Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 87
Filtrar
1.
Nature ; 600(7888): 314-318, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34819664

RESUMEN

Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes1,2. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized3-6. Here we define a critical role of IL-27-IL-27Rα signalling in improving thermogenesis, protecting against diet-induced obesity and ameliorating insulin resistance. Mechanistic studies demonstrate that IL-27 directly targets adipocytes, activating p38 MAPK-PGC-1α signalling and stimulating the production of UCP1. Notably, therapeutic administration of IL-27 ameliorated metabolic morbidities in well-established mouse models of obesity. Consistently, individuals with obesity show significantly decreased levels of serum IL-27, which can be restored after bariatric surgery. Collectively, these findings show that IL-27 has an important role in orchestrating metabolic programs, and is a highly promising target for anti-obesity immunotherapy.


Asunto(s)
Adipocitos/metabolismo , Metabolismo Energético , Interleucina-27/metabolismo , Termogénesis , Animales , Cirugía Bariátrica , Modelos Animales de Enfermedad , Femenino , Humanos , Resistencia a la Insulina , Interleucina-27/sangre , Interleucina-27/uso terapéutico , Masculino , Ratones , Obesidad/sangre , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/prevención & control , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Receptores de Interleucina/metabolismo , Transducción de Señal , Proteína Desacopladora 1/biosíntesis , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
2.
J Biol Chem ; 298(3): 101671, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35120926

RESUMEN

Human AlkB homolog 6, ALKBH6, plays key roles in nucleic acid damage repair and tumor therapy. However, no precise structural and functional information are available for this protein. In this study, we determined atomic resolution crystal structures of human holo-ALKBH6 and its complex with ligands. AlkB members bind nucleic acids by NRLs (nucleotide recognition lids, also called Flips), which can recognize DNA/RNA and flip methylated lesions. We found that ALKBH6 has unusual Flip1 and Flip2 domains, distinct from other AlkB family members both in sequence and conformation. Moreover, we show that its unique Flip3 domain has multiple unreported functions, such as discriminating against double-stranded nucleic acids, blocking the active center, binding other proteins, and in suppressing tumor growth. Structural analyses and substrate screening reveal how ALKBH6 discriminates between different types of nucleic acids and may also function as a nucleic acid demethylase. Structure-based interacting partner screening not only uncovered an unidentified interaction of transcription repressor ZMYND11 and ALKBH6 in tumor suppression but also revealed cross talk between histone modification and nucleic acid modification in epigenetic regulation. Taken together, these results shed light on the molecular mechanism underlying ALKBH6-associated nucleic acid damage repair and tumor therapy.


Asunto(s)
Enzimas AlkB , Proteínas de Ciclo Celular , Proteínas Co-Represoras , Proteínas de Unión al ADN , Enzimas AlkB/genética , Enzimas AlkB/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Co-Represoras/metabolismo , ADN/genética , ADN/metabolismo , Reparación del ADN , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Epigénesis Genética , Proteínas de Escherichia coli/metabolismo , Humanos , Proteínas/metabolismo , ARN/metabolismo
3.
J Virol ; 96(3): e0171321, 2022 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-34787453

RESUMEN

Rift Valley fever virus (RVFV) belongs to the order Bunyavirales and is the type species of genus Phlebovirus, which accounts for over 50% of family Phenuiviridae species. RVFV is mosquito-borne and causes severe diseases in both humans and livestock, and consists of three segments (S, M, L) in the genome. The L segment encodes an RNA-dependent RNA polymerase (RdRp, L protein) that is responsible for facilitating the replication and transcription of the virus. It is essential for the virus and has multiple drug targets. Here, we established an expression system and purification procedures for full-length L protein, which is composed of an endonuclease domain, RdRp domain, and cap-binding domain. A cryo-EM L protein structure was reported at 3.6 Å resolution. In this first L protein structure of genus Phlebovirus, the priming loop of RVFV L protein is distinctly different from those of other L proteins and undergoes large movements related to its replication role. Structural and biochemical analyses indicate that a single template can induce initiation of RNA synthesis, which is notably enhanced by 5' viral RNA. These findings help advance our understanding of the mechanism of RNA synthesis and provide an important basis for developing antiviral inhibitors. IMPORTANCE The zoonosis RVF virus (RVFV) is one of the most serious arbovirus threats to both human and animal health. RNA-dependent RNA polymerase (RdRp) is a multifunctional enzyme catalyzing genome replication as well as viral transcription, so the RdRp is essential for studying the virus and has multiple drug targets. In our study, we report the structure of RVFV L protein at 3.6 Å resolution by cryo-EM. This is the first L protein structure of genus Phlebovirus. Strikingly, a single template can initiate RNA replication. The structure and assays provide a comprehensive and in-depth understanding of the catalytic and substrate recognition mechanism of RdRp.


Asunto(s)
Modelos Moleculares , Conformación Proteica , ARN Polimerasa Dependiente del ARN/química , Virus de la Fiebre del Valle del Rift/enzimología , Secuencias de Aminoácidos , Dominio Catalítico , Fenómenos Químicos , Secuencia Conservada , Microscopía por Crioelectrón , Dominios y Motivos de Interacción de Proteínas , ARN Polimerasa Dependiente del ARN/metabolismo , Proteínas Recombinantes de Fusión , Proteínas Virales/química
4.
FASEB J ; 36(7): e22410, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35713937

RESUMEN

Excessive cardiac fibrosis and inflammation aberrantly contribute to the progressive pathogenesis of arrhythmogenic cardiomyopathy (ACM). Whether sodium-glucose cotransporter-2 inhibitor (SGLT2i), as a new hypoglycemic drug, benefits ACM remains unclear. Cardiomyocyte-specific Dsg2 exon-11 knockout and wild-type (WT) littermate mice were used as the animal model of ACM and controls, respectively. Mice were administered by gavage with either SGLT2i dapagliflozin (DAPA, 1 mg/kg/day) or vehicle alone for 8 weeks. HL-1 cells were treated with DAPA to identify the molecular mechanism in vitro. All mice presented normal glucose homeostasis. DAPA not only significantly ameliorated cardiac dysfunction, adverse remodeling, and ventricular dilation in ACM but also attenuated ACM-associated cardiac fibrofatty replacement, as demonstrated by the echocardiography and histopathological examination. The protein expressions of HIF-2α and HIF-1α were decreased and increased respectively in cardiac tissue of ACM, which were compromised after DAPA treatment. Additionally, NF-κB P65 and IκB phosphorylation, as well as fibrosis indicators (including TGF-ß, α-SMA, Collagen I, and Collagen III) were increased in ACM. However, these trends were markedly suppressed by DAPA treatment. Consistent with these results in vitro, DAPA alleviated the IκB phosphorylation and NF-κB p65 transcriptional activity in DSG2-knockdown HL-1 cells. Interestingly, the elective HIF-2α inhibitor PT2399 almost completely blunted the DAPA-mediated downregulation of indicators concerning cardiac fibrosis and inflammation. SGLT2i attenuated the ACM-associated cardiac dysfunction and adverse remodeling in a glucose-independent manner by suppressing cardiac fibrosis and inflammation via reverting the HIF-2α signaling pathway, suggesting that SGLT2i is a novel and available therapy for ACM.


Asunto(s)
Cardiomiopatías , Diabetes Mellitus Tipo 2 , Cardiopatías , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Compuestos de Bencidrilo/farmacología , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/etiología , Cardiomiopatías/metabolismo , Colágeno , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fibrosis , Glucosa , Glucósidos , Inflamación/tratamiento farmacológico , Ratones , FN-kappa B/metabolismo , Transducción de Señal , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
5.
Molecules ; 27(21)2022 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-36364220

RESUMEN

Protein-surfactant interactions have a significant influence on food functionality, which has attracted increasing attention. Herein, the effect of glycolipid mannosylerythritol lipid-A (MEL-A) on the heat-induced soy glycinin (11S) aggregates was investigated by measuring the structure, binding properties, interfacial behaviors, and emulsification characteristics of the aggregates. The results showed that MEL-A led to a decrease in the surface tension, viscoelasticity, and foaming ability of the 11S aggregates. In addition, MEL-A with a concentration above critical micelle concentration (CMC) reduced the random aggregation of 11S protein after heat treatment, thus facilitating the formation of self-assembling core-shell particles composed of a core of 11S aggregates covered by MEL-A shells. Infrared spectroscopy, circular dichroism spectroscopy, fluorescence spectroscopy, and isothermal titration calorimetry also confirmed that the interaction forces between MEL-A and 11S were driven by hydrophobic interactions between the exposed hydrophobic groups of the protein and the fatty acid chains or acetyl groups of MEL-A, as well as the hydrogen bonding between mannosyl-D-erythritol groups of MEL-A and amino acids of 11S. The findings of this study indicated that such molecular interactions are responsible for the change in surface behavior and the enhancement of foaming stability and emulsifying property of 11S aggregates upon heat treatment.


Asunto(s)
Globulinas , Calor , Globulinas/química , Glucolípidos/química , Lípido A
6.
Compr Rev Food Sci Food Saf ; 21(6): 5272-5290, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36161470

RESUMEN

Cyclic peptides possess advanced structural characteristics of stability and play a vital role in medical treatment and agriculture. However, the biological functions of microorganism-derived cyclic peptides (MDCPs) and their applications in food industry were relatively absent. MDCPs are derived from extensive fermented food or soil. In this review, the synthesis approaches and structural characteristics are overviewed, while the interrelationship between bioactivities and functions is emphasized. This review summarizes the bioactivities of MDCPs from in vitro to in vivo, including antimicrobial activities, immune regulation, and antiviral cell activation. Their multiple functions as well as applications during food product processing, packaging, and storage are also comprehensively reviewed. Remarkably, some potential risks and cytotoxicity of MDCPs are also critically discussed. Moreover, future applications of MDCPs in the development of novel food additives and bioengineering materials are organized. Based on this review of native MDCPs, it is noteworthy that expected improvements of synthetic cyclic peptides in bioactive properties present potential valuable applications in future food, including artificial meat.


Asunto(s)
Carne , Péptidos Cíclicos , Carne/análisis , Manipulación de Alimentos , Inocuidad de los Alimentos
7.
Bioprocess Biosyst Eng ; 44(11): 2303-2313, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34296328

RESUMEN

Agaricus bitorquis (Quél.) Sacc. Chaidam (ABSC) is a wild edible fungus uniquely found in the Tibet Plateau. ABSC is rich in polysaccharides that are considered biologically active. This study aimed to determine the feasibility of enhancing exopolysaccharide (EPS) production by ABSC in shake flask culture by supplementing the fermentation medium with anthocyanin extract. Different concentrations of Lycium ruthenicum Murr. (LRM) anthocyanin crude extract were tested on ABSC fermentation. The activity of phosphoglucose isomerase (PGI), phosphoglucose mutase (PGM), and phosphomannose isomerase (PMI), enzymes presumably involved in EPS synthesis by ABSC, was determined. ABSC transcriptomic profile in response to the presence of anthocyanins during fermentation was also investigated. LRM anthocyanin crude extract (0.06 mg/mL) was most effective in increasing EPS content and mycelial biomass (by 208.10% and 105.30%, respectively, P < 0.01). The activity of PGI, PGM, and PMI was increased in a medium where LRM anthocyanin extract and its main components (proanthocyanidins and petunia anthocyanin) were added. RNA-Seq analysis showed that 349 genes of ABSC were differentially expressed during fermentation in the medium containing anthocyanin extract of LRM; 93 genes were up-regulated and 256 genes down-regulated. From gene ontology enrichment analysis, differentially expressed genes were mostly assigned to carbohydrate metabolism and signal transduction categories. Collectively, LRM anthocyanins extract positively affected EPS production and mycelial biomass during ABSC fermentation. Our study provides a novel strategy for improving EPS production and mycelial growth during ABSC liquid submerged fermentation.


Asunto(s)
Agaricus/metabolismo , Fermentación , Polisacáridos Fúngicos/biosíntesis , Lycium/metabolismo , Extractos Vegetales/metabolismo , Agaricus/genética , Agaricus/crecimiento & desarrollo , Medios de Cultivo , Microscopía Electrónica de Rastreo , ARN de Hongos/genética , Análisis de Secuencia de ARN/métodos , Transcriptoma
8.
Molecules ; 26(18)2021 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-34577056

RESUMEN

Betulinic acid, a pentacyclic triterpene, is distributed in a variety of plants, such as birch, eucalyptus and plane trees. It shows a wide spectrum of biological and pharmacological properties, such as anti-inflammatory, antibacterial, antiviral, antidiabetic, antimalarial, anti-HIV and antitumor effects. Among them, the antitumor activity of betulinic acid has been extensively studied. However, obtaining betulinic acid from natural resources can no longer meet the needs of medicine and nutrition, so methods such as chemical synthesis and microbial biotransformation have also been used to prepare betulinic acid. At the same time, with the development of synthetic biology and genetic engineering, and the elucidation of the biosynthetic pathways of terpenoid, the biosynthesis of betulinic acid has also been extensively researched. This article reviews the preparation of betulinic acid and its pharmacological activities, in order to provide a reference for the research and utilization of betulinic acid.


Asunto(s)
Triterpenos Pentacíclicos , Triterpenos , Fármacos Anti-VIH , Antiinflamatorios , Ácido Betulínico
9.
Molecules ; 26(15)2021 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-34361675

RESUMEN

Flavonoids belong to a class of plant secondary metabolites that have a polyphenol structure. Flavonoids show extensive biological activity, such as antioxidative, anti-inflammatory, anti-mutagenic, anti-cancer, and antibacterial properties, so they are widely used in the food, pharmaceutical, and nutraceutical industries. However, traditional sources of flavonoids are no longer sufficient to meet current demands. In recent years, with the clarification of the biosynthetic pathway of flavonoids and the development of synthetic biology, it has become possible to use synthetic metabolic engineering methods with microorganisms as hosts to produce flavonoids. This article mainly reviews the biosynthetic pathways of flavonoids and the development of microbial expression systems for the production of flavonoids in order to provide a useful reference for further research on synthetic metabolic engineering of flavonoids. Meanwhile, the application of co-culture systems in the biosynthesis of flavonoids is emphasized in this review.


Asunto(s)
Reactores Biológicos/microbiología , Escherichia coli/metabolismo , Flavonoides/biosíntesis , Ingeniería Metabólica/métodos , Saccharomyces cerevisiae/metabolismo , Técnicas de Cocultivo/métodos , Escherichia coli/genética , Fermentación , Flavonoides/química , Flavonoides/clasificación , Estructura Molecular , Plantas/metabolismo , Saccharomyces cerevisiae/genética , Metabolismo Secundario , Biología Sintética/métodos
10.
Molecules ; 26(21)2021 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-34771119

RESUMEN

High content of citric acid in lemon juice leads to poor sensory experience. The study aimed to investigate the dynamics changes in organic acids, phenolic compounds, and antioxidant activities of lemon juice fermented with Issatchenkia terricola WJL-G4. The sensory evaluation of fermented lemon juice was conducted as well. Issatchenkia terricola WJL-G4 exhibited a potent capability of reducing the contents of citric acid (from 51.46 ± 0.11 g/L to 8.09 ± 0.05 g/L within 60 h fermentation) and increasing total phenolic level, flavonoid contents, and antioxidant activities compared to those of unfermented lemon juice. A total of 20 bioactive substances, including 10 phenolic acids and 10 flavonoid compounds, were detected both in fermented and unfermented lemon juice. The lemon juice fermented for 48 h had better sensory characteristics. Our findings demonstrated that lemon juice fermented with Issatchenkia terricola exhibited reduced citric acid contents, increased levels of health-promoting phenolic compounds, and enhanced antioxidant activities.


Asunto(s)
Ácidos/análisis , Antioxidantes/análisis , Antioxidantes/farmacología , Citrus/química , Fermentación , Jugos de Frutas y Vegetales , Fenoles/análisis , Saccharomycetales/metabolismo , Ácidos/química , Fenómenos Químicos , Flavonoides/análisis , Compuestos Orgánicos , Fenoles/química , Análisis de Componente Principal
11.
Appl Microbiol Biotechnol ; 104(11): 5053-5064, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32248439

RESUMEN

Mannosylerythritol lipids (MELs) are novel biosurfactants performing excellent physical-chemical properties as well as bioactivities. This study is aimed to explore the antibacterial and antibiofilm activity of mannosylerythritol lipids against foodborne gram-positive Staphylococcus aureus. The results of growth curve and survival rate revealed the significant inhibitory effect of MELs against S. aureus. The visualized pictures by scanning electron microscope and transmission electron microscope exposed apparent morphological and ultrastructure changes of MEL-treated cells. Furthermore, flow cytometry confirmed that MELs have promoted cell apoptosis and damaged the cell membrane. Notably, MEL-A also exhibited outstanding antibiofilm activity against S. aureus biofilm on different material surfaces including polystyrene, glass, and stainless steel, verified by confocal laser scanning microscope. These findings suggest that the antimicrobial activity of MELs is related to inhibit planktonic cells and biofilm of S. aureus, indicating that it has potential to be an alternative to antibacterial agents and preservatives applied into food processing.Key Points • MELs have strong antibacterial activity against Staphylococcus aureus.• MELs mainly damage the cell membrane of Staphylococcus aureus.• Mannosylerythritol lipids inhibit the bacterial adhesion to remove biofilm.


Asunto(s)
Antibacterianos/farmacología , Apoptosis/efectos de los fármacos , Membrana Externa Bacteriana/efectos de los fármacos , Biopelículas/efectos de los fármacos , Glucolípidos/farmacología , Staphylococcus aureus/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Microbiología de Alimentos , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Tensoactivos/farmacología
12.
Ann Noninvasive Electrocardiol ; 25(1): e12694, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31565860

RESUMEN

INTRODUCTION: Long QT syndrome (LQTS) increases the risk of life-threatening arrhythmia in young individuals with structurally normal hearts. Sixteen genes such as the KCNQ1, KCNH2, and SCN5A have been reported for association with LQTS. CASE PRESENTATION: We identified the compound heterozygous mutations in the KCNQ1 gene at c. G527A (p.W176X) and c.G1765A (p.G589S) predicted as "damaging." The in-silico analysis showed that when compared to the characteristics of mRNA and protein of wild-type KCNQ1, the mRNA of c.G527A mutation was significantly different in the centroid secondary structure. The subunit coded by W176X would lose the transmembrane domains S3-S6 and helices A-D. The protein secondary structure of G589S was slightly shortened in helix structure; the protein physics-chemical parameters of W176X and G589S significantly and slightly changed, respectively. CONCLUSIONS: The compound heterozygous mutations of W176X and G589S coexisting in KCNQ1 gene of homologous chromosomes, resulting in more severe phenotype, are the likely pathogenic and genetic risks of LQTS and USD in this Chinese family.


Asunto(s)
Muerte Súbita , Secuenciación del Exoma/métodos , Predisposición Genética a la Enfermedad/genética , Canal de Potasio KCNQ1/genética , Síndrome de QT Prolongado/genética , Mutación/genética , Femenino , Humanos , Persona de Mediana Edad
13.
Molecules ; 25(20)2020 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-33096616

RESUMEN

Hypoxia is a common pathological process in various clinical diseases. However, there is still a lack of effective anti-hypoxia active substances. Agaricus bitorguis (Quél.) Sacc Chaidam (ABSC) is a rare wild edible macrofungus that grows underground at high altitudes. Herein, intracellular phenolic acids-rich fractions (IPA) were extracted from ABSC ZJU-CDMA-12, and the structural characterization and anti-hypoxia activity of IPA on PC12 cells were elucidated as well. The results of HPLC-Q-TOF-MS illustrated that five kinds of IPA were isolated from ABSC, including (-)-epicatechin gallate, arabelline, yunnaneic acid D, 2'-O-p-hydroxybenzoyl-6'-O-trans-caffeoylgardoside,4'-O-methylgallocatechin-(4->8)-4'-O-methylepigallocatechin. IPA extracted from ABSC proved to show anti-hypoxia activity on hypoxia-damaged PC12 cells. Hypoxia enhanced reactive oxygen species (ROS) generation and reduced the mitochondrial membrane potential (ΔΨm) in PC12 cells, resulting in the inhibition of survival and induction of apoptosis in PC12 cells. Measurements of 100 µg/mL and 250 µg/mL IPA could significantly reduce hypoxia-induced damage in PC12 cells by decreasing overproduced intracellular ROS, improving ΔΨm, and reducing cell apoptosis rate. Our findings indicated that the IPA from ABSC potentially could be used as novel bioactive components applied to anti-hypoxia functional foods or medicines.


Asunto(s)
Agaricus/química , Hipoxia de la Célula/efectos de los fármacos , Hidroxibenzoatos/farmacología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Hidroxibenzoatos/química , Hidroxibenzoatos/aislamiento & purificación , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Ratas
14.
Compr Rev Food Sci Food Saf ; 19(5): 2333-2356, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-33336985

RESUMEN

The production of macrofungi (mushrooms) as well as their economic value have been steadily increasing globally. The use of functional foods, dietary supplements, and traditional medicines derived from macrofungi is increasing as they have numerous health benefits as well as abundant nutrients. Macrofungi are diverse with complex and highly varied growth conditions and bioactive constituents, most macrofungal resources have not yet been fully explored and applicated, leading to an urgent need for appropriate strategies to address the problem. Increasing attention has been paid to the macrofungal cultivation and application, in particular, potential prebiotics. Herein, the present review comprehensively summarizes recent progress in the cultivation, newly identified bioactive constituents, and their effects on gut microbiota as well as the potential ways in which they affect human health. Moreover, the macrofungal food development is discussed to improve food nutritional value and change the quality characteristics of food. Finally, the review addresses consumer safety concerns and the prospective genetic manipulation of macrofungi. We hope that this review can provide a comprehensive research reference for ensuring the safety and efficacy, along with maximizing the value and profitability of macrofungi production.


Asunto(s)
Agaricales/química , Agaricales/crecimiento & desarrollo , Agricultura/métodos , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Valor Nutritivo , Prebióticos
15.
Am J Physiol Endocrinol Metab ; 317(4): E710-E722, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31430204

RESUMEN

This study aimed to investigate whether hypoxia can affect nonalcoholic fatty liver disease (NAFLD) progression and the associated mechanisms, specifically regarding the hypoxia-inducible factor (HIF)-2α/peroxisome proliferator-activated receptor (PPAR)α pathway in vitro and in vivo. Recent studies have reported that, compared with HIF-1α, HIF-2α has different effects on lipid metabolism. We propose hypoxia may exacerbate NAFLD by the HIF-2α upregulation-induced suppression of PPARα in the liver. To verify this hypothesis, a steatotic human hepatocyte (L02) cell line treated with free fatty acids and a mouse model of NAFLD fed a high-fat diet were used. Steatotic hepatocytes were treated with hypoxia, HIF-2α siRNA, PPARα agonists, and inhibitors, respectively. Meanwhile, the NAFLD mice were exposed to intermittent hypoxia or intermittent hypoxia with PPARα agonists. The relative gene expression levels of HIF-1α, HIF-2α, mitochondrial function, fatty acid ß-oxidation and lipogenesis were examined. Evidence of lipid accumulation was observed, which demonstrated that, compared with normal hepatocytes, steatotic hepatocytes exhibited higher sensitivity to hypoxia. This phenomenon was closely associated with HIF-2α. Moreover, lipid accumulation in hepatocytes was ameliorated by HIF-2α silencing or a PPARα agonist, despite the hypoxia treatment. HIF-2α overexpression under hypoxic conditions suppressed PPARα, leading to PGC-1α, NRF-1, ESRRα downregulation, and mitochondrial impairment. Additionally, ß-oxidation genes such as CPT1α, CPT2α, ACOX1, and ACOX2 were downregulated and lipogenesis genes including LXRα, FAS, and SCD1 were upregulated by hypoxia. Therefore, we concluded that HIF-2α overexpression induced by hypoxia aggravated NAFLD progression by suppressing fatty acid ß-oxidation and inducing lipogenesis in the liver via PPARα.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Hipoxia/genética , Enfermedad del Hígado Graso no Alcohólico/genética , PPAR alfa/genética , Transducción de Señal/genética , Animales , Línea Celular , Dieta Alta en Grasa , Hepatocitos/metabolismo , Humanos , Hipoxia/complicaciones , Metabolismo de los Lípidos/genética , Ratones , Ratones Endogámicos C57BL , Mitocondrias Hepáticas/genética , Mitocondrias Hepáticas/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , ARN Interferente Pequeño/farmacología
17.
Br J Clin Pharmacol ; 81(1): 78-88, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27099876

RESUMEN

This review summarizes current knowledge about glucagon-like peptide 1 receptor agonists (GLP-1 RA) and their effects on bone metabolism and fracture risk. Recent in vivo and in vitro experiments indicated that GLP-1 RA could improve bone metabolism. GLP-1 could affect the fat-bone axis by promoting osteogenic differentiation and inhibiting adipogenic differentiation of bone mesenchymal precursor cells (BMSCs), which express the GLP-1 receptor. GLP-1 RA may also influence the balance between osteoclasts and osteoblasts, thus leading to more bone formation and less bone resorption. Wnt/ß-catenin signalling is involved in this process. Mature osteocytes, which also express the GLP-1 receptor, produce sclerostin which inhibits Wnt/ß-catenin signalling by binding to low density lipoprotein receptor-related protein (LRP) 5 and preventing the binding of Wnt. GLP-1 RA also decreases the expression of sclerostin (SOST) and circulating levels of SOST. In addition, GLP-1 receptors are expressed in thyroid C cells, where GLP-1 induces calcitonin release and thus indirectly inhibits bone resorption. Furthermore, GLP-1 RA influences the osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK) system by increasing OPG gene expression, and thus reverses the decreased bone mass in rats models. However, a recent meta-analysis and a cohort study did not show a significant relationship between GLP-RA use and fracture risk. Future clinical trials will be necessary to investigate thoroughly the relationship between GLP-1 RA use and fracture risk in diabetic patients.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Fracturas Óseas/prevención & control , Receptor del Péptido 1 Similar al Glucagón/agonistas , Animales , Densidad Ósea , Calcitonina/fisiología , Péptido 1 Similar al Glucagón/fisiología , Humanos , Osteoporosis/etiología , Ligando RANK/fisiología , Riesgo , Vía de Señalización Wnt , beta Catenina/fisiología
18.
ScientificWorldJournal ; 2014: 841608, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24757441

RESUMEN

A quality scalable extension design is proposed for the upcoming 3D video on the emerging standard for High Efficiency Video Coding (HEVC). A novel interlayer simplified depth coding (SDC) prediction tool is added to reduce the amount of bits for depth maps representation by exploiting the correlation between coding layers. To further improve the coding performance, the coded prediction quadtree and texture data from corresponding SDC-coded blocks in the base layer can be used in interlayer simplified depth coding. In the proposed design, the multiloop decoder solution is also extended into the proposed scalable scenario for texture views and depth maps, and will be achieved by the interlayer texture prediction method. The experimental results indicate that the average Bjøntegaard Delta bitrate decrease of 54.4% can be gained in interlayer simplified depth coding prediction tool on multiloop decoder solution compared with simulcast. Consequently, significant rate savings confirm that the proposed method achieves better performance.


Asunto(s)
Aumento de la Imagen , Grabación en Video
19.
J Biosci Bioeng ; 137(3): 211-220, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38272723

RESUMEN

To improve the flavor profile and sensory quality of baijiu, the utilization of bioaugmented fermentation inoculated with functional microbiota normally serves as an effective method for directional regulation during the baijiu fermentation process. In this study, a systematic analysis of the succession patterns and volatile flavor compound profiles of microbial communities was carried out by high-throughput sequencing and solid-phase microextraction gas chromatography-mass spectrometry, respectively. The results demonstrated that the Saccharomyces cerevisiae YS222-related bioaugmentation clearly altered the microbial composition, particularly the assembly of bacteria, and promoted the quantity of the most volatile flavoring compounds, including alcohols, esters, and pyrazines. In addition, the correlation analysis showed that Saccharomyces and Lactobacillus in the augmented group were the main biomarkers associated with the dynamics of microbial community and greatly contributed to the brewing of sauce-flavor baijiu, which congruent with the outcomes of the enrichment analysis of integrated metabolic pathway. Thus, this work is beneficial for promoting the quality of baijiu and will serve as a useful reference for clarifying the possible mechanism of augmented fermentation on flavor development.


Asunto(s)
Ésteres , Alimentos , Fermentación , Cromatografía de Gases y Espectrometría de Masas , Secuenciación de Nucleótidos de Alto Rendimiento , Saccharomyces cerevisiae
20.
Int J Biol Macromol ; 257(Pt 1): 128341, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38029904

RESUMEN

The current requirements of food safety regulations and the environmental impact stemming from plastic packaging can only be addressed by developing suitable bio-nanocomposite films. Therefore, this study is dedicated to the fabrication of multifunctional film composed of gelatin, bacterial cellulose nanofibrils (BCNF), and black pepper essential oil nanoemulsion (BPEONE) and application for duck meat preservation. BCNF was prepared through ultrasonication of cellulose derived from Komagataeibacter xylinus. BPEONE observed spherical morphology with a diameter ranging from 83.7 to 118 nm. A film matrix containing a higher gelatin proportion than BCNF was more effective in trapping BPEONE. However, increasing the BPEONE fraction showed more surface abrasion and voids in the film morphology. A flexible film with good interaction, crystallinity, and greater thermal stability (421 °C) was developed. Nevertheless, film hydrophobicity (118.89°) declined, resulting in a notable effect on water solubility, swelling, and water vapor permeability. Moreover, the film had improved antibacterial and antioxidant activities, coupled with controlled release characteristics. Consequently, the developed film effectively retarded the lipid oxidation, inhibited microbial growth, and extended the shelf life of duck meat at refrigeration (4 °C) by 3 days, and made the film a promising alternative in the realm of bio-active packaging technology.


Asunto(s)
Celulosa , Gelatina , Embalaje de Alimentos/métodos , Antibacterianos/farmacología , Antioxidantes/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA