Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Trends Immunol ; 43(11): 901-916, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36253275

RESUMEN

Group 2 innate lymphoid cells (ILC2s) contribute to the maintenance of mammalian barrier tissue homeostasis. We review how ILC2s integrate epithelial signals and neurogenic components to preserve the tissue microenvironment and modulate inflammation. The epithelium that overlies barrier tissues, including the skin, lungs, and gut, generates epithelial cytokines that elicit ILC2 activation. Sympathetic, parasympathetic, sensory, and enteric fibers release neural signals to modulate ILC2 functions. We also highlight recent findings suggesting neuro-epithelial-ILC2 crosstalk and its implications in immunity, inflammation and resolution, tissue repair, and restoring homeostasis. We further discuss the pathogenic effects of disturbed ILC2-centered neuro-epithelial-immune cell interactions and putative areas for therapeutic targeting.


Asunto(s)
Inmunidad Innata , Linfocitos , Humanos , Animales , Citocinas , Pulmón , Inflamación , Mamíferos
2.
Ecotoxicol Environ Saf ; 275: 116206, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38518608

RESUMEN

Although the association between changes in human telomere length (TL) and ambient fine particulate matter (PM2.5) has been documented, there remains disagreement among the related literature. Our study conducted a systematic review and meta-analysis of epidemiological studies to investigate the health effects of outdoor PM2.5 exposure on human TL after a thorough database search. To quantify the overall effect estimates of TL changes associated with every 10 µg/m3 increase in PM2.5 exposure, we focused on two main topics, which were outdoor long-term exposure and prenatal exposure of PM2.5. Additionally, we included a summary of short-term PM2.5 exposure and its impact on TL due to limited data availability. Our qualitative analysis included 20 studies with 483,600 participants. The meta-analysis showed a statistically significant association between outdoor PM2.5 exposure and shorter human TL, with pooled impact estimates (ß) of -0.12 (95% CI: -0.20, -0.03, I2= 95.4%) for general long-term exposure and -0.07 (95% CI: -0.15, 0.00, I2= 74.3%) for prenatal exposure. In conclusion, our findings suggest that outdoor PM2.5 exposure may contribute to TL shortening, and noteworthy associations were observed in specific subgroups, suggesting the impact of various research variables. Larger, high-quality studies using standardized methodologies are necessary to strengthen these conclusions further.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Efectos Tardíos de la Exposición Prenatal , Femenino , Embarazo , Humanos , Material Particulado/toxicidad , Material Particulado/análisis , Contaminación del Aire/análisis , Acortamiento del Telómero , Telómero , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis
3.
Pflugers Arch ; 475(7): 889-905, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37043045

RESUMEN

Hypertensive disorders of pregnancy are complications that can lead to maternal and infant mortality and morbidity. Hypertensive disorders of pregnancy are generally defined as hypertension and may be accompanied by other end organ damages including proteinuria, maternal organ disturbances including renal insufficiency, neurological complications, thrombocytopenia, impaired liver function, or uteroplacental dysfunction such as fetal growth restriction and stillbirth. Although the causes of these hypertensive disorders of pregnancy are multifactorial and elusive, they seem to share some common vascular-related mechanisms, including diseased spiral arteries, placental ischemia, and endothelial dysfunction. Recently, preeclampsia is being considered as a vascular disorder. Unfortunately, due to the complex etiology of preeclampsia and safety concerns on drug usage during pregnancy, there is still no effective pharmacological treatments available for preeclampsia yet. An emerging area of interest in this research field is the potential beneficial effects of dietary intervention on reducing the risk of preeclampsia. Recent studies have been focused on the association between deficiencies or excesses of some nutrients and complications during pregnancy, fetal growth and development, and later risk of cardiovascular and metabolic diseases in the offspring. In this review, we discuss the involvement of placental vascular dysfunction in preeclampsia. We summarize the current understanding of the association between abnormal placentation and preeclampsia in a vascular perspective. Finally, we evaluate several studied dietary supplementations to prevent and reduce the risk of preeclampsia, targeting placental vascular development and function, leading to improved pregnancy and postnatal outcomes.


Asunto(s)
Hipertensión Inducida en el Embarazo , Preeclampsia , Embarazo , Femenino , Humanos , Preeclampsia/metabolismo , Placenta/irrigación sanguínea , Placenta/metabolismo , Placentación , Suplementos Dietéticos
4.
Hepatology ; 76(4): 1135-1149, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35218234

RESUMEN

BACKGROUND AND AIMS: Growing evidence suggests an important role of B cells in the development of NAFLD. However, a detailed functional analysis of B cell subsets in NAFLD pathogenesis is lacking. APPROACH AND RESULTS: In wild-type mice, 21 weeks of high fat diet (HFD) feeding resulted in NAFLD with massive macrovesicular steatosis, modest hepatic and adipose tissue inflammation, insulin resistance, and incipient fibrosis. Remarkably, Bnull (JHT) mice were partially protected whereas B cell harboring but antibody-deficient IgMi mice were completely protected from the development of hepatic steatosis, inflammation, and fibrosis. The common feature of JHT and IgMi mice is that they do not secrete antibodies, whereas HFD feeding in wild-type mice led to increased levels of serum IgG2c. Whereas JHT mice have no B cells at all, regulatory B cells were found in the liver of both wild-type and IgMi mice. HFD reduced the number of regulatory B cells and IL-10 production in the liver of wild-type mice, whereas these increased in IgMi mice. Livers of patients with advanced liver fibrosis showed abundant deposition of IgG and stromal B cells and low numbers of IL-10 expressing cells, compatible with our experimental data. CONCLUSIONS: B lymphocytes have both detrimental and protective effects in HFD-induced NAFLD. The lack of secreted pathogenic antibodies protects partially from NAFLD, whereas the presence of certain B cell subsets provides additional protection. IL-10-producing regulatory B cells may represent such a protective B cell subset.


Asunto(s)
Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Animales , Linfocitos B , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Fibrosis , Inmunoglobulina G , Inflamación/patología , Resistencia a la Insulina/fisiología , Interleucina-10 , Hígado/patología , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología
5.
Molecules ; 28(3)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36771063

RESUMEN

The urgent problem to be solved in heavy oil exploitation is to reduce viscosity and improve fluidity. Emulsification and viscosity reduction technology has been paid more and more attention and its developments applied. This paper studied the viscosity reduction performance of three types of viscosity reducers and obtained good results. The viscosity reduction rate, interfacial tension, and emulsification performance of three types of viscosity reducers including anionic sulfonate, non-ionic (polyether and amine oxide), and amphoteric betaine were compared with Daqing crude oil. The results showed that the viscosity reduction rate of petroleum sulfonate and betaine was 75-85%. The viscosity reduction rate increased as viscosity reducer concentration increased. An increase in the oil-water ratio and polymer decreased viscosity reduction. When the concentration of erucamide oxide was 0.2%, the ultra-low interfacial tension was 4.41 × 10-3 mN/m. When the oil-water ratio was 1:1, the maximum water separation rates of five viscosity reducers were different. With an increase in the oil-water ratio, the emulsion changed from o/w emulsion to w/o emulsion, and the stability was better. Erucamide oxide and erucic betaine had good viscosity reduction and emulsification effects on Daqing crude oil. This work can enrich knowledge of the viscosity reduction of heavy oil systems with low relative viscosity and enrich the application of viscosity reducer varieties.

6.
Horm Metab Res ; 54(10): 686-695, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36206762

RESUMEN

Accumulating evidence has shown that the rs738409 polymorphism of patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with non-alcoholic fatty liver disease (NAFLD). Since NAFLD has been reported to be associated with lipid metabolism, this study is conducted to explore whether the rs738409 polymorphism of PNPLA3 was associated with lipid levels. By searching PubMed and the Cochrane database from May 31, 2020, to June 30, 2021. Sixty-three studies (81 003 subjects) were included for the analysis. The consistent findings for the associations of rs738409 polymorphism with lipid levels were the significantly decreased triglycerides (TG) (SMD=-0.04, 95% CI=-0.07 to -0.01, p=0.02) and total cholesterol (TC) (SMD=-0.03, 95% CI=-0.05 to -0.01, p<0.01) levels. Subgroup analysis indicated that the associations of rs738409 polymorphism with TG and TC levels were stronger in Caucasians, obesity patients, and adult subjects than in Asians, T2DM patients, and children subjects. The rs738409 polymorphism of PNPLA3 was associated with lower TG and TC levels in Caucasians, obese and adult subjects, which may contribute to the reduced coronary artery disease (CAD) risk between PNPLA3 rs738409 polymorphism and CAD.


Asunto(s)
Aciltransferasas/genética , Enfermedad del Hígado Graso no Alcohólico , Fosfolipasas A2 Calcio-Independiente/genética , Adulto , Estudios de Casos y Controles , Niño , Colesterol , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lipasa/genética , Proteínas de la Membrana/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Obesidad , Fosfolipasas , Polimorfismo de Nucleótido Simple/genética , Triglicéridos
7.
Int J Mol Sci ; 23(17)2022 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-36077061

RESUMEN

Low catalytic activity is a key factor limiting the widespread application of type II L-asparaginase (ASNase) in the food and pharmaceutical industries. In this study, smart libraries were constructed by semi-rational design to improve the catalytic activity of type II ASNase from Bacillus licheniformis. Mutants with greatly enhanced catalytic efficiency were screened by saturation mutations and combinatorial mutations. A quintuple mutant ILRAC was ultimately obtained with specific activity of 841.62 IU/mg and kcat/Km of 537.15 min-1·mM-1, which were 4.24-fold and 6.32-fold more than those of wild-type ASNase. The highest specific activity and kcat/Km were firstly reported in type II ASNase from Bacillus licheniformis. Additionally, enhanced pH stability and superior thermostability were both achieved in mutant ILRAC. Meanwhile, structural alignment and molecular dynamic simulation demonstrated that high structure stability and strong substrate binding were beneficial for the improved thermal stability and enzymatic activity of mutant ILRAC. This is the first time that enzymatic activity of type II ASNase from Bacillus licheniformis has been enhanced by the semi-rational approach, and results provide new insights into enzymatic modification of L-asparaginase for industrial applications.


Asunto(s)
Asparaginasa , Bacillus licheniformis , Asparaginasa/química , Asparaginasa/genética , Bacillus licheniformis/genética , Bacillus licheniformis/metabolismo , Catálisis , Simulación de Dinámica Molecular
8.
Hum Brain Mapp ; 41(6): 1505-1519, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-31816152

RESUMEN

Support vector machine (SVM)-based multivariate pattern analysis (MVPA) has delivered promising performance in decoding specific task states based on functional magnetic resonance imaging (fMRI) of the human brain. Conventionally, the SVM-MVPA requires careful feature selection/extraction according to expert knowledge. In this study, we propose a deep neural network (DNN) for directly decoding multiple brain task states from fMRI signals of the brain without any burden for feature handcrafts. We trained and tested the DNN classifier using task fMRI data from the Human Connectome Project's S1200 dataset (N = 1,034). In tests to verify its performance, the proposed classification method identified seven tasks with an average accuracy of 93.7%. We also showed the general applicability of the DNN for transfer learning to small datasets (N = 43), a situation encountered in typical neuroscience research. The proposed method achieved an average accuracy of 89.0 and 94.7% on a working memory task and a motor classification task, respectively, higher than the accuracy of 69.2 and 68.6% obtained by the SVM-MVPA. A network visualization analysis showed that the DNN automatically detected features from areas of the brain related to each task. Without incurring the burden of handcrafting the features, the proposed deep decoding method can classify brain task states highly accurately, and is a powerful tool for fMRI researchers.


Asunto(s)
Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Aprendizaje Profundo , Adulto , Conectoma , Bases de Datos Factuales , Juego de Azar/psicología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo/fisiología , Desempeño Psicomotor/fisiología , Reproducibilidad de los Resultados , Máquina de Vectores de Soporte , Transferencia de Experiencia en Psicología
9.
Neuroradiology ; 61(6): 695-702, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30949745

RESUMEN

PURPOSE: Previous studies have focused on global cerebral alterations observed in cirrhosis. However, little was known about the specific abnormalities of vision-related brain regions in cirrhotic patients. In this study, we sought to explore neurological alterations of vision-related regions by measuring brain resting-state network connectivity, based on the structural investigation in cirrhotic patients without clinical sign of hepatic encephalopathy (HE). METHODS: Structural and functional magnetic resonance image (MRI) data were collected from 20 hepatitis B virus (HBV)-related cirrhotic patients without clinical sign of HE and from 20 healthy controls (HC). Voxel-based morphometric (VBM) analysis and brain functional network analysis were performed to detect abnormalities in cerebral structure and function. RESULTS: Cirrhotic patients showed regions with the most significant gray matter reduction primarily in vision-related brain regions, including the bilateral lingual gyri, left putamen, right fusiform gyrus, and right calcarine gyrus, and other significant gray matter reductions were distributed in bilateral hippocampus. Based on structural investigation focused on vision-related regions, brain functional network analysis revealed decreased functional connectivity between brain functional networks within vision-related regions (primary visual network (PVN), higher visual network (HVN), visuospatial network (VSN)) in the patient group compared with HC group. CONCLUSION: These results indicate that structural and functional impairment were evident in the vision-related brain regions in cirrhotic patients without clinical sign of hepatic encephalopathy. The physiopathology and clinical relevance of these changes could not be ascertained from the present study, which provided a basis for further evolution of the disease.


Asunto(s)
Sustancia Gris/diagnóstico por imagen , Encefalopatía Hepática/diagnóstico , Imagen por Resonancia Magnética/métodos , Corteza Visual/diagnóstico por imagen , Estudios de Casos y Controles , Femenino , Sustancia Gris/patología , Encefalopatía Hepática/virología , Humanos , Masculino , Persona de Mediana Edad , Corteza Visual/patología
10.
J Neurovirol ; 24(5): 587-596, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29785582

RESUMEN

In addition to the role of planning and executing movement, the cerebellum greatly contributes to cognitive process. Numerous studies have reported structural and functional abnormalities in the cerebellum for HIV-infected patients, but little is known about the altered functional connectivity of particular cerebellar subregions and the cerebrum. Therefore, this study aimed to explore the resting-state functional connectivity (rsFC) changes of the cerebellum and further analyze the relationship between the rsFC changes and the neuropsychological evaluation. The experiment involved 26 HIV-infected men with asymptomatic neurocognitive impairment (ANI) and 28 healthy controls (HC). We selected bilateral hemispheric lobule VI and lobule IX as seed regions and mapped the whole-brain rsFC for each subregion. Results revealed that right lobule VI showed significant increased rsFC with the anterior cingulate cortex (ACC) in HIV-infected subjects. In addition, the correlation analysis on HIV-infected subjects illustrated the increased rsFC was negatively correlated with the attention/working memory score. Moreover, significantly increased cerebellar rsFCs were also observed in HIV-infected patients related to right inferior frontal gyrus (IFG) and right superior medial gyrus (SMG) while decreased rsFC was just found between right lobule VI and the left hippocampus (HIP). These findings suggested that, abnormalities of cerebro-cerebellar functional connectivity might be associated with cognitive dysfunction in HIV-infected men, particularly working memory impairment. It could also be the underlying mechanism of ANI, providing further evidence for early injury in the neural substrate of HIV-infected patients.


Asunto(s)
Complejo SIDA Demencia/patología , Cerebelo/patología , Cerebro/patología , Vías Nerviosas/patología , Complejo SIDA Demencia/fisiopatología , Adulto , Cerebelo/fisiopatología , Cerebro/fisiopatología , Humanos , Masculino , Vías Nerviosas/fisiopatología , Descanso
11.
Epilepsy Behav ; 84: 127-134, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29793134

RESUMEN

The aim of this study was to automatically detect focal cortical dysplasia (FCD) lesions in patients with extratemporal lobe epilepsy by relying on diffusion tensor imaging (DTI) and T2-weighted magnetic resonance imaging (MRI) data. We implemented an automated classifier using voxel-based multimodal features to identify gray and white matter abnormalities of FCD in patient cohorts. In addition to the commonly used T2-weighted image intensity feature, DTI-based features were also utilized. A Gaussian processes for machine learning (GPML) classifier was tested on 12 patients with FCD (8 with histologically confirmed FCD) scanned at 1.5 T and cross-validated using a leave-one-out strategy. Moreover, we compared the multimodal GPML paradigm's performance with that of single modal GPML and classical support vector machine (SVM). Our results demonstrated that the GPML performance on DTI-based features (mean AUC = 0.63) matches with the GPML performance on T2-weighted image intensity feature (mean AUC = 0.64). More promisingly, GPML yielded significantly improved performance (mean AUC = 0.76) when applying DTI-based features to multimodal paradigm. Based on the results, it can also be clearly stated that the proposed GPML strategy performed better and is robust to unbalanced dataset contrary to SVM that performed poorly (AUC = 0.69). Therefore, the GPML paradigm using multimodal MRI data containing DTI modality has promising result towards detection of the FCD lesions and provides an effective direction for future researches.


Asunto(s)
Imagen de Difusión Tensora/métodos , Epilepsias Parciales/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Adolescente , Adulto , Niño , Preescolar , Epilepsias Parciales/etiología , Epilepsias Parciales/patología , Femenino , Humanos , Aprendizaje Automático , Masculino , Malformaciones del Desarrollo Cortical/complicaciones , Malformaciones del Desarrollo Cortical/patología , Adulto Joven
12.
Diabetologia ; 60(3): 464-474, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28011992

RESUMEN

AIMS/HYPOTHESIS: Beta cell inflammation and demise is a feature of type 1 diabetes. The insulin-sensitising molecule 'adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1' (APPL1), which contains an NH2-terminal Bin/Amphiphysin/Rvs domain, a central pleckstrin homology domain and a COOH-terminal phosphotyrosine-binding domain, has been shown to modulate inflammatory response in various cell types but its role in regulating beta cell mass and inflammation in type 1 diabetes remains unknown. Thus, we investigated whether APPL1 prevents beta cell apoptosis and inflammation in diabetes. METHODS: Appl1-knockout mice and their wild-type littermates, as well as C57BL/6N mice injected with adeno-associated virus encoding APPL1 or green fluorescent protein, were treated with multiple-low-dose streptozotocin (MLDS) to induce experimental type 1 diabetes. Their glucose metabolism and beta cell function were assessed. The effect of APPL1 deficiency on beta cell function upon exposure to a diabetogenic cytokine cocktail (CKS; consisting of TNF-α, IL-1ß and IFN-γ) was assessed ex vivo. RESULTS: Expression of APPL1 was significantly reduced in pancreatic islets from mouse models of type 1 diabetes or islets treated with CKS. Hyperglycaemia, beta cell loss and insulitis induced by MLDS were exacerbated by genetic deletion of Appl1 but were alleviated by beta cell-specific overexpression of APPL1. APPL1 preserved beta cell mass by reducing beta cell apoptosis upon treatment with MLDS. Mechanistically, APPL1 deficiency potentiate CKS-induced phosphorylation of NFκB inhibitor, α (IκBα) and subsequent phosphorylation and transcriptional activation of p65, leading to a dramatic induction of NFκB-regulated apoptotic and proinflammatory programs in beta cells. Pharmacological inhibition of NFκB or inducible NO synthase (iNOS) largely abrogate the detrimental effects of APPL1 deficiency on beta cell functions. CONCLUSIONS/INTERPRETATION: APPL1 negatively regulates inflammation and apoptosis in pancreatic beta cells by dampening the NFκB-iNOS-NO axis, representing a promising target for treating type 1 diabetes.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Inflamación/metabolismo , FN-kappa B/metabolismo , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Apoptosis/genética , Apoptosis/fisiología , Caspasa 3/genética , Caspasa 3/metabolismo , Línea Celular , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Diabetes Mellitus Tipo 1/genética , Células HEK293 , Humanos , Inmunohistoquímica , Inflamación/genética , Células Secretoras de Insulina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxidos de Nitrógeno/metabolismo , Páncreas/metabolismo , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/genética , Transducción de Señal/fisiología , Estreptozocina/toxicidad
13.
Neuroradiology ; 59(11): 1133-1142, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28889255

RESUMEN

PURPOSE: It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. METHODS: In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. RESULTS: We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. CONCLUSION: This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND.


Asunto(s)
Encefalopatías/diagnóstico por imagen , Encefalopatías/fisiopatología , Mapeo Encefálico/métodos , Infecciones por VIH/complicaciones , Imagen por Resonancia Magnética/métodos , Corteza Motora/diagnóstico por imagen , Corteza Motora/fisiopatología , Imagen Multimodal , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino
14.
Drug Metab Dispos ; 44(5): 647-52, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26932815

RESUMEN

Liver regeneration after surgical liver resection is crucial for the restoration of liver mass and the recovery of liver function.Schisandra sphenanthera extract (Wuzhi tablet, WZ) is a preparation of an extract from the dried ripe fruit of Schisandra sphenanthera Rehd. et Wils, a traditional hepatoprotective herb. Previously, we found that WZ could induce liver regeneration-related genes against acetaminophen-induced liver injury. However, whether WZ can directly facilitate liver regeneration after liver resection remains unknown. We investigated whether WZ has potential in promoting liver regeneration after a partial hepatectomy (PHX) in mice. Remnant livers were collected 1, 1.5, 2, 3, 5, 7, and 10 days after PHX. Hepatocyte proliferation was assessed using the Ki-67 labeling index. Western blot analysis was performed on proteins known to be involved in liver regeneration. The results demonstrated that WZ significantly increased the liver-to-body weight ratio of mice after PHX but had no effect on that of mice after a sham operation. Additionally, the peak hepatocyte proliferation was observed at 1.5 days in PHX/WZ-treated mice but at 2 days in PHX/saline-treated mice, as evidenced by the Ki-67 positive ratio. Furthermore, WZ significantly increased the protein expression of ligand-induced phosphorylation of epidermal growth factor receptor and up-regulated cyclin D1, cyclin D-dependent kinase 4, phosphorylated retinoblastoma, and proliferating cell nuclear antigen protein expression and down-regulated the expression of cell cycle inhibitors p21 and p27 in the regenerative process after PHX. These results demonstrate that WZ significantly facilitates hepatocyte proliferation and liver regeneration after PHX.


Asunto(s)
Hepatocitos/efectos de los fármacos , Regeneración Hepática/efectos de los fármacos , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Schisandra/química , Acetaminofén/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Hepatectomía/métodos , Hepatocitos/metabolismo , Hígado/metabolismo , Hepatopatías/tratamiento farmacológico , Hepatopatías/metabolismo , Ratones , Fosforilación/efectos de los fármacos , Extractos Vegetales/química , Transducción de Señal/efectos de los fármacos , Comprimidos/química , Comprimidos/farmacología
15.
Drug Metab Dispos ; 44(3): 337-42, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26658429

RESUMEN

We previously reported that the ethanol extract of Schisandra sphenanthera [Wuzhi (WZ) tablet] significantly protects against acetaminophen-induced hepatoxicity. However, whether WZ exerts a protective effect against cholestasis remains unclear. In this study, the protective effect of WZ on lithocholic acid (LCA)-induced intrahepatic cholestasis in mice was characterized and the involved mechanisms were investigated. WZ pretreatment (350 mg/kg) with LCA significantly reversed liver necrosis and decreased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activity. More importantly, serum total bile acids and total bilirubin were also remarkably reduced. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis showed that hepatic expression of pregnane X receptor (PXR) target genes such as CYP3A11 and UDP-glucuronosyltransferase (UGT) 1A1 were significantly increased by WZ treatment. Luciferase assays performed in LS174T cells illustrated that WZ extract and its six bioactive lignans could all activate human PXR. In addition, WZ treatment significantly promoted liver regeneration via inhibition of p53/p21 to induce cell proliferation-associated proteins such as cyclin D1 and proliferating cell nuclear antigen. In conclusion, WZ has a protective effect against LCA-induced intrahepatic cholestasis, partially owing to activation of the PXR pathway and promotion of liver regeneration.


Asunto(s)
Colestasis/tratamiento farmacológico , Regeneración Hepática/efectos de los fármacos , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Receptores de Esteroides/metabolismo , Schisandra/química , Acetaminofén/farmacología , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Colestasis/inducido químicamente , Colestasis/metabolismo , Citocromo P-450 CYP3A/metabolismo , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Glucuronosiltransferasa/metabolismo , Lignanos/farmacología , Ácido Litocólico/efectos adversos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/química , Receptor X de Pregnano , Sustancias Protectoras/química , Transducción de Señal/efectos de los fármacos
16.
Neuroradiology ; 58(9): 921-8, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27278455

RESUMEN

INTRODUCTION: Complaint about attention disorders is common among breast cancer patients who have undergone chemotherapy, which may be associated with the default mode network (DMN). To validate this hypothesis, we investigated the DMN functional connectivity (FC) change and its relationship with the attention function in breast cancer patients (BC) using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Twenty-two BC treated with chemotherapy and 22 healthy controls (HC) were recruited into this study. The FC between the DMN's hubs and regions of the dorsal medial prefrontal cortex (dMPFC) and medial temporal lobe (MTL) subsystems was respectively calculated for each participant. RESULTS: The statistical result showed significantly lower connectivity in dMPFC and MTL subsystems in the BC group. In addition, the partial correlation analysis result indicated that the low connectivity of some brain regions in MTL subsystem was correlated with attention dysfunction following BC chemotherapy. CONCLUSION: These results suggest that the functional disconnection in MTL subsystem of the DMN may have association with attention function of BC after chemotherapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Atención/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/fisiopatología , Adulto , Antineoplásicos/administración & dosificación , Conectoma/métodos , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiopatología , Descanso , Taxoides/administración & dosificación , Resultado del Tratamiento
17.
Int J Biol Macromol ; 257(Pt 2): 128690, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38092107

RESUMEN

Type II L-asparaginase (ASNase) has been approved by the FDA for treating acute lymphoid leukemia (ALL), but its therapeutic effect is limited by low catalytic efficiency and L-glutaminase (L-Gln) activity. This study utilized free energy based molecular dynamics calculations to identify residues associated with substrate binding in Bacillus licheniformis L-asparaginase II (BLASNase) with high catalytical activity. After saturation and combination mutagenesis, the mutant LGT (74 L/75G/111 T) with intensively reduced l-glutamine catalytic activity was generated. The l-glutamine/L-asparagine activity (L-Gln/L-Asn) of LGT was only 6.6 % of parent BLASNase, whereas the L-asparagine (L-Asn) activity was preserved >90 %. Furthermore, structural comparison and molecular dynamics calculations indicated that the mutant LGT had reduced binding ability and affinity towards l-glutamine. To evaluate its effect on acute leukemic cells, LGT was supplied in treating MOLT-4 cells. The experimental results demonstrated that LGT was more cytotoxic and promoted apoptosis compared with commercial Escherichia coli ASNase. Overall, our findings firstly provide insights into reducing l-glutamine activity without impacting L-asparagine activity for BLASNase to possess remarkable potential for anti-leukemia therapy.


Asunto(s)
Antineoplásicos , Bacillus licheniformis , Asparaginasa/genética , Asparaginasa/farmacología , Bacillus licheniformis/genética , Bacillus licheniformis/metabolismo , Asparagina/metabolismo , Glutaminasa/metabolismo , Glutamina/metabolismo , Antineoplásicos/química
18.
Food Chem X ; 23: 101548, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-38974200

RESUMEN

Granaticins are natural pigments derived from microorganisms with promising bioactivity. However, their practical applications have been restricted due to inherent instability. To improve the stability of granaticins from the novel strain Streptomyces vilmorinianum YP1, microcapsules were prepared using gum Arabic (GA) by a freeze-drying method. The optimal parameters for microencapsulation were determined using response surface methodology. Under the optimal conditions (GA 9.2% (v/v), a wall/-core ratio 4.8 (w/w), encapsulating temperature 29 °C), the maximum encapsulation efficiency achieved was 93.64%. The microcapsules were irregular single crystals with an average particle size of 206.37 ± 2.51 nm. Stability testing indicated improved stability of the microencapsulated granaticins. Notably, granaticnic B retention increased by 17.0% and 6.6% after exposure to sunlight and storage at 4 °C, respectively. These finding suggest that GA as a well material significantly enhances the stability of granaticins from S. vilmorinianum YP1, facilitating their potential applications.

19.
Int J Biol Macromol ; 259(Pt 2): 129235, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38211916

RESUMEN

Three green non-enzymatic catalysis pretreatments (NECPs) including autohydrolysis, subcritical CO2-assisted seawater autohydrolysis, and inorganic salt catalysis were utilized to simultaneously produce xylo-oligosaccharides (XOS), glucose, and cellulolytic enzyme lignin (CEL) from sugarcane bagasse (SCB). The yield of XOS in all three NECPs was over 50 % with a competitive glucose yield of enzymatic hydrolysis. And the effects of different pretreatments on the chemical structure and composition of CEL samples were also investigated. The pretreatments significantly increased the thermal stability, yield, and purity of the CEL samples. Moreover, the net yield of lignin was 58.3 % with lignin purity was 98.9 % in the autohydrolysis system. Furthermore, there was a decrease in the molecular weight of CEL samples as the pretreatment intensity increased. And the original lignin structural units sustained less damage during the NECPs, due to the cleavage of the ß-O-4 bonds dominating lignin degradation. Meanwhile, these pretreatments increased the phenolic-OH in CEL samples, making the lignin more reactive, and enhancing its subsequent modification and utilization. Collectively, the described techniques have demonstrated practical significance for the coproduction of XOS and glucose, and lignin, providing a promising strategy for full utilization of biomass.


Asunto(s)
Lignina , Saccharum , Lignina/química , Celulosa/química , Glucosa/metabolismo , Biomasa , Saccharum/química , Oligosacáridos/química , Hidrólisis
20.
Antioxidants (Basel) ; 12(8)2023 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-37627590

RESUMEN

Perivascular adipose tissue (PVAT) adheres to most systemic blood vessels in the body. Healthy PVAT exerts anticontractile effects on blood vessels and further protects against cardiovascular and metabolic diseases. Healthy PVAT regulates vascular homeostasis via secreting an array of adipokine, hormones, and growth factors. Normally, homeostatic reactive oxygen species (ROS) in PVAT act as secondary messengers in various signalling pathways and contribute to vascular tone regulation. Excessive ROS are eliminated by the antioxidant defence system in PVAT. Oxidative stress occurs when the production of ROS exceeds the endogenous antioxidant defence, leading to a redox imbalance. Oxidative stress is a pivotal pathophysiological process in cardiovascular and metabolic complications. In obesity, PVAT becomes dysfunctional and exerts detrimental effects on the blood vessels. Therefore, redox balance in PVAT emerges as a potential pathophysiological mechanism underlying obesity-induced cardiovascular diseases. In this review, we summarise new findings describing different ROS, the major sources of ROS and antioxidant defence in PVAT, as well as potential pharmacological intervention of PVAT oxidative stress in obesity.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA