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1.
Br J Nutr ; 128(3): 369-376, 2022 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-34470675

RESUMEN

Dietary modification plays a vital role in the treatment of non-alcoholic liver diseases. We investigated the effects of the consumption of a different amount of dehulled adlay, which has hypolipidaemic and anti-inflammatory properties, on non-alcoholic fatty liver disease (NAFLD). We fed rats a high-fat-high-fructose liquid diet for 16 weeks to induce NAFLD. The rats were divided into three groups fed the NAFLD diet only (NN) or a diet containing 44·9 or 89·8 g/l of dehulled adlay (NA and NB groups, respectively). After 8 weeks, the NA and NB groups had lower C-reactive protein levels and improvement in insulin resistance. In addition, the NB group had lower liver weight and hepatic TAG and cholesterol concentrations than did the NN group. Compared with the NN group, the high-dose NB group had improved steatosis, lower hepatic TNF-α, IL-1ß and IL-6 levels and lower adipose leptin levels. Our results suggest that a diet containing dehulled adlay can ameliorate NAFLD progression by decreasing of insulin resistance, steatosis and inflammation.


Asunto(s)
Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Ratas , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Hígado/metabolismo , Inflamación/metabolismo , Dieta Alta en Grasa
2.
Br J Nutr ; 123(5): 508-515, 2020 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-31771682

RESUMEN

Consumption of a high-fat diet increases fat accumulation and may further lead to inflammation and hepatic injuries. The aim of the study was to investigate the effects of Camellia oleifera seed extract (CSE) on non-alcoholic fatty liver disease (NAFLD). After a 16-week NAFLD-inducing period, rats were assigned to experimental groups fed an NAFLD diet with or without CSE. At the end of the study, we found that consuming CSE decreased the abdominal fat weight and hepatic fat accumulation and modulated circulating adipokine levels. We also found that CSE groups had lower hepatic cytochrome P450 2E1 and transforming growth factor (TGF)-ß protein expressions. In addition, we found that CSE consumption may have affected the gut microbiota and reduced toll-like receptor (TLR)-4, myeloid differentiation primary response gene 88, toll/IL-1 receptor domain-containing adaptor-inducing interferon-ß (TRIF) expression and proinflammatory cytokine concentrations in the liver. Our results suggest that CSE may alleviate the progression of NAFLD in rats with diet-induced steatosis through reducing fat accumulation and improving lipid metabolism and hepatic inflammation.


Asunto(s)
Camellia , Resistencia a la Insulina/fisiología , Metabolismo de los Lípidos/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Inflamación , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/etiología , Ratas
3.
Mov Disord ; 33(8): 1287-1297, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29701258

RESUMEN

BACKGROUND: Ubiquitous digital technologies such as smartphone sensors promise to fundamentally change biomedical research and treatment monitoring in neurological diseases such as PD, creating a new domain of digital biomarkers. OBJECTIVES: The present study assessed the feasibility, reliability, and validity of smartphone-based digital biomarkers of PD in a clinical trial setting. METHODS: During a 6-month, phase 1b clinical trial with 44 Parkinson participants, and an independent, 45-day study in 35 age-matched healthy controls, participants completed six daily motor active tests (sustained phonation, rest tremor, postural tremor, finger-tapping, balance, and gait), then carried the smartphone during the day (passive monitoring), enabling assessment of, for example, time spent walking and sit-to-stand transitions by gyroscopic and accelerometer data. RESULTS: Adherence was acceptable: Patients completed active testing on average 3.5 of 7 times/week. Sensor-based features showed moderate-to-excellent test-retest reliability (average intraclass correlation coefficient = 0.84). All active and passive features significantly differentiated PD from controls with P < 0.005. All active test features except sustained phonation were significantly related to corresponding International Parkinson and Movement Disorder Society-Sponsored UPRDS clinical severity ratings. On passive monitoring, time spent walking had a significant (P = 0.005) relationship with average postural instability and gait disturbance scores. Of note, for all smartphone active and passive features except postural tremor, the monitoring procedure detected abnormalities even in those Parkinson participants scored as having no signs in the corresponding International Parkinson and Movement Disorder Society-Sponsored UPRDS items at the site visit. CONCLUSIONS: These findings demonstrate the feasibility of smartphone-based digital biomarkers and indicate that smartphone-sensor technologies provide reliable, valid, clinically meaningful, and highly sensitive phenotypic data in Parkinson's disease. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.


Asunto(s)
Antiparkinsonianos/uso terapéutico , Actividad Motora/fisiología , Evaluación de Resultado en la Atención de Salud/métodos , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/fisiopatología , Teléfono Inteligente , Anciano , Estudios de Casos y Controles , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Examen Neurológico , Enfermedad de Parkinson/psicología , Cooperación del Paciente/psicología , Desempeño Psicomotor , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Factores de Tiempo
4.
Bioinformatics ; 32(1): 151-3, 2016 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-26363178

RESUMEN

MOTIVATION: A plethora of sequenced and genotyped disease cohorts is available to the biomedical research community, spread across many portals and represented in various formats. RESULTS: We have gathered several large studies, including GERA and GRU, and computed population- and disease-specific genetic variant frequencies. In total, our portal provides fast access to genetic variants observed in 84,928 individuals from 39 disease populations. We also include 66,335 controls, such as the 1000 Genomes and Scripps Wellderly. CONCLUSION: Combining multiple studies helps validate disease-associated variants in each underlying data set, detect potential false positives using frequencies of control populations, and identify novel candidate disease-causing alterations in known or suspected genes. AVAILABILITY AND IMPLEMENTATION: https://rvs.u.hpc.mssm.edu/divas CONTACT: rong.chen@mssm.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Bases de Datos Genéticas , Enfermedad/genética , Variación Genética , Programas Informáticos , Estudios de Cohortes , Humanos , Interfaz Usuario-Computador
5.
BMC Bioinformatics ; 17: 24, 2016 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-26746786

RESUMEN

BACKGROUND: Data from a plethora of high-throughput sequencing studies is readily available to researchers, providing genetic variants detected in a variety of healthy and disease populations. While each individual cohort helps gain insights into polymorphic and disease-associated variants, a joint perspective can be more powerful in identifying polymorphisms, rare variants, disease-associations, genetic burden, somatic variants, and disease mechanisms. DESCRIPTION: We have set up a Reference Variant Store (RVS) containing variants observed in a number of large-scale sequencing efforts, such as 1000 Genomes, ExAC, Scripps Wellderly, UK10K; various genotyping studies; and disease association databases. RVS holds extensive annotations pertaining to affected genes, functional impacts, disease associations, and population frequencies. RVS currently stores 400 million distinct variants observed in more than 80,000 human samples. CONCLUSIONS: RVS facilitates cross-study analysis to discover novel genetic risk factors, gene-disease associations, potential disease mechanisms, and actionable variants. Due to its large reference populations, RVS can also be employed for variant filtration and gene prioritization. AVAILABILITY: A web interface to public datasets and annotations in RVS is available at https://rvs.u.hpc.mssm.edu/.


Asunto(s)
Bases de Datos Genéticas , Enfermedad/genética , Variación Genética , Anotación de Secuencia Molecular/métodos , Genoma Humano , Técnicas de Genotipaje , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Bases del Conocimiento , Valores de Referencia , Factores de Riesgo
6.
Ind Crops Prod ; 89: 543-549, 2016 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-32288271

RESUMEN

Lonicera japonica Thunberg (LJ) has long been used as an antipyretic, anti-inflammatory and anti-infectious agent in East Asia. The subspecies L. japonica Thunb. var. sempervillosa Hayata (LJv) is a variant that mainly grows in Taiwan. This study examined the antioxidant and anti-inflammatory activities of the extracts from the flower buds of these two species. The extracts were obtained by three extraction methods: water extraction, ethanol extraction, and supercritical-CO2 fluid extraction (SFE). The antioxidant activities of dry LJ (dLJ) extracts were superior to those of LJv extracts. Water extracts possessed higher activities than that prepared by ethanol or SFE. The total polyphenols content, total flavonoids content, and the amount of chlorogenic acid and luteolin-7-O-glucoside were all higher in the water extracts compared to the other two. The SFE extracts of these two species all exhibited excellent anti-inflammatory activities. Although the water and ethanol extracts of dLJ extracts had higher anti-inflammatory activity than that of LJv extracts, the SFE extracts prepared from fresh LJv flower buds (fLJv) exhibited the highest activity among all extracts. The SFE effectively isolates the bioactive components of L. japonica and can obtain the L. japonica extracts with high anti-inflammatory activity.

7.
BMC Genomics ; 16 Suppl 8: S3, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26110593

RESUMEN

BACKGROUND: The invention of high throughput sequencing technologies has led to the discoveries of hundreds of thousands of genetic variants associated with thousands of human diseases. Many of these genetic variants are located outside the protein coding regions, and as such, it is challenging to interpret the function of these genetic variants by traditional genetic approaches. Recent genome-wide functional genomics studies, such as FANTOM5 and ENCODE have uncovered a large number of regulatory elements across hundreds of different tissues or cell lines in the human genome. These findings provide an opportunity to study the interaction between regulatory elements and disease-associated genetic variants. Identifying these diseased-related regulatory elements will shed light on understanding the mechanisms of how these variants regulate gene expression and ultimately result in disease formation and progression. RESULTS: In this study, we curated and categorized 27,558 Mendelian disease variants, 20,964 complex disease variants, 5,809 cancer predisposing germline variants, and 43,364 recurrent cancer somatic mutations. Compared against nine different types of regulatory regions from FANTOM5 and ENCODE projects, we found that different types of disease variants show distinctive propensity for particular regulatory elements. Mendelian disease variants and recurrent cancer somatic mutations are 22-fold and 10- fold significantly enriched in promoter regions respectively (q<0.001), compared with allele-frequency-matched genomic background. Separate from these two categories, cancer predisposing germline variants are 27-fold enriched in histone modification regions (q<0.001), 10-fold enriched in chromatin physical interaction regions (q<0.001), and 6-fold enriched in transcription promoters (q<0.001). Furthermore, Mendelian disease variants and recurrent cancer somatic mutations share very similar distribution across types of functional effects. We further found that regulatory regions are located within over 50% coding exon regions. Transcription promoters, methylation regions, and transcription insulators have the highest density of disease variants, with 472, 239, and 72 disease variants per one million base pairs, respectively. CONCLUSIONS: Disease-associated variants in different disease categories are preferentially located in particular regulatory elements. These results will be useful for an overall understanding about the differences among the pathogenic mechanisms of various disease-associated variants.


Asunto(s)
Enfermedad/genética , Variación Genética , Elementos Reguladores de la Transcripción , Cromatina/genética , Biología Computacional , Estudio de Asociación del Genoma Completo , Secuenciación de Nucleótidos de Alto Rendimiento , Histonas/genética , Humanos , Isoformas de Proteínas/genética
8.
PLoS Comput Biol ; 9(2): e1002920, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23468608

RESUMEN

Mining gene expression profiles has proven valuable for identifying signatures serving as surrogates of cancer phenotypes. However, the similarities of such signatures across different cancer types have not been strong enough to conclude that they represent a universal biological mechanism shared among multiple cancer types. Here we present a computational method for generating signatures using an iterative process that converges to one of several precise attractors defining signatures representing biomolecular events, such as cell transdifferentiation or the presence of an amplicon. By analyzing rich gene expression datasets from different cancer types, we identified several such biomolecular events, some of which are universally present in all tested cancer types in nearly identical form. Although the method is unsupervised, we show that it often leads to attractors with strong phenotypic associations. We present several such multi-cancer attractors, focusing on three that are prominent and sharply defined in all cases: a mesenchymal transition attractor strongly associated with tumor stage, a mitotic chromosomal instability attractor strongly associated with tumor grade, and a lymphocyte-specific attractor.


Asunto(s)
Biología Computacional/métodos , Modelos Biológicos , Neoplasias/genética , Algoritmos , Minería de Datos , Bases de Datos Genéticas , Transición Epitelial-Mesenquimal , Perfilación de la Expresión Génica/métodos , Genoma/genética , Humanos , Estimación de Kaplan-Meier , Cinetocoros , Mitosis/genética , Neoplasias/metabolismo , Neoplasias/patología , Oncogenes , Fenotipo , Pronóstico
9.
Eur J Pharmacol ; 971: 176552, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38580181

RESUMEN

AIM OF THE STUDY: Chronic cholestasis leads to liver fibrosis, which lacks effective treatment. In this study, we investigated the role and mechanisms of action of loureirin B (LB) in cholestatic liver fibrosis. MATERIALS AND METHODS: Bile duct ligation (BDL)-induced hepatic fibrosis mice were used as in vivo models. Transforming growth factor-ß1 (TGF-ß1)-pretreated HSC-T6 cells were used to explore the mechanism by which LB attenuates liver fibrosis in vitro. RNA sequencing, quantitative PCR (qPCR), western blotting, immunohistochemistry and immunofluorescence were performed to detect the fibrosis markers and measure autophagy levels. Flow cytometry, cell counting kit-8 (CCK-8) assay, and 5'-ethynyl-2'-deoxyuridine (EdU) assay were conducted to detect cell proliferation and viability. GFP-RFP-LC3 adenovirus, autophagy-related protein 7 (ATG7) siRNA, and bafilomycin A1 (BafA1) were used to verify autophagic flux. RESULTS: Our results showed that LB ameliorates liver injury, inhibits collagen deposition, and decreases the expressions of fibrosis-related markers in BDL-induced mouse livers. In vitro, we found that LB inhibited proliferation and migration, promoted apoptosis, and inhibited the activation of HSC-T6 cells pretreated with TGF-ß1. RNA sequencing analysis of HSC-T6 cells showed that LB treatment predominantly targeted autophagy-related pathways. Further protein analysis indicated that LB downregulated the expression of phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR), and upregulated LC3-II, p62, and ATG7 both in vivo and in vitro. Intriguingly, ATG7 inactivation reversed the antifibrotic effects of LB on HSC-T6 cells. CONCLUSIONS: LB can improve BDL-induced liver fibrosis by inhibiting the activation and proliferation of HSCs and is expected to be a promising antifibrotic drug.


Asunto(s)
Colestasis , Proteínas Proto-Oncogénicas c-akt , Resinas de Plantas , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismo , Células Estrelladas Hepáticas , Cirrosis Hepática/inducido químicamente , Serina-Treonina Quinasas TOR/metabolismo , Hígado/metabolismo , Autofagia , Colestasis/patología
10.
Cell Genom ; 4(1): 100469, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38190103

RESUMEN

Epigenetics underpins the regulation of genes known to play a key role in the adaptive and innate immune system (AIIS). We developed a method, EpiNN, that leverages epigenetic data to detect AIIS-relevant genomic regions and used it to detect 2,765 putative AIIS loci. Experimental validation of one of these loci, DNMT1, provided evidence for a novel AIIS-specific transcription start site. We built a genome-wide AIIS annotation and used linkage disequilibrium (LD) score regression to test whether it predicts regional heritability using association statistics for 176 traits. We detected significant heritability effects (average |τ∗|=1.65) for 20 out of 26 immune-relevant traits. In a meta-analysis, immune-relevant traits and diseases were 4.45× more enriched for heritability than other traits. The EpiNN annotation was also depleted of trans-ancestry genetic correlation, indicating ancestry-specific effects. These results underscore the effectiveness of leveraging supervised learning algorithms and epigenetic data to detect loci implicated in specific classes of traits and diseases.


Asunto(s)
Genómica , Sitios de Carácter Cuantitativo , Fenotipo , Desequilibrio de Ligamiento/genética , Epigénesis Genética/genética
11.
Front Immunol ; 15: 1352632, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39035007

RESUMEN

Introduction: This study investigates the role of Fibroblast Activation Protein (FAP)-positive cancer-associated fibroblasts (FAP+CAF) in shaping the tumor immune microenvironment, focusing on its association with immune cell functionality and cytokine expression patterns. Methods: Utilizing immunohistochemistry, we observed elevated FAP+CAF density in metastatic versus primary renal cell carcinoma (RCC) tumors, with higher FAP+CAF correlating with increased T cell infiltration in RCC, a unique phenomenon illustrating the complex interplay between tumor progression, FAP+CAF density, and immune response. Results: Analysis of immune cell subsets in FAP+CAF-rich stromal areas further revealed significant correlations between FAP+ stroma and various T cell types, particularly in RCC and non-small cell lung cancer (NSCLC). This was complemented by transcriptomic analyses, expanding the range of stromal and immune cell subsets interrogated, as well as to additional tumor types. This enabled evaluating the association of these subsets with tumor infiltration, tumor vascularization and other components of the tumor microenvironment. Our comprehensive study also encompassed cytokine, angiogenesis, and inflammation gene signatures across different cancer types, revealing heterogeneous cellular composition, cytokine expressions and angiogenic profiles. Through cytokine pathway profiling, we explored the relationship between FAP+CAF density and immune cell states, uncovering potential immunosuppressive circuits that limit anti-tumor activity in tumor-resident immune cells. Conclusions: These findings underscore the complexity of tumor biology and the necessity for personalized therapeutic and patient enrichment approaches. The insights gathered from FAP+CAF prevalence, immune infiltration, and gene signatures provide valuable perspectives on tumor microenvironments, aiding in future research and clinical strategy development.


Asunto(s)
Fibroblastos Asociados al Cáncer , Inmunoterapia , Serina Endopeptidasas , Microambiente Tumoral , Microambiente Tumoral/inmunología , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/inmunología , Inmunoterapia/métodos , Serina Endopeptidasas/metabolismo , Serina Endopeptidasas/genética , Citocinas/metabolismo , Endopeptidasas , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Gelatinasas/metabolismo , Gelatinasas/genética , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias Renales/inmunología , Neoplasias Renales/patología , Neoplasias Renales/terapia , Neoplasias Renales/metabolismo , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/metabolismo , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/metabolismo
12.
Front Immunol ; 15: 1352615, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38558814

RESUMEN

Introduction: Fibroblast activation protein (FAP) is predominantly upregulated in various tumor microenvironments and scarcely expressed in normal tissues. Methods: We analyzed FAP across 1216 tissue samples covering 23 tumor types and 70 subtypes. Results: Elevated FAP levels were notable in breast, pancreatic, esophageal, and lung cancers. Using immunohistochemistry and RNAseq, a correlation between FAP gene and protein expression was found. Evaluating FAP's clinical significance, we assessed 29 cohorts from 12 clinical trials, including both mono and combination therapies with the PD-L1 inhibitor atezolizumab and chemotherapy. A trend links higher FAP expression to poorer prognosis, particularly in RCC, across both treatment arms. However, four cohorts showed improved survival with high FAP, while in four others, FAP had no apparent survival impact. Conclusions: Our results emphasize FAP's multifaceted role in therapy response, suggesting its potential as a cancer immunotherapy biomarker.


Asunto(s)
Neoplasias Pulmonares , Serina Endopeptidasas , Humanos , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Inmunoterapia , Neoplasias Pulmonares/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Fibroblastos/metabolismo , Microambiente Tumoral/genética
13.
Sci Rep ; 13(1): 10270, 2023 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-37355730

RESUMEN

Challenges in social communication is one of the core symptom domains in autism spectrum disorder (ASD). Novel therapies are under development to help individuals with these challenges, however the ability to show a benefit is dependent on a sensitive and reliable measure of treatment effect. Currently, measuring these deficits requires the use of time-consuming and subjective techniques. Objective measures extracted from natural conversations could be more ecologically relevant, and administered more frequently-perhaps giving them added sensitivity to change. While several studies have used automated analysis methods to study autistic speech, they require manual transcriptions. In order to bypass this time-consuming process, an automated speaker diarization algorithm must first be applied. In this paper, we are testing whether a speaker diarization algorithm can be applied to natural conversations between autistic individuals and their conversational partner in a natural setting at home over the course of a clinical trial. We calculated the average duration that a participant would speak for within their turn. We found a significant correlation between this feature and the Vineland Adaptive Behaviour Scales (VABS) expressive communication score (r = 0.51, p = 7 × 10-5). Our results show that natural conversations can be used to obtain measures of talkativeness, and that this measure can be derived automatically, thus showing the promise of objectively evaluating communication challenges in ASD.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Humanos , Trastorno Autístico/terapia , Trastorno del Espectro Autista/terapia , Trastorno del Espectro Autista/diagnóstico , Comunicación , Habla
14.
Neuromuscul Disord ; 33(11): 845-855, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37722988

RESUMEN

Spinal muscular atrophy (SMA) is characterized by progressive muscle weakness and paralysis. Motor function is monitored in the clinical setting using assessments including the 32-item Motor Function Measure (MFM-32), but changes in disease severity between clinical visits may be missed. Digital health technologies may assist evaluation of disease severity by bridging gaps between clinical visits. We developed a smartphone sensor-based assessment suite, comprising nine tasks, to assess motor and muscle function in people with SMA. We used data from the risdiplam phase 2 JEWELFISH trial to assess the test-retest reliability and convergent validity of each task. In the first 6 weeks, 116 eligible participants completed assessments on a median of 6.3 days per week. Eight of the nine tasks demonstrated good or excellent test-retest reliability (intraclass correlation coefficients >0.75 and >0.9, respectively). Seven tasks showed a significant association (P < 0.05) with related clinical measures of motor function (individual items from the MFM-32 or Revised Upper Limb Module scales) and seven showed significant association (P < 0.05) with disease severity measured using the MFM-32 total score. This cross-sectional study supports the feasibility, reliability, and validity of using smartphone-based digital assessments to measure function in people living with SMA.


Asunto(s)
Atrofia Muscular Espinal , Atrofias Musculares Espinales de la Infancia , Humanos , Reproducibilidad de los Resultados , Teléfono Inteligente , Estudios de Factibilidad , Estudios Transversales , Extremidad Superior , Atrofias Musculares Espinales de la Infancia/complicaciones
15.
Nat Commun ; 14(1): 6764, 2023 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-37938580

RESUMEN

Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up. Through histologic, mutational, and transcriptomic profiling of tumor and adjacent-normal tissue, we identified an inflammatory gene signature in tumor-adjacent tissue as the strongest clinical predictor of disease progression. Single-cell transcriptomic analysis demonstrated the progression-associated inflammatory signature was expressed in both immune and non-immune cells, and cell type-specific profiling in monocytes further improved outcome predictions. Additional analyses of tumor-adjacent transcriptomic data from The Cancer Genome Atlas validated the association of the inflammatory signature with worse outcomes across cancers. Collectively, our study suggests that molecular profiling of tumor-adjacent tissue can identify patients at high risk for disease progression.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Inflamación/genética , Neoplasias Pulmonares/genética , Pulmón , Progresión de la Enfermedad
16.
Nutrients ; 14(11)2022 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-35684050

RESUMEN

Obesity is a major public health concern worldwide with a rising prevalence. Diets containing whole grains have been demonstrated to benefit body composition and inflammatory conditions in individuals at a high risk of metabolic disorders. This study investigated the effects of dehulled adlay on blood lipids and inflammation in overweight and obese adults. We recruited 21 individuals with abdominal obesity to participate in a 6-week experiment, providing them 60 g of dehulled adlay powder per day as a substitute for their daily staple. Before and after the 6-week intervention, we performed anthropometric analyses and measured blood lipid profiles, adipokines, and markers of inflammation. At the end of the study, the percentage of body fat mass, blood total cholesterol, and triglyceride levels were significantly decreased compared with the baseline. Plasma tumor necrosis factor alpha, interleukin-6, leptin, and malondialdehyde levels were also reduced. In addition, participants with higher basal blood lipid levels exhibited enhanced lipid lowering effects after the dehulled adlay intervention. These results suggest that a dietary pattern containing 60 g of dehulled adlay per day may have a beneficial effect on lipid profiles and inflammatory markers in individuals that are overweight and obese.


Asunto(s)
Metabolismo de los Lípidos , Sobrepeso , Adulto , Humanos , Inflamación , Lípidos , Obesidad/complicaciones , Sobrepeso/complicaciones , Proyectos Piloto
17.
Abdom Radiol (NY) ; 47(7): 2279-2288, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35596776

RESUMEN

PURPOSES: To investigate the relationships and interactions between temporal and radiological features of gangrene and perforation of inflamed appendices. METHODS: A total of 402 patients were included who underwent laparoscopic appendectomies between January 1, 2016 and March 30, 2020 and had pathologically proved acute appendicitis and preoperative non-enhanced CT examinations. The radiological features (appendix diameter, appendicolith, appendiceal intraluminal gas, periappendiceal gas, periappendiceal fat stranding/fluid, and short axial diameter of the mesenteric lymph nodes) were obtained from the preoperative CT images of 382 patients with visible appendices. Clinical parameters and temporal variables (pre-CT delay, preoperative delay, estimated complication delay, symptom delay, and system delay) were recorded. RESULTS: Among simple/suppurative, gangrenous, and perforated appendicitis, the radiological characteristics except for short axial diameters of lymph nodes, and the temporal variables other than system delay were significantly different. The Cox regression analysis identified the appendicolith as the independent risk factor for both gangrene and perforation of inflamed appendices by using the preoperative delay or estimated complication delay. By the preoperative delay, the median time for gangrene and perforation was 76.23 (95%CI 73.89-78.58) h and 77.55 (95%CI 74.12-80.98) h, respectively, if appendicolith was present. If estimated complication delay was used as the elapsed time and the appendicolith was perceptible, the median time for gangrene and perforation and was 72.33 (95%CI 62.93-81.74) h and 75.07 (95%CI 69.48-80.65) h, respectively. CONCLUSION: There were interactions between the time evolution and radiological features of acute appendicitis. The evaluation of gangrene and perforation rate of acute appendicitis could be benefitted from combining the preoperative delay/estimated complication delay with CT characteristics in the preoperative urgent radiological analysis.


Asunto(s)
Apendicitis , Gangrena , Enfermedad Aguda , Apendicectomía , Apendicitis/diagnóstico por imagen , Apendicitis/cirugía , Gangrena/diagnóstico por imagen , Gangrena/patología , Humanos , Factores de Tiempo , Tomografía Computarizada por Rayos X/métodos
18.
Sci Rep ; 12(1): 12081, 2022 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-35840753

RESUMEN

Digital health technologies enable remote and therefore frequent measurement of motor signs, potentially providing reliable and valid estimates of motor sign severity and progression in Parkinson's disease (PD). The Roche PD Mobile Application v2 was developed to measure bradykinesia, bradyphrenia and speech, tremor, gait and balance. It comprises 10 smartphone active tests (with ½ tests administered daily), as well as daily passive monitoring via a smartphone and smartwatch. It was studied in 316 early-stage PD participants who performed daily active tests at home then carried a smartphone and wore a smartwatch throughout the day for passive monitoring (study NCT03100149). Here, we report baseline data. Adherence was excellent (96.29%). All pre-specified sensor features exhibited good-to-excellent test-retest reliability (median intraclass correlation coefficient = 0.9), and correlated with corresponding Movement Disorder Society-Unified Parkinson's Disease Rating Scale items (rho: 0.12-0.71). These findings demonstrate the preliminary reliability and validity of remote at-home quantification of motor sign severity with the Roche PD Mobile Application v2 in individuals with early PD.


Asunto(s)
Aplicaciones Móviles , Enfermedad de Parkinson , Tecnología de Sensores Remotos , Humanos , Enfermedad de Parkinson/fisiopatología , Reproducibilidad de los Resultados , Teléfono Inteligente , Temblor/fisiopatología
19.
Nutrients ; 13(7)2021 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-34371815

RESUMEN

High blood pressure is a crucial risk factor for many cardiovascular diseases, and a diet rich in whole-grain foods may modulate blood pressure. This study investigated the effects of dehulled adlay consumption on blood pressure in vivo. We initially fed spontaneous hypertensive rats diets without (SHR group) or with 12 or 24% dehulled adlay (SHR + LA and SHR + HA groups), and discovered that it could limit blood pressure increases over a 12-week experimental period. Although we found no significant changes in plasma, heart, and kidney angiotensin-converting enzyme activities, both adlay-consuming groups had lower endothelin-1 and creatinine concentrations than the SHR group; the SHR + HA group also had lower aspartate aminotransferase and uric acid levels than the SHR group did. We later recruited 23 participants with overweight and obesity, and they consumed 60 g of dehulled adlay daily for a six-week experimental period. At the end of the study, we observed a significant decrease in the group's systolic blood pressure (SBP), and the change in SBP was even more evident in participants with high baseline SBP. In conclusion, our results suggested that daily intake of dehulled adlay had beneficial effects in blood-pressure management. Future studies may further clarify the possible underlying mechanisms for the consuming of dehulled adlay as a beneficial dietary approach for people at risk of hypertension.


Asunto(s)
Presión Sanguínea/fisiología , Coix , Dieta/métodos , Hipertensión/dietoterapia , Granos Enteros , Adulto , Animales , Modelos Animales de Enfermedad , Ingestión de Alimentos/fisiología , Femenino , Humanos , Hipertensión/etiología , Masculino , Fenómenos Fisiológicos de la Nutrición , Obesidad/complicaciones , Obesidad/dietoterapia , Obesidad/fisiopatología , Sobrepeso/complicaciones , Sobrepeso/dietoterapia , Sobrepeso/fisiopatología , Ratas , Ratas Endogámicas SHR
20.
Gait Posture ; 84: 120-126, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33310432

RESUMEN

BACKGROUND: People living with multiple sclerosis (MS) experience impairments in gait and mobility, that are not fully captured with manually timed walking tests or rating scales administered during periodic clinical visits. We have developed a smartphone-based assessment of ambulation performance, the 5 U-Turn Test (5UTT), a quantitative self-administered test of U-turn ability while walking, for people with MS (PwMS). RESEARCH QUESTION: What is the test-retest reliability and concurrent validity of U-turn speed, an unsupervised self-assessment of gait and balance impairment, measured using a body-worn smartphone during the 5UTT? METHODS: 76 PwMS and 25 healthy controls (HCs) participated in a cross-sectional non-randomised interventional feasibility study. The 5UTT was self-administered daily and the median U-turn speed, measured during a 14-day session, was compared against existing validated in-clinic measures of MS-related disability. RESULTS: U-turn speed, measured during a 14-day session from the 5UTT, demonstrated good-to-excellent test-retest reliability in PwMS alone and combined with HCs (intraclass correlation coefficient [ICC] = 0.87 [95 % CI: 0.80-0.92]) and moderate-to-excellent reliability in HCs alone (ICC = 0.88 [95 % CI: 0.69-0.96]). U-turn speed was significantly correlated with in-clinic measures of walking speed, physical fatigue, ambulation impairment, overall MS-related disability and patients' self-perception of quality of life, at baseline, Week 12 and Week 24. The minimal detectable change of the U-turn speed from the 5UTT was low (19.42 %) in PwMS and indicates a good precision of this measurement tool when compared with conventional in-clinic measures of walking performance. SIGNIFICANCE: The frequent self-assessment of turn speed, as an outcome measure from a smartphone-based U-turn test, may represent an ecologically valid digital solution to remotely and reliably monitor gait and balance impairment in a home environment during MS clinical trials and practice.


Asunto(s)
Marcha/fisiología , Esclerosis Múltiple/complicaciones , Calidad de Vida/psicología , Teléfono Inteligente/instrumentación , Adulto , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Esclerosis Múltiple/terapia , Evaluación de Resultado en la Atención de Salud , Equilibrio Postural , Reproducibilidad de los Resultados
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