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2.
J Cardiothorac Surg ; 15(1): 126, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503570

RESUMO

BACKGROUND: Owing to the high patency, the use of the left internal mammary artery (LIMA) for left anterior descending artery (LAD) grafting has been a cornerstone of coronary artery bypass grafting surgery (CABG). However, for some patients whose LIMA cannot be used, surgeons have to choose other conduit materials to revascularize the LAD. The purpose of this study was to explore the differences in different conduit materials used for LAD in terms of parameters measured by transit-time flow measurement (TTFM) and the early graft patency detected by computed tomography angiography. METHODS: We retrospectively collected the data of 410 patients who underwent isolated primary OPCAB with intraoperative TTFM data. According to the strategy of the LAD revascularization, 410 patients were assigned to three groups: a left internal mammal artery (LIMA) group (n = 333), a right IMA (RIMA) group (n = 34) and a great saphenous vein (SVG) group (n = 43). The baseline and perioperative blood parameters were compared for the three groups, as well as the early graft patency rates. RESULTS: Compared with the LIMA-LAD group, the SVG-LAD group had a significantly higher mean graft flow volume (MGF) (37.15 ± 23.29 vs 29.71 ± 20.94 ml/min, P = 0.036), however, had a lower value of pulse index (PI) (2.07 ± 0.62 vs 2.65 ± 1.01, P<0.001). There was no significant difference between the two groups in terms of DF (P>0.05). Compared with the RIMA-LAD group, the SVG-LAD group just had a lower value of PI (2.07 ± 0.62 vs 2.56 ± 0.96, P = 0.029). However, there was no significant difference between the two groups in terms of MGF and DF (P>0.05). Compared with the LIMA-LAD group, the RIMA-LAD group had a slightly lower value of DF (70.76 ± 11.87 vs 74.06 ± 7.09, P = 0.018), while there was no difference in terms of MGF and PI between the two groups (P>0.05). The patency rate of the LIMA-LAD group was 98.72% (309/313), that of RIMA-LAD group was 97.06% (33/34), and that of SVG-LAD group was 100%. There was no difference among the three groups in patency rate (P = 0.405). CONCLUSIONS: SVG-LAD has a higher intraoperative MGF and a lower value of the PI than both LIMA-LAD and RIMA-LAD. RIMA has a higher preoperative blood flow and a lower value of the PI than LIMA; however, there were no significant difference between RIMA grafted to LAD and LIMA grafted to LAD in terms of MGF, PI and DF. In situ skeletonized RIMA did not increase blood flow compared to pedicled LIMA.

3.
Small ; : e2001858, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32519440

RESUMO

The recent ban of titanium dioxide (TiO2 ) as a food additive (E171) in France intensified the controversy on safety of foodborne-TiO2 nanoparticles (NPs). This study determines the biological effects of TiO2 NPs and TiO2 (E171) in obese and non-obese mice. Oral consumption (0.1 wt% in diet for 8 weeks) of TiO2 (E171, 112 nm) and TiO2 NPs (33 nm) does not cause severe toxicity in mice, but significantly alters composition of gut microbiota, for example, increased abundance of Firmicutes phylum and decreased abundance of Bacteroidetes phylum and Bifidobacterium and Lactobacillus genera, which are accompanied by decreased cecal levels of short-chain fatty acids. Both TiO2 (E171) and TiO2 NPs increase abundance of pro-inflammatory immune cells and cytokines in the colonic mucosa, indicating an inflammatory state. Importantly, TiO2 NPs cause stronger colonic inflammation than TiO2 (E171), and obese mice are more susceptible to the effects. A microbiota transplant study demonstrates that altered fecal microbiota by TiO2 NPs directly mediate inflammatory responses in the mouse colon. Furthermore, proteomic analysis shows that TiO2 NPs cause more alterations in multiple pathways in the liver and colon of obese mice than non-obese mice. This study provides important information on the health effects of foodborne inorganic nanoparticles.

4.
PLoS One ; 15(6): e0234046, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32585680

RESUMO

The recent ban of the antimicrobial compound triclosan from use in consumer soaps followed research that showcased the risk it poses to the environment and to human health. Triclosan has been found in human plasma, urine and milk, demonstrating that it is present in human tissues. Previous work has also demonstrated that consumption of triclosan disrupts the gut microbial community of mice and zebrafish. Due to the widespread use of triclosan and ubiquity in the environment, it is imperative to understand the impact this chemical has on the human body and its symbiotic resident microbes. To that end, this study is the first to explore how triclosan impacts the human gut microbial community in vitro both during and after treatment. Through our in vitro system simulating three regions of the human gut; the ascending colon, transverse colon, and descending colon regions, we found that treatment with triclosan significantly impacted the community structure in terms of reduced population, diversity, and metabolite production, most notably in the ascending colon region. Given a 2 week recovery period, most of the population levels, community structure, and diversity levels were recovered for all colon regions. Our results demonstrate that the human gut microbial community diversity and population size is significantly impacted by triclosan at a high dose in vitro, and that the community is recoverable within this system.

5.
Neural Netw ; 129: 193-202, 2020 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-32544866

RESUMO

The p-norm finite-time stabilization (FTS) issue of a class of state-based switched inertial chaotic neural networks (SBSCINNs) with distributed time-varying delays is investigated. By using a suitable variable transformation, such second-order SBSCINNs are turned into the first-order differential equations. Then some novel criteria are obtained to stabilize SBSCINNs in a finite time based on the theory of finite-time control and non-smooth analysis together with designing two proper delay-dependent feedback controllers. Besides, the settling time of FTS is also estimated and discussed. Finally, the validity and practicability of the deduced theoretical results are verified by examples and applications.

6.
J Agric Food Chem ; 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32594738

RESUMO

Dietary intake of linoleic acid (LA, 18:2ω-6) has risen dramatically in recent decades. Previous studies have suggested a high intake of LA could increase tissue concentrations of proinflammatory and protumorigenic ω-6-series eicosanoid metabolites, increasing risks of inflammation and associated diseases. However, the effects of a LA-rich diet on in vivo profiles of eicosanoids and development of inflammatory diseases are understudied. Here, we treated spontaneous colitis-prone (Il-10-/-) mice with a control diet (∼3 Cal% LA) or a LA-rich diet (∼9 Cal% LA) for 18 weeks and analyzed the effects of the LA-rich diet on profiles of eicosanoids and development of colitis. We found that treatment with the LA-rich diet increased the tissue level of LA: the liver levels of LA were 5.8 ± 0.6% in the control diet-treated mice versus 11.7 ± 0.7% in the LA-rich diet-treated mice (P < 0.01). The plasma concentrations of a series of LA-derived metabolites, including 9-hydroxyoctadecadienoic acid (HODE), 9,10-dihydroxyoctadecenoic acid (DiHOME), 12,13-DiHOME, and 13-HODE were significantly increased by treatment with the LA-rich diet (P < 0.05). However, the LA-rich diet had little effect on the severity of colitis in the treated Il-10-/- mice. These results suggest a limited role of increased consumption of dietary LA on promoting colitis in the Il-10-/- model.

7.
J Phys Chem Lett ; : 5625-5631, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32584580

RESUMO

The metal halide perovskite CsPbBr3 bulk crystals present electrical and optical performance discrepancy since the grown-in defects. Here, we first report the well-defined secondary phase (SP) particles of CsPb2Br5 with polyhedral morphology in CsPbBr3 crystals grown by the vertical Bridgman method. The resulting polyhedral morphology of CsPb2Br5 particles associated with the trapping of PbBr2-rich droplets have been discussed on the basis of the "matrix-controlled" growth. Two morphological evolution paths are proposed, which result in a regular cube SP particle comprised by {100} facets for the final equilibrium. Furthermore, the wafer with superior optical transmittance exhibits a higher photoelectric response on-off ratio (∼2000) in contrast to ∼80 for the wafer with high density SP particles. The corresponding hole mobility (µh) is calculated with the values 289.99 and 26.91 cm-2·V-1·s-1, respectively. The variation of µh is attributed to the carrier transport trajectory affected by SP induced trapping defects and the weak combination.

8.
J Chem Phys ; 152(23): 234308, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32571069

RESUMO

A recent high resolution photoabsorption study revealed that the Rydberg W1Π(ν = 1) level of carbon monoxide (CO) is perturbed by the valence E″1Π(ν = 0) level, and the predissociation linewidth shows drastic variation at the crossing point due to the interference effect [Heays et al., J. Chem. Phys. 141(14), 144311 (2014)]. Here, we reinvestigate the Rydberg W1Π(ν = 1) level for the three CO isotopologues, 12C16O, 13C16O, and 12C18O, by measuring the rotationally dependent photodissociation branching ratios. The C+ ion photofragment spectra obtained here reproduce the recent high resolution photoabsorption spectra very well, including the presence of the valence E″1Π(ν = 0) level. The photodissociation branching ratios into the spin-forbidden channel C(1D) + O(3P) show sudden increases at the crossing point between the W1Π(ν = 1) and E″1Π(ν = 0) levels, which is in perfect accordance with the drastic variation of the linewidth observed in the recent spectroscopic study. Further analysis reveals that the partial predissociation rate into the lowest channel C(3P) + O(3P) shows a much more prominent decrease at the crossing point, which is caused by the interference effect between the W1Π(ν = 1) and E″1Π(ν = 0) levels, than that into the spin-forbidden channel C(1D) + O(3P), and this is the reason of the sudden increase as observed in the photodissociation branching ratio measurements. We hope that the current experimental investigation will stimulate further theoretical studies, which could thoroughly address all the experimental observations in a quantitative way.

9.
Bioresour Technol ; 310: 123463, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32387978

RESUMO

This study investigated the effects of operational temperature on cathodic performances of five bioelectrochemical reactors operated in parallel at 25-7 °C, and on the biofilm microbial community at the end of tests. Compared with the anodic biofilm, the cathodic biofilm has high stability subjected to temperature shift in the aspect of cathode potentials, redox activities, and internal resistances. The maximum power density was reduced linearly with temperature at a rate of 1.1 W/m3 °C. The bacterial community at 7 °C cathodic biofilm was dominated by four phyla including Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes with percentages of 81.7%, 8.9%, 3.3% and 1.3%, and the predominant genera were affiliated with Azoarcus sp. (56.45%), Acidovorax sp. (7.32%), Rhodococcus sp. (5.02%), Halomonas sp. (2.6%). The most vigorous metabolism of cathodic biofilm at low temperature was proposed to be biosynthesis and energy generation. The cathodic biofilm has resilient microbial community to temperature challenges.


Assuntos
Fontes de Energia Bioelétrica , Bactérias , Biofilmes , Eletrodos , Temperatura
10.
Drug Des Devel Ther ; 14: 855-866, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32161445

RESUMO

Objective: The present study aimed to assess the effect of curcumin (Cur) on carotid artery restenosis following carotid endarterectomy (CEA) and its associated mechanism in vivo and in vitro. Methods: Ang II was used to induce excessive proliferation of rabbit aortic smooth muscle cells (CCC-SMC-1) in order to establish a hemadostenosis cell model. Similarly, the animal model of carotid artery restenosis was established by carotid artery gas drying injury combined with high-fat feed prior to CEA. CCC-SMC-1 cells and animals were treated by Cur and its effects on neointimal hyperplasia, inflammation and oxidative stress were detected and observed. The proteins that were associated with the Raf/MEK/ERK pathway were detected in cells and rabbit carotid artery tissues. Results: Cur inhibited the proliferation of smooth muscle cells and neointimal formation and reduced the inflammation and oxidative stress indices. Concomitantly, Cur reduced the phosphorylation of the Raf/MEK/ERK pathway proteins. Conclusion: Cur could inhibit carotid restenosis following CEA by inhibiting the activation of the Raf/MEK/ERK pathway.

11.
J Agric Food Chem ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32159344

RESUMO

Substantial studies have shown that ω-3 polyunsaturated fatty acids (PUFAs) have various health-promoting effects; however, there are inconsistent results from animal studies that showed that ω-3 PUFAs have no effects or even detrimental effects. Emerging research suggests that oxidized ω-3 PUFAs have different effects compared to unoxidized ω-3 PUFAs; therefore, lipid oxidation of dietary ω-3 PUFAs could contribute to the mixed results of ω-3 PUFAs in animal studies. Here, we prepared an AIN-93G-based, semi-purified, powder diet, which is one of the most commonly used rodent diets in animal studies, to study the oxidative stability of fortified ω-3 PUFAs in animal feed. We found that lowering the storage temperature or the addition of a certain antioxidant, notably tert-butylhydroquinone (TBHQ), helps to stabilize ω-3 PUFAs and suppress ω-3 oxidation in the animal diet, while reducing the level of oxygen in the storage atmosphere is not very effective. The addition of 50 ppm of TBHQ in the diet inhibited 99.5 ± 0.1% formation of primary oxidation products and inhibited 96.1 ± 0.7% formation of secondary oxidation products, after 10 days of storage of the prepared diet at a typical animal-feeding experiment condition. Overall, our results highlight that ω-3 PUFAs are highly prone to lipid oxidation in a typical animal-feeding experiment, emphasizing the critical importance to stabilize ω-3 PUFAs in animal studies.

12.
Proc Natl Acad Sci U S A ; 117(15): 8431-8436, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32220957

RESUMO

Intestinal barrier dysfunction, which leads to translocation of bacteria or toxic bacterial products from the gut into bloodstream and results in systemic inflammation, is a key pathogenic factor in many human diseases. However, the molecular mechanisms leading to intestinal barrier defects are not well understood, and there are currently no available therapeutic approaches to target intestinal barrier function. Here we show that soluble epoxide hydrolase (sEH) is an endogenous regulator of obesity-induced intestinal barrier dysfunction. We find that sEH is overexpressed in the colons of obese mice. In addition, pharmacologic inhibition or genetic ablation of sEH abolishes obesity-induced gut leakage, translocation of endotoxin lipopolysaccharide or bacteria, and bacterial invasion-induced adipose inflammation. Furthermore, systematic treatment with sEH-produced lipid metabolites, dihydroxyeicosatrienoic acids, induces bacterial translocation and colonic inflammation in mice. The actions of sEH are mediated by gut bacteria-dependent mechanisms, since inhibition or genetic ablation of sEH fails to attenuate obesity-induced gut leakage and adipose inflammation in mice lacking gut bacteria. Overall, these results support that sEH is a potential therapeutic target for obesity-induced intestinal barrier dysfunction, and that sEH inhibitors, which have been evaluated in human clinical trials targeting other human disorders, could be promising agents for prevention and/or treatment.

13.
Nurs Health Sci ; 22(2): 300-308, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32115837

RESUMO

Within Chinese culture, one way that family and friends demonstrate that they care about one-another is by making body-related comments. How such comments are experienced by young women, in particular, including how they relate to their psychological disposition and/or use of unhealthy weight control behaviors, is unknown. The purposes of this study were to understand the frequency and type of body-related comments Chinese college women received, from whom, and their associations with body mass index (BMI), body satisfaction, body change motivations, and unhealthy weight control behaviors. Women from a comprehensive university in Southwest China (N = 236) participated in this cross-sectional study. Results showed that female Chinese college students received body-related comments most frequently from their friends, followed by parents, and romantic partners. While the frequency of receiving body-related comments was not associated with BMI, higher frequencies were associated with stronger motivation to lose weight/fat and to practice unhealthy weight control behaviors. Additionally, positive body-related comments from romantic partners were associated with higher motivation to gain weight/muscle and/or to maintain weight. Furthermore, positive body-related comments from friends were associated with higher body satisfaction. Educational programs are needed to help female Chinese college students and members of their social networks recognize and understand the potential impact associated with giving body-related comments. Screening protocols for unhealthy weight control behaviors and appropriate counseling services should also be developed and made available.

14.
Clin Chim Acta ; 504: 155-162, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32059947

RESUMO

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease caused by deficiency or dysfunction of C1 esterase inhibitor (C1-INH). Timely and accurate diagnosis is an ongoing challenge. Measurement of plasma C1-INH activity is currently the critical standard test. We describe a novel and highly robust point-of-care assay to quantify C1-INH activity in dried blood spot (DBS). METHODS: C1-INH was extracted from 3 mm punches of DBS samples and incubated with excess amount of C1 esterase (C1s). The mixture was subsequentially incubated with C1s substrate, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantitation of the enzyme reaction product. RESULTS: The assay was validated within a quantification range from 100 to 1500 mU/mL. The intra-day precision and accuracy ranged from 4.0% to 11.6% and -11.1% to -2.1%, and the inter-day precision and accuracy were 8.1-13.1% and -10.3% to 0.9%, respectively. Normal C1-INH activity (n = 103) ranged from 311 to 1090 mU/mL, whereas 23 out of 24 HAE patients exhibited C1-INH activity lower than 100 mU/mL. CONCLUSION: DBS specimen collection for measurement of functional C1-INH activity in a physician's office is straightforward and not limited by logistic considerations and therefore, appropriate for the diagnosis of HAE in high throughput diagnostic laboratories.

15.
Biomed Pharmacother ; 125: 109768, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32106387

RESUMO

Malignant glioma is a highly aggressive cancer, known as one of the most dangerous types of primary brain tumor occurring in the central nervous system (CNS). Septin 9 (SEPT9) has been involved in tumor growth. However, its exact roles in regulating glioma development have not been fully understood. In the present study, we found that SEPT9 expression levels were markedly up-regulated in glioma tissues and cell lines. High expression of SEPT9 predicted a poor overall survival in patients with glioma. SEPT9 knockdown significantly reduced the proliferation, migration and invasion of glioma cells. Moreover, epithelial-mesenchymal transition (EMT) markers, including N-cadherin, matrix metalloproteinase-9 (MMP9), Vimentin and Twist, were significantly reduced by SEPT9 knockdown; however, the expression of E-cadherin was elevated by SEPT9 silence. This EMT process in glioma cells was dependent on the expression transforming growth factor (TGF)-ß1. In addition, the clinical analysis suggested that SEPT9 gene expression had a positive correlation with TGF-ß1 in patients with primary glioma at different grades. Furthermore, knockdown of SEPT9 significantly reduced the glioma progression in vivo. The anti-metastasis regulated by the knockdown of SEPT9 was further confirmed in mouse model, as evidenced by the reduced number of lung metastatic nodules. Our results supported that reducing SEPT9 expression could inhibit glioma progression through the suppression of EMT induced by TGF-ß1.

16.
Food Funct ; 11(2): 1684-1691, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32037431

RESUMO

Previous studies have shown that curcumin, a bioactive dietary compound with a thiol-reactive α,ß-unsaturated carbonyl moiety, can covalently modify protein thiols. However, most of the previous studies were performed in cultured cells or cell-free enzyme systems, and so it remains unknown whether curcumin could covalently modify proteins after oral administration in vivo. Using click chemistry-based fluorescence imaging, here we show that oral administration of dialkyne-curcumin (Di-Cur), a "click" probe mimicking curcumin, results in covalent modifications of cellular proteins in colon and liver tissues, but not in other tissues, in mice. This result suggests that oral administration of curcumin leads to the formation of the curcumin-protein complex in a tissue-specific manner, which could contribute to the biological effects and/or pharmacokinetics of curcumin. Further studies to elucidate the identities of curcumin-binding proteins could greatly help us to better understand the molecular mechanisms of curcumin, and develop novel strategies for disease prevention.

17.
Cell Cycle ; 19(5): 551-566, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32054404

RESUMO

Recently, the role of microRNAs (miRs) in human diseases has been verified. This study was determined to explore the protective effects of microRNA-26a (miR-26a) in steroid-induced osteonecrosis of the femoral head (SONFH) with the involvement of enhancer of zeste homologue 2 (EZH2).Femoral head (FH) samples from SONFH patients and patients with femoral neck fracture were collected, and rat SONFH models were established by Escherichia coli endotoxin combining with large dose steroid pulse assay. The hemorheology, blood lipid, inflammatory factors, and pathologic changes were measured by a series of experiments. Moreover, the detection of osteoblasts, osteoclasts, miR-26a expression, EZH2 expression, osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL), and the apoptosis of osteocytes were conducted. The target relation between miR-26a and EZH2 was clarified by bioinformatics and dual-luciferase reporter gene assay.MiR-26a was poorly expressed, while EZH2 was highly expressed in SONFH, and the elevation of miR-26a could repress EZH2 expression. Elevated miR-26a and reduced EZH2 were able to decelerate the apoptosis of osteocytes, increase osteoblasts, and decrease osteoclasts, resulting in a repression of SONFH progression. Additionally, EZH2 was a target gene of miR-26a. Furthermore, the elevation of EZH2 could reverse the repression of SONFH progression that is induced by elevated miR-26a.We found that up-regulation of miR-26a and knockdown of EZH2 could suppress the development of SONFH, which would contribute to the therapy of SONFH.

18.
Sci Total Environ ; 716: 137097, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32045763

RESUMO

Triclosan (TCS) is a synthetic antimicrobial compound that has been widely used in consumer products. However, increasing evidence suggests adverse effects of TCS to human health and environment, raising great public concerns. The existing methods for detecting TCS are limited to time-consuming and complicated procedure. Here, we developed a rapid method for capture and detection of TCS using surface-enhanced Raman spectroscopy (SERS) based on a silver nanoparticle (Ag NP) core - protein satellite nanostructure. Bovine serum albumin (BSA) assembled on Ag NPs as satellites configuration could anchor a large number of TCS molecules close to the surface of Ag NPs, producing amplified SERS signals. As low as 50 nM TCS standard was successfully detected within 30 min. We also demonstrated its capability for TCS detection in pond water. The developed SERS method holds a great promise for rapid screening of TCS in environmental and food samples.


Assuntos
Nanopartículas Metálicas , Animais , Humanos , Soroalbumina Bovina , Prata , Análise Espectral Raman , Triclosan
19.
Chemosphere ; 242: 125269, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31896199

RESUMO

The occurrence and distribution of 14 antibiotics in the surface water and sediment of Nansi Lake's inflowing rivers were studied. The concentrations of the antibiotics in the sediment and water were not detected (ND)-193,440 ng kg-1 and ND-694 ng L-1, respectively, and ofloxacin was identified as the main antibiotic. The target antibiotics were identified at decreased levels in the study area compared with the inflowing rivers of other lakes. The decreased antibiotic concentrations resulted from the dilution effect, strong biodegradation, and rapid photolysis during the wet season. The spatial variations were due to the differences in regional contributions; the concentrations of antibiotics from Jining and Peixian were the highest. Antibiotic pollution in different seasons originated from different sources; pollution levels were determined by water levels and rainfall as well as complicated runoff generation and confluence mechanisms. Based on the risk quotients, ofloxacin, sulfamethoxazole and sulfadiazine were identified as the main antibiotics that contributed to high ecological risks. Algae and aquatic plants were the main model organisms exposed to these risks. This study has great significance for environmental prevention and the control of antibiotic contamination in Nansi Lake, which is an important water transport channel and the main impounded lake for the eastern route of the south-to-north water diversion project.


Assuntos
Antibacterianos/análise , Monitoramento Ambiental/métodos , Lagos/química , Rios/química , Poluentes Químicos da Água/análise , China , Modelos Lineares , Análise de Componente Principal , Estações do Ano
20.
J Nutr Biochem ; 76: 108286, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31918337

RESUMO

Peroxidation of polyunsaturated fatty acids leads to the formation of a large array of lipid-derived electrophiles (LDEs), many of which are important signaling molecules involved in the pathogenesis of human diseases. Previous research has shown that one of such LDEs, trans, trans-2,4-decadienal (tt-DDE), increases inflammation, however, the underlying mechanisms are not well understood. Here we used click chemistry-based proteomics to identify the cellular targets which are required for the pro-inflammatory effects of tt-DDE. We found that treatment with tt-DDE increased cytokine production, JNK phosphorylation, and activation of NF-κB signaling in macrophage cells, and increased severity of dextran sulfate sodium (DSS)-induced colonic inflammation in mice, demonstrating its pro-inflammatory effects in vitro and in vivo. Using click chemistry-based proteomics, we found that tt-DDE directly interacts with Hsp90 and 14-3-3ζ, which are two important proteins involved in inflammation and tumorigenesis. Furthermore, siRNA knockdown of Hsp90 or 14-3-3ζ abolished the pro-inflammatory effects of tt-DDE in macrophage cells. Together, our results support that tt-DDE increases inflammatory responses via Hsp90- and 14-3-3ζ-dependent mechanisms.

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