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1.
Sci Rep ; 14(1): 17466, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075120

RESUMO

Globally, hip fractures represent a significant and growing public health concern, particularly as the elderly population increases. The timing for surgery following hospitalization for hip fractures is a crucial indicator of acute quality care following recommended surgical guidelines of within two days to minimize complications and mortality. However, factors influencing delayed surgery and its outcomes remain debated. This study, used a national administrative database in South Korea, aimed to examine surgery performed within two days of hospitalization and investigate factors affecting delayed surgical interventions and associated outcomes. Of the hip fracture patients analyzed, 40.6% underwent surgery within two days of hospitalization. Factors associated with delayed surgery included: male patients (OR 1.190; 95% CI 1.022 ~ 1.385), medical aid beneficiary (OR 1.385; 95% CI 1.120 ~ 1.713), higher comorbidity index (OR 1.365; 95% CI 1.163 ~ 1.603, OR 1.612, 95% CI 1.327 ~ 1.958), weekends admission (OR 2.384; 95% CI 2.804 ~ 2.729), admission via outpatient department (OR 1.298, 95% CI 1.071 ~ 1.574). ORIF (OR 0.823, 95% CI 0.691 ~ 0.980) was associated with a significantly low risk of late surgery. While early surgery did not significantly impact in-hospital mortality or complications, it was associated with short and postoperative lengths of stay. This study underscores the need for prompt surgical intervention, particularly in high-risk patient populations, as well as highlights the importance of further research to elucidate the relationship between the timing of surgery and postoperative outcomes.


Assuntos
Bases de Dados Factuais , Fraturas do Quadril , Hospitalização , Humanos , Fraturas do Quadril/cirurgia , Fraturas do Quadril/mortalidade , Masculino , Idoso , Feminino , Hospitalização/estatística & dados numéricos , República da Coreia/epidemiologia , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Fatores de Risco , Tempo de Internação , Mortalidade Hospitalar , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Tempo
2.
Healthcare (Basel) ; 12(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891139

RESUMO

The use of mobile-based personal health record (m-PHR) applications at the hospital level has been minimally studied. This study aimed to investigate the relationship between m-PHR use and quality of care. A cross-sectional study design was employed, analyzing data from 99 hospitals. Two data sources were utilized: a previous m-PHR investigation conducted from 26 May to 30 June 2022 and a hospital evaluation dataset on quality of care. The use of m-PHR applications was measured by the number of m-PHR application downloads. Three independent variables were assessed: quality of care in the use of antibiotic drugs, injection drugs, and polypharmacy with ≥6 drugs. A generalized linear model was used for the analysis. The hospitals providing high-quality care, as evaluated based on the rate of antibiotic prescription (relative risk [RR], 3.328; 95% confidence interval [CI], 1.840 to 6.020; p < 0.001) and polypharmacy (RR, 2.092; 95% CI, 1.027 to 4.261; p = 0.042), showed an increased number of m-PHR downloads. Among the hospital covariates, public foundation status and being part of multi-hospital systems were associated with the number of m-PHR downloads (p < 0.05). This exploratory study found a positive relationship between quality of care and m-PHR use. Hospitals providing high-quality care may also excel in various activities, including m-PHR application use.

3.
BMB Rep ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38649147

RESUMO

Parkinson's disease (PD), characterized by dopaminergic neuron degeneration in the substantia nigra, is caused by various genetic and environmental factors. Current treatment methods are medication and surgery; however, a primary therapy has not yet been proposed. In this study, we aimed to develop a new treatment for PD that induces direct reprogramming of dopaminergic neurons (iDAN). Achaete-scute family bHLH transcription factor 1 (ASCL1) is a primary factor that initiates and regulates central nervous system development and induces neurogenesis. In addition, it interacts with BRN2 and MYT1L, which are crucial transcription factors for the direct conversion of fibroblasts into neurons. Overexpression of ASCL1 along with the transcription factors NURR1 and LMX1A can directly reprogram iDANs. Using a retrovirus, GFP-tagged ASCL1 was overexpressed in astrocytes. One week of culture in iDAN convertsion medium reprogrammed the astrocytes into iDANs. After 7 days of differentiation, TH+/TUJ1+ cells emerged. After 2 weeks, the number of mature TH+/TUJ1+ dopaminergic neurons increased. Only ventral midbrain (VM) astrocytes exhibited these results, not cortical astrocytes. Thus, VM astrocytes can undergo direct iDAN reprogramming with ASCL1 alone, in the absence of transcription factors that stimulate dopaminergic neuron development.

4.
Clin Chem Lab Med ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38630027

RESUMO

OBJECTIVES: This study evaluates the HYDRASHIFT assay's effectiveness in mitigating daratumumab interference on serum protein tests during multiple myeloma (MM) treatment, aiming to ensure an accurate assessment of treatment response. METHODS: We analyzed 113 serum samples from 68 MM patients undergoing daratumumab treatment, employing both standard IF and the HYDRASHIFT assay. The assay's precision was determined through intra-day and inter-day variability assessments, while its specificity was verified using serum samples devoid of daratumumab. Comparative analysis of IF results, before and after the application of the HYDRASHIFT assay, facilitated the categorization of treatment responses in alignment with the International Myeloma Working Group's response criteria. RESULTS: The precision underscored the assay's consistent repeatability and reproducibility, successfully eliminating interference of daratumumab-induced Gκ bands. Specificity assessments demonstrated the assay's capability to distinguish daratumumab from both isatuximab and naturally occurring M-proteins. Of the analyzed cases, 91 exhibited successful migration of daratumumab-induced Gκ bands, thereby enhancing the accuracy of treatment response classification. The remaining 22 cases did not show a visible migration complex, likely due to the low concentration of daratumumab in the serum. These findings underscore the assay's critical role in distinguishing daratumumab from endogenous M-protein, particularly in samples with a single Gκ band on standard IF, where daratumumab and endogenous M-protein had co-migrated. CONCLUSIONS: The HYDRASHIFT assay demonstrates high precision, specificity, and utility in the accurate monitoring of treatment responses in MM patients receiving daratumumab. This assay represents a significant advancement in overcoming the diagnostic challenges posed by daratumumab interference.

5.
Arch Pathol Lab Med ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38576184

RESUMO

CONTEXT.­: New-generation antiseizure medications (ASMs) are increasingly prescribed, and therapeutic drug monitoring (TDM) has been proposed to improve clinical outcome. However, clinical TDM data on new-generation ASMs are scarce. OBJECTIVE.­: To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for therapeutic drug monitoring (TDM) of 6 new-generation ASMs in serum and analyze the clinical TDM data from a large cohort of Korean patients with epilepsy. DESIGN.­: Stable isotope-labeled internal standards were added to protein precipitations of serum. One microliter of sample was separated on Agilent Poroshell EC-C18 column, and lacosamide, perampanel, gabapentin, pregabalin, vigabatrin, and rufinamide were simultaneously quantified by Agilent 6460 triple-quad mass spectrometer in multiple-reaction monitoring mode. Linearity, sensitivity, precision, accuracy, specificity, carryover, extraction recovery, and matrix effect were evaluated. TDM data of 458 samples from 363 Korean epilepsy patients were analyzed. RESULTS.­: The method was linear with limit of detection less than 0.05 µg/mL in all analytes. Intraassay and interassay imprecisions were less than 5% coefficient of variation. Accuracy was within ±15% bias. Extraction recovery ranged from 85.9% to 98.8%. A total of 88% (403 of 458) were on polypharmacy, with 29% (118 of 403) using concomitant enzyme inducers. Only 38% (175 of 458) of the concentrations were therapeutic, with 53% (244 of 458) being subtherapeutic. Drug concentration and concentration-to-dose ratio were highly variable among individuals in all 6 ASMs. CONCLUSIONS.­: A simple and rapid LC-MS/MS method for TDM of 6 ASMs was developed and successfully applied to clinical practice. This large-scale TDM data could help establish an effective monitoring strategy for these drugs.

6.
Int J Mol Sci ; 24(18)2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37762604

RESUMO

Since the majority of patients with pancreatic cancer (PC) develop insulin resistance and/or diabetes mellitus (DM) prior to PC diagnosis, PC-induced diabetes mellitus (PC-DM) has been a focus for a potential platform for PC detection. In previous studies, the PC-derived exosomes were shown to contain the mediators of PC-DM. In the present study, the response of normal pancreatic islet cells to the PC-derived exosomes was investigated to determine the potential biomarkers for PC-DM, and consequently, for PC. Specifically, changes in microRNA (miRNA) expression were evaluated. The miRNA specimens were prepared from the untreated islet cells as well as the islet cells treated with the PC-derived exosomes (from 50 patients) and the healthy-derived exosomes (from 50 individuals). The specimens were subjected to next-generation sequencing and bioinformatic analysis to determine the differentially expressed miRNAs (DEmiRNAs) only in the specimens treated with the PC-derived exosomes. Consequently, 24 candidate miRNA markers, including IRS1-modulating miRNAs such as hsa-miR-144-5p, hsa-miR-3148, and hsa-miR-3133, were proposed. The proposed miRNAs showed relevance to DM and/or insulin resistance in a literature review and pathway analysis, indicating a potential association with PC-DM. Due to the novel approach used in this study, additional evidence from future studies could corroborate the value of the miRNA markers discovered.


Assuntos
Diabetes Mellitus , Exossomos , Resistência à Insulina , Ilhotas Pancreáticas , MicroRNAs , Neoplasias Pancreáticas , Humanos , Exossomos/genética , Exossomos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/metabolismo , Diabetes Mellitus/metabolismo , Ilhotas Pancreáticas/metabolismo , Neoplasias Pancreáticas
7.
Ann Hum Genet ; 86(6): 361-368, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36000290

RESUMO

Mucopolysaccharidosis type IVA (MPS IVA; Morquio syndrome type A) is an autosomal recessive disorder caused by defects in the lysosomal hydrolase N-acetylgalactosamine-6-sulfatase (GALNS) gene, leading to progressive systemic skeletal dysplasia. Early diagnosis and early intervention with enzyme replacement therapy are crucial for improving outcomes in these patients. However, a relatively high number of patients are genetically undiagnosed due to high allelic heterogeneity and the absence of robust functional evidence for most variants of the GALNS gene. Herein, we report a novel intronic variant identified with RNA analysis and an allele dropout (ADO) event caused by a common benign variant in the primer-binding site in a Korean boy with MPS IVA. A 28-month-old boy presented with pectus carinatum, kyphoscoliosis, and joint hypermobility with multiple skeletal dysplasia involving the vertebrae and hip joint. Total urinary glycosaminoglycans were elevated with a predominant keratan sulfate fraction, and GALNS (EC 3.1.6.4) activity was significantly decreased in leukocytes. Sanger sequencing was performed; however, only one heterozygous intronic variant with uncertain clinical significance, c.566+3A > T (p.(?)), was identified. As the patient exhibited clinical and biochemical features of MPS IVA, we conducted whole genome sequencing (WGS) of the patient and his family to clarify the molecular diagnosis. WGS revealed a compound heterozygous genotype, c.1019G > A (p.(Gly340Asp)) and c.566+3A > T (p.(?)), in the GALNS gene. On mRNA sequencing, c.566+3A > T, was confirmed to cause exon 5 skipping and a premature stop codon. With subsequent investigation, we discovered that the variant, c.1019G > A, was undetected on initial sequencing because of ADO due to a common benign variant (rs3859024:G > C) at the primer annealing location. We present a novel intronic variant with a splicing defect in the GALNS gene and suggest that clinicians review primer sequences in cases not diagnosed on Sanger sequencing before progressing to diagnostic steps such as WGS.


Assuntos
Condroitina Sulfatases , Mucopolissacaridose IV , Pré-Escolar , Humanos , Masculino , Acetilgalactosamina , Condroitina Sulfatases/genética , Códon sem Sentido , Glicosaminoglicanos , Sulfato de Queratano , Mucopolissacaridose IV/genética , Mucopolissacaridose IV/diagnóstico
8.
Ann Lab Med ; 42(4): 467-472, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35177567

RESUMO

Blood gas, electrolyte, glucose, and lactate level measurement have an immediate and critical impact on patient care. We evaluated the performance of i-SmartCare 10 (i-SENS Inc., Seoul, Korea) and conducted a method comparison study of five point-of-care (POC) analyzers with i-SmartCare 10 as the comparator, according to the CLSI guidelines. Ten analytes (pH, pCO2, pO2, Na+, K+, Cl-, iCa2+, glucose, lactate, and Hct) were tested on six analyzers: i-SmartCare 10, ABL90 FLEX PLUS (Radiometer Medical ApS, Copenhagen, Denmark), i-Stat (Abbott Point of Care Inc., Princeton, NJ, USA), RapidLab 1265 (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA), Stat Profile pHOx Ultra (Nova Biomedical, Waltham, MA, USA), and Gem Premier 5000 (Instrumentation Laboratory, Bedford, MA, USA). The total imprecision and linearity (r2>0.99) were excellent, except for a few analytes that narrowly escaped the preset criteria. Interference was noted for Na+ in the presence of a high K+ level and for iCa2+ in the presence of high K+ and Mg2+ levels. Forty of 48 items demonstrated either a proportional or systematic difference in regression analysis; the relative mean difference (%) of 14/48 items escaped the allowable total error in the difference plot analysis. i-SmartCare 10 shows acceptable performance, and using a single POC blood gas analyzer is recommended for monitoring.


Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Sódio , Gasometria/métodos , Eletrólitos , Humanos , Ácido Láctico
9.
J Clin Med ; 10(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34768522

RESUMO

Acute kidney injury (AKI) is a major contributor to in-hospital morbidity and mortality. Vancomycin, one of the most commonly used antibiotics in a clinical setting, is associated with AKI, with its incidence ranging up to 43%. Despite the high demand, few studies have investigated serum biomarkers to detect vancomycin-induced kidney injury (VIKI). Here, we evaluated the diagnostic value of nine candidate serum biomarkers for VIKI. A total of 23,182 cases referred for vancomycin concentration measurement from January 2018 to December 2019 were screened and 28 subjects with confirmed VIKI were enrolled (VIKI group). Age- and sex- matched control group consisted of 21 subjects who underwent vancomycin therapy without developing VIKI (non-VIKI group), and 23 healthy controls (HC group). The serum concentrations of clusterin, retinol binding protein 4 (RBP4), interleukin-18 (IL-18), tumor necrosis factor receptor 1 (TNF-R1), C-X-C motif chemokine ligand 10 (CXCL10), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, trefoil factor-3 (TFF3), and cystatin C were compared among the three groups, and their correlations with estimated glomerular filtration rate (eGFR) and diagnostic values for VIKI were assessed. All of the biomarkers except clusterin and RBP4 exhibited significant elevation in the VIKI group. Serum TFF3, cystatin C, TNF-R1, and osteopontin demonstrated an excellent diagnostic value for VIKI (TFF3, area under the curve (AUC) 0.932; cystatin C, AUC 0.917; TNF-R1, AUC 0.866; osteopontin, AUC 0.787); and except osteopontin, a strong negative correlation with eGFR (TFF3, r = -0.71; cystatin C, r = -0.70; TNF-R1, r = -0.60). IL-18, CXCL10, and NGAL showed weak correlation with eGFR and moderate diagnostic value for VIKI. This study tested multiple serum biomarkers for VIKI and showed that serum TFF3, cystatin C, TNF-R1, and osteopontin could efficiently discriminate VIKI patients. Further studies are warranted to clarify the diagnostic value of these biomarkers in VIKI.

10.
J Clin Apher ; 36(5): 737-749, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34283414

RESUMO

BACKGROUND: An automated hematopoietic progenitor cell count measurement in Sysmex XN analyzer (XN-HPC) has been developed to assist flow cytometry CD34+ cell count measurement, which requires technical expertise and a long turnaround time. Here, we evaluated the correlation between XN-HPC count and flow cytometric CD34+ cell count in pre-harvest peripheral blood (PB) samples from patients undergoing autologous peripheral blood stem cell (PBSC) transplantation according to diagnosis and investigated the possible cause of the decreased correlation in plasma cell neoplasm patients. MATERIALS AND METHODS: We retrospectively included 399 patient data that had matched PB XN-HPC count and CD34+ cell count of PB and apheresis product from Samsung Medical Center (SMC) and the Hematopoietic Stem Cell (HSC) registry. We assessed the diagnostic accuracy and the potential cutoff values of XN-HPC count for predicting adequate PBSC collection. RESULTS: The PB XN-HPC count was 1.6 and 1.3-fold higher than the CD34+ cell count in SMC (25.0 vs 15.9/µl) and the HSC registry (20.0 vs 15.2/µl), respectively. Overall the correlation between the PB XN-HPC and CD34+ cell count was moderate (SMC, r = 0.71; HSC registry, r = 0.66). A significant proportional and systemic bias with overestimation of XN-HPC count were noted in the plasma cell neoplasm patients in both SMC and the HSC registry. However, no significant difference in correlation was observed according to myeloma-related laboratory parameters in plasma cell neoplasm patients. CONCLUSION: Our results suggest that XN-HPC count should be interpreted cautiously in cancer patients undergoing autologous PBSC transplantation, especially in those with plasma cell neoplasm.


Assuntos
Contagem de Células Sanguíneas , Remoção de Componentes Sanguíneos/métodos , Citometria de Fluxo/métodos , Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Adulto , Idoso , Antígenos CD34/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo
11.
Diabetol Metab Syndr ; 13(1): 4, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407809

RESUMO

BACKGROUND: Metabolic syndrome is a cluster of conditions that occur together, increasing the risk of cardiovascular disease. However, the relationship between metabolic syndrome and dementia has remained controversial. Using nationwide population cohort data, we investigated the association between metabolic syndrome and dementia, according to the dementia type. METHODS: We analyzed data of 84,144 individuals, in the aged group of more than 60 years, between January 1, 2009, to December 31, 2009, at Gangwon province by using the information of the (Korean) National Health Insurance Service. After eight years of gap, in 2017, we investigated the relationship between metabolic syndrome and dementia. We classified Dementia either as dementia of the Alzheimer type (AD) or vascular dementia (VD). AD and VD were defined as per the criteria of International Classification of Disease, Tenth Revision, Clinical Modification codes. Multiple logistic regression analyses examined the associations between metabolic syndrome or five metabolic syndrome components and dementia. Analyses included factors like age, sex, smoking, alcohol, physical inactivity, previous stroke, and previous cardiac disease. RESULTS: Metabolic syndrome was associated with AD (OR = 11.48, 95% CI 9.03-14.59), not with VD. Each of five components of metabolic syndrome were also associated with AD. (high serum triglycerides: OR = 1.87, 95% CI 1.60-2.19; high blood pressure: OR = 1.85, 95% CI 1.55-2.21; high glucose: OR = 1.77, 95% CI 1.52-2.06; abdominal obesity: OR = 1.88, 95% CI 1.57-2.25; low serum high-density lipoprotein cholesterol: OR = 1.91, 95% CI 1.63-2.24) However, among components of metabolic syndrome, only the high glucose level was associated with VD. (OR = 1.26, 95% CI 1.01-1.56) body mass index (BMI), fasting glucose, and smoking were also associated with AD. (BMI: OR = 0.951, 95% CI 0.927-0.975; fasting glucose: OR = 1.003, 95% CI 1.001-1.005; smoking: OR = 1.020, 95% CI 1.003-1.039) A history of the previous stroke was associated with both AD and VD. (AD: OR = 1.827, 95% CI 1.263-2.644; VD: OR 2.775, 95% CI 1.747-4.406) CONCLUSIONS: Metabolic syndrome was associated with AD but not with VD. Patients with metabolic syndrome had an 11.48 times more likeliness to develop AD compared to those without metabolic syndrome. VD was associated only with several risk factors that could affect the vascular state rather than a metabolic syndrome. We suggested that the associations between metabolic syndrome and dementia would vary depending on the type of dementia.

12.
Biomater Sci ; 8(11): 3063-3071, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32348398

RESUMO

Ischemic stroke is a cerebrovascular disease caused by narrowed cerebral arteries. Thrombolytic agents such as tissue-plasminogen activators have been used for recanalization of the blood supply into the ischemic region. However, ischemia-reperfusion damage continues to increase the infarction volume. In this study, heme oxygenase-1 (HO1)-mRNA was delivered into the brain, using a non-viral carrier. Various non-viral carriers such as polyethylenimine (25 kDa, PEI25k), lipofectamine, dexamethasone-conjugated PEI2k (Dexa-PEI2k), deoxycholic acid-conjugated PEI2k (DA-PEI2k), and R3V6 peptides were evaluated as carriers of mRNA into the brain. Gene delivery assays showed that DA-PEI2k and lipofectamine had a higher mRNA delivery efficiency than the other carriers in Neuro2A cells in vitro and a rat brain in vivo. Cytotoxicity assays showed that lipofectamine had higher toxicity than DA-PEI2k. Therefore, DA-PEI2k was used for delivery of HO1-mRNA. Unlike plasmid DNA (pDNA), mRNA is expressed in the cytosol without nuclear translocation. This suggests that mRNA may have higher gene expression than pDNA, since the nuclear location of pDNA is an inefficient step. Indeed, in in vitro transfection assays, HO1-mRNA/DA-PEI2k had higher gene expression than HO1-pDNA/DA-PEI2k without induction of a pro-inflammatory cytokine. The therapeutic effects of HO1-mRNA delivery using DA-PEI2k were evaluated in the middle cerebral artery occlusion animal model after local injection. HO1-mRNA delivery had higher gene expression than HO1-pDNA delivery 24 h after the local injection. In addition, HO1-mRNA delivery reduced the infarct size more efficiently than HO1-pDNA delivery. The results suggest that the delivery of mRNA using DA-PEI2k may be useful for gene therapy of ischemic stroke.


Assuntos
Ácido Desoxicólico/administração & dosagem , Técnicas de Transferência de Genes , Heme Oxigenase-1/genética , Infarto da Artéria Cerebral Média/terapia , Nanopartículas/administração & dosagem , Polietilenoimina/administração & dosagem , RNA Mensageiro/administração & dosagem , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ácido Desoxicólico/química , Dexametasona/administração & dosagem , Proteínas de Fluorescência Verde/genética , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Lipídeos/administração & dosagem , Masculino , Camundongos , Peptídeos/administração & dosagem , Polietilenoimina/química , Células RAW 264.7 , Ratos Sprague-Dawley
13.
Food Chem ; 272: 688-693, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30309599

RESUMO

Anthocyanins are major components of purple sweet potatoes (PSP) with antioxidant, anti-obesity, and antidiabetic activity. In this study, we evaluated the hypoglycemic effects of 12 individual anthocyanins purified from PSP (Korean variety Shinzami). We separated the anthocyanins using liquid chromatography with diode array detection and electrospray ionization/mass spectrometry (LC-DAD-ESI/MS). Three anthocyanins were selected through a radical scavenging activity test. We examined whether individual anthocyanins inhibited glucose secretion in HepG2 cells (hepatic gluconeogenesis). Additionally, we determined the effect of each anthocyanin on fasting blood glucose levels in 6-week-old male C57BL/6J mice fed a 60% high-fat diet for 14 weeks. Mice were evaluated at 0, 1, 2, and 4 h after oral administration of anthocyanins (80 mg/kg), an anthocyanin-rich-fraction (80 mg/kg), positive control (metformin, 80 mg/kg), and distilled water (control). Cyanidin 3-caffeoyl-p-hydroxybenzoylsophoroside-5-glucoside (PEAK9) was the main PSP anthocyanin that inhibited hepatic glucose secretion and reduced blood glucose.


Assuntos
Antocianinas/química , Glucosídeos/química , Hipoglicemiantes/química , Ipomoea batatas/química , Animais , Antocianinas/administração & dosagem , Antocianinas/isolamento & purificação , Antioxidantes/química , Glicemia/análise , Cromatografia Líquida de Alta Pressão , Dieta Hiperlipídica , Glucosídeos/administração & dosagem , Glucosídeos/isolamento & purificação , Células Hep G2 , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/isolamento & purificação , Ipomoea batatas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray
14.
BMB Rep ; 52(5): 324-329, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30293549

RESUMO

Recent progress in cellular reprogramming technology and lineage-specific cell differentiation has provided great opportunities for translational research. Because virus-based gene delivery is not a practical reprogramming protocol, protein-based reprogramming has been receiving attention as a safe way to generate reprogrammed cells. However, the poor efficiency of the cellular uptake of reprogramming proteins is still a major obstacle. Here, we reported key factors which improve the cellular uptake of these proteins. Purified red fluorescent proteins fused with 9xLysine (dsRED-9K) as a cell penetrating peptide were efficiently delivered into the diverse primary cells. Protein delivery was improved by the addition of amodiaquine. Furthermore, purified dsRED-9K was able to penetrate all cell lineages derived from mouse embryonic stem cells efficiently. Our data may provide important insights into the design of protein-based reprogramming or differentiation protocols [BMB Reports 2019; 52(5): 324-329].


Assuntos
Peptídeos Penetradores de Células/metabolismo , Técnicas de Reprogramação Celular/métodos , Polilisina/metabolismo , Amodiaquina/farmacologia , Animais , Técnicas de Cultura de Células , Diferenciação Celular/genética , Peptídeos Penetradores de Células/farmacologia , Reprogramação Celular/genética , Células-Tronco Embrionárias/citologia , Fibroblastos/metabolismo , Técnicas de Transferência de Genes , Células HEK293 , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Camundongos , Peptídeos/uso terapêutico , Polilisina/uso terapêutico , Fatores de Transcrição/metabolismo
15.
Brain ; 139(Pt 10): 2722-2739, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27538419

RESUMO

The original properties of tissue-specific stem cells, regardless of their tissue origins, are inevitably altered during in vitro culturing, lessening the clinical and research utility of stem cell cultures. Specifically, neural stem cells derived from the ventral midbrain lose their dopamine neurogenic potential, ventral midbrain-specific phenotypes, and repair capacity during in vitro cell expansion, all of which are critical concerns in using the cultured neural stem cells in therapeutic approaches for Parkinson's disease. In this study, we observed that the culture-dependent changes of neural stem cells derived from the ventral midbrain coincided with loss of RNA-binding protein LIN28A expression. When LIN28A expression was forced and sustained during neural stem cell expansion using an inducible expression-vector system, loss of dopamine neurogenic potential and midbrain phenotypes after long-term culturing was blocked. Furthermore, dopamine neurons that differentiated from neural stem cells exhibited remarkable survival and resistance against toxic insults. The observed effects were not due to a direct action of LIN28A on the differentiated dopamine neurons, but rather its action on precursor neural stem cells as exogene expression was switched off in the differentiating/differentiated cultures. Remarkable and reproducible behavioural recovery was shown in all Parkinson's disease rats grafted with neural stem cells expanded with LIN28A expression, along with extensive engraftment of dopamine neurons expressing mature neuronal and midbrain-specific markers. These findings suggest that LIN28A expression during stem cell expansion could be used to prepare therapeutically competent donor cells.

16.
Endocrinol Metab (Seoul) ; 30(4): 494-501, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26354491

RESUMO

BACKGROUND: Several inflammatory biomarkers, especially a high preoperative neutrophil-to-lymphocyte count ratio (NLR) and platelet-to-lymphocyte count ratio (PLR), are known to be indicator of poor prognosis in several cancers. However, very few studies have evaluated the significance of the NLR and PLR in papillary thyroid cancer (PTC). We evaluated the association of the preoperative NLR and PLR with clinicopathological characteristics in patients with PTC. METHODS: This study included 1,066 female patients who underwent total thyroidectomy for PTC. Patients were stratified into 4 quartiles by preoperative NLR and PLR. And the combination of preoperative NLR and PLR was calculated on the basis of data obtained value of tertile as follows: patients with both an elevated PLR and an elevated NLR were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. RESULTS: The preoperative NLR and PLR were significantly lower in patients aged ≥45 years and in patients with Hashimoto's thyroiditis. The PLR was significantly higher in patients with tumor size >1 cm (P=0.021).When the patients were categorized into the aforementioned four groups, the group with the higher preoperative PLR was found to have a significantly increased incidence of lateral lymph node metastasis (LNM) (P=0.018). However, there are no significant association between the combination of preoperative NLR and PLR and prognostic factors in PTC patients. CONCLUSION: These results suggest that a preoperative high PLR were significant associated with lateral LNM in female patients with PTC.

17.
Intern Med ; 53(18): 2095-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25224195

RESUMO

We identified a rare follicular thyroid carcinoma (FTC) metastasis to the pancreas in a patient of FTC. A 65-year-old woman presented at our hospital for evaluation of a pancreatic mass. She had a history of FTC. After total thyroidectomy, I-131 whole body scan showed increased I-131 uptake in the thyroid bed, but there was no evidence of distant metastasis. However, F-18 FDG PET/CT showed a mass with FDG uptake in the pancreatic head. Follow-up PET/CT showed FDG uptake in the pancreatic head and thyroid bed. Pylorus preserving pancreaticoduodenectomy was performed. Histopathological examination supported the diagnosis of metastatic FTC to pancreas.


Assuntos
Adenocarcinoma Folicular/secundário , Radioisótopos do Iodo , Neoplasias Pancreáticas/secundário , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Glândula Tireoide/patologia , Tomografia Computadorizada por Raios X/métodos , Imagem Corporal Total/métodos , Adenocarcinoma Folicular/diagnóstico , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico por imagem
18.
Thyroid ; 24(11): 1618-24, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25133449

RESUMO

BACKGROUND: Vitamin D has recently attracted attention because reduced levels are associated with the prevalence and aggressiveness of several cancers. This study aimed to evaluate the relationship between preoperative serum 25 hydroxyvitamin D (25(OH) vitamin D) levels and clinicopathologic characteristics in female patients with papillary thyroid cancer (PTC). METHODS: A total of 548 female patients who underwent total thyroidectomy for PTC between June 2012 and May 2013 were included. Blood samples were obtained within two weeks prior to surgery. Patients were categorized into four quartiles by preoperative serum 25(OH) vitamin D levels. The clinicopathologic features of PTC were analyzed retrospectively. RESULTS: Preoperative 25(OH) vitamin D was significantly lower in patients with a tumor size of >1 cm (p = 0.041) or lymph node metastasis (LNM; p = 0.043). No significant trends in several clinicopathologic features were observed in relation to increasing serum vitamin D concentrations except decreasing tumor size (p = 0.010). Patients in the second quartile had a greater occurrence of T stage 3/4 (odds ratio (OR) 2.03 [confidence interval (CI) 1.19-3.44]; p = 0.009), LNM (OR 2.03 [CI 1.19-3.44]; p = 0.009), lateral LNM (OR 5.03 [CI 1.66-15.28]; p = 0.004), and extrathyroidal extension (ETE; OR 1.95 [CI 1.15-3.29]; p = 0.013) than those in the fourth quartile. Multivariate analysis showed that patients in the second quartile had a greater occurrence of T stage 3/4 (OR 1.89 [CI 1.08-3.30]; p = 0.026), LNM (OR 2.04 [CI 1.20-3.47]; p = 0.009), lateral LNM (OR 5.12 [CI 1.68-15.59]; p = 0.004), and ETE (OR 1.81 [CI 1.04-3.15]; p = 0.036) than those in the fourth quartile. When the subjects were recategorized into two groups by median 25(OH) vitamin D levels, those with values below the median had a significantly higher risk of T stage 3/4, LNM, lateral LNM, stage III/IV, and ETE. All values except ETE sustained significance after adjustment. CONCLUSION: Lower preoperative serum 25(OH) vitamin D levels appear to be associated with poor clinicopathologic features in female patients with PTC.


Assuntos
Carcinoma Papilar/sangue , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/sangue , Vitamina D/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Vitamina D/sangue , Adulto Jovem
19.
Osong Public Health Res Perspect ; 4(6): 329-41, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24524022

RESUMO

OBJECTIVES: The study objective was to identify the factors that influence the length of stay (LOS) in hospital for stroke patients and to provide data for managing hospital costs by managing the LOS. METHODS: This study used data from the Discharge Injury Survey of the Korea Centers for Disease Control and Prevention, which included 17,364 cases from 2005 to 2008. RESULT: The LOS for stroke, cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage was 18.6, 15.0, 28.9, and 25.3 days, respectively. Patients who underwent surgery had longer LOS. When patients were divided based on whether they had surgery, there was a 2.4-time difference in the LOS for patients with subarachnoid hemorrhage, 2.0-time difference for patients with cerebral infarction, and 1.4-time difference for patients with intracerebral hemorrhage. The emergency route of admission and other diagnosis increased LOS, whereas hypertension and diabetic mellitus reduced LOS. CONCLUSION: In the present rapidly changing hospital environments, hospitals approach an efficient policy for LOS, to maintain their revenues and quality of assessment. If LOS is used as the indicator of treatment expenses, there is a need to tackle factors that influence the LOS of stroke patients for each disease group who are divided based on whether surgery is performed or not for the proper management of the LOS.

20.
Korean J Hematol ; 47(3): 207-12, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23071476

RESUMO

BACKGROUND: Maximum standardized uptake value (SUVmax) and maximum tumor diameter (MTD) have been shown to reflect survival outcome in diffuse large B cell lymphoma (DLBCL). However, applying these values to primary extranodal DLBCL is difficult because they are separate nosological entities with differences in genetic origin. We therefore decided to evaluate whether SUVmax and MTD on 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18-FDG) positron emission tomography (PET) would affect the survival outcome in primary extranodal DLBCL. METHODS: From October 2005 to November 2010, 76 primary extranodal DLBCL patients receiving R-CHOP therapy were analyzed. All patients had undergone an initial 18-FDG PET/CT and conventional computed tomography (CT) of the neck, chest, abdomen, and pelvis for staging. Median follow-up period was 35 months. RESULTS: The SUVmax and MTD cut-off values were 11.0 and 7.5 cm, respectively. SUVmax≥11.0 predicted a short progression free survival (PFS, P=0.002) and overall survival (OS, P=0.002). MTD≥7.5 cm was associated with poor PFS (P=0.003) and OS (P=0.003). High International Prognostic Index (IPI) was also associated with the survival outcome (PFS, P=0.046; OS, P=0.030). Multivariate analysis revealed that SUVmax≥11.0 (PFS, hazard ratio [HR]=10.813, P=0.024; OS, HR=6.312, P=0.015); MTD≥7.5 cm (PFS, HR=5.631, P=0.008; OS, HR=4.072, P=0.008); and high IPI (PFS, P=0.027; OS, P=0.046) were independent prognostic factors. CONCLUSION: It appears that both MTD and SUVmax can be independent prognostic factors in primary extranodal DLBCL.

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