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1.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946862

RESUMO

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

2.
Surg Oncol ; 37: 101570, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33839443

RESUMO

BACKGROUND: Plasma D-dimer levels have been associated with tumor progression and oncological outcomes in several cancers. This study assessed the relationships of D-dimer levels with clinicopathological features and survival outcomes in patients with gastric cancer undergoing gastrectomy. METHODS: Data from 666 patients with gastric cancer who underwent gastrectomy between June 2012 and December 2015 were collected and analyzed; these data were acquired during a previous randomized clinical trial (PROTECTOR trial, NCT01448746). Optimal cut-off values of preoperative, immediate postoperative, postoperative-day 1, postoperative-day 4, and postoperative-day 30 D-dimer levels for predicting overall survival (OS) and disease-free survival (DFS) were determined using Contal and O'Quigley's method. The optimal cut-off value of the immediate postoperative D-dimer level for predicting OS was 3.33. Patients were divided into D-dimer high and low groups based on these cut-off values. RESULTS: High immediate postoperative D-dimer levels were significantly associated with advanced T stage and TNM stage (P = 0.001 and P = 0.006, respectively). OS and DFS were significantly lower for patients in the D-dimer high group than for patients in the D-dimer low group; this relationship was consistent for preoperative, immediate postoperative, postoperative-day 1, and postoperative-day 30 D-dimer levels. Multivariate analysis identified the immediate postoperative D-dimer level as an independent prognostic factor for OS (hazard ratio, 2.52; P = 0.010). CONCLUSIONS: Elevated immediate postoperative D-dimer level was predictive of poor long-term outcomes in patients with gastric cancer after gastrectomy. Immediate postoperative D-dimer levels may offer simple and inexpensive clinical decision-making guidance for patients with gastric cancer after gastrectomy.

3.
Nutrients ; 13(3)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806628

RESUMO

Cone of Pinus densiflora (CP), or Korean red pinecone, is a cluster of Pinus densiflora fruit. CP has also been verified in several studies to have anti-oxidation, anti-fungal, anti-bacterial, and anti-melanogenic effects. However, anti-inflammatory effects have not yet been confirmed in the inflammatory responses of pinecones to allergic contact dermatitis. The purpose of this study is to prove the anti-inflammatory effect of CP on allergic contact dermatitis (ACD) in vitro and in vivo. CP inhibited the expression of TSLP, TARC, MCP-1, TNF-α, and IL-6 in TNF-α/IFN-γ-stimulated HaCaT cells and MCP-1, GM-CSF, TNF-α, IL-6, and IL-8 in PMACI (phorbol-12-myristate-13-acetate plus A23187)-stimulated HMC-1 cells. CP inhibited the phosphorylation of mitogen-activated protein kinase (MAPKs), as well as the translocation of NF-κB on TNF-α/IFN-γ stimulated in HaCaT cells. In vivo, CP decreased major symptoms of ACD, levels of IL-6 in skin lesion, thickening of the epidermis and dermis, infiltration of eosinophils and mast cells, and the infiltration of CD4+ T cells and CD8+ T cells. This result suggests that CP represents a potential alternative medicine to ACD for diseases such as chronic skin inflammation.

4.
Thorac Cancer ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33829665

RESUMO

BACKGROUND: Skeletal muscle depletion (sarcopenia) is associated with poor prognosis in patients with lung cancer. We analyzed changes in skeletal muscle area using serial computed tomography (CT) until the death of patients with advanced squamous cell lung cancer (SQCLC). METHODS: This retrospective study comprised 70 consecutive patients who underwent palliative chemotherapy for SQCLC. The cross-sectional area of the skeletal muscle at the level of the first lumbar vertebra (L1) was measured using chest CT. An artificial intelligence algorithm was developed and used for the serial assessment of the muscle area. Sarcopenia was defined as an L1 skeletal muscle index <46 cm2 /m2 in men and < 29 cm2 /m2 in women. RESULTS: The median age was 69 years; 62 patients (89%) had metastatic disease at the time of initial diagnosis. Sarcopenia was present in 58 patients (82.9%) at baseline; all patients experienced net muscle loss over the disease trajectory. The median overall survival was 8.7 (95% confidence interval 5.9-11.5) months. The mean percentage loss of skeletal muscle between the first and last CT was 16.5 ± 11.0%. Skeletal muscle loss accelerated over time and was the highest in the last 3 months of life (p < 0.001). Patients losing skeletal muscle rapidly (upper tertile, >3.24 cm2 /month) had shorter overall survival than patients losing skeletal muscle slowly (median, 5.7 vs. 12.0 months, p < 0.001). CONCLUSIONS: Patients with advanced SQCLC lose a significant amount of skeletal muscle until death. The rate of muscle area reduction is faster at the end of life.

5.
Mol Reprod Dev ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33843103

RESUMO

This study investigated the effect of the antioxidant dieckol, a component of Ecklonia cava, on maturation and developmental competence of porcine oocytes exposed to oxidative stress in vitro. Oocytes were matured in in vitro maturation (IVM) medium containing various concentrations of dieckol. The blastocyst formation rate was highest in the 0.5 µM dieckol-treated (0.5 DEK) group. The reactive oxygen species level was decreased, and the level of glutathione and expression of antioxidant genes (NFE2L, SOD1, and SOD2) at metaphase II were increased in the 0.5 DEK group. Abnormal spindle organization and chromosome misalignment were prevented in the 0.5 DEK group. Expression of maternal markers (CCNB1 and MOS) and activity of p44/42 mitogen-activated protein kinase were increased in the 0.5 DEK group. After parthenogenetic activation, the total number of cells per blastocyst was increased and the percentage of apoptotic cells was decreased in the 0.5 DEK group. Expression of development-related genes (CX45, CDX2, POU5F1, and NANOG), antiapoptotic genes (BCL2L1 and BIRC5), and a proapoptotic gene (CASP3) were altered in the 0.5 DEK group. These results indicate that the antioxidant dieckol improves IVM and subsequent development of porcine oocytes and can be used to improve the quality of oocytes under peroxidation experimental conditions.

6.
Cells ; 10(4)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918778

RESUMO

Canonical transient receptor potential 6 (TRPC6) channels have been implicated in familial and acquired forms of focal and segmental glomerulosclerosis (FSGS) in patients and animal models, as well as in renal fibrosis following ureteral obstruction in mice. Aging also evokes declines in renal function owing to effects on almost every renal compartment in humans and rodents. Here, we have examined the role of TRPC6 in driving inflammation and fibrosis during aging in Sprague-Dawley rats. This was assessed in rats with non-functional TRPC6 channels owing to CRISPR-Cas9 deletion of a portion of the ankyrin repeat domain required for the assembly of functional TRPC6 channels (Trpc6del/del rats). Wild-type littermates (Trpc6wt/wt rats) were used as controls. Animals were evaluated at 2 months and 12 months of age. There was no sign of kidney disease at 2 months of age, regardless of genotype. However, by 12 months of age, all rats examined showed declines in renal function associated with albuminuria, azotemia and increased urine excretion of ß2-microglobulin, a marker for proximal tubule pathology. These changes were equally severe in Trpc6wt/wt and Trpc6del/del rats. We also observed age-related increases in renal cortical expression of markers of fibrosis (α-smooth muscle actin and vimentin) and inflammation (NLRP3 and pro-IL-1ß), and there was no detectable protective effect of TRPC6 inactivation. Tubulointerstitial fibrosis assessed from histology also appeared equally severe in Trpc6wt/wt and Trpc6del/del rats. By contrast, glomerular pathology, blindly scored from histological sections, suggested a significant protective effect of TRPC6 inactivation, but only within the glomerular compartment.

7.
PLoS One ; 16(4): e0249399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33857181

RESUMO

OBJECTIVE: The chest X-ray (CXR) is the most readily available and common imaging modality for the assessment of pneumonia. However, detecting pneumonia from chest radiography is a challenging task, even for experienced radiologists. An artificial intelligence (AI) model might help to diagnose pneumonia from CXR more quickly and accurately. We aim to develop an AI model for pneumonia from CXR images and to evaluate diagnostic performance with external dataset. METHODS: To train the pneumonia model, a total of 157,016 CXR images from the National Institutes of Health (NIH) and the Korean National Tuberculosis Association (KNTA) were used (normal vs. pneumonia = 120,722 vs.36,294). An ensemble model of two neural networks with DenseNet classifies each CXR image into pneumonia or not. To test the accuracy of the models, a separate external dataset of pneumonia CXR images (n = 212) from a tertiary university hospital (Gachon University Gil Medical Center GUGMC, Incheon, South Korea) was used; the diagnosis of pneumonia was based on both the chest CT findings and clinical information, and the performance evaluated using the area under the receiver operating characteristic curve (AUC). Moreover, we tested the change of the AI probability score for pneumonia using the follow-up CXR images (7 days after the diagnosis of pneumonia, n = 100). RESULTS: When the probability scores of the models that have a threshold of 0.5 for pneumonia, two models (models 1 and 4) having different pre-processing parameters on the histogram equalization distribution showed best AUC performances of 0.973 and 0.960, respectively. As expected, the ensemble model of these two models performed better than each of the classification models with 0.983 AUC. Furthermore, the AI probability score change for pneumonia showed a significant difference between improved cases and aggravated cases (Δ = -0.06 ± 0.14 vs. 0.06 ± 0.09, for 85 improved cases and 15 aggravated cases, respectively, P = 0.001) for CXR taken as a 7-day follow-up. CONCLUSIONS: The ensemble model combined two different classification models for pneumonia that performed at 0.983 AUC for an external test dataset from a completely different data source. Furthermore, AI probability scores showed significant changes between cases of different clinical prognosis, which suggest the possibility of increased efficiency and performance of the CXR reading at the diagnosis and follow-up evaluation for pneumonia.

8.
Psychiatry Res ; 299: 113850, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33711561

RESUMO

Emerging high-throughput proteomic technologies have recently been considered as a powerful means of identifying substrates involved in mood disorders. We performed proteomic profiling using liquid chromatography-tandem mass spectrometry to identify dysregulated proteins in plasma samples of 42 and 45 patients with major depressive disorder (MDD) and bipolar disorder (BD), respectively, in comparison to 51 healthy controls (HCs). Fourteen and six proteins in MDD and BD patients, respectively, were differentially expressed compared to HCs, among which coagulation factor XIII A chain (F13A1), platelet basic protein (PPBP), platelet facor 4 (PF4), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and thymosin beta-4 (TMSB4X) were altered in both disorders. For proteins dysregulated in both, except F13A1, higher fold changes were observed in MDD than in BD patients. These findings may help identify candidate biomarkers of mood disorders and elucidate their underlying pathophysiology and biochemical abnormalities.

9.
BMC Cardiovasc Disord ; 21(1): 129, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750304

RESUMO

BACKGROUND: Annual influenza vaccination is an important public health measure to prevent influenza infections and is strongly recommended for cardiovascular disease (CVD) patients, especially in the current coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to develop a machine learning model to identify Korean adult CVD patients with low adherence to influenza vaccination METHODS: Adults with CVD (n = 815) from a nationally representative dataset of the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V) were analyzed. Among these adults, 500 (61.4%) had answered "yes" to whether they had received seasonal influenza vaccinations in the past 12 months. The classification process was performed using the logistic regression (LR), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGB) machine learning techniques. Because the Ministry of Health and Welfare in Korea offers free influenza immunization for the elderly, separate models were developed for the < 65 and ≥ 65 age groups. RESULTS: The accuracy of machine learning models using 16 variables as predictors of low influenza vaccination adherence was compared; for the ≥ 65 age group, XGB (84.7%) and RF (84.7%) have the best accuracies, followed by LR (82.7%) and SVM (77.6%). For the < 65 age group, SVM has the best accuracy (68.4%), followed by RF (64.9%), LR (63.2%), and XGB (61.4%). CONCLUSIONS: The machine leaning models show comparable performance in classifying adult CVD patients with low adherence to influenza vaccination.


Assuntos
Doenças Cardiovasculares/epidemiologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Adesão à Medicação , Máquina de Vetores de Suporte , Vacinação , Adulto , Fatores Etários , Idoso , Doenças Cardiovasculares/diagnóstico , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , República da Coreia/epidemiologia , Medição de Risco , Fatores de Risco , Adulto Jovem
10.
Sci Rep ; 11(1): 5762, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707643

RESUMO

Interstitial lung disease (ILD), particularly idiopathic pulmonary fibrosis (IPF), has a poor prognosis. Corticosteroids are widely used in the treatment of acute exacerbation of ILD (AE-ILD). This study aimed to clarify the causes of AE-ILD, determine the efficacy of corticosteroids for treating AE-ILD, and detect differences in the mortality rate among subgroups of ILD. This was an observational retrospective single-center study. Patients with ILD who presented to the emergency department with acute respiratory symptoms from January 1, 2016, to December 31, 2018, were included. Patients with AE-ILD were classified into two groups depending on the prednisolone dose: low dose (0 to 1.0 mg/kg) or high dose (> 1.0 mg/kg). Mortality rates between patients with and without IPF were compared. This study included 182 patients with AE-ILD, including IPF (n = 117) and non-IPF (n = 65). Multivariate Cox regression analysis showed that corticosteroid dose (HR: 0.221, CI: 0.102-0.408, P < 0.001), initial P/F ratio (HR:0.995, CI:0.992-0.999, P = 0.006), and mechanical ventilation within 3 days of hospitalization (HR:4.205, CI:2.059-8.589, P < 0.001) were independent risk factors for mortality in patients with AE-ILD. This study showed that outcomes improve with higher doses of corticosteroids (> 1 mg/kg prednisolone) in patients with AE-non-IPF-ILD. However, this was not the case in patients with AE-IPF.

11.
Sci Rep ; 11(1): 2777, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531571

RESUMO

There is no validated clinical biomarker for disease severity or treatment response for nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the correlation between elevated serum carbohydrate antigen (CA) 19-9 levels and NTM-PD disease activity, defined using an imaging severity score based on chest computed tomography (CT). We retrospectively examined 79 patients with NTM-PD who underwent serum CA19-9 level assessments and chest CT less than 1 month apart. NTM-PD severity was rated using a CT-based scoring system. The correlation between the CT score and serum CA19-9 levels was evaluated. Chest CT revealed nodular bronchiectasis without cavitation in most patients (78.5%). Serum CA19-9 levels were elevated in 19 (24%) patients. Serum CA19-9 levels were positively correlated with the total CT score and bronchiectasis, bronchiolitis, cavity, and consolidation subscores. Partial correlation analysis revealed a significant positive correlation between serum CA19-9 levels and CT scores for total score and bronchiectasis, bronchiolitis, cavitation, and consolidation subscores after controlling for age, sex, and BMI. Serum CA19-9 levels were positively correlated with the CT severity score for NTM-PD. Serum CA19-9 may be useful in evaluating disease activity or therapeutic response in patients with NTM-PD.

12.
PLoS One ; 16(2): e0246472, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33606779

RESUMO

PURPOSE: This study evaluated the performance of a commercially available deep-learning algorithm (DLA) (Insight CXR, Lunit, Seoul, South Korea) for referable thoracic abnormalities on chest X-ray (CXR) using a consecutively collected multicenter health screening cohort. METHODS AND MATERIALS: A consecutive health screening cohort of participants who underwent both CXR and chest computed tomography (CT) within 1 month was retrospectively collected from three institutions' health care clinics (n = 5,887). Referable thoracic abnormalities were defined as any radiologic findings requiring further diagnostic evaluation or management, including DLA-target lesions of nodule/mass, consolidation, or pneumothorax. We evaluated the diagnostic performance of the DLA for referable thoracic abnormalities using the area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity using ground truth based on chest CT (CT-GT). In addition, for CT-GT-positive cases, three independent radiologist readings were performed on CXR and clear visible (when more than two radiologists called) and visible (at least one radiologist called) abnormalities were defined as CXR-GTs (clear visible CXR-GT and visible CXR-GT, respectively) to evaluate the performance of the DLA. RESULTS: Among 5,887 subjects (4,329 males; mean age 54±11 years), referable thoracic abnormalities were found in 618 (10.5%) based on CT-GT. DLA-target lesions were observed in 223 (4.0%), nodule/mass in 202 (3.4%), consolidation in 31 (0.5%), pneumothorax in one 1 (<0.1%), and DLA-non-target lesions in 409 (6.9%). For referable thoracic abnormalities based on CT-GT, the DLA showed an AUC of 0.771 (95% confidence interval [CI], 0.751-0.791), a sensitivity of 69.6%, and a specificity of 74.0%. Based on CXR-GT, the prevalence of referable thoracic abnormalities decreased, with visible and clear visible abnormalities found in 405 (6.9%) and 227 (3.9%) cases, respectively. The performance of the DLA increased significantly when using CXR-GTs, with an AUC of 0.839 (95% CI, 0.829-0.848), a sensitivity of 82.7%, and s specificity of 73.2% based on visible CXR-GT and an AUC of 0.872 (95% CI, 0.863-0.880, P <0.001 for the AUC comparison of GT-CT vs. clear visible CXR-GT), a sensitivity of 83.3%, and a specificity of 78.8% based on clear visible CXR-GT. CONCLUSION: The DLA provided fair-to-good stand-alone performance for the detection of referable thoracic abnormalities in a multicenter consecutive health screening cohort. The DLA showed varied performance according to the different methods of ground truth.

13.
Ecotoxicol Environ Saf ; 211: 111947, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33503546

RESUMO

The chicken (Gallus gallus), which has three aryl hydrocarbon receptor (AHR) isoforms (ckAHR1, ckAHR2, and ckAHR1ß) and two AHR nuclear translocator (ARNT) isoforms (ckARNT1 and ckARNT2), is highly sensitive to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and can serve as an avian model to gain an understanding of the mechanism underlying dioxin toxicity. To elucidate the mechanism of TCDD-induced immunotoxicity in avian species, we treated chicken embryos in ovo with graded concentrations of TCDD (1.5, 2.5, 3.0, 3.3, 3.5, and 4.0 µM). Initially, we measured mRNA expression levels of ckAHR and ckARNT isoforms and analyzed the T cell populations and transcriptome in the thymuses of TCDD-treated chicken embryos. Quantitative polymerase chain reaction analysis revealed that mRNA expressions of ckAHR1 and ckARNT2 were dominant in the thymus. Severe weight loss and thymus atrophy were observed in the TCDD-treated embryos. Immunophenotyping analyses demonstrated significant increases in CD4+CD8-CD25+ and CD4+CD8+CD25+ regulatory T cells (Tregs) populations following TCDD exposure, suggesting that TCDD suppresses T cell-mediated immune responses in chicken embryos. In addition, thymic transcriptome analyses intimated that alteration of the signaling pathways related to erb-b2 receptor tyrosine kinase 4 (ERBB4) and wnt family member 5A (WNT5A), and bone morphogenetic protein (BMP) may be associated with the TCDD-induced thymus atrophy. We also observed significantly altered expression levels of genes including interleukine 13 receptor subunit alpha 2 (IL13RA2), transforming growth factor beta 1 (TGFß1), collagen type III alpha 1 chain (COL3A1), and collagen type IX alpha 3 chain (COL9A3), implying immunosuppression, fibrosis development, and collagen deposition. Collectively, these findings suggest that TCDD exposure activates the ckAHR1-ckARNT2 signaling pathway and suppresses immune responses through the prompted differentiation to CD4+CD8-CD25+ and CD4+CD8+CD25+ Tregs and altered expressions of immune-related genes in the thymus of chicken embryos.


Assuntos
Poluentes Ambientais/toxicidade , Dibenzodioxinas Policloradas/toxicidade , Animais , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Linfócitos T CD8-Positivos/metabolismo , Diferenciação Celular , Embrião de Galinha , Galinhas/metabolismo , Sistema Imunitário/efeitos dos fármacos , Isoformas de Proteínas/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Linfócitos T , Transcriptoma
14.
Sci Rep ; 11(1): 1360, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446731

RESUMO

Despite the tremendous advancements made in cell tracking, in vivo imaging and volumetric analysis, it remains difficult to accurately quantify the number of infused cells following stem cell therapy, especially at the single cell level, mainly due to the sensitivity of cells. In this study, we demonstrate the utility of both liquid scintillator counter (LSC) and accelerator mass spectrometry (AMS) in investigating the distribution and quantification of radioisotope labeled adipocyte derived mesenchymal stem cells (AD-MSCs) at the single cell level after intravenous (IV) transplantation. We first show the incorporation of 14C-thymidine (5 nCi/ml, 24.2 ng/ml) into AD-MSCs without affecting key biological characteristics. These cells were then utilized to track and quantify the distribution of AD-MSCs delivered through the tail vein by AMS, revealing the number of AD-MSCs existing within different organs per mg and per organ at different time points. Notably, the results show that this highly sensitive approach can quantify one cell per mg which effectively means that AD-MSCs can be detected in various tissues at the single cell level. While the significance of these cells is yet to be elucidated, we show that it is possible to accurately depict the pattern of distribution and quantify AD-MSCs in living tissue. This approach can serve to incrementally build profiles of biodistribution for stem cells such as MSCs which is essential for both research and therapeutic purposes.

15.
Cells ; 10(1)2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33401457

RESUMO

Calcific aortic valve disease (CAVD) accompanies inflammatory cell infiltration, fibrosis, and ultimately calcification of the valve leaflets. We previously demonstrated that dipeptidyl peptidase-4 (DPP-4) is responsible for the progression of aortic valvular calcification in CAVD animal models. As evogliptin, one of the DPP-4 inhibitors displays high specific accumulation in cardiac tissue, we here evaluated its therapeutic potency for attenuating valvular calcification in CAVD animal models. Evogliptin administration markedly reduced calcific deposition accompanied by a reduction in proinflammatory cytokine expression in endothelial nitric oxide synthase-deficient mice in vivo, and significantly ameliorated the mineralization of the primary human valvular interstitial cells (VICs), with a reduction in the mRNA expression of bone-associated and fibrosis-related genes in vitro. In addition, evogliptin ameliorated the rate of change in the transaortic peak velocity and mean pressure gradients in our rabbit model as assessed by echocardiography. Importantly, evogliptin administration in a rabbit model was found to suppress the effects of a high-cholesterol diet and of vitamin D2-driven fibrosis in association with a reduction in macrophage infiltration and calcific deposition in aortic valves. These results have indicated that evogliptin prohibits inflammatory cytokine expression, fibrosis, and calcification in a CAVD animal model, suggesting its potential as a selective therapeutic agent for the inhibition of valvular calcification during CAVD progression.

16.
Expert Rev Med Devices ; 18(1): 91-106, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33307881

RESUMO

BACKGROUND: Growth hormone (GH) treatment preference and adherence are affected by delivery device convenience, injection-site pain, confidence in correct dose administration, and device satisfaction. This survey investigated if switching device to NordiFlex® improved treatment experience in pediatric patients in South Korea. DESIGN AND METHODS: Patients aged 4-≤18 years were surveyed. Participants were NordiFlex® users who previously used NordiLet®/other devices. Participants compared preference, self-reported adherence, satisfaction, perceived ease of use, and device subjective benefits (across four domains: ease of use, self-efficacy, minimal disruption of daily life, positive feelings about injections) of NordiFlex® vs. previous device. RESULTS: Ninety-four patients were enrolled, of which 91.5% previously used NordiLet®. Significantly more patients preferred, and were more satisfied with NordiFlex® vs. previous device; mean score: 0.65 (95% confidence interval [CI]:0.41;0.88) and 0.61 (95% CI:0.36;0.85), respectively. Participants reported greater perceived ease of use (0.49 [95% CI:0.26;0.72]) and fewer missed injections (0.20 [95% CI:0.06;0.34], with NordiFlex® vs. previous device. Bivariate analysis showed significant associations between preference for NordiFlex® and higher scores on self-efficacy, ease of use, minimal disruption of daily life, and positive feelings about injection (all p < 0.001). CONCLUSION: These results suggest that improvements in device features could be associated with improved treatment experience.


Assuntos
Hormônio do Crescimento Humano/farmacologia , Injeções/instrumentação , Medidas de Resultados Relatados pelo Paciente , Adolescente , Cuidadores , Criança , Feminino , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Masculino , Análise Multivariada , Cooperação do Paciente , Satisfação do Paciente , República da Coreia , Autorrelato , Inquéritos e Questionários , Resultado do Tratamento
17.
Ecotoxicol Environ Saf ; 207: 111263, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32916532

RESUMO

Tris(2-chloroethyl) phosphate (TCEP) is an organophosphate flame retardant that used in textiles, industrial materials, and furniture to delay the spread of fire after ignition. TCEP has been detected in the tissues and eggs of fish and birds. However, there are no studies regarding the effects of TCEP on avian embryos. In the present study, we investigated the developmental toxicity of TCEP exposure on chicken embryos in a shell-less incubation system, which enables in situ observation. Chicken embryos were treated with graded doses of TCEP (50, 250, and 500 nmol/g egg) on incubation day 0. The survival rate, morphological biometrics, heart rate, and length and branch number of extraembryonic blood vessels were measured on incubation days 3-9. Survival rates were reduced from incubation day 3 and were significantly decreased until day 9. Body length, head + bill length and eye diameter were significantly reduced by TCEP exposure. Regarding skeletal effects, spine length was decreased in a dose-dependent manner on day 9. Body weight on day 9 significantly reduced in all TCEP treatment groups. These results suggest that TCEP exposure to >50 nmol/g egg retards development in chicken embryos. TCEP exposure to 500 nmol/g egg significantly increased heart weight to body weight ratio in the embryos. More than 250 nmol/g egg of TCEP significantly reduced the heart rate of embryos in the early developmental stage. The formation of extraembryonic blood vessels and the number of erythrocytes were significantly reduced even with 50 nmol/g egg of TCEP. These findings suggest that TCEP exposure specifically affects the cardiovascular system in chicken embryos, which leads to developmental delay. The results of this study also demonstrate that the shell-less incubation system can be used to continuously monitor the effects of chemicals on developing avian embryos.


Assuntos
Retardadores de Chama/toxicidade , Compostos Organofosforados/toxicidade , Animais , Embrião de Galinha , Galinhas , Organofosfatos/toxicidade , Fosfatos
18.
Psychiatry Investig ; 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33301669

RESUMO

OBJECTIVE: Adjustment disorder (AD) remains an ambiguous diagnosis that overlaps with major depressive disorder (MDD). This study compared autonomic reactivity to the stress between AD and MDD to test for biological differences. METHODS: Physically healthy Korean male soldiers admitted to a psychiatric ward were recruited for participation. Clinical diagnoses indicated that 62 patients with AD and 47 with MDD were selected. Procedures consisted of electrocardiogram measurements according to three consecutive phases lasting five minutes each [i.e., resting, stress (including a mental arithmetic task and Stroop color word test), and recovery]. RESULTS: The reactive trends of all heart rate variability (HRV) parameters related to the stress tasks in participants with AD did not differ from those with MDD. High-frequency HRV (a proxy of parasympathetic activity) increased during times of stress for participants with AD and MDD. Despite similar reactive trends, AD participants had higher HRV values than participants with MDD during whole phases, particularly for variables reflecting overall autonomic activity. CONCLUSION: AD is associated with higher basal activity in the autonomous nervous system when compared to MDD. However, both are associated with pathophysiology indicating an altered autonomic reactivity to stress.

19.
Clin Exp Pediatr ; 63(12): 454-462, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33264558

RESUMO

The Committee on Dyslipidemia of Korean Pediatric and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidence-based clinical practice guidelines for dyslipidemia in Korean children and adolescents. These guidelines were formulated with the Grading of Recommendations, which include both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. These guidelines are based on the 2011 National Heart, Lung, and Blood Institute Guidelines, which focus on the prevention of cardiovascular disease in children and draw from a comprehensive review of evidence. These guidelines contain the definition of and screening process for dyslipidemia and introduce new dietary methods: the Cardiovascular Health Integrated Lifestyle Diet (CHILD)-1, the CHILD-2-low-density lipoprotein cholesterol, and the CHILD-2-triglyceride. Potential drug therapies for dyslipidemia along with their main effects and doses were also included.

20.
Ann Pediatr Endocrinol Metab ; 25(4): 199-207, Dec. 31, 2020.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1146623

RESUMO

The Committee on Dyslipidemia of Korean Pediatric and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidence-based clinical practice guidelines for dyslipidemia in Korean children and adolescents. These guidelines were formulated with the Grading of Recommendations, which include both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. These guidelines are based on the 2011 National Heart, Lung, and Blood Institute Guidelines, which focus on the prevention of cardiovascular disease in children and draw from a comprehensive review of evidence. These guidelines contain the definition of and screening process for dyslipidemia and introduce new dietary methods: the Cardiovascular Health Integrated Lifestyle Diet (CHILD)-1, the CHILD-2-low-density lipoprotein cholesterol, and the CHILD-2-triglyceride. Potential drug therapies for dyslipidemia along with their main effects and doses were also included.


Assuntos
Humanos , Criança , Adolescente , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco , Aterosclerose/prevenção & controle , Dislipidemias/prevenção & controle , Comportamento Alimentar , República da Coreia/epidemiologia , Estilo de Vida
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