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1.
Am J Hum Genet ; 111(5): 954-965, 2024 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-38614075

RESUMEN

Variability in quantitative traits has clinical, ecological, and evolutionary significance. Most genetic variants identified for complex quantitative traits have only a detectable effect on the mean of trait. We have developed the mean-variance test (MVtest) to simultaneously model the mean and log-variance of a quantitative trait as functions of genotypes and covariates by using estimating equations. The advantages of MVtest include the facts that it can detect effect modification, that multiple testing can follow conventional thresholds, that it is robust to non-normal outcomes, and that association statistics can be meta-analyzed. In simulations, we show control of type I error of MVtest over several alternatives. We identified 51 and 37 previously unreported associations for effects on blood-pressure variance and mean, respectively, in the UK Biobank. Transcriptome-wide association studies revealed 633 significant unique gene associations with blood-pressure mean variance. MVtest is broadly applicable to studies of complex quantitative traits and provides an important opportunity to detect novel loci.


Asunto(s)
Presión Sanguínea , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Humanos , Presión Sanguínea/genética , Polimorfismo de Nucleótido Simple , Modelos Genéticos , Genotipo , Variación Genética , Simulación por Computador , Fenotipo
2.
Chem Soc Rev ; 53(12): 6021-6041, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38738520

RESUMEN

High-entropy alloys (HEAs) involving more than four elements, as emerging alloys, have brought about a paradigm shift in material design. The unprecedented compositional diversities and structural complexities of HEAs endow multidimensional exploration space and great potential for practical benefits, as well as a formidable challenge for synthesis. To further optimize performance and promote advanced applications, it is essential to synthesize HEAs with desired characteristics to satisfy the requirements in the application scenarios. The properties of HEAs are highly related to their chemical compositions, microstructure, and morphology. In this review, a comprehensive overview of the controllable synthesis of HEAs is provided, ranging from composition design to morphology control, structure construction, and surface/interface engineering. The fundamental parameters and advanced characterization related to HEAs are introduced. We also propose several critical directions for future development. This review can provide insight and an in-depth understanding of HEAs, accelerating the synthesis of the desired HEAs.

3.
J Am Chem Soc ; 146(11): 7118-7123, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38437170

RESUMEN

High-entropy oxides (HEOs) with an ultrathin geometric structure are especially expected to exhibit extraordinary performance in different fields. The phase structure is deemed as a key factor in determining the properties of HEOs, rendering their phase control synthesis tempting. However, the disparity in intrinsic phase structures and physicochemical properties of multiple components makes it challenging to form single-phase HEOs with the target phase. Herein, we proposed a self-lattice framework-guided strategy to realize the synthesis of ultrathin HEOs with desired phase structures, including rock-salt, spinel, perovskite, and fluorite phases. The participation of the Ga assistor was conducive to the formation of the high-entropy mixing state by decreasing the formation energy. The as-prepared ultrathin spinel HEOs were demonstrated to be an excellent catalyst with high activity and stability for the oxygen evolution reaction in water electrolysis. Our work injects new vitality into the synthesis of HEOs for advanced applications and undoubtedly expedites their phase engineering.

4.
Anal Chem ; 96(5): 2152-2157, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38279912

RESUMEN

Sensing materials innovation plays a crucial role in the development of high-performance film-based fluorescent sensors (FFSs). In our current study, we present the innovative fabrication of four fluorescent nanofilms via interfacially confined dynamic reaction of a specially designed fluorescent building block, a new boron-coordinated compound (NI-CHO), with a chosen one, benzene-1,3,5-tricarbohydrazide (BTH). The nanofilms as prepared are robust, uniform, flexible, and thickness tunable, at least from 40 to 1500 nm. The fabricated FFSs based on Film 3, one of the four nanofilms, shows highly selective and fully reversible response to NH3 vapor with an experimental detection limit of <0.1 ppm and a response time of 0.2 s. The unprecedented high performance of the nanofilm is ascribed to the specific quenching of its fluorescence emission owing to formation of an excited-state complex between the sensing unit and the analyte molecule. Efficient mass transfer also contributes to the high performance owing to the porous adlayer structure of the nanofilm. This work provides an example to show how to develop a high-performance sensing film via controlling the film's structure, especially the thickness.

5.
Crit Rev Food Sci Nutr ; : 1-17, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38965668

RESUMEN

Most studies on the beneficial effects of polyphenols on human health have focused on polyphenols extracted using aqueous organic solvents, ignoring the fact that a portion of polyphenols form complexes with polysaccharides. Polysaccharides and polyphenols are interrelated, and their interactions affect the physicochemical property, quality, and nutritional value of foods. In this review, the distribution of bound polyphenols in major food sources is summarized. The effect of food processing on the interaction between polyphenols and cell wall polysaccharides (CWP) is discussed in detail. We also focus on the digestion, absorption, and metabolic behavior of polysaccharide-polyphenol complexes. Different food processing techniques affect the interaction between CWP and polyphenols by altering their structure, solubility, and strength of interactions. The interaction influences the free concentration and extractability of polyphenols in food and modulates their bioaccessibility in the gastrointestinal tract, leading to their major release in the colon. Metabolism of polyphenols by gut microbes significantly enhances the bioavailability of polyphenols. The metabolic pathway and product formation rate of polyphenols and the fermentation characteristics of polysaccharides are affected by the interaction. Furthermore, the interaction exhibits synergistic or antagonistic effects on the stability, solubility, antioxidant and functional activities of polyphenols. In summary, understanding the interactions between polysaccharides and polyphenols and their changes in food processing is of great significance for a comprehensive understanding of the health benefits of polyphenols and the optimization of food processing technology.

6.
Int J Mol Sci ; 25(11)2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38891803

RESUMEN

Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To elucidate the molecular mechanism of RABV-induced neuronal damage, we used hematoxylin-eosin staining, transmission electron microscopy, transcriptomics analysis, and immune response factor testing to investigate RABV-infected neurons. We successfully isolated the neurons from murine brains. The specificity of the isolated neurons was identified by a monoclonal antibody, and the viability of the neurons was 83.53-95.0%. We confirmed that RABV infection induced serious damage to the neurons according to histochemistry and transmission electron microscope (TEM) scanning. In addition, the transcriptomics analysis suggested that multiple genes related to the pyroptosis pathway were significantly upregulated, including gasdermin D (Gsdmd), Nlrp3, caspase-1, and IL-1ß, as well as the chemokine genes Ccl2, Ccl3, Ccl4, Ccl5, Ccl7, Ccl12, and Cxcl10. We next verified this finding in the brains of mice infected with the rRC-HL, GX074, and challenge virus standard strain-24 (CVS-24) strains of RABV. Importantly, we found that the expression level of the Gsdmd protein was significantly upregulated in the neurons infected with different RABV strains and ranged from 691.1 to 5764.96 pg/mL, while the basal level of mock-infected neurons was less than 100 pg/mL. Taken together, our findings suggest that Gsdmd-induced pyroptosis is involved in the neuron damage caused by RABV infection.


Asunto(s)
Neuronas , Proteínas de Unión a Fosfato , Piroptosis , Virus de la Rabia , Rabia , Animales , Neuronas/virología , Neuronas/metabolismo , Neuronas/patología , Virus de la Rabia/patogenicidad , Virus de la Rabia/fisiología , Rabia/virología , Rabia/patología , Rabia/metabolismo , Ratones , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Fosfato/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Encéfalo/virología , Encéfalo/patología , Encéfalo/metabolismo , Gasderminas
7.
Compr Rev Food Sci Food Saf ; 23(4): e13398, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38925595

RESUMEN

Food science encounters increasing complexity and challenges, necessitating more efficient, accurate, and sensitive analytical techniques. Mass spectrometry imaging (MSI) emerges as a revolutionary tool, offering more molecular-level insights. This review delves into MSI's applications and challenges in food science. It introduces MSI principles and instruments such as matrix-assisted laser desorption/ionization, desorption electrospray ionization, secondary ion mass spectrometry, and laser ablation inductively coupled plasma mass spectrometry, highlighting their application in chemical composition analysis, variety identification, authenticity assessment, endogenous substance, exogenous contaminant and residue analysis, quality control, and process monitoring in food processing and food storage. Despite its potential, MSI faces hurdles such as the complexity and cost of instrumentation, complexity in sample preparation, limited analytical capabilities, and lack of standardization of MSI for food samples. While MSI has a wide range of applications in food analysis and can provide more comprehensive and accurate analytical results, challenges persist, demanding further research and solutions. The future development directions include miniaturization of imaging devices, high-resolution and high-speed MSI, multiomics and multimodal data fusion, as well as the application of data analysis and artificial intelligence. These findings and conclusions provide valuable references and insights for the field of food science and offer theoretical and methodological support for further research and practice in food science.


Asunto(s)
Análisis de los Alimentos , Tecnología de Alimentos , Espectrometría de Masas , Tecnología de Alimentos/métodos , Espectrometría de Masas/métodos , Análisis de los Alimentos/métodos
8.
J Headache Pain ; 25(1): 122, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39048956

RESUMEN

BACKGROUND: The relationship between lifestyle and migraine is complex, as it remains uncertain which specific lifestyle factors play the most prominent role in the development of migraine, or which modifiable metabolic traits serve as mediators in establishing causality. METHODS: Independent genetic variants strongly associated with 20 lifestyle factors were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for migraine were obtained from the FinnGen consortium (18,477 cases and 287,837 controls) as a discovery set and the GWAS meta-analysis data (26,052 cases and 487,214 controls) as a replication set. Estimates derived from the two datasets were combined using fixed-effects meta-analysis. Two-step univariable MR (UVMR) and multivariable Mendelian randomization (MVMR) analyses were conducted to evaluate 19 potential mediators of association and determine the proportions of these mediators. RESULTS: The combined effect of inverse variance weighted revealed that a one standard deviation (SD) increase in genetically predicted Leisure screen time (LST) was associated with a 27.7% increase (95% CI: 1.14-1.44) in migraine risk, while Moderate or/and vigorous physical activity (MVPA) was associated with a 26.9% decrease (95% CI: 0.61-0.87) in migraine risk. The results of the mediation analysis indicated that out of the 19 modifiable metabolic risk factors examined, hypertension explains 24.81% of the relationship between LST and the risk of experiencing migraine. Furthermore, hypertension and diastolic blood pressure (DBP) partially weaken the association between MVPA and migraines, mediating 4.86% and 4.66% respectively. CONCLUSION: Our research findings indicated that both LST and MVPA in lifestyle have independent causal effects on migraine. Additionally, we have identified that hypertension and DBP play a mediating role in the causal pathway between these two factors and migraine.


Asunto(s)
Ejercicio Físico , Estudio de Asociación del Genoma Completo , Hipertensión , Análisis de la Aleatorización Mendeliana , Trastornos Migrañosos , Tiempo de Pantalla , Humanos , Trastornos Migrañosos/genética , Trastornos Migrañosos/epidemiología , Trastornos Migrañosos/fisiopatología , Ejercicio Físico/fisiología , Hipertensión/genética , Hipertensión/epidemiología , Actividades Recreativas
9.
Angew Chem Int Ed Engl ; 63(25): e202402453, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38622832

RESUMEN

Fabrication of large-area thin films through irreversible reactions remains a formidable task. This study reports a breakthrough strategy for in situ synthesis of large-area, free-standing, robust and multi-stimulus responsive thin films through a catalyst-free and irreversible Katritzky reaction at a liquid-liquid interface. The as resulted films are featured with adjustable thickness of 1-3 µm and an area up to 50 cm2. The thin films exhibit fast photo-mechanical motions (a response time of ca 0.1 s), vapor-mechanical motions, as well as photo-chromic and solvato-chromic behaviors. It was revealed that the reason behind the observable motions is proton transfer from the imine groups to the carbonyl structures within the film induced by photo- and/or dimethyl sulfoxide-stimulus. In addition, the films can harvest anionic radicals and the radicals as captured can be efficiently degraded under UV light illumination. This study provides a new strategy for fabricating smart thin films via interfacially confined irreversible Katritzky reaction.

10.
J Adv Res ; 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38471648

RESUMEN

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease with an increasing incidence worldwide. Single drug therapy may have toxic side effects and disrupt gut microbiota balance. Polyphenols are widely used in disease intervention due to their distinctive nutritional properties and medicinal value, which a potential gut microbiota modulator. However, there is a lack of comprehensive review to explore the efficacy and mechanism of combined therapy with drugs and polyphenols for NAFLD. AIM OF REVIEW: Based on this, this review firstly discusses the link between NAFLD and gut microbiota, and outlines the effects of polyphenols and drugs on gut microbiota. Secondly, it examined recent advances in the treatment and intervention of NAFLD with drugs and polyphenols and the therapeutic effect of the combination of the two. Finally, we highlight the underlying mechanisms of polyphenol combined drug therapy in NAFLD. This is mainly in terms of signaling pathways (NF-κB, AMPK, Nrf2, JAK/STAT, PPAR, SREBP-1c, PI3K/Akt and TLR) and gut microbiota. Furthermore, some emerging mechanisms such as microRNA potential biomarker therapies may provide therapeutic avenues for NAFLD. KEY SCIENTIFIC CONCEPTS OF REVIEW: Drawing inspiration from combination drug strategies, the use of active substances in combination with drugs for NAFLD intervention holds transformative and prospective potential, both improve NAFLD and restore gut microbiota balance while reducing the required drug dosage. This review systematically discusses the bidirectional interactions between gut microbiota and NAFLD, and summarizes the potential mechanisms of polyphenol synergistic drugs in the treatment of NAFLD by modulating signaling pathways and gut microbiota. Future researches should develop multi-omics technology to identify patients who benefit from polyphenols combination drugs and devising individualized treatment plans to enhance its therapeutic effect.

11.
Behav Sci (Basel) ; 14(3)2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38540547

RESUMEN

Attentional bias towards threatening information is a crucial factor contributing to the development and persistence of social anxiety. However, the attentional bias towards threat information and the preferential processing pattern of emotional cues in individuals with social anxiety disorder during integrated facial and physical stimuli processing remain unclear. In this study, we employed a dot-probe paradigm to investigate the attentional bias towards integrated emotions (facial-body) among students with high and low levels of social anxiety (Experiment 1). Experiments 2 and 3 examined the attentional bias of socially anxious individuals when faced with conflicting emotional cues from faces or bodies in relation to integrated emotions. The data revealed that participants both high and low levels of social anxiety participants exhibited accelerated orienting and biased attention towards facial-body emotional processing. When there was inconsistency between emotional cues from faces or bodies and integrated emotions, higher levels of social anxiety were associated with increased vigilance towards threatening faces or bodies. These findings underscore that individuals with social anxiety possess an ability to rapidly capture threatening cues during the processing of facial-body emotional stimuli while also demonstrating a tendency to avoid relying solely on facial cues by compensating through bodily cues for emotion perception.

12.
Front Cell Neurosci ; 18: 1386205, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38988662

RESUMEN

Epilepsy is a common neurological disorder that affects approximately 10.5 million children worldwide. Approximately 33% of affected patients exhibit resistance to all available antiseizure medications, but the underlying mechanisms are unknown and there is no effective treatment. Increasing evidence has shown that an abnormal gut microbiota may be associated with epilepsy. The gut microbiota can influence the function of the brain through multiple pathways, including the neuroendocrine, neuroimmune, and autonomic nervous systems. This review discusses the interactions between the central nervous system and the gastrointestinal tract (the brain-gut axis) and the role of the gut microbiota in the pathogenesis of epilepsy. However, the exact gut microbiota involved in epileptogenesis is unknown, and no consistent results have been obtained based on current research. Moreover, the target that should be further explored to identify a novel antiseizure drug is unclear. The role of the gut microbiota in epilepsy will most likely be uncovered with the development of genomics technology.

13.
Heliyon ; 10(11): e32124, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38882338

RESUMEN

As a medicine-food homology herb, Dendrobium spp. has versatile applications in modern medicine and food industry. Herein, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) based method was established for simultaneous quantification of six active components, including gigantol, erianin, naringenin, quercetin, rutin, and p-coumaric acid in Dendrobium spp., on the basis of optimized sample preparation, mass spectrometry conditions, and chromatography conditions. Sample extraction was carried out using methanol at a temperature of 60 °C, followed by separation on a T3 C18 column utilizing a gradient eluting program. The results demonstrated excellent linearity (r > 0.999) for the six active components within a specified concentration range. The average recovery rates ranged from 84.7 % to 106.9 %, and the precision (RSD) was within 7.4 %. The detection and quantification limits of this method ranged from 0.34 to 4.17 ng mL-1 and 1.12-13.91 ng mL-1, respectively. The established method demonstrates high accuracy and reliability and is applicable in practical sample detection. Different Dendrobium spp. exhibit specific variations in compound composition, with D. fimbriatum Hook. having a higher content of benzyl compounds and D. crystallinum. Rchb. f. having a higher content of flavonoids. This study provides experimental evidence for the quality and safety regulation of Dendrobium spp.

14.
Food Res Int ; 179: 114036, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38342549

RESUMEN

Polysaccharides and polyphenols are biologically active components that coexist in Lycium barbarum fruit, and there may be interactions between them that affect the release of each other. In this study, polyphenols bound to L. barbarum polysaccharide (LBP) were characterized, and the stability of bound phenolics (BP) was assessed by gastrointestinal digestion and colon fermentation. The results showed that a total of 65 phytochemicals such as flavonoids, phenolic acids, and coumarins were identified by UPLC-MS/MS. Quantitative analysis revealed that the major phenolic constituents were rutin, p-coumaric acid, catechin, ferulic acid, protocatechuic acid, and gallic acid, and their contents were 58.72, 24.03, 14.24, 13.28, 10.39, and 6.7 mg GAE/100 g DW, respectively. The release of BP by gastric digestion and gastrointestinal digestion was 9.67 % and 19.39 %, respectively. Most polyphenols were greatly affected by gastric digestion, while rutin was released in small intestine. The BP were fully released (49.77 %) and metabolized by gut microorganisms, and a considerable number of intermediates and end-products were detected, such as phloroglucinol, phenylacetic acid, and phenyllactic acid. Microbiomics data emphasized the positive impact of LBP on gut bacteria of Bacteroides, Parabacteroides, and Clostridioides. These findings could deepen our understanding of the bioavailability and biological fate of BP and also provide reference data for nutrient release and utilization of L. barbarum as a whole.


Asunto(s)
Medicamentos Herbarios Chinos , Polifenoles , Espectrometría de Masas en Tándem , Polifenoles/análisis , Fermentación , Cromatografía Liquida , Fenoles/metabolismo , Digestión , Rutina/metabolismo , Colon/metabolismo
15.
J Agric Food Chem ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38838169

RESUMEN

Inflammatory bowel disease (IBD) is a recurrent inflammatory condition affecting the gastrointestinal tract, and its clinical treatment remains suboptimal. Probiotics have shown effectiveness in alleviating dextran sulfate sodium salt (DSS)-induced colitis, exhibiting strain-specific anti-inflammatory properties. In this study, we compared the therapeutic effects of five strains of Bifidobacterium bifidum isolated from healthy adult feces on DSS-induced colitis in mice. Additionally, we investigated the underlying mechanisms by examining gut microbiota composition and microbial metabolome. Our findings highlighted the superior efficacy of B. bifidum M1-3 compared to other strains. It significantly improved colitis symptoms, mitigated gut barrier disruption, and reduced colonic inflammation in DSS-treated mice. Moreover, gut microbiota composition analysis revealed that B. bifidum M1-3 treatment increased the abundance and diversity of gut microbiota. Specifically, it significantly increased the abundance of Muribaculaceae, Lactobacillus, Bacteroides, and Enterorhabdus, while decreasing the abundance of Escherichia-Shigella. Furthermore, our nontargeted metabolomics analysis illustrated that B. bifidum M1-3 treatment had a regulatory effect on various metabolic pathways, including tyrosine metabolism, lysine degradation, and tryptophan metabolism. Importantly, we confirmed that the therapeutic efficiency of B. bifidum M1-3 was dependent on the gut microbiota. These results are conducive to the development of probiotic products for alleviating colitis.

16.
Artículo en Inglés | MEDLINE | ID: mdl-38703096

RESUMEN

CONTEXT: Childhood obesity continues to be a critical public health concern with far-reaching implications for the well-being. OBJECTIVE: This study aimed to investigate the association between metabolites in plasma and feces and indicators including body mass index (BMI), BMI for age Z score (BMIZ), and body fat distribution among children aged 6-9 years in China. METHODS: This cross-sectional study enrolled 424 healthy children, including 186 girls and 238 boys. Dual-energy X-ray absorptiometry (DXA) was used to determine the body fat content and regional fat distribution. Plasma and fecal metabolites were analyzed using targeted metabolomic technologies. RESULTS: A total of 200 plasma metabolites and 212 fecal metabolites were accurately quantified via ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). By using Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and random forest model, we discovered that 9 plasma metabolites and 11 fecal metabolites were associated with different weight statuses. After adjusting for potential covariates and false discovery rate (FDR) correction, multiple linear regression analyses revealed that plasma metabolites (fumaric acid, glycine, l-glutamine, methylmalonic acid, and succinic acid) and fecal metabolites (protocatechuic acid) were negatively associated (ß: -1.373--0.016, pFDR: <0.001-0.031; ß: -1.008--0.071, pFDR: 0.005-0.033), while plasma metabolites (isovaleric acid, isovalerylcarnitine, l-glutamic acid, and pyroglutamic acid) and fecal metabolites (3-aminoisobutanoic acid, butyric acid, N-acetylneuraminic acid, octanoylcarnitine, oleoylcarnitine, palmitoylcarnitine, stearoylcarnitine, taurochenodesoxycholic acid, and taurodeoxycholic acid) exhibited positive associations with BMI, BMIZ, and body fat distribution (ß: 0.023-2.396, pFDR: <0.001; ß: 0.014-1.736, pFDR: <0.001-0.049). CONCLUSION: Plasma and fecal metabolites such as glutamine may serve as a potential therapeutic target for the development of obesity.

17.
Oncol Rep ; 51(6)2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38695244

RESUMEN

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the Transwell cell migration and invasion assay data featured in Figs. 5C and 6C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published elsewhere prior to the submission of this paper to Oncology Reports, or were submitted for consideration for publication at around the same time. In view of the fact that certain of these data had already apparently been published prior to the submission of this article for publication, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 37: 2743­2750, 2017; DOI: 10.3892/or.2017.5555].

18.
Int J Biol Macromol ; 269(Pt 1): 132063, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705329

RESUMEN

Probiotic therapy has emerged as a promising approach for the treatment of gastrointestinal diseases, offering advantages in terms of safety and convenience. However, oral probiotics encounter significant challenges, including exposure to a hostile gastric environment with low pH, bile salts, elevated levels of reactive oxygen species (ROS), and damage to the protective mucus layer. These factors reduce probiotic survival rates and limit their physiological activity. To address these challenges, we developed a layer-by-layer coated probiotics with curcumin-loaded liposome and polymer. Through DSS-induced colitis mice experiments, we demonstrated that the coated probiotics exhibited an improved survival rate in the gastrointestinal tract and enhanced adhesion to the intestinal mucosa. Furthermore, multi-layered coated probiotics exhibited remarkable efficacy in alleviating colitis by efficiently repairing the gut barrier, modulating gut microbial homeostasis, and reducing bacterial motility at sites of colonic inflammation. Our innovative approach holds promise for effectively treating gastrointestinal diseases.


Asunto(s)
Quitosano , Colitis , Sulfato de Dextran , Liposomas , Probióticos , Animales , Probióticos/administración & dosificación , Probióticos/farmacología , Colitis/inducido químicamente , Colitis/terapia , Colitis/tratamiento farmacológico , Liposomas/química , Ratones , Quitosano/química , Quitosano/farmacología , Curcumina/farmacología , Curcumina/química , Modelos Animales de Enfermedad , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos
19.
Carbohydr Polym ; 338: 122205, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38763727

RESUMEN

Developing multifunctional films with antibacterial, antioxidant, and sustained-release properties is a robust strategy for preventing contamination of perishable fruits by foodborne microorganisms. This study engineered a sustained-release biodegradable antibacterial film loaded with EGCG (Pickering emulsion (PE)/α-Cyclodextrin (α-CD)/Konjac glucomannan (KGM)) through multi-strategy cross-linking for fruit preservation. EGCG is stabilized using PE and incorporated into the α-CD/KGM inclusion compound; the unique structure of α-CD enhances EGCG encapsulation, while KGM provides the film toughness and surface adhesion. The composite film's physicochemical properties, antioxidant, bacteriostatic and biodegradability were studied. Results showed that Pickering emulsions with 3 % oil phase exhibited excellent stability. Moreover, α-CD introduction increased the loading and sustained release of EGCG from the film, and its concentration significantly affected the light transmission, thermal stability, mechanical strength, mechanical characteristics and antioxidant capacity of the composite membrane. Antioxidant and antimicrobial activities of the composite film increased significantly with increasing α-CD concentration. Application of the film to tomatoes and strawberries effectively inhibited Escherichia coli and Staphylococcus aureus growth, prolonging the shelf-life of the fruits. Notably, the composite film exhibits superior biodegradability in soil. This EGCG-loaded PE/α-CD/KGM composite film is anticipated to be a multifunctional antimicrobial preservation material with sustained-release properties and biodegradable for perishable food applications.


Asunto(s)
Antibacterianos , Antioxidantes , Catequina , Emulsiones , Escherichia coli , Frutas , Mananos , alfa-Ciclodextrinas , alfa-Ciclodextrinas/química , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Mananos/química , Mananos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Frutas/química , Emulsiones/química , Antioxidantes/química , Antioxidantes/farmacología , Escherichia coli/efectos de los fármacos , Conservación de Alimentos/métodos , Staphylococcus aureus/efectos de los fármacos , Embalaje de Alimentos/métodos , Pruebas de Sensibilidad Microbiana , Reactivos de Enlaces Cruzados/química , Liberación de Fármacos
20.
Nat Commun ; 15(1): 6953, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138205

RESUMEN

Filovirus-host interactions play important roles in all stages of the virus lifecycle. Here, we identify LATS1/2 kinases and YAP, key components of the Hippo pathway, as critical regulators of EBOV transcription and egress. Specifically, we find that when YAP is phosphorylated by LATS1/2, it localizes to the cytoplasm (Hippo "ON") where it sequesters VP40 to prevent egress. In contrast, when the Hippo pathway is "OFF", unphosphorylated YAP translocates to the nucleus where it transcriptionally activates host genes and promotes viral egress. Our data reveal that LATS2 indirectly modulates filoviral VP40-mediated egress through phosphorylation of AMOTp130, a positive regulator of viral egress, but more surprisingly that LATS1/2 kinases directly modulate EBOV transcription by phosphorylating VP30, an essential regulator of viral transcription. In sum, our findings highlight the potential to exploit the Hippo pathway/filovirus axis for the development of host-oriented countermeasures targeting EBOV and related filoviruses.


Asunto(s)
Ebolavirus , Vía de Señalización Hippo , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Factores de Transcripción , Transcripción Genética , Liberación del Virus , Humanos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Fosforilación , Ebolavirus/fisiología , Ebolavirus/genética , Ebolavirus/metabolismo , Células HEK293 , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Señalizadoras YAP/metabolismo , Proteínas de la Matriz Viral/metabolismo , Proteínas de la Matriz Viral/genética , Fiebre Hemorrágica Ebola/virología , Fiebre Hemorrágica Ebola/metabolismo , Interacciones Huésped-Patógeno , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética
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