0.298, 95% CI 0.108-0.824, P = 0.020). CONCLUSION: In octogenarian Asian patients with AF, NOACs might be associated with lower risks of thromboembolic events, major bleeding, and all-cause death than warfarin. Although most patients had received reduced doses, on-label use of NOACs was effective and safe.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Administração Oral , Idoso de 80 Anos ou mais , Fibrilação Atrial/epidemiologia , Dabigatrana/uso terapêutico , Feminino , Seguimentos , Hemorragia/epidemiologia , Humanos , Masculino , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Estudos Retrospectivos , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento , Varfarina/uso terapêutico
17.
J Am Heart Assoc ; 8(5): e011002, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30813812

RESUMO

Background Total atherosclerosis disease burden is associated with clinical outcomes in patients with coronary artery disease. However, the influence of sex on the relationship between total anatomical and physiologic disease burdens and their prognostic implications have not been well defined. Methods and Results A total of 1136 patients who underwent fractional flow reserve (FFR) measurement in all 3 major coronary arteries were included in this study. Anatomical and physiologic total disease burden was assessed by SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score, residual SYNTAX score, a total sum of FFR in 3 vessels (3-vessel FFR), and functional SYNTAX score. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization at 2 years. There were no differences in angiographic diameter stenosis, SYNTAX score, or residual SYNTAX score between women and men. However, both per-vessel FFR (0.89±0.10 versus 0.87±0.11, P<0.001) and 3-vessel FFR (2.72±0.13 versus 2.69±0.15, P<0.001) were higher in women. Multivariable Cox regression analyses showed that total anatomical and physiologic disease burdens were significantly associated with 2-year major adverse cardiac events, and there was no significant interaction between sex and total disease burden for clinical outcomes. Conclusions Despite similar angiographic disease severity, both per-vessel and per-patient physiologic disease severity was less in women than in men. There was no influence of sex on prognostic implications of total anatomical and physiologic disease burdens in patients with coronary artery disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01621438.

18.
Korean J Intern Med ; 34(2): 353-364, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29132199

RESUMO

BACKGROUND/AIMS: Associations between non-fasting triglyceride (TG) levels and a risk of ischemic heart disease (IHD) and cerebrovascular accident (CVA) have been suggested in Caucasians. We aimed to investigate whether non-fasting TG levels reflect the risk of IHD/CVA in Koreans. METHODS: We conducted an analysis of patients aged ≥ 30 years from the nationwide survey database. Fasting TG was defined as a measurement taken ≥ 12 hours since the last meal. Non-fasting TG was categorized by fasting duration of 0 to 3, 4 to 7, and 8 to 11 hours. RESULTS: In subjects without history of IHD/CVA, diabetes, or lipid-lowering medication, the TG level was significantly elevated for 7 hours in men compared to fasting TG levels (p = 0.011); the mean TG levels were 154.9 mg/dL (standard error [SE], 13.0), 177.0 mg/dL (SE, 12.1), 148.8 mg/dL (SE, 2.8), and 141.5 mg/dL (SE, 1.4) for 0 to 3, 4 to 7, 8 to 11, and ≥12 hours' fasting, respectively. In women, there was no difference in TG level according to fasting duration after adjustment for confounders. In men without diabetes, the TG level from 4 to 7 hours' fasting showed a significant difference between subjects with or without IHD/CVA even after adjustments for age, body mass index, lipid medication, exercise, and dietary factors (215.1 mg/dL vs. 177.3 mg/dL, p < 0.001). CONCLUSION: In men, non-fasting TG levels from 4 to 7 hours' fasting were significantly associated with IHD/CVA, and were superior to fasting TG levels level in the significant association with the history of IHD or CVA.


Assuntos
Isquemia Miocárdica/sangue , Acidente Vascular Cerebral/sangue , Triglicerídeos/sangue , Idoso , Jejum/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais
19.
Oncogene ; 38(10): 1597-1610, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30348990

RESUMO

The point mutation that substitutes lysine with arginine at position 120 of human p53 has been characterized as a missense mutation. The K120R mutation renders the p53 protein disabled for acetylation and, as a result, defective for apoptotic function, which provides a mechanistic link between the missense mutation and tumorigenesis. However, we noticed the failures of tumorigenesis in mice with the mutation, and of the related studies to notice that it has arbitrarily reflected in amino acid change through a sequence modification (AGA) of the original tumor mutation (AGG) by codon degeneracy. Unlike this modified version, we also discovered a novel splicing site the original mutation, TP53 c.359A>G, may induce. Using a human induced pluripotent stem cell line that was engineered to be homozygous for the original mutation, we here identified that the accidental splicing site generates a defective transcript variant with a frame-shifted premature termination codon which is subjected to nonsense-mediated mRNA decay. The authentic splicing still occurs but in extremely low amounts. Taken together, this mutation causes depletion of cellular p53 via defective mRNA, suggesting a new link to tumorigenesis.


Assuntos
Mutação de Sentido Incorreto , Degradação do RNAm Mediada por Códon sem Sentido , RNA Mensageiro/química , Proteína Supressora de Tumor p53/genética , Processamento Alternativo , Linhagem Celular , Códon sem Sentido , Técnicas de Introdução de Genes , Humanos , Sítios de Splice de RNA
20.
Opt Express ; 26(22): 28453-28460, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30470016

RESUMO

We present a cost-effective and bandwidth-enhanced 64-Gbaud micro-intradyne coherent receiver based on hybrid integration of InP waveguide-photodetector (WG-PD) and silica planar lightwave circuit (PLC). InP waveguide-photodetector (WG-PD) arrays are simply chip-to-chip bonded and optically butt-coupled to a silica-based dual-polarization optical hybrid chip. Multiple flexible printed circuit boards are adapted for electrical RF and DC wirings, which provide low-cost integration and good RF performance of the receiver. A 3-dB bandwidth of the fabricated coherent receiver is extended to ~36 GHz by optimization of bondwire inductance between the WG-PD array and the transimpedance amplifier (TIA), even when commercial TIAs with a typical bandwidth of ~29 GHz are used. Through optimization of the silica hybrid integrated coherent receiver, 64-Gbaud DP-16QAM signal transmission over 1050-km standard single-mode fiber is successfully demonstrated below a bit error rate of 2 × 10-3. This is the threshold for a soft decision-based forward error correction, at the optical signal to noise ratio of 23.8 dB.

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