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1.
Cell ; 182(1): 226-244.e17, 2020 07 09.
Artículo en Inglés | MEDLINE | ID: mdl-32649875

RESUMEN

Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.


Asunto(s)
Progresión de la Enfermedad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteogenómica , Fumar/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinógenos/toxicidad , Estudios de Cohortes , Citosina Desaminasa/metabolismo , Asia Oriental , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Genoma Humano , Humanos , Metaloproteinasas de la Matriz/metabolismo , Mutación/genética , Análisis de Componente Principal
2.
EMBO Rep ; 23(8): e54265, 2022 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-35766227

RESUMEN

The aggressive nature and poor prognosis of lung cancer led us to explore the mechanisms driving disease progression. Utilizing our invasive cell-based model, we identified methylthioadenosine phosphorylase (MTAP) and confirmed its suppressive effects on tumorigenesis and metastasis. Patients with low MTAP expression display worse overall and progression-free survival. Mechanistically, accumulation of methylthioadenosine substrate in MTAP-deficient cells reduce the level of protein arginine methyltransferase 5 (PRMT5)-mediated symmetric dimethylarginine (sDMA) modification on proteins. We identify vimentin as a dimethyl-protein whose dimethylation levels drop in response to MTAP deficiency. The sDMA modification on vimentin reduces its protein abundance but trivially affects its filamentous structure. In MTAP-deficient cells, lower sDMA modification prevents ubiquitination-mediated vimentin degradation, thereby stabilizing vimentin and contributing to cell invasion. MTAP and PRMT5 negatively correlate with vimentin in lung cancer samples. Taken together, we propose a mechanism for metastasis involving vimentin post-translational regulation.


Asunto(s)
Neoplasias Pulmonares , Purina-Nucleósido Fosforilasa , Humanos , Neoplasias Pulmonares/genética , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Purina-Nucleósido Fosforilasa/metabolismo , Vimentina/genética
3.
J Proteome Res ; 22(4): 1056-1070, 2023 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-36349894

RESUMEN

The fundamental pursuit to complete the human proteome atlas and the unmet clinical needs in lung adenocarcinoma have prompted us to study the functional role of uncharacterized proteins and explore their implications in cancer biology. In this study, we characterized SEL1L3, a previously uncharacterized protein encoded from chromosome 4 as a dysregulated protein in lung adenocarcinoma from the large-scale tissue proteogenomics data set established using the cohort of Taiwan Cancer Moonshot. SEL1L3 was expressed in abundance in the tumor parts compared with paired adjacent normal tissues in 90% of the lung adenocarcinoma patients in our cohorts. Moreover, survival analysis revealed the association of SEL1L3 with better clinical outcomes. Intriguingly, silencing of SEL1L3 imposed a reduction in cell viability and activation of ER stress response pathways, indicating a role of SEL1L3 in the regulation of cell stress. Furthermore, the immune profiles of patients with higher SEL1L3 expression were corroborated with its active role in immunophenotype and favorable clinical outcomes in lung adenocarcinoma. Taken together, our study revealed that SEL1L3 might play a vital role in the regulation of cell stress, interaction with cancer cells and the immune microenvironment. Our research findings provide promising insights for further investigation of its molecular signaling network and also suggest SEL1L3 as a potential emerging adjuvant for immunotherapy in lung adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Proteogenómica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/metabolismo , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/terapia , Adenocarcinoma del Pulmón/patología , Transducción de Señal , Inmunoterapia , Microambiente Tumoral , Pronóstico , Biomarcadores de Tumor/genética
4.
Immunology ; 168(2): 331-345, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36183155

RESUMEN

Methylthioadenosine phosphorylase (MTAP) deficiency occurs in various malignancies and is associated with poor survival in cancer patients. However, the mechanisms underlying tumour progression due to MTAP loss are yet to be elucidated. Utilizing integrated analyses of the transcriptome, proteome and secretome, we demonstrated that MTAP deficiency alters tumour-intrinsic, immune-related pathways and reprograms cytokine profiles towards a tumour-favourable environment. Additionally, MTAP-knockout cells exhibited a marked increase in the immune checkpoint protein PD-L1. Upon co-culturing primary T cells with cancer cells, MTAP loss-mediated PD-L1 upregulation inhibited T cell-mediated killing activity and induced several T cell exhaustion markers. In two xenograft tumour models, we showed a modest increase in average volume of tumours derived from MTAP-deficient cells than that of MTAP-proficient tumours. Surprisingly, a remarkable increase in tumour size was observed in humanized mice bearing MTAP-deficient tumours, as compared to their MTAP-expressing counterparts. Following immunophenotypic characterization of tumour-infiltrating leukocytes by mass cytometry analysis, MTAP-deficient tumours were found to display decreased immune infiltrates with lower proportions of both T lymphocytes and natural killer cells and higher proportions of immunosuppressive cells as compared to MTAP-expressing tumour xenografts. Taken together, our results suggest that MTAP deficiency restructures the tumour immune microenvironment, promoting tumour progression and immune evasion.


Asunto(s)
Antígeno B7-H1 , Neoplasias , Humanos , Animales , Ratones , Antígeno B7-H1/metabolismo , Purina-Nucleósido Fosforilasa/metabolismo , Neoplasias/metabolismo , Linfocitos T/metabolismo , Microambiente Tumoral
5.
Respir Res ; 24(1): 132, 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37194070

RESUMEN

BACKGROUND: Myo-inositol (or inositol) and its derivatives not only function as important metabolites for multiple cellular processes but also act as co-factors and second messengers in signaling pathways. Although inositol supplementation has been widely studied in various clinical trials, little is known about its effect on idiopathic pulmonary fibrosis (IPF). Recent studies have demonstrated that IPF lung fibroblasts display arginine dependency due to loss of argininosuccinate synthase 1 (ASS1). However, the metabolic mechanisms underlying ASS1 deficiency and its functional consequence in fibrogenic processes are yet to be elucidated. METHODS: Metabolites extracted from primary lung fibroblasts with different ASS1 status were subjected to untargeted metabolomics analysis. An association of ASS1 deficiency with inositol and its signaling in lung fibroblasts was assessed using molecular biology assays. The therapeutic potential of inositol supplementation in fibroblast phenotypes and lung fibrosis was evaluated in cell-based studies and a bleomycin animal model, respectively. RESULTS: Our metabolomics studies showed that ASS1-deficient lung fibroblasts derived from IPF patients had significantly altered inositol phosphate metabolism. We observed that decreased inositol-4-monophosphate abundance and increased inositol abundance were associated with ASS1 expression in fibroblasts. Furthermore, genetic knockdown of ASS1 expression in primary normal lung fibroblasts led to the activation of inositol-mediated signalosomes, including EGFR and PKC signaling. Treatment with inositol significantly downregulated ASS1 deficiency-mediated signaling pathways and reduced cell invasiveness in IPF lung fibroblasts. Notably, inositol supplementation also mitigated bleomycin-induced fibrotic lesions and collagen deposition in mice. CONCLUSION: These findings taken together demonstrate a novel function of inositol in fibrometabolism and pulmonary fibrosis. Our study provides new evidence for the antifibrotic activity of this metabolite and suggests that inositol supplementation may be a promising therapeutic strategy for IPF.


Asunto(s)
Fibrosis Pulmonar Idiopática , Inositol , Ratones , Animales , Inositol/farmacología , Inositol/uso terapéutico , Inositol/metabolismo , Pulmón/metabolismo , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/metabolismo , Bleomicina/toxicidad , Transducción de Señal/genética , Fibroblastos/metabolismo
6.
Nanotechnology ; 34(40)2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37399801

RESUMEN

We report on the formation of bendable and edge-on poly[3-(4-carboxybutyl)thiophene-2,5-diyl] (P3CT) polymers thin layer used as a hole modification layer (HML) in the inverted perovskite solar cell. The aggregations of 2D layer-like P3CT polymers in dimethylformamide (DMF) solution can be formed via aromaticπ-πstacking interactions and/or hydrogen-bonding interactions with the different concentration from 0.01 to 0.02 wt%, which highly influences the photovoltaic performance of the inverted perovskite solar cells. The atomic-force microscopic images and water droplet contact angle images show that the P3CT polymers modify the surface properties of the transparent conductive substrate and thereby dominating the formation of perovskite crystalline thin films, which play important roles in the highly efficient and stable perovskite solar cells. It is noted that theVOC(JSC) of the encapsulated solar cells values are maintained to be higher than 1.115 V (22 mA cm-2) after 104 d when an optimizedπ-πstacked and hydrogen-bonded P3CT polymer is used as the HML. On the other hand, the solar cell showed a high long-term stability by maintaining 85% of the initial power conversion efficiency in the ambient air for 103 d.

7.
Nanotechnology ; 34(15)2023 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-36657161

RESUMEN

Second harmonic generation (SHG) intensity, Raman scattering stress, photoluminescence and reflected interference pattern are used to determine the distributions of threading dislocations (TDs) and horizontal dislocations (HDs) in thec-plane GaN epitaxial layers on 6 inch Si wafer which is a structure of high electron mobility transistor (HEMT). The Raman scattering spectra show that the TD and HD result in the tensile stress and compressive stress in the GaN epitaxial layers, respectively. Besides, the SHG intensity is confirmed that to be proportional to the stress value of GaN epitaxial layers, which explains the spatial distribution of SHG intensity for the first time. It is noted that the dislocation-mediated SHG intensity mapping image of the GaN epitaxial layers on 6 inch Si wafer can be obtained within 2 h, which can be used in the optimization of high-performance GaN based HEMTs.

8.
Am J Respir Cell Mol Biol ; 64(6): 734-746, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33730527

RESUMEN

Tobacco smoking is a well-known risk factor for both fibrogenesis and fibrotic progression; however, the mechanisms behind these processes remain enigmatic. RTKs (receptor tyrosine kinases) have recently been reported to drive profibrotic phenotypes in fibroblasts during pulmonary fibrosis (PF). Using a phospho-RTK array screen, we identified the RTK AXL as a top upregulated RTK in response to smoke. Both expression and signaling activity of AXL were indeed elevated in lung fibroblasts exposed to tobacco smoke, whereas no significant change to the levels of a canonical AXL ligand, Gas6 (growth arrest-specific 6), was seen upon smoke treatment. Notably, we found that smoke-exposed human lung fibroblasts exhibited highly proliferative and invasive activities and were capable of inducing fibrotic lung lesions in mice. Conversely, genetic suppression of AXL in smoke-exposed fibroblasts cells led to suppression of AXL downstream pathways and aggressive phenotypes. We further demonstrated that AXL interacted with MARCKS (myristoylated alanine-rich C kinase substrate) and cooperated with MARCKS in regulating downstream signaling activity and fibroblast invasiveness. Pharmacological inhibition of AXL with AXL-specific inhibitor R428 showed selectivity for smoke-exposed fibroblasts. In all, our data suggest that AXL is a potential marker for smoke-associated PF and that targeting of the AXL pathway is a potential therapeutic strategy in treating tobacco smoking-related PF.


Asunto(s)
Proteínas Proto-Oncogénicas/metabolismo , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Fumar/efectos adversos , Animales , Supervivencia Celular , Modelos Animales de Enfermedad , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Pulmón/patología , Ratones Endogámicos C57BL , Sustrato de la Proteína Quinasa C Rico en Alanina Miristoilada/metabolismo , Fenotipo , Fibrosis Pulmonar/patología , Transducción de Señal , Regulación hacia Arriba/genética , Tirosina Quinasa del Receptor Axl
9.
Int J Mol Sci ; 18(11)2017 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-29125538

RESUMEN

Cigarette smoke has been shown to trigger aberrant signaling pathways and pathophysiological processes; however, the regulatory mechanisms underlying smoke-induced gene expression remain to be established. Herein, we observed that two smoke-responsive genes, HO-1 and CYP1A1, are robustly induced upon smoke by different mechanisms in human bronchial epithelia. CYP1A1 is mediated by aryl hydrocarbon receptor signaling, while induction of HO-1 is regulated by oxidative stress, and suppressed by N-acetylcysteine treatment. In light of a pivotal role of NRF2 and BACH1 in response to oxidative stress and regulation of HO-1, we examined if smoke-induced HO-1 expression is modulated through the NRF2/BACH1 axis. We demonstrated that smoke causes significant nuclear translocation of NRF2, but only a slight decrease in nuclear BACH1. Knockdown of NRF2 attenuated smoke-induced HO-1 expression while down-regulation of BACH1 had stimulatory effects on both basal and smoke-induced HO-1 with trivial influence on NRF2 nuclear translocation. Chromatin immunoprecipitation assays showed that smoke augments promoter-specific DNA binding of NRF2 but suppresses BACH1 binding to the HO-1 promoter ARE sites, two of which at -1.0 kb and -2.6 kb are newly identified. These results suggest that the regulation of NRF2 activator and BACH1 repressor binding to the ARE sites are critical for smoke-mediated HO-1 induction.


Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Hemo-Oxigenasa 1/genética , Factor 2 Relacionado con NF-E2/genética , Fumar/genética , Bronquios/metabolismo , Bronquios/patología , Línea Celular , Núcleo Celular/genética , Citocromo P-450 CYP1A1/genética , Proteínas de Unión al ADN/genética , Células Epiteliales/metabolismo , Células Epiteliales/patología , Regulación de la Expresión Génica/genética , Humanos , Estrés Oxidativo/genética , Regiones Promotoras Genéticas , Mapas de Interacción de Proteínas/genética , Transducción de Señal/genética , Fumar/patología
10.
BMC Cancer ; 16: 583, 2016 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-27485439

RESUMEN

BACKGROUND: Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, and lncRNA taurine-upregulated gene 1 (TUG1) has been proven to be associated with several human cancers. However, the mechanisms of TUG1-involved regulation remain largely unknown. METHODS: We examined the expressions of TUG1 in a cohort of 89 patients with non-small cell lung cancer (NSCLC) to determine the association between TUG1 expression and clinical parameters. We used circular chromosome conformation capture (4C) coupled with next-generation sequencing to explore the genome regions that interact with TUG1 and the TUG1-mediated regulation. RESULTS: TUG1 was significantly downregulated, and the TUG1 downregulation correlated with sex (p = 0.006), smoking status (p = 0.016), and tumor differentiation grade (p = 0.001). Knockdown of TUG1 significantly promoted the proliferation of NSCLC cells. According to the bioinformatic analysis result of TUG1 4C sequencing data, 83 candidate genes and their interaction regions were identified. Among these candidate genes, CUGBP and Elav-like family member 1 (CELF1) are potential targets of TUG1 in-trans regulation. To confirm the interaction between TUG1 and CELF1, relative expressions of CELF1 were examined in TUG1 knockdown H520 cells; results showed that CELF1 was significantly upregulated in TUG1 knockdown H520 cells. RNA immunoprecipitation was then performed to examine whether TUG1 RNA was bound to PRC2, a TUG1-involved regulation mechanism reported in previous studies. The results demonstrated that TUG1 RNA was bound to enhancer of zeste protein 2/embryonic ectoderm development (EZH2/EED), which is essential for PRC2. Finally, our designed ChIP assay revealed that the EZH2/EED was bound to the promotor region of CELF1 within 992 bp upstream of the transcript start site. CONCLUSION: TUG1 is downregulated in NSCLC. Using TUG1 4C sequencing and bioinformatic analysis, we found CELF1 to be a potential target of TUG1 RNA in in-trans regulation. Moreover, subsequent experiments showed that TUG1 RNA could bind to PRC2 in the promotor region of CELF1 and negatively regulate CELF1 expressions in H520 cells. Our results may facilitate developing new treatment modalities targeting TUG1/PRC2/CELF1 interactions in patients with NSCLC.


Asunto(s)
Proteínas CELF1/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación hacia Abajo , Neoplasias Pulmonares/genética , Complejo Represivo Polycomb 2/metabolismo , ARN Largo no Codificante/genética , Proteínas CELF1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular , Inmunoprecipitación de Cromatina , Femenino , Regulación Neoplásica de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Neoplasias Pulmonares/patología , Masculino , Regiones Promotoras Genéticas , ARN Largo no Codificante/metabolismo , Análisis de Supervivencia , Activación Transcripcional
11.
Int J Qual Health Care ; 28(2): 183-90, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26819445

RESUMEN

OBJECTIVE: Few studies address quality of care in pay-for-performance (P4P) programs from the perspective of patients' perceptions. This study aimed to examine and compare the patient assessment of diabetes chronic care as perceived by diabetic patients enrolled and not enrolled in a P4P program from the patients' self-reported perspectives. DESIGN: A cross-sectional study with case and comparison group design. SETTING: A large-scale survey was conducted from February to November 2013 in 18 healthcare institutions in Taiwan. PARTICIPANTS: A total of 1458 P4P (n = 1037) and non-P4P (n = 421) diabetic patients participated in this large survey. The Chinese version of the Patient Assessment of Chronic Illness Care (PACIC) instrument was used and patients' clinical outcome data (e.g. HbA1c, LDL) were collected. INTERVENTION: None. MAIN OUTCOME MEASURES: Five subscales from the PACIC were measured, including patient activation, delivery system design/system support, goal setting/tailoring, problem solving/contextual and follow-up/coordination. Patient clinical outcomes were also measured. Multiple linear regression and logistic regression models were used and controlled for patient demographic and health institution characteristics statistically. RESULTS: After adjusting for covariates, P4P patients had higher overall scores on the PACIC and five subscales than non-P4P patients. P4P patients also had better clinical processes of care (e.g. HbA1c test) and intermediate outcomes. CONCLUSIONS: Patients who participated in the program likely received better patient-centered care given the original Chronic Care Model. Better perceptions of diabetic care assessment also better clinical outcomes. The PACIC instrument can be used for the patient assessment of chronic care in a P4P program.


Asunto(s)
Diabetes Mellitus/terapia , Satisfacción del Paciente , Garantía de la Calidad de Atención de Salud/métodos , Reembolso de Incentivo/normas , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Garantía de la Calidad de Atención de Salud/estadística & datos numéricos , Encuestas y Cuestionarios , Taiwán
12.
Front Immunol ; 15: 1372956, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38953033

RESUMEN

Our study aimed to elucidate the role of Galectin-1 (Gal-1) role in the immunosuppressive tumor microenvironment (TME) of prostate cancer (PCa). Our previous findings demonstrated a correlation between elevated Gal-1 expression and advanced PCa stages. In this study, we also observed that Gal-1 is expressed around the tumor stroma and its expression level is associated with PCa progression. We identified that Gal-1 could be secreted by PCa cells, and secreted Gal-1 has the potential to induce T cell apoptosis. Gal-1 knockdown or inhibition of Gal-1 function by LLS30 suppresses T cell apoptosis resulting in increased intratumoral T cell infiltration. Importantly, LLS30 treatment significantly improved the antitumor efficacy of anti-PD-1 in vivo. Mechanistically, LLS30 binds to the carbohydrate recognition domain (CRD) of Gal-1, disrupting its binding to CD45 leading to the suppression of T cell apoptosis. In addition, RNA-seq analysis revealed a novel mechanism of action for LLS30, linking its tumor-intrinsic oncogenic effects to anti-tumor immunity. These findings suggested that tumor-derived Gal-1 contributes to the immunosuppressive TME in PCa by inducing apoptosis in effector T cells. Targeting Gal-1 with LLS30 may offer a strategy to enhance anti-tumor immunity and improve immunotherapy.


Asunto(s)
Apoptosis , Galectina 1 , Inmunoterapia , Neoplasias de la Próstata , Linfocitos T , Microambiente Tumoral , Masculino , Galectina 1/genética , Galectina 1/metabolismo , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Humanos , Animales , Microambiente Tumoral/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Ratones , Inmunoterapia/métodos , Línea Celular Tumoral , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo
13.
Eur J Nutr ; 52(3): 927-35, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22722891

RESUMEN

PURPOSE: Almond consumption is associated with ameliorations in obesity, hyperlipidemia, hypertension, and hyperglycemia. The hypothesis of this 12-week randomized, crossover, controlled feeding trial was that almond consumption would ameliorate inflammation and oxidative stress in Chinese patients with type 2 diabetes mellitus (T2DM) (9 M, 11 F; 58 years; BMI: 26 kg/m²) with mild hyperlipidemia. METHODS: After a 2-week run-in period, the patients were assigned to either a control NCEP step II diet (control diet) or almond diet for 4 weeks with a 2-week washout period between alternative diets. Almonds approximately at 56 g/day were added to the control diet to replace 20 % of total daily calorie intake. RESULTS: As compared to the control diet, the almond diet decreased IL-6 by a median 10.3 % (95 % confidence intervals 5.2, 12.6 %), CRP by a median 10.3 % (-24.1, 40.5), and TNF-α by a median 15.7 % (-0.3, 29.9). The almond diet also decreased plasma protein carbonyl by a median 28.2 % (4.7, 38.2) as compared to the C diet but did not alter plasma malondialdehyde. The A diet enhanced the resistance of LDL against Cu²âº-induced oxidation by a median 16.3 % (7.4, 44.3) as compared to the C diet. Serum intercellular adhesion molecule-1 and vascular adhesion molecule-1 were not changed by both diets. CONCLUSIONS: Our results suggested that incorporation of almonds into a healthy diet could ameliorate inflammation and oxidative stress in patients with T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2/dietoterapia , Dieta con Restricción de Grasas , Hiperlipidemias/prevención & control , Nueces , Estrés Oxidativo , Prunus , Índice de Masa Corporal , Estudios de Cohortes , Estudios Cruzados , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/inmunología , Regulación hacia Abajo , Femenino , Humanos , Hiperlipidemias/complicaciones , Hiperlipidemias/fisiopatología , Mediadores de Inflamación/sangre , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Sobrepeso/complicaciones , Carbonilación Proteica , Índice de Severidad de la Enfermedad , Taiwán
14.
Nanomedicine ; 9(8): 1274-82, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23751373

RESUMEN

Early detection of pathogens is crucial for the effective surveillance of diseases. Many efforts have been made to explore methods which can detect these pathogens within a short period of time without requiring a tedious protocol. However, these developed methods have disadvantages such as they are relatively time-consuming or require specialized laboratory facilities. In this work, we have developed an integrated microfluidic system for rapid and automatic detection of viruses by direct analysis from fresh Phalaenopsis orchid leaves. The entire protocol, including ribonucleic acid (RNA) purification, reverse transcription loop-mediated-isothermal-amplification (RT-LAMP) and optical detection by measuring changes in turbidity was performed on a single chip. This is the first time that an integrated microfluidic system for the detection of viruses infecting the Phalaenopsis orchid has been demonstrated. The sensitivity of the developed system was also explored in this study to validate its performance. FROM THE CLINICAL EDITOR: In this study, the authors report the development of an integrated microfluidic system for rapid and automatic detection of viruses by direct analysis of fresh Phalaenopsis orchid leaves, performing the 3-step protocol using a single chip. Similar methods may find clinical application for fast and accurate detection of viral infections.


Asunto(s)
Técnicas Analíticas Microfluídicas/instrumentación , Orchidaceae/virología , Enfermedades de las Plantas/virología , Hojas de la Planta/virología , ARN Viral/aislamiento & purificación , Virus/aislamiento & purificación , Diseño de Equipo , ARN Viral/genética , Virus/genética
15.
ScientificWorldJournal ; 2013: 950548, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24453929

RESUMEN

The diagnosis of periprosthetic joint infection is sometimes straightforward with purulent discharge from the fistula tract communicating to the joint prosthesis. However it is often difficult to differentiate septic from aseptic loosening of prosthesis because of the high culture-negative rates in conventional microbiologic culture. This study used quantitative reverse transcription polymerase chain reaction (RT-qPCR) to amplify bacterial 16S ribosomal RNA in vitro and in 11 clinical samples. The in vitro analysis demonstrated that the RT-qPCR method was highly sensitive with the detection limit of bacterial 16S rRNA being 0.148 pg/ µ l. Clinical specimens were analyzed using the same protocol. The RT-qPCR was positive for bacterial detection in 8 culture-positive cases (including aerobic, anaerobic, and mycobacteria) and 2 culture-negative cases. It was negative in one case that the final diagnosis was confirmed without infection. The molecular diagnosis of bacterial infection using RT-qPCR to detect bacterial 16S rRNA around a prosthesis correlated well with the clinical findings. Based on the promising clinical results, we were attempting to differentiate bacterial species or drug-resistant strains by using species-specific primers and to detect the persistence of bacteria during the interim period before the second stage reimplantation in a larger scale of clinical subjects.


Asunto(s)
Bacterias/genética , Infecciones Bacterianas , Farmacorresistencia Bacteriana/genética , Contaminación de Equipos , Prótesis Articulares , ARN Bacteriano/genética , ARN Ribosómico 16S/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Adulto , Anciano , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad
16.
Nutrients ; 15(18)2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37764676

RESUMEN

This study estimates the association between sarcopenia and blood biochemical parameters, nutritional intake, anthropometric measurements, physical performance, and physical activity in patients with type 2 diabetes mellitus (T2DM). Participants were recruited from a primary care clinic in Kaohsiung City. According to the diagnosis criteria of the Asian Working Group for Sarcopenia (AWGS) in 2019, 110 patients with T2DM (aged 50-80 years) were divided into three groups: non-sarcopenia (n = 38), possible sarcopenia (n = 31), and sarcopenia (n = 41). Blood samples were collected, and nutritional intake was evaluated by a registered dietitian. A food frequency questionnaire and a Godin leisure-time exercise questionnaire were used to assess their daily vitamin D intake and physical activity. There were significant differences in age, serum vitamin D levels, nutritional intake, anthropometric measurements, and physical performance between the three groups. In elderly patients with T2DM, reduced serum 25-hydroxyvitamin D [25(OH)D] levels and daily energy intake were significantly associated with possible sarcopenia. Age, lower BMI, reduced serum 25(OH)D, and reduced dietary protein and vitamin D intake were significantly associated with sarcopenia. These findings may serve as the basis for intervention trials to reduce the prevalence of sarcopenia.


Asunto(s)
Diabetes Mellitus Tipo 2 , Sarcopenia , Anciano , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Taiwán/epidemiología , Sarcopenia/epidemiología , Sarcopenia/etiología , Composición Corporal , Ingestión de Alimentos , Ejercicio Físico , Vitamina D
17.
Mater Horiz ; 10(6): 2254-2261, 2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37021482

RESUMEN

Here we report on the growth of thin crystalline films of the metastable phase GeTe2. Direct observation by transmission electron microscopy revealed a Te-Ge-Te stacking with van der Waals gaps. Moreover, electrical and optical measurements revealed the films exhibted semiconducting properties commensurate with electronics applications. Feasibility studies in which device structures were fabricated demonstrated the potential application of GeTe2 as an electronic material.

18.
Food Chem ; 394: 133538, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-35759841

RESUMEN

Mislabelling the geographic origin of same-species aquaculture products is difficult to identify. This study applied untargeted small-molecule fingerprinting to discriminating between Atlantic salmon originating from Chile and Norway. The acquired liquid chromatography-high-resolution mass spectrometry data from Chilean (n = 32) and Norwegian (n = 29) salmon were chemometrically processed. The partial least squares discriminant analysis (PLS-DA) models successfully discriminated between Chilean and Norwegian salmon at both positive and negative ionisation modes (R2 > 0.96, Q2 > 0.81). Univariate analyses facilitated the selection of approximately 100 candidate markers with high statistical confidence (> 95%). Of these, 37 confirmed markers of Chilean and Norwegian salmon were primarily associated with feed formulations, including lipid derivatives and feed additives. None of the markers were residues or contaminants of potential food safety concern.


Asunto(s)
Salmo salar , Animales , Acuicultura , Cromatografía Liquida , Inocuidad de los Alimentos , Alimentos Marinos/análisis
19.
ACS Nano ; 16(8): 13069-13081, 2022 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-35849128

RESUMEN

The control of crystal polymorphism and exploration of metastable, two-dimensional, 1T'-phase, transition-metal dichalcogenides (TMDs) have received considerable research attention. 1T'-phase TMDs are expected to offer various opportunities for the study of basic condensed matter physics and for its use in important applications, such as devices with topological states for quantum computing, low-resistance contact for semiconducting TMDs, energy storage devices, and as hydrogen evolution catalysts. However, due to the high energy difference and phase change barrier between 1T' and the more stable 2H-phase, there are few methods that can be used to obtain monolayer 1T'-phase TMDs. Here, we report on the chemical vapor deposition (CVD) growth of 1T'-phase WS2 atomic layers from gaseous precursors, i.e., H2S and WF6, with alkali metal assistance. The gaseous nature of the precursors, reducing properties of H2S, and presence of Na+, which acts as a countercation, provided an optimal environment for the growth of 1T'-phase WS2, resulting in the formation of high-quality submillimeter-sized crystals. The crystal structure was characterized by atomic-resolution scanning transmission electron microscopy, and the zigzag chain structure of W atoms, which is characteristic of the 1T' structure, was clearly observed. Furthermore, the grown 1T'-phase WS2 showed superconductivity with the transition temperature in the 2.8-3.4 K range and large upper critical field anisotropy. Thus, alkali metal assisted gas-source CVD growth is useful for realizing large-scale, high-quality, phase-engineered TMD atomic layers via a bottom-up synthesis.

20.
Artículo en Inglés | MEDLINE | ID: mdl-36011919

RESUMEN

Background: Sweating and increased skin temperature caused by exercise can reduce physical activity and the willingness to exercise in adolescents with atopic dermatitis. This study was conducted to investigate the exercise load capacity of adolescents with atopic dermatitis and analyzed their exercise behavior and motivation. Methods: Adolescents with and without atopic dermatitis were assigned to the atopic dermatitis group and control group (n = 27 each). Both groups completed a cardiopulmonary exercise test and questionnaires to assess their exercise capacity, weekly exercise volume, exercise motivation, and self-efficacy, respectively. Results: The ratio of measured forced vital capacity to the predicted forced vital capacity and the peak oxygen consumption of the atopic dermatitis group were significantly lower than those of the control group. The Godin Leisure-Time Exercise Questionnaire scores of the atopic dermatitis group were significantly lower than those of the control group. As for the Behavioral Regulation in Exercise Questionnaire 2, the scores for the introjected and identified regulations of the atopic dermatitis group were significantly lower than those of the control group. Regarding the Multidimensional Self-Efficacy for Exercise Scale, the scheduling efficacy and total scores of the atopic dermatitis group were significantly lower than those of the control group. Conclusions: Adolescents with atopic dermatitis had lower peak exercise capacity and lower weekly exercise volume. Furthermore, they lacked the negative feelings toward inactivity and the self-confidence to plan regular exercise independently. The results of this study suggest that adolescents with atopic dermatitis should be encouraged to engage in regular indoor exercise.


Asunto(s)
Dermatitis Atópica , Adolescente , Ejercicio Físico , Humanos , Conducta Sedentaria , Autoeficacia , Encuestas y Cuestionarios
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