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1.
Food Chem ; 462: 140909, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39208727

RESUMEN

Probiotics serve a very important role in human health. However, probiotics have poor stability during processing, storage, and gastrointestinal digestion. The gellan gum (GG) is less susceptible to enzymatic degradation and resistant to thermal and acidic environments. This study investigated the effect of casein (CS)-GG emulsions to encapsulate Lactiplantibacillus plantarum CICC 6002 (L. plantarum CICC 6002) on its storage stability, thermal stability, and gastrointestinal digestion. L. plantarum CICC 6002 was suspended in palm oil and emulsions were prepared using CS or CS-GG complexes. We found the CS-GG emulsions improved the viability of L. plantarum CICC 6002 after storage, pasteurization, and digestion compared to the CS emulsions. In addition, we investigated the influence of the gellan gum concentration on emulsion stability, and the optimal stability was observed in the emulsion prepared by CS-0.8% GG complex. This study provided a new strategy for the protection of probiotics based on CS-GG delivery system.


Asunto(s)
Caseínas , Emulsiones , Lactobacillus plantarum , Polisacáridos Bacterianos , Probióticos , Emulsiones/química , Probióticos/química , Polisacáridos Bacterianos/química , Caseínas/química , Humanos , Lactobacillus plantarum/química , Lactobacillus plantarum/metabolismo , Pasteurización , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/metabolismo , Viabilidad Microbiana/efectos de los fármacos , Composición de Medicamentos , Digestión , Almacenamiento de Alimentos
2.
EMBO Rep ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271775

RESUMEN

Osteoclasts are bone resorbing cells that are essential to maintain skeletal integrity and function. While many of the growth factors and molecular signals that govern osteoclastogenesis are well studied, how the metabolome changes during osteoclastogenesis is unknown. Using a multifaceted approach, we identified a metabolomic signature of osteoclast differentiation consisting of increased amino acid and nucleotide metabolism. Maintenance of the osteoclast metabolic signature is governed by elevated glutaminolysis. Mechanistically, glutaminolysis provides amino acids and nucleotides which are essential for osteoclast differentiation and bone resorption in vitro. Genetic experiments in mice found that glutaminolysis is essential for osteoclastogenesis and bone resorption in vivo. Highlighting the therapeutic implications of these findings, inhibiting glutaminolysis using CB-839 prevented ovariectomy induced bone loss in mice. Collectively, our data provide strong genetic and pharmacological evidence that glutaminolysis is essential to regulate osteoclast metabolism, promote osteoclastogenesis and modulate bone resorption in mice.

3.
Ecotoxicol Environ Saf ; 285: 117038, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39277997

RESUMEN

The impact of microplastics (MPs) on plant growth, particularly root development, remains underexplored. To address this, a laboratory pot experiment and meta-analysis were conducted to assess how varying concentrations of MPs affect plant root growth. In pot experiments, the response of root traits to MPs differed by plant species. For F. arundinacea, a higher addition (1 % and 2 %) of polypropylene (PP) significantly increased the total length, surface area, volume, as well as fine root (<1 mm) surface area and volume. Partial least squares path modeling (PLS-PM) analysis showed that high concentrations of MPs affected plant root growth and plant root biomass by promoting fine root growth. Meta-analysis indicated that MPs increased shoot dry biomass by 32.7 % but reduced root dry biomass by 4.1 % and root length by 14.3 %. Higher concentrations (>0.5 %) of MPs significantly increased root length (35.2 %) and root dry biomass (6.3 %), whereas decreased shoot dry biomass (-8.6 %). Under the lower MPs concentration (<0.5 %), the root length and root dry biomass were decreased by 18.6 % and 11.1 %, respectively, and the shoot dry biomass was increased by 53.2 % compared with the treatment without MPs. The results emphasize the differences in performance between species for different MPs concentrations, implying that there may be future scope to select for species/varieties that are most resilient to the presence of MPs.

4.
Food Chem X ; 23: 101659, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39157659

RESUMEN

The objective of this study was to investigate the potential of Lacticaseibacillus rhamnosus L08 (L. rhamnosus L08) to enhance the functionality, improve the taste, and explore efficient storage methods of blue honeysuckle juice (BHJ). The fermentation process resulted in an increase in the levels of polyphenols, flavonoids, and anthocyanins in blue honeysuckle juice, which was attributed to the action of ß-glucosidase on specific phenolic compounds, namely Cyanidin-3-Glucoside and Quinic acid. The increase in phenolic content resulted in an enhancement of the antioxidant capacity of BHJ. The fermentation processed, utilizing L. rhamnosus L08, not only enhanced the flavor and taste of BHJ, but also mitigated its bitter aftertaste while minimizing the loss of bioactive components during storage. In conclusion, this study demonstrated a potential avenue for enhancing the commercial value and dietary significance of this lesser-known superfruit, with fermented BHJ emerging as a promising innovation in the field of functional foods.

5.
Res Sq ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38947036

RESUMEN

The Cystine-xCT transporter-Glutathione (GSH)-GPX4 axis is the canonical pathway to protect against ferroptosis. While not required for ferroptosis-inducing compounds (FINs) targeting GPX4, FINs targeting the xCT transporter require mitochondria and its lipid peroxidation to trigger ferroptosis. However, the mechanism underlying the difference between these FINs is still unknown. Given that cysteine is also required for coenzyme A (CoA) biosynthesis, here we show that CoA supplementation specifically prevents ferroptosis induced by xCT inhibitors but not GPX4 inhibitors. We find that, auranofin, a thioredoxin reductase inhibitor, abolishes the protective effect of CoA. We also find that CoA availability determines the enzymatic activity of thioredoxin reductase, but not thioredoxin. Importantly, the mitochondrial thioredoxin system, but not the cytosolic thioredoxin system, determines CoA-mediated ferroptosis inhibition. Our data show that the CoA regulates the in vitro enzymatic activity of mitochondrial thioredoxin reductase (TXNRD2) by covalently modifying the thiol group of cysteine (CoAlation) on Cys-483. Replacing Cys-483 with alanine on TXNRD2 abolishes its in vitro enzymatic activity and ability to protect cells from ferroptosis. Targeting xCT to limit cysteine import and, therefore, CoA biosynthesis reduced CoAlation on TXNRD2, an effect that was rescued by CoA supplementation. Furthermore, the fibroblasts from patients with disrupted CoA metabolism demonstrate increased mitochondrial lipid peroxidation. In organotypic brain slice cultures, inhibition of CoA biosynthesis leads to an oxidized thioredoxin system, mitochondrial lipid peroxidation, and loss in cell viability, which were all rescued by ferrostatin-1. These findings identify CoA-mediated post-translation modification to regulate the thioredoxin system as an alternative ferroptosis protection pathway with potential clinical relevance for patients with disrupted CoA metabolism.

6.
J Dairy Sci ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38969003

RESUMEN

Human milk oligosaccharides (HMOs) promote the growth and adhesion of bifidobacteria, thus exerting multiple biological functions on intestinal epithelial cells. Bacterial surface proteins play an important role in bacterial-host intestinal epithelial interactions. In this study, we aim to investigate the effects of surface proteins extracted from Bifidobacterium bifidum DNG6 (B. bifidum DNG6) consuming 2'-fucosyllactose (2'-FL) on Caco-2 cells monolayer barrier injury induced by lipopolysaccharide, compared with lactose (Lac) and galacto-oligosaccharides (GOS). Our results indicated that 2'-FL may promote the surface proteins of B. bifidum DNG6 to improve intestinal barrier injury by positively regulating the NF-κB signaling pathway, reducing inflammation(TNF-α reduced to 50.34%, IL-6 reduced to 22.83%, IL-1ß reduced to 37.91%, and IL-10 increased to 63.47%)and strengthening tight junction (ZO-1 2.39 times, Claudin-1 2.79 times, and Occludin 4.70 times). The findings of this study indicate that 2'-FL can further regulate intestinal barrier damage by promoting the alteration of B. bifidum DNG6 surface protein. The findings of this research will also provide theoretical support for the development of synbiotic formulations.

7.
Chem Sci ; 15(28): 10838-10850, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39027281

RESUMEN

Macrophages are plastic and play a key role in the maintenance of tissue homeostasis. In cancer progression, macrophages also take part in all processes, from initiation to progression, to final tumor metastasis. Although energy deprivation and autophagy are widely used for cancer therapy, most of these strategies do not target macrophages, resulting in undesired effects and unsatisfactory outcomes for cancer immunotherapy. Herein, we developed a lanthanum nickel oxide (LNO) nanozyme with phosphatase-like activity for ATP hydrolysis. Meanwhile, the autophagy of macrophages induced by LNO promotes the polarization of macrophages from M2-like macrophages (M2) to M1-like macrophages (M1) and reduces tumor-associated macrophages in tumor-bearing mice, exhibiting the capability of killing tumor-associated macrophages and antitumor effects in vivo. Furthermore, pre-coating the surface of LNO with a myeloid cell membrane significantly enhanced antitumor immunity. Our findings demonstrate that phosphatase-like nanozyme LNO can specifically induce macrophage autophagy, which improves therapeutic efficacy and offers valuable strategies for cancer immunotherapy.

8.
Basic Res Cardiol ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992300

RESUMEN

Propionic acidemia (PA), arising from PCCA or PCCB variants, manifests as life-threatening cardiomyopathy and arrhythmias, with unclear pathophysiology. In this work, propionyl-CoA metabolism in rodent hearts and human pluripotent stem cell-derived cardiomyocytes was investigated with stable isotope tracing analysis. Surprisingly, gut microbiome-derived propionate rather than the propiogenic amino acids (valine, isoleucine, threonine, and methionine) or odd-chain fatty acids was found to be the primary cardiac propionyl-CoA source. In a Pcca-/-(A138T) mouse model and PA patients, accumulated propionyl-CoA and diminished acyl-CoA synthetase short-chain family member 3 impede hepatic propionate disposal, elevating circulating propionate. Prolonged propionate exposure induced significant oxidative stress in PCCA knockdown HL-1 cells and the hearts of Pcca-/-(A138T) mice. Additionally, Pcca-/-(A138T) mice exhibited mild diastolic dysfunction after the propionate challenge. These findings suggest that elevated circulating propionate may cause oxidative damage and functional impairment in the hearts of patients with PA.

9.
Plants (Basel) ; 13(12)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38931110

RESUMEN

Arbuscular mycorrhizal inoculation can promote plant growth, but specific research on the difference in the symbiosis effect of arbuscular mycorrhizal fungi and plant combination is not yet in-depth. Therefore, this study selected Medicago sativa L., Bromus inermis Leyss, and Festuca arundinacea Schreb., which were commonly used for restoring degraded land in China to inoculate with three AMF separately, to explore the effects of different AMF inoculation on the growth performance and nutrient absorption of different plants and to provide a scientific basis for the research and development of the combination of mycorrhiza and plants. We set up four treatments with inoculation Entrophospora etunicata (EE), Funneliformis mosseae (FM), Rhizophagus intraradices (RI), and non-inoculation. The main research findings are as follows: the three AMF formed a good symbiotic relationship with the three grassland plants, with RI and FM having more significant inoculation effects on plant height, biomass, and tiller number. Compared with C, the aboveground biomass of Medicago sativa L., Bromus inermis Leyss, and Festuca arundinacea Schreb. inoculated with AMF increased by 101.30-174.29%, 51.67-74.14%, and 110.67-174.67%. AMF inoculation enhanced the plant uptake of N, P, and K, and plant P and K contents were significantly correlated with plant biomass. PLS-PM analyses of three plants all showed that AMF inoculation increased plant nutrient uptake and then increased aboveground biomass and underground biomass by increasing plant height and root tillering. This study showed that RI was a more suitable AMF for combination with grassland degradation restoration grass species and proposed the potential mechanism of AMF-plant symbiosis to increase yield.

10.
Nano Lett ; 24(26): 7895-7902, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38913401

RESUMEN

On-demand engineering of cell membrane receptors to nongenetically intervene in cellular behaviors is still a challenge. Herein, a membraneless enzyme biofuel cell-based self-powered biosensor (EBFC-SPB) was developed for autonomously and precisely releasing Zn2+ to initiate DNAzyme-based reprogramming of cell membrane receptors, which further mediates signal transduction to regulate cellular behaviors. The critical component of EBFC-SPB is a hydrogel film on a biocathode which is prepared using a Fe3+-cross-linked alginate hydrogel film loaded with Zn2+ ions. In the working mode in the presence of glucose/O2, the hydrogel is decomposed due to the reduction of Fe3+ to Fe2+, accompanied by rapid release of Zn2+ to specifically activate a Zn2+-responsive DNAzyme nanodevice on the cell surface, leading to the dimerization of homologous or nonhomologous receptors to promote or inhibit cell proliferation and migration. This EBFC-SPB platform provides a powerful "sensing-actuating-treating" tool for chemically regulating cellular behaviors, which holds great promise in precision biomedicine.


Asunto(s)
Técnicas Biosensibles , Zinc , Zinc/química , Zinc/metabolismo , Receptores de Superficie Celular/metabolismo , ADN Catalítico/metabolismo , ADN Catalítico/química , Humanos , Hidrogeles/química , Proliferación Celular/efectos de los fármacos , Fuentes de Energía Bioeléctrica , Alginatos/química , Movimiento Celular/efectos de los fármacos
11.
Int J Biol Macromol ; 274(Pt 1): 133315, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38914390

RESUMEN

In this study, changes in the structural and functional properties of soybean protein isolate (SPI)-naringenin (NG) complexes under different amounts of naringenin treatments were explored, elucidating the effect of the complexes as fat replacers at the 15 % substitution level on the properties of low-fat cream. Finally, the correlation between the structure and function of the complex and the properties of low-fat cream was further analyzed. The addition of NG promotes the increase of SPI aggregation and particle size, and reduces the interfacial tension of the complex. Meanwhile, at the mass ratio of 48:3, NG and SPI formed a dendritic network structure suitable for stabilizing cream. The fat properties of cream indicate that low-fat creams stabilized by appropriate proportions of SPI-NG complexes displayed small and dense fat crystal network structures. In addition, low-fat cream stabilized by the SPI-NG complexes have improved whipping time, overrun, firmness, storage stability and rheological properties compared to natural SPI. It is worth noting that the overall quality of the cream stabilized by the SPI-NG complex with a mass ratio of 48:3 was almost close to that of full-fat cream. Therefore, this study promotes the potential applications of protein-polyphenol complexes as fat replacers in the food industry.


Asunto(s)
Flavanonas , Proteínas de Soja , Proteínas de Soja/química , Adsorción , Flavanonas/química , Conformación Proteica , Agregado de Proteínas , Reología , Tamaño de la Partícula
12.
Front Med ; 18(4): 664-677, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38926249

RESUMEN

Pathological cardiac hypertrophy, a major contributor to heart failure, is closely linked to mitochondrial function. The roles of long noncoding RNAs (lncRNAs), which regulate mitochondrial function, remain largely unexplored in this context. Herein, a previously unknown lncRNA, Gm20257, was identified. It markedly increased under hypertrophic stress in vivo and in vitro. The suppression of Gm20257 by using small interfering RNAs significantly induced cardiomyocyte hypertrophy. Conversely, the overexpression of Gm20257 through plasmid transfection or adeno-associated viral vector-9 mitigated angiotensin II-induced hypertrophic phenotypes in neonatal mouse ventricular cells or alleviated cardiac hypertrophy in a mouse TAC model respectively, thus restoring cardiac function. Importantly, Gm20257 restored mitochondrial complex IV level and enhanced mitochondrial function. Bioinformatics prediction showed that Gm20257 had a high binding score with peroxisome proliferator-activated receptor coactivator-1 (PGC-1α), which could increase mitochondrial complex IV. Subsequently, Western blot analysis results revealed that Gm20257 substantially affected the expression of PGC-1α. Further analyses through RNA immunoprecipitation and immunoblotting following RNA pull-down indicated that PGC-1α was a direct downstream target of Gm20257. This interaction was demonstrated to rescue the reduction of mitochondrial complex IV induced by hypertrophic stress and promote the generation of mitochondrial ATP. These findings suggest that Gm20257 improves mitochondrial function through the PGC-1α-mitochondrial complex IV axis, offering a novel approach for attenuating pathological cardiac hypertrophy.


Asunto(s)
Cardiomegalia , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , ARN Largo no Codificante , Animales , Masculino , Ratones , Cardiomegalia/genética , Cardiomegalia/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Humanos
13.
Commun Biol ; 7(1): 659, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811689

RESUMEN

Propionic acidemia (PA), resulting from Pcca or Pccb gene mutations, impairs propionyl-CoA metabolism and induces metabolic alterations. While speculation exists that fasting might exacerbate metabolic crises in PA patients by accelerating the breakdown of odd-chain fatty acids and amino acids into propionyl-CoA, direct evidence is lacking. Our investigation into the metabolic effects of fasting in Pcca-/-(A138T) mice, a PA model, reveals surprising outcomes. Propionylcarnitine, a PA biomarker, decreases during fasting, along with the C3/C2 (propionylcarnitine/acetylcarnitine) ratio, ammonia, and methylcitrate. Although moderate amino acid catabolism to propionyl-CoA occurs with a 23-h fasting, a significant reduction in microbiome-produced propionate and increased fatty acid oxidation mitigate metabolic alterations by decreasing propionyl-CoA synthesis and enhancing acetyl-CoA synthesis. Fasting-induced gluconeogenesis further facilitates propionyl-CoA catabolism without changing propionyl-CoA carboxylase activity. These findings suggest that fasting may alleviate metabolic alterations in Pcca-/-(A138T) mice, prompting the need for clinical evaluation of its potential impact on PA patients.


Asunto(s)
Ayuno , Metilmalonil-CoA Descarboxilasa , Mutación , Animales , Ratones , Metilmalonil-CoA Descarboxilasa/metabolismo , Metilmalonil-CoA Descarboxilasa/genética , Acidemia Propiónica/genética , Acidemia Propiónica/metabolismo , Masculino , Ratones Noqueados , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Acilcoenzima A/metabolismo
14.
Front Plant Sci ; 15: 1360190, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38779065

RESUMEN

Introduction: Arid and semi-arid regions are climate-sensitive areas, which account for about 40% of the world's land surface area. Future environment change will impact the environment of these area, resulting in a sharp expansion of arid and semi-arid regions. Cotoneaster multiflorus is a multi-functional tree species with extreme cold, drought and barren resistance, as well as ornamental and medicinal functions. It was found to be one of the most important tree species for ecological restoration in arid and semi-arid areas. However, bioclimatic factors play an important role in the growth, development and distribution of plants. Therefore, exploring the response pattern and ecological adaptability of C. multiflorus to future climate change is important for the long-term ecological restoration of C. multiflorus in arid and semi-arid areas. Methods: In this study, we predicted the potential distribution of C. multiflorus in China under different climate scenarios based on the MaxEnt 2.0 model, and discussed its adaptability and the major factors affecting its geographical distribution. Results: The major factors that explained the geographical distribution of C. multiflorus were Annual precipitation (Bio12), Min air temperature of the coldest month (Bio6), and Mean air temperature of the coldest quarter (Bio11). However, C. multiflorus could thrive in environments where Annual precipitation (Bio12) >150 mm, Min air temperature of the coldest month (Bio6) > -42.5°C, and Mean air temperature of the coldest quarter (Bio11) > -20°C, showcasing its characteristics of cold and drought tolerance. Under different future climate scenarios, the total suitable area for C. multiflorus ranged from 411.199×104 km² to 470.191×104 km², which was 0.8~6.14 percentage points higher than the current total suitable area. Additionally, it would further shift towards higher latitude. Discussion: The MaxEnt 2.0 model predicted the potential distribution pattern of C. multiflorus in the context of future climate change, and identified its ecological adaptability and the main climatic factors affecting its distribution. This study provides an important theoretical basis for natural vegetation restoration in arid and semi-arid areas.

15.
Biosens Bioelectron ; 258: 116370, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38744115

RESUMEN

Protein phosphorylation is a significant post-translational modification that plays a decisive role in the occurrence and development of diseases. However, the rapid and accurate identification of phosphoproteins remains challenging. Herein, a high-throughput sensor array has been constructed based on a magnetic bimetallic nanozyme (Fe3O4@ZNP@UiO-66) for the identification and discrimination of phosphoproteins. Attributing to the formation of Fe-Zr bimetallic dual active centers, the as-prepared Fe3O4@ZNP@UiO-66 exhibits enhanced peroxidase-mimicking catalytic activity, which promotes the electron transfer from Zr center to Fe(II)/Fe(III). The catalytic activity of Fe3O4@ZNP@UiO-66 can be selectively inhibited by phosphoproteins due to the strong interaction between phosphate groups and Zr centers, as well as the ultra-robust antifouling capability of zwitterionic dopamine nanoparticle (ZNP). Considering the diverse binding affinities between various proteins with the nanozyme, the catalytic activity of Fe3O4@ZNP@UiO-66 can be changed to various degree, leading to the different absorption responses at 420 nm in the hydrogen peroxide (H2O2) - 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) system. By simply extracting different absorbance intensities at various time points, a sensor array based on reaction kinetics for the discrimination of phosphoproteins from other proteins is constructed through linear discriminant analysis (LDA). Besides, the quantitative determination of phosphoproteins and identification of protein mixtures have been realized. Further, based on the differential level of phosphoproteins in cells, the differentiation of cancer cells from normal cells can also be implemented by utilizing the proposed sensor array, showing great potential in disease diagnosis.


Asunto(s)
Técnicas Biosensibles , Peróxido de Hidrógeno , Neoplasias , Fosfoproteínas , Circonio , Técnicas Biosensibles/métodos , Humanos , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Peróxido de Hidrógeno/química , Circonio/química , Peroxidasa/química , Dopamina/química , Límite de Detección , Materiales Biomiméticos/química , Catálisis
16.
Int Immunopharmacol ; 133: 112069, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38643710

RESUMEN

Epigallocatechin-3-gallate (EGCG) is an important tea polyphenol with anti-tumor potential. Our previous studies revealed that EGCG was a promising immune checkpoint inhibitor (ICI) as it could downregulate expression of programmed cell death 1 ligand 1 (PD-L1) in tumor cells, thereby resulting tumor killing effect. In particular, EGCG can effectively avoid the inflammatory storm caused by anti-tumor therapy, which is a healthy green capacity absent from many ICIs. However, the relationship between EGCG and programmed cell death 1 (PD-1) of T cells remains unclear. In this work, we explored the effect of EGCG on T cells and found that EGCG suppressed PD-1 via inhibiting NF-κB phosphorylation and nuclear translocation. Furtherly, the capability of EGCG was confirmed in tumor-bearing mice to inhibit PD-1 expression in T cells and enhance apoptosis in tumor cells. These results implied that EGCG could inhibit the expression of PD-1 in T cells, thereby promoting anti-tumor effects of T cells. EGCG will be a promising candidate in anti-tumor therapy.


Asunto(s)
Transporte Activo de Núcleo Celular , Catequina , FN-kappa B , Receptor de Muerte Celular Programada 1 , Linfocitos T , Animales , Femenino , Humanos , Ratones , Transporte Activo de Núcleo Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Catequina/análogos & derivados , Catequina/farmacología , Línea Celular Tumoral , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Fosforilación/efectos de los fármacos , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo
17.
Cell ; 187(10): 2359-2374.e18, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38653240

RESUMEN

Brown adipose tissue (BAT) is best known for thermogenesis. Rodent studies demonstrated that enhanced BAT thermogenesis is tightly associated with increased energy expenditure, reduced body weight, and improved glucose homeostasis. However, human BAT is protective against type 2 diabetes, independent of body weight. The mechanism underlying this dissociation remains unclear. Here, we report that impaired mitochondrial catabolism of branched-chain amino acids (BCAAs) in BAT, by deleting mitochondrial BCAA carriers (MBCs), caused systemic insulin resistance without affecting energy expenditure and body weight. Brown adipocytes catabolized BCAA in the mitochondria as nitrogen donors for the biosynthesis of non-essential amino acids and glutathione. Impaired mitochondrial BCAA-nitrogen flux in BAT resulted in increased oxidative stress, decreased hepatic insulin signaling, and decreased circulating BCAA-derived metabolites. A high-fat diet attenuated BCAA-nitrogen flux and metabolite synthesis in BAT, whereas cold-activated BAT enhanced the synthesis. This work uncovers a metabolite-mediated pathway through which BAT controls metabolic health beyond thermogenesis.


Asunto(s)
Tejido Adiposo Pardo , Aminoácidos de Cadena Ramificada , Resistencia a la Insulina , Mitocondrias , Nitrógeno , Termogénesis , Tejido Adiposo Pardo/metabolismo , Animales , Aminoácidos de Cadena Ramificada/metabolismo , Ratones , Nitrógeno/metabolismo , Mitocondrias/metabolismo , Masculino , Humanos , Metabolismo Energético , Ratones Endogámicos C57BL , Estrés Oxidativo , Insulina/metabolismo , Dieta Alta en Grasa , Adipocitos Marrones/metabolismo , Transducción de Señal
18.
Compr Rev Food Sci Food Saf ; 23(2): e13311, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38445543

RESUMEN

ß-Casein, an important protein found in bovine milk, has significant potential for application in the food, pharmaceutical, and other related industries. This review first introduces the composition, structure, and functional properties of ß-casein. It then reviews the techniques for isolating ß-casein. Chemical and enzymatic isolation methods result in inactivity of ß-casein and other components in the milk, and it is difficult to control the production conditions, limiting the utilization range of products. Physical technology not only achieves high product purity and activity but also effectively preserves the biological activity of the components. The isolated ß-casein needs to be utilized effectively and efficiently for various purity products in order to achieve optimal targeted application. Bovine ß-casein, which has a purity higher than or close to that of breast ß-casein, can be used in infant formulas. This is achieved by modifying its structure through dephosphorylation, resulting in a formula that closely mimics the composition of breast milk. Bovine ß-casein, which is lower in purity than breast ß-casein, can be maximized for the preparation of functional peptides and for use as natural carriers. The remaining byproducts can be utilized as food ingredients, emulsifiers, and carriers for encapsulating and delivering active substances. Thus, realizing the intensive processing and utilization of bovine ß-casein isolation. This review can promote the industrial production process of ß-casein, which is beneficial for the sustainable development of ß-casein as a food and material. It also provides valuable insights for the development of other active substances in milk.


Asunto(s)
Ingredientes Alimentarios , Leche , Humanos , Femenino , Lactante , Animales , Caseínas , Emulsionantes , Fórmulas Infantiles
19.
Ultrason Sonochem ; 104: 106843, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38471387

RESUMEN

The primary significance of this work is that the commercial yeast proteins particles were successfully used to characterize the high internal phase Pickering emulsions (HIPPEs). The different sonication time (0,3,7,11,15 min) was used to modulate the structure and interface characteristics of yeast proteins (YPs) that as Pickering particles. Immediately afterward, the influence of YPs particles prepared at different sonication time on the rheological behavior and coalescence mechanism of HIPPEs was investigated. The results indicate that the YPs sonicated for 7 min exhibited a more relaxed molecular structures and conformation, the smallest particle size, the highest H0 and optimal amphiphilicity (the three-phase contact (θ) was 88.91°). The transition from extended to compact conformations of YPs occurred when the sonication time exceeded 7 min, resulting in an augmentation of size of YPs particles, a reduction in surface hydrophobicity (H0), and an elevation in hydrophilicity. The HIPPEs stabilized by YPs particles sonicated for 7 min exhibited the highest adsorption interface protein percentage and a more homogeneous three-dimensional (3D) protein network, resulting in the smallest droplet size and the highest storage (G'). The HIPPEs sample that stabilized by YPs particles sonicated for 15 min showed the lowest adsorption protein percentage. This caused a reduction in the thickness of its interface protein layer and an enlargement in the droplet diameter (D [3,2]). It was prone to droplet coalescence according to the equation used to evaluate the coalescence probability of droplets (Eq (2)). And the non-adsorbed YPs particles form larger aggregation structures in the continuous phase and act as "structural agents" in 3D protein network. Therefore, mechanistically, the interface protein layer formed by YPs particles sonicated 7 min contributed more to HIPPEs stability. Whereas the "structural agents" contributed more to HIPPEs stability when the sonication time exceeded 7 min. The present results shed important new light on the application of commercial YPs in the functional food fields, acting as an available and effective alternative protein.


Asunto(s)
Proteínas Fúngicas , Sonicación , Emulsiones/química , Interacciones Hidrofóbicas e Hidrofílicas , Tamaño de la Partícula
20.
Cell Metab ; 36(2): 422-437.e8, 2024 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-38325337

RESUMEN

Time-restricted feeding (TRF) has gained attention as a dietary regimen that promotes metabolic health. This study questioned if the health benefits of an intermittent TRF (iTRF) schedule require ketone flux specifically in skeletal and cardiac muscles. Notably, we found that the ketolytic enzyme beta-hydroxybutyrate dehydrogenase 1 (BDH1) is uniquely enriched in isolated mitochondria derived from heart and red/oxidative skeletal muscles, which also have high capacity for fatty acid oxidation (FAO). Using mice with BDH1 deficiency in striated muscles, we discover that this enzyme optimizes FAO efficiency and exercise tolerance during acute fasting. Additionally, iTRF leads to robust molecular remodeling of muscle tissues, and muscle BDH1 flux does indeed play an essential role in conferring the full adaptive benefits of this regimen, including increased lean mass, mitochondrial hormesis, and metabolic rerouting of pyruvate. In sum, ketone flux enhances mitochondrial bioenergetics and supports iTRF-induced remodeling of skeletal muscle and heart.


Asunto(s)
Cetonas , Miocardio , Ratones , Animales , Cetonas/metabolismo , Miocardio/metabolismo , Mitocondrias/metabolismo , Oxidación-Reducción , Corazón , Músculo Esquelético/metabolismo
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