Identification and the molecular mechanism of novel duck liver-derived anti-inflammatory peptides in lipopolysaccharide-induced RAW264.7 cell model

In this study,10 novel anti-inflammatory peptides were identified from duck liver,and their molecular mechanism was demonstrated based on machine learning and molecular docking.Using Sephadex G-15 gel chromatography separation,reversed-phase high-performance liquid chromatography purification,liquid chromatography-tandem mass spectrometry identification,and BIOPEP database comparison,10 novel antiinflammatory peptides were initially found.Their splendid angiotensin-converting enzyme(ACE)inhibition and anti-inflammatory properties were confirmed by machine learning.With binding energies less than–20.93 kJ/mol,molecular docking revealed that they could efficiently bind to the active pockets of tumor necrosis factorα(TNF-α),interleukin 6(IL-6),cyclooxygenase 2(COX-2),and nuclear factorκB(NF-κB)proteins with efficiency,indicating that the compounds can spontaneously form complexes through hydrogen bonding and hydrophobic interactions with the protein binding pockets.In the lipopolysaccharide-induced RAW264.7 cell model,the release of NO,TNF-α,and IL-6 and the mRNA expression of inflammatory factors(TNF-α,IL-6,COX-2,and NF-κB)were significantly inhibited by these peptides.We concluded it might be due to their anti-inflammatory effects by inhibiting the protein phosphorylation of inhibitor of NF-κB(IκBα)in the cytoplasm and preventing the translocation of NF-κB p65 in the cytoplasm to the nucleus,thereby regulating the NF-κB signaling pathway.This study is essential for the screening of anti-inflammatory peptides and the investigation of the mechanism of action.

Significance of low level infliximab in the absence of anti-infliximab antibodies

AIM:To evaluate the prevalence of double negative(DN)sera and the mechanisms responsible for DN status.METHODS:Sera of inflammatory bowel disease patients treated with infliximab(IFX)were tested for drug/antibodies to infliximab(ATI)trough levels and the proportion of DN results was compared between a commercially available double antigen ELISA(with labeled IFX as the detection antibody)and an antilambda ELISA(with anti-human lambda chain detection antibody).Repeat testing with lower than customary serum dilution(1:10)was performed.Patients with DN status were matched with IFX+/ATI-controls and were followed-up for subsequent development of nontransient ATI to investigate if DN status precedes ATI.RESULTS:Of 67 sera obtained at time of loss of response,only 6/67(9%)were DN by anti-lambda ELISA compared to 27/67(40%)with double antigen ELISA(P<0.001,Fisher’s Exact test).Of the latter27 sera,22%were also DN by anti-lambda ELISA,whereas 44%were actually IFX positive(IFX+ATI-),30%were ATI positive(IFX-ATI+)and 4%were double positive(IFX+ATI+).Re-testing using a 1:10 dilution converted most DN results into IFX+and/or ATI+status.Patients with DN status had shorter survival free of non-transient ATI compared with matched controls(log rank test,P<0.001).In 9/30(30%)of these patients,non transient ATI occurred before and after the event at which the DN serum was obtained,supporting the view that a DN result may represent aparticular time-point along the two curves of ATI titer rise and infliximab drug level decline.CONCLUSION:DN status may result from false negative detection of IFX or ATI by double antigen ELISA,suggesting a transitional state of low-level immunogenicity,rather than non-immunological clearance.

Antrodia Cinnamomea ameliorates neointimal formation by inhibiting infl ammatory cell infi ltration through downregulation of adhesion molecule expression in vitro and in vivo

The increased vascular infl ammation is a key event in the development of atherosclerotic lesions.Antrodia cinnamomea has been shown to promote anticancerogenic activity through decreasing infl ammation.However,the potential role of A.cinnamomea in cardiovascular diseases remains unexplored.Herein,using carotid arterial ligation models,we found that ethanol extract from A.cinnamomea(EEAC)signifi cantly inhibited neointimal hyperplasia in a dose-dependent manner,accompanied with the reduced expression of activated p65 and infl ammatory cytokines.We also show that EEAC ameliorated TNF-α-induced phosphorylation of p65 and pro-infl ammatory cytokine expression in both vascular smooth muscle cells(VSMCs)and macrophages in vitro.Mechanistically,EEAC suppressed expression levels of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule(VCAM-1)in VSMCs,which attenuates the ability of monocytes/macrophages adhesion to VSMCs.Furthermore,the expression level of these adhesion molecules and infi ltration of monocytes/macrophages were also decreased in neointimal VSMCs of arteries pretreated with EEAC.Altogether,our results reveal a novel function of A.cinnamomea in suppressing vascular infl ammation upon ligation injury during neointimal formation,likely through inhibition of infl ammatory cell infi ltration via downregulating the adhesion molecules in VSMCs.Thus,A.cinnamomea may offer a pharmacological therapy to slow down disease progression in patients with vascular injury.

Spatial Distribution of Traditional Villages and Influence Factors in Hunan Province

To develop and protect traditional villages reasonably, this paper applied Arc GIS Spatial Analyst Tools to analyze spatial distribution and infl uence factors of 101 traditional villages in Hunan Province. The research showed the agglomerate distribution of traditional villages in Hunan; from the city scale, distribution of traditional villages was concentrated mainly in West Hunan Tujia Nationality Autonomous Prefecture, Chenzhou, Yongzhou, Huaihua and Shaoyang; concentrated distribution of traditional villages in the fi ve major geographic regions showed poor equilibrium, West Hunan had the most concentrated traditional villages, and South Hunan has the second most; relatively closed regional environment, perilous hills, inconvenient transportation, and underdeveloped social economy contributed to the protection of traditional villages, and they were all signifi cant infl uence factors for the distribution of traditional villages in Hunan.

Phycocyanin attenuates X-ray-induced pulmonary inflammation via the TLR2-MyD88-NF-κB signaling pathway

Phycocyanin (PC), a natural algal protein, is reported for having anti-oxidant and antiinfl ammatory properties. We investigated its ability to attenuate lung infl ammation in mice subjected to X-ray radiation. Male C57BL/6 mice were assigned to the control, total body irradiation, PC pretreatment, and PC treatment groups. Mice in the PC pretreatment group were gavaged with 200 mg/kg PC for 7 consecutive days before irradiation, and those in the PC treatment group were gavaged with 200 mg/kg PC for 7 consecutive days after irradiation. Lungs were collected on Day 7 after irradiation exposure. Hematoxylin and eosin staining of mouse lung sections showed considerable infl ammation damage 7 days after irradiation compared with the control lung but a reduction in pathological injury in the PC treatment group. Pretreatment or treatment with PC signifi cantly decreased levels of interleukin-6 and tumor necrosis factor-α in the lung, and also increased the relative mRNA expression of superoxide dismutase and glutathione. In vivo, PC signifi cantly reduced the expression of Toll-like receptor TLR2, myeloid diff erentiation primary response Myd88, and nuclear factor NF-κB, at both the transcriptional and translation level. Taken together, these data indicated that PC attenuated lung infl ammatory damage induced by radiation by blocking the TLR2- MyD88-NF-κB signaling pathway. Therefore, PC could be a protective agent against radiation-induced infl ammatory damage in normal tissues.

Influence Factors of the Regional Industrial Structure Evolution in Shandong Province of China against the Background of Low Carbon

Low-carbon development as the th eme of modern times is the premise to upgrade industrial structure. The authors adopt the PCA(Principle Component Analysis) to carry on a quantitative analysis about the factors that affect the changing industrial structure in Shandong Province and then incorporate them into three principal components,namely,development-consumption,speed-structure and urbanization-technology. In other words,economic development is a direct factor while consumption demand and industrial upgrading are major driving forces. Moreover,urbanization accelerates the changes of industrial structure.

Biochanin A and CPe-Ⅲ Peptide Improved Hepatic Infl ammation by Regulating the Hepatic Lipid Metabolic Pathways in Diet-Induced Obese Mice

Biochanin A(BCA) and CPe-Ⅲ peptide, which both exist in chickpea(Cicer arietinum L.), possess significant antihyperlipidemic properties. However, the actualmechanisms ofthose compounds in inhibiting the dysregulation oflipid metabolism and complicated inflammation have not been wellcharacterized. This study investigated the effects ofBCA, CPe-Ⅲ peptide, and combined BCA and CPe-Ⅲ peptide(BC) on the expression ofgenes involved in hepatic lipid and inflammation metabolism. Results demonstrated that BCA, CPe-Ⅲ peptide, and BC significantly attenuated hepatitis and hyperlipidemia by downregulating those genes involved in pro-inflammatory cytokines(TNF-α), hepatic fatty acid(FA) synthesis(ACC1 and FAS), cholesterolmetabolism(SREBP2, HMGCR, and PCSK9), and upregulating key regulators involved in FA oxidation(PPARα and FABP1), lipolysis(ATGL), LDLR, reverse cholesteroltransport(ABCA1, SR-B1, and LXRα), and cholesterolcatabolism(CYP7 A1). Moreover, they also altered the expression oflipid metabolism-related proteins, including SREBP2, PCSK9, LDLR, ABCA1, and CYP7 A1. Finally, these results revealed that the combination treatment ofBCA and CPe-Ⅲ peptide resulted in greater antihyperlipidemic activity compared with individualcompounds.

Moringa oleifera Lam. leaf extract mitigates carbon tetrachloride-mediated hepatic inflammation and apoptosis via targeting oxidative stress and toll-like receptor 4/nuclear factor kappa B pathway in mice

Carbon tetrachloride(CCl4)is a hepatotoxin that triggers liver damage.This study aimed to evaluate the protective effect of phytochemicals detected in Moringa oleifera Lam.leaf extract(MOLE)on CCl4-induced hepatotoxicity in mice.Phytochemicals,total phenolics,and total fl avonoids were detected in MOLE.MOLE markedly decreased the elevation of serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in consistence with the ameliorating effect on CCl4-induced histopathological abnormalities.Moreover,MOLE significantly alleviated the decrease in the antioxidant defense mechanism induced by CCl4.The suppressing effect of MOLE on the boosted inflammatory pathway triggered by CCl4 was detected by measuring the protein levels of nuclear factor kappa-light-chain-enhancer of activated B-cells(NF-κB-p65),toll-like receptor 4(TLR4),tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,and IL-8 as well as the relative expressions of nuclear factor kappa B(NF-κB),TNF-α,IL-1β,and TLR4 genes.Apoptosis and genotoxicity induced by CCl4 were signifi cantly alleviated by MOLE.MOLE co-administration modulated TLR4/NF-κB pathway as presented by the suppressed gene expression of TLR4 and NF-κB as well as by the reduced protein expression of TLR4 and NF-κB-p65.In conclusion,MOLE has a multifarious protective role against hepatotoxicity through control of oxidative stress and modulation of TLR4/NF-κB.

Early monitoring of gas infl ux of drilling fl uid in risers during deepwater drilling using Lamb waves

Early warning of gas in deepwater drilling risers is critical to the timely detection of seepage and consequently blowout reduction. We numerically simulate the acoustic fi eld in water-based drilling fl uids from a sound source outside the riser by using a 3D cylindrical coordinates finite-difference method. By changing the gas content of the drilling fluid, the relation between the amplitude and attenuation of the A0- and the S0-mode Lamb waves in the riser, the fl uid properties in the pipe, and the position of the top and bottom interfaces of the slug fl ow were assessed. The simulation results suggests that the amplitude and attenuation of the Lamb waves refl ect the gas content in the riser and are sensitive to low gas content. Moreover, the Lamb waves amplitude and attenuation reflect the position of the top and bottom interface of the slug fl ow.

HOW DOES BACKGROUND KNOWLEDGE INFLUENCE READING COMPREHENSION OF FOREIGN LANGUAGE LEARNERS？

ＨＯＷＤＯＥＳＢＡＣＫＧＲＯＵＮＤＫＮＯＷＬＥＤＧＥＩＮＦＬＵＥＮＣＥＲＥＡＤＩＮＧＣＯＭＰＲＥＨＥＮＳＩＯＮＯＦＦＯＲＥＩＧＮＬＡＮＧＵＡＧＥＬＥＡＲＮＥＲＳ？Ⅰ．ＩＮＴＲＯＤＵＣＴＩＯＮＯｆｔｈｅｆｏｕｒｌａｎｇｕａｇｅｓｋｉｌｌｓ＇ｒｅａｄｉｎ...

Lunasin protease inhibitor concentrate decreases pro-infl ammatory cytokines and improves histopathological markers in dextran sodium sulfate-induced ulcerative colitis

Lunasin protease inhibitor concentrate(LPIC)is a novel combination of soy bioactive peptide lunasin,Kunitz and Bowman-Birk protease inhibitors.The reported anti-inflammatory and anticancer properties of each one of them suggest LPIC as a promising candidate for the treatment of infl ammatory-related diseases.Our objective was to assess the in vivo anti-infl ammatory properties of LPIC.First,an in vitro test was performed in lipopolysaccharide(LPS)-activated RAW264.7 murine macrophages by measuring the production of nitric oxide(NO),interleukin-6(IL-6),and tumor necrosis factorα(TNF-α)as infl ammatory markers.For the in vivo model,ulcerative colitis(UC)was induced in mice via oral administration of dextran sodium sulfate(DSS).LPIC treatment was performed via daily intraperitoneal injection of 50 mg/kg body weight.Body weight,visible blood in stool and stool consistency were scored daily as macroscopic indicators of disease progression.Occult blood was evaluated by the presence of hemoglobin in stool every third day.Colon length,caecum weight,colonic myeloperoxidase activity(MPO),presence of pro-inflammatory cytokines in blood and colon,changes in the architecture,and expression of inducible nitric oxide synthase(i NOS)in colonic tissue were evaluated.In vitro,LPIC induced production of NO and maintained cytokine levels in comparison to activated untreated macrophages.In vivo,LPIC increased colonic bleeding and did not improve macroscopic markers of the disease,but reduced colonic IL-1βand IL-6,decreased systemic circulation of TNF-α,attenuated neutrophils infi ltration and i NOS expression in colonic tissue,and diminished the damage in colonic architecture.Our results suggest that combinations of peptides in LPIC may counteract the antiinfl ammatory properties in vitro;while in vivo,LPIC can signifi cantly reduce the histopathological damage,hence is a possible therapeutic strategy to attenuate UC.

Relation between Cardiac Injury and Elevated Levels of Inflammatory Biomarkers in Patients with Severe COVID-19

Background:Since early December 2019,coronavirus disease 2019(COVID-19)has emerged as a global pandemic and public health crisis.This study aims to explore the relationship between cardiac injury and infl ammatory biomarkers in patients with severe COVID-19.Methods:We collected data on 91 patients with a confi rmed diagnosis of severe COVID-19 from February 8 to March 31,2020.Demographic characteristics,clinical data,and in-hospital outcomes were compared.The relationship between cardiac injury and infl ammatory biomarkers was analyzed.Logistic regression was used to explore the independent risk factors for cardiac injury.Results:The mean age of all patients was 61 years±14 years.About half of the patients were male.Hypertension and coronary heart disease were more common in the cardiac injury group.The levels of infl ammatory biomarkers in patients who experienced cardiac injury were generally higher than the levels of those without cardiac injury,including interleukin-6,interleukin-2 receptor(IL-2R),procalcitonin,and high-sensitivity C-reactive protein.There were positive correlations between the levels of high-sensitivity troponin I and N-terminal prohormone of brain natriuretic peptide and the levels of infl ammatory biomarkers.Logistic regression shows that IL-2R(odds ratio 1.001,95%confi dence interval 1.000–1.002,P=0.045)and comorbidities(odds ratio 4.909,95%confi dence interval 1.231–19.579,P=0.024)are independent risk factors for cardiac injury in patients with severe COVID-19.Conclusion:High levels of infl ammatory biomarkers are associated with higher risk of cardiac injury in patients with severe COVID-19.IL-2R and comorbidities are predictors of cardiac injury.

Lyme Borrelia as the etiological factor in three cases of primary inflammatory choriocapillaropathies

Citation： Jovanovic SV, Petrovic NT, Zivkovic MLJ, Toncic ZG, Sarenac Vulovic TS. Lyme Borrelia as the etiological factor in three cases of primary inflammatory choriocapillaropathies, lnt J Ophthalmo12017 ; 10（12）：1940-1944

Spatial Distribution Characteristics and Influencing Factors of National Wetland Parks in Shandong Province

Taking 68 national wetland parks(including pilot sites)in Shandong Province as the research objects,three time sections of 2011,2014 and 2017 were selected,to analyze the spatial distribution characteristics of national wetland parks in Shandong Province by using geographic concentration index,imbalance index and standard deviation ellipse method,and explore the infl uencing factors by using SPSS stepwise regression analysis.The results show that the spatial distribution of national wetland parks is extensive but unbalanced,with more in central Shandong and less in eastern Shandong,and the distribution of other regions is relatively uniform.National wetland parks in Shandong Province are distributed along the northeast-southwest direction and are increasingly moving east-west direction.The impacts of natural factors such as topography,hydrology and climate on the spatial distribution of national wetland parks are consistent.At the same time,human factors such as economic environment,traffi c accessibility and population status also play an important driving role.

Research on the Sphere of Infl uence of the Core Value of Confucianism under the Perspective of Life View and Values

In this paper, we conduct research on the sphere of the infl uence of the core value of basic Confucianism under the perspective of life view and values. Value pluralism, as a kind of general phenomenon, the progress of the social values in the value of awakening diversifi ed value orientation, expanded the value choice and choice of the degrees of the freedom at the same time that caused the phenomenon such as value confl ict, value confl ict as make people in social life has a value lost and confused. Value is to reveal the external relationship between the signifi cance of the objective world to meet the needs of the people that serve as a specifi c attributes of the object to the subject needs. We integrate the Confucianism to introduce our understanding of the core value that will promote further development of the science and society management.

Research on Infl uence of Macroeconomic Management of the Enterprise from the Perspective of Analysis of Inertial

In this paper, we conduct research on the infl uence of macroeconomic management of the enterprise from the perspective of general analysis of inertial. Enterprise economic management and economic development is the relationship between the local and global, between enterprises is global economic development, guide and lead the enterprise smooth and orderly economic management; Enterprise economic management is local while the collaboration and auxiliary enterprise economic development. Only under the guidance of holistic view of the enterprise economic development, the enterprise economic management was able to fi nd right direction. Actively explore peopleoriented human resources management system, new measures. People-oriented human resources management of new system, new initiatives, and throughout its intrinsic nature factors to respect, understanding, and give full play to the role of the basic guiding ideology. Our research provides the new paradigm.

Research on the Applications of Big Data on Artistic Designing and Its Infl uences on the Design Behavior

In this paper, we conduct research on the applications of big data on artistic designing and its infl uences on the design behavior. Modern art design enhance the grade of the product, increase the added value of products, promote the development of the economy, make the product of the aesthetic value and economic value of the perfect unity. In today’s society due to the value of the product are much more than the product itself contains the value of performance, usage, etc. is more of a product in gradually improve the aesthetic value, sometimes even more than the use of the product value and exchange value, therefore the product has become the dominant value. Under this basis, we propose the new idea on the design pattern that will be meaningful.

Research on the Influence Factors of Building China＇s Adult Education System under the Open Education Resource Perspective

In this paper, we conduct research on the influence factors of building the China’s adult education system under the openeducation resource perspective. Network education to build the learning society offers the best models and tools. All kinds of technical training,continuing education and so on all can through the network education. With the progress of the science and technology, at present on the networkis hard to experiment and practice activity will also been largely resolved. Therefore, to make full use of the advantages of network education,we can establish a learning society and construct lifelong education system. This paper starts from this perspective to propose the new idea on thecountermeasures and suggestions that will be benefi cial.

Negative regulation of NLRP3 infl ammasome signaling

Infl ammasomes are multiprotein complexes that serve as a platform for caspase-1 activation and interleukin-1β(IL-1β)maturation as well as pyroptosis.Though a number of infl ammasomes have been described,the NLRP3 inflammasome is the most extensively studied.NLRP3 inflammasome is triggered by a variety of stimuli,including infection,tissue damage and metabolic dysregulation,and then activated through an integrated cellular signal.Many regulatory mechanisms have been identifi ed to attenuate NLRP3 infl ammasome signaling at multiple steps.Here,we review the developments in the negative regulation of NLRP3 inflammasome that protect host from inflammatory damage.