scholarly journals Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A 1H NMR-Based Metabolomics Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Hao ◽  
Hong Zheng ◽  
Ruo-Han Wang ◽  
Hui Li ◽  
Li-Li Yang ◽  
...  

Maresin1 (MaR1), a new anti-inflammatory and proresolving lipid mediator, has been proven to exert organ-protective effects in septic animal models. However, the potential mechanisms are still not fully elucidated. In this study, we sought to explore the impact of MaR1 on metabolic dysfunction in cecal ligation and puncture- (CLP-) induced septic mice. We found that MaR1 significantly increased the overall survival rate and attenuated lung and liver injuries in septic mice. In addition, MaR1 markedly reduced the levels of proinflammatory cytokines (TNF-α and IL-6) and alleviated mitochondrial damage. Based on a 1H NMR-based metabolomics analysis, CLP-induced septic mice had increased levels of acetate, pyruvate, and lactate in serum and decreased levels of alanine, aspartate, glutamate, and fumarate in lungs. However, these metabolic disorders, mainly involving energy and amino acid metabolism, can be recovered by MaR1 treatment. Therefore, our results suggest that the protective effects of MaR1 on sepsis could be related to the recovery of metabolic dysfunction and the alleviation of inflammation and mitochondrial damage.

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen Luo ◽  
Li Jia ◽  
Jia-Wen Zhang ◽  
Dong-Jie Wang ◽  
Qiu Ren ◽  
...  

Andrographolide (Andro) has known to treat various illnesses such as colds, diarrhea, fever and infectious diseases. However, the effect mechanism of Andro is still unclear. Therefore, we used high-throughput metabolomics analysis to discover biomarkers, metabolic profiles and pathways to reveal the pharmacological action and effective mechanism of Andro against lung cancer. The metabolic effects of Andro on lung cancer animal was explored by ultra-performance liquid chromatography-triple-time of flight/mass spectrometry (UPLC-TOF/MS) analysis. Our results showed that Andro exhibited significant protective effects against lung cancer. Compared with control group, a total of 25 metabolites biomarkers was identified in urine of model animals, which 18 of them were regulated toward the normal direction after Andro treatment, and network pharmacology analysis showed that they were related with 570 proteins. Biological pathways analysis showed that the 11 metabolism pathways were regulated by Andro treatment in lung cancer mouse, and amino acid metabolism and arachidonic acid metabolism have great potential as target pathways for Andro against lung cancer. It revealed that high-throughput metabolomics combined with network pharmacology analysis provides deeply insight into the therapeutic mechanisms of natural product for promoting medicine development and disease treatment.


2019 ◽  
Vol 25 (40) ◽  
pp. 5503-5511 ◽  
Author(s):  
Abdulaziz Alhasaniah ◽  
Michael J. Sherratt ◽  
Catherine A. O'Neill

A competent epidermal barrier is crucial for terrestrial mammals. This barrier must keep in water and prevent entry of noxious stimuli. Most importantly, the epidermis must also be a barrier to ultraviolet radiation (UVR) from the sunlight. Currently, the effects of ultraviolet radiation on epidermal barrier function are poorly understood. However, studies in mice and more limited work in humans suggest that the epidermal barrier becomes more permeable, as measured by increased transepidermal water loss, in response UVR, at doses sufficiently high to induce erythema. The mechanisms may include disturbance in the organisation of lipids in the stratum corneum (the outermost layer of the epidermis) and reduction in tight junction function in the granular layer (the first living layer of the skin). By contrast, suberythemal doses of UVR appear to have positive effects on epidermal barrier function. Topical sunscreens have direct and indirect protective effects on the barrier through their ability to block UV and also due to their moisturising or occlusive effects, which trap water in the skin, respectively. Some topical agents such as specific botanical extracts have been shown to prevent the loss of water associated with high doses of UVR. In this review, we discuss the current literature and suggest that the biology of UVR-induced barrier dysfunction, and the use of topical products to protect the barrier, are areas worthy of further investigation.


Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 801
Author(s):  
Maria Detopoulou ◽  
Agathi Ntzouvani ◽  
Filio Petsini ◽  
Labrini Gavriil ◽  
Εlizabeth Fragopoulou ◽  
...  

Platelet-activating factor (PAF), a proinflammatory lipid mediator, plays a crucial role in the formation of the atherosclerotic plaque. Therefore, the inhibition of endothelium inflammation by nutraceuticals, such as PAF inhibitors, is a promising alternative for preventing cardiovascular diseases. The aim of the present study was to evaluate the impact of a new functional yogurt enriched with PAF inhibitors of natural origin from olive oil by-products on PAF metabolism. Ninety-two apparently healthy, but mainly overweight volunteers (35–65 years) were randomly allocated into three groups by block-randomization. The activities of PAF’s biosynthetic and catabolic enzymes were measured, specifically two isoforms of acetyl-CoA:lyso-PAF acetyltransferase (LPCATs), cytidine 5′-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT) and two isoforms of platelet activating factor acetylhydrolase in leucocytes (PAF-AH) and plasma (lipoprotein associated phospholipase-A2, LpPLA2). The intake of the enriched yogurt resulted in reduced PAF-CPT and LpPLA2 activities. No difference was observed in the activities of the two isoforms of lyso PAF-AT. In conclusion, intake of yogurt enriched in PAF inhibitors could favorably modulate PAF biosynthetic and catabolic pathways.


Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1144
Author(s):  
Aliyu Dantani Abdullahi ◽  
Pratthana Kodchasee ◽  
Kridsada Unban ◽  
Thanawat Pattananandecha ◽  
Chalermpong Saenjum ◽  
...  

The study investigated the impact of the fermentation process on the phenolic contents and antioxidant and anti-inflammatory activities in extracts of Miang, an ethnic fermented tea product of northern Thailand. The acetone (80%) extraction of Miang samples fermented by a non-filamentous fungi-based process (NFP) and filamentous fungi-based process (FFP) had elevated levels of total polyphenols, total tannins, and condensed tannins compared to young and mature tea leaves. The antioxidant studies also showed better the half-maximal inhibitory concentration (IC50) values for fermented leaves in both 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity assays as well as improved ferric reducing antioxidant power (FRAP) compared to young and mature tea leaves. Extracts of NFP and FFP samples at concentrations of 50 and 100 ppm showed better protective effects against hydrogen peroxide (H2O2)-induced intracellular reactive oxygen species (ROS) production in HT-29 colorectal cells without exerting cytotoxicity. Additionally, lipopolysaccharide (LPS)-induced production of nitric oxide (a proinflammatory mediator as well as a reactive nitrogen species) was also inhibited by these fermented Miang extracts with an IC50 values of 17.15 μg/mL (NFP), 20.17 μg/mL (FFP), 33.96 μg/mL (young tea leaves), and 31.33 μg/mL (mature tea leaves). Therefore, both NFP-Miang and FFP-Miang showed the potential to be targeted as natural bioactive functional ingredients with preventive properties against free radical and inflammatory-mediated diseases.


Author(s):  
Fatma Boukid ◽  
Elena Curti ◽  
Agoura Diantom ◽  
Eleonora Carini ◽  
Elena Vittadini

AbstractIndustrial processing of tomato includes its cutting and mincing, thermal treatments, and the addition of ingredients, which might induce changes in physicochemical properties of the final products. In this frame, the impact of texturing/thickening [xanthan gum (X) or potato fiber (F)] on the macroscopic, mesoscopic and molecular properties of tomato double concentrate (TDC) was investigated to determine if F can efficiently substitute X, in association with small solutes (sugar and salt) and thermal treatment (cold and hot). At a macroscopic level, multivariate statistics (MANOVA) underlined that color change (ΔE) was increased by X and F addition contrary to heating and the addition of salt and sugar. MANOVA revealed that texture was greatly enhanced through the use of F over X. 1H NMR molecular mobility changes were more controlled by texturing agents (F and X) than thermal treatment and small solutes. Particularly F increased the more rigid population indicating stronger interaction with water molecules resulting in shear-thinning flow. However, adding X contributed into the increase of the dynamic and mobile populations. Therefore, F can be a valid “clean label” substitute of X in modulating tomato products properties.


2021 ◽  
Vol 46 (3) ◽  
pp. 699-700
Author(s):  
Xia Liu ◽  
Zhi Ruan ◽  
Xing-cheng Shao ◽  
Hong-xuan Feng ◽  
Lei Wu ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xin-Yang Wang ◽  
Xin-Yu Li ◽  
Cheng-Hua Wu ◽  
Yu Hao ◽  
Pan-Han Fu ◽  
...  

Abstract Background Endothelial glycocalyx loss is integral to increased pulmonary vascular permeability in sepsis-related acute lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel macrophage-derived lipid mediator exhibiting potential anti-inflammatory and pro-resolving benefits. Methods PCTR1 was administrated intraperitoneally with 100 ng/mouse after lipopolysaccharide (LPS) challenged. Survival rate and lung function were used to evaluate the protective effects of PCTR1. Lung inflammation response was observed by morphology and inflammatory cytokines level. Endothelial glycocalyx and its related key enzymes were measured by immunofluorescence, ELISA, and Western blot. Afterward, related-pathways inhibitors were used to identify the mechanism of endothelial glycocalyx response to PCTR1 in mice and human umbilical vein endothelial cells (HUVECs) after LPS administration. Results In vivo, we show that PCTR1 protects mice against lipopolysaccharide (LPS)-induced sepsis, as shown by enhanced the survival and pulmonary function, decreased the inflammatory response in lungs and peripheral levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, PCTR1 restored lung vascular glycocalyx and reduced serum heparin sulphate (HS), syndecan-1 (SDC-1), and hyaluronic acid (HA) levels. Furthermore, we found that PCTR1 downregulated heparanase (HPA) expression to inhibit glycocalyx degradation and upregulated exostosin-1 (EXT-1) protein expression to promote glycocalyx reconstitution. Besides, we observed that BAY11-7082 blocked glycocalyx loss induced by LPS in vivo and in vitro, and BOC-2 (ALX antagonist) or EX527 (SIRT1 inhibitor) abolished the restoration of HS in response to PCTR1. Conclusion PCTR1 protects endothelial glycocalyx via ALX receptor by regulating SIRT1/NF-κB pathway, suggesting PCTR1 may be a significant therapeutic target for sepsis-related acute lung injury.


2021 ◽  
Author(s):  
Carsten T. Herz ◽  
Johanna M. Brix ◽  
Bernhard Ludvik ◽  
Guntram Schernthaner ◽  
Gerit-Holger Schernthaner

Abstract Purpose Dipeptidyl peptidase 4 (DPP4) is expressed and secreted by adipocytes. DPP4 induces insulin resistance independently of its effect on glucagon-like peptide 1, thus it is conceivable that DPP4 directly contributes to metabolic dysfunction in patients with morbid obesity. The aim of this study was to investigate the impact of weight loss induced by bariatric surgery on DPP4 activity, and whether these changes are associated with improvements in markers of metabolic dysfunction and fatty liver disease. Materials and Methods We included 68 non-diabetic patients who underwent bariatric surgery. Serum DPP4 activity was measured using a fluorogenic substrate before and after surgery. Results Results: After a median follow-up period of 12 (IQR 11-17) months, median serum DPP4 activity decreased from 230 (IQR: 194-273) to 193 (164-252) pmol/min (p=0.012). The decrease in DPP4 activity was significantly correlated with decreases in BMI, improved cholesterol levels, reduced hepatic injury markers as well as improved post-prandial insulin sensitivity. After multivariable adjustment, ΔDPP4 activity remained significantly associated with Δcholesterol (beta=0.341, p=0.025), ΔLDL cholesterol (beta=0.350, p=0.019), Δgamma-glutamyltransferase (beta=0.323, p=0.040) and ΔMatsuda index (beta=-0.386, p=0.045). Conclusion We demonstrated that weight loss induced by bariatric surgery results in decreased circulating DPP4 activity beyond the initial phase of weight loss. The associations between decreased DPP4 activity and improved cholesterol levels as well as hepatic injury markers point towards pleiotropic effects of DPP4 beyond glucose metabolism which warrant further investigation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wuyang Huang ◽  
Ky Young Cho ◽  
Di Meng ◽  
W. Allan Walker

AbstractAn excessive intestinal inflammatory response may have a role in the pathogenesis of necrotizing enterocolitis (NEC) in very preterm infants. Indole-3-lactic acid (ILA) of breastmilk tryptophan was identified as the anti-inflammatory metabolite involved in probiotic conditioned media from Bifidobacteria longum subsp infantis. This study aimed to explore the molecular endocytic pathways involved in the protective ILA effect against inflammation. H4 cells, Caco-2 cells, C57BL/6 pup and adult mice were used to compare the anti-inflammatory mechanisms between immature and mature enterocytes in vitro and in vivo. The results show that ILA has pleiotropic protective effects on immature enterocytes including anti-inflammatory, anti-viral, and developmental regulatory potentials in a region-dependent and an age-dependent manner. Quantitative transcriptomic analysis revealed a new mechanistic model in which STAT1 pathways play an important role in IL-1β-induced inflammation and ILA has a regulatory effect on STAT1 pathways. These studies were validated by real-time RT-qPCR and STAT1 inhibitor experiments. Different protective reactions of ILA between immature and mature enterocytes indicated that ILA’s effects are developmentally regulated. These findings may be helpful in preventing NEC for premature infants.


2019 ◽  
Vol 202 (8) ◽  
Author(s):  
Courtney E. Price ◽  
Dustin G. Brown ◽  
Dominique H. Limoli ◽  
Vanessa V. Phelan ◽  
George A. O’Toole

ABSTRACT Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are monoinfected with either P. aeruginosa or S. aureus. We showed previously that mucoid strains of P. aeruginosa can coexist with S. aureus in vitro due to the transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here, we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm coculture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to the transcriptional downregulation of pvdA, a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS (Pseudomonas quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid P. aeruginosa with nonmucoid P. aeruginosa strains can mitigate the killing of S. aureus by the nonmucoid strain of P. aeruginosa, indicating that the mechanism that we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill S. aureus at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the S. aureus-protective effects of mucoidy in a strain-specific manner. IMPORTANCE CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are P. aeruginosa and S. aureus, with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus coexistence, despite evidence that P. aeruginosa kills S. aureus when these organisms are cocultured in vitro. Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.


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