Background:The nuclear receptor coactivator(NCOA)family,including NCOA1,NCOA2,and NCOA3,is critical in regulating gene expression through interactions with nuclear receptors and other transcription factors.These coact...Background:The nuclear receptor coactivator(NCOA)family,including NCOA1,NCOA2,and NCOA3,is critical in regulating gene expression through interactions with nuclear receptors and other transcription factors.These coactivators are implicated in various cancers,but their comprehensive roles across different cancer types remain poorly understood.Methods:We performed a pan-cancer bioinformatics analysis using data from The Cancer Genome Atlas and the Genotype-Tissue Expression project.We assessed the differential expression,copy number variations,mutations,methylation status,tumor mutation burden,microsatellite instability,and immune cell infiltration associated with NCOA family members across various cancers.Differential expression analysis was conducted using the DESeq2 package.Methylation data were analyzed using the ChAMP package,and immune cell infiltration was estimated using the CIBERSORT algorithm.Results:NCOA1 and NCOA2 were predominantly downregulated in multiple cancers,suggesting potential tumor suppressor roles,whereas NCOA3 was largely upregulated,indicating a consistent oncogenic function.These expression patterns significantly correlated with patient prognosis.Frequent copy number variations,particularly gains,and high mutation rates were observed in NCOA2.NCOA3 demonstrated consistent hypomethylation in tumors,which was associated with increased gene expression.Significant correlations were found between NCOA expression and tumor mutation burden,microsatellite instability,and immune cell infiltration,indicating their involvement in genomic instability and immune modulation.Conclusion:This comprehensive analysis reveals significant alterations in the expression,genomic,and epigenetic profiles of NCOA family members across various cancers.The findings highlight the multifaceted roles of NCOA1,NCOA2,and NCOA3 in tumorigenesis and their potential as biomarkers and therapeutic targets.Future research should focus on elucidating the mechanisms underlying the associations between NCOA expression,genomic alterations,and immune modulation to develop targeted cancer therapies.展开更多
The emergence of SARS-CoV-2 variants and drug-resistant mutants emphasizes the urgent need to develop novel antiviral agents.In the present study,we examined the therapeutic effect of the Chinese medicinal herb,Scutel...The emergence of SARS-CoV-2 variants and drug-resistant mutants emphasizes the urgent need to develop novel antiviral agents.In the present study,we examined the therapeutic effect of the Chinese medicinal herb,Scutellaria barbata D.Don(SBD),against SARS-CoV-2 infection both in vitro and in vivo.Using a viral replicon particle(VRP)-based mouse model of SARS-CoV-2 infection,our study revealed that SBD extracts can reduce viral load in mouse lungs and alleviate the viral induced pneumonia.In vitro antiviral determination further validated the direct acting antiviral efficacy of SBD extracts against SARS-CoV-2 replication.Mechanistic studies demonstrated that SBD can act against SARS-CoV2 replication by targeting both 3-chymotrypsin-like and papain-like cysteine proteases,via a combination of multiple active constituents.Moreover,SBD can modulate the host inflammation response in a bi-directional manner,which also contribute to the mitigation of viral induced acute lung injury.In summary,our study provides SBD as a promising therapeutic agent to combat SARS-CoV-2 infections that merit further development.展开更多
In order to verify the synthesis pathway of linoleic acid(LA)to generate arachidonic acid(ARA),the functions ofΔ6 FAD and Elovl 5 in Apostichopus japonicus were tested by heterologous expression in Pichia pastoris.A ...In order to verify the synthesis pathway of linoleic acid(LA)to generate arachidonic acid(ARA),the functions ofΔ6 FAD and Elovl 5 in Apostichopus japonicus were tested by heterologous expression in Pichia pastoris.A 60-day feeding experiment was conducted to evaluate the effects of dietary LA and ARA on growth,polyunsaturated fatty acids(PUFA)biosynthesis and im-mune function of A.japonicus.Seven diets containing graded levels of LA or ARA were formulated,and one diet without PUFA was applied as a control.The results confirmed thatΔ6 FAD from A.japonicus has a double desaturation ability ofΔ6 andΔ5 for PUFA,and it works together with Elovl 5 enzyme play important roles in biosynthesis of ARA from LA.With increasing dietary LA from 4.9 to 12.1 g/kg,the expressions ofΔ6 FAD and Elovl 5,levels of LA,ARA and EPA in tissues increased,and the activities of ACP,AKP and CAT enzymes in intestine initially increased and then decreased.Additionally,by increasing dietary ARA from 0.7 to 3.8 g/kg,the contents of ALA,EPA and DHA decreased,while theΔ6 FAD expression and the activities of ACP,AKP and CAT in intes-tine increased significantly.Therefore,appropriate dietary levels of LA(12.1 g/kg)or ARA(3.8 g/kg)build a reasonable composi-tion of n-3/n-6 PUFA in A.japonicus,and improved its growth,antioxidant capacity and immunological defenses.展开更多
The immune system is the body's main cancer surveillance system.Unlike surgery,radiation,and chemotherapy,which are typically nonspecific,cancer immunotherapy holds tremendous promise as it harnesses the high spec...The immune system is the body's main cancer surveillance system.Unlike surgery,radiation,and chemotherapy,which are typically nonspecific,cancer immunotherapy holds tremendous promise as it harnesses the high specificity of a person's immune system to kill cancer cells selectively.This promising approach includes checkpoint inhibitors,chimeric antigen receptor (CAR)-T cell therapy,cancer vaccines,cytokines,and monoclonal antibodies,among others.Cancer immunotherapy has progressed tremendously,resulting from basic science discoveries in the molecular and cellular biology of T cells.展开更多
The concept of neuroimmune interactions has shown significant advancements over the years. Modern research has revealed many areas of connection between fields, which were previously viewed as distinct disciplines. Fo...The concept of neuroimmune interactions has shown significant advancements over the years. Modern research has revealed many areas of connection between fields, which were previously viewed as distinct disciplines. For example, the nervous system can sense changes in the external environment and convey these changes through molecules and mediators with receptors in the immune system to modulate immune responses. Neuromediators can act on different receptors in the same group of cells, producing antipodal effects. Identification of the anti-inflammatory role of glucocorticoids highlighted that the body functions properly in an integrated manner. These interactions and crosstalk are not unidirectional, as the immune system can also influence various aspects of the nervous system, such as synaptic plasticity and fever. Strict integration of neuro-immuno-endocrine circuits is indispensable for homeostasis. Understanding these circuits and molecules can lead to advances in the understanding of various immune diseases, which will offer promising therapeutic options.展开更多
Objectives:The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery,particularly in cancer therapy.This study aimed to evaluate the cytotoxicity,apoptosis ind...Objectives:The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery,particularly in cancer therapy.This study aimed to evaluate the cytotoxicity,apoptosis induction,and immune-modulatory activities of extracts from three herbal medicines with historical use in traditional medicine—Acanthopanax sessiliflorus,Phragmites communis,and Pinus densiflora,as well as their combined extract(GMAS 01/COM),on human lung cancer cells(A549)and normal cell lines,including murine macrophages(RAW 264.7)and human keratinocytes(HaCaT).Methods:Plant extracts were prepared using aqueous extraction,sonication,and rotary evaporation.The total phenolic and flavonoid contents were quantified using the Folin-Ciocalteu and AlCl3 colorimetric methods,respectively.Antioxidant potential was evaluated via 2,2-Diphenyl-1-picrylhydrazyl(DPPH)scavenging and reducing power assays.Cytotoxicity was assessed using an MTT assay,while reactive oxygen species(ROS)generation was quantified using a 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA)assay.Anticancer properties,including colony formation inhibition and migration suppression,were examined using colony formation and wound healing assays.The expression of apoptotic and inflammatory mediators was analysed through qPCR.Results:GMAS 01 selectively induced apoptosis in A549 cells without cytotoxic effects on RAW264.7 and HaCaT cells.Mechanistically,it elevated intracellular ROS and activated the intrinsic mitochondrial apoptotic pathway,evidenced by p53 upregulation,increased Bax,and decreased Bcl-2 expression.GMAS 01 also significantly inhibited colony formation and migration in A549 cells.In RAW264.7 cells,it reduced nitric oxide(NO)production and downregulated iNOS,COX-2,IL-6,and IL-8,indicating strong immunomodulatory activity.Conclusion:GMAS 01 exhibits potent antioxidant,anti-inflammatory,and anticancer effects,likely mediated through ROS-induced mitochondrial apoptosis.However,mechanistic interpretations are limited by the absence of protein-level validation and pathway inhibition studies.Upcoming studies should aim to verify the underlying mechanisms and evaluate their potential for real-world application.展开更多
Hepatocellular carcinoma(HCC),a primary malignancy of the liver and leading cause of cancer-related mortality worldwide,poses substantial therapeutic challenges,particularly in advanced and unresectable stages.Immune ...Hepatocellular carcinoma(HCC),a primary malignancy of the liver and leading cause of cancer-related mortality worldwide,poses substantial therapeutic challenges,particularly in advanced and unresectable stages.Immune checkpoint inhibitors(ICIs)have emerged as critical therapeutic agents,targeting immune checkpoint pathways to restore antitumor immune responses.Combinations such as atezolizumab(anti-programmed cell death ligand 1 with bevacizumab antivascular endothelial growth factor),as well as antibodies directed against cytotoxic T-lymphocyte associated protein 4 and programmed cell death protein 1(e.g.,ipilimumab and nivolumab),have demonstrated improved clinical outcome in selected patients.However,the overall efficacy of ICIs remains hindered by variable response rate and primary or acquired resistance.Recent evidence suggests that the gut microbiome plays a pivotal role in modulating host immune responses and may significantly influence the therapeutic efficacy of ICIs.Dysbiosis within the gut-liver axis has been implicated not only in pathogenesis and progression of HCC but also diminishing immunotherapy effectiveness.Emerging studies highlight the potential of microbiome-targeted interventions including dietary modulation,prebiotics,probiotics,and fecal microbiota transplantation to enhance ICIs responsiveness.This review explores the evolving interplay between the gut microbiota and immunotherapy in HCC,with a focus on microbiome-based strategies aimed at optimizing clinical outcomes.展开更多
Gibberella stalk rot(GSR)caused by Fusarium graminearum is one of the most devastating diseases of maize,seriously impacting maize yield and quality,as well as the ability to use technology of mechanical harvesting.En...Gibberella stalk rot(GSR)caused by Fusarium graminearum is one of the most devastating diseases of maize,seriously impacting maize yield and quality,as well as the ability to use technology of mechanical harvesting.Environmental conditions including photoperiod affect crop disease resistance.However,the mechanism underlying photoperiod-regulated maize GSR resistance remains unexplored.We found in this study that GSR resistance is regulated by the ZmPIF4.1(Phytochrome-Interacting Factor4)-ZmPTI1c(Pto-Interacting 1)-ZmMYB31 module coupled with photoperiod.The functional analysis of zmpti1c mutant indicated that ZmPTI1c negatively regulates maize GSR resistance.Short day promoted the disease progression in both zmpti1c and wild-type plants.ZmPTI1c promoter contains multiple predicted cis-acting elements for light responses.Yeast one-hybrid assay(Y1H),Electrophoretic mobility shift analysis(EMSA),and Dual-luciferase(LUC)reporter assays demonstrated that ZmPIF4.1 binds to the G-box in ZmPTI1c promoter and activates its expression.Moreover,expression levels of ZmPIF4 and ZmPTI1c were significantly higher under short day than under long day.ZmPTI1c interacted with and phosphorylated ZmMYB31.GSR resistance in zmmyb31 mutant was significantly increased than in wild type,indicating that ZmMYB31 also negatively regulated GSR resistance.Furthermore,ZmMYB31 suppressed the transcriptional activation of ZmPTI1c by ZmPIF4.1.Overall,ZmPIF4.1-ZmPTI1c-ZmMYB31negatively regulates maize immunity to GSR,which is likely modulated by photoperiod.展开更多
BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related morbidity and mor-tality globally.Exosomal microRNAs(miRNAs)are known to modulate tumor progression by influencing immune responses and vascular dy...BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related morbidity and mor-tality globally.Exosomal microRNAs(miRNAs)are known to modulate tumor progression by influencing immune responses and vascular dynamics.However,the roles of specific exosomal miRNAs,such as miR-425-5p and miR-135b-3p,in CRC remain unclear.AIM To explore the specific roles and underlying mechanisms of exosomal miR-425-5p and miR-135b-3p in CRC progression.METHODS Differentially expressed miRNAs were identified through microarray analysis of exosomes isolated from CRC tissues and adjacent normal mucosa.Functional roles of miR-425-5p and miR-135b-3p were evaluated in vitro using macrophage polarization,T cell differentiation,and vascular permeability assays,as well as in vivo tumor formation and metastasis experiments in nude mice.Validation expe-riments were performed using CRC cell lines(HCT116 and SW620).RESULTS Exosomal miR-425-5p and miR-135b-3p were significantly upregulated in CRC compared to normal tissues.Functional studies revealed that miR-425-5p promo-tes macrophage M2-like polarization and suppresses T cell proinflammatory responses,while miR-135b-3p enhances vascular permeability and angiogenesis.Inhibition of these miRNAs in CRC cell-derived exosomes significantly supp-ressed tumor growth and metastasis in nude mice,reprogramming the tumor microenvironment toward reduced angiogenesis and enhanced immune acti-vation.Combined inhibition of both miRNAs resulted in the most pronounced effects.CONCLUSION Exosomal miR-425-5p and miR-135b-3p drive CRC progression by promoting immune suppression and vascular permeability.Their inhibition offers a promising strategy for modulating the tumor microenvironment and limiting CRC metastasis.展开更多
Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have con...Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial resistance.Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated.Lactoferrin has shown promising results against porcine enterotoxigenic E.coli strains,both in vitro and in vivo.Results We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned piglets.Additionally,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E.coli(STEC)infection.Therefore,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC strain.BLF did not affect theα-andβ-diversity.However,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa.When analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF group.Conclusion Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned piglets.Nevertheless,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut homeostasis.Furthermore,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.展开更多
Enteral nutrition has been strongly recommended by major scientific societies for the nutritional management of patients with acute pancreatitis.Providing severe acute pancreatitis patients with enteral nutrition with...Enteral nutrition has been strongly recommended by major scientific societies for the nutritional management of patients with acute pancreatitis.Providing severe acute pancreatitis patients with enteral nutrition within the first 24-48 h of hospital admission can help improve outcomes compared to parenteral nutrition and no feeding.New research is focusing in on when and what to feed to best improve outcomes for acute pancreatitis patients.Early enteral nutrition have the potential to modulate the immune responses.Despite this consistent evidence of early enteral nutrition in patients with acute pancreatitis,clinical practice continues to vary due to individual clinician preference.Achieving the immune modulating effects of enteral nutrition heavily depend on proper placement of the feeding tube and managing any tube feeding associated complications.The current article reviews the immune modulating effects of enteral nutrition and pro-and prebiotics and suggests some practical tools that help improve the patient adherence and tolerance to the tube feeding.Proper selection of the type of the tube,close monitoring of the tube for its placement,patency and securing its proper placement and routine checking the gastric residual volume could all help improve the outcome.Using peptide-based and high medium chaintriglycerides feeding formulas help improving feeding tolerance.展开更多
In this study, the influences of immersion bathing in different concentrations of Bacillus velezensis DY-6 on the body weight gain rate and non-specific immune enzyme activities of the coelom fluid of sea cucumber (Ap...In this study, the influences of immersion bathing in different concentrations of Bacillus velezensis DY-6 on the body weight gain rate and non-specific immune enzyme activities of the coelom fluid of sea cucumber (Apostichopus japonicus) were determined in order to obtain the optimum bacterial concentration. The gut microbiota change in A. japonicus was then analyzed through high-throughput sequencing during the immersion bathing in B. velezensis DY-6 at the optimum concentration for 49 d. The results illustrate that the body weight growth rate of all bathing groups was higher than that of the control. The highest growth rate (25.3%) was achieved when the bacterial concentration was 1×10^3 CFU/mL. The activities of non-specific immune enzymes (ACP, AKP, SOD and LZM) of all bathing groups increased, and the activities of the enzymes of groups bathed with the bacterium at 1×10^3 and 1×10^4 CFU/mL reached the highest on day 21 and day 28. Taking the growth rate and economic cost into consideration, the optimum concentration of B. velezensis DY-6 was 1×10^3 CFU/mL. The influences of immersion bathing in B. velezensis DY-6 at 1×10^3 CFU/mL on the gut microbiota of A. japonicus were then evaluated through 16S rDNA sequencing analysis. Results showed that the gut microbiota changed with the addition of B. velezensis DY-6, and the richness and diversity of the gut microbiota peaked twice on day 14 and day 21, respectively. In association with the non-specific immune enzyme activities and if day 28 was selected as the dividing point, the community structure of the gut microbiota could be obviously divided into two types. The correlation analysis revealed that the non-specific immune enzyme activities were correlated significantly to some gut bacteria (in the phyla Firmicutes, Proteobacteria, and Bacteroidetes) after immersion bathing in B. velezensis DY-6. Our findings will provide the theoretical foundation for probiotic application in sea cucumber farming.展开更多
Based on Immune Programming(IP), a novel Radial Basis Function (RBF) networkdesigning method is proposed. Through extracting the preliminary knowledge about the widthof the basis function as the vaccine to form the im...Based on Immune Programming(IP), a novel Radial Basis Function (RBF) networkdesigning method is proposed. Through extracting the preliminary knowledge about the widthof the basis function as the vaccine to form the immune operator, the algorithm reduces thesearching space of canonical algorithm and improves the convergence speed. The application ofthe RBF network trained with the algorithm in the modulation-style recognition of radar signalsdemonstrates that the network has a fast convergence speed with good performances.展开更多
Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The...Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liverdisease(MELD) score helped to reduce waiting list mortality in liver transplantation(LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients' infectious and immunologic risk profiles. The administration of intravenous immunoglobulins(IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.展开更多
Non-specific immune response of bullfrog Rana catesbeiana to pathogenic Aeromonas hydrophila was studied to 60 individuals in two groups.Each bullfrog in bacterium-injected group was injected intraperitoneally(i.p.) w...Non-specific immune response of bullfrog Rana catesbeiana to pathogenic Aeromonas hydrophila was studied to 60 individuals in two groups.Each bullfrog in bacterium-injected group was injected intraperitoneally(i.p.) with 0.2 ml bacterial suspension at a density of 5.2 × 106 CFU/ml,while each one in control group injected i.p.with 0.2 ml sterile saline solution(0.85%,w/v).Three bullfrogs in both groups were sampled at 0,1,3,7,11,15 and 20 days post-injection(dpi) for the evaluation of non-specific immune parameters.It was observed that intraperitoneal injection of A.hydrophila significantly increased the number of leucocytes and that of NBT-positive cells in peripheral blood.Significant increases in serum bactericidal activity and serum acid phosphatase activity were also observed in the bacterium-injected frogs when compared with those in the control group.However,a significant reduction was detected in vitro in phagocytosis activity of peripheral blood phagocytes.No significant difference in changes in the number of peripheral erythrocytes,serum superoxide dismutase(SOD) activity,and lysozyme activity was detected between the two groups.It is suggested that bullfrogs may produce a series of non-specific immune reactions in response to the A.hydrophila infection.展开更多
A recent study published in the World Journal of Gastroenterology,suggests that transplanting the gut microbiota from healthy donors can alleviate the pathological processes linked to inflammatory bowel disease(IBD),p...A recent study published in the World Journal of Gastroenterology,suggests that transplanting the gut microbiota from healthy donors can alleviate the pathological processes linked to inflammatory bowel disease(IBD),particularly Crohn's disease.In addition,that paper illustrates the effect of changes in the gut microbiota on IBD and points out that altered mesenteric adipose tissue caused by the gut microbiota and creeping fat lead to increased inflammation,which exacerbates IBD.Moreover,recent research has shown that the interaction between Helicobacter pylori(H.pylori)and the gut microbiota is mediated through immune mechanisms,resulting in a synergistic impact on IBD.Therefore,in this manuscript,we will focus on the role of the gut microbiota and H.pylori in the immune response to IBD,as well as the possible impact of H.pylori on the gut microbiota.We will also explore their individual and synergistic immune effects on IBD and look at future therapeutic perspectives for IBD.展开更多
Inflammatory responses are essential in eliminating harmful substrates from damaged tissue and inducing recovery.Several cytokines participate in and facilitate this response. Certain cytokines such as interleukin(IL...Inflammatory responses are essential in eliminating harmful substrates from damaged tissue and inducing recovery.Several cytokines participate in and facilitate this response. Certain cytokines such as interleukin(IL)-1β and IL-18 are initially produced in precursor form in response to toll-like receptor(TLR) ligands and undergo maturation by inflammasomes, which are cytosolic multi-protein complexes containing nucleotide-binding oligomerization domain(NOD)-containing protein 2-like receptors(NLRs). Immune modulators targeting inflammasomes have been investigated to control inflammatory diseases such as metabolic syndrome. However, most immune modulators possessing anti-inflammasome properties attenuate production of other cytokines, which are essential for host defense. In this review, we analyzed the effect of anti-inflammasome agents on the production of cytokines which are not regulated by inflammasome and involving in initial immune responses. As a result, the infiammasome inhibitors are put into three categories: non-effector, stimulator, or inhibitor of cytokine production. Even the stimulator of cytokine production ameliorated symptoms resulting from inflammasome activation in mouse models. Thus, we suggest ideal immune modulators targeting inflammasomes in order to enhance cytokine production while inhibiting cytokine maturation.展开更多
Exogenous alanyl-glutamine（Aln-Gln） was evaluated for its effects on growth performance, intestinal structure and function, antioxidant status and non-specific immunity of young carp（Cyprinus carpio L.）. Six diets...Exogenous alanyl-glutamine（Aln-Gln） was evaluated for its effects on growth performance, intestinal structure and function, antioxidant status and non-specific immunity of young carp（Cyprinus carpio L.）. Six diets supplemented with 0, 2.5, 5.0, 7.5, 10.0, or 15.0 g · kg-1 of Aln-Gln were fed to fish for 12 weeks. Supplementation with 7.5, 10.0, or 15.0 g · kg-1 of Aln-Gln significantly increased weight gain rate（WGR）, protein efficiency ratio（PER）, but feed conservation rate（FCR） and survival were not affected（P〉0.05）. The intestinal fold height and number, digestive enzyme, Na＋, K＋-ATPase activities was found to be significantly high（P〈0.05） with increasing dietary Aln-Gln supplementation up to 7.5 g · kg-1, but there were no significant differences for Aln-Gln supplementation from 7.5 to 15.0 g · kg-1. The glutathione peroxidase（GPX） activity, glutathione（GSH）, superoxide dismutase（SOD） activity increased and malondialdehyde（MDA） levels decreased significantly（P〈0.05） in the intestine, hepatopancreas, plasma and muscles. The plasma complement-3（C3） and complement-4（C4） levels were significantly（P〈0.05） improved at 5.0 g · kg-1 level and decreased when over 7.5 g · kg-1. The plasma lysozyme（LSZ） activity increased significantly（P〈0.05） at 7.5, 10.0, or 15.0 g · kg-1 level. In summary, the results showed that Aln-Gln improved growth performance, development and function of the intestine, the activity of the antioxidant defense system and the plasma non-specific immunity of the carps. The optimal Aln-Gln level was 8.24 g · kg-1 diet for WGR based on broken-line regression model analysis.展开更多
The study aims to determine the effects of graded farming on growth performance and non-specific immunity factors of shrimp Litopenaeus vannamei Boone. Three size groups of shrimp, i.e., the small size group [Gs, with...The study aims to determine the effects of graded farming on growth performance and non-specific immunity factors of shrimp Litopenaeus vannamei Boone. Three size groups of shrimp, i.e., the small size group [Gs, with an average body length （BL） of （3.04 ± 0.36） cm and body weight （BW） （0.412± 0.35） g], the large group [GL, with a BL of （4.29±0.55） cm and BW of （1.098 ±0.42） g], and the ungraded group [Gm, with a BL of （3.47±0.81） cm and BW of （0.611 ±0.79） g], were reared under the same conditions for 8 wk. Growth performance and non- specific immunity factors were measured. The results showed that BW gain, biomass gain and the specific growth rate of body length （SGRL） were significantly influenced by size grading （one-way ANOVA, P 〈 0.05）. The peroxidase （POD） and antibacterial （Ua） activities of GL were lower than those of G. Superoxide dismutase （SOD） and lysozyme （U1） activities of Gm were lower than those of G. No significant difference （P = 0.121 〉 0.05） was found on phenoloxidase （PO） activity among the three size groups. Synthetically, size grading could enhance growth and rearing efficiency, and did not have a significant influence on the immunity of L. vannamei Boone. Therefore, graded fanning in L. vannamei Boone was feasible in the culture practice.展开更多
Acute pancreatitis(AP) is one of the most common diseases of the gastrointestinal tract,bearing significant morbidity and mortality worldwide.Current treatment of AP remains unspecific and supportive and is mainly tar...Acute pancreatitis(AP) is one of the most common diseases of the gastrointestinal tract,bearing significant morbidity and mortality worldwide.Current treatment of AP remains unspecific and supportive and is mainly targeted to aggressively prevent systemic complications and organ failure by intensive care.As acute pancreatitis shares an indistinguishable profile of inflammation with sepsis,therapeutic approaches have turned towards modulating the systemic inflammatory response.Targets,among others,have included pro- and antiinflammatory modulators,cytokines,chemokines,immune cells,adhesive molecules and platelets.Even though,initial results in experimental models have been encouraging,clinical implementation of immuneregulating therapies in acute pancreatitis has had a slow progress.Main reasons include difficulty in clinical translation of experimental data,poor understanding of inflammatory response time-course,flaws in experimental designs,need for multimodal approaches and commercial drawbacks.Whether immune-modulation in acute pancreatitis remains a fact or just fiction remains to be seen in the future.展开更多
基金supported by grants from the Tianjin Health Technology Project(Grant No.2022QN106).
文摘Background:The nuclear receptor coactivator(NCOA)family,including NCOA1,NCOA2,and NCOA3,is critical in regulating gene expression through interactions with nuclear receptors and other transcription factors.These coactivators are implicated in various cancers,but their comprehensive roles across different cancer types remain poorly understood.Methods:We performed a pan-cancer bioinformatics analysis using data from The Cancer Genome Atlas and the Genotype-Tissue Expression project.We assessed the differential expression,copy number variations,mutations,methylation status,tumor mutation burden,microsatellite instability,and immune cell infiltration associated with NCOA family members across various cancers.Differential expression analysis was conducted using the DESeq2 package.Methylation data were analyzed using the ChAMP package,and immune cell infiltration was estimated using the CIBERSORT algorithm.Results:NCOA1 and NCOA2 were predominantly downregulated in multiple cancers,suggesting potential tumor suppressor roles,whereas NCOA3 was largely upregulated,indicating a consistent oncogenic function.These expression patterns significantly correlated with patient prognosis.Frequent copy number variations,particularly gains,and high mutation rates were observed in NCOA2.NCOA3 demonstrated consistent hypomethylation in tumors,which was associated with increased gene expression.Significant correlations were found between NCOA expression and tumor mutation burden,microsatellite instability,and immune cell infiltration,indicating their involvement in genomic instability and immune modulation.Conclusion:This comprehensive analysis reveals significant alterations in the expression,genomic,and epigenetic profiles of NCOA family members across various cancers.The findings highlight the multifaceted roles of NCOA1,NCOA2,and NCOA3 in tumorigenesis and their potential as biomarkers and therapeutic targets.Future research should focus on elucidating the mechanisms underlying the associations between NCOA expression,genomic alterations,and immune modulation to develop targeted cancer therapies.
基金supported by the National Natural Science Foundation of China(82274204 and 82104134)the Natural Science Foundation of Shandong Province,China(ZR2024QH110)+1 种基金the Major Basic Program of Shandong Natural Science Foundation,China(ZR2021ZD17)the Project of Youth Innovation Team of Shandong Province(2022KJ254).
文摘The emergence of SARS-CoV-2 variants and drug-resistant mutants emphasizes the urgent need to develop novel antiviral agents.In the present study,we examined the therapeutic effect of the Chinese medicinal herb,Scutellaria barbata D.Don(SBD),against SARS-CoV-2 infection both in vitro and in vivo.Using a viral replicon particle(VRP)-based mouse model of SARS-CoV-2 infection,our study revealed that SBD extracts can reduce viral load in mouse lungs and alleviate the viral induced pneumonia.In vitro antiviral determination further validated the direct acting antiviral efficacy of SBD extracts against SARS-CoV-2 replication.Mechanistic studies demonstrated that SBD can act against SARS-CoV2 replication by targeting both 3-chymotrypsin-like and papain-like cysteine proteases,via a combination of multiple active constituents.Moreover,SBD can modulate the host inflammation response in a bi-directional manner,which also contribute to the mitigation of viral induced acute lung injury.In summary,our study provides SBD as a promising therapeutic agent to combat SARS-CoV-2 infections that merit further development.
基金supported by the Natural Sci-ence Foundation of Shandong(Nos.ZR2022MC086 and ZR2023MC162).
文摘In order to verify the synthesis pathway of linoleic acid(LA)to generate arachidonic acid(ARA),the functions ofΔ6 FAD and Elovl 5 in Apostichopus japonicus were tested by heterologous expression in Pichia pastoris.A 60-day feeding experiment was conducted to evaluate the effects of dietary LA and ARA on growth,polyunsaturated fatty acids(PUFA)biosynthesis and im-mune function of A.japonicus.Seven diets containing graded levels of LA or ARA were formulated,and one diet without PUFA was applied as a control.The results confirmed thatΔ6 FAD from A.japonicus has a double desaturation ability ofΔ6 andΔ5 for PUFA,and it works together with Elovl 5 enzyme play important roles in biosynthesis of ARA from LA.With increasing dietary LA from 4.9 to 12.1 g/kg,the expressions ofΔ6 FAD and Elovl 5,levels of LA,ARA and EPA in tissues increased,and the activities of ACP,AKP and CAT enzymes in intestine initially increased and then decreased.Additionally,by increasing dietary ARA from 0.7 to 3.8 g/kg,the contents of ALA,EPA and DHA decreased,while theΔ6 FAD expression and the activities of ACP,AKP and CAT in intes-tine increased significantly.Therefore,appropriate dietary levels of LA(12.1 g/kg)or ARA(3.8 g/kg)build a reasonable composi-tion of n-3/n-6 PUFA in A.japonicus,and improved its growth,antioxidant capacity and immunological defenses.
文摘The immune system is the body's main cancer surveillance system.Unlike surgery,radiation,and chemotherapy,which are typically nonspecific,cancer immunotherapy holds tremendous promise as it harnesses the high specificity of a person's immune system to kill cancer cells selectively.This promising approach includes checkpoint inhibitors,chimeric antigen receptor (CAR)-T cell therapy,cancer vaccines,cytokines,and monoclonal antibodies,among others.Cancer immunotherapy has progressed tremendously,resulting from basic science discoveries in the molecular and cellular biology of T cells.
文摘The concept of neuroimmune interactions has shown significant advancements over the years. Modern research has revealed many areas of connection between fields, which were previously viewed as distinct disciplines. For example, the nervous system can sense changes in the external environment and convey these changes through molecules and mediators with receptors in the immune system to modulate immune responses. Neuromediators can act on different receptors in the same group of cells, producing antipodal effects. Identification of the anti-inflammatory role of glucocorticoids highlighted that the body functions properly in an integrated manner. These interactions and crosstalk are not unidirectional, as the immune system can also influence various aspects of the nervous system, such as synaptic plasticity and fever. Strict integration of neuro-immuno-endocrine circuits is indispensable for homeostasis. Understanding these circuits and molecules can lead to advances in the understanding of various immune diseases, which will offer promising therapeutic options.
文摘Objectives:The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery,particularly in cancer therapy.This study aimed to evaluate the cytotoxicity,apoptosis induction,and immune-modulatory activities of extracts from three herbal medicines with historical use in traditional medicine—Acanthopanax sessiliflorus,Phragmites communis,and Pinus densiflora,as well as their combined extract(GMAS 01/COM),on human lung cancer cells(A549)and normal cell lines,including murine macrophages(RAW 264.7)and human keratinocytes(HaCaT).Methods:Plant extracts were prepared using aqueous extraction,sonication,and rotary evaporation.The total phenolic and flavonoid contents were quantified using the Folin-Ciocalteu and AlCl3 colorimetric methods,respectively.Antioxidant potential was evaluated via 2,2-Diphenyl-1-picrylhydrazyl(DPPH)scavenging and reducing power assays.Cytotoxicity was assessed using an MTT assay,while reactive oxygen species(ROS)generation was quantified using a 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA)assay.Anticancer properties,including colony formation inhibition and migration suppression,were examined using colony formation and wound healing assays.The expression of apoptotic and inflammatory mediators was analysed through qPCR.Results:GMAS 01 selectively induced apoptosis in A549 cells without cytotoxic effects on RAW264.7 and HaCaT cells.Mechanistically,it elevated intracellular ROS and activated the intrinsic mitochondrial apoptotic pathway,evidenced by p53 upregulation,increased Bax,and decreased Bcl-2 expression.GMAS 01 also significantly inhibited colony formation and migration in A549 cells.In RAW264.7 cells,it reduced nitric oxide(NO)production and downregulated iNOS,COX-2,IL-6,and IL-8,indicating strong immunomodulatory activity.Conclusion:GMAS 01 exhibits potent antioxidant,anti-inflammatory,and anticancer effects,likely mediated through ROS-induced mitochondrial apoptosis.However,mechanistic interpretations are limited by the absence of protein-level validation and pathway inhibition studies.Upcoming studies should aim to verify the underlying mechanisms and evaluate their potential for real-world application.
文摘Hepatocellular carcinoma(HCC),a primary malignancy of the liver and leading cause of cancer-related mortality worldwide,poses substantial therapeutic challenges,particularly in advanced and unresectable stages.Immune checkpoint inhibitors(ICIs)have emerged as critical therapeutic agents,targeting immune checkpoint pathways to restore antitumor immune responses.Combinations such as atezolizumab(anti-programmed cell death ligand 1 with bevacizumab antivascular endothelial growth factor),as well as antibodies directed against cytotoxic T-lymphocyte associated protein 4 and programmed cell death protein 1(e.g.,ipilimumab and nivolumab),have demonstrated improved clinical outcome in selected patients.However,the overall efficacy of ICIs remains hindered by variable response rate and primary or acquired resistance.Recent evidence suggests that the gut microbiome plays a pivotal role in modulating host immune responses and may significantly influence the therapeutic efficacy of ICIs.Dysbiosis within the gut-liver axis has been implicated not only in pathogenesis and progression of HCC but also diminishing immunotherapy effectiveness.Emerging studies highlight the potential of microbiome-targeted interventions including dietary modulation,prebiotics,probiotics,and fecal microbiota transplantation to enhance ICIs responsiveness.This review explores the evolving interplay between the gut microbiota and immunotherapy in HCC,with a focus on microbiome-based strategies aimed at optimizing clinical outcomes.
基金supported financially by the grants from the JBGS[2021]002 project from the Jiangsu Governmentthe National Nature Science Foundation of China(32472095)+2 种基金the National Key Research and Development Program of China(2020YFE02029002)Collaborative Innovation Center for Modern Crop Production(CIC-MCP)to Xiquan Gaosupported in part by the high-performance computing platform of Bioinformatics Center,Nanjing Agricultural University。
文摘Gibberella stalk rot(GSR)caused by Fusarium graminearum is one of the most devastating diseases of maize,seriously impacting maize yield and quality,as well as the ability to use technology of mechanical harvesting.Environmental conditions including photoperiod affect crop disease resistance.However,the mechanism underlying photoperiod-regulated maize GSR resistance remains unexplored.We found in this study that GSR resistance is regulated by the ZmPIF4.1(Phytochrome-Interacting Factor4)-ZmPTI1c(Pto-Interacting 1)-ZmMYB31 module coupled with photoperiod.The functional analysis of zmpti1c mutant indicated that ZmPTI1c negatively regulates maize GSR resistance.Short day promoted the disease progression in both zmpti1c and wild-type plants.ZmPTI1c promoter contains multiple predicted cis-acting elements for light responses.Yeast one-hybrid assay(Y1H),Electrophoretic mobility shift analysis(EMSA),and Dual-luciferase(LUC)reporter assays demonstrated that ZmPIF4.1 binds to the G-box in ZmPTI1c promoter and activates its expression.Moreover,expression levels of ZmPIF4 and ZmPTI1c were significantly higher under short day than under long day.ZmPTI1c interacted with and phosphorylated ZmMYB31.GSR resistance in zmmyb31 mutant was significantly increased than in wild type,indicating that ZmMYB31 also negatively regulated GSR resistance.Furthermore,ZmMYB31 suppressed the transcriptional activation of ZmPTI1c by ZmPIF4.1.Overall,ZmPIF4.1-ZmPTI1c-ZmMYB31negatively regulates maize immunity to GSR,which is likely modulated by photoperiod.
文摘BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related morbidity and mor-tality globally.Exosomal microRNAs(miRNAs)are known to modulate tumor progression by influencing immune responses and vascular dynamics.However,the roles of specific exosomal miRNAs,such as miR-425-5p and miR-135b-3p,in CRC remain unclear.AIM To explore the specific roles and underlying mechanisms of exosomal miR-425-5p and miR-135b-3p in CRC progression.METHODS Differentially expressed miRNAs were identified through microarray analysis of exosomes isolated from CRC tissues and adjacent normal mucosa.Functional roles of miR-425-5p and miR-135b-3p were evaluated in vitro using macrophage polarization,T cell differentiation,and vascular permeability assays,as well as in vivo tumor formation and metastasis experiments in nude mice.Validation expe-riments were performed using CRC cell lines(HCT116 and SW620).RESULTS Exosomal miR-425-5p and miR-135b-3p were significantly upregulated in CRC compared to normal tissues.Functional studies revealed that miR-425-5p promo-tes macrophage M2-like polarization and suppresses T cell proinflammatory responses,while miR-135b-3p enhances vascular permeability and angiogenesis.Inhibition of these miRNAs in CRC cell-derived exosomes significantly supp-ressed tumor growth and metastasis in nude mice,reprogramming the tumor microenvironment toward reduced angiogenesis and enhanced immune acti-vation.Combined inhibition of both miRNAs resulted in the most pronounced effects.CONCLUSION Exosomal miR-425-5p and miR-135b-3p drive CRC progression by promoting immune suppression and vascular permeability.Their inhibition offers a promising strategy for modulating the tumor microenvironment and limiting CRC metastasis.
基金The research that yielded these results,was funded by the Belgian Federal Public Service of Health,Food Chain Safety and Environment through the contract RF 17/6314 LactoPigHealthMatthias Dierick is supported by the Flemish fund for scientific research(FWO3S036319).
文摘Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial resistance.Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated.Lactoferrin has shown promising results against porcine enterotoxigenic E.coli strains,both in vitro and in vivo.Results We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned piglets.Additionally,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E.coli(STEC)infection.Therefore,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC strain.BLF did not affect theα-andβ-diversity.However,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa.When analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF group.Conclusion Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned piglets.Nevertheless,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut homeostasis.Furthermore,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.
文摘Enteral nutrition has been strongly recommended by major scientific societies for the nutritional management of patients with acute pancreatitis.Providing severe acute pancreatitis patients with enteral nutrition within the first 24-48 h of hospital admission can help improve outcomes compared to parenteral nutrition and no feeding.New research is focusing in on when and what to feed to best improve outcomes for acute pancreatitis patients.Early enteral nutrition have the potential to modulate the immune responses.Despite this consistent evidence of early enteral nutrition in patients with acute pancreatitis,clinical practice continues to vary due to individual clinician preference.Achieving the immune modulating effects of enteral nutrition heavily depend on proper placement of the feeding tube and managing any tube feeding associated complications.The current article reviews the immune modulating effects of enteral nutrition and pro-and prebiotics and suggests some practical tools that help improve the patient adherence and tolerance to the tube feeding.Proper selection of the type of the tube,close monitoring of the tube for its placement,patency and securing its proper placement and routine checking the gastric residual volume could all help improve the outcome.Using peptide-based and high medium chaintriglycerides feeding formulas help improving feeding tolerance.
基金Supported by the Special Scientific Research Funds for Central Non-profit Institutes,Yellow Sea Fisheries Research Institute,Chinese Academy of Fishery Sciences(No.20603022016008)the National Key R&D Program of China(No.2018YFD0901603)the Agriculture Seed Improvement Project of Shandong Province(No.2017LZGC010)
文摘In this study, the influences of immersion bathing in different concentrations of Bacillus velezensis DY-6 on the body weight gain rate and non-specific immune enzyme activities of the coelom fluid of sea cucumber (Apostichopus japonicus) were determined in order to obtain the optimum bacterial concentration. The gut microbiota change in A. japonicus was then analyzed through high-throughput sequencing during the immersion bathing in B. velezensis DY-6 at the optimum concentration for 49 d. The results illustrate that the body weight growth rate of all bathing groups was higher than that of the control. The highest growth rate (25.3%) was achieved when the bacterial concentration was 1×10^3 CFU/mL. The activities of non-specific immune enzymes (ACP, AKP, SOD and LZM) of all bathing groups increased, and the activities of the enzymes of groups bathed with the bacterium at 1×10^3 and 1×10^4 CFU/mL reached the highest on day 21 and day 28. Taking the growth rate and economic cost into consideration, the optimum concentration of B. velezensis DY-6 was 1×10^3 CFU/mL. The influences of immersion bathing in B. velezensis DY-6 at 1×10^3 CFU/mL on the gut microbiota of A. japonicus were then evaluated through 16S rDNA sequencing analysis. Results showed that the gut microbiota changed with the addition of B. velezensis DY-6, and the richness and diversity of the gut microbiota peaked twice on day 14 and day 21, respectively. In association with the non-specific immune enzyme activities and if day 28 was selected as the dividing point, the community structure of the gut microbiota could be obviously divided into two types. The correlation analysis revealed that the non-specific immune enzyme activities were correlated significantly to some gut bacteria (in the phyla Firmicutes, Proteobacteria, and Bacteroidetes) after immersion bathing in B. velezensis DY-6. Our findings will provide the theoretical foundation for probiotic application in sea cucumber farming.
文摘Based on Immune Programming(IP), a novel Radial Basis Function (RBF) networkdesigning method is proposed. Through extracting the preliminary knowledge about the widthof the basis function as the vaccine to form the immune operator, the algorithm reduces thesearching space of canonical algorithm and improves the convergence speed. The application ofthe RBF network trained with the algorithm in the modulation-style recognition of radar signalsdemonstrates that the network has a fast convergence speed with good performances.
文摘Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liverdisease(MELD) score helped to reduce waiting list mortality in liver transplantation(LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients' infectious and immunologic risk profiles. The administration of intravenous immunoglobulins(IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.
基金Supported by National High-Tech Research and Development Program of China (863 Program, No.2001AA5070, 2002AA639600)Natural Science Foundation of Fujian Province of China (No.B0410022, 2006F5066)
文摘Non-specific immune response of bullfrog Rana catesbeiana to pathogenic Aeromonas hydrophila was studied to 60 individuals in two groups.Each bullfrog in bacterium-injected group was injected intraperitoneally(i.p.) with 0.2 ml bacterial suspension at a density of 5.2 × 106 CFU/ml,while each one in control group injected i.p.with 0.2 ml sterile saline solution(0.85%,w/v).Three bullfrogs in both groups were sampled at 0,1,3,7,11,15 and 20 days post-injection(dpi) for the evaluation of non-specific immune parameters.It was observed that intraperitoneal injection of A.hydrophila significantly increased the number of leucocytes and that of NBT-positive cells in peripheral blood.Significant increases in serum bactericidal activity and serum acid phosphatase activity were also observed in the bacterium-injected frogs when compared with those in the control group.However,a significant reduction was detected in vitro in phagocytosis activity of peripheral blood phagocytes.No significant difference in changes in the number of peripheral erythrocytes,serum superoxide dismutase(SOD) activity,and lysozyme activity was detected between the two groups.It is suggested that bullfrogs may produce a series of non-specific immune reactions in response to the A.hydrophila infection.
文摘A recent study published in the World Journal of Gastroenterology,suggests that transplanting the gut microbiota from healthy donors can alleviate the pathological processes linked to inflammatory bowel disease(IBD),particularly Crohn's disease.In addition,that paper illustrates the effect of changes in the gut microbiota on IBD and points out that altered mesenteric adipose tissue caused by the gut microbiota and creeping fat lead to increased inflammation,which exacerbates IBD.Moreover,recent research has shown that the interaction between Helicobacter pylori(H.pylori)and the gut microbiota is mediated through immune mechanisms,resulting in a synergistic impact on IBD.Therefore,in this manuscript,we will focus on the role of the gut microbiota and H.pylori in the immune response to IBD,as well as the possible impact of H.pylori on the gut microbiota.We will also explore their individual and synergistic immune effects on IBD and look at future therapeutic perspectives for IBD.
基金supported by 2015 Research Grant from Kangwon National University(No.520150280)
文摘Inflammatory responses are essential in eliminating harmful substrates from damaged tissue and inducing recovery.Several cytokines participate in and facilitate this response. Certain cytokines such as interleukin(IL)-1β and IL-18 are initially produced in precursor form in response to toll-like receptor(TLR) ligands and undergo maturation by inflammasomes, which are cytosolic multi-protein complexes containing nucleotide-binding oligomerization domain(NOD)-containing protein 2-like receptors(NLRs). Immune modulators targeting inflammasomes have been investigated to control inflammatory diseases such as metabolic syndrome. However, most immune modulators possessing anti-inflammasome properties attenuate production of other cytokines, which are essential for host defense. In this review, we analyzed the effect of anti-inflammasome agents on the production of cytokines which are not regulated by inflammasome and involving in initial immune responses. As a result, the infiammasome inhibitors are put into three categories: non-effector, stimulator, or inhibitor of cytokine production. Even the stimulator of cytokine production ameliorated symptoms resulting from inflammasome activation in mouse models. Thus, we suggest ideal immune modulators targeting inflammasomes in order to enhance cytokine production while inhibiting cytokine maturation.
基金Supported by the Earmarked Fund for China Agriculture Research System(CARS-46)the Special Scientific Research Funds for Central Non-profit Institutes,Chinese Academy of Fishery Sciences(2014A08XK03)
文摘Exogenous alanyl-glutamine（Aln-Gln） was evaluated for its effects on growth performance, intestinal structure and function, antioxidant status and non-specific immunity of young carp（Cyprinus carpio L.）. Six diets supplemented with 0, 2.5, 5.0, 7.5, 10.0, or 15.0 g · kg-1 of Aln-Gln were fed to fish for 12 weeks. Supplementation with 7.5, 10.0, or 15.0 g · kg-1 of Aln-Gln significantly increased weight gain rate（WGR）, protein efficiency ratio（PER）, but feed conservation rate（FCR） and survival were not affected（P〉0.05）. The intestinal fold height and number, digestive enzyme, Na＋, K＋-ATPase activities was found to be significantly high（P〈0.05） with increasing dietary Aln-Gln supplementation up to 7.5 g · kg-1, but there were no significant differences for Aln-Gln supplementation from 7.5 to 15.0 g · kg-1. The glutathione peroxidase（GPX） activity, glutathione（GSH）, superoxide dismutase（SOD） activity increased and malondialdehyde（MDA） levels decreased significantly（P〈0.05） in the intestine, hepatopancreas, plasma and muscles. The plasma complement-3（C3） and complement-4（C4） levels were significantly（P〈0.05） improved at 5.0 g · kg-1 level and decreased when over 7.5 g · kg-1. The plasma lysozyme（LSZ） activity increased significantly（P〈0.05） at 7.5, 10.0, or 15.0 g · kg-1 level. In summary, the results showed that Aln-Gln improved growth performance, development and function of the intestine, the activity of the antioxidant defense system and the plasma non-specific immunity of the carps. The optimal Aln-Gln level was 8.24 g · kg-1 diet for WGR based on broken-line regression model analysis.
基金supported by the National High-TechR&D Program of China (2004BA526B02)the Natural Science Foundation of Qingdao Agricultural Univesity,China (610804)the High Level Talents Fund of Qingdao Agricultural University, China (630628)
文摘The study aims to determine the effects of graded farming on growth performance and non-specific immunity factors of shrimp Litopenaeus vannamei Boone. Three size groups of shrimp, i.e., the small size group [Gs, with an average body length （BL） of （3.04 ± 0.36） cm and body weight （BW） （0.412± 0.35） g], the large group [GL, with a BL of （4.29±0.55） cm and BW of （1.098 ±0.42） g], and the ungraded group [Gm, with a BL of （3.47±0.81） cm and BW of （0.611 ±0.79） g], were reared under the same conditions for 8 wk. Growth performance and non- specific immunity factors were measured. The results showed that BW gain, biomass gain and the specific growth rate of body length （SGRL） were significantly influenced by size grading （one-way ANOVA, P 〈 0.05）. The peroxidase （POD） and antibacterial （Ua） activities of GL were lower than those of G. Superoxide dismutase （SOD） and lysozyme （U1） activities of Gm were lower than those of G. No significant difference （P = 0.121 〉 0.05） was found on phenoloxidase （PO） activity among the three size groups. Synthetically, size grading could enhance growth and rearing efficiency, and did not have a significant influence on the immunity of L. vannamei Boone. Therefore, graded fanning in L. vannamei Boone was feasible in the culture practice.
文摘Acute pancreatitis(AP) is one of the most common diseases of the gastrointestinal tract,bearing significant morbidity and mortality worldwide.Current treatment of AP remains unspecific and supportive and is mainly targeted to aggressively prevent systemic complications and organ failure by intensive care.As acute pancreatitis shares an indistinguishable profile of inflammation with sepsis,therapeutic approaches have turned towards modulating the systemic inflammatory response.Targets,among others,have included pro- and antiinflammatory modulators,cytokines,chemokines,immune cells,adhesive molecules and platelets.Even though,initial results in experimental models have been encouraging,clinical implementation of immuneregulating therapies in acute pancreatitis has had a slow progress.Main reasons include difficulty in clinical translation of experimental data,poor understanding of inflammatory response time-course,flaws in experimental designs,need for multimodal approaches and commercial drawbacks.Whether immune-modulation in acute pancreatitis remains a fact or just fiction remains to be seen in the future.
