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1.
Adv Mater ; : e2406179, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39003621

RESUMEN

Hydroxyapatite (HA) exhibits outstanding biocompatibility, bioactivity, osteoconductivity, and natural anti-inflammatory properties. Pure HA, ion-doped HA, and HA-polymer composites are investigated, but critical limitations such as brittleness remain; numerous efforts are being made to address them. Herein, the novel self-crystallization of a polymeric single-stranded deoxyribonucleic acid (ssDNA) without additional phosphate ions for synthesizing deoxyribonucleic apatite (DNApatite) is presented. The synthesized DNApatite, DNA1Ca2.2(PO4)1.3OH2.1, has a repetitive dual phase of inorganic HA crystals and amorphous organic ssDNA at the sub-nm scale, forming nanorods. Its mechanical properties, including toughness and elasticity, are significantly enhanced compared with those of HA nanorod, with a Young's modulus similar to that of natural bone.

2.
Mol Cell Biol ; 44(6): 245-258, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38804232

RESUMEN

Betaine-homocysteine S-methyltransferase (BHMT) is one of the most abundant proteins in the liver and regulates homocysteine metabolism. However, the molecular mechanisms underlying Bhmt transcription have not yet been elucidated. This study aimed to assess the molecular mechanisms underlying Bhmt transcription and the effect of BHMT deficiency on metabolic functions in the liver mediated by liver receptor homolog-1 (LRH-1). During fasting, both Bhmt and Lrh-1 expression increased in the liver of Lrh-1f/f mice; however, Bhmt expression was decreased in LRH-1 liver specific knockout mice. Promoter activity analysis confirmed that LRH-1 binds to a specific site in the Bhmt promoter region. LRH-1 deficiency was associated with elevated production of reactive oxygen species (ROS), lipid peroxidation, and mitochondrial stress in hepatocytes, contributing to hepatic triglyceride (TG) accumulation. In conclusion, this study suggests that the absence of an LRH-1-mediated decrease in Bhmt expression promotes TG accumulation by increasing ROS levels and inducing mitochondrial stress. Therefore, LRH-1 deficiency not only leads to excess ROS production and mitochondrial stress in hepatocytes, but also disrupts the methionine cycle. Understanding these regulatory pathways may pave the way for novel therapeutic interventions against metabolic disorders associated with hepatic lipid accumulation.


Asunto(s)
Betaína-Homocisteína S-Metiltransferasa , Hepatocitos , Hígado , Metionina , Ratones Noqueados , Especies Reactivas de Oxígeno , Receptores Citoplasmáticos y Nucleares , Triglicéridos , Animales , Hígado/metabolismo , Ratones , Especies Reactivas de Oxígeno/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Betaína-Homocisteína S-Metiltransferasa/metabolismo , Betaína-Homocisteína S-Metiltransferasa/genética , Hepatocitos/metabolismo , Metionina/metabolismo , Triglicéridos/metabolismo , Regiones Promotoras Genéticas/genética , Masculino , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Peroxidación de Lípido
3.
Exp Mol Med ; 56(4): 1001-1012, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38622198

RESUMEN

Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl4), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4-induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH.


Asunto(s)
Hierro , Lipocalina 2 , Cirrosis Hepática , Ratones Noqueados , Enfermedad del Hígado Graso no Alcohólico , Proteína 1 de Unión a los Elementos Reguladores de Esteroles , Animales , Humanos , Masculino , Ratones , Tetracloruro de Carbono/farmacología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Hepatocitos/metabolismo , Hepatocitos/patología , Hierro/metabolismo , Lipocalina 2/metabolismo , Lipocalina 2/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Cirrosis Hepática/etiología , Cirrosis Hepática/genética , Cirrosis Hepática/inducido químicamente , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética
4.
J Biomech ; 168: 112059, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38631187

RESUMEN

The progression of cardiovascular disease is intricately influenced by a complex interplay between physiological pathways, biochemical processes, and physical mechanisms. This study aimed to develop an in-silico physics-based approach to comprehensively model the multifaceted vascular pathophysiological adaptations. This approach focused on capturing the progression of proximal pulmonary arterial hypertension, which is significantly associated with the irreversible degradation of arterial walls and compensatory stress-induced growth and remodeling. This study incorporated critical characteristics related to the distinct time scales for the deformation, thus reflecting the impact of mean pressure on artery growth and tissue damage. The in-silico simulation of the progression of pulmonary hypertension was realized based on computational code combined with the finite element method (FEM) for the simulation of disease progression. The parametric studies further explored the consequences of these irreversible processes. This computational modeling approach may advance our understanding of pulmonary hypertension and its progression.


Asunto(s)
Simulación por Computador , Progresión de la Enfermedad , Hipertensión Pulmonar , Modelos Cardiovasculares , Arteria Pulmonar , Humanos , Hipertensión Pulmonar/fisiopatología , Arteria Pulmonar/fisiopatología , Análisis de Elementos Finitos
5.
Adv Sci (Weinh) ; 11(16): e2400304, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38408158

RESUMEN

Interest has grown in services that consume a significant amount of energy, such as large language models (LLMs), and research is being conducted worldwide on synaptic devices for neuromorphic hardware. However, various complex processes are problematic for the implementation of synaptic properties. Here, synaptic characteristics are implemented through a novel method, namely side chain control of conjugated polymers. The developed devices exhibit the characteristics of the biological brain, especially spike-timing-dependent plasticity (STDP), high-pass filtering, and long-term potentiation/depression (LTP/D). Moreover, the fabricated synaptic devices show enhanced nonvolatile characteristics, such as long retention time (≈102 s), high ratio of Gmax/Gmin, high linearity, and reliable cyclic endurance (≈103 pulses). This study presents a new pathway for next-generation neuromorphic computing by modulating conjugated polymers with side chain control, thereby achieving high-performance synaptic properties.


Asunto(s)
Polímeros , Sinapsis , Polímeros/química , Sinapsis/fisiología , Plasticidad Neuronal/fisiología , Redes Neurales de la Computación
6.
Artículo en Inglés | MEDLINE | ID: mdl-38083125

RESUMEN

Vertebral Compression Fracture (VCF) is one of the common fractures, especially for elderlies. As it affects postural deformation that may cause secondary disorders in the respiratory or digestive system if not treated in time, diagnosis of VCF is crucial. Using deep learning model based detection technology in diagnosis can reduce the workload of healthcare workers and misdiagnosis. Hence in this work, we propose ALiGN, a compression fracture detection model in the lumbar vertebra based on a deep convolutional neural network (CNN). Specifically, we take the location of each vertebral body into account via a feature pyramid network with an attention mechanism. Our proposed model outperforms the earlier works with a sensitivity 0.9729, specificity 0.9914, and mAP 0.7882.


Asunto(s)
Fracturas por Compresión , Fracturas de la Columna Vertebral , Humanos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/complicaciones , Fracturas por Compresión/diagnóstico por imagen , Fracturas por Compresión/complicaciones , Vértebras Lumbares/diagnóstico por imagen
7.
Biosensors (Basel) ; 13(10)2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37887108

RESUMEN

Microfluidic paper-based analytical devices (µPADs) have been developed for use in a variety of diagnosis and analysis fields. However, conventional µPADs with an open-channel system have limitations for application as analytical platforms mainly because of the evaporation and contamination of the sample solution. This study demonstrates the design and fabrication of an enclosed three-dimensional(3D)-µPAD and its application as a primary early analysis platform for ionic contaminants. To generate the hydrophobic PDMS barrier, double-sided patterning is carried out using a PDMS blade-coated stamp mold that is fabricated using 3D printing. The selective PDMS patterning can be achieved with controlled PDMS permeation of the cellulose substrate using 3D-designed stamp molds. We find the optimal conditions enabling the formation of enclosed channels, including round shape pattern and inter-pattern distance of 10 mm of stamp design, contact time of 0.5 min, and spacer height of 300 µm of double-sided patterning procedure. As a proof of concept, this enclosed 3D-µPAD is used for the simultaneous colorimetric detection of heavy metal ions in a concentration range of 0.1-2000 ppm, including nickel (Ni2+), copper (Cu2+), mercury (Hg2+), and radioactive isotope cesium-137 ions (Cs+). We confirm that qualitative analysis and image-based quantitative analysis with high reliability are possible through rapid color changes within 3 min. The limits of detection (LOD) for 0.55 ppm of Ni2+, 5.05 ppm of Cu2+, 0.188 ppm of Hg2+, and 0.016 ppm of Cs+ are observed, respectively. In addition, we confirm that the analysis is highly reliable in a wide range of ion concentrations with CV values below 3% for Ni2+ (0.56%), Cu2+ (0.45%), Hg2+ (1.35%), and Cs+ (2.18%). This method could be a promising technique to develop a 3D-µPAD with various applications as a primary early analysis device in the environmental and biological industries.


Asunto(s)
Mercurio , Metales Pesados , Técnicas Analíticas Microfluídicas , Cobre , Reproducibilidad de los Resultados , Iones
8.
Nanoscale Horiz ; 8(10): 1417-1427, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37538027

RESUMEN

Recently, two-dimensional transition metal dichalcogenides (TMDs) such as molybdenum disulfide (MoS2) have attracted great attention due to their unique properties. To modulate the electronic properties and structure of TMDs, it is crucial to precisely control chalcogenide vacancies and several methods have already been suggested. However, they have several limitations such as plasma damage by ion bombardment. Herein, we introduced a novel solvent-assisted vacancy engineering (SAVE) method to modulate sulfur vacancies in MoS2. Considering polarity and the Hansen solubility parameter (HSP), three solvents were selected. Sulfur vacancies can be modulated by immersing MoS2 in each solvent, supported by X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy analyses. The SAVE method can further expand its application in memory devices representing memristive performance and synaptic behaviors. We represented the charge transport mechanism of sulfur vacancy migration in MoS2. The non-destructive, scalable, and novel SAVE method controlling sulfur vacancies is expected to be a guideline for constructing a vacancy engineering system of TMDs.

9.
Korean J Fam Med ; 44(6): 319-326, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37648400

RESUMEN

BACKGROUND: Diet and physical activity are key factors related to depressive mood. Previous studies have demonstrated the effects of diet and physical activity on depression. However, the effect of energy intake-expenditure balance (EIEB) on mental health has not been fully evaluated. This study aimed to analyze the association between EIEB and depression. METHODS: A total of 13,460 participants (5,660 men and 7,800 women) aged ≥19 years were obtained from the 2014, 2016, and 2018 Korea National Health and Nutrition Examination Survey (KNHANES). EIEB was defined as the difference between the daily energy intake and energy expenditure. Energy intake was calculated and provided by the KNHANES using a 24-hour recall survey. Energy expenditure was estimated as the sum of basal metabolic rate and physical activity. Logistic regression analyses were used to investigate the association between sex-specific quartile groups (Q1-Q4) of EIEB and depression after adjusting for socioeconomic status, body mass index, lifestyle factors, and underlying diseases. RESULTS: Women in Q3 of EIEB (211-669 kcal) had a significantly lower risk of depression (odd ratio [OR], 0.78; 95% confidence interval [CI], 0.67-0.92) than those in Q1 of EIEB (<-167 kcal). The adjusted ORs of depression were 0.87 (95% CI, 0.75-1.02) in Q2 and 0.86 (95% CI, 0.74-1.01) in Q4, with P for trend=0.030. There were no significant associations between the EIEB quartile groups and depression in men after adjusting for potential confounders (P for trend=0.564). CONCLUSION: Our results suggested that the EIEB is negatively associated with depression in Korean women.

10.
Crit Care ; 27(1): 286, 2023 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-37443130

RESUMEN

BACKGROUND: To maintain adequate oxygenation is of utmost importance in intraoperative care. However, clinical evidence supporting specific oxygen levels in distinct surgical settings is lacking. This study aimed to compare the effects of 30% and 80% oxygen in off-pump coronary artery bypass grafting (OPCAB). METHODS: This multicenter trial was conducted in three tertiary hospitals from August 2019 to August 2021. Patients undergoing OPCAB were cluster-randomized to receive either 30% or 80% oxygen intraoperatively, based on the month when the surgery was performed. The primary endpoint was the length of hospital stay. Intraoperative hemodynamic data were also compared. RESULTS: A total of 414 patients were cluster-randomized. Length of hospital stay was not different in the 30% oxygen group compared to the 80% oxygen group (median, 7.0 days vs 7.0 days; the sub-distribution hazard ratio, 0.98; 95% confidence interval [CI] 0.83-1.16; P = 0.808). The incidence of postoperative acute kidney injury was significantly higher in the 30% oxygen group than in the 80% oxygen group (30.7% vs 19.4%; odds ratio, 1.94; 95% CI 1.18-3.17; P = 0.036). Intraoperative time-weighted average mixed venous oxygen saturation was significantly higher in the 80% oxygen group (74% vs 64%; P < 0.001). The 80% oxygen group also had a significantly greater intraoperative time-weighted average cerebral regional oxygen saturation than the 30% oxygen group (56% vs 52%; P = 0.002). CONCLUSIONS: In patients undergoing OPCAB, intraoperative administration of 80% oxygen did not decrease the length of hospital stay, compared to 30% oxygen, but may reduce postoperative acute kidney injury. Moreover, compared to 30% oxygen, intraoperative use of 80% oxygen improved oxygen delivery in patients undergoing OPCAB. Trial registration ClinicalTrials.gov (NCT03945565; April 8, 2019).


Asunto(s)
Lesión Renal Aguda , Puente de Arteria Coronaria Off-Pump , Daucus carota , Humanos , Puente de Arteria Coronaria/efectos adversos , Oxígeno/uso terapéutico , Puente de Arteria Coronaria Off-Pump/efectos adversos , Lesión Renal Aguda/complicaciones , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología
11.
Med Phys ; 50(11): 7203-7213, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37517077

RESUMEN

BACKGROUND: Many studies have utilized optical camera systems with volumetric scintillators for quality assurances (QA) to estimate the proton beam range. However, previous analytically driven range estimation methods have the difficulty to derive the dose distributions from the scintillation images with quenching and optical effects. PURPOSE: In this study, a deep learning method utilized to QA was used to predict the beam range and spread-out Bragg peak (SOBP) for two-dimensional (2D) map conversion from the scintillation light distribution (LD) into the dose distribution in a water phantom. METHODS: The 2D residual U-net modeling for deep learning was used to predict the 2D water dose map from a 2D scintillation LD map. Monte Carlo simulations for dataset preparation were performed with varying monoenergetic proton beam energies, field sizes, and beam axis shifts. The LD was reconstructed using photons backpropagated from the aperture as a virtual lens. The SOBP samples were constructed based on monoenergetic dose distributions. The training set, including the validation set, consisted of 8659 image pairs of LD and water dose maps. After training, dose map prediction was performed using a 300 image pair test set generated under random conditions. The pairs of simulated and predicted dose maps were analyzed by Bragg peak fitting and gamma index maps to evaluate the model prediction. RESULT: The estimated beam range and SOBP width resolutions were 0.02 and 0.19 mm respectively for varying beam conditions, and the beam range and SOBP width deviations from the reference simulation result were less than 0.1 and 0.8 mm respectively. The simulated and predicted distributions showed good agreement in the gamma analysis, except for rare cases with failed gamma indices in the proximal and field-marginal regions. CONCLUSION: The deep learning conversion method using scintillation LDs in an optical camera system with a scintillator is feasible for estimating proton beam range and SOBP width with high accuracy.


Asunto(s)
Aprendizaje Profundo , Terapia de Protones , Protones , Terapia de Protones/métodos , Simulación por Computador , Método de Montecarlo , Agua , Dosificación Radioterapéutica
12.
BMC Geriatr ; 23(1): 262, 2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-37131138

RESUMEN

BACKGROUND: Prediction of preoperative frailty risk in the emergency setting is a challenging issue because preoperative evaluation cannot be done sufficiently. In a previous study, the preoperative frailty risk prediction model used only diagnostic and operation codes for emergency surgery and found poor predictive performance. This study developed a preoperative frailty prediction model using machine learning techniques that can be used in various clinical settings with improved predictive performance. METHODS: This is a national cohort study including 22,448 patients who were older than 75 years and visited the hospital for emergency surgery from the cohort of older patients among the retrieved sample from the Korean National Health Insurance Service. The diagnostic and operation codes were one-hot encoded and entered into the predictive model using the extreme gradient boosting (XGBoost) as a machine learning technique. The predictive performance of the model for postoperative 90-day mortality was compared with those of previous frailty evaluation tools such as Operation Frailty Risk Score (OFRS) and Hospital Frailty Risk Score (HFRS) using the receiver operating characteristic curve analysis. RESULTS: The predictive performance of the XGBoost, OFRS, and HFRS for postoperative 90-day mortality was 0.840, 0.607, and 0.588 on a c-statistics basis, respectively. CONCLUSIONS: Using machine learning techniques, XGBoost to predict postoperative 90-day mortality, using diagnostic and operation codes, the prediction performance was improved significantly over the previous risk assessment models such as OFRS and HFRS.


Asunto(s)
Fragilidad , Mortalidad , Periodo Posoperatorio , Anciano , Humanos , Pueblo Asiatico , Estudios de Cohortes , Fragilidad/diagnóstico , Programas Nacionales de Salud , Estudios Retrospectivos , Factores de Riesgo
13.
Nat Commun ; 14(1): 1801, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37002230

RESUMEN

Higher-order topological insulators are recently discovered quantum materials exhibiting distinct topological phases with the generalized bulk-boundary correspondence. Td-WTe2 is a promising candidate to reveal topological hinge excitation in an atomically thin regime. However, with initial theories and experiments focusing on localized one-dimensional conductance only, no experimental reports exist on how the spin orientations are distributed over the helical hinges-this is critical, yet one missing puzzle. Here, we employ the magneto-optic Kerr effect to visualize the spinful characteristics of the hinge states in a few-layer Td-WTe2. By examining the spin polarization of electrons injected from WTe2 to graphene under external electric and magnetic fields, we conclude that WTe2 hosts a spinful and helical topological hinge state protected by the time-reversal symmetry. Our experiment provides a fertile diagnosis to investigate the topologically protected gapless hinge states, and may call for new theoretical studies to extend the previous spinless model.

14.
ACS Appl Mater Interfaces ; 15(12): 15839-15847, 2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-36919898

RESUMEN

Neuromorphic computing based on two-dimensional transition-metal dichalcogenides (2D TMDs) has attracted significant attention recently due to their extraordinary properties generated by the atomic-thick layered structure. This study presents sulfur-defect-assisted MoS2 artificial synaptic devices fabricated by a simple sputtering process, followed by a precise sulfur (S) vacancy-engineering process. While the as-sputtered MoS2 film does not show synaptic behavior, the S vacancy-controlled MoS2 film exhibits excellent synapse with remarkable nonvolatile memory characteristics such as a high switching ratio (∼103), a large memory window, and long retention time (∼104 s) in addition to synaptic functions such as paired-pulse facilitation (PPF) and long-term potentiation (LTP)/depression (LTD). The synaptic device working mechanism of Schottky barrier height modulation by redistributing S vacancies was systemically analyzed by electrical, physical, and microscopy characterizations. The presented MoS2 synaptic device, based on the precise defect engineering of sputtered MoS2, is a facile, low-cost, complementary metal-oxide semiconductor (CMOS)-compatible, and scalable method and provides a procedural guideline for the design of practical 2D TMD-based neuromorphic computing.

15.
Sensors (Basel) ; 23(4)2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36850698

RESUMEN

Network pruning reduces the number of parameters and computational costs of convolutional neural networks while maintaining high performance. Although existing pruning methods have achieved excellent results, they do not consider reconstruction after pruning in order to apply the network to actual devices. This study proposes a reconstruction process for channel-based network pruning. For lossless reconstruction, we focus on three components of the network: the residual block, skip connection, and convolution layer. Union operation and index alignment are applied to the residual block and skip connection, respectively. Furthermore, we reconstruct a compressed convolution layer by considering batch normalization. We apply our method to existing channel-based pruning methods for downstream tasks such as image classification, object detection, and semantic segmentation. Experimental results show that compressing a large model has a 1.93% higher accuracy in image classification, 2.2 higher mean Intersection over Union (mIoU) in semantic segmentation, and 0.054 higher mean Average Precision (mAP) in object detection than well-designed small models. Moreover, we demonstrate that our method can reduce the actual latency by 8.15× and 5.29× on Raspberry Pi and Jetson Nano, respectively.

16.
Food Sci Biotechnol ; 32(1): 91-100, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36606089

RESUMEN

This study aimed to assess apple blossom extracts as potential natural whitening agents due to their ability to inhibit melanogenesis. Ethanol extracts of apple blossom (ABE) were assessed for biological activity in the B16F10 mouse melanoma cell line. ABE toxicity was assessed by thiazolyl blue tetrazolium bromide (MTT) assay. Levels of melanogenic enzyme expression in response to ABE supplementation were assessed by western blotting. Also assessed purified kaempferol, one of the phenolic compounds extracted from apple blossom, was evaluated using western blot analysis. The expression levels of cellular tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase-related protein (TRP)-1, and TRP-2 proteins related to melanogenesis decreased in a dose-dependent manner with ABE treatment of cells. Using nuclear magnetic resonance, we identified kaempferol in the ABE. Treatment of cells with purified kaempferol decreased the expression levels of tyrosinase and the MITF protein to a similar degree as that observed with ABE treatment. This suggests that the efficacy of melanogenesis-related inhibition demonstrated by ABE was due to kaempferol. ABE has an inhibitive effect on melanogenic enzymes and potentially can be applied to functional foods and cosmetics having a whitening effect as a natural material.

17.
J Adv Res ; 45: 1-13, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35659922

RESUMEN

INTRODUCTION: Sterol regulatory element binding protein (SREBP) cleavage-associating protein (SCAP) is a sterol-regulated escort protein that translocates SREBPs from the endoplasmic reticulum to the Golgi apparatus, thereby activating lipid metabolism and cholesterol synthesis. Although SCAP regulates lipid metabolism in metabolic tissues, such as the liver and muscle, the effect of macrophage-specific SCAP deficiency in adipose tissue macrophages (ATMs) of patients with metabolic diseases is not completely understood. OBJECTIVES: Here, we examined the function of SCAP in high-fat/high-sucrose diet (HFHS)-fed mice and investigated its role in the polarization of classical activated macrophages in adipose tissue. METHODS: Macrophage-specific SCAP knockout (mKO) mice were generated through crossbreeding lysozyme 2-cre mice with SCAP floxed mice which were then fed HFHS for 12 weeks. Primary macrophages were derived from bone marrow cells and analyzed further. RESULTS: We found that fat accumulation and the appearance of proinflammatory M1 macrophages were both higher in HFHS-fed SCAP mKO mice relative to floxed control mice. We traced the effect to a defect in the lipopolysaccharide-mediated increase in SREBP-1a that occurs in control but not SCAP mKO mice. Mechanistically, SREBP-1a increased expression of cholesterol 25-hydroxylase transcription, resulting in an increase in the production of 25-hydroxycholesterol (25-HC), an endogenous agonist of liver X receptor alpha (LXRα) which increased expression of cholesterol efflux to limit cholesterol accumulation and M1 polarization. In the absence of SCAP mediated activation of SREBP-1a, increased M1 macrophage polarization resulted in reduced cholesterol efflux downstream from 25-HC-dependent LXRα activation. CONCLUSION: Overall, the activation of the SCAP-SREBP-1a pathway in macrophages may provide a novel therapeutic strategy that ameliorates obesity by controlling cholesterol homeostasis in ATMs.


Asunto(s)
Resistencia a la Insulina , Ratones , Animales , Proteína 1 de Unión a los Elementos Reguladores de Esteroles , Péptidos y Proteínas de Señalización Intracelular , Colesterol , Obesidad
19.
Ann Surg Oncol ; 29(11): 6871-6881, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35622181

RESUMEN

BACKGROUND: The effects of specific body mass index (BMI) category and sarcopenia within each BMI category on outcomes in patients undergoing esophageal surgery with esophageal squamous cell carcinoma have not been thoroughly examined. METHODS: This study included 1141 patients. Sarcopenia was determined with a total psoas muscle cross-sectional area at the level of the third lumbar vertebra in computed tomography. The outcomes were long-term survival, including overall survival (OS) and recurrence-free survival (RFS), and postoperative complications. RESULTS: The overweight and no sarcopenia group was considered as the reference. After adjusting covariates, the underweight and the normal weight and sarcopenia groups both showed worse OS (underweight group: hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.33-3.13, p = 0.001; normal weight and sarcopenia group: HR 1.93, 95% CI 1.39-2.69, p < 0.001) and worse RFS (underweight group: HR 1.78, 95% CI 1.19-2.67, p = 0.005; normal weight and sarcopenia group: HR 1.70, 95% CI 1.25-2.30, p = 0.001). In addition, the underweight group (odds ratio [OR] 4.74, 95% CI 2.05-10.96, p < 0.001), the normal weight and sarcopenia group (OR 3.26, 95% CI 1.60-6.62, p = 0.001), the overweight and sarcopenia group (OR 2.54, 95% CI 1.14-5.68, p = 0.023), and the obese and no sarcopenia group (OR 2.44, 95% CI 1.14-5.22, p = 0.021) were at significantly higher risk of postoperative 30-day composite complications. CONCLUSIONS: Compared with the overweight and no sarcopenia group, the underweight and the normal weight and sarcopenia groups were associated with worse short- and long-term outcomes.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Sarcopenia , Índice de Masa Corporal , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/cirugía , Humanos , Sobrepeso , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Sarcopenia/complicaciones , Sarcopenia/patología , Delgadez/complicaciones
20.
3 Biotech ; 12(4): 100, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35463046

RESUMEN

Apple peel has several bioactive properties. The fruit is grown worldwide, and its ingredients are used medicinally. However, its anti-inflammatory activities are poorly characterized. In this study, isoquercitrin isolated from newly bred Green ball apple peel from Korea showed anti-inflammatory effects. To confirm its anti-inflammatory effects, isoquercitrin was treated with lipopolysaccharide, which induces proinflammatory factors in Raw 264.7 macrophage cells. Proinflammatory effects were measured by real-time polymerase chain reaction and Western blotting as well as enzyme-linked immunosorbent assay. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to define the isoquercitrin concentration nontoxic to cells. Nitric oxide (NO) production, prostaglandin E2, inducible NO synthase, cyclooxygenase-2 (COX-2), and nuclear factor-κB p65 protein expression decreased in a concentration-dependent manner by isoquercitrin. mRNA expression of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein-1, and prostaglandin E synthase 2 (PTGES2) as proinflammatory factors significantly decreased. PTGES2, which was stimulated by COX-2 and involved in PGE2 expression, was inhibited. Therefore, this study rendered isoquercitrin isolated from the newly bred Green ball apple peel as a potential pharmacological alternative to treat inflammation-related diseases.

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