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1.
J Colloid Interface Sci ; 665: 1054-1064, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38579388

RESUMEN

The rational design of morphology and heterogeneous interfaces for non-precious metal electrocatalysts is crucial in electrochemical water decomposition. In this paper, a bifunctional electrocatalyst (Ni/NiFe LDH), which coupling nickel with nickel-iron layer double hydroxide (NiFe LDH), is synthesized on carbon cloth. At current density of 10 mA cm-2, the Ni/NiFe LDH exhibits a low hydrogen evolution reaction (HER) overpotential of only 36 mV due to the accelerated electrolyte penetration, which is caused by superhydrophilic interface. Moreover, an alkaline electrolyzer is formed and provide a current density of 10 mA cm-2 with a voltage of only 1.49 V. It is confirmed by the density functional theory (DFT) that electron from the Ni layer is transferred to NiFe LDH layer, redistributing the local electron density around the heterogeneous phase interface. Thus, the Gibbs free energy for hydrogen adsorption is optimized. This work provides a promising strategy for the rational regulation of electrons at heterogeneous interfaces and the synthesis of flexible electrocatalysts.

2.
Biomed Mater ; 19(3)2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38430567

RESUMEN

In our previous study, the pristine bilayer small-diameterin situtissue engineered vascular grafts (pTEVGs) were electrospun from a heparinized polycaprolactone (PCL45k) as an inner layer and a non-heparinized PCL80k as an outer layer in the thickness of about 131 µm and 202 µm, respectively. However, the hydrophilic enhancement of inner layer stemmed from the heparinization accelerated the degradation of grafts leading to the early formation of arterial aneurysms in a period of 3 months, severely hindering the perennial observation of the neo-tissue regeneration, host cell infiltration and graft remodeling in those implanted pTEVGs. Herein to address this drawback, the thickness of the outer layers was increased with PCL80k to around 268 µm, while the inner layer remained unchangeable. The thickened TEVGs named as tTEVGs were evaluated in six rabbits via a carotid artery interpositional model for a period of 9 months. All the animals kept alive and the grafts remained patent until explantation except for one whose one side of arterial blood vessels was occluded after an aneurysm occurred at 6 months. Although a significant degradation was observed in the implanted grafts at 9 month, the occurrence of aneurysms was obviously delayed compared to pTEVGs. The tissue stainings indicated that the endothelial cell remodeling was substantially completed by 3 months, while the regeneration of elastin and collagen remained smaller and unevenly distributed in comparison to autologous vessels. Additionally, the proliferation of macrophages and smooth muscle cells reached the maximum by 3 months. These tTEVGs possessing a heparinized inner layer and a thickened outer layer exhibited good patency and significantly delayed onset time of aneurysms.


Asunto(s)
Aneurisma , Poliésteres , Ingeniería de Tejidos , Animales , Conejos , Prótesis Vascular , Arterias Carótidas
3.
Cardiovasc Diabetol ; 23(1): 58, 2024 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-38336692

RESUMEN

AIM: Patients with diabetes mellitus have poor prognosis after myocardial ischemic injury. However, the mechanism is unclear and there are no related therapies. We aimed to identify regulators of diabetic myocardial ischemic injury. METHODS AND RESULTS: Mass spectrometry-based, non-targeted metabolomic approach was used to profile coronary sinus blood from diabetic and non-diabetic Bama-mini pigs at 0.5-h post coronary artery ligation. Six metabolites had a |log2 (Fold Change)|> 1.3. Among them, the most changed is arachidonic acid (AA), levels of which were 32 times lower in diabetic pigs than in non-diabetic pigs. The AA-derived products, PGI2 and 6-keto-PGF1α, were also significantly reduced. AA treatment of cultured cardiomyocytes protected against cell death by 30% at 48 h of high glucose and oxygen deprivation, which coincided with increased mitophagic activity (as indicated by increased LC3II/LC3I, decreased p62 and increased parkin & PINK1), improved mitochondrial renewal (upregulation of Drp1 and FIS1), reduced ROS generation and increased ATP production. These cardioprotective effects were abolished by PINK1(a crucial mitophagy protein) knockdown or the autophagy inhibitor 3-Methyladenine. The protective effect of AA was also inhibited by indomethacin and Cay10441, a prostacyclin receptor antagonist. Furthermore, diabetic Sprague Dawley rats were subjected to coronary ligation for 40 min and AA treatment (10 mg/day per animal gavaged) decreased myocardial infarct size, cell apoptosis index, inflammatory cytokines and improved heart function. Scanning electron microscopy showed more intact mitochondria in the border zone of infarcted myocardium in AA treated rats. Lastly, diabetic patients after myocardial infarction had lower plasma levels of AA and 6-keto-PGF1α and reduced cardiac ejection fraction, compared with non-diabetic patients after myocardial infarction. Plasma AA level was inversely correlated with fasting blood glucose. CONCLUSIONS: AA protects against diabetic ischemic myocardial damage by promoting mitochondrial autophagy and renewal, which is related to AA derived PGI2 signaling. AA may represent a new strategy to treat diabetic myocardial ischemic injury.


Asunto(s)
Diabetes Mellitus , Infarto del Miocardio , Humanos , Ratas , Animales , Porcinos , Ratas Sprague-Dawley , Ácido Araquidónico/farmacología , Porcinos Enanos/metabolismo , Infarto del Miocardio/metabolismo , Proteínas Quinasas/metabolismo , Apoptosis
4.
J Colloid Interface Sci ; 657: 219-228, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38039882

RESUMEN

The development of efficient bifunctional catalysts for overall water splitting is highly desirable and essential for the advancement of hydrogen technology. In this work, Mo-Ni(OH)2/FexNiy(OH)3x+2y with hierarchical nanotube structure is constructed on flexible carbon cloth (CC) through simple electrochemical deposition and hydrothermal method. The hollow tube-structure is in favor of both exposing active sites and enhancing mass transfer capability. Moreover, the doping of Mo can enhance the electronic conductivity of heterostructures. The interfacial interaction between amorphous and crystal can enhance effectively the charge transfer kinetics across the interface. Therefore, Mo-Ni(OH)2/FexNiy(OH)3x+2y can achieve a low overpotential of 57 mV for hydrogen evolution reaction (HER) and 229 mV for oxygen evolution reaction (OER) at 10 mA·cm-2. In addition, Mo-Ni(OH)2/FexNiy(OH)3x+2y needs a potential of only 1.54 V at 10 mA·cm-2 for overall water splitting, and retains for a long period of time (60 h) reliable. The work will provide a valuable approach to the construction of highly efficient electrocatalysts for overall water splitting.

5.
Sci Immunol ; 8(90): eabo5558, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38100544

RESUMEN

Regulatory T (Treg) cells contribute to immune homeostasis but suppress immune responses to cancer. Strategies to disrupt Treg cell-mediated cancer immunosuppression have been met with limited clinical success, but the underlying mechanisms for treatment failure are poorly understood. By modeling Treg cell-targeted immunotherapy in mice, we find that CD4+ Foxp3- conventional T (Tconv) cells acquire suppressive function upon depletion of Foxp3+ Treg cells, limiting therapeutic efficacy. Foxp3- Tconv cells within tumors adopt a Treg cell-like transcriptional profile upon ablation of Treg cells and acquire the ability to suppress T cell activation and proliferation ex vivo. Suppressive activity is enriched among CD4+ Tconv cells marked by expression of C-C motif receptor 8 (CCR8), which are found in mouse and human tumors. Upon Treg cell depletion, CCR8+ Tconv cells undergo systemic and intratumoral activation and expansion, and mediate IL-10-dependent suppression of antitumor immunity. Consequently, conditional deletion of Il10 within T cells augments antitumor immunity upon Treg cell depletion in mice, and antibody blockade of IL-10 signaling synergizes with Treg cell depletion to overcome treatment resistance. These findings reveal a secondary layer of immunosuppression by Tconv cells released upon therapeutic Treg cell depletion and suggest that broader consideration of suppressive function within the T cell lineage is required for development of effective Treg cell-targeted therapies.


Asunto(s)
Neoplasias , Linfocitos T Reguladores , Ratones , Humanos , Animales , Interleucina-10/metabolismo , Neoplasias/terapia , Neoplasias/metabolismo , Inmunoterapia , Factores de Transcripción Forkhead/metabolismo
6.
Nat Commun ; 14(1): 7740, 2023 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-38007572

RESUMEN

Gut microbiota plays a key role in insulin resistance (IR). Here we perform a case-control study of Chinese adults (ChiCTR2200065715) and identify that Parabacteroides distasonis is inversely correlated with IR. Treatment with P. distasonis improves IR, strengthens intestinal integrity, and reduces systemic inflammation in mice. We further demonstrate that P. distasonis-derived nicotinic acid (NA) is a vital bioactive molecule that fortifies intestinal barrier function via activating intestinal G-protein-coupled receptor 109a (GPR109a), leading to ameliorating IR. We also conduct a bioactive dietary fiber screening to induce P. distasonis growth. Dendrobium officinale polysaccharide (DOP) shows favorable growth-promoting effects on P. distasonis and protects against IR in mice simultaneously. Finally, the reduced P. distasonis and NA levels were also validated in another human type 2 diabetes mellitus cohort. These findings reveal the unique mechanisms of P. distasonis on IR and provide viable strategies for the treatment and prevention of IR by bioactive dietary fiber.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Animales , Humanos , Ratones , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fibras de la Dieta
7.
Langmuir ; 39(49): 18152-18160, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38019648

RESUMEN

Nickel-iron layered double hydroxide (NiFe LDH) is still one of the hot catalysts for electrochemical water decomposition applications, despite its drawbacks, such as intrinsic activity and poor stability. In this work, the NiFe LDH-D1 electrocatalyst with cationic vacancies is successfully prepared by alkaline etching of Zn ion-doped NiFe LDH. The tightly arranged flocculated nanosheet structure on its surface provided a large active area. The cationic vacancies formed by strong alkaline etching not only promote the conversion of active phases such as NiOOH but also strengthen the stability of the electrode and the binding ability with oxygen so that the material has excellent catalytic properties along with alkaline long-term stability. At a current density of 10 and 100 mA cm-2, NiFe LDH-D1 shows a small voltage of 1.56 and 1.94 V, and at a current density of 200 mA cm-2, it performs well in a 72 h electrochemical water decomposition stability test. The present work demonstrates a simple etching strategy for cation vacancy engineering and provides an example of the construction of efficient bifunctional electrocatalysts with long-term stability.

8.
Int J Biol Macromol ; 253(Pt 7): 127326, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37820907

RESUMEN

Dietary fiber is crucial for human health mainly due to its impact on gut microbiota structure and metabolites. This study aimed to investigate the impact of Dendrobium officinale polysaccharides (DOP) and two common fibers (ß-glucan and inulin) on the gut microbiome structure and metabolic profile in vitro. Fecal samples were obtained from 30 healthy volunteers, which were then individually subjected to fermentation with each type of fiber. The results revealed that all fibers were efficiently degraded by gut microbiota, with DOP exhibiting a slower fermentation rate compared to ß-glucan and inulin. The fermentation of all fibers led to a significant increase in the production of short-chain fatty acids (SCFAs) and a reduction in branched-chain fatty acids (BCFAs), sulfides, phenols, and indole. Moreover, the abundance of unclassified Enterobacteriaceae, which was positively correlated with sulfide, phenols, and indole levels, was significantly reduced by all fibers. Additionally, DOP specifically promoted the growth of Parabacteroides, while ß-glucan and inulin promoted the growth of Bifidobacterium and Faecalibacterium. Taken together, these findings enhance our understanding of the role of DOP, ß-glucan, and inulin in modulating gut microbiota and metabolites, where the fermentation with fecal bacteria from different volunteers could provide valuable insights for personalized therapeutic approaches.


Asunto(s)
Dendrobium , beta-Glucanos , Humanos , Prebióticos/análisis , Inulina/farmacología , Inulina/metabolismo , Fermentación , beta-Glucanos/farmacología , beta-Glucanos/metabolismo , Multiómica , Polisacáridos/farmacología , Polisacáridos/análisis , Fibras de la Dieta/metabolismo , Ácidos Grasos Volátiles/metabolismo , Heces/microbiología , Indoles , Fenoles/análisis
10.
Inorg Chem ; 62(26): 10490-10496, 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37340884

RESUMEN

Realizing a highly efficient oxygen evolution reaction (OER) process is of great significance for hydrogen energy development. The main challenge still lies in fabricating superior electrocatalysts with favorable performance. Constructing electrocatalysts with ingenious lattice modifications is a considerable way for the rational design of highly active catalytic centers. Here, theoretical calculations predict that the lattice incorporation of Se atoms can effectively enhance the reaction activity of OER with a decreased energy barrier for the rate-determining step. To obtain the corresponding desired electrocatalyst, the optimized lattice Se-modified CoOOH, with the ideal OER performance of low overpotential and stability, was delicately designed and fabricated by the electrochemical activation of the Co0.85Se precatalyst. X-ray absorption spectroscopy (XAS) demonstrates that lattice incorporation is more likely to be generated in Co0.85Se compared to CoSe2 and CoO precatalysts, which promoted the subsequent OER process. This work clarified the correlation between the precatalyst and the lattice-modified final catalyst in connection with electrochemical reconstruction.

11.
Front Nutr ; 10: 1149094, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37032784

RESUMEN

Objective: The present study aimed to investigate the lipid-lowering effects and mechanisms of fenugreek gum (FG), hawthorn pectin (HP), and burdock inulin (BI) on high-fat diet (HFD)-induced hyperlipidemic rats. Methods: In this study, high-fat diet (HFD) together with fat emulsion administration were used to establish hyperlipidemia model. The biochemical indices were assayed after administration of FG, HP, and BI. Their effects were evaluated by factor analysis. Alterations of gut microbiota and short chain fatty acids (SCFAs) in the cecal were assessed to illustrate the mechanism of lipid lowering. Results: The supplementation of FG, HP, and BI on HFD-fed rats decreased the levels of serum lipid and reduced the HFD-related liver and testicle damage. In the scatter plot of factor analysis, HP and BI were closer to normal fat diet (NFD) group in restoring the severity of hyperlipidemia, while FG and HP enhanced the excretion of cholesterol and bile acids (BAs). The levels of total SCFAs, especially butyric acid reduced by HFD were increased by HP. The ratio of Firmicutes to Bacteroidetes increased by HFD was reduced by HP and BI. FG, HP, and BI enriched intestinal probiotics, which were related to bile acid excretion or lipid-lowering. Conclusions: FG inhibited the absorption of cholesterol and enhanced the excretion of it, as well as increased the abundance of beneficial bacteria. While BI restored the imbalance of intestinal microbiota. HP enhanced the excretion of cholesterol and BAs, and restored the imbalance of intestinal microbiota. It was also utilized by intestinal microorganisms to yield SCFAs. This study suggested that FG, HP, and BI possessed the potential to be utilized as dietary supplements for obesity management.

12.
J Colloid Interface Sci ; 641: 277-288, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36934575

RESUMEN

It is crucial to create a bifunctional catalyst with high efficiency and low cost for electrochemical water splitting under alkaline and neutral pH conditions. This study investigated the in-situ creation of ultrafine Mo-NiS and NiFe LDH nanosheets as an effective and stable electrocatalyst with a three-dimensional (3D) flower-cluster hierarchical structure (Mo-NiS@NiFe LDH). The strong interfacial connection between Mo-NiS and NiFe LDH enhances the formation of metal higher chemical states in the material, optimizes the electronic structure, increases OH- adsorption capacity improves electron transfer/mass diffusion, and promotes O2/H2 gas release. As a result, at 10 mA cm-2, Mo-NiS@NiFe LDH/NF demonstrates the outstanding bifunctional electrocatalytic activity of just 107 mV (HER, hydrogen evolution reaction) and 184 mV (hydrogen evolution reaction) (OER, oxygen evolution reaction). The catalytic performance is remarkably stable after 72 h of continuous operation in 1 M KOH at high current densities (300 mA cm-2). More interestingly, in the overall water splitting system, the cell voltages for anode and cathode in both alkaline and neutral electrolytes for Mo-NiS@NiFe LDH/NF are only 1.54 V (alkaline) and 2.06 V (neutral) at 10 mA cm-2. These results demonstrated that the bifunctional electrocatalyst design concept is a viable solution for water splitting in both alkaline and neutral systems.

13.
Materials (Basel) ; 15(10)2022 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-35629551

RESUMEN

Traditional solid nanoparticle aerogels have been unable to meet the requirements of practical application due to their inherent brittleness and poor infrared shielding performance. Herein, combining vacuum impregnation and high-temperature pyrolysis, a novel micro/nano-composite fibrous aerogel was prepared via in situ synthesis of silicon carbide nanowires (SiC NWS) in mullite fiber (MF) preform. During this process, uniformly distributed SiC NWS in the MF preform serve as an enhancement phase and also act as an infrared shielding agent to reduce radiation heat transfer, which can significantly improve the mechanical properties of the mullite fiber/silicon carbide nanowire composite aerogels (MF/SiC NWS). The fabricated MF/SiC NWS exhibited excellent thermal stability (1400 °C), high compressive strength (~0.47 MPa), and outstanding infrared shielding performance (infrared transmittance reduced by ~70%). These superior properties make them appealing for their potential in practical application as high-temperature thermal insulators.

14.
Carbohydr Polym ; 286: 119271, 2022 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-35337525

RESUMEN

Xylan as the second most abundant indigestible carbohydrate found in nature attracts great interests of researchers, nutritionist and consumers due to its various health benefits. However, accumulated studies indicate the interactions with gut microbiota greatly affect these benefits, and significant progress has been made over the past few years to understand how microbes utilize xylan at gene level. In this review, we focused on gut xylanolytic microbes and xylan's physico-chemical features, summarized the xylanases needed for complete xylan decomposition, their substrate specificity and the presence in gut microbes, as well as microbial degradation of xylan in single strain mode and cooperation mode. Xylan utilization system were discussed with different phyla. Furthermore, the implications on intestinal homeostasis and metabolic response were reviewed with clinical effects emphasized, and highlight is placed on specific gut microbes and the complexity of xylan structure to provide a clue for the inconsistent results in human studies. CHEMICAL COMPOUNDS: xylan; arabinoxylan, glucuronoxylans; glucuronoarabinoxylans; xylo-oligosaccharides; arabinoxylo-oligosaccharides.


Asunto(s)
Microbioma Gastrointestinal , Xilanos , Homeostasis , Humanos , Oligosacáridos/metabolismo , Especificidad por Sustrato , Xilanos/química
15.
ACS Appl Mater Interfaces ; 13(19): 22765-22773, 2021 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-33947180

RESUMEN

Nanofibrous aerogels constructed by ceramic fiber components (CNFAs) feature lightweight, compressibility, and high-temperature resistance, which are superior to brittle ceramic aerogels assembled from nanoparticles. Up to now, in order to obtain CNFAs with stable framework and multifunctionality such as hydrophobicity and gas absorption, it is necessary to perform binding and surface modification processes, respectively. However, the microstructure as well as properties of CNFAs are deteriorated by the direct addition of binders and modifiers. To tackle these problems, we introduced a unique low-temperature (100 °C) chemical vapor deposition method (LTCVD) to achieve the cross-linking and hydrophobization of Si3N4 CNFA in only one step. More importantly, during the LTCVD process, SiOx coatings and nanowire arrays were in situ formed via vapor-solid (VS) and vapor-liquid-solid (VLS) mechanisms on the surface and intersection of Si3N4 nanofibers, which cemented the aerogel framework, endowed it with hydrophobicity, and improved its oxidation resistance at high temperature. Compared to most of its counterparts, the Si3N4/SiOx CNFA exhibited better mechanical properties, higher capability of oil/water separation (33-76 g·g-1), lower thermal conductivity (0.0157 W/m·K-1), and superior structural stability in a wide temperature range of -196-1200 °C. This work not only presents an excellent Si3N4/SiOx CNFA for the first time but also provides fresh insights for the exquisite preparation strategy of CNFAs.

16.
Environ Sci Pollut Res Int ; 28(33): 46020-46034, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33884555

RESUMEN

Environmental values are key factors influencing consumers' purchase intentions and improving consumers' willingness to buy green products is crucial for the sustainable development of ecological environments. Based on environmental values and green product trust, the present study classified environmental values into egoistic, altruistic, and biospheric values and discussed the influence mechanisms of environmental values on green product purchase intention. On this basis, the study verified the mediating role of environmental concern and the moderating role of green trust on the relationship between environmental concern and green product purchase intention. The research results revealed that (1) altruistic and biospheric values had a significant positive impact on green product purchase intention, while egoistic values had a negative impact on green product purchase intention; (2) environmental concern had a partial mediating effect on the relationship between environmental values and green product purchase intention; and (3) green trust had a positive moderating effect on the relationship between environmental concern and green product purchase intention. The present study expanded on the existing research on green product purchase intention driven by values, and the conclusions provided theoretical guidance for green marketing by enterprises and the establishment of customers' trust in the green attributes of products.


Asunto(s)
Intención , Confianza , Comportamiento del Consumidor , Ambiente , Encuestas y Cuestionarios
17.
Artículo en Inglés | MEDLINE | ID: mdl-33572419

RESUMEN

The issue of environmental protection and sustainable development is a key research focus across multiple fields. Employee green behavior is considered to be an important micro-activity to address this. Researchers in the field of organizational behavior and sustainable development have been focusing on the influencing factors of employee green behavior. However, few have explored the beneficial effects of employee green behavior on behavioral implementers. The objective of this study is to investigate the relationships among employee green behavior, self-esteem, perceived organizational support for employee environmental efforts, and employee well-being, and to explore a new dimension of employee green behavior. We empirically examined the underlying framework by conducting two surveys to collect data from 900 employees working in manufacturing, construction, and the service industry in China. We performed multilevel path analysis using SPSS and AMOS software, and confirmed that employee green behavior includes four dimensions: green learning, individual practice, influencing others, and organizational voices. Further, employee green behavior has a significant positive impact on self-esteem, which in turn is converted into employee well-being. Finally, perceived organizational support for employee environmental efforts not only positively moderated the relationship between employee green behavior and self-esteem, but was also confirmed as a moderated mediation model. This study enriches the current literature on the measurement framework and variables of employee green behavior.


Asunto(s)
Organizaciones , Conducta Social , China , Conservación de los Recursos Naturales , Humanos , Industrias
18.
Ann Transl Med ; 8(21): 1388, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33313133

RESUMEN

BACKGROUND: The objective of this study was to investigate the effects of glycaemic variability (GV) on intimal hyperplasia and plaque stability after coronary stenting via autophagy-mediated G3BP1/NLRP3 inflammasome signalling. METHODS: In the clinical study, between July 2017 and December 2017, 95 patients with acute myocardial infarction (AMI) and diabetes mellitus (DM) comorbidity received stent implantation. The patients were followed up for 2 years after discharge. The patients were divided into a low-GV (n=61) and high-GV (n=34) group, and the incidence of recurrent AMI was measured. In the animal study, thirteen pigs were divided into a sham (n=3), low-GV DM (n=5) and high-GV DM group (n=5). Intima samples were analysed by optical coherence tomography 22 weeks after coronary stenting. Becn1, LC3B, p62, G3BP1 and NLRP3 protein levels in the intima were examined by western blot. In vitro experiments with THP-1 cells were also conducted. RESULTS: In the high-GV group, patients exhibited a higher recurrent AMI, greater neointimal thickness, increased p62 and NLRP3 expression, and decreased Becn1, LC3B and G3BP1 expression compared with the low-GV group (P<0.05). The effects of high GV could be abolished by rapamycin but were aggravated by 3-methyladenine. CONCLUSIONS: GV might impact the intimal hyperplasia and plaque stability via autophagy-mediated G3BP1/NLRP3 inflammasome signalling. GV and the autophagy-mediated G3BP1/NLRP3 inflammasome may be promising targets for the treatment of coronary heart disease.

19.
Front Cell Dev Biol ; 8: 318, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32509779

RESUMEN

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is considered to be a promising antitumor drug because of its selective proapoptotic properties on tumor cells. However, the clinical application of TRAIL is until now limited because of the resistance of several cancer cells, which can occur at various levels in the TRAIL signaling pathway. The role of decoy receptors that can side-track TRAIL, thereby preventing the formation of an activated death receptor, has been extensively studied. In this study, we have focused on extracellular vesicles (EVs) that are known to play a role in cell-to-cell communication and that can be released by donor cells into the medium transferring their components to recipient cells. TRAIL-induced apoptotic signaling is triggered upon the binding of two death receptors, DR4 and DR5. Here, we found that DR5 but not DR4 is present in the conditioned medium (CM)-derived from various cancer cells. Moreover, we observed that DR5 was exposed on EVs and can act as "decoy receptor" for binding to TRAIL. This results in a strongly reduced number of apoptotic cells upon treatment with DR5-specific TRAIL variant DHER in CM. This reduction happened with EVs containing either the long or short isoform of DR5. Taken together, we demonstrated that colon rectal tumor cells can secrete DR5-coated EVs, and this can cause TRAIL resistance. This is to our knowledge a novel finding and provides new insights into understanding TRAIL sensitivity.

20.
Front Pharmacol ; 11: 372, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32273846

RESUMEN

OBJECTIVE: This study aimed to explore whether treatment with the glucagon-like peptide-1 (GLP-1) analog liraglutide reduces intimal hyperplasia after coronary stent implantation via regulation of glycemic variability, the NLRP3 inflammasome, and IL-10 in diabetic swine. METHODS: Fifteen pigs were divided into a diabetes mellitus (DM) group (n = 6), a DM + liraglutide treatment group (L group) (n = 6) and a sham group (n = 3). A total of 24 everolimus-eluting stents were implanted in the left anterior descending and right coronary arteries at 3 weeks. A novel continuous glucose monitoring system (GMS) was used for 2 weeks. The means and standard deviations (SDs) were measured and calculated by the GMS. At 22 weeks, the lumen area (LA), neointimal thickness (NIT), neointimal area (NIA), and percent area stenosis (%AS) were analyzed by optical coherence tomography. Plasma tumor necrosis factor-α, interleukin-6, and interleukin-10 were assayed by ELISA. The intima protein expression levels of NLRP3, interleukin-1ß, interleukin-18 and interleukin-10 were examined using Western blot analysis. Histology was used to evaluate the healing response. In an in vitro study, THP-1 cells were divided into control, high glucose (HG), HG + liraglutide, and HG + liraglutide + Exe(9-39) (a GLP-1 receptor inhibitor) groups. RESULTS: The L group had a lower SD, NIT, NIA, and %AS; a larger LA; reduced inflammation and injury scores; lower expression levels of tumor necrosis factor-α, interleukin-6, NLRP3, interleukin-1ß, and interleukin-18; and higher expression of interleukin-10 compared with those of the DM group (p < 0.05). In the in vitro study, similar results were obtained in the HG + liraglutide group, and Exe(9-39) abolished the effect of liraglutide (p < 0.05). CONCLUSIONS: Liraglutide treatment reduces intimal hyperplasia after stent implantation via regulation of glycemic variability, the NLRP3 inflammasome, and IL-10 in diabetic pigs in a GLP-1 receptor-dependent manner. Reducing the inflammation induced by glycemic variability may be one of the cardioprotective mechanisms of liraglutide.

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