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BACKGROUND AND AIMS: Overnutrition-induced activation of mammalian target of rapamycin (mTOR) dysregulates intracellular lipid metabolism and contributes to hepatic lipid deposition. Apolipoprotein J (ApoJ) is a molecular chaperone and participates in pathogen-induced and nutrient-induced lipid accumulation. This study investigates the mechanism of ApoJ-regulated ubiquitin-proteasomal degradation of mTOR, and a proof-of-concept ApoJ antagonist peptide is proposed to relieve hepatic steatosis. APPROACH AND RESULTS: By using omics approaches, upregulation of ApoJ was found in high-fat medium-fed hepatocytes and livers of patients with NAFLD. Hepatic ApoJ level associated with the levels of mTOR and protein markers of autophagy and correlated positively with lipid contents in the liver of mice. Functionally, nonsecreted intracellular ApoJ bound to mTOR kinase domain and prevented mTOR ubiquitination by interfering FBW7 ubiquitin ligase interaction through its R324 residue. In vitro and in vivo gain-of-function or loss-of-function analysis further demonstrated that targeting ApoJ promotes proteasomal degradation of mTOR, restores lipophagy and lysosomal activity, thus prevents hepatic lipid deposition. Moreover, an antagonist peptide with a dissociation constant (Kd) of 2.54 µM interacted with stress-induced ApoJ and improved hepatic pathology, serum lipid and glucose homeostasis, and insulin sensitivity in mice with NAFLD or type II diabetes mellitus. CONCLUSIONS: ApoJ antagonist peptide might be a potential therapeutic against lipid-associated metabolic disorders through restoring mTOR and FBW7 interaction and facilitating ubiquitin-proteasomal degradation of mTOR.
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Humanos , Ratones , Animales , Clusterina/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Sirolimus , Hígado/patología , Serina-Treonina Quinasas TOR/metabolismo , Metabolismo de los Lípidos/fisiología , Ubiquitinas/metabolismo , Lípidos , Ratones Endogámicos C57BL , Mamíferos/metabolismoRESUMEN
The increasing prevalence of overcrowding in Emergency Departments (EDs) threatens the effective delivery of urgent healthcare. Mitigation strategies include the deployment of monitoring systems capable of tracking and managing patient disposition to facilitate appropriate and timely care, which subsequently reduces patient revisits, optimizes resource allocation, and enhances patient outcomes. This study used â¼ 250,000 emergency department visit records from Taipei Medical University-Shuang Ho Hospital to develop a natural language processing model using BlueBERT, a biomedical domain-specific pre-trained language model, to predict patient disposition status and unplanned readmissions. Data preprocessing and the integration of both structured and unstructured data were central to our approach. Compared to other models, BlueBERT outperformed due to its pre-training on a diverse range of medical literature, enabling it to better comprehend the specialized terminology, relationships, and context present in ED data. We found that translating Chinese-English clinical narratives into English and textualizing numerical data into categorical representations significantly improved the prediction of patient disposition (AUROC = 0.9014) and 72-hour unscheduled return visits (AUROC = 0.6475). The study concludes that the BlueBERT-based model demonstrated superior prediction capabilities, surpassing the performance of prior patient disposition predictive models, thus offering promising applications in the realm of ED clinical practice.
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Servicio de Urgencia en Hospital , Procesamiento de Lenguaje Natural , Readmisión del Paciente , Servicio de Urgencia en Hospital/estadística & datos numéricos , Humanos , Readmisión del Paciente/estadística & datos numéricos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Registros Electrónicos de Salud , Narración , AncianoRESUMEN
Since early identification of potential critical patients in the Emergency Department (ED) can lower mortality and morbidity, this study seeks to develop a machine learning model capable of predicting possible critical outcomes based on the history and vital signs routinely collected at triage. We compare emergency physicians and the predictive performance of the machine learning model. Predictors including patients' chief complaints, present illness, past medical history, vital signs, and demographic data of adult patients (aged ≥ 18 years) visiting the ED at Shuang-Ho Hospital in New Taipei City, Taiwan, are extracted from the hospital's electronic health records. Critical outcomes are defined as in-hospital cardiac arrest (IHCA) or intensive care unit (ICU) admission. A clinical narrative-aware deep neural network was developed to handle the text-intensive data and standardized numerical data, which is compared against other machine learning models. After this, emergency physicians were asked to predict possible clinical outcomes of thirty visits that were extracted randomly from our dataset, and their results were further compared to our machine learning model. A total of 4,308 (2.5 %) out of the 171,275 adult visits to the ED included in this study resulted in critical outcomes. The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) of our proposed prediction model is 0.874 and 0.207, respectively, which not only outperforms the other machine learning models, but even has better sensitivity (0.95 vs 0.41) and accuracy (0.90 vs 0.67) as compared to the emergency physicians. This model is sensitive and accurate in predicting critical outcomes and highlights the potential to use predictive analytics to support post-triage decision-making.
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Servicio de Urgencia en Hospital , Hospitalización , Adulto , Humanos , Pronóstico , Redes Neurales de la Computación , Aprendizaje Automático , Estudios RetrospectivosRESUMEN
BACKGROUND: This study aims to analyze the impact of Framework of Convention of Tobacco Control (FCTC) on regulatory contents of trade agreements from 2001 to 2019. METHODS: A search of trade agreements from'WTO Regional Free Trade Agreement Database' using keywords including "tobacco", "cigarette", "smoking" and "FCTC" from May to August 2020 resulted in a total sample of 268 trade agreements, from which 69 trade agreements were coded and analyzed. Provisions in trade agreements, identified via the aforementioned keywords, were categorized into 6 trade measures. The word counts of the provisions containing; FCTC; were calculated. Chi-square tests were applied to analyze the differences of regulatory patterns between different time frames. The import and export values (USD) of tobacco products under trade agreements containing the term "FCTC" were further collected from the "International Trade Statistics 2001-2020" for understanding the impact of the provision on the trade flow. RESULTS: Among 69 agreements, the percentage of trade agreements containing keyword as "FCTC" increased significantly from 0% to 2011 to 12% after 2011. A significant decrease of using trade measures as "the exclusion list" was found after 2011 (from 10% to 0). The word counts of provisions containing; FCTC; increased from 24 words in 2011 to 164 words in 2018, and the content of the provisions became more concrete over time. There are six trade agreements containing "FCTC", and all these 6 agreements were ratified by European Union (EU). Despite EU ratified trade agreements with "FCTC", the import and export values of tobacco products between EU and the other party countries increased with time. But the gap of average trade values between trade agreements with and without "FCTC" being widened with time. CONCLUSIONS: As a first study evaluated the impact of FCTC on regulatory contents of trade agreements, our study results showed that after countries signed trade agreements containing keyword FCTC, the regulatory contents changed significantly. Further studies are recommended to understand the reason and criteria for incorporating FCTC provisions into trade agreements, especially in the EU.
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Industria del Tabaco , Productos de Tabaco , Humanos , Control del Tabaco , Comercio , Prevención del Hábito de Fumar , Internacionalidad , Políticas , Organización Mundial de la SaludRESUMEN
We developed a new questionnaire-the Sarcopenia Knowledge Questionnaire (SKQ)-to evaluate the level of awareness about sarcopenia among older adults and tested the reliability and validity of this tool. A total of 293 older adults completed the questionnaire. The SKQ comprises three domains including 23 items: screening and diagnosis (10 items), sarcopenia outcomes (7 items), and lifestyle factors (6 items). The Cronbach's α value was 0.969, which indicated excellent internal consistency. The SKQ correlated well with the Mandarin Multidimensional Health Literacy Questionnaire (r = 0.511; p < 0.001), confirming its moderate convergent validity. The absolute values of the critical ratio ranged from 9.90 to 25.82 (p < 0.001), indicating satisfactory item discrimination. Thus, the SKQ appears to be a valid and reliable instrument for evaluating the knowledge of older adults about sarcopenia.
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Alfabetización en Salud , Sarcopenia , Humanos , Anciano , Sarcopenia/diagnóstico , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Estilo de Vida , PsicometríaRESUMEN
Photodermatosis is an abnormal skin inflammatory reaction to light. The major classifications of photodermatoses are idiopathic photodermatoses, photodermatoses due to exogenous or endogenous agents, photo-exacerbated dermatoses, and photosensitive genodermatoses. In this chapter, we focus on idiopathic photodermatoses and drug-related photodermatoses and emphasize on the epidemiology and immunogenetic backgrounds. Idiopathic photodermatoses, a spectrum of diseases with abnormal responses to ultraviolet radiation (UVR), include polymorphous light eruption, actinic prurigo, hydroa vacciniforme, chronic actinic dermatitis, and solar urticaria. Young people are more susceptible to most idiopathic photodermatoses except for chronic actinic dermatitis. Interestingly, idiopathic photodermatoses exhibit different characteristics between Caucasians and Asians. For example, the average age of Asian actinic prurigo patients is older than that of Caucasians in which genetic backgrounds or Fitzpatrick skin type might play a role. Drug-induced photodermatoses can be classified into phototoxic and photoallergic drug reactions. Certain drug-induced photodermatoses may mimic other dermatoses. For instance, drug-induced lupus erythematosus (LE) should be considered if an old man is diagnosed with LE but had a poor response to standard treatments.
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Trastornos por Fotosensibilidad , Rayos Ultravioleta , Adolescente , Humanos , Inmunogenética , Masculino , Trastornos por Fotosensibilidad/diagnóstico , Trastornos por Fotosensibilidad/genética , Rayos Ultravioleta/efectos adversosRESUMEN
We reviewed 20 randomized controlled trials concerning the intervention methods and effects of lavender essential oil on adults' sleep quality. Fourteen showed positive intervention effects. A mixture of subjective and objective indicators was used. Lavender essential oil was associated with improved sleep quality before insomnia or other sleep disorders occurred.
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Lavandula , Aceites Volátiles , Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos del Sueño-Vigilia , Adulto , Humanos , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Sueño , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Calidad del SueñoRESUMEN
This study aimed to understand the characteristics of chronic pruritus (CP), its correlations with sleep quality and demographic characteristics, and its impacts on sleep of older adults. This study used convenience sampling to recruit adults aged 65 or older and living at home. The prevalence rate of CP in older adults was 25.8%. Most subjects with CP reported mild pruritus on 1-2 anatomical parts, especially the lower extremities. Overall, the five domains of CP were correlated with the seven components of sleep quality (r > .14; p > .05) except for sleep disturbance. The global itchy scores were significantly different between different sexes, educational attainments, and marital statuses (p<.05-.001). CP, sex, and the number of comorbid diseases significantly contributed to global sleep quality (ß = .26, -.19, .15, respectively; .000 ≤ p ≤ .011). This study provides new insight into the correlations of CP with marital status and educational attainment.
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Vida Independiente , Sueño , Anciano , Estudios Transversales , Humanos , Prurito/epidemiología , Taiwán/epidemiologíaRESUMEN
INTRODUCTION: Xeroderma pigmentosum complementation group C (XPC) protein is an important DNA damage recognition factor involved in nucleotide excision repair and regulation of non-small-cell lung cancer (NSCLC) cell proliferation and viability. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) blocks ATP binding to heat shock protein 90 (Hsp90), resulting in destabilization of Hsp90-client protein complexes. Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor expressed by many types of tumors. Bevacizumab (Avastin) is a humanized monoclonal antibody against human VEGF used as an antiangiogenesis agent in the therapy of many cancers, proving successful in increasing objective tumor response rate and prolonging overall survival in NSCLC patients. METHODS: After the bevacizumab and/or 17-AAG treatment, the expressions of XPC mRNA were determined by quantitative real-time PCR analysis. Protein levels of XPC and phospho-AKT were determined by Western blot analysis. We used specific XPC small interfering RNA and PI3K inhibitor (LY294002) to examine the role of the AKT-XPC signal in regulating the chemosensitivity of bevacizumab and 17-AAG. Cell viability was assessed by the MTS assay and trypan blue exclusion assay. RESULTS: In this study, bevacizumab decreased XPC expression in human lung squamous cell carcinoma H520 and H1703 cells via AKT inactivation. Enhancement of AKT activity by transfection with constitutively active AKT vectors increased XPC expression and cell survival after treatment with bevacizumab. In addition, 17-AAG synergistically enhanced bevacizumab-induced cytotoxicity and cell growth inhibition in H520 and H1703 cells, associated with downregulation of XPC expression and inactivation of AKT. DISCUSSION/CONCLUSION: Together, these results may provide a rationale to combine bevacizumab with Hsp90 inhibitors in future to enhance therapeutic effects for lung cancer.
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Inhibidores de la Angiogénesis/farmacología , Antineoplásicos/farmacología , Benzoquinonas/farmacología , Bevacizumab/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Proteínas de Unión al ADN/genética , Lactamas Macrocíclicas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cromonas/farmacología , Proteínas de Unión al ADN/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Sinergismo Farmacológico , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Neoplasias Pulmonares/patología , Morfolinas/farmacología , Proteaceae/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genéticaRESUMEN
Bacterial strain TWA-58T, isolated from irrigation water in Taiwan, was characterized using a polyphasic taxonomy approach. Phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of 92 protein clusters indicated that strain TWA-58T formed a phylogenetic lineage in the genus Oleiharenicola of the family Opitutaceae. Strain TWA-58T was most closely related to Oleiharenicola alkalitolerans NVTT with a 96.7â% 16S rRNA gene sequence similarity. Strain TWA-58T showed 75.2â% average nucleotide identity, 70.9â% average amino acid identity and 21.0â% digital DNA-DNA hybridization identity with O. alkalitolerans NVTT. Cells were Gram-stain-negative, aerobic, motile, coccoid-shaped and formed transparent colonies. Optimal growth occurred at 25 °C, pH 6, and 0â% NaCl. The major fatty acids of strain TWA-58T were iso-C15â:â0 and anteiso-C15â:â0. The predominant hydroxy fatty acid was iso-C13â:â0 3-OH. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and two unidentified aminophospholipids. The major isoprenoid quinone was MK-7. Genomic DNA G+C content of strain TWA-58T was 65.3 mol%. On the basis of phenotypic and genotypic properties and phylogenetic inference, strain TWA-58T should be classified in a novel species of the genus Oleiharenicola, for which the name Oleiharenicola lentus sp. nov. is proposed. The type strain is TWA-58T (=BCRC 81161T=LMG 31019T=KCTC 62872T).
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Filogenia , Verrucomicrobia/clasificación , Microbiología del Agua , Riego Agrícola , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Taiwán , Verrucomicrobia/aislamiento & purificación , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
A bacterial strain designated CAR-16T was isolated from a freshwater lake in Taiwan and characterized using the polyphasic taxonomic approach. Cells were Gram-stain-negative, aerobic, motile by gliding, rod-shaped and formed rose-colored colonies. Optimal growth occurred at 30 °C, pH 7 and with 0â% NaCl. Phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of 92 protein clusters indicated that CAR-16T represented a member of the family Cytophagaceae and formed a phylogenetic lineage in the genus Aquirufa. CAR-16T was most closely related to Aquirufa nivalisilvae 59G-WUEMPELT with a 99.7â% 16S rRNA gene sequence similarity. CAR-16T showed 71.2-79.5â% average nucleotide identity and 17.8-21.7â% digital DNA-DNA hybridization identity with the strains of other species of the genus Aquirufa. The major fatty acids of strain CAR-16T were iso-C15â:â0, iso-C15â:â0 3-OH, C16â:â1ω5c and summed feature 3 (C16â:â1ω7c/C16â:â1ω6c and/or iso-C15â:â0 2-OH). The polar lipid profile consisted of a mixture of phosphatidylethanolamine and several uncharacterized aminophospholipids, phospholipids and lipids. The major isoprenoid quinone was MK-7. The genomic DNA G+C content of CAR-16T was 38.8 mol%. On the basis of phenotypic and genotypic properties and phylogenetic inference, CAR-16T should be classified as representing a novel species of the genus Aquirufa, for which the name Aquirufa rosea sp. nov. is proposed. The type strain is CAR-16T (=BCRC 81153T=LMG 30923T=KCTC 62869T).
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Cytophagaceae/clasificación , Lagos/microbiología , Filogenia , Técnicas de Tipificación Bacteriana , Composición de Base , Cytophagaceae/aislamiento & purificación , ADN Bacteriano/genética , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Taiwán , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
A novel bacterial strain, designated KMB7T, isolated from a freshwater pond in Taiwan, was characterized using a polyphasic taxonomic approach. Cells were Gram-stain-negative, motile by means of a single polar flagellum, rod-shaped and formed cream colonies. Optimal growth occurred at 25 °C, pH 7, and in the absence of NaCl. Phylogenetic analyses based on 16S rRNA gene sequences and an up-to-date bacterial core gene set (92 protein clusters) indicated that strain KMB7T is affiliated with species in the genus Aquabacterium. The 16S rRNA gene sequence similarity indicated that strain KMB7T is closely related to species within the genus Aquabacterium (95.2-97.6â% sequence similarity) and is most similar to A. fontiphilum CS-6T (97.6 %), followed by A. parvum B6T (97.5 %). The average nucleotide identity and digital DNA-DNA hybridization identity between strain KMB7T and the closely related strains were 74.6-78.0â% and 19.0-21.2â%, respectively. The major fatty acids of strain KMB7T were summed feature 3 (C16â:â1 ω7c and/or C16â:â1 ω6c), C18â:â1 ω7c and C16â:â0. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, diphosphatidylglycerol and four unidentified phospholipids. The sole isoprenoid quinone was ubiquinone-8 (Q-8). Genomic DNA G+C content of strain KMB7T was 65.4â%. On the basis of phenotypic and genotypic properties and phylogenetic inference, strain KMB7T should be classified in a novel species of the genus Aquabacterium, for which the name Aquabacterium lacunae sp. nov. is proposed. The type strain is KMB7T (=BCRC 81156T=LMG 30924T=KCTC 62867T).
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Burkholderiales/clasificación , Filogenia , Estanques/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , Burkholderiales/aislamiento & purificación , ADN Bacteriano/genética , Ácidos Grasos/química , Genes Bacterianos , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Taiwán , Ubiquinona/químicaRESUMEN
An isolate, designated TTM-7T, recovered from a freshwater river in Taiwan, was characterized using a polyphasic taxonomy approach. Phylogenetic analyses based on 16S rRNA gene sequences and an up-to-date bacterial core gene set (92 protein clusters) indicated that strain TTM-7T is affiliated with species in the genus Lacibacter. Strain TTM-7T was most closely related to Lacibacter cauensis NJ-8T with a 98.2â% 16S rRNA gene sequence similarity, followed by Lacibacter daechungensis H32-4T (97.4 %) and Lacibacter nakdongensis SS2-56T (96.3â%). Cells were Gram-stain-negative, aerobic, motile by gliding, rod-shaped and formed orange colonies. Optimal growth occurred at 25 °C, pH 7 and 0â% NaCl. The major fatty acids of strain TTM-7T were iso-C15â:â0, summed feature 3 (comprising C16â:â1ω7c/C16â:â1ω6c and/or iso-C15â:â0 2-OH) and iso-C15â:â1 G. The predominant hydroxy fatty acid was iso-C17â:â0 3-OH. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, two unidentified aminoglycolipids, five unidentified aminophospholipids and one unidentified lipid. The major isoprenoid quinone was MK-7. Genomic DNA G+C content of strain TTM-7T was 40.6 mol%. Strain TTM-7T showed 83.6â% average nucleotide identity and 16.0â% digital DNA-DNA hybridization identity with Lacibacter cauensis NJ-8T. On the basis of phenotypic and genotypic properties and phylogenetic inference, strain TTM-7T should be classified in a novel species of the genus Lacibacter, for which the name Lacibacter luteus sp. nov. is proposed. The type strain is TTM-7T (=BCRC 81159T=LMG 30926T=KCTC 62870T).
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Bacteroidetes/clasificación , Filogenia , Ríos/microbiología , Técnicas de Tipificación Bacteriana , Bacteroidetes/aislamiento & purificación , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Fosfolípidos/química , Pigmentación , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Taiwán , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
Strain TTM-71T, isolated from a freshwater river in Taiwan, was characterized using a polyphasic taxonomic approach. Phylogenetic analyses based on 16S rRNA gene sequences and an up-to-date bacterial core gene set (92 protein clusters) indicated that strain TTM-71T is affiliated with species in the genus Filimonas. The 16S rRNA gene sequence similarity indicated that strain TTM-71T is closely related to species within the genus Filimonas (94.7-95.5â% sequence similarity) and had a high sequence similarity with Filimonas endophytica SR 2-06T (95.5 %). Strain TTM-71T showed 70.3â% average nucleotide identity and 24.9â% digital DNA-DNA hybridization identity with Filimonas lacunae YT21T. Cells were Gram-stain-negative, aerobic, motile by gliding, rod-shaped and formed beige-colored colonies. Optimal growth occurred at 20 °C, pH 8, and in the presence of 0.5â% NaCl. The major fatty acids of strain TTM-71T were iso-C15â:â0, iso-C15â:â1 G and summed feature 3 (comprising C16â:â1 ω7c and/or C16â:â1 ω6c). The predominant hydroxy fatty acid was iso-C17â:â0 3-OH. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, four uncharacterized aminophospholipids, one uncharacterized aminolipid, one uncharacterized phospholipid and one uncharacterized lipid. The predominant polyamine was homospermidine. The only isoprenoid quinone was MK-7. Genomic DNA G+C content was 45.6 mol%. On the basis of the polyphasic evidence presented, strain TTM-71T is considered to represent a novel species of the genus Filimonas, for which the name Filimonas effusa sp. nov. is proposed. The type strain is TTM-71T (=BCRC 81160T=LMG 31017T=KCTC 62871T).
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Bacteroidetes/clasificación , Filogenia , Ríos/microbiología , Técnicas de Tipificación Bacteriana , Bacteroidetes/aislamiento & purificación , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Taiwán , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
OBJECTIVE: This in vitro study aimed to evaluate the expression of cyclophilin A (CyPA) in U937 monocytic cells after coculturing with the human gingival fibroblasts (HGFs) and the effect of CyPA on the augmentation of MMP-2 expression in the coculture environment. BACKGROUND: Leukocyte infiltration in gingival connective tissue is one of the major findings in the lesions of inflammatory periodontal diseases. A crosstalk between the resident gingival fibroblasts and the recruited inflammatory cells that promote the expression of matrix metalloproteinases (MMPs) was proposed based on recent findings, whereas the cluster of differentiation 147 (CD147)-CyPA pathway was suggested to be involved with the crosstalk. MATERIAL AND METHODS: CyPA was released into media, in the independent or transwell coculture of HGF and U937 cells, as determined by enzyme-linked immunosorbent assay, whereas intracellular mRNA expressions for CyPA and MMP-2 were examined by quantitative real-time polymerase chain reaction, in the transwell coculture or conditional medium models. Zymography was conducted to analyze the activities of pro-MMP-2/MMP-2 released into the media. RESULTS: (a) A significantly increased CyPA protein level was observed in the transwell coculture media compared with that in the independent culture. (b) The transwell coculture-enhanced mRNA expression for CyPA was noticed in U937 cells but not in HGFs. After adding with HGF-conditioned medium, the mRNA enhancement in U937 cells occurred in a dose-dependent manner. (c) Although the MMP-2 activities significantly increased after transwell coculturing, the MMP-2 mRNA enhancement was observed only in HGFs. (d) Exogenous CyPA could enhance MMP-2 activities in HGFs in a dose-dependent manner. However, the CyPA antagonist reduced the MMP-2 activities in the transwell cocultures. (e) Moreover, the CyPA-enhanced MMP-2 activity in HGF was decreased significantly by the pathway inhibitor for c-Jun amino-terminal kinase (JNK). CONCLUSION: Based on the present findings, we suggest that gingival fibroblasts could enhance the CyPA release from U937 cells, via the JNK pathway, resulting in MMP-2 enhancement in fibroblasts. The finding shed light on a new mechanism of cellular interaction involving MMP-2 and CyPA, in two cells.
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Ciclofilina A , Encía , Metaloproteinasa 2 de la Matriz , Células Cultivadas , Ciclofilina A/fisiología , Fibroblastos/metabolismo , Encía/metabolismo , Humanos , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Células U937RESUMEN
Nitroglycerin (NTG), a nitric oxide-donating drug, may increase tumor blood flow and consequently increase cancer drug delivery to tumor cells. Thymidylate synthase (TS) is an essential enzyme for the de novo synthesis of deoxythymidine monophosphate; we had found that knocking down the expression of TS sensitizes lung cancer cells to cisplatin-induced cytotoxicity. However, whether NTG and cisplatin could induce synergistic cytotoxicity in nonsmall cell lung cancer (NSCLC) cells through modulating TS expression is unknown. In this study, NTG decreased TS expression in an AKT, also known as Protein kinase B (PKB) inactivation dependent manner in human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells. Enhancement of AKT activity by transfection with constitutive active AKT vectors increased the TS expression level as well as the cell survival pretreated by NTG. Moreover, NTG synergistically enhanced cytotoxicity and cell growth inhibition by cisplatin treatment in NSCLC cells, which were associated with downregulation of TS expression and inactivation of AKT in A549 and H1703 cells. Together, these results may provide a rationale to combine NTG with cisplatin-based chemotherapy to enhance the therapeutic effect for lung cancer in the future.
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Adenocarcinoma del Pulmón/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Nitroglicerina/farmacología , Células A549 , Adenocarcinoma del Pulmón/patología , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cisplatino/administración & dosificación , Regulación hacia Abajo , Sinergismo Farmacológico , Humanos , Neoplasias Pulmonares/patología , Nitroglicerina/administración & dosificación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Timidilato Sintasa/genéticaRESUMEN
A novel bacterial strain, designated THS-13T, isolated from a freshwater mesocosm in Taiwan, was characterized by taking a polyphasic taxonomic approach. Cells of strain THS-13T were Gram-stain-negative, aerobic, rod-shaped, motile by means of a single polar flagellum and formed translucent white coloured colonies. Growth occurred at 20-35 °C (optimum, 25 °C), at pH 5-8 (pH 6) and with 0-2â% NaCl (1â%). Phylogenetic analyses based on 16S rRNA gene and coding sequences of 92 protein clusters revealed that the strain belonged to the family Nevskiaceae in the class Gammaproteobacteria and represented an independent taxon separated from other genera. Strain THS-13T shared low level of 16S rRNA gene sequence similarity (less than 93.0â%) to members of other genera in the family Nevskiaceae and was most closely related to Nevskia aquatilis F2-63T (92.9â%). Strain THS-13T showed less than 73.4â% average nucleotide identity and less than 23.8â% digital DNA-DNA hybridization identity compared to the type strains of related genera within the family Nevskiaceae. The predominant fatty acids were C18â:â1ω7c, summed feature 3 (C16â:â1ω7c and/or C16â:â1ω6c) and iso-C16â:â0. The major isoprenoid quinone was Q-8 and the DNA G+C content was 67.6 mol%. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, an uncharacterized aminophospholipid, an uncharacterized phospholipid and an uncharacterized aminolipid. On the basis of the genotypic and phenotypic data, strain THS-13T represents a novel species of a new genus in the family Nevskiaceae, for which we propose the name Stagnimonas aquatica gen. nov., sp. nov. The type strain is THS-13T (=BCRC 81158T=LMG 30925T=KCTC 62868T).
Asunto(s)
Agua Dulce/microbiología , Gammaproteobacteria/clasificación , Filogenia , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Gammaproteobacteria/aislamiento & purificación , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Taiwán , Ubiquinona/químicaRESUMEN
PURPOSE: This retrospective study evaluated the volume of blood loss and operative time associated with management of nongrowing patients with cleft lip and palate (CLP) using bimaxillary orthognathic surgery (OGS) designed by a three-dimensional (3D) computer-assisted simulation and navigation for orthognathic surgery (CASNOS) system. METHODS: This study included 53 skeletal Class III nongrowing patients with unilateral CLP who underwent bimaxillary OGS using either the CASNOS protocol (n = 30) or the traditional two-dimensional (2D) method (n = 23). The skeletal parameters of jaw-bone components, the levels of hemoglobin (Hb) and hematocrit (Hct) were measured before and after surgery. The estimated blood loss and actual blood loss (ABL) were also calculated. RESULTS: The two groups did not differ significantly with regard to the demographic parameters (age, gender, and body mass index), the preoperative skeletal parameters and surgical changes of jaw-bone components. The mean ABL of the CASNOS group was significantly lower than that of the control group (915.6 ± 280.5 vs. 1204.9 ± 201.0 ml, p < 0.001), and the changes in Hb and Hct level also followed a similar pattern in both groups. The mean operative time was significantly shorter in the CASNOS group compared with the control group (384.2 ± 48.5 vs. 469.0 ± 94.9 min, p < 0.001). CONCLUSION: This study demonstrated that the application of the 3D CASNOS approach in OGS for the management of complicated Class III nongrowing patients with CLP significantly shortened the operative time and reduced ABL in comparison with the traditional 2D methods.
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Pérdida de Sangre Quirúrgica , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Tempo Operativo , Procedimientos Quirúrgicos Ortognáticos/instrumentación , Adolescente , Adulto , Volumen Sanguíneo , Femenino , Humanos , Imagenología Tridimensional , Masculino , Procedimientos Quirúrgicos Ortognáticos/métodos , Estudios Retrospectivos , Cirugía Asistida por Computador/métodos , Taiwán , Adulto JovenRESUMEN
PURPOSE: To investigate the clinical effects of preoperative nasoalveolar molding (NAM) and nasal conformer use in patients with unilateral incomplete cleft lip on the basis of their medical records and images. PATIENTS AND METHODS: Data and images of 16 patients born with unilateral incomplete cleft lip who were hospitalized between January 2015 and August 2017 were retrieved from the medical records. The primary outcome was the extent of improvement in columella height (CH) before cheiloplasty. Other outcome measurements included the CH, nostril width, and nostril height, which were measured by ImageJ image processing software (version 1.4; National Institutes of Health, Bethesda, MD) and presented as ratios. Mann-Whitney U tests were used to compare the non-normally distributed data. RESULTS: Patients in the NAM group and those in the nasal conformer group showed significantly improved (P < .05) preoperative cleft-side CH-to-normal-side CH ratios compared with the corresponding ratios at birth. There was no significant difference in terms of the extent of improvement in CH between the groups. CONCLUSIONS: Preoperative use of nasal conformers in patients with unilateral incomplete cleft lip not only corrects the deformed nasal cartilage but also increases the CH and improves the overall preoperative nasal symmetry. In addition, compared with NAM, this method costs less, is more straightforward, and requires fewer outpatient clinic visits.
Asunto(s)
Proceso Alveolar/cirugía , Labio Leporino/cirugía , Procedimientos de Cirugía Plástica , Cuidados Preoperatorios/instrumentación , Proceso Alveolar/diagnóstico por imagen , Labio Leporino/diagnóstico por imagen , Femenino , Humanos , Lactante , Masculino , Cuidados Preoperatorios/métodos , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Here we introduce a new synthetic approach to grow mesoporous silica thin films with vertical mesochannels on centimeter-sized substrates via an oil-induced co-assembly process. Adding an oil, i.e., decane, into a CTAB-EtOH-TEOS ammonia solution leads to thin-film formation of mesoporous silica of controlled thickness between 20 and 100 nm with vertical mesochannels on various surfaces. The vertical mesoporous channels were evidenced by grazing incidence small-angle X-ray scattering (GISAXS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) characterizations. Decane played two roles: (a) as a pore expansion agent (up to 5.7 ± 0.5 nm) and (b) inducing vertically oriented hexagonal mesophases of micelle-silica composite. The production of periodic and vertical nanochannels is very robust, over many different substrate surfaces (from silicon to polystyrene), various silica precursors (TEOS, fumed silica, or zeolite seed), and many oils (decane, petroleum ether, or ethyl acetate). This wide robustness in the formation of vertical nanophases is attributed to a unique mechanism of confined synthesis of surfactant-silicate between two identical thin layers of oils on a substrate.