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1.
Food Chem ; 463(Pt 1): 141042, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39241412

RESUMEN

Textured vegetable proteins (TVP) are an alternative to meet the increasing demand for non-animal food. This study aimed to develop a TVP from mixtures with 45 % pea protein isolate (PPI) enriched with amaranth (AF) and oat (OF) flours using high-moisture extrusion technology (HME) varying the moisture (50-70 %) and the temperature in the second heating zone of the extruder (110-140 °C). After extrusion, all samples demonstrated higher values of water absorption capacity (WAC) than non-extruded mixtures. Mixture of AF:OF:PPI (40:15:45 %) extruded at 60 % moisture and 135 °C showed promising functional properties with WAC and WSI values of 3.2 ± 0.2 g H2O/g and 24.89 ± 2.31 %, respectively, and oil absorption capacity (OAC) of 1.3 g oil/g. The extrusion process altered the thermal and structural properties of proteins promoting a desirable fibrous structure. This confirms the feasibility of using HME to develop TVP based on PPI, AF, and OF.

2.
Int J Biol Macromol ; 280(Pt 2): 135800, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39307506

RESUMEN

In this work, the performance of oat hull-filled sodium alginate (SA-O) biocomposite microbeads in the adsorptive removal of methylene blue (MB) dye was examined. First, oat hulls were pulverized and biocomposite gels containing different weight ratios of oat hulls (10 %, 20 %, and 30 %, concerning the SA amount) were prepared by dispersing them in SA solution by ultrasonic homogenization method. Finally, gels were cross-linked by dropping into a 2 % CaCl2 solution. The study revealed that the optimal adsorbent dosage was 0.025 g/50 mL, pH was roughly 6-8, and the contact time was 120 min. According to isotherm models, the non-linear Sips and Langmuir model was more appropriate compare to other isotherms from error analysis, with a maximum adsorption capacity of 687.65 mg/g and 757.57 mg/g at 298 K, respectively. Furthermore, the non-linear kinetic data and error analyzes demonstrated that the process followed the pseudo-second-order kinetic. The adsorption process was exothermic (∆H°=-17.71 kJ/mol) and spontaneous (∆G°=-26.23 kJ/mol) at 298 K, based on thermodynamic characteristics. Furthermore, reusability investigations demonstrated that the adsorbent retained its performance with no major changes in characteristics. This work reveals that highly efficient, low-cost, sustainable, and eco-friendly SA-O composites with properties might be useful adsorbents for cationic dye adsorption.

3.
J Sci Food Agric ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39314063

RESUMEN

BACKGROUND: Obesity is a non-communicable complex disease that is the fifth leading cause of death worldwide. According to a novel viewpoint, the brain plays a significant role in the central regulation of satiety and energy homeostasis. Because of its rich nutritional profile and versatile uses, oat (Avena sativa) is one of the most popular functional foods recommended by many nutritionists. The anti-obesity effect of oat was hypothesized, focusing on the brain as the target organ. In the current study, the interplay between brain biomarkers, obesity, and its related complications was evaluated in diet-induced obese rats for 25 weeks, in which 60 adult male white albino Wistar rats were divided into three control and seven treatment groups given oat extracts in a dose-dependent manner. RESULTS: Oat significantly improved obesity-related metabolic complications. In terms of brain function, oat significantly increased dopaminergic signaling, brain-derived neurotrophic factor levels, vaspin, irisin, and uncoupling protein-1 brain levels, while decreasing the expression of agouti-related peptide and neuropeptide Y (P-value < 0.05). CONCLUSION: The current study proposes oat supplementation as a new conceptual framework with numerous implications for hedonic and homeostatic mechanisms that control satiety. © 2024 Society of Chemical Industry.

4.
Foods ; 13(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39272597

RESUMEN

As a protein extracted from soybeans, soy protein isolate (SPI) may undergo the Maillard reaction (MR) with co-existing saccharides during the processing of soy-containing foods, potentially altering its structural and functional properties. This work aimed to investigate the effect of mono- and polysaccharides on the structure and functional properties of SPI during MR. The study found that compared to oat ß-glucan, the reaction rate between SPI and D-galactose was faster, leading to a higher degree of glycosylation in the SPI-galactose conjugate. D-galactose and oat ß-glucan showed different influences on the secondary structure of SPI and the microenvironment of its hydrophobic amino acids. These structural variations subsequently impact a variety of the properties of the SPI conjugates. The SPI-galactose conjugate exhibited superior solubility, surface hydrophobicity, and viscosity. Meanwhile, the SPI-galactose conjugate possessed better emulsifying stability, capability to produce foam, and stability of foam than the SPI-ß-glucan conjugate. Interestingly, the SPI-ß-glucan conjugate, despite its lower viscosity, showed stronger hypoglycemic activity, potentially due to the inherent activity of oat ß-glucan. The SPI-galactose conjugate exhibited superior antioxidant properties due to its higher content of hydroxyl groups on its molecules. These results showed that the type of saccharides had significant influences on the SPI during MR.

5.
J Mol Graph Model ; 133: 108869, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39317004

RESUMEN

Oat contains a large amount of polysaccharides and peptides, among which oat peptides have the function of reducing blood sugar levels in the body. This paper reviewed the peptides obtained from oat extraction and identification from literature and constructed the corresponding oat peptide database. Based on the DPP4 protein, a virtual screening of the peptide database was performed. One hundred nanosecond molecular dynamics simulations were performed for the six peptides obtained from the screening. The interaction information between different peptide molecules and DPP4 was analyzed from the stable binding conformations after the simulation, and the binding free energy between different peptide molecules and DPP4 was calculated. The results show that the peptide molecules obtained from the virtual screening can all stably bind to the DPP4 protein, among which two peptide molecules have relatively strong affinity with DPP4 and can be used as lead molecules for the subsequent design and modification of DPP4 inhibitors. The simulation results are informative for a deeper understanding of the structural characteristics of DPP4 and the molecular recognition mechanism between DPP4 and oat peptides.

6.
Contemp Clin Trials ; 146: 107690, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39265780

RESUMEN

INTRODUCTION: Ukraine has high HIV prevalence, concentrated among people who inject drugs (PWID), mostly of opioids. Maintenance on opioid agonist therapies (OAT) is the most effective evidence-based treatment for opioid use disorder. As PWID experience high morbidity and mortality from preventable and treatable non-communicable diseases, international agencies recommend integrating OAT into primary care centers (PCC). METHODS: A randomized, type-2 hybrid implementation trial was carried out to compare outcomes of OAT integration in PCC to OAT delivery at specialty treatment centers (STC) - standard-of-care. Tele-education supporting PCC providers in managing OAT, HIV, tuberculosis and non-communicable diseases along with pay-for-performance incentives were used to facilitate implementation. Consenting patients underwent 1:2 randomization to either STC or PCC. Quality health indicators (QHIs), a composite percentage of recommended primary and specialty services accessed by patients (blood/urine tests, cancer screenings, etc.), were defined as efficacy outcomes and were assessed by participant self-report at baseline and every 6 months over 24 months and electronic chart reviews after the completion of the follow-up. The primary outcome is defined as the difference in composite QHI scores at 24 months, in which a repeated measures likelihood-based mixed model with missing at random assumptions will be used. Providers at PCC completed surveys at baseline, 12 and 24 months to assess implementation outcomes including changes in stigma and attitudes towards OAT and PWID. PRELIMINARY RESULTS: Among the 1459 participants allocated to STC (N = 509) or PCC (N = 950), there were no differences in clinical and demographic characteristics. Self-reported prevalences were available for HIV (42 %), HCV (57 %), and prior tuberculosis (17 %). Study retention at 6, 12, 18, and 24 months was as 91 %, 85 %, 80 %, and 74 %, respectively. CONCLUSION: PWID have a high prevalence of medical comorbidities and integrating OAT into primary care settings has the potential to improve the health of PWID. Findings from this study can help guide implementation of integrated care in Ukraine and throughout similar low-resource, high-burden countries in the Eastern European and Central Asian region.

7.
Plant Biotechnol J ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39321029

RESUMEN

The endeavour to elevate the nutritional value of oat (Avena sativa) by altering the oil composition and content positions it as an optimal crop for fostering human health and animal feed. However, optimization of oil traits on oat through conventional breeding is challenging due to its quantitative nature and complexity of the oat genome. We introduced two constructs containing three key genes integral to lipid biosynthesis and/or regulatory pathways from Arabidopsis (AtWRI1 and AtDGAT1) and Sesame (SiOLEOSIN) into the oat cultivar 'Park' to modify the fatty acid composition. Four homozygous transgenic lines were generated with a transformation frequency of 7%. The expression of these introduced genes initiated a comprehensive transcriptional reprogramming in oat grains and leaves. Notably, endogenous DGAT, WRI1 and OLEOSIN genes experienced upregulation, while genes associated with fatty acid biosynthesis, such as KASII, SACPD and FAD2, displayed antagonistic expression patterns between oat grains and leaves. Transcriptomic analyses highlighted significant differential gene expression, particularly enriched in lipid metabolism. Comparing the transgenic oat plants with the wild type, we observed a remarkable increase of up to 34% in oleic acid content in oat grains. Furthermore, there were marked improvements in the total oil content in oat leaves, as well as primary metabolites changes in both oat grains and leaves, while maintaining homeostasis in the transgenic oat plants. These findings underscore the effectiveness of genetic engineering in manipulating oat oil composition and content, offering promising implications for human consumption and animal feeding through oat crop improvement programmes.

8.
Mol Pharmacol ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39322412

RESUMEN

The creatine transporter-1 (CRT-1/SLC6A8) maintains the uphill transport of creatine into cells against a steep concentration gradient. Cellular creatine accumulation is required to support the ATP-buffering by phosphocreatine. More than 60 compounds have been explored in the past for their ability to inhibit cellular creatine uptake, but the number of active compounds is very limited. Here, we show that all currently known inhibitors are full alternative substrates. We analyzed their structure-activity relation for inhibition of CRT-1 to guide a rational approach to the synthesis of novel creatine transporter ligands. Measurements of both, inhibition of [3H]creatine uptake and transport associated currents, allowed for differentiating between full and partial substrates and true inhibitors. This combined approach led to a refined understanding of the structural requirements for binding to CRT-1, which translated into the identification of three novel compounds - i.e. compound 1 (2-(N-benzylcarbamimidamido)acetic acid), and MIPA572 (=carbamimidoylphenylalanine) and MIPA573 (=carbamimidoyltryptophane) that blocked CRT-1 transport, albeit with low affinity. In addition, we found two new alternative full substrates, namely MIP574 (carbamimidoylalanine) and GiDi1257 (1-carbamimidoylazetidine-3-carboxylic acid), which was superior in affinity to all known CTR-1 ligands, and one partial substrate, namely GiDi1254 (1-carbamimidoylpiperidine-4-carboxylic acid). Significance Statement The creatine transporter-1 (CRT-1) is required to maintain intracellular creatine levels. Inhibition of CRT-1 has been recently proposed as a therapeutic strategy for cancer, but pharmacological tools are scarce. In fact, all available inhibitors are alternative substrates. We tested existing and newly synthesized guanidinocarboxylic acids for CRT-1 inhibition and identified three blockers, one partial and two full substrates of CRT-1. Our results support a refined structural understanding of ligand binding to CRT-1 and provide a proof-of-principle for blockage of CRT-1.

9.
Cureus ; 16(8): e66127, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39229425

RESUMEN

Background Heart valve replacement surgery is one of the most commonly performed cardiac surgeries in India. Post-surgery, the patient requires lifetime anticoagulation therapy with regular follow-up, leading to financial and nonfinancial burdens for the patients. This study aimed to determine the out-of-pocket (OOP) expenditure (OOPE) for follow-up visits to the heart valve clinic and explore and assess the challenges faced by patients during these follow-ups. Methodology This mixed methods study was conducted at a tertiary care center from June 2018 to August 2018, focusing on patients attending the Valve Replacement clinic. The qualitative component of the study involved conducting three focus group discussions, which were transcribed and manually analyzed using thematic analysis to generate categories. The monthly OOPE and the proportion of irregular patients were assessed using a pretested and validated questionnaire developed based on the findings from the qualitative study. The data from the quantitative study were entered into EpiData version 3.1 (EpiData, Odense, Denmark) and analyzed using Stata 14 (StataCorp., College Station, TX). Results The median (interquartile range [IQR]) total OOPE for patients was Rs. 765 (475-1,100). The median (IQR) direct and indirect expenditures were Rs. 420 (210-600) and Rs. 590 (330-948), respectively. The patients faced difficulties in the categories of financial, travel, hospital, family, and personal. Out of a total of 143 participants, 86 (60.14%) had incurred catastrophic health expenditures. The cost also significantly increased with the presence of an accompanying person and longer travel durations. Conclusions The major difficulties faced by the patients were distance and expense. Telemedicine can help overcome these challenges by decentralizing follow-up care to the primary care level.

10.
Carbohydr Polym ; 344: 122535, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39218555

RESUMEN

Oat ß-(1 â†’ 3, 1 â†’ 4)-d-glucan (OBG), a linear polysaccharide primarily found in oat bran, has been demonstrated to possess immunomodulatory properties and regulate gut microbiota. This study aimed to investigate the impact of low molecular weight (Mw) OBG (155.2 kDa) on colonic injury and allergic symptoms induced by food allergy (FA), and to explore its potential mechanism. In Experiment 1, results indicated that oral OBG improved colonic inflammation and epithelial barrier, and significantly relieved allergy symptoms. Importantly, the OBG supplement altered the gut microbiota composition, particularly increasing the abundance of Lachnospiraceae and its genera, and promoted the production of short-chain fatty acids, especially butyrate. However, in Experiment 2, the gut microbial depletion eliminated these protective effects of OBG on the colon in allergic mice. Further, in Experiment 3, fecal microbiota transplantation and sterile fecal filtrate transfer directly validated the role of OBG-mediated gut microbiota and its metabolites in relieving FA and its induced colonic injury. Our findings suggest that low Mw OBG can alleviate FA-induced colonic damage by increasing Lachnospiraceae abundance and butyrate production, and provide novel insights into the health benefits and mechanisms of dietary polysaccharide intervention for FA.


Asunto(s)
Avena , Butiratos , Colon , Hipersensibilidad a los Alimentos , Microbioma Gastrointestinal , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Colon/patología , Colon/efectos de los fármacos , Colon/metabolismo , Butiratos/metabolismo , Avena/química , Clostridiales , beta-Glucanos/farmacología , beta-Glucanos/química , Ratones Endogámicos BALB C , Masculino , Glucanos/farmacología , Glucanos/química , Ácidos Grasos Volátiles/metabolismo , Trasplante de Microbiota Fecal
11.
Heliyon ; 10(16): e35801, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39220917

RESUMEN

Camel milk is a nutrient-rich diet and fermentation affects its nutritional value and probiotic function. In this study, sour camel milk and oat jujube sour camel milk were prepared using fermentation bacteria agent TR1, and the metabolites of camel milk, sour camel milk and oat jujube sour camel milk were detected using a non-targeted metabolomics approach using liquid chromatography-mass spectrometry (LC-MS).The results showed that the partial least squares discriminant analysis (PLS-DA) with 100 % accuracy and good predictive power detected 343 components in positive ion mode and 220 components in negative ion mode. The differential metabolites were mainly organic acids, amino acids, esters, vitamins and other substances contained in camel milk.It showed that there were significant differences in the metabolites of camel milk, sour camel milk and oat jujube sour camel milk. Based on the pathway enrichment analysis of the three dairy products in the KEGG database, 12 metabolic pathways mainly involved in the positive ion mode and 20 metabolic pathways mainly involved in the negative ion mode were identified. The main biochemical metabolic pathways and signal transduction pathways of the differential metabolites of the three dairy products were obtained. This study provides theoretical support for improving the nutritional quality and probiotic function of camel milk and fermented camel milk products and provides a basis for the development of relevant processing technologies and products for camel milk and fermented camel milk.

12.
J Pharmacol Exp Ther ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39284625

RESUMEN

The disruption of dopamine neurotransmission by the HIV-1 Transactivator of transcription (Tat) during HIV-1 infection has been linked to the development of neurocognitive disorders, even under combined antiretroviral therapy (cART) treatment. We have demonstrated that SRI-32742, a novel allosteric modulator of dopamine (DA) transporter (DAT), attenuates cocaine- and Tat-binding to DAT, alleviates Tat-induced cognitive deficits and potentiation of cocaine reward in inducible Tat transgenic mice. The current study determined the in vitro pharmacological profile of SRI-32743 and its optimized second-generation analogs and their effects as allosteric modulators. Through structure-activity relationship studies of SRI-32743, 170 compounds were synthesized and evaluated for their ability to modulate DAT function. We identified 21 analogs as atypical competitors of DAT (Emax {less than or equal to}60%). Four compounds, SRI-46564, SRI-47056, SRI-46286 and SRI-47867, displayed IC50 values for [3H]DA uptake inhibition from 9.33 {plus minus} 0.50 to 0.96 {plus minus} 0.05 µM and from 3.96 {plus minus} 1.36 to 1.29 {plus minus} 0.19 for DAT binding, respectively. The four analogs also displayed high potency at two different concentrations (0.5 nM and 0.05 nM) to attenuate Tat-induced inhibition of [3H]DA uptake and cocaine-mediated dissociation of [3H]WIN35,428 binding in CHO cells expressing hDAT, suggesting that the effects occur through an allosteric mechanism. In further ex vivo studies using Fast-Scan Cyclic Voltammetry, we demonstrated that the analogs do not disrupt the baseline phasic-like DA release. These findings provide a new insight into the potential for development of novel therapeutic agents to attenuate DAT-Tat interactions to normalize DA neurotransmission in NeuroHIV. Significance Statement The allosteric inhibition of the dopamine (DA) transporter by the HIV-1 Transactivator of transcription (Tat) disrupts dopamine homeostasis, leading to HIV-associated neurocognitive disorders (HANDs). Analogs of SRI-32743, a novel allosteric modulator of the Tat-DAT interaction, were evaluated in the current study and characterized as atypical ligands of DA uptake. Four novel lead compounds demonstrated high potency to attenuate Tat-induced inhibition of hDAT-mediated DA uptake in an allosteric modulatory manner with no effects on the dynamics of DA uptake-release in DAT.

13.
J Agric Food Chem ; 72(36): 19891-19903, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39225266

RESUMEN

Oat straw, a residue of Avena sativa L., is recognized for its abundance in cellulose, hemicelluloses, and lignin. However, its potential as a source of lipophilic compounds within the framework of a biorefinery concept still remains unexplored. In this study, we conducted an extensive investigation into the content and chemical composition of the lipophilic compounds present in acetone extracts from oat straws of two distinct oat varieties, namely, Karen and Isaura. Furthermore, we examined their seasonal variability in content and composition in straw samples from oats planted in both spring and winter seasons. The extracted lipophilic compounds were predominantly composed of high molecular weight esters (26.0-38.1%), steroids (16.6-24.0%), n-fatty alcohols (10.9-20.7%), n-fatty acids (10.9-16.0%), and n-aldehydes (10.7-15.8%), with lower amounts of n-alkanes (1.1-3.0%), acylglycerides (2.3-3.8%), phytol and phytyl esters (0.6-2.9%), ß-diketones (0.1-2.5%), triterpenoids (0.9-1.2%), tocopherols and tocopheryl esters (0.2-0.7%), 2-hydroxy fatty acids (0.1-0.2%), and n-alkylresorcinols (0.1%). Notably, these different classes of compounds exhibited variations in their contents depending on the oat variety and the specific planting season. Of particular interest was the Karen variety, which presented significant amounts of high molecular weight esters, free fatty acids, and acylglycerols, especially when it was cultivated during the winter season. These findings underline the potential of oat straw as a valuable resource for lipid extraction within a biorefinery context and emphasize the importance of selecting the appropriate variety and season for optimal lipid yield.


Asunto(s)
Avena , Ácidos Grasos , Estaciones del Año , Avena/química , Ácidos Grasos/química , Ácidos Grasos/análisis , Ésteres/análisis , Ésteres/química , Extractos Vegetales/química , Tallos de la Planta/química , Lípidos/química , Lípidos/análisis
14.
Food Chem ; 460(Pt 3): 140766, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39126946

RESUMEN

Vitamin B12 deficiency poses significant health risks, especially among populations with limited access to animal-based foods. This study explores the utilisation of cereal bran by-products, wheat (WB) and oat bran (OB), as substrates for in situ vitamin B12 fortification through solid-state fermentation (SSF) using Propionibacterium freudenreichii. The impact of various precursors addition, including riboflavin, cobalt, nicotinamide and DMBI on vitamin B12 production, along with changes in microbial growth, chemical profiles, and vitamin B12 yields during fermentation was evaluated. Results showed that WB and OB possess favourable constituents for microbial growth and vitamin B12 synthesis. The substrates supplemented with riboflavin, cobalt, and DMBI demonstrated enhanced B12 production. In addition, pH levels are essential in microbial viability and cobalamin biosynthesis. Monosaccharides and organic acids play a crucial role, with maltose showing a strong positive association with B12 production in OB, while in WB, citric acid exhibits significant correlations with various factors.


Asunto(s)
Avena , Fermentación , Alimentos Fortificados , Triticum , Vitamina B 12 , Vitamina B 12/análisis , Vitamina B 12/metabolismo , Avena/química , Avena/metabolismo , Avena/microbiología , Triticum/química , Triticum/metabolismo , Triticum/microbiología , Triticum/crecimiento & desarrollo , Alimentos Fortificados/análisis , Grano Comestible/química , Grano Comestible/microbiología , Grano Comestible/metabolismo
15.
Food Chem ; 460(Pt 3): 140787, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39128371

RESUMEN

This study aimed to optimize an alternative frozen dessert formulation using the response surface method (RSM). The formulation utilized oat-based milk substitute (OBMS) due to its desirable texture, sensory appeal, and nutritional benefits for vegans and lactose intolerant individuals. Xanthan gum (XG) was also incorporated to enhance the rheological properties of the dessert. With a coefficient of consistency of 192.58 Pa.s and a hysteresis field of 10,999 Pa/s, the ice cream formulation with the greatest rheological structure was discovered to be the combination of 20% oats, 0.5% xanthan gum (XG), and pasteurized at 65 °C. It also showed <10% melting in the first 10 min, confirming that it has a very stable structure. At the same pasteurization conditions and XG ratios, it was observed that rheological stability decreased with increasing oat milk addition. However, the shear thinning behavior of frozen dessert was improved by creating a more complex network structure with increasing XG concentration. The overrun values of the frozen desserts ranged from 21.55% to 34.63%, with the majority being statistically similar. The vegan frozen dessert formulation obtained with 40% oats, 0.37% XG and pasteurization at 60 °C showed a high level of sensory acceptance. This research contributes to the field of vegan food product development by providing innovative rheological and sensory alternatives to traditional frozen desserts using oats and XG.


Asunto(s)
Avena , Polisacáridos Bacterianos , Reología , Polisacáridos Bacterianos/química , Avena/química , Humanos , Gusto , Congelación , Animales , Leche/química , Helados/análisis
16.
Cell Rep Med ; 5(8): 101690, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39168099

RESUMEN

Hyperuricemic nephropathy (HN) is a global metabolic disorder characterized by uric acid (UA) metabolism dysfunction, resulting in hyperuricemia (HUA) and tubulointerstitial fibrosis (TIF). Sodium-dependent glucose transporter 2 inhibitor, dapagliflozin, has shown potential in reducing serum UA levels in patients with chronic kidney disease (CKD), though its protective effects against HN remain uncertain. This study investigates the functional, pathological, and molecular changes in HN through histological, biochemical, and transcriptomic analyses in patients, HN mice, and UA-stimulated HK-2 cells. Findings indicate UA-induced tubular dysfunction and fibrotic activation, which dapagliflozin significantly mitigates. Transcriptomic analysis identifies estrogen-related receptor α (ERRα), a downregulated transcription factor in HN. ERRα knockin mice and ERRα-overexpressed HK-2 cells demonstrate UA resistance, while ERRα inhibition exacerbates UA effects. Dapagliflozin targets ERRα, activating the ERRα-organic anion transporter 1 (OAT1) axis to enhance UA excretion and reduce TIF. Furthermore, dapagliflozin ameliorates renal fibrosis in non-HN CKD models, underscoring the therapeutic significance of the ERRα-OAT1 axis in HN and CKD.


Asunto(s)
Compuestos de Bencidrilo , Fibrosis , Glucósidos , Hiperuricemia , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Animales , Glucósidos/farmacología , Glucósidos/uso terapéutico , Compuestos de Bencidrilo/farmacología , Fibrosis/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/complicaciones , Humanos , Ratones , Masculino , Receptor Relacionado con Estrógeno ERRalfa , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/patología , Enfermedades Renales/metabolismo , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Ratones Endogámicos C57BL , Ácido Úrico/sangre , Receptores de Estrógenos/metabolismo , Proteína 1 de Transporte de Anión Orgánico/metabolismo , Proteína 1 de Transporte de Anión Orgánico/genética , Línea Celular , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/patología , Modelos Animales de Enfermedad , Femenino
17.
Nutrients ; 16(15)2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39125425

RESUMEN

Male infertility represents a significant public health concern. There is a negative impact of inflammatory bowel diseases (IBDs) on the male reproductive system. The aim of this study was to investigate whether oat beta-glucan (OBG) with different molar mass can modulate parameters of antioxidant defense and inflammatory response in the testes of adult Sprague-Dawley rats with TNBS-induced colitis and whether the OBG intervention can modulate the inflammatory response in association with the RAS system. Results: higher testicular superoxide dismutase (SOD), glutathione reductase (GR) activities and glutathione (GSH) concentration, and lower testosterone (T) level and glutathione peroxidase (GPx) activity, were observed in rats with colitis than in healthy control ones. TNBS-induced colitis resulted in decreased the angiotensin 1-7 (ANG 1-7) level in the testes of rats fed with low-molar mass OBG compared to control animals. Conclusions: although colitis induced moderate pro-oxidant changes in the gonads, it seems plausible that dietary intervention with different fractions of oat beta-glucans mass may support the maintenance of reproductive homeostasis via the stimulation of the local antioxidant defense system.


Asunto(s)
Antioxidantes , Avena , Colitis , Ratas Sprague-Dawley , Testículo , beta-Glucanos , Animales , Masculino , beta-Glucanos/farmacología , beta-Glucanos/administración & dosificación , Testículo/metabolismo , Testículo/efectos de los fármacos , Antioxidantes/metabolismo , Avena/química , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/dietoterapia , Ratas , Angiotensina I/metabolismo , Ácido Trinitrobencenosulfónico , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Fragmentos de Péptidos/metabolismo , Glutatión/metabolismo , Testosterona/sangre , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo
18.
Cell Rep ; 43(8): 114628, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39146184

RESUMEN

High serum urate levels are the major risk factor for gout. URAT1, the primary transporter for urate absorption in the kidneys, is well known as an anti-hyperuricemia drug target. However, the clinical application of URAT1-targeted drugs is limited because of their low specificity and severe side effects. The lack of structural information impedes elucidation of the transport mechanism and the development of new drugs. Here, we present the cryoelectron microscopy (cryo-EM) structures of human URAT1(R477S), its complex with urate, and its closely related homolog OAT4. URAT1(R477S) and OAT4 exhibit major facilitator superfamily (MFS) folds with outward- and inward-open conformations, respectively. Structural comparison reveals a 30° rotation between the N-terminal and C-terminal domains, supporting an alternating access mechanism. A conserved arginine (OAT4-Arg473/URAT1-Arg477) is found to be essential for chloride-mediated inhibition. The URAT1(R477S)-urate complex reveals the specificity of urate recognition. Taken together, our study promotes our understanding of the transport mechanism and substrate selection of URAT1.


Asunto(s)
Microscopía por Crioelectrón , Transportadores de Anión Orgánico , Proteínas de Transporte de Catión Orgánico , Ácido Úrico , Humanos , Ácido Úrico/metabolismo , Transportadores de Anión Orgánico/metabolismo , Transportadores de Anión Orgánico/química , Proteínas de Transporte de Catión Orgánico/metabolismo , Proteínas de Transporte de Catión Orgánico/química , Especificidad por Sustrato , Células HEK293 , Transporte Biológico , Modelos Moleculares , Transportadores de Anión Orgánico Sodio-Independiente
19.
J Agric Food Chem ; 72(32): 17847-17857, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39088794

RESUMEN

The mechanisms of insecticide resistance are complex. Recent studies have revealed a novel mechanism involving the chemosensory system in insecticide resistance. However, the specific binding mechanism between olfactory-related genes and insecticides needs to be clarified. In this study, the binding mechanism between pyrethroid insecticide deltamethrin and RpCSP6 from Rhopalosiphum padi was investigated by using computational and multiple experimental methods. RpCSP6 was expressed in different tissues and developmental stages of R. padi and can be induced by deltamethrin. Knockdown of RpCSP6 significantly increased the susceptibility of R. padi to deltamethrin. The binding affinity of RpCSP6 to 24 commonly used insecticides was measured. Seven key residues were found to steadily interact with deltamethrin, indicating their significance in the binding affinity to the insecticide. Our research provided insights for effectively analyzing the binding mechanism of insect CSPs with insecticides, facilitating the development of new and effective insecticides that target insect CSPs.


Asunto(s)
Proteínas de Insectos , Resistencia a los Insecticidas , Insecticidas , Nitrilos , Piretrinas , Piretrinas/metabolismo , Piretrinas/farmacología , Nitrilos/metabolismo , Nitrilos/farmacología , Nitrilos/química , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Insecticidas/farmacología , Insecticidas/metabolismo , Insecticidas/química , Resistencia a los Insecticidas/genética , Animales , Unión Proteica
20.
Sci Rep ; 14(1): 19414, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169032

RESUMEN

A field investigation took place at Central Research Farm of Bidhan Chandra Krishi Viswavidyalaya, West Bengal, India during winter seasons of 2020-21 and 2021-22 with the aim to evaluate system productivity, economics, energetics and carbon footprint (CF) of oat + grasspea intercropping systems under different integrated nutrient managements (INM). The experiment was executed in split-plot design with 4 cropping systems in main plots and 4 levels of nutrient management in sub plots. The 3:3 intercropping system of oat + grasspea ensured highest system productivity, whereas sole grasspea stood best in terms of economics, energetics and environment safety by lowering CF. Notably, INM involving 75% N through urea + 25% N through vermicompost registered significantly higher system productivity in case of 3:3 oat + grasspea intercropping system (CS4N3) (18.77 q ha-1). Further, this intercropping system yielded high economic profitability (net return: US$ 430.4 ha-1, benefit-cost ratio: 1.71) as well as energy indices (energy output: 71179.1 MJ ha-1, net energy gain: 60352.0 MJ ha-1, energy ratio: 6.57 and energy profitability: 5.57). CF was also found relatively low under CS4N3 (Yield scaled CF: 62.2 kg CO2-e q-1). Furthermore, high carbon efficiency (7.92) and carbon sustainability index (6.92) were also exhibited by CS4N3 as it produced maximum carbon output (1801.2 kg ha-1). In conclusion, the 3:3 oat + grasspea intercropping system using INM can be viable option to ensure economic and energy viability and minimize greenhouse gas emissions without compromising system productivity. Particularly, this intercropping system combined with 75% N through urea + 25% N through vermicompost as INM option can be recommended for the cereal and legume growers of India, specifically under intensive cropping scenario.

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