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1.
Heliyon ; 10(1): e23694, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38205329

RESUMEN

The outcomes and prognosis of autoimmune diseases depend on early diagnosis and effective treatments. However, symptoms of early autoimmune diseases are often remarkably similar to many inflammatory diseases, leading to difficulty in precise diagnosis. Circular RNAs (circRNAs) belong to a novel class of endogenous RNAs, functioning as microRNA (miRNA) sponges or participating in protein coding. It has been shown in many studies that patients with autoimmune diseases have aberrant circRNA expression in liquid biopsy samples (such as plasma, saliva, and urine). Thus, circRNAs are potential biomarkers for the diagnosis and prognosis of autoimmune diseases. Moreover, overexpression and depletion of target circRNAs can be utilized as possible therapeutic approaches for treating autoimmune diseases. In this review, we summarized recent progress in the roles of circRNAs in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes. We also discussed their potential as biomarkers and therapeutic targets.

2.
J Chem Theory Comput ; 19(24): 9093-9101, 2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38084039

RESUMEN

Understanding nucleation from aqueous solutions is of fundamental importance in a multitude of fields, ranging from materials science to biophysics. The complex solvent-mediated interactions in aqueous solutions hamper the development of a simple physical picture, elucidating the roles of different interactions in nucleation processes. In this work, we make use of three complementary techniques to disentangle the role played by short- and long-range interactions in solvent-mediated nucleation. Specifically, the first approach we utilize is the local molecular field (LMF) theory to renormalize long-range Coulomb electrostatics. Second, we use well-tempered metadynamics to speed up rare events governed by short-range interactions. Third, the deep learning-based State Predictive Information Bottleneck approach is employed in analyzing the reaction coordinate of the nucleation processes obtained from the LMF treatment coupled with well-tempered metadynamics. We find that the two-step nucleation mechanism can largely be captured by the short-range interactions, while the long-range interactions further contribute to the stability of the primary crystal state under ambient conditions. Furthermore, by analyzing the reaction coordinate obtained from the combined LMF-metadynamics treatment, we discern the fluctuations on different time scales, highlighting the need for long-range interactions when accounting for metastability.

3.
Int J Biol Macromol ; 253(Pt 5): 127197, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37797854

RESUMEN

In this study, we aimed to use electrical impedance spectroscopy (EIS) to assess the freeze-damage level of starches from potato tubers treated with multiple freezing-thawing (FT) cycles. The results showed that the relationship between the physicochemical properties of starches and the impedance characteristics of starch paste is temperature-dependent. As the temperature rises to 70-90 °C, the impedance modules show a significant correlation with the amylose and mineral contents, gelatinization and pasting properties, short-range ordered structure, relative crystallinity, and damage level within the range of 10-1 MHz (p < 0.01). This could be because FT leads to a reduction in amylose and ion content. Compared to a high level of freeze-damaged starch (FDS), a low level of FDS has less amylopectin and more amylose. Additionally, the ions could be typically evenly distributed throughout the unbranched linear amylose structure in starch paste. At the peak gelatinization temperature, the starch paste made from a low level of FDS exhibits a weakened network structure, allowing more unbound water for ion movement and enhancing electric conduction. In conclusion, EIS can predict the damage level and properties of FDS, which can benefit the frozen starchy food industry.


Asunto(s)
Amilosa , Almidón , Almidón/química , Amilosa/química , Espectroscopía Dieléctrica , Congelación , Amilopectina/química
4.
J Nutr Biochem ; 119: 109401, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37276891

RESUMEN

Type 2 diabetes mellitus (T2DM) is the most common type of diabetes globally and poses a major concern for human health. This study aimed to investigate the effects on T2DM of low-glycemic index (GI) potato biscuits with oat bran and inulin as functional additives. T2DM was induced in rats by streptozotocin (STZ) and a high-sugar and high-fat diet. The alleviation of T2DM by low-GI potato biscuits at different doses was evaluated based on the analysis of glycolipid levels, histological observations, inflammatory markers, and gut microbiota structure. Compared to wheat biscuits, low-GI potato biscuits resulted in lower postprandial blood glucose levels. After 8 weeks of intervention, fasting blood sugar levels were 16.9% lower in T2DM rats fed high-dose low-GI potato biscuits than in untreated T2DM rats. Moreover, the intervention with low-GI potato biscuits significantly alleviated T2DM-induced pathological damage, glucose and lipid metabolic disorders, and inflammation by reversing the levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, transforming growth factor-ß, interleukin-1ß, interleukin-6 and tumor necrosis factor-α. Moreover, the levels of short-chain fatty acids and gut microbiota structure in T2DM rats were significantly reversed. The abundance of beneficial bacteria (e.g., Bifidobacterium, Lachnoclostridium, Roseburia) in the gut of T2DM rats was significantly increased whereas the abundance of Escherichia-Shigella and Desulfovibrio decreased. The present study revealed that low-GI potato biscuits alleviated damages caused by high-sugar and high-fat diet- and STZ-induced T2DM in rats, as well as reversed disturbances in the gut microbiota. Thus, low-GI potato biscuits are potentially beneficial to T2DM patients.


Asunto(s)
Diabetes Mellitus Tipo 2 , Solanum tuberosum , Humanos , Ratas , Animales , Diabetes Mellitus Tipo 2/metabolismo , Índice Glucémico , Estreptozocina/efectos adversos , Solanum tuberosum/metabolismo , Dieta Alta en Grasa/efectos adversos , Disbiosis , HDL-Colesterol , Glucemia/metabolismo
5.
Mar Pollut Bull ; 193: 115169, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37354832

RESUMEN

Bohai Bay, as a significant economic bay area in China, has experienced considerable ecological consequences during its rapid economic development. One of the major environmental challenges is the emission of air pollutants from ships, which has had a severe impact on regional air quality and the health of residents. To assess the influence of pollutants on the air quality around the Bohai Bay area, a Weather Research and Forecasting and Community Multiscale Air Quality (WRF-CMAQ) model was established using a 9 km × 9 km high-resolution ship emission gridded inventory from 2018. The WRF-CMAQ model was employed to compare two scenarios: vessel emissions and non-vessel emissions, in order to evaluate the impact of ship emissions. By analyzing the pollutant concentrations in Bohai Bay and the degree of change in pollutant concentration in six cities under these two scenarios, significant differences were observed. Furthermore, a comparison of the hourly concentration contributions of ship emissions between port cities and inland cities within the same region revealed that inland cities were less affected by ship emissions. The main contributing factors to this disparity were identified as wind direction and wind speed.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Navíos , Material Particulado/análisis , Emisiones de Vehículos/análisis , Monitoreo del Ambiente , Contaminación del Aire/análisis , Contaminantes Atmosféricos/análisis , China
6.
Crit Rev Food Sci Nutr ; 63(10): 1437-1463, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34521280

RESUMEN

Food-derived antihypertensive peptides have attracted increasing attention in functional foods for health promotion, due to their high biological activity, low toxicity and easy metabolism in the human body. Angiotensin converting enzyme (ACE) is a key enzyme that causes the increase in blood pressure in mammals. However, few reviews have summarized the current understanding of ACE inhibitory peptides and their knowledge gaps. This paper focuses on the food origins and production methods of ACE inhibitory peptides. Compared with conventional methods, the advanced technologies and emerging bioinformatics approaches have recently been applied for efficient and targeted release of ACE inhibitory peptides from food proteins. Furthermore, the transport and underlying mechanisms of ACE inhibitory peptides are emphatically described. Molecular modeling and the Michaelis-Menten equation can provide information on how ACE inhibitors function. Finally, we discuss the structure-activity relationships and other bio-functional properties of ACE inhibitory peptides. Molecular weight, hydrophobic amino acid residues, charge, amino acid composition and sequence (especially at the C-terminal and N-terminal) have a significant influence on ACE inhibitory activity. Some studies are required to increase productivity, improve bioavailability of peptides, evaluate their bio-accessibility and efficiency on reducing blood pressure to provide a reference for the development and application of health products and auxiliary treatment drugs.


Asunto(s)
Péptidos , Peptidil-Dipeptidasa A , Animales , Humanos , Peptidil-Dipeptidasa A/metabolismo , Péptidos/farmacología , Péptidos/química , Antihipertensivos/farmacología , Relación Estructura-Actividad , Alimentos Funcionales , Mamíferos/metabolismo
7.
Front Psychol ; 13: 1002647, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36337571

RESUMEN

This article aims to answer the question that whether higher education would lead to happier life in China and tries to provide some explanations from the perspective of housing asset. Using data from four waves of China Household Finance Survey (CHFS), we find that higher education on average is significantly negatively correlated with people's happiness in urban China. Higher education tends to prevent people from achieving "extremely happy" lives; instead, it is more likely to lead to "acceptable" lives. Based on the realities of housing market in urban China, we find that housing asset plays the mediating role in the relationship between higher education and happiness. Specifically, years of schooling could evidently compress the years of being homeowners; as a result, highly educated people generally have more unpaid housing debts and bear more housing purchase costs due to the soaring housing prices. Meanwhile, higher education has negative effect on people's happiness in cities with relatively high housing prices, while this effect is insignificant in cities with relatively low housing prices. Moreover, the market-oriented housing reform that launched in 1998 has negative impact on highly educated people's happiness, since it has dramatically boosted housing prices and essentially changed housing distribution system for urban employees. Besides, we also find that Ph.D graduates are the relatively unhappiest people compared to bachelors or masters. Obviously, our findings have important policy implications for Chinese government to understand and resolve the "education-happiness paradox."

8.
Curr Res Food Sci ; 5: 2033-2044, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36337912

RESUMEN

Garlic saccharides have prebiotic activity, but the association between their function and structure is still poorly known. In present study, four different garlic saccharides were obtained from garlic polysaccharides (GPs) after acidolysis by ultrafiltration. Obtained GPs were constituted by different monosaccharides, among which fructose and glucose were the main components, while galactose was a major component of GPs-U6. All four saccharides were partly degraded by the simulated digestive system, and most could reach the large intestine to be utilized by the gut microbiota. Except for GPs-U6, the other three garlic saccharide fractions had good prebiotic activity in vitro and in vivo. Furthermore, GPs-U0.3 with lower molecular weight (Mw) showed better prebiotic activity, including promoting the production of short-chain fatty acids (SCFAs), increasing the abundance of beneficial bacteria such as Bifidobacterium, Lachnospiraceae NK4A136 group and Phoscolarctobacterium, and inhibiting the growth of potentially harmful bacteria. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis showed that GPs-U0.3 could reduce the risk of cancer and cardiovascular diseases. Overall, this findings of the present study revealed the digestive properties of GPs, as well as the potential association between their chemical structures and fermentation characteristics by gut microbiota. Thus, it can be stated that GPs-U0.3 can be used as potential prebiotics in functional foods, which provides a theoretical basis for the targeted preparation of functionalized garlic saccharides.

9.
Food Chem X ; 15: 100361, 2022 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-36211731

RESUMEN

This study explored the potential of garlic polysaccharides (GPs) as a carrier for synthesizing GP-Zn (II) complexes to supplement Zn. According to the response surface analysis, the optimal preparation conditions were: mass ratio of GPs to Zn2+ 1:0.21, temperature 53 °C, pH 5.9 and time 148.75 min, with the maximum chelation rate of 90.11%. The chelation of GPs and Zn2+ involved O-H/C-O/O-C-O groups, increased crystallinity and altered absorption peaks of circular dichroism spectra, with a higher thermal stability, particle size and negative zeta potential. Compared with inorganic zinc salts, supplementation of GP-Zn (II) complexes showed enhance zinc supplementation effects in Zn-deficient mice model: increased body weight, organ index and Zn (II) levels in serum and liver, enhanced Superoxidedismutase (SOD) activity and alkaline phosphatase activity, decreased NO content and Malondialdehyde (MDA) content and improved colon and testicular morphology. Therefore, GP-Zn (II) complex can be used as a potential zinc supplement for Zn-deficient individuals.

10.
Phytomedicine ; 106: 154414, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36057144

RESUMEN

BACKGROUND: Renal interstitial fibrosis (RIF) is the main pathological feature of end-stage renal disease (ESRD) caused by various chronic kidney diseases (CKD), and is closely related to renal dysfunction and patient prognosis. Salvianolic acid A (Sal A) and salvianolic acid B (Sal B), isolated from traditional Chinese medicine Salviae miltiorrhizae, have been confirmed to have anti-fibrotic effects on liver, cardiac and kidney. However, the precise molecular mechanism underlying the nephroprotective effects of Sal A and Sal B, and whether there is a difference between the two in RIF are still unclear. PURPOSE: This study investigated the pharmacological effects of Sal A and Sal B in RIF and explore the underlying mechanisms by in vivo and in vitro experiments. METHODS: The nephroprotective effects of Sal A, Sal B and Sal A+B were evaluated by assessing the parameters related to kidney function such as renal histology, renal function, urinary protein NAG, urinary ß2 microglobulin. In addition, RIF-related markers such as CTCF and Par3 were also detected. Thereafter, the related protein or gene levels of PDGF-C/PDGFR-α signaling pathways, apoptosis and endoplasmic reticulum stress (ERS) were determined by western blot, real-time PCR, flow cytometry or immunofluorescence staining. RESULTS: In vivo, the results showed that Sal A, Sal B and Sal A+B partially improved kidney dysfunction, increased the expression of Par-3 and reduced the expression of CTGF, PDGF-C and PDGFR-α. In vitro, the results also showed that Sal A, Sal B and Sal A+B reversed apoptosis and ERS in HSA-induced HK-2 cells via regulating PDGF-C/PDGFR-α signaling pathway. CONCLUSION: This article revealed a novel mechanism linking PDGF-C/PDGFR-α signaling pathway to RIF and suggested that Sal A, Sal B and Sal A+B were considered as potential therapeutic agents for the amelioration of RIF.


Asunto(s)
Enfermedades Renales , Transducción de Señal , Benzofuranos , Ácidos Cafeicos , Depsidos , Fibrosis , Humanos , Enfermedades Renales/tratamiento farmacológico , Lactatos , Linfocinas , Factor de Crecimiento Derivado de Plaquetas
11.
Endokrynol Pol ; 73(4): 725-735, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36059165

RESUMEN

INTRODUCTION: Yerba mate is widely consumed in South American countries and is gaining popularity around the world. Long-term consumption of yerba mate has been proven to have health-care functions and therapeutic effects on many diseases; however, its underlying mechanism has not been clearly elucidated. In this research, we explored the pharmacological mechanism of yerba mate through a network pharmacological approach. MATERIAL AND METHODS: The bioactive components of yerba mate were screened from published literature and the Traditional Chinese Medicine System Pharmacology Database (TCMSP), and the targets and related diseases were retrieved by TCMSP. Furthermore, the component-target-disease network an protein-protein interaction (PPI) network were constructed, and combined with gene ontology (GO) functional analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis to explore the pharmacological mechanism of yerba mate. RESULTS: As a result, 16 bioactive components of yerba mate were identified, which acted on 229 targets in total. Yerba mate can be used to treat 305 diseases, such as breast cancer, asthma, Alzheimer's disease, osteoarthritis, diabetes mellitus, atherosclerosis, and obesity. Protein kinase B (AKT1), signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 1 (MAPK1), transcription factor AP-1 (JUN), cellular tumour antigen (p53) TP53, tumour necrosis factor (TNF), transcription factor p65 (RELA), interleukin-6 (IL6), amyloid-beta precursor protein (APP), and vascular endothelial growth factor A (VEGFA) were identified as the key targets of yerba mate playing pharmacological roles. The signalling pathways identified by KEGG pathway enrichment analysis that were most closely related to the effects of yerba mate included pathways in cancer, fluid shear stress and atherosclerosis, and human cytomegalovirus infection. CONCLUSION: the results of our study preliminarily verify the basic pharmacological action and possible mechanism of yerba mate and provide a reference for the further development of its medicinal value.


Asunto(s)
Aterosclerosis , Ilex paraguariensis , Neoplasias , Humanos , Farmacología en Red , Factor A de Crecimiento Endotelial Vascular
12.
Brain Sci ; 12(9)2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36138897

RESUMEN

Emotion analysis has emerged as one of the most prominent study areas in the field of Brain Computer Interface (BCI) due to the critical role that the human brain plays in the creation of human emotions. In this study, a Multi-objective Immunogenetic Community Division Algorithm Based on Memetic Framework (MFMICD) was suggested to study different emotions from the perspective of brain networks. To improve convergence and accuracy, MFMICD incorporates the unique immunity operator based on the traditional genetic algorithm and combines it with the taboo search algorithm. Based on this approach, we examined how the structure of people's brain networks alters in response to different emotions using the electroencephalographic emotion database. The findings revealed that, in positive emotional states, more brain regions are engaged in emotion dominance, the information exchange between local modules is more frequent, and various emotions cause more varied patterns of brain area interactions than in negative brain states. A brief analysis of the connections between different emotions and brain regions shows that MFMICD is reliable in dividing emotional brain functional networks into communities.

13.
Phytomedicine ; 104: 154140, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35752081

RESUMEN

BACKGROUND: Rheumatoid arthritis (RA) is a long-term, progressive, and disabling autoimmune disease. It causes inflammation, swelling and pain in and around the joints and other body organs. Currently, no cure is available for RA. Clinical interventions can only relieve the condition, and at least 30% of RA patients do not respond to first­line therapy. This means that the development of more effective therapies against RA is urgently needed. OBJECTIVE: This study aimed to assess the anti-rheumatoid arthritis effect of chelerythrine (CLT) and explore its mechanism of action. METHODS: The cytotoxic effect of CLT on human rheumatoid arthritis fibroblast-like synoviocyte (HFLS-RA) cells and HFLS-normal cells were measured by MTT assay. The growth and migration of HFLS-RA cells were determined by colony-formation and wound-healing assay. The level of intracellular reactive oxygen species (ROS) was detected using the DCFH-DA reagent. Cell apoptosis was measured by flow cytometry, TUNEL staining, caspase 3 activity, as well as the activation of apoptosis related proteins. In addition, the levels of autophagy related markers such as LC3B and P62 were determined by immunocytochemistry and western blotting. Lastly, the anti-RA effect of CLT was evaluated in an Adjuvant-Induced Arthritis(AIA) rat model and the severity of arthritis was detected and quantified using macroscopic inspection and X­ray imaging. RESULTS: We discovered that treatment with CLT effectively inhibited the migration and colony-formation of the HFLS-RA cells and resulted in cell death. Moreover, CLT increased the intracellular level of ROS and the apoptotic rate of HFLS-RA by activating the AMPK/mTOR/ULK-1 signaling pathways. In vivo study showed CLT effectively ameliorated AIA in rats, protecting them from inflammation and bone damage. CONCLUSION: Our study shows CLT is an effective agent for ameliorating RA in vitro and in vivo by modulation of the AMPK/mTOR/ULK-1 signaling pathway. These findings indicate that CLT is a great potential candidate for development as a therapeutic agent for the prevention and treatment of RA.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Artritis Reumatoide , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Apoptosis , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Benzofenantridinas , Proliferación Celular , Humanos , Inflamación/complicaciones , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratas , Especies Reactivas de Oxígeno , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo
14.
J Phys Chem B ; 126(2): 545-551, 2022 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-34985884

RESUMEN

We study NaCl ion-pair dissociation in a dilute aqueous solution using computer simulations both for the full system with long-range Coulomb interactions and for a well-chosen reference system with short-range intermolecular interactions. Analyzing results using concepts from Local Molecular Field (LMF) theory and the recently proposed AI-based analysis tool "State predictive information bottleneck" (SPIB), we show that the system with short-range interactions can accurately reproduce the transition rate for the dissociation process, the dynamics for moving between the underlying metastable states, and the transition state ensemble. Contributions from long-range interactions can be largely neglected for these processes because long-range forces from the direct interionic Coulomb interactions are almost completely canceled (>90%) by those from solvent interactions over the length scale where the transition takes place. Thus, for this important monovalent ion-pair system, short-range forces alone are able to capture detailed consequences of the collective solvent motion, allowing the use of physically suggestive and computationally efficient short-range models for the dissociation event. We believe that the framework here should be applicable to disentangling mechanisms for more complex processes such as multivalent ion disassociation, where previous work has suggested that long-range contributions may be more important.


Asunto(s)
Cloruro de Sodio , Agua , Simulación por Computador , Solventes
15.
Front Nutr ; 8: 798450, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34957191

RESUMEN

Fructans and oligofructose are usually used as prebiotics without any limitation in functional food or food ingredients. The degree of polymerization (DP) of polysaccharides affects the utilization of probiotics. Garlic is rich in fructans. The objective of this study was to extract and purify polysaccharides from garlic, analyze its composition, hydrolyze them using HCl, and then evaluate the prebiotic potential of the garlic neutral polysaccharides (GPs) before and after hydrolysis. GPs were 6.57 × 103 Da with a composition of fructose and glucose at a ratio of 4:1. After acid hydrolysis, low molecular weight fraction in garlic oligofructose (GOs) may be eliminated through ultrafiltration. The content of oligosaccharides with an average DP < 10 increased from 15 to 75%. GPs and GOS had a stronger resistance to acid conditions in human stomach than fructooligosaccharide, and GOs showed better prebiotic properties on the growth of lactobacilli than GPs. This study evaluates the prebiotic potential of the garlic frutctans and oligosaccharides mixtures obtained by acid hydrolysis, which may be used as an ingredient in functional food and nutraceutical products.

16.
Sci Total Environ ; 796: 148908, 2021 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-34274672

RESUMEN

Renewable energy technological innovation (RETI) is an important way to reduce carbon emissions and achieve sustainable development. Exploring whether RETI is beneficial to the improvement of carbon emission efficiency and how the market environment affects the role of RETI on carbon emission efficiency is critical to the design of effective policies. Therefore, based on the data from 25 provinces in China from 2002 to 2015, the Tobit fixed-effect model and the panel threshold model are used to investigate the impact and the mechanism of RETI on total factor carbon performance index (TCPI) from a market perspective. The results show that: (1) RETI can effectively improve TCPI, but this effect is affected by market factors; (2) With the reduction of market segmentation or the increase of market potential, the improvement effect of RETI on TCPI is significantly enhanced; (3) The panel threshold model further verifies that the impact of RETI on TCPI has a significant single threshold effect in terms of market segmentation and market potential; (4) There is an inverted "U-shaped" relationship between market segmentation and TCPI, and the increase of market potential is conducive to the improvement of TCPI. This paper provides corresponding policy implications for China to achieve the dual goals of economic transformation and carbon emission reduction.


Asunto(s)
Carbono , Invenciones , Carbono/análisis , Dióxido de Carbono/análisis , China , Desarrollo Económico , Eficiencia , Energía Renovable
17.
J Cell Mol Med ; 25(15): 7500-7512, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34258872

RESUMEN

Clinical studies have shown that dapagliflozin can reduce cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM), but the exact mechanism is unclear. In this study, we used the molecular docking and network pharmacology methods to explore the potential mechanism of dapagliflozin on T2DM complicated with cardiovascular diseases (CVD). Dapagliflozin's potential targets were predicted via the Swiss Target Prediction platform. The pathogenic targets of T2DM and CVD were screened by the Online Mendelian Inheritance in Man (OMIM) and Gene Cards databases. The common targets of dapagliflozin, T2DM and CVD were used to establish a protein-protein interaction (PPI) network; the potential protein functional modules in the PPI network were found out by MCODE. Metascape tool was used for Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis. A potential protein functional module with the best score was obtained from the PPI network and 9 targets in the protein functional module all showed good binding properties when docking with dapagliflozin. The results of KEGG pathway enrichment analysis showed that the underlying mechanism mainly involved AGE-RAGE signalling pathway in diabetic complications, TNF signalling pathway and MAPK signalling pathway. Significantly, the MAPK signalling pathway was considered as the key pathway. In conclusion, we speculated that dapagliflozin played a therapeutic role in T2DM complicated with CVD mainly through MAPK signalling pathway. This study preliminarily reveals the possible mechanism of dapagliflozin in the treatment of T2DM complicated with CVD and provides a theoretical basis for future clinical research.


Asunto(s)
Compuestos de Bencidrilo/farmacología , Cardiomiopatías Diabéticas/tratamiento farmacológico , Glucósidos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Farmacología en Red , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Compuestos de Bencidrilo/uso terapéutico , Cardiomiopatías Diabéticas/metabolismo , Glucósidos/uso terapéutico , Humanos , Simulación del Acoplamiento Molecular , Mapeo de Interacción de Proteínas , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
18.
Aquat Toxicol ; 177: 190-7, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27289584

RESUMEN

Triadimefon (TDF) is a triazole-derivative fungicide that is detectable in the environment and target agricultural products, prompting concern over its risk to wildlife and human health. In our study, Nieuwkoop & Faber stage 51 Xenopus laevis tadpoles were exposed to different nominal concentrations TDF (0, 0.112, and 1.12mg/L) for 21 days while the tadpoles were undergoing pre-morphological development. Developmental condition, bioaccumulation and thyroid hormone levels, and mRNA expression of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were examined. Exposure to TDF caused a reduction in developmental rates on pre-metamorphosis of X. laevis. TDF exposure significantly decreased thyroid hormone (T4 and T3) concentrations, indicating thyroid endocrine disruption. The downregulation of thyroglobulin and upregulation of genes related to thyroid hormone metabolism (ugt1ab) might be responsible for the decreased thyroid hormone concentrations. Treatment with TDF also significantly increased mRNA expression of genes involved in thyroid-stimulating hormone as a compensatory mechanism response to decreased thyroid hormone concentrations. Gene expression and in silico ligand docking studies were combined to study the interaction between TDF and thyroid hormone receptor. Results showed that TDF could consequently affect the HPT axis signaling pathway. In addition, bioconcentration of TDF was observed in tadpoles, indicating the bioactivity of this compound. Taken together, the results suggest that TDF alters the HPT axis-related genes and changes thyroid hormone contents in X. laevis tadpoles, thus causing thyroid endocrine disruption and consequently delaying thyroid hormones-dependent metamorphic development.


Asunto(s)
Disruptores Endocrinos/toxicidad , Fungicidas Industriales/toxicidad , Glándula Tiroides/efectos de los fármacos , Hormonas Tiroideas/metabolismo , Triazoles/toxicidad , Contaminantes Químicos del Agua/toxicidad , Xenopus laevis/fisiología , Animales , Biomarcadores/metabolismo , Disruptores Endocrinos/metabolismo , Fungicidas Industriales/metabolismo , Larva/fisiología , Metamorfosis Biológica/efectos de los fármacos , Metamorfosis Biológica/fisiología , Glándula Tiroides/metabolismo , Pruebas de Toxicidad , Triazoles/metabolismo , Contaminantes Químicos del Agua/metabolismo
19.
Nanoscale ; 8(16): 8559-67, 2016 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-26693806

RESUMEN

The photoelectrochemical (PEC) performance of Cu2S nanowire arrays (NWAs) has been demonstrated to be greatly enhanced by dipping-assembly of carbon quantum dots (CQDs) on the surfaces of Cu2S NWAs. Experimental results show that the pristine Cu2S NWAs with higher aspect ratios exhibit better PEC performance due to the longer length scale for light absorption and the shorter length scale for minority carrier diffusion. Importantly, the CQDs decorated Cu2S NWAs exhibit remarkably enhanced photocurrent density, giving a photocurrent density of 1.05 mA cm(-2) at 0 V vs. NHE and an optimal photocathode efficiency of 0.148% under illumination of AM 1.5G (100 mW cm(-2)), which is 4 times higher than that of the pristine Cu2S NWAs. This can be attributed to the improved electron transfer and the energy-down-shift effect of CQDs. We believe that this inexpensive Cu2S/CQD photocathode with increased photocurrent density opens up new opportunities in PEC water splitting.

20.
J Tradit Chin Med ; 35(5): 564-70, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26591687

RESUMEN

OBJECTIVE: To investigate the effect of salvianolic acid A and C component molecules, which are involved in drug compatibility, on inflammatory cytokine expression that affects human chemokine ligand 5 (CCL5) and chemokine ligand 10 (CXCL10) levels in rats with unilateral ureteral obstruction (UUO). METHODS: Fifty Sprague Dawley rats were randomly divided into five groups: normal, model, salvianolic acid A, salvianolic acid C and salvianolic acid A and C groups. The normal group was used as the control, and the other groups of rats had a UUO model established. The control group had free access to food and water, and the other groups received the corresponding drugs for 2 weeks. After the last administration, urine ß2-microglobulin (ß 2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) levels were analyzed. After 24 h, all rats were sacrificed and the serum was analyzed for creatinine (Cr) and blood urea nitrogen (BUN) levels. Rat kidneys were removed, and CCL5 and CXCL10 inflammatory cytokine mRNA expression was measured using real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR). Kidney fibrosis was observed using hematoxylin-eosin (HE) staining and Masson trichrome staining. RESULTS: In the salvianolic acid A and salvianolic acid C treatment groups, serum Cr and urine NAG levels were significantly lower than in the model group (both P < 0.05). In all treatment groups, urine ß2-MG levels were significantly lower than in the model group (all P < 0.05). Compared with model group, the pathological changes and collagen deposition improved to varying degrees (both P < 0.05). CCL5 and CXCL10 mRNA expression decreased to different degrees compared with the model group (both P < 0.05). CONCLUSION: Salvianolic acid A and C are component molecules of drug compatibility, and they may protect renal function and improve tubular function and renal pathology to a certain degree in UUO. This improvement may be related to a reduction in inflammatory cytokines CCL5 and CXCL10 secretion in the UUO rat kidney.


Asunto(s)
Alquenos/administración & dosificación , Ácidos Cafeicos/administración & dosificación , Citocinas/inmunología , Medicamentos Herbarios Chinos/administración & dosificación , Lactatos/administración & dosificación , Polifenoles/administración & dosificación , Obstrucción Ureteral/tratamiento farmacológico , Animales , Quimiocina CCL5/genética , Quimiocina CCL5/inmunología , Quimiocina CXCL10/genética , Quimiocina CXCL10/inmunología , Citocinas/genética , Humanos , Masculino , Ratas , Obstrucción Ureteral/genética , Obstrucción Ureteral/inmunología
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