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1.
Int J Mol Sci ; 25(2)2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38256069

RESUMO

Obesity is the excessive accumulation of body fat resulting from impairment in energy balance mechanisms. In this study, we aimed to investigate the mechanism whereby GABA (γ-aminobutyric acid) prevents high-fat diet-induced obesity, and whether it induces lipolysis and browning in white adipose tissue (WAT), using high-fat diet (HFD)-fed obese mice and 3T3-L1 adipocytes. We demonstrated that GABA substantially inhibits the body mass gain of mice by suppressing adipogenesis and lipogenesis. Consistent with this result, histological analysis of WAT demonstrated that GABA decreases adipocyte size. Moreover, we show that GABA administration decreases fasting blood glucose and improves serum lipid profiles and hepatic lipogenesis in HFD-fed obese mice. Furthermore, Western blot and immunofluorescence analyses showed that GABA activates protein kinase A (PKA) signaling pathways that increase lipolysis and promote uncoupling protein 1 (UCP1)-mediated WAT browning. Overall, these results suggest that GABA exerts an anti-obesity effect via the regulation of lipid metabolism.


Assuntos
Adipócitos , Dieta Hiperlipídica , Animais , Camundongos , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Células 3T3-L1 , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Ácido gama-Aminobutírico/farmacologia
2.
Mar Drugs ; 20(10)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36286432

RESUMO

Ecklonia stolonifera Okamura (ES) is mainly distributed in the coastal areas of the middle Pacific, around Korea and Japan, and has a long-standing edible value. It is rich in various compounds, such as polysaccharides, fatty acids, alginic acid, fucoxanthin, and phlorotannins, among which the polyphenol compound phlorotannins are the main active ingredients. Studies have shown that the extracts and active components of ES exhibit anti-cancer, antioxidant, anti-obesity, anti-diabetic, antibacterial, cardioprotective, immunomodulatory, and other pharmacological properties in vivo and in vitro. Although ES contains a variety of bioactive compounds, it is not widely known and has not been extensively studied. Based on its potential health benefits, it is expected to play an important role in improving the nutritional value of food both economically and medically. Therefore, ES needs to be better understood and developed so that it can be utilized in the development and application of marine medicines, functional foods, bioactive substances, and in many other fields. This review provides a comprehensive overview of the bioactivities and bioactive compounds of ES to promote in-depth research and a reference for the comprehensive utilization of ES in the future.


Assuntos
Antioxidantes , Phaeophyceae , Antioxidantes/farmacologia , Polifenóis/farmacologia , Ácido Algínico , Ácidos Graxos , Antibacterianos
3.
J Korean Med Sci ; 35(20): e167, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32449325

RESUMO

BACKGROUND: This study aimed to describe the current status of acute stroke care in Korea and explore disparities among hospitals and regions. METHODS: The 2013 and 2014 national stroke audit data and the national health insurance claims data were linked and used for this study. Stroke patients hospitalized via emergency rooms within 7 days of stroke onset were selected. RESULTS: A total of 19,608 patients treated in 216 hospitals were analyzed. Among them 76% had ischemic stroke; 15%, intracerebral hemorrhage (ICH); and 9%, subarachnoid hemorrhage (SAH). Of the hospitals, 31% provided inpatient stroke unit care. Ambulances were used in 56% of cases, and the median interval from onset to arrival was 4.5 hours. One-quarter of patients were referred from other hospitals. Intravenous thrombolysis (IVT) and endovascular treatment (EVT) rates were 11% and 4%, respectively. Three-quarters of the analyzed hospitals provided IVT and/or EVT, whereas 47% of hospitals providing IVT and 67% of hospitals providing EVT had less than one case per month. Decompressive surgery was performed on 28% of ICH patients, and clipping and coiling were performed in 17.2% and 14.3% of SAH patients, respectively. There were noticeable regional disparities between the various interventions, ambulance use, arrival time, and stroke unit availability. CONCLUSION: This study describes the current status of acute stroke care in Korea. Despite quite acceptable quality of stroke care, it suggests regional and hospital disparities. Expansion of stroke units, stroke center certification or accreditation, and connections between stroke centers and emergency medical services are highly recommended.


Assuntos
Acidente Vascular Cerebral/epidemiologia , Idoso , Serviços Médicos de Emergência , Serviço Hospitalar de Emergência , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Resultado do Tratamento
4.
Int J Mol Sci ; 21(6)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32245100

RESUMO

Obesity results from an imbalance between energy intake and energy expenditure, in which excess fat is stored as triglycerides (TGs) in white adipocytes. Recent studies have explored the anti-obesity effects of certain edible phytochemicals, which suppress TG accumulation and stimulate a brown adipocyte-like phenotype in white adipocytes. Gomisin N (GN) is an important bioactive component of Schisandra chinensis, a woody plant endemic to Asia. GN has antioxidant, anti-inflammatory and hepatoprotective effects in vivo and in vitro. However, the anti-obesity effects of GN in lipid metabolism and adipocyte browning have not yet been investigated. In the present study, we aimed to determine whether GN suppresses lipid accumulation and regulates energy metabolism, potentially via AMP-activated protein kinase (AMPK), in 3T3-L1 adipocytes. Our findings demonstrate that GN inhibited adipogenesis and lipogenesis in adipocyte differentiation. Also, GN not only increased the expression of thermogenic factors, including uncoupling protein 1 (UCP1), but also enhanced fatty acid oxidation (FAO) in 3T3-L1 cells. Therefore, GN may have a therapeutic benefit as a promising natural agent to combat obesity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/metabolismo , Tecido Adiposo Marrom/metabolismo , Lignanas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Compostos Policíclicos/farmacologia , Schisandra/química , Células 3T3-L1 , Acetil-CoA Carboxilase/metabolismo , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Tecido Adiposo Marrom/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Proteína Morfogenética Óssea 4/farmacologia , Ciclo-Octanos/química , Ciclo-Octanos/farmacologia , Ativação Enzimática/efeitos dos fármacos , Ácidos Graxos/metabolismo , Lignanas/química , Camundongos , Oxirredução/efeitos dos fármacos , Fenótipo , Compostos Policíclicos/química , Termogênese/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo
5.
J Stroke Cerebrovasc Dis ; 29(5): 104753, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32151475

RESUMO

OBJECTIVE: Stroke severity of 1 hospital is a crucial information when assessing hospital performance. We aimed to determine the effect of stroke severity in the association between hospital patient volume and outcome after acute ischemic stroke. METHODS: Data from National Acute Stroke Quality Assessment in 2013 and 2014 were analyzed. Hospital patient volume was defined as the annual number of acute ischemic stroke patients who admitted to each hospital. Comparisons among hospital patient volume quartiles before and after adjusting age, sex, onset to arrival and stroke severity were made to determine the associations between hospital patient volume and mortality at 30 days, 90 days and 1 year. Assessments for the nonlinear associations, with treating hospital patient volume as a continuous variable, and the associations between hospital patient volume and quality of care were also made. RESULTS: A total of 14,666 acute ischemic stroke patients admitted to 202 hospitals were analyzed. In the crude analysis, patients admitted to hospitals with lower patient volume showed higher mortality with a non-linear inverse association with a cut-off value of 227 patients/year. While the associations remained significant after adjusting age, sex and onset to arrival time (P's < .05), they disappeared when stroke severity was further adjusted (P's > .05). In contrary, hospital patient volume showed a nonlinear positive association with a plateau for summary measures of quality indicators even after adjustments for covariates including stroke severity (P < .001). CONCLUSIONS: Our study implicates that stroke severity should be considered when assessing hospital performance regarding outcomes of acute stroke care.


Assuntos
Isquemia Encefálica/mortalidade , Mortalidade Hospitalar , Indicadores de Qualidade em Assistência à Saúde , Acidente Vascular Cerebral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Bases de Dados Factuais , Feminino , Hospitais com Alto Volume de Atendimentos , Hospitais com Baixo Volume de Atendimentos , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Prognóstico , República da Coreia , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Fatores de Tempo
6.
Molecules ; 25(5)2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32106493

RESUMO

Heat stress can be caused by various environmental factors. When exposed to heat stress, oxidative stress and inflammatory reaction occur due to an increase of reactive oxygen species (ROS) in the body. In particular, inflammatory responses induced by heat stress are common in muscle cells, which are the most exposed to heat stress and directly affected. Gintonin-Enriched Fraction (GEF) is a non-saponin component of ginseng, a glycolipoprotein. It is known that it has excellent neuroprotective effects, therefore, we aimed to confirm the protective effect against heat stress by using GEF. C2C12 cells were exposed to high temperature stress for 1, 12 and 15 h, and the expression of signals was analyzed over time. Changes in the expression of the factors that were observed under heat stress were confirmed at the protein level. Exposure to heat stress increases phosphorylation of p38 and extracellular signal-regulated kinase (ERK) and increases expression of inflammatory factors such as NLRP3 inflammasome through lysophosphatidic acid (LPA) receptor. Activated inflammatory signals also increase the secretion of inflammatory cytokines such as interleukin 6 (IL-6) and interleukin 18 (IL-18). Also, expression of glutathione reductase (GR) and catalase related to oxidative stress is increased. However, it was confirmed that the changes due to the heat stress were suppressed by the GEF treatment. Therefore, we suggest that GEF helps to protect heat stress in muscle cell and prevent tissue damage by oxidative stress and inflammation.


Assuntos
Inflamação/tratamento farmacológico , Panax/química , Extratos Vegetais/farmacologia , Receptores de Ácidos Lisofosfatídicos/genética , Animais , Cálcio/metabolismo , Linhagem Celular , Resposta ao Choque Térmico/efeitos dos fármacos , Resposta ao Choque Térmico/fisiologia , Humanos , Camundongos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo
7.
Bioorg Chem ; 85: 274-281, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30641321

RESUMO

Seven new chalcones, lanceolein A-G (compounds 5 and 7-12), as well as five known chalcones (1-4 and 6), were isolated from the methanolic extract of Coreopsis lanceolata flowers. The chemical structures of 5 and 7-12 were determined on the basis of spectroscopic data interpretation. All compounds inhibited the production of nitrite oxide (NO) induced by LPS in RAW264.7 macrophage cells. Also, compounds 1-6 showed moderated cytotoxicity against human colon cancer cell lines, while compounds 7-12 hardly showed the cytotoxicity. Especially, compounds 2, 5, and 6 exhibited a little higher cytotoxicity on HCT15 cells, with IC50 values of 43.7 ±â€¯2.17 µM, 35.6 ±â€¯0.24 µM, and 47.9 ±â€¯1.18 µM, respectively. In the Tali assay, compounds 2 and 5 increased the numeral of apoptotic cells. These compounds also significantly promoted the expression of apoptotic proteins including PARP and caspase-3.


Assuntos
Anticarcinógenos/farmacologia , Chalconas/farmacologia , Coreopsis/química , Flores/química , Animais , Anticarcinógenos/química , Anticarcinógenos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Chalconas/química , Chalconas/isolamento & purificação , Humanos , Camundongos , Óxido Nítrico/antagonistas & inibidores , Células RAW 264.7
8.
Anesth Pain Med (Seoul) ; 19(2): 117-124, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38725166

RESUMO

BACKGROUND: This study investigated the relationship between intraoperative requirement for an inhalational anesthetic (sevoflurane) or an opioid (remifentanil) and postoperative analgesic consumption. METHODS: The study included 200 adult patients undergoing elective laparoscopic colectomy. In the sevoflurane group, the effect-site concentration of remifentanil was fixed at 1.0 ng/ml, while the inspiratory sevoflurane concentration was adjusted to maintain an appropriate anesthetic depth. In the remifentanil group, the end-expiratory sevoflurane concentration was fixed at 1.0 vol.%, and the remifentanil concentration was adjusted. Pain scores and cumulative postoperative analgesic consumptions were evaluated at 2, 6, 24, and 48 h after surgery. RESULTS: Average end-tidal concentration of sevoflurane and effect-site concentration of remifentanil were 2.0 ± 0.4 vol.% and 3.9 ± 1.4 ng/ml in the sevoflurane and remifentanil groups, respectively. Cumulative postoperative analgesic consumption at 48 h postoperatively was 55 ± 26 ml in the sevoflurane group and 57 ± 33 ml in the remifentanil group. In the remifentanil group, the postoperative cumulative analgesic consumptions at 2 and 6 h were positively correlated with intraoperative remifentanil requirements (2 h: r = 0.36, P < 0.001; 6 h: r = 0.38, P < 0.001). However, there was no significant correlation in the sevoflurane group (r = 0.04, P = 0.691). CONCLUSIONS: The amount of intraoperative requirement of short acting opioid, remifentanil, is correlated with postoperative analgesic consumption within postoperative 6 h. It may be contributed by the development of acute opioid tolerance. However, intraoperative sevoflurane requirement had no effect on postoperative analgesic consumption.

9.
Medicine (Baltimore) ; 103(14): e37573, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579041

RESUMO

BACKGROUND: Postoperative quality of recovery (QoR) and patient satisfaction have gained increasing significance in medical services. This study aimed to compare these 2 parameters between 2 types of regional anesthetics (spinal anesthesia and combined sciatic-femoral nerve block) in orthopedic lower knee surgery. METHODS: A total of 101 patients were classified into 2 groups (combined sciatic-femoral nerve block, group N; spinal anesthesia, group S) according to patient preference. In group N, sciatic and femoral nerve blocks were performed on the popliteal and groin regions, respectively, under ultrasound guidance. Spinal anesthesia was performed in group S. The primary outcomes were QoR and patient satisfaction. QoR was measured using the Korean translation of the QoR-15K. Patient satisfaction was assessed using an 11-point Likert scale (0-10) and a dichotomous question addressing anesthesia preferences for future surgeries. RESULTS: The physical independence of the postoperative QoR-15K was significantly higher in group N than in group S (14.2 vs 12.0, P = .04). On the 11-point Likert scale, group N scored 8.8, and group S scored 7.8 (P = .001). In the dichotomous question, 93.8% of the group N and 52.8% of the group S answered that they would like to choose the same anesthesia method for the next surgery (P < .001). In addition, fewer participants in group N complained of backache than those in group S, and the time to first urination after anesthesia was shorter in group N than in group S (P = .004, <.001, respectively). CONCLUSION: Combined sciatic-femoral nerve block may provide better physical independence and satisfaction than spinal anesthesia in orthopedic below-knee surgeries.


Assuntos
Raquianestesia , Bloqueio Nervoso , Humanos , Raquianestesia/métodos , Artroscopia , Nervo Femoral , Bloqueio Nervoso/métodos , Dor Pós-Operatória , Satisfação Pessoal , Estudos Prospectivos , Nervo Isquiático
10.
Front Cell Dev Biol ; 12: 1449232, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239557

RESUMO

Despite recent advances in cancer diagnostics and treatment, the mortality associated with lung cancer is still the highest in the world. Late-stage diagnosis, often accompanied by metastasis, is a major contributor to the high mortality rates, emphasizing the urgent need for reliable and readily accessible diagnostic tools that can detect biomarkers unique to lung cancer. Circulating factors, such as circulating tumor DNA and extracellular vesicles, from liquid biopsy have been recognized as diagnostic or prognostic markers in lung cancer. Numerous clinical studies are currently underway to investigate the potential of circulating tumor DNA, circulating tumor RNA, exosomes, and exosomal microRNA within the context of lung cancer. Those clinical studies aim to address the poor diagnostics and limited treatment options for lung cancer, with the ultimate goal of developing clinical markers and personalized therapies. In this review, we discuss the roles of each circulating factor, its current research status, and ongoing clinical studies of circulating factors in non-small cell lung cancer. Additionally, we discuss the circulating factors specifically found in lung cancer stem cells and examine approved diagnostic assays designed to detect circulating biomarkers in lung cancer patients.

11.
Cells ; 12(17)2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37681878

RESUMO

Sarcopenic obesity is characterized by concurrent obesity and muscle wasting (sarcopenia) and is common in the elderly. Sarcopenic obesity has steadily increased as the aging population has grown and is an increasing public health burden. Both obesity and sarcopenia independently increase health risks of the elderly, but sarcopenic obesity has a greater effect on metabolic disease than either obesity or sarcopenia alone. The metabolic mechanisms of obesity and sarcopenia are strongly interconnected, and obesity and sarcopenia form a vicious cycle, with each pathology exacerbating the other. The pathogenesis of sarcopenic obesity is more complex than either disease alone and remains incompletely understood, underscoring the significant unmet clinical need for effective sarcopenic obesity treatments. We aimed to determine the efficacy and underlying regulatory mechanisms of Gamma-aminobutyric acid (GABA) in sarcopenic obesity in high-fat-diet-fed obese aged mice and alterations in related mechanisms to determine the potential of GABA as a therapeutic modality for sarcopenic obesity. In this study, we used young (3 months) and aged (20 months) mice to evaluate age-related sarcopenic obesity. The daily administration of GABA for 8 weeks resulted in decreased fat mass and increased muscle mass and strength in aged mice. GABA also enhanced energy expenditure in both adipose tissue and skeletal muscle. In addition, GABA promoted muscle synthesis and decreased muscle degradation by activating the phosphatidylinositol-3-kinase (PI3K)/Akt pathway. These findings demonstrate that GABA has potential uses in preventing age-related sarcopenic obesity and related metabolic diseases.


Assuntos
Sarcopenia , Animais , Camundongos , Sarcopenia/etiologia , Sarcopenia/prevenção & controle , Dieta Hiperlipídica/efeitos adversos , Músculo Esquelético , Camundongos Obesos , Obesidade/complicações , Ácido gama-Aminobutírico
12.
Cells ; 12(15)2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37566094

RESUMO

Faced with a globally aging society, the maintenance of health and quality of life in older people is very important. The age-related loss of muscle mass and strength, known as sarcopenia, severely reduces quality of life and increases the risks of various diseases. In this study, we investigated the inhibitory effect of hesperidin (HES) on inflammaging, with the intention of evaluating its potential use as a treatment for sarcopenia. We studied 22-26-month-old mice, corresponding to humans aged ≥70 years, with aging-related sarcopenia, and young mice aged 3-6 months. The daily administration of HES for 8 weeks resulted in greater muscle mass and strength and increased the fiber size of the old mice. HES also restored the immune homeostasis that had been disrupted by aging, such as the imbalance in M1/M2 macrophage ratio. In addition, we found that HES ameliorated the sarcopenia by regulating AKT/mammalian target of rapamycin/forkhead box 3a signaling through an increase in insulin-like growth factor (IGF)-1 expression in the old mice. Therefore, HES represents a promising candidate inhibitor of sarcopenia in older people, and its effects are achieved through the maintenance of immune homeostasis.

13.
Cells ; 12(18)2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37759480

RESUMO

As populations around the world age, interest in healthy aging is growing. One of the first physical changes that occurs with aging is the loss of muscle mass and strength, termed sarcopenia. Sarcopenia limits the activity of older people, reduces their quality of life, and increases the likelihood of their developing disease. In the present study, we aimed to evaluate the effects of the ingestion of acid-hydrolyzed silk peptide (SP) on the muscle mass and strength of mice of >22 months of age with naturally occurring sarcopenia, and to identify the mechanisms involved. The daily administration of SP for 8 weeks increased the activation of the Akt/mTOR/FoxO3a signaling pathways and increased the muscle mass and strength of the old mice. In addition, SP inhibited oxidative stress and inflammation in muscle, which are direct causes of sarcopenia. Therefore, SP represents a promising potential treatment for sarcopenia that may improve the healthy lifespan and quality of life of older people.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Sarcopenia , Humanos , Animais , Camundongos , Idoso , Sarcopenia/tratamento farmacológico , Qualidade de Vida , Serina-Treonina Quinases TOR , Inflamação/tratamento farmacológico , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Seda , Transdução de Sinais
14.
J Clin Med ; 12(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36675541

RESUMO

Several research studies suggest that obese patients are at a higher risk of developing lumbar spinal disorder, including degenerative lumbar spinal stenosis (LSS), compared to normal-weight individuals. However, there are few investigations of how obesity affects functional disability in activities of daily living (ADL) in patients who were diagnosed with LSS. This prospective observational study aimed to determine if an association exists between body composition parameters, such as body fat and skeletal muscle, and functional disability in ADL of LSS patients. In the results of the current study, there were significant differences in percent body fat between the mild/moderate and severe disability groups. However, there were no differences in skeletal muscle mass or index between the two groups. Furthermore, we found a positive linear relationship between percent body fat and functional disability in male sex. This study suggests that increased percent body fat predicts potential severe functional disability in ADL in LSS patients. Body composition analysis may provide useful information for predicting the disease severity of various lumbar spinal disorders in clinical practice.

15.
PLoS One ; 18(5): e0285089, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37146026

RESUMO

PURPOSE: We aimed to validate the diagnostic performance of accelerated post-contrast magnetization-prepared rapid gradient-echo (MPRAGE) using wave-controlled aliasing in parallel imaging (Wave-CAIPI) for enhancing intracranial lesions, compared with conventional MPRAGE. METHODS: A total of 233 consecutive patients who underwent post-contrast Wave-CAIPI and conventional MPRAGE (scan time: 2 min 39 s vs. 4 min 30 s) were retrospectively evaluated. Two radiologists independently assessed whole images for the presence and diagnosis of enhancing lesions. The diagnostic performance for non-enhancing lesions, quantitative parameters (diameter of enhancing lesions, signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], and contrast rate), qualitative parameters (grey-white matter differentiation and conspicuity of enhancing lesions), and image qualities (overall image quality and motion artifacts) were also surveyed. The weighted kappa and percent agreement were used to evaluate the diagnostic agreement between the two sequences. RESULTS: Wave-CAIPI MPRAGE achieved significantly high agreement for the detection (98.7%[460/466], κ = 0.965) and diagnosis (97.8%[455/466], κ = 0.955) of enhancing intracranial lesions with conventional MPRAGE in pooled analysis. Detection and diagnosis of non-enhancing lesions (97.6% and 96.9% agreement), and diameter of enhancing lesions (P>0.05) also demonstrated high agreements between two sequences. Although Wave-CAIPI MPRAGE show lower SNR (P<0.01) than conventional MRAGE, it fulfilled comparable CNR (P = 0.486) and higher contrast rate (P<0.01). The qualitative parameters show similar value (P>0.05). The overall image quality was slightly poor, however, motion artifacts were better in Wave-CAIPI MPRAGE (both P = 0.005). CONCLUSION: Wave-CAIPI MPRAGE provides reliable diagnostic performance for enhancing intracranial lesions within half of the scan time compared with conventional MPRAGE.


Assuntos
Imageamento por Ressonância Magnética , Substância Branca , Humanos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Substância Cinzenta , Razão Sinal-Ruído , Encéfalo/diagnóstico por imagem , Imageamento Tridimensional/métodos
16.
Theranostics ; 13(3): 1198-1216, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36793862

RESUMO

Rationale: ß-catenin is a component for cell adhesion and a transcriptional coactivator in epithelial-mesenchymal transition (EMT). Previously we found that catalytically active PLK1 drives EMT in non-small cell lung cancer (NSCLC), upregulating extracellular matrix factors including TSG6, laminin γ2, and CD44. To understand the underlying mechanism and clinical significance of PLK1 and ß-catenin in NSCLC, their relationship and function in metastatic regulation were investigated. Methods: The clinical relevance between the survival rate of NSCLC patients and the expression of PLK1 and ß-catenin was analyzed by a KM plot. Immunoprecipitation, kinase assay, LC-MS/MS spectrometry, and site-directed mutagenesis were performed to reveal their interaction and phosphorylation. A lentiviral doxycycline-inducible system, Transwell-based 3D culture, tail-vein injection model, confocal microscopy, and chromatin immunoprecipitation assays were used to elucidate the function of phosphorylated ß-catenin in the EMT of NSCLC. Results: Clinical analysis revealed that the high expression of CTNNB1/PLK1 was inversely correlated with the survival rates of 1,292 NSCLC patients, especially in metastatic NSCLC. In TGF-ß-induced or active PLK1-driven EMT, ß-catenin, PLK1, TSG6, laminin γ2, and CD44 were concurrently upregulated. ß-catenin is a binding partner of PLK1 in TGF-ß-induced EMT and is phosphorylated at S311. Phosphomimetic ß-catenin promotes cell motility, invasiveness of NSCLC cells, and metastasis in a tail-vein injection mouse model. Its upregulated stability by phosphorylation enhances transcriptional activity through nuclear translocation for the expression of laminin γ2, CD44, and c-Jun, therefore enhancing PLK1 expression by AP-1. Conclusions: Our findings provide evidence for the critical role of the PLK1/ß-catenin/AP-1 axis in metastatic NSCLC, implying that ß-catenin and PLK1 may serve as a molecular target and prognostic indicator of the therapeutic response in metastatic NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Proteínas Serina-Treonina Quinases , beta Catenina , Animais , Camundongos , beta Catenina/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Cromatografia Líquida , Matriz Extracelular/metabolismo , Laminina/metabolismo , Neoplasias Pulmonares/patologia , Fosforilação , Espectrometria de Massas em Tandem , Fator de Transcrição AP-1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Humanos , Proteínas Serina-Treonina Quinases/metabolismo , Quinase 1 Polo-Like
17.
J Med Food ; 26(4): 232-243, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36897318

RESUMO

Ecklonia stolonifera, belonging to the Laminariaceae family, is an edible widely distributed perennial brown marine alga that is rich in polyphenols. Dieckol, a bioactive component of the E. stolonifera extract (ESE), is a major phlorotannin compound found only in brown algae. This study aimed to evaluate the ability of ESE to inhibit lipid accumulation caused by oxidative stress in 3T3-L1 adipocytes and high-fat diet-fed obese ICR mice. We report that ESE-treated obese ICR mice, which were fed a high-fat diet, showed reduced whole-body and adipose tissue weights with improved plasma lipid profiles. In vitro and in vivo studies have indicated that ESE inhibited the expression of adipogenesis-related genes associated with fat accumulation through AMP-activated protein kinase activity and increased the expression of lipolysis-related genes. In addition, ESE reduced the expression of enzymes involved in reactive oxygen species (ROS) production and increased the expression of antioxidant enzymes, thereby reducing ROS levels. These findings suggest that ESE possesses strong antioxidant properties and inhibits oxidative stress-induced lipid accumulation by reducing ROS production during adipocyte generation.


Assuntos
Fármacos Antiobesidade , Phaeophyceae , Animais , Camundongos , Camundongos Endogâmicos ICR , Dieta Hiperlipídica/efeitos adversos , Fármacos Antiobesidade/farmacologia , Antioxidantes/farmacologia , Células 3T3-L1 , Espécies Reativas de Oxigênio , Obesidade/etiologia , Adipogenia , Lipídeos , Camundongos Endogâmicos C57BL
18.
J Ginseng Res ; 46(6): 809-818, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36312735

RESUMO

Background: The non-saponin fraction (NSF) of Korean Red Ginseng is a powder in which saponin is eliminated from red ginseng concentrate by fractionation. In this study, we examined the effect of NSF on age-associated sarcopenia in old mice. Methods: NSF (50 or 200 mg/kg/day) was administered orally daily to young (3-6-month-old) and old (20-24-month-old) C57BL/6 J mice for 6 weeks. Body weight and grip strength were assessed once a week during the oral administration period. The gastrocnemius and quadriceps muscle were excised, and the muscle fiber size was compared through hematoxylin and eosin staining. In addition, the effect of NSF on sarcopenia and inflammation/oxidative stress-related factors in hindlimb muscles was investigated by western blotting. Flow cytometry analysis was conducted to investigate the effect of NSF on immune homeostasis. Blood samples were collected by cardiac puncture, and the serum levels of insulin-like growth factor 1, pro-inflammatory cytokines, and glutathione were evaluated. Results: NSF significantly alleviated muscle strength, mass, and also fiber size in old mice. Age-associated impairment of immune homeostasis was recovered by NSF through retaining CD11b+F4/80+ macrophages and regulating inflammatory biomarkers. NSF also decreased the age-induced expression of oxidative stress factors. Taken together, NSF showed the effect of improving sarcopenia by inhibiting low-grade chronic inflammatory/oxidative stress factors. Conclusion: NSF exhibited anti-sarcopenia effects by regulating chronic inflammation and oxidative stress in old mice. Thus, we suggest that NSF is a promising restorative agent that can be used to improve sarcopenia in the elderly as well as maintain immune homeostasis.

19.
J Ginseng Res ; 46(3): 454-463, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35600770

RESUMO

Background: Gintonin-enriched fraction (GEF), a non-saponin fraction of ginseng, is a novel glycolipoprotein rich in hydrophobic amino acids. GEF has recently been shown to regulate lipid metabolism and browning in adipocytes; however, the mechanisms underlying its effects on energy metabolism and whether it affects sarcopenic obesity are unclear. We aimed to evaluate the effects of GEF on skeletal muscle atrophy in high-fat diet (HFD)-induced obese mice. Methods: To examine the effect of GEF on sarcopenic obesity, 4-week-old male ICR mice were used. The mice were divided into four groups: chow diet (CD), HFD, HFD supplemented with 50 mg/kg/day GEF, or 150 mg/kg/day GEF for 6 weeks. We analyzed body mass gain and grip strength, histological staining, western blot analysis, and immunofluorescence to quantify changes in sarcopenic obesity-related factors. Results: GEF inhibited body mass gain while HFD-fed mice gained 22.7 ± 2.0 g, whereas GEF-treated mice gained 14.3 ± 1.2 g for GEF50 and 11.8 ± 1.6 g for GEF150 by downregulating adipogenesis and inducing lipolysis and browning in white adipose tissue (WAT). GEF also enhanced mitochondrial biogenesis threefold in skeletal muscle. Furthermore, GEF-treated skeletal muscle exhibited decreased expression of muscle-specific atrophic genes, and promoted myogenic differentiation and increased muscle mass and strength in a dose-dependent manner (p < 0.05). Conclusion: These findings indicate that GEF may have potential uses in preventing sarcopenic obesity by promoting energy expenditure and attenuating skeletal muscle atrophy.

20.
Cells ; 11(20)2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36291111

RESUMO

Since skeletal muscle atrophy resulting from various causes accelerates the progression of several diseases, its prevention should help maintain health and quality of life. A range of natural materials have been investigated for their potential preventive effects against muscle atrophy. Here, ethanol extracts of Angelica gigas and Artemisia dracunculus were concentrated and dried, and mixed at a ratio of 7:3 to create the mixture CHDT. We then evaluated the potential for CHDT to prevent muscle atrophy and explored the mechanisms involved. CHDT was orally administered to C57BL/6 mice daily for 30 days, and dexamethasone (Dex) was intraperitoneally injected daily to induce muscle atrophy from 14 days after the start of oral administration. We found that CHDT prevented the Dex-induced reductions in muscle strength, mass, and fiber size, likely by upregulating the Akt/mTOR signaling pathway. In addition, CHDT reduced the Dex-induced increase in the serum concentrations of pro-inflammatory cytokines, which directly induce the degradation of muscle proteins. These findings suggest that CHDT could serve as a natural food supplement for the prevention of muscle atrophy.


Assuntos
Angelica , Artemisia , Atrofia Muscular , Extratos Vegetais , Animais , Camundongos , Citocinas/sangue , Dexametasona , Etanol , Camundongos Endogâmicos C57BL , Proteínas Musculares/metabolismo , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/prevenção & controle , Atrofia Muscular/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Qualidade de Vida , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Quimioterapia Combinada
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