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1.
Biochem Biophys Res Commun ; 707: 149781, 2024 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-38492244

RESUMEN

BACKGROUND & AIMS: CD36, a membrane protein widely present in various tissues, is crucial role in regulating energy metabolism. The rise of HCC as a notable outcome of NAFLD is becoming more apparent. Patients with hereditary CD36 deficiency are at increased risk of NAFLD. However, the impact of CD36 deficiency on NAFLD-HCC remains unclear. METHODS: Global CD36 knockout mice (CD36KO) and wild type mice (WT) were induced to establish NAFLD-HCC model by N-nitrosodiethylamine (DEN) plus high fat diet (HFD). Transcriptomics was employed to examine genes that were expressed differentially. RESULTS: Compared to WT mice, CD36KO mice showed more severe HFD-induced liver issues and increased tumor malignancy. The MEK1/2-ERK1/2 pathway activation was detected in the liver tissues of CD36KO mice using RNA sequencing and Western blot analysis. CONCLUSION: Systemic loss of CD36 leaded to the advancement of NAFLD to HCC by causing lipid disorders and metabolic inflammation, a process that involves the activation of MAPK signaling pathway. We found that CD36 contributes significantly to the maintenance of metabolic homeostasis in NAFLD-HCC.


Asunto(s)
Trastornos de las Plaquetas Sanguíneas , Carcinoma Hepatocelular , Enfermedades Genéticas Congénitas , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Sistema de Señalización de MAP Quinasas , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Hígado/metabolismo , Transducción de Señal , Antígenos CD36/genética , Antígenos CD36/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BL , Ratones Noqueados
2.
EPMA J ; 14(4): 571-583, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38094575

RESUMEN

Background: The human gut microbiota (GM) has been recognized as a significant factor in the development of insomnia, primarily through inflammatory pathways, making it a promising target for therapeutic interventions. Considering the principles of primary prediction, targeted prevention, and personalized treatment medicine (PPPM), identifying specific gut microbiota associated with insomnia and exploring the underlying mechanisms comprehensively are crucial steps towards achieving primary prediction, targeted prevention, and personalized treatment of insomnia. Working hypothesis and methodology: We hypothesized that alterations in the composition of specific GM could induce insomnia through an inflammatory response, which postulates the existence of a GM-inflammation-insomnia pathway. Mendelian randomization (MR) analyses were employed to examine this pathway and explore the mediative effects of inflammation. We utilized genetic proxies representing GM, insomnia, and inflammatory indicators (including 41 circulating cytokines and C-reactive protein (CRP)), specifically identified from European ancestry. The primary method used to identify insomnia-related GM and examine the medicative effect of inflammation was the inverse variance weighted method, supplemented by the MR-Egger and weighted median methods. Our findings have the potential to identify individuals at risk of insomnia through screening for GM imbalances, leading to the development of targeted prevention and personalized treatment strategies for the condition. Results: Nine genera and three circulating cytokines were identified to be associated with insomnia; only the associations of Clostridium (innocuum group) and ß-NGF on insomnia remained significant after the FDR test, OR = 1.08 (95% CI = 1.04-1.12, P = 1.45 × 10-4, q = 0.02) and OR = 1.06 (95% CI = 1.02-1.10, P = 1.06 × 10-3, q = 0.04), respectively. CRP was associated with an increased risk of insomnia, OR = 1.05 (95% CI = 1.01-1.10, P = 6.42 × 10-3). CRP mediated the association of Coprococcus 1, Holdemania, and Rikenellaceae (RC9gut group) with insomnia. No heterogeneity or pleiotropy were detected. Conclusions: Our study highlights the role of specific GM alterations in the development of insomnia and provides insights into the mediating effects of inflammation. Targeting these specific GM alterations presents a promising avenue for advancing the transition from reactive medicine to PPPM in managing insomnia, potentially leading to significant clinical benefits. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00345-1.

3.
Math Biosci Eng ; 18(2): 1833-1844, 2021 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-33757213

RESUMEN

In this paper, we present an SEIIaHR epidemic model to study the influence of recessive infection and isolation in the spread of COVID-19. We first prove that the infection-free equilibrium is globally asymptotically stable with condition R0<1 and the positive equilibrium is uniformly persistent when the condition R0>1. By using the COVID-19 data in India, we then give numerical simulations to illustrate our results and carry out some sensitivity analysis. We know that asymptomatic infections will affect the spread of the disease when the quarantine rate is within the range of [0.3519, 0.5411]. Furthermore, isolating people with symptoms is important to control and eliminate the disease.


Asunto(s)
COVID-19/epidemiología , Epidemias , Modelos Biológicos , SARS-CoV-2 , Infecciones Asintomáticas/epidemiología , Número Básico de Reproducción/estadística & datos numéricos , COVID-19/prevención & control , COVID-19/transmisión , Simulación por Computador , Epidemias/prevención & control , Epidemias/estadística & datos numéricos , Humanos , India/epidemiología , Cadenas de Markov , Conceptos Matemáticos , Método de Montecarlo , Pandemias/prevención & control , Pandemias/estadística & datos numéricos , Cuarentena/estadística & datos numéricos
4.
Math Biosci Eng ; 10(4): 1159-71, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23906206

RESUMEN

Hand, foot and mouth disease (HFMD) is one of the major public-health problems in China. Based on the HFMD data of the Department of Health of Shandong Province, we propose a dynamic model with periodic transmission rates to investigate the seasonal HFMD. After evaluating the basic reproduction number, we analyze the dynamical behaviors of the model and simulate the HFMD data of Shandong Province. By carrying out the sensitivity analysis of some key parameters, we conclude that the recessive subpopulation plays an important role in the spread of HFMD, and only quarantining the infected is not an effective measure in controlling the disease.


Asunto(s)
Portador Sano/virología , Enterovirus/aislamiento & purificación , Enfermedad de Boca, Mano y Pie/epidemiología , Adulto , Número Básico de Reproducción , Portador Sano/inmunología , Preescolar , China/epidemiología , Simulación por Computador , Enterovirus/inmunología , Enfermedad de Boca, Mano y Pie/inmunología , Enfermedad de Boca, Mano y Pie/transmisión , Enfermedad de Boca, Mano y Pie/virología , Humanos , Lactante , Modelos Estadísticos , Estaciones del Año
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