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1.
Medicina (Kaunas) ; 59(3)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36984593

RESUMO

Background and Objectives: The Child-Pugh (CP) score and Model for End-Stage Liver Disease (MELD) are classical systems for predicting mortality in patients with liver cirrhosis (LC). The MELD-GFR assessment in liver disease-sodium (MELD-GRAIL-Na) was designed to better reflect renal function and, therefore, provide better mortality predictions. This study aimed to compare the prediction accuracy of MELD-GRAIL-Na compared to CP and MELD in predicting short-term (1- and 3-month) mortality in Korean patients. Materials and Methods: Medical records of patients with LC admitted to the Konkuk University Hospital from 2015 to 2020 were retrospectively reviewed. Predictive values of the CP, MELD, and MELD-GRAIL-Na for 1-month and 3-month mortality were calculated using the area under the receiver operating curve (AUROC) and were compared using DeLong's test. Results: In total, 1249 patients were enrolled; 102 died within 1 month, and 146 within 3 months. AUROCs of CP, MELD, and MELD-GRAIL-Na were 0.831, 0.847, and 0.857 for 1-month mortality and 0.837, 0.827, and 0.835 for 3-month mortality, respectively, indicating no statistical significance. For patients with CP classes B and C, AUROCs of CP, MELD, and MELD-GRAIL-Na were 0.782, 0.809, and 0.825 for 1-month mortality and 0.775, 0.769, and 0.786 for 3-month mortality, respectively. There was a significant difference between CP and MELD-GRAIL-Na in predicting 1-month mortality (p = 0.0428) and between MELD and MELD-GRAIL-Na in predicting 1-month (p = 0.0493) and 3-month mortality (p = 0.0225). Conclusions: Compared to CP and MELD, MELD-GRAIL-Na was found to be a better and more useful system for evaluating short-term (1- and 3-month) mortality in Korean patients with cirrhosis, especially those with advanced cirrhosis (CP class B and C).


Assuntos
Doença Hepática Terminal , Cirrose Hepática , Humanos , Doença Hepática Terminal/mortalidade , Cirrose Hepática/mortalidade , Valor Preditivo dos Testes , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Curva ROC , Índice de Gravidade de Doença , Sódio , População do Leste Asiático
2.
Langmuir ; 37(38): 11301-11308, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34519211

RESUMO

In imparting wetting properties, a fabrication process without the addition of new compounds and deposition of coating layers would be the most desirable because it does not introduce additional complexities. Hence, the ion beam irradiation technique is used as it enables the chemistry of materials to be modified through simple adjustments of irradiation parameters such as the type of accelerated particles, beam energy, and fluence. In this study, the hydrophilicity of alumina surfaces was weakened by irradiating He ion beams of different energy levels (200 keV and 20 MeV). These transitions become more pronounced as the total beam fluence increases. In low-energy irradiation, the effect of irradiation is predominant near the surface, and hydrophilicity is weakened by the increase in carbon adsorption and suppression of dissociative adsorption of water molecules owing to the introduction of oxygen vacancies. In contrast, nuclear transmutations are induced by irradiation with high-energy beams. Consequently, fluorine is generated, and hydrophobic functional groups are formed on the surface. By varying the beam conditions, the wetting properties of the target ceramic can be controlled to the desired level, which is required in various industries, via appropriate adjustments of the beam parameters. In addition, the beam irradiation technique may be applicable to all ceramic materials, including lattice oxygen and alumina.

3.
J Appl Toxicol ; 40(2): 270-284, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31515828

RESUMO

Herbal medicines are widely utilized for disease prevention and health promotion. GHX02 consists of mixtures including Gwaruin (Trichosanthes kirilowii), Haengin (Prunus armeniaca), Hwangryeon (Coptis japonica) and Hwangkeum (Scutellaria baicalensis). It has been purported to have therapeutic effectiveness in cases of severe bronchitis. Non-clinical safety testing comprised a single-dose oral toxicity study and a 28-day repeated-dose oral toxicity study with a 14-day recovery period, and genotoxicity was assessed by a bacterial reverse mutation test, in vitro chromosomal aberration test, in vivo mouse bone marrow micronucleus test and single cell gel electrophoresis assay (comet assay). In the single-dose oral toxicity study, the approximate lethal dosage is estimated to be higher than 5000 mg/kg in rats. Thus, the dosage levels were set at 0, 1250, 2500 and 5000 mg/kg/day in the 28-day repeated-dose oral toxicity study, and 10 male rats and 10 female rats/dose were administered GHX02. No clinical signs of toxicological significance were recorded in any animal during the dosing and the observation period in the single-dose study. The no-observed-adverse-effect level of GHX02 was 5000 mg/kg/day when administered orally for 28 days to male and female Sprague-Dawley rats. Despite increases in the frequencies of cells with numerical chromosomal aberration in the in vitro test, the increases were not considered relevant to the in vivo genetic risk. Except for the increase of in vitro numerical chromosomal aberration, clear negative results were obtained from other genetic toxicity studies.


Assuntos
Bronquite/tratamento farmacológico , Relação Dose-Resposta a Droga , Extratos Vegetais/toxicidade , Extratos Vegetais/uso terapêutico , Plantas Medicinais/toxicidade , Administração Oral , Animais , Coptis/química , Testes de Mutagenicidade , Prunus armeniaca/química , Ratos Sprague-Dawley , Scutellaria baicalensis/química , Testes de Toxicidade , Trichosanthes/química
4.
Nano Lett ; 19(12): 8488-8494, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31726005

RESUMO

Synthesizing ceramic materials with a significant amount of deformability is one of the most important engineering pursuits. In this study, we demonstrate the emergence of metal-like plasticity through the crystallinity control in the monolithic zirconia with the vertically aligned honeycomb-like periodic nanopore structures fabricated using the anodizing technique. The crystalline orders of the nanoporous zirconia films vary between monoclinic, tetragonal, and amorphous phases after the heat treatment and/or proton irradiation, whereas the vertical pore structures are maintained. The micropillar compression tests on those samples reveal a large amount of plasticity, more than 20% of total stains, in the as-anodized and proton-irradiated samples, both of which contain the amorphous phase. In contrast, the fully crystallized zirconia that resulted from annealing at 500 °C shows the brittle failure, the typical characteristic of conventional ceramic foams. These results offer a new opportunity for the nanoporous ceramic materials to be used in various applications, benefited from the tunable structural stability.

5.
Biochem Biophys Res Commun ; 520(2): 459-465, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31607484

RESUMO

The peroxisome proliferator-activated receptor (PPAR)-α agonist fenofibrate is used as a lipid-lowering agent to reduce cholesterol and triglyceride in blood. In this study, we investigated whether fenofibrate affects osteoblast differentiation of osteogenic precursor cells. Quantitative real-time PCR and alkaline phosphatase (ALP) staining assays revealed that fenofibrate can enhance the osteoblast differentiation of C3H10T1/2 and MC3T3-E1 cells. In contrast with fenofibrate, the PPARγ agonist rosiglitazone decreased or did not affect the expression of osteogenic genes in these cells. Fenofibrate dose- and time-dependently increased PPARα expression, and concomitantly increased the expression of bone morphogenetic protein 2 (BMP2). Knockdown of PPARα abolished fenofibrate-induced BMP2 expression, activity of the BMP2 promoter gene, and calcium deposition. The chromatin immunoprecipitation assay demonstrated that fenofibrate increased BMP2 expression by inducing direct binding of PPARα to the BMP2 promoter region. Taken together, we suggest that fenofibrate has a stimulatory effect on osteoblast differentiation via the elevation of PPARα levels and the PPARα-mediated BMP2 expression. Our findings provide fenofibrate as a useful agent for controlling hypercholesterolemic patients with osteoporosis.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Fenofibrato/farmacologia , Osteoblastos/efeitos dos fármacos , PPAR alfa/metabolismo , Animais , Proteína Morfogenética Óssea 2/genética , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Osteoblastos/citologia , Osteoblastos/fisiologia , PPAR alfa/agonistas , PPAR alfa/genética , Regiões Promotoras Genéticas , Transcrição Gênica
6.
Omega (Westport) ; 79(1): 90-105, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-28622733

RESUMO

The purpose of this study is to examine suicide trends in South Korea, which has one of the highest suicide rates in the world. The results show that the male suicide rate outweighs that of females, the likelihood of committing suicide increases with age, and that, in regard to marital status, nonmarried people are the most at risk. In addition, several methods of reducing suicide rates are identified: the wider use of social networks to reduce social burden, the development of a social atmosphere where aging is accepted as a natural process, and the development of protection factors within families.


Assuntos
Estado Civil/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Fatores de Risco , Distribuição por Sexo
7.
J Virol ; 89(20): 10453-66, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26246563

RESUMO

UNLABELLED: The native envelope gene (env) of Jaagsiekte sheep retrovirus (JSRV) also acts as an oncogene. To investigate the mechanism of transformation, we performed yeast 2-hybrid screening for cellular proteins that interact with Env. Among several candidates, we identified mouse or rat zinc finger protein 111 (zfp111). The interaction between Env and Zfp111 was confirmed through in vivo coimmunoprecipitation assays. Knockdown of endogenous Zfp111 caused a decrease in cell transformation by JSRV Env, while overexpression of Zfp111 increased overall Env transformation, supporting a role for Zfp111 in Env transformation. Knockdown of Zfp111 had no effect on the growth rate of parental rat 208F cells, while it decreased the proliferation rate of JSRV-transformed 208F cells, suggesting that JSRV-transformed cells became dependent on Zfp111. In addition, Zfp111 preferentially bound to a higher-mobility form of JSRV Env that has not been described previously. The higher-mobility form of Env (P70(env)) was found exclusively in the nuclear fraction, and size of its polypeptide backbone was the same as that of the cytoplasmic Env polyprotein (Pr80(env)). The differences in glycosylation between the two versions of Env were characterized. These results identify a novel cellular protein, Zfp111, that binds to the JSRV Env protein, and this binding plays a role in Env transformation. These results indicate that JSRV transformation also involves proteins and interactions in the nucleus. IMPORTANCE: The envelope protein (Env) of Jaagsiekte sheep retrovirus (JSRV) is an oncogene, but its mechanism of cell transformation is still unclear. Here we identified seven candidate cellular proteins that can interact with JSRV Env by yeast two-hybrid screening. This study focused on one of the seven candidates, zinc finger protein 111 (Zfp111). Zfp111 was shown to interact with JSRV Env in cells and to be involved in JSRV transformation. Moreover, coexpression of JSRV Env and Zfp111 led to the identification of a novel nuclear form of the JSRV Env protein that binds Zfp111. Nuclear Env was found to differ by glycosylation from the cytoplasmic Env precursor to the virion envelope proteins. These results suggest that JSRV Env transformation may involve nuclear events such as an alteration in transcription mediated by Env-Zfp111 interactions.


Assuntos
Transformação Celular Neoplásica , Transformação Celular Viral , Fibroblastos/virologia , Retrovirus Jaagsiekte de Ovinos/química , Proteínas do Envelope Viral/química , Dedos de Zinco/genética , Animais , Linhagem Celular , Núcleo Celular/química , Núcleo Celular/metabolismo , Núcleo Celular/virologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Expressão Gênica , Vetores Genéticos , Glicosilação , Interações Hospedeiro-Patógeno , Humanos , Retrovirus Jaagsiekte de Ovinos/metabolismo , Lentivirus/genética , Camundongos , Ligação Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Ovinos , Transdução de Sinais , Técnicas do Sistema de Duplo-Híbrido , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
8.
Biochem Biophys Res Commun ; 456(4): 919-25, 2015 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-25534852

RESUMO

Estrogen receptors are activated by the hormone estrogen and they control cell growth by altering gene expression as a transcription factor. So far two estrogen receptors have been found: ERα and ERß. Estrogen receptors are also implicated in the development and progression of breast cancer. Here, we found that ERα localized on the spindle and spindle poles at the metaphase during mitosis. Depletion of ERα generated unaligned chromosomes in metaphase cells and lagging chromosomes in anaphase cells in a transcription-independent manner. Furthermore, the levels of ß-tubulin and γ-tubulin were reduced in ERα-depleted cells. Consistent with this, polymerization of microtubules in ERα-depleted cells and turnover rate of α/ß-tubulin were decreased than in control cells. We suggest that ERα regulates chromosome alignment and spindle dynamics by stabilizing microtubules during mitosis.


Assuntos
Cromossomos de Mamíferos/metabolismo , Receptor alfa de Estrogênio/metabolismo , Mitose , Fuso Acromático/metabolismo , Sobrevivência Celular , Segregação de Cromossomos , Células HeLa , Humanos , Metáfase , Transporte Proteico , Transcrição Gênica
9.
J Biol Chem ; 288(38): 27343-27357, 2013 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-23902763

RESUMO

Radioresistance is a major cause of decreasing the efficiency of radiotherapy for non-small cell lung cancer (NSCLC). To understand the radioresistance mechanisms in NSCLC, we focused on the radiation-induced Notch-1 signaling pathway involved in critical cell fate decisions by modulating cell proliferation. In this study, we investigated the use of Notch-1-regulating flavonoid compounds as novel therapeutic drugs to regulate radiosensitivity in NSCLC cells, NCI-H1299 and NCI-H460, with different levels of radioresistance. Rhamnetin and cirsiliol were selected as candidate Notch-1-regulating radiosensitizers based on the results of assay screening for activity and pharmacological properties. Treatment with rhamnetin or cirsiliol reduced the proliferation of NSCLC cells through the suppression of radiation-induced Notch-1 expression. Indeed, rhamnetin and cirsiliol increased the expression of tumor-suppressive microRNA, miR-34a, in a p53-dependent manner, leading to inhibition of Notch-1 expression. Consequently, reduced Notch-1 expression promoted apoptosis through significant down-regulation of the nuclear factor-κB pathway, resulting in a radiosensitizing effect on NSCLC cells. Irradiation-induced epithelial-mesenchymal transition was also notably attenuated in the presence of rhamnetin and cirsiliol. Moreover, an in vivo xenograft mouse model confirmed the radiosensitizing and epithelial-mesenchymal transition inhibition effects of rhamnetin and cirsiliol we observed in vitro. In these mice, tumor volume was significantly reduced by combinational treatment with irradiation and rhamnetin or cirsiliol compared with irradiation alone. Taken together, our findings provided evidence that rhamnetin and cirsiliol can act as promising radiosensitizers that enhance the radiotherapeutic efficacy by inhibiting radiation-induced Notch-1 signaling associated with radioresistance possibly via miR-34a-mediated pathways.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Transição Epitelial-Mesenquimal , Flavonas/farmacologia , Raios gama , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/terapia , MicroRNAs/biossíntese , Quercetina/análogos & derivados , RNA Neoplásico/biossíntese , Tolerância a Radiação/efeitos dos fármacos , Receptor Notch1/biossíntese , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , Quercetina/farmacologia , Tolerância a Radiação/efeitos da radiação , Proteína Supressora de Tumor p53/metabolismo
10.
Surg Endosc ; 28(11): 3134-42, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24879136

RESUMO

INTRODUCTION: Transaxillary robotic thyroidectomy is considered a technically feasible and safe treatment option for patients with low-risk papillary thyroid carcinoma (PTC). The aim of the present study was to determine the factors that contribute to the perioperative surgical outcomes of robotic thyroidectomy and to suggest guidelines for patient selection to be used by surgeons inexperienced in the technique. METHOD: We reviewed the records of 275 patients with PTC who underwent robotic total thyroidectomy using a gasless, transaxillary single-incision approach at Yonsei University Health System, South Korea, between January 2011 and May 2012. The association between surgical outcomes and clinicopathologic factors was assessed using linear and logistic regression analysis. RESULTS: The contributing factors for surgical outcomes of robotic thyroidectomy were categorized as patient factors, including gender and body mass index (BMI), and thyroid-specific factors, including thyroid gland size, coexistent thyroiditis, tumor size, and serum anti-thyroglobulin antibody and anti-microsomal antibody titers. Of these, male gender, a large thyroid gland, and thyroiditis significantly increased the total operation time. Male gender, thyroiditis, and overweight BMI increased the working space time, and a large thyroid gland and overweight BMI affected the console time. A large thyroid gland and histological thyroiditis were associated with increased intraoperative blood loss. There was no association between postoperative complications and clinicopathologic parameters. CONCLUSION: Male gender, overweight BMI, a large thyroid gland, and coexistent thyroiditis adversely affected the surgical outcome of robotic thyroidectomy. Surgeons inexperienced in the technique should avoid or carefully approach individuals with these factors.


Assuntos
Carcinoma/cirurgia , Robótica/métodos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adolescente , Adulto , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Índice de Massa Corporal , Carcinoma/epidemiologia , Carcinoma Papilar , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Tamanho do Órgão , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores Sexuais , Câncer Papilífero da Tireoide , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/epidemiologia , Tireoidite/epidemiologia , Resultado do Tratamento , Adulto Jovem
11.
JMIR Med Inform ; 12: e56893, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968600

RESUMO

BACKGROUND: To circumvent regulatory barriers that limit medical data exchange due to personal information security concerns, we use homomorphic encryption (HE) technology, enabling computation on encrypted data and enhancing privacy. OBJECTIVE: This study explores whether using HE to integrate encrypted multi-institutional data enhances predictive power in research, focusing on the integration feasibility across institutions and determining the optimal size of hospital data sets for improved prediction models. METHODS: We used data from 341,007 individuals aged 18 years and older who underwent noncardiac surgeries across 3 medical institutions. The study focused on predicting in-hospital mortality within 30 days postoperatively, using secure logistic regression based on HE as the prediction model. We compared the predictive performance of this model using plaintext data from a single institution against a model using encrypted data from multiple institutions. RESULTS: The predictive model using encrypted data from all 3 institutions exhibited the best performance based on area under the receiver operating characteristic curve (0.941); the model combining Asan Medical Center (AMC) and Seoul National University Hospital (SNUH) data exhibited the best predictive performance based on area under the precision-recall curve (0.132). Both Ewha Womans University Medical Center and SNUH demonstrated improvement in predictive power for their own institutions upon their respective data's addition to the AMC data. CONCLUSIONS: Prediction models using multi-institutional data sets processed with HE outperformed those using single-institution data sets, especially when our model adaptation approach was applied, which was further validated on a smaller host hospital with a limited data set.

12.
J Korean Soc Radiol ; 85(2): 445-450, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38617873

RESUMO

Gastric metastasis (GM) from cervical cancer is extremely rare, and only a few cases have been reported in the English literature. Gastric-type mucinous adenocarcinomas (GAS) of the uterine cervix are rare. GAS is an aggressive cancer commonly found in advanced stages; however, GM has not been reported. This study presents a rare case of GM from GAS of the uterine cervix in a 61-year-old female and describes the radiological findings of both the GM and cervical mucinous adenocarcinoma. GM appeared as a poor enhancing submucosal mass. The cervical mucinous adenocarcinoma appeared as an infiltrating mass with poor contrast enhancement. It exhibited mildly high and low signal intensities on the diffusion-weighted image and apparent diffusion coefficient map, respectively. This case is extremely rare and challenging to diagnose; however, if cervical cancer is an human papillomavirus-independent GAS type and a submucosal lesion is found in the stomach, the possibility of metastasis with a pattern similar to our case could be considered.

13.
Biomed Pharmacother ; 176: 116781, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38805966

RESUMO

Influenza A virus causes numerous deaths and infections worldwide annually. Therefore, we have considered nanobodies as a potential treatment for patients with severe cases of influenza. We developed a nanobody that was expected to have protective efficacy against the A/California/04/2009 (CA/04; pandemic 2009 flu strain) and evaluated its therapeutic efficacy against CA/04 in mice experiments. This nanobody was derived from the immunization of the alpaca, and the inactivated CA/04 virus was used as an immunogen. We successfully generated a nanobody library through bio-panning, phage ELISA, and Bio-layer interferometry. Moreover, we confirmed that administering nanobodies after lethal doses of CA/04 reduced viral replication in the lungs and influenza-induced clinical signs in mice. These research findings will help to develop nanobodies as viral therapeutics for CA/04 and other infectious viruses.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Infecções por Orthomyxoviridae , Anticorpos de Domínio Único , Animais , Anticorpos de Domínio Único/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Camundongos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/virologia , Feminino , Camundongos Endogâmicos BALB C , Camelídeos Americanos/imunologia , Pulmão/imunologia , Pulmão/virologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Anticorpos Antivirais/imunologia , Replicação Viral/efeitos dos fármacos
14.
Ann Clin Lab Sci ; 53(2): 173-180, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37094848

RESUMO

OBJECTIVE: Recent advances in hematology analyzers have generated cell population data (CPD), which quantify features of cells. The characteristics of CPD in pediatric systemic inflammatory response syndrome (SIRS) and sepsis were evaluated with 255 patients. METHODS: The ADVIA 2120i hematology analyzer was used for measurement of the delta neutrophil index (DN) including DNI and DNII. The XN-2000 was used for measurement of immature granulocytes (IG), neutrophil reactivity intensity (NEUT-RI), neutrophil granularity intensity (NEUT-GI), reactive lymphocytes (RE-LYMP), antibody synthesizing lymphocytes (AS-LYMP), RBC hemoglobin equivalent (RBC-He), and difference between RBC and reticulocyte hemoglobin equivalent (Delta-He). Measurement of high-sensitivity C-reactive protein (hsCRP) was performed using the Architect ci16200. RESULTS: The area under the receiver operating characteristic curve (AUC) values with confidence interval (CI) of IG (0.65, CI 0.58-0.72), DNI (0.70, CI 0.63-0.77), DNII (0.69, CI 0.62-0.76), and AS-LYMP (0.58, CI 0.51-0.65) were significant for diagnosis of sepsis. The levels of IG, NEUT-RI, DNI, DNII, RE-LYMP, and hsCRP exhibited gradual increasing trends from control to sepsis. In Cox regression analysis, the highest hazard ratio was observed for NEUT-RI (39.57, CI 4.87-321.75), higher than those for hsCRP (12.33, CI 2.49-61.12) and DNII (16.13, CI 1.98-131.08). IG (10.34, CI 2.47-43.26), DNI (11.60, CI 2.34-57.49), and RE-LYMP (8.20, CI 1.96-34.33) also showed high hazard ratios. CONCLUSION: NEUT-RI along with DNI and DNII can provide additional information regarding the diagnosis of sepsis and prediction of mortality in the pediatric ward.


Assuntos
Neutrófilos , Sepse , Humanos , Criança , Neutrófilos/metabolismo , Prognóstico , Proteína C-Reativa/metabolismo , Sepse/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Estudos Retrospectivos , Biomarcadores/metabolismo
15.
BMB Rep ; 56(10): 545-550, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37574806

RESUMO

Osteoporosis is a major public health concern, which requires novel therapeutic strategies to prevent or mitigate bone loss. Natural compounds have attracted attention as potential therapeutic agents due to their safety and efficacy. In this study, we investigated the regulatory activities of boeravinone B (BOB), a natural rotenoid isolated from the medicinal plant Boerhavia diffusa, on the differentiation of osteoclasts and mesenchymal stem cells (MSCs), the two main cell components responsible for bone remodeling. We found that BOB inhibited osteoclast differentiation and function, as determined by TRAP staining and pit formation assay, with no significant cytotoxicity. Furthermore, our results showing that BOB ameliorates ovariectomyinduced bone loss demonstrated that BOB is also effective in vivo. BOB exerted its inhibitory effects on osteoclastogenesis by downregulating the RANKL/RANK signaling pathways, including NF-κB, MAPK, and PI3K/Akt, resulting in the suppression of osteoclast-specific gene expression. Further experiments revealed that, at least phenomenologically, BOB promotes osteoblast differentiation of bone marrow-derived MSCs but inhibits their differentiation into adipocytes. In conclusion, our study demonstrates that BOB inhibits osteoclastogenesis and promotes osteoblastogenesis in vitro by regulating various signaling pathways. These findings suggest that BOB has potential value as a novel therapeutic agent for the prevention and treatment of osteoporosis. [BMB Reports 2023; 56(10): 545-550].


Assuntos
NF-kappa B , Osteoporose , Humanos , NF-kappa B/metabolismo , Osteoclastos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Diferenciação Celular , Osteoporose/metabolismo
16.
Tissue Eng Regen Med ; 19(3): 565-575, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34973125

RESUMO

BACKGROUND: The use of mouse bone marrow mesenchymal stem cells (mBMSCs) represents a promising strategy for performing preclinical studies in the field of cell-based regenerative medicine; however, mBMSCs obtained via conventional isolation methods have two drawbacks, i.e., (i) they are heterogeneous due to frequent macrophage contamination, and (ii) they require long-term culturing for expansion. METHODS: In the present study, we report a novel strategy to generate highly pure mBMSCs using liposomal clodronate. This approach is based on the properties of the two cell populations, i.e., BMSCs (to adhere to the plasticware in culture dishes) and macrophages (to phagocytose liposomes). RESULTS: Liposomal clodronate added during the first passage of whole bone marrow culture was selectively engulfed by macrophages in the heterogeneous cell population, resulting in their effective elimination without affecting the MSCs. This method allowed the generation of numerous high-purity Sca-1+CD44+F4/80- mBMSCs (> 95%) with just one passaging. Comparative studies with mBMSCs obtained using conventional methods revealed that the mBMSCs obtained in the present study had remarkably improved experimental utilities, as demonstrated by in vitro multilineage differentiation and in vivo ectopic bone formation assays. CONCLUSION: Our newly developed method, which enables the isolation of mBMSCs using simple and convenient protocol, will aid preclinical studies based on the use of MSCs.


Assuntos
Ácido Clodrônico , Células-Tronco Mesenquimais , Animais , Diferenciação Celular , Ácido Clodrônico/farmacologia , Lipossomos , Macrófagos , Camundongos
17.
Biochem Biophys Res Commun ; 414(3): 523-7, 2011 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-21968017

RESUMO

Human ribosomal protein S3 (rpS3) acts as a DNA repair endonuclease. The multiple functions of this protein are regulated by post-translational modifications including phosphorylation and methylation. Using a yeast-two hybrid screen, we identified small ubiquitin-related modifier-1 (SUMO-1) as a new interacting partner of rpS3. rpS3 interacted with SUMO-1 via the N- and C-terminal regions. We also observed sumoylation of rpS3 in Escherichia coli and mammalian cell systems. Furthermore, we discovered that one of three lysine residues, Lys18, Lys214, or Lys230, was sumoylated in rpS3. Interestingly, sumoylated rpS3 was resistant to proteolytic activity, indicating that SUMO-1 increased the stability of the rpS3 protein. We concluded that rpS3 is covalently modified by SUMO-1 and this post-translational modification regulates rpS3 function by increasing rpS3 protein stability.


Assuntos
Proteínas Ribossômicas/metabolismo , Proteína SUMO-1/metabolismo , Sumoilação , Escherichia coli/metabolismo , Células HEK293 , Humanos , Imunoprecipitação , Estabilidade Proteica , Proteínas Ribossômicas/genética , Proteína SUMO-1/genética , Técnicas do Sistema de Duplo-Híbrido
18.
J Ethnopharmacol ; 280: 114412, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34265383

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonica A. Berger, also known as Wa-song in Korea, has traditionally been used as a folk medicine, but the potential anti-cancer effects of aqueous extract of Orostachys japonica (OJe) have not yet been thoroughly investigated. AIM OF THE STUDY: To evaluate the anti-cancer effects of OJe, its possible mechanisms of action were investigated in 5-fluorouracil (5-FU) resistant SNU-C5/5-FUR colorectal cancer cells. MATERIALS AND METHODS: The functional compounds of OJe were identified with high performance liquid chromatography. The anti-cancer effects of OJe in SNU-C5/5-FUR cells were investigated by a cell viability assays, flow cytometry analysis, and a subcutaneous xenograft model employing BALB/c-nude mice. Possible signalling pathways were assayed with Western blotting. RESULTS: OJe (250 µg/ml) showed anti-cancer effects in SNU-C5/5-FUR cells, that were mediated via apoptosis as well as cell cycle arrest at the G0/G1 phase. Gallic acid and (-)-epicatechin, the major functional components of OJe, induced cell cycle arrest. OJe treatment (250 mg/kg, p.o.) produced a significant anti-proliferative effect in the xenograft model via decreased ß-catenin/GSK3ß and increased p27 expression. OJe treatment significantly activated ERK and p38 both in vitro and in vivo. CONCLUSIONS: These results suggest that OJe has anti-proliferative effects on 5-FU-resistant colorectal cancer cells via regulation of MAPK signalling pathways.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Crassulaceae/química , Fluoruracila/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Humanos , Camundongos , Camundongos Nus , Extratos Vegetais/química , Distribuição Aleatória , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J Prev Med Public Health ; 54(1): 1-7, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33618493

RESUMO

The Korean government's strategy to combat coronavirus disease 2019 (COVID-19) has focused on non-pharmaceutical interventions, such as social distancing and wearing masks, along with testing, tracing, and treatment; overall, its performance has been relatively good compared to that of many other countries heavily affected by COVID-19. However, little attention has been paid to health equity in measures to control the COVID-19 pandemic. The study aimed to examine the unequal impacts of COVID-19 across socioeconomic groups and to suggest potential solutions to tackle these inequalities. The pathways linking social determinants and health could be entry points to tackle the unequal consequences of this public health emergency. It is crucial for infectious disease policy to consider social determinants of health including poor housing, precarious working conditions, disrupted healthcare services, and suspension of social services. Moreover, the high levels of uncertainty and complexity inherent in this public health emergency, as well as the health and socioeconomic inequalities caused by the pandemic, underscore the need for good governance other than top-down measures by the government. We emphasize that a people-centered perspective is a key approach during the pandemic era. Mutual trust between the state and civil society, strong accountability of the government, and civic participation are essential components of cooperative disaster governance.


Assuntos
COVID-19/prevenção & controle , Equidade em Saúde/normas , Política de Saúde , Infectologia/legislação & jurisprudência , COVID-19/fisiopatologia , Programas Governamentais/legislação & jurisprudência , Programas Governamentais/métodos , Equidade em Saúde/estatística & dados numéricos , Humanos , Infectologia/métodos , Infectologia/tendências , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Saúde Pública/legislação & jurisprudência , Saúde Pública/métodos , Saúde Pública/tendências , República da Coreia
20.
World J Clin Cases ; 9(7): 1741-1747, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33728320

RESUMO

BACKGROUND: Vasculitis, a systemic disorder with inflammation of blood vessel walls, can develop broad spectrum of signs and symptoms according to involvement of various organs, and therefore, early diagnosis of vasculitis is challenging. We herein describe a patient who developed a special case of systemic vasculitis with mononeuropathy multiplex, rectal perforation and antiphospholipid syndrome (APS) presented with pulmonary embolism. CASE SUMMARY: A 61-year-old woman visited hospital with complaints of myalgia and occasional fever. She was initially diagnosed as proctitis and treated with antibiotics, however, there was no improvement. In addition, she also complained right foot drop with hypesthesia, and left 2nd and 3rd finger tingling sensation. She underwent nerve conduction study for evaluation, and it revealed sensorimotor polyneuropathy in the left arm and bilateral legs. Subsequent sural nerve biopsy strongly suggested vasculitic neuropathy. Based on nerve biopsy and clinical manifestation, she was diagnosed with vasculitis and treated with immuno-suppressive therapy. During treatment, sudden rectal perforation and pulmonary thromboembolism occurred, and further laboratory study suggested probable concomitant APS. Emergency Hartmann operation was performed for rectal perforation, and anti-coagulation therapy was started for APS. After few cycles of immunosuppressive therapy, tingling sensation and weakness in her hand and foot had been partially recovered and vasculitis was considered to be stationary. CONCLUSION: Vasculitis can be presented with a variety of signs and symptoms, therefore, clinicians should always consider the possibility of diagnosis.

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