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1.
Plant J ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825226

RESUMO

Phytoene synthase (PSY1), Capsanthin-capsorubin synthase (CCS), and Pseudo response regulator2-like (PRR2) are three major genes controlling fruit color in pepper. However, the diversity of fruit color in pepper cannot be completely explained by these three genes. Here, we used an F2 population derived from C. annuum 'SNU-mini Orange' (SO) and C. annuum 'SNU-mini Yellow' (SY), both harboring functional PSY1 and mutated CCS, and observed that yellow color was dominant over orange color. We performed genotyping-by-sequencing (GBS) and mapped the genetic locus to a 6.8 Mb region on chromosome 2, which we named CaOr. Among the genes located within the region, we discovered that a splicing mutation in the Zeaxanthin epoxidase (ZEP) leading to premature stop codon of the gene. HPLC analysis showed that SO contained higher amounts of zeaxanthin and total carotenoids in mature fruits than SY. A color complementation assay using E. coli harboring carotenoid biosynthetic genes showed that the mutant ZEP protein had reduced enzymatic activity. Transmission electron microscopy of plastids revealed that the ZEP mutation affected plastid development with more rod-shaped inner membrane structures in chromoplasts of mature SO fruits. To validate the role of ZEP in fruit color formation, we performed virus-induced gene silencing (VIGS) of ZEP in the yellow-fruit cultivar C. annuum 'Micropep Yellow' (MY). The silencing of ZEP caused significant changes in the ratios of zeaxanthin to its downstream products and increased total carotenoid contents. Thus, we conclude that the ZEP genotype can determine orange or yellow mature fruit color in pepper.

2.
Ann Clin Transl Neurol ; 8(1): 238-246, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33389803

RESUMO

OBJECTIVE: Parkinson's disease (PD) is the second most common neurodegenerative disorder associated with various morbidities. Although the relationship between cardiovascular disease and PD has been studied, a paucity of information on PD and atrial fibrillation (AF) association exists. Thus, we aimed to investigate whether patients with PD have an increased risk of AF. METHODS: This study included 57,585 patients with newly diagnosed PD (≥40-year-old, mean age 69.7 years, men 40.2%) and without a history of AF from the Korean National Health Insurance Service (NHIS) database between 2010 and 2015. Furthermore, an equal number of age- and sex-matched subjects without PD were selected for comparison. The primary outcome was new-onset AF. RESULTS: During the mean follow-up period of 3.4 ± 1.8 years, AF was newly diagnosed in 3,665 patients. A significantly higher incidence rate of AF was noted among patients with PD than among patients without PD (10.75 and 7.86 per 1000 person-year, respectively). Multivariate Cox-regression analysis revealed that PD was an independent risk factor for AF (hazard ratio [HR]: 1.27, 95% confidence interval [CI]: 1.18-1.36). Furthermore, subgroup analyses revealed that AF risk was higher in the younger age subgroups, and compared with the non-PD group, the youngest PD group (age: 40-49 years) had a threefold increased risk of AF (HR: 3.06, 95% CI: 1.20-7.77). INTERPRETATION: Patients with PD, especially the younger age subgroups, have an increased risk of AF. Active surveillance and management of AF should be considered to prevent further complications.

3.
Epilepsy Behav ; 115: 107700, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33421853

RESUMO

Avoiding valproate is recommended in women of childbearing age due to possible teratogenicity and infertility. We aimed to examine the recent trend of valproate prescriptions in Korea to review the adequacy of anticonvulsant prescriptions in women with epilepsy (WWE). Oral valproate utilization was assessed using nationwide and unselected data from the Korean National Health Insurance Service from 2009 to 2017. The temporal trends of the proportions of valproate prescriptions were analyzed using the Poisson regression model and expressed as average annual percentage change (AAPC). Among the WWE of childbearing age, valproate was prescribed in 37.0% overall and 29.4% as initial prescription in 2017. The proportion of valproate utilization showed a decreasing trend in overall prescription (AAPC = -1.10%) and initial prescription (AAPC = -2.63%). However, the proportion was static over time in the initial monotherapy group (AAPC = -0. 53%), while it was significantly decreasing in the initial polytherapy group (AAPC = -8.25%). A noticeable proportion of WWE was still being prescribed valproate in Korea. In particular, the use of valproate for initial monotherapy has not decreased over the past nine years. This result calls not only for reinforcement of education regarding anticonvulsant selection but also for monitoring the actual prescription.

4.
Support Care Cancer ; 2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33486599

RESUMO

PURPOSE: Although anticholinergic burden has been known to be associated with adverse outcomes in older adults, its clinical importance has been less studied in patients with advanced cancer. We aimed to assess clinical impacts of using anticholinergic medications in older patients with cancer. METHODS: This is a single-center retrospective database study. This study included patients with stage IV solid cancer aged 65 years or older who were hospitalized in a hospitalist-operated medical unit of a tertiary hospital. We calculated anticholinergic cognitive burden (ACB) scores on admission and during hospitalization by reviewing all medications during hospital stays and collected the following data: demographic, medical history and clinical severity, occurrence of delirium, location of discharge, in-hospital mortality, and after discharge mortality data. RESULTS: When we divided the patients into two groups based on the change in ACB during hospitalization, the in-hospital mortality rate, incidence of delirium, frequency of transfers to long-term care hospitals, and length of hospital stay were higher in the ACB-increased group than those in the non-increased group. Even after excluding patients with clinically detected delirium, increased ACB were associated with increased in-hospital mortality. Patients in the ACB-increased group showed higher mortality risk after discharge than those in the non-increased group based on the Cox proportional hazard model. CONCLUSION: Increased ACB during hospitalization is a predictor of worsening clinical features and higher mortality in older patients with cancer. Further studies investigating causal relationship between an increased ACB and poor prognosis are warranted.

5.
Life (Basel) ; 10(12)2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33297425

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disease, causing movement defects. The incidence of PD is constantly increasing and this disease is still incurable. Thus, understanding PD pathophysiology would be pivotal for the development of PD therapy, and various PD models have thus been already developed. Through recent advances in reprogramming techniques, a primitive neural stem cell (pNSC) derived from PD patient induced pluripotent stem cells (iPSCs) could be potentially used as a reproducible and reliable experimental system to analyze the effect of the leucine-rich repeat kinase 2 G2019S mutation (LK2GS) in neural cells. Here, we investigated the advantages of such a model system through quantitative proteomic analysis of pNSCs from normal control iPSCs and familial PD patient iPSCs harboring LK2GS. We confirmed that the expression of molecules known to be involved in PD pathogenesis, such as oxidative stress-, cell adhesion-, and cytoskeleton-related proteins, were altered in the LK2GS pNSC. In addition, we showed that down-regulation of Ku80, which was found in the proteomic analysis with LK2GS pNSCs, resulted in apoptosis induced by DNA damage response. Taken together, we suggest that pNSCs from PD iPSCs could provide a reliable and useful model system to study PD. Moreover, the highly expandable pNSC is suitable for multi-omics approaches to understand PD pathologies and discover therapeutic targets for PD.

6.
Int J Cardiol ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33045277

RESUMO

BACKGROUND: Although the survival benefit of obesity has been suggested in patients with heart failure (HF), the impact of sex on obesity paradox is less clear. This study was performed to investigate whether there is a sex difference in the association between body mass index (BMI) and long-term clinical outcomes in patients hospitalized for HF. METHOD: A total of 2616 patients hospitalized for HF (Mean age 66 years and 52% males) from the nation-wide registry database were analyzed. Patients were categorized using baseline BMI as normal (18.5 to 22.9 kg/m2), overweight (23 to 27.4 kg/m2) and obese (≥ 27.5 kg/m2). Their all-cause mortality and long-term composite events, including all-cause mortality and HF readmission, were assessed according to the BMI groups. RESULTS: During the median follow-up period of 1499 days, there were 662 patients (25.3%) with all-cause mortality and 1071 patients (40.9%) with composite events. Compared to the normal weight group, the overweight (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.51-0.99; P = 0.045) and obese (HR, 0.53; 95% CI, 0.29-0.95; P = 0.032) group showed lower all-cause mortality rates even after adjusting for confounding factors in the male patients. Otherwise, BMI was not associated with composite events in males; it was not associated with all-cause mortality or composite events in females in the multivariable analyses (P > 0.05 for each). CONCLUSIONS: Among patients with HF, a greater BMI was associated with low all-cause mortality in males, but not in females. Obesity paradox should be considered in the management of HF patients.

7.
Sleep Med ; 76: 43-47, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33091725

RESUMO

BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) is a modifiable risk factor for stroke, but there are limited data on which stroke subtypes are associated with OSA. The aim of this study was to assess the risk for wake-up stroke (WUS) associated with OSA according to each etiologic subtype to elucidate the pathophysiologic mechanism of OSA-associated stroke. METHOD: We investigated 557 consecutive patients who were admitted with acute ischemic stroke in two regional comprehensive stroke centers using a standardized protocol including the Berlin questionnaire to identify symptoms of OSA prior to stroke. The collected stroke data included the time of onset, risk factors, and etiologic subtype. Stratified analysis according to sex was conducted because sex has been reported to be an effect modifier of OSA on cardiovascular outcomes. The association between preexisting OSA symptoms and WUS depending on etiologic subtypes was assessed using multivariate logistic regression analysis. RESULTS: Preexisting OSA symptoms were associated with the risk of overall WUS in men. Snoring was associated with WUS in large artery atherosclerosis [adjusted odds ratio, 2.67 (1.15-6.23)], and apnea was associated with WUS in small vessel occlusion [adjusted odds ratio, 8.21 (1.15-58.53)], whereas OSA symptoms were not significantly associated with WUS in cardioembolism. Associations between OSA and WUS were not found in women. CONCLUSION: This study demonstrated the differential influences of OSA on WUS depending on etiologic subtypes, suggesting more vulnerability in large artery atherosclerosis and small vessel occlusion. Sex is a significant effect modifier of the association between OSA and WUS.

8.
Sleep Med ; 76: 72-79, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33120131

RESUMO

BACKGROUND: Sleep technicians are at high risk of shift work sleep disorders. We therefore aimed to identify the optimal shift system for sleep technicians. METHODS: We performed a nationwide survey of the work schedules, health and quality of life of sleep technicians using e-mail questionnaires including the Insomnia Severity Index (ISI), Epworth Sleep Scale (ESS), Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), Short Form-12 Health Survey (SF-12), and Hospital Anxiety and Depression Scale (HADS) in Korea. A multivariate general linear model was used to assess the effect of shift schedules on health and quality of life. RESULTS: Fifty-four technicians from 30 sleep laboratories participated. Their work schedules were classified as fixed night (F) (n = 18), slow rotation alternating from a night-only to a day-only schedule with a 3-months to one-year interval (S) (n = 20), rapid rotation within a week (R) (n = 5), night once a week (D+) (n = 5) and day (D) (n = 6). The adjusted ISI and HADS-anxiety scores were higher in F, S, and R than D and D+. Among night shift-dominant schedules, a less favorable profile was observed for R followed by F, and S regarding the ISI, FOSQ-10, mental SF-12 and HADS-depression. The physical SF-12 was lower in the order of R, S and F. The HADS-anxiety score was higher in the order of F, R and S. CONCLUSIONS: The S system appears to have the least negative effect on health and quality of life among night shift-dominant systems. The development of consensus guidelines for scheduling shifts in sleep laboratories is urged.

9.
J Cardiol ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32863081

RESUMO

BACKGROUND: Heart failure (HF) and cancer are currently two leading causes of mortality, and sometimes coexist. However, the relationship between them is not completely elucidated. We aimed to investigate whether patients with HF are predisposed to cancer development using the large Korean National Health Insurance claims database. METHODS: This study included 128,441 HF patients without a history of cancer and 642,205 age- and sex-matched individuals with no history of cancer and HF between 1 January 2010 and 31 December 2015. RESULTS: During a median follow-up of 4.06 years, 11,808 patients from the HF group and 40,805 participants from the control were newly diagnosed with cancer (cumulative incidence, 9.2% vs. 6.4%, p < 0.0001). Patients with HF presented a higher risk for cancer development compared to controls in multivariable Cox analysis [hazard ratio (HR) 1.64, 95% confidence interval (CI) 1.61-1.68]. The increased risk was consistent for all site-specific cancers. To minimize potential surveillance bias, additional analysis was performed by eliminating participants who developed cancer within the initial 2 years of HF diagnosis (i.e. 2-year lag analysis). In the 2-year lag analysis, the higher risk of overall cancer remained significant in patients with HF (HR 1.09, 95% CI 1.05-1.13), although the association was weaker. Among the site-specific cancers, three types of cancer (lung, liver/biliary/pancreas, and hematologic malignancy) were consistently at higher risk in patients with HF. An exploratory analysis showed that patients with repeated HF hospitalization had a higher risk of cancer development compared to those without, in a pattern of stepwise increases across the three groups [controls vs. HF without re-hospitalization vs. HF with re-hospitalization ≥1; HR (95% CI), 1.00 (reference) vs. 1.55 (1.51-1.59) vs. 1.96 (1.89-2.03), respectively]. CONCLUSIONS: Cancer incidence is higher in patients with HF than the general population. Active surveillance of coexisting malignancy needs to be considered in these patients.

10.
Endocrinol Metab (Seoul) ; 35(2): 367-376, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32615721

RESUMO

BACKGROUND: This study assessed the proportion of risk-stratified Korean patients with dyslipidemia achieving their low-density lipoprotein cholesterol (LDL-C) targets as defined by the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) (2011) guidelines while receiving lipid-modifying treatments (LMTs). METHODS: In this multicenter, cross-sectional, observational study, we evaluated data from Korean patients aged ≥19 years who were receiving LMTs for ≥3 months and had an LDL-C value within the previous 12 months on the same LMT. Data were collected for demographics, cardiovascular (CV) risk factors, medical history, and healthcare consumption. Patients were risk-stratified according to the ESC Systematic COronary Risk Evaluation (SCORE) chart and LDL-C target achievement rate was assessed. RESULTS: Guideline-based risk-stratification of the 1,034 patients showed the majority (72.2%) to be in the very high-risk category. Investigators' assessment of risk was underestimated in 71.6% compared to ESC/EAS guidelines. Overall LDL-C target achievement rate was 44.3%; target achievement was the highest (66.0%) in moderate-risk patients and the lowest (39.0%) in very high-risk patients. Overall 97.1% patients were receiving statin therapy, mostly as a single-agent (89.2%). High-intensity statins and the highest permissible dose of high-intensity statins had been prescribed to only 9.1% and 7.3% patients in the very high-risk group, respectively. Physician satisfaction with patients' LDL-C levels was the primary reason for non-intensification of statin therapy. CONCLUSION: Achievement of target LDL-C level is suboptimal in Korean patients with dyslipidemia, especially in those at very high-risk of CV events. Current practices in LMTs need to be improved based on precise CV risk evaluation posed by dyslipidemia.

11.
Obstet Gynecol Sci ; 63(3): 379-386, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32489984

RESUMO

Objective: To compare the perioperative outcomes of transumbilical morcellation (TUM) and transvaginal morcellation (TVM) of a large uterus (≥500 g) during single-port-access total laparoscopic hysterectomy (SPA-TLH). Methods: A total of 57 patients who underwent SPA-TLH for a large uterine myoma and/or adenomyosis (uterine weight ≥500 g) between March 2013 and July 2017 were included. For specimen retrieval, TUM was performed for 30 patients and TVM for 27 patients. Results: Perioperative outcomes, including total operative time, tissue extraction time, extension of skin incision length, estimated volume of blood loss, changes in postoperative hemoglobin level, length of postoperative hospital stay, postoperative pain, and uterine weight, were compared between the 2 groups. No significant differences were observed in the baseline characteristics except for a history of cesarean section (TUM vs. TVM: 83.3% vs. 14.8%, P=0.002) and history of vaginal delivery (TUM vs. TVM: 6.7% vs. 88.8%, P=0.001). The total operative time, tissue extraction time, extension of skin incision length, estimated volume of blood loss, changes in postoperative hemoglobin level, length of postoperative hospital stay, and postoperative pain did not significantly differ between the two groups. The uterine weight was significantly higher for patients who underwent TUM than for those who had TVM (median [range]: 735 g [520-1,380 g] vs. 622 g [514-975 g]; P=0.042). Conclusion: TUM during SPA-TLH is a feasible technique for extracting large uteri weighing ≥500 g. This procedure is suitable for patients without a history of vaginal delivery or a narrow vaginal cavity.

12.
Int J Mol Sci ; 21(9)2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32380745

RESUMO

Induced pluripotent stem cells (iPSCs) are regarded as a promising option for cell-based regenerative medicine. To obtain safe and efficient iPSC-based cell products, it is necessary to selectively eliminate the residual iPSCs prior to in vivo implantation due to the risk of teratoma formation. Bee venom (BV) has long been used in traditional Chinese medicine to treat inflammatory diseases and relieve pain, and has been shown to exhibit anti-cancer, anti-mutagenic, anti-nociceptive, and radioprotective activities. However, the potential benefits of BV in iPSC therapy, particularly its anti-teratoma activity, have not been examined. In this study, we found that BV selectively induced cell death in iPSCs, but not in iPSC-derived differentiated cells (iPSCs-Diff). BV rapidly disrupted cell membrane integrity and focal adhesions, followed by induction of apoptosis and necroptosis in iPSCs. We also found that BV remarkably enhanced intracellular calcium levels, calpain activation, and reactive oxygen speciesgeneration in iPSCs. BV treatment before in ovo grafting efficiently prevented iPSC-derived teratoma formation. In contrast, no DNA damage was observed in iPSCs-Diff following BV treatment, further demonstrating the safety of BV for use with iPSCs-Diff. Taken together, these findings show that BV has potent anti-teratoma activity by eliminating residual iPSCs, and can be used for the development of effective and safe iPSC-based cell therapies.

13.
J Clin Med ; 9(5)2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32423155

RESUMO

We aimed to describe temporal trends in emergency department (ED) visits of patients with atrial fibrillation (AF) over 12 years. A repeated cross-sectional analysis of ED visits in AF patients using the Korean nationwide claims database between 2006 and 2017 were conducted. We identified AF patients who had ≥1 ED visits. The incidence of ED visits among total AF population, cause of ED visit, and clinical outcomes were evaluated. During 12 years, the annual numbers of AF patients who attended ED at least once a year continuously increased (40,425 to 99,763). However, the annual incidence of ED visits of AF patients was stationary at about 30% because the number of total AF patients also increased during the same period. The most common cause of ED visits was cerebral infarction. Although patients had a higher risk profile over time, the 30-day and 90-day mortality after ED visit decreased over time. ED visits due to ischemic stroke, intracranial hemorrhage, and myocardial infarction decreased, whereas ED visits due to AF, gastrointestinal bleeding, and other major bleeding slightly increased among total AF population over 12 years. A substantial proportion of AF patients attended ED every year, and the annual numbers of AF patients who visited the ED significantly increased over 12 years. Optimized management approaches in a holistic and integrated manner should be provided to reduce ED visits of AF patients.

14.
Int J Cardiol ; 313: 25-31, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32360645

RESUMO

BACKGROUND: Although percutaneous coronary intervention (PCI) has been the mainstay of revascularization strategy for significant coronary artery disease, future cancer risk after PCI has never been explored. We aimed to investigate the risk of incident cancer in patients undergoing PCI for the first time. METHODS: We studied 125,613 patients who underwent the first PCI between 2010 and 2015 without a prior history of cancer. For comparison, we selected 628,065 age- and sex-matched controls without any history of cancer or PCI who completed the assigned national health examination during the same period. RESULTS: During a median 4.56 years (interquartile range, 3.06-6.13 years), 8528 patients from the PCI group and 40,166 controls were newly diagnosed with cancer (incidence rate, 15.1 vs. 13.9 per 1000 person-years, p < 0.0001). Patients undergoing PCI presented a higher risk for cancer development than the controls in multivariable Cox analysis (adjusted HR [aHR] 1.06, 95% CI 1.04-1.09, p < 0.0001). To minimize potential surveillance bias, we performed 1-year lag analysis by eliminating participants who developed cancer within 1 year from the PCI. In this analysis, the increased risk of overall cancer in the PCI group became insignificant (aHR 1.02, 95% CI 0.99-1.05, p = 0.2017). Regarding site-specific cancers, however, the risk of lung and hematologic malignancies remained higher and the risk of gastrointestinal, liver/biliary/pancreas, thyroid, and breast cancers remained lower in the PCI group. CONCLUSIONS: Differential future cancer risks were observed in patients undergoing PCI. The results suggest that specialized surveillance strategy might be warranted for this expanding population.

15.
Epilepsy Behav ; 110: 107129, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32473520

RESUMO

PURPOSE: Literature regarding family stigma related to epilepsy is scarce. This study investigated the prevalence of family stigma and depressive symptoms and the associated factors among the family members of patients with epilepsy. METHODS: In a cross-sectional study, Stigma Scale-Revised score ≥ 4 and Patient Health Questionnaire-9 score ≥ 10 were considered indicative of moderate-to-severe stigma and depressive symptoms, respectively. Stepwise logistic regression analyses were performed. RESULTS: Of the 482 family members, a mean age was 47.1 ±â€¯9.4 years, and 73.4% were female. Of the patients, a mean age was 25.5 ±â€¯16.7 years, and 45.0% were female. Idiopathic generalized epilepsy and focal epilepsy were noted in 22.4% and 65.6% of patients, respectively. Family stigma and depressive symptoms were noted in 10.0% and 11.2% of family members, respectively. Family stigma was significantly associated with high seizure frequency and being a sibling or offspring of a patient independent of their depressive symptoms. By contrast, depressive symptoms in family members were significantly associated with polytherapy, being parents of a patient, and neurological comorbidities independent of family stigma. In a subset of patients and their family, patients had higher proportion of stigma and depressive symptoms than their family. Depressive symptoms and stigma among patients were significantly correlated with those among parents, but not spouse. CONCLUSION: Family stigma is common in families with epilepsy and is closely related to depressive symptoms. Frequent seizures, polytherapy, neurological comorbidities, and the relationship to a patient may be factors that are independently associated with family stigma and depressive symptoms in family members.

16.
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.

17.
Endocrinol Metab (Seoul) ; 35(1): 188-191, 2020 03.
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).

18.
Phytomedicine ; 69: 153198, 2020 Apr.
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.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Magnolia/química , Extratos Vegetais/farmacologia , Teratoma/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Embrião de Galinha , Etanol/química , Hepatócitos/citologia , Hepatócitos/fisiologia , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Extratos Vegetais/química , Teratoma/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
19.
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.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/epidemiologia , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Pirimidinas/uso terapêutico , Fosfato de Sitagliptina/uso terapêutico , Tiazolidinedionas/uso terapêutico , Biomarcadores/análise , Glicemia/análise , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Quimioterapia Combinada , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Incidência , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Prognóstico , República da Coreia/epidemiologia
20.
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.


Assuntos
Cardiomiopatia Hipertrófica/epidemiologia , Idoso , Fibrilação Atrial/etiologia , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/patologia , Dor no Peito/etiologia , Estudos de Coortes , Comorbidade/tendências , Bases de Dados Factuais , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Fatores de Risco
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