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
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
This editorial discusses the insightful minireview by Rahmati et al.The minireview delves into the role of the aryl hydrocarbon receptor in the development and progression of esophageal squamous cell carcinoma,highlig...This editorial discusses the insightful minireview by Rahmati et al.The minireview delves into the role of the aryl hydrocarbon receptor in the development and progression of esophageal squamous cell carcinoma,highlighting its potential as a promising therapeutic target.The authors concisely summarize the current understanding of how aryl hydrocarbon receptor modula-tion influences immune responses and the tumor microenvironment,offering fresh perspectives on therapeutic strategies.This editorial aimed to emphasize the significance of these findings and their potential impact on future research and clinical practices for the management of esophageal squamous cell carcinoma.展开更多
Haptoglobin,a protein primarily recognized for its role in sequestering free hemoglobin,has been identified as a molecule with diverse and underexplored functions in the pathophysiology of various diseases.This editor...Haptoglobin,a protein primarily recognized for its role in sequestering free hemoglobin,has been identified as a molecule with diverse and underexplored functions in the pathophysiology of various diseases.This editorial explores the multifaceted roles of haptoglobin,highlighting its involvement in inflammatory responses and immune regulation and its potential implications in chronic diseases such as diabetes,cardiovascular disorders,and cancer.Through a synthesis of recent research findings,this editorial reveals the importance of haptoglobin in disease mechanisms and underscores the need for further investigation to fully elucidate its therapeutic potential.A comprehensive understanding of haptoglobin’s novel functions may catalyze the development of innovative diagnostic and therapeutic modalities in clinical practice.展开更多
Two hundred and forty specific pathogen free leghorn chickens were randomly divided into four groups and reared in isolated pens. The tested chickens were negative to infectious bursal disease virus （IBDV） at 25 d o...Two hundred and forty specific pathogen free leghorn chickens were randomly divided into four groups and reared in isolated pens. The tested chickens were negative to infectious bursal disease virus （IBDV） at 25 d old. Group 1 was treated with saline, whereas Groups 2, 3, and 4 were inoculated with 0.3 mL IBDV suspension intranasally the next day. Groups 3 and 4 were also administered with Astragalus polysaccharides （APS） intramuscularly twice daily at 5 or 10 mg kg-1 BW, respectively, until 31 d old. The erythrocyte-C3b receptor rosette rate （E-C3bRR） and the erythrocyte-C3b immune complex rosette rate （E-ICRR） were measured at 25, 29, 32, 35, and 38 d old. The results showed that IBDV significantly reduced E-C3bRR and E-ICRR when compared with the control group （P 〈 0.05）, while simultaneous administration of APS with 1BDV maintained E-C3bRR at similar levels to the control group （P 〉 0.05） and increased E-ICRR when compared with the control group and the group non-treated with APS （P 〈 0.05）. APS treatment reduced the morbidity and mortality of chickens inoculated with IBDV （P 〈 0.05）. The results suggest that APS may enhance the immune adherence of chickens erythrocytes by affecting the activity and/or the number of complement receptors on the erythrocyte membrane. These findings can be beneficial in providing an understanding of the basic mechanisms required for the rational application of APS in modern medicine.展开更多
AIM： To investigate cytokine production and cell surface phenotypes of dendritic cells （DC） in the presence of epithelial cells stimulated by probiotics.METHODS： Mouse DC were cultured alone or together with mouse...AIM： To investigate cytokine production and cell surface phenotypes of dendritic cells （DC） in the presence of epithelial cells stimulated by probiotics.METHODS： Mouse DC were cultured alone or together with mouse epithelial cell monolayers in normal or in- verted systems and were stimulated with heat-killed probiotic bacteria, Bifidobacterium lactis ADO 11 （BL）, Bifidobacterium bilfidum BGN4 （BB）, Lactobacillus casei IBS041 （LC）, and Lactobacillus acidophilus AD031 （LA）, for 12 h. Cytokine levels in the culture supernatants were determined by enzyme-linked immunosorbent as say and phenotypic analysis of DC was investigated by flow cytometry.RESULTS： BB and LC in singlecultured DC increased the expression of I-Ad, CD86 and CD40 （I-Ad, 18.51 vs 30.88, 46.11, CD86, 62.74 vs 92.7, 104.12; CD40, 0.67 vs 6.39, 3.37, P 〈 0.05）. All of the experimental probiot-ics increased the production of inflammatory cytokines, interleukin （IL）-6 and tumor necrosis factor （TNF）-α. However, in the normal coculture systems, LC and LA decreased the expression of I-A^α （39.46 vs 30.32, 33.26, P 〈 0.05）, and none of the experimental probiotics increased the levels of IL-6 or TNF-α. In the inverted coculture systems, LC decreased the expression of CD40 （1.36 vs -2.27, P 〈 0.05）, and all of the experimental probiotics decreased the levels of IL-6. In addition, BL increased the production of IL-10 （103.8 vs 166.0, P 〈 0.05） and LC and LA increased transforming growth factor-13 secretion （235.9 vs 618.9, 607.6, P 〈 0.05）.CONCLUSION： These results suggest that specific pro- biotic strains exert differential immune modulation mediated by the interaction of dendritic cells and epithelial cells in the homeostasis of gastrointestinal tract.展开更多
In the immune oncology era,the clinical efficacy of immune checkpoint inhibitors(ICIs)against most solid cancers is well known.In hepatocellular carcinoma,the recent success of combination therapy with targeting agent...In the immune oncology era,the clinical efficacy of immune checkpoint inhibitors(ICIs)against most solid cancers is well known.In hepatocellular carcinoma,the recent success of combination therapy with targeting agents has accelerated the search for novel combination strategies.Radiotherapy(RT),an attractive modality,can be combined with ICIs,which act as strong modulators of the tumor immune microenvironment.Herein,we discuss immune modulation caused by radiation and the current trials of RT-ICI combination treatment as well as future perspectives.展开更多
An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,decipherin...An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.展开更多
Respiratory viral co-infections present significant challenges in clinical settings due to their impact on disease severity and patient outcomes.Current diagnostic methods often miss these co-infections,complicating t...Respiratory viral co-infections present significant challenges in clinical settings due to their impact on disease severity and patient outcomes.Current diagnostic methods often miss these co-infections,complicating the epidemiology and management of these cases.Research,primarily conducted in vitro and in vivo,suggests that co-infections can lead to more severe illnesses,increased hospitalization rates,and greater healthcare utilization,especially in high-risk groups such as children,the elderly,and immunocompromised individuals.Common coinfection patterns,risk factors,and their impact on disease dynamics highlight the need for advanced diagnostic techniques and tailored therapeutic strategies.Understanding the virological interactions and immune response modulation during co-infections is crucial for developing effective public health interventions and improving patient outcomes.Future research should focus on the molecular mechanisms of co-infection and the development of specific therapies to mitigate the adverse effects of these complex infections.展开更多
Objective: To study mechanisms by which human gliomas may escape immune surveillance Methods: The effect of supernatant (SN) obtained from cultured media of malignant glioma cell lines on the proliferation of phyto...Objective: To study mechanisms by which human gliomas may escape immune surveillance Methods: The effect of supernatant (SN) obtained from cultured media of malignant glioma cell lines on the proliferation of phytohemagglutinin p stimulated peripheral blood lymphocytes (PBLs) from healthy subjects and patients with gliomas was examined by MTT assay The immunosuppressive factor which might be existed in the SN was identified by neutralization method with specific antibodies and Northern blot hybridization of glioma cells In addition, the cellular immunity of patients with gliomas and relevant hormone and catecholamine were determined Results: It was found that the malignant glioma cells could release an immunosuppressive factor in an autocrine fashion which was further identified as the transforming growth factor β 2 (TGF β 2) It was also demonstrated that the plasma levels of norepinephrine in glioma patients were significantly reduced and correlated well with the suppression of the patients' own cellular immunity Conclusions: Two distinct mechanisms by which human gliomas may evade immune surveillance: 1 The secretion of an immunosuppressive factor which was identified as TGF β 2; 2 The dysfunction of Neuro Immune modulation in the presence of cerebral gliomas展开更多
Blinding diseases such as photoreceptor degenerations are debilitating conditions that severely impair daily lives of affected patients.This group of diseases are amenable to photoreceptor replacement therapies and re...Blinding diseases such as photoreceptor degenerations are debilitating conditions that severely impair daily lives of affected patients.This group of diseases are amenable to photoreceptor replacement therapies and recent transplantation studies provided proof-of-principle for functional recovery at the retinal and behavioral level,though the actual mechanism of repair still needs further investigations.The immune system responds in several ways upon photoreceptor engraftment,resulting in T-cell and macrophage infiltrations and,consequently,decrease in graft survival.Most studies on the role of the immune system suggest a detrimental effect in a therapeutic setting.Conversely,the opposite idea wherein the immune system can be activated towards a protective state was also explored in other experimental paradigms.Here,Neves and colleagues explored the potential of cross-species studies and,to a certain extent,the concept of a protective immune system in retinal degeneration and therapy.Mesencephalic astrocyte-derived neurotrophic factor(MANF)was identified in this study as a novel factor that,by modulating the immune system,can slow down photoreceptor degeneration and improve transplantation outcome.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
Immune checkpoint blockade(ICB)therapy is a revolutionary approach to treat cancers,but still have limited clinical applications.Accumulating evidence pinpoints the immunosuppressive characteristics of the tumor micro...Immune checkpoint blockade(ICB)therapy is a revolutionary approach to treat cancers,but still have limited clinical applications.Accumulating evidence pinpoints the immunosuppressive characteristics of the tumor microenvironment(TME)as one major obstacle.The TME,characterized by acidity,hypoxia and elevated ROS levels,exerts its detrimental effects on infiltrating anti-tumor immune cells.Here,we developed a TME-responsive and immunotherapeutic catalase-loaded calcium carbonate nanoparticles(termed as CAT@CaCO_(3) NPs)as the simple yet versatile multi-modulator for TME remodeling.CaCO_(3) NPs can consume protons in the acidic TME to normalize the TME pH.CAT catalyzed the decomposition of ROS and thus generated O2.The released Ca^(2+)led to Ca^(2+)overload in the tumor cells which then triggered the release of damage-associated molecular patterns(DAMP)signals to initiate anti-tumor immune responses,including tumor antigen presentation by dendritic cells.Meanwhile,CAT@CaCO_(3) NPs-induced immunosupportive TME also promoted the polarization of the M2 tumor-associated macrophages to the M1 phenotype,further enhancing tumor antigen presentation.Consequently,T cell-mediated anti-tumor responses were activated,the efficacy of which was further boosted by aPD-1 immune checkpoint blockade.Our study demonstrated that local treatment of CAT@CaCO_(3) NPs and aPD-1 combination can effectively evoke local and systemic anti-tumor immune responses,inhibiting the growth of treated tumors and distant diseases.展开更多
The antitumor effects of conventional drug carriers are often attenuated and limited in application by biological barriers associated with tumor heterogeneity and resistance brought about by low tumor immunogenicity.W...The antitumor effects of conventional drug carriers are often attenuated and limited in application by biological barriers associated with tumor heterogeneity and resistance brought about by low tumor immunogenicity.With the rapid development of nanotechnology,naturally derived bioactive materials,and live cell carriers,a promising strategy emerges for targeting the tumor microenvironment(TME)for precision cancer therapy.The unique injury-targeting properties of platelets can significantly extend functional activity,which cannot be achieved with conventional nanocarriers.In this review,three strategies based on platelet-engineered materials are systematically described,namely nanoparticles for platelet membrane camouflage,engineered activated platelets,and targeted-platelets nanosystems.Platelet-based nanomaterials can effectively coordinate local and distant tumor-host crosstalk with controlled active tumor site recognition and killing effects due to the presence of specific membrane proteins on the surface and the self-secretion of a large number of particles.Further advances in platelets for effectively overcoming biological barriers and reducing immune resistance in cancer immunotherapy applications will be discussed in future clinical practice.This review provides an overview of recent research advances in platelet-based bioactive material-directed immunotherapy and chemotherapy to inform future antitumor combination therapies.展开更多
Autism spectrum disorder(ASD)is a group of heterogeneous,multi-factorial,neurodevelopmental disorders resulting from genetic and environmental factors interplay.Infection is a significant trigger of autism,especially ...Autism spectrum disorder(ASD)is a group of heterogeneous,multi-factorial,neurodevelopmental disorders resulting from genetic and environmental factors interplay.Infection is a significant trigger of autism,especially during the critical developmental period.There is a strong interplay between the viral infection as a trigger and a result of ASD.We aim to highlight the mutual relationship between autism and viruses.We performed a thorough literature review and included 158 research in this review.Most of the literature agreed on the possible effects of the viral infection during the critical period of development on the risk of developing autism,especially for specific viral infections such as Rubella,Cytomegalovirus,Herpes Simplex virus,Varicella Zoster Virus,Influenza virus,Zika virus,and severe acute respiratory syndrome coronavirus 2.Viral infection directly infects the brain,triggers immune activation,induces epigenetic changes,and raises the risks of having a child with autism.At the same time,there is some evidence of increased risk of infection,including viral infections in children with autism,due to lots of factors.There is an increased risk of developing autism with a specific viral infection during the early developmental period and an increased risk of viral infections in children with autism.In addition,children with autism are at increased risk of infection,including viruses.Every effort should be made to prevent maternal and early-life infections and reduce the risk of autism.Immune modulation of children with autism should be considered to reduce the risk of infection.展开更多
AIM: To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy.
Severe alcoholic hepatitis is implicated as a costly,worldwide public health issue with high morbidity and mortality. The one-month survival for severe alcoholic hepatitis is low with mortality rates high as 30%-50%. ...Severe alcoholic hepatitis is implicated as a costly,worldwide public health issue with high morbidity and mortality. The one-month survival for severe alcoholic hepatitis is low with mortality rates high as 30%-50%. Abstinence from alcohol is the recommended firstline treatment. Although corticosteroids remain as the current evidence based option for selected patients with discriminant function > 32, improvement of short-term survival rate may be the only benefit. Identification of individuals with risk factors for the development of severe alcoholic hepatitis may provide insight to the diverse clinical spectrum and prognosis of the disease. The understanding of the complex pathophysiologic processes of alcoholic hepatitis is the key to elucidating new therapeutic treatments. Newer research describes the use of gut microbiota modification, immune modulation, stimulation of liver regeneration, caspase inhibitors, farnesoid X receptors, and the extracorporeal liver assist device to aid in hepatocellular recovery. Liver transplantation can be considered as the last medical option for patients failing conventional medical interventions. Although the preliminary data is promising in patients with low risk of recividism, controversy remains due to organ scarcity. This review article comprehensively summarizes the epidemiology, pathophysiology, risk factors, and prognostic indicators of severe alcoholic hepatitis with a focus on the current and emerging therapeutics.展开更多
The Manchurian walnut(Juglans mandshurica Maxim.) is rich in proteins, whereas this resource has not been used efficiently. The antifatigue, antioxidative and immunoregulatory effects of Manchurian walnut hydrolysate ...The Manchurian walnut(Juglans mandshurica Maxim.) is rich in proteins, whereas this resource has not been used efficiently. The antifatigue, antioxidative and immunoregulatory effects of Manchurian walnut hydrolysate peptides(MWHPs)were evaluated in this study. MWHPs with a degree of hydrolysis of 32.23% were ultrafiltered and divided into three fractions,namely, high(> 10 k Da), medium(3–10 kDa), and low molecular weight(< 3 kDa), and then fed to mice continuously at doses of 200, 400 or 800 mg/(kg·d). The antifatigue, antioxidative, and immunoregulatory effects of the peptides were tested on the second and fourth weeks of MWHP administration. Results showed that low-molecular-weight MWHPs exerted significant antifatigue(prolonging swimming time, elevating liver glycogen contents, and reducing lactic acid contents), antioxidative(enhancing superoxide dismutase(SOD), GSH-Px, and catalase(CAT) activities and reducing malondialdehyde(MDA) content), and immunoregulatory(raising the immune-organ index and promoting T-lymphocyte proliferation and s Ig A secretion in the intestinal tract) effects. This research indicates that MWHPs have potential applications in health care and may be developed as a base for new functional foods.展开更多
Medline/Pubmed articles relevant to this topic were considered using the search terms ?-microseminoprotein, MSMB, prostate secretory protein of 94 amino acids and PSP94. Full articles were retrieved when the abstract ...Medline/Pubmed articles relevant to this topic were considered using the search terms ?-microseminoprotein, MSMB, prostate secretory protein of 94 amino acids and PSP94. Full articles were retrieved when the abstract was considered relevant. In addition, other data related to this topic including our own are discussed. Summary of fi ndings-?-microseminoprotein(MSMB) is increasingly being considered as a marker for prostatecancer, as reduced levels have been associated with the disease. Here we review various aspects of this protein including its biological and physiological variants, binding proteins and immune modulation; its importance as a marker for biochemical recurrence of prostate cancer; prostate cancer related splice variants and its therapeutic utility. Two of the most important properties of MSMB are related to anticancer functions and immune modulation. Predominant expression of two(short and full-length) splice variants of MSMB has been observed from normal prostate and several other tissues. In benign prostate hyperplasia the short isoform is dominant, constituting 98% of this isoform, whereas in prostate cancer 96% constitute the fulllength isoform. The MSMB promoter single nucleotide polymorphism rs10993994 with the C allele functions as an activated cyclic adenosine monophosphate response element binding protein binding site. This C variant of rs10993994 could be responsible for the production of splice variants under variable conditions. MSMB has binding motifs to a few known proteins including immunoglobulin G and several Cysteine-rich secretory proteins family proteins. MSMB bound to these proteins is considered as immune modulating. Use of MSMB as a urinary marker for detecting aggressive prostate cancers that could resist radiation and surgical treatments, seems possible, but needs further investigation. The ratio of MSMB splice variants could also be a possible approach in understanding prostate cancers, with higher ratios indicating severe disease.展开更多
AIM: To determine the immunomodulatory effect of Shiitake (a mushroom extract),we tested its effect on liver-mediated immune regulation in a model of immune-mediated colitis. METHODS: Four groups of mice were studied....AIM: To determine the immunomodulatory effect of Shiitake (a mushroom extract),we tested its effect on liver-mediated immune regulation in a model of immune-mediated colitis. METHODS: Four groups of mice were studied. Colitis was induced by intracolonic instillation of TNBS in groups A and B. Groups A and C were treated daily with Shiitake extract,while groups B and D received bovine serum albumin. Mice were evaluated for development of macroscopic and microscopic. The immune effects of Shiitake were determined by FACS analysis of intra-hepatic and intrasplenic lymphocytes and IFN-γ ELISPOT assay. RESULTS: Administration of Shiitake resulted in marked alleviation of colitis,manifested by signifi cant improvement in the macroscopic and microscopic scores,and by reduction in IFN-γ-producing colonies in group A,compared to group B mice (1.5 pfu/mL vs 3.7 pfu/mL,respectively). This beneficial effect was associated with a significant increase in the intra-hepatic CD8+ lymphocyte trapping,demonstratedby an increased intrasplenic/intrahepatic CD4/CD8 lymphocyte ratio. These effects were accompanied by a 17% increase in the number of intrahepatic natural killer T (NKT) cells. A similar effect was observed when Shiitake was administered to animals without disease induction. CONCLUSION: Shiitake extract affected liver-mediated immune regulation by altering the NKT lymphocyte distribution and increasing intrahepatic CD8+ T lymphocyte trapping,thereby leading to alleviation of immune-mediated colitis.展开更多
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This editorial discusses the insightful minireview by Rahmati et al.The minireview delves into the role of the aryl hydrocarbon receptor in the development and progression of esophageal squamous cell carcinoma,highlighting its potential as a promising therapeutic target.The authors concisely summarize the current understanding of how aryl hydrocarbon receptor modula-tion influences immune responses and the tumor microenvironment,offering fresh perspectives on therapeutic strategies.This editorial aimed to emphasize the significance of these findings and their potential impact on future research and clinical practices for the management of esophageal squamous cell carcinoma.
文摘Haptoglobin,a protein primarily recognized for its role in sequestering free hemoglobin,has been identified as a molecule with diverse and underexplored functions in the pathophysiology of various diseases.This editorial explores the multifaceted roles of haptoglobin,highlighting its involvement in inflammatory responses and immune regulation and its potential implications in chronic diseases such as diabetes,cardiovascular disorders,and cancer.Through a synthesis of recent research findings,this editorial reveals the importance of haptoglobin in disease mechanisms and underscores the need for further investigation to fully elucidate its therapeutic potential.A comprehensive understanding of haptoglobin’s novel functions may catalyze the development of innovative diagnostic and therapeutic modalities in clinical practice.
文摘Two hundred and forty specific pathogen free leghorn chickens were randomly divided into four groups and reared in isolated pens. The tested chickens were negative to infectious bursal disease virus （IBDV） at 25 d old. Group 1 was treated with saline, whereas Groups 2, 3, and 4 were inoculated with 0.3 mL IBDV suspension intranasally the next day. Groups 3 and 4 were also administered with Astragalus polysaccharides （APS） intramuscularly twice daily at 5 or 10 mg kg-1 BW, respectively, until 31 d old. The erythrocyte-C3b receptor rosette rate （E-C3bRR） and the erythrocyte-C3b immune complex rosette rate （E-ICRR） were measured at 25, 29, 32, 35, and 38 d old. The results showed that IBDV significantly reduced E-C3bRR and E-ICRR when compared with the control group （P 〈 0.05）, while simultaneous administration of APS with 1BDV maintained E-C3bRR at similar levels to the control group （P 〉 0.05） and increased E-ICRR when compared with the control group and the group non-treated with APS （P 〈 0.05）. APS treatment reduced the morbidity and mortality of chickens inoculated with IBDV （P 〈 0.05）. The results suggest that APS may enhance the immune adherence of chickens erythrocytes by affecting the activity and/or the number of complement receptors on the erythrocyte membrane. These findings can be beneficial in providing an understanding of the basic mechanisms required for the rational application of APS in modern medicine.
基金Supported by The Small and Medium Business Administration,No. S1072365the Next-Generation BioGreen 21 Program,No. PJ008005,Rural Development Administration,South Korea
文摘AIM： To investigate cytokine production and cell surface phenotypes of dendritic cells （DC） in the presence of epithelial cells stimulated by probiotics.METHODS： Mouse DC were cultured alone or together with mouse epithelial cell monolayers in normal or in- verted systems and were stimulated with heat-killed probiotic bacteria, Bifidobacterium lactis ADO 11 （BL）, Bifidobacterium bilfidum BGN4 （BB）, Lactobacillus casei IBS041 （LC）, and Lactobacillus acidophilus AD031 （LA）, for 12 h. Cytokine levels in the culture supernatants were determined by enzyme-linked immunosorbent as say and phenotypic analysis of DC was investigated by flow cytometry.RESULTS： BB and LC in singlecultured DC increased the expression of I-Ad, CD86 and CD40 （I-Ad, 18.51 vs 30.88, 46.11, CD86, 62.74 vs 92.7, 104.12; CD40, 0.67 vs 6.39, 3.37, P 〈 0.05）. All of the experimental probiot-ics increased the production of inflammatory cytokines, interleukin （IL）-6 and tumor necrosis factor （TNF）-α. However, in the normal coculture systems, LC and LA decreased the expression of I-A^α （39.46 vs 30.32, 33.26, P 〈 0.05）, and none of the experimental probiotics increased the levels of IL-6 or TNF-α. In the inverted coculture systems, LC decreased the expression of CD40 （1.36 vs -2.27, P 〈 0.05）, and all of the experimental probiotics decreased the levels of IL-6. In addition, BL increased the production of IL-10 （103.8 vs 166.0, P 〈 0.05） and LC and LA increased transforming growth factor-13 secretion （235.9 vs 618.9, 607.6, P 〈 0.05）.CONCLUSION： These results suggest that specific pro- biotic strains exert differential immune modulation mediated by the interaction of dendritic cells and epithelial cells in the homeostasis of gastrointestinal tract.
文摘In the immune oncology era,the clinical efficacy of immune checkpoint inhibitors(ICIs)against most solid cancers is well known.In hepatocellular carcinoma,the recent success of combination therapy with targeting agents has accelerated the search for novel combination strategies.Radiotherapy(RT),an attractive modality,can be combined with ICIs,which act as strong modulators of the tumor immune microenvironment.Herein,we discuss immune modulation caused by radiation and the current trials of RT-ICI combination treatment as well as future perspectives.
基金Supported by the European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.
文摘Respiratory viral co-infections present significant challenges in clinical settings due to their impact on disease severity and patient outcomes.Current diagnostic methods often miss these co-infections,complicating the epidemiology and management of these cases.Research,primarily conducted in vitro and in vivo,suggests that co-infections can lead to more severe illnesses,increased hospitalization rates,and greater healthcare utilization,especially in high-risk groups such as children,the elderly,and immunocompromised individuals.Common coinfection patterns,risk factors,and their impact on disease dynamics highlight the need for advanced diagnostic techniques and tailored therapeutic strategies.Understanding the virological interactions and immune response modulation during co-infections is crucial for developing effective public health interventions and improving patient outcomes.Future research should focus on the molecular mechanisms of co-infection and the development of specific therapies to mitigate the adverse effects of these complex infections.
文摘Objective: To study mechanisms by which human gliomas may escape immune surveillance Methods: The effect of supernatant (SN) obtained from cultured media of malignant glioma cell lines on the proliferation of phytohemagglutinin p stimulated peripheral blood lymphocytes (PBLs) from healthy subjects and patients with gliomas was examined by MTT assay The immunosuppressive factor which might be existed in the SN was identified by neutralization method with specific antibodies and Northern blot hybridization of glioma cells In addition, the cellular immunity of patients with gliomas and relevant hormone and catecholamine were determined Results: It was found that the malignant glioma cells could release an immunosuppressive factor in an autocrine fashion which was further identified as the transforming growth factor β 2 (TGF β 2) It was also demonstrated that the plasma levels of norepinephrine in glioma patients were significantly reduced and correlated well with the suppression of the patients' own cellular immunity Conclusions: Two distinct mechanisms by which human gliomas may evade immune surveillance: 1 The secretion of an immunosuppressive factor which was identified as TGF β 2; 2 The dysfunction of Neuro Immune modulation in the presence of cerebral gliomas
文摘Blinding diseases such as photoreceptor degenerations are debilitating conditions that severely impair daily lives of affected patients.This group of diseases are amenable to photoreceptor replacement therapies and recent transplantation studies provided proof-of-principle for functional recovery at the retinal and behavioral level,though the actual mechanism of repair still needs further investigations.The immune system responds in several ways upon photoreceptor engraftment,resulting in T-cell and macrophage infiltrations and,consequently,decrease in graft survival.Most studies on the role of the immune system suggest a detrimental effect in a therapeutic setting.Conversely,the opposite idea wherein the immune system can be activated towards a protective state was also explored in other experimental paradigms.Here,Neves and colleagues explored the potential of cross-species studies and,to a certain extent,the concept of a protective immune system in retinal degeneration and therapy.Mesencephalic astrocyte-derived neurotrophic factor(MANF)was identified in this study as a novel factor that,by modulating the immune system,can slow down photoreceptor degeneration and improve transplantation outcome.
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 start-up package from McGill University(to G.C.)CIHR grants(to G.C.)+2 种基金CCS-Challenge Grants(to G.C.)the Rolande and Marcel Gosselin Graduate Studentship,Dr.Victor KS Lui Studentship,Charlotte and Leo Karassik Foundation Oncology Ph.D.Fellowship from the Rosalind&Morris Goodman Cancer Institute as well as the BME recruitment awardThe authors thank Dr.Peter Siegel at McGill University for providing the 4T1 cell line.
文摘Immune checkpoint blockade(ICB)therapy is a revolutionary approach to treat cancers,but still have limited clinical applications.Accumulating evidence pinpoints the immunosuppressive characteristics of the tumor microenvironment(TME)as one major obstacle.The TME,characterized by acidity,hypoxia and elevated ROS levels,exerts its detrimental effects on infiltrating anti-tumor immune cells.Here,we developed a TME-responsive and immunotherapeutic catalase-loaded calcium carbonate nanoparticles(termed as CAT@CaCO_(3) NPs)as the simple yet versatile multi-modulator for TME remodeling.CaCO_(3) NPs can consume protons in the acidic TME to normalize the TME pH.CAT catalyzed the decomposition of ROS and thus generated O2.The released Ca^(2+)led to Ca^(2+)overload in the tumor cells which then triggered the release of damage-associated molecular patterns(DAMP)signals to initiate anti-tumor immune responses,including tumor antigen presentation by dendritic cells.Meanwhile,CAT@CaCO_(3) NPs-induced immunosupportive TME also promoted the polarization of the M2 tumor-associated macrophages to the M1 phenotype,further enhancing tumor antigen presentation.Consequently,T cell-mediated anti-tumor responses were activated,the efficacy of which was further boosted by aPD-1 immune checkpoint blockade.Our study demonstrated that local treatment of CAT@CaCO_(3) NPs and aPD-1 combination can effectively evoke local and systemic anti-tumor immune responses,inhibiting the growth of treated tumors and distant diseases.
基金supported by the National Key Research and Development Program of China(Nos.2022YFC2402400 and 2023YFA0915400)Guangdong Provincial Key Area R&D Program(No.2020B1111540001)+5 种基金the Natural Science Foundation of Guangdong Province(Nos.2024A1515010825,2024A1515030063,2022A1515010780,and 2022A1515011337)Guangdong Province Universities and Colleges Characteristic Innovation(No.2021KTSCX036)Traditional Chinese Medicine Research Project of Guangdong Province Traditional Chinese Medicine Bureau(No.20221206)Shenzhen Medical Research Fund(No.A2303057),Discipline Construction Project of Guangdong Medical University(No.4SG24015G)Construction Project of Nano Technology and Application Engineering Research Center of Guangdong Medical University(No.4SG24179G)Funds for PHD researchers of Guangdong Medical University in 2024.
文摘The antitumor effects of conventional drug carriers are often attenuated and limited in application by biological barriers associated with tumor heterogeneity and resistance brought about by low tumor immunogenicity.With the rapid development of nanotechnology,naturally derived bioactive materials,and live cell carriers,a promising strategy emerges for targeting the tumor microenvironment(TME)for precision cancer therapy.The unique injury-targeting properties of platelets can significantly extend functional activity,which cannot be achieved with conventional nanocarriers.In this review,three strategies based on platelet-engineered materials are systematically described,namely nanoparticles for platelet membrane camouflage,engineered activated platelets,and targeted-platelets nanosystems.Platelet-based nanomaterials can effectively coordinate local and distant tumor-host crosstalk with controlled active tumor site recognition and killing effects due to the presence of specific membrane proteins on the surface and the self-secretion of a large number of particles.Further advances in platelets for effectively overcoming biological barriers and reducing immune resistance in cancer immunotherapy applications will be discussed in future clinical practice.This review provides an overview of recent research advances in platelet-based bioactive material-directed immunotherapy and chemotherapy to inform future antitumor combination therapies.
文摘Autism spectrum disorder(ASD)is a group of heterogeneous,multi-factorial,neurodevelopmental disorders resulting from genetic and environmental factors interplay.Infection is a significant trigger of autism,especially during the critical developmental period.There is a strong interplay between the viral infection as a trigger and a result of ASD.We aim to highlight the mutual relationship between autism and viruses.We performed a thorough literature review and included 158 research in this review.Most of the literature agreed on the possible effects of the viral infection during the critical period of development on the risk of developing autism,especially for specific viral infections such as Rubella,Cytomegalovirus,Herpes Simplex virus,Varicella Zoster Virus,Influenza virus,Zika virus,and severe acute respiratory syndrome coronavirus 2.Viral infection directly infects the brain,triggers immune activation,induces epigenetic changes,and raises the risks of having a child with autism.At the same time,there is some evidence of increased risk of infection,including viral infections in children with autism,due to lots of factors.There is an increased risk of developing autism with a specific viral infection during the early developmental period and an increased risk of viral infections in children with autism.In addition,children with autism are at increased risk of infection,including viruses.Every effort should be made to prevent maternal and early-life infections and reduce the risk of autism.Immune modulation of children with autism should be considered to reduce the risk of infection.
基金Supported by The Shanghai Natural Science Fund,No.09ZR1400500the National Natural Science Foundation of China,No.30972600+1 种基金the GuangHui Fund of Hepatitis Prevention Fund Committee China,No.GHZ20100204the Shanghai Health Bureau Fund,No.2012092
文摘AIM: To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy.
文摘Severe alcoholic hepatitis is implicated as a costly,worldwide public health issue with high morbidity and mortality. The one-month survival for severe alcoholic hepatitis is low with mortality rates high as 30%-50%. Abstinence from alcohol is the recommended firstline treatment. Although corticosteroids remain as the current evidence based option for selected patients with discriminant function > 32, improvement of short-term survival rate may be the only benefit. Identification of individuals with risk factors for the development of severe alcoholic hepatitis may provide insight to the diverse clinical spectrum and prognosis of the disease. The understanding of the complex pathophysiologic processes of alcoholic hepatitis is the key to elucidating new therapeutic treatments. Newer research describes the use of gut microbiota modification, immune modulation, stimulation of liver regeneration, caspase inhibitors, farnesoid X receptors, and the extracorporeal liver assist device to aid in hepatocellular recovery. Liver transplantation can be considered as the last medical option for patients failing conventional medical interventions. Although the preliminary data is promising in patients with low risk of recividism, controversy remains due to organ scarcity. This review article comprehensively summarizes the epidemiology, pathophysiology, risk factors, and prognostic indicators of severe alcoholic hepatitis with a focus on the current and emerging therapeutics.
基金Supported by National High Technology Research and Development Program(No.2013AA102206-2)
文摘The Manchurian walnut(Juglans mandshurica Maxim.) is rich in proteins, whereas this resource has not been used efficiently. The antifatigue, antioxidative and immunoregulatory effects of Manchurian walnut hydrolysate peptides(MWHPs)were evaluated in this study. MWHPs with a degree of hydrolysis of 32.23% were ultrafiltered and divided into three fractions,namely, high(> 10 k Da), medium(3–10 kDa), and low molecular weight(< 3 kDa), and then fed to mice continuously at doses of 200, 400 or 800 mg/(kg·d). The antifatigue, antioxidative, and immunoregulatory effects of the peptides were tested on the second and fourth weeks of MWHP administration. Results showed that low-molecular-weight MWHPs exerted significant antifatigue(prolonging swimming time, elevating liver glycogen contents, and reducing lactic acid contents), antioxidative(enhancing superoxide dismutase(SOD), GSH-Px, and catalase(CAT) activities and reducing malondialdehyde(MDA) content), and immunoregulatory(raising the immune-organ index and promoting T-lymphocyte proliferation and s Ig A secretion in the intestinal tract) effects. This research indicates that MWHPs have potential applications in health care and may be developed as a base for new functional foods.
基金the Auckland Medical Research Foundation, New Zealand and Goodfellow Trust, Urology Department, Auckland Hospital, New Zealand for funding the patient recruitment related to this communication.
文摘Medline/Pubmed articles relevant to this topic were considered using the search terms ?-microseminoprotein, MSMB, prostate secretory protein of 94 amino acids and PSP94. Full articles were retrieved when the abstract was considered relevant. In addition, other data related to this topic including our own are discussed. Summary of fi ndings-?-microseminoprotein(MSMB) is increasingly being considered as a marker for prostatecancer, as reduced levels have been associated with the disease. Here we review various aspects of this protein including its biological and physiological variants, binding proteins and immune modulation; its importance as a marker for biochemical recurrence of prostate cancer; prostate cancer related splice variants and its therapeutic utility. Two of the most important properties of MSMB are related to anticancer functions and immune modulation. Predominant expression of two(short and full-length) splice variants of MSMB has been observed from normal prostate and several other tissues. In benign prostate hyperplasia the short isoform is dominant, constituting 98% of this isoform, whereas in prostate cancer 96% constitute the fulllength isoform. The MSMB promoter single nucleotide polymorphism rs10993994 with the C allele functions as an activated cyclic adenosine monophosphate response element binding protein binding site. This C variant of rs10993994 could be responsible for the production of splice variants under variable conditions. MSMB has binding motifs to a few known proteins including immunoglobulin G and several Cysteine-rich secretory proteins family proteins. MSMB bound to these proteins is considered as immune modulating. Use of MSMB as a urinary marker for detecting aggressive prostate cancers that could resist radiation and surgical treatments, seems possible, but needs further investigation. The ratio of MSMB splice variants could also be a possible approach in understanding prostate cancers, with higher ratios indicating severe disease.
基金(in part) The Roman-Epstein Liver Research Foundation (to Y.I.)
文摘AIM: To determine the immunomodulatory effect of Shiitake (a mushroom extract),we tested its effect on liver-mediated immune regulation in a model of immune-mediated colitis. METHODS: Four groups of mice were studied. Colitis was induced by intracolonic instillation of TNBS in groups A and B. Groups A and C were treated daily with Shiitake extract,while groups B and D received bovine serum albumin. Mice were evaluated for development of macroscopic and microscopic. The immune effects of Shiitake were determined by FACS analysis of intra-hepatic and intrasplenic lymphocytes and IFN-γ ELISPOT assay. RESULTS: Administration of Shiitake resulted in marked alleviation of colitis,manifested by signifi cant improvement in the macroscopic and microscopic scores,and by reduction in IFN-γ-producing colonies in group A,compared to group B mice (1.5 pfu/mL vs 3.7 pfu/mL,respectively). This beneficial effect was associated with a significant increase in the intra-hepatic CD8+ lymphocyte trapping,demonstratedby an increased intrasplenic/intrahepatic CD4/CD8 lymphocyte ratio. These effects were accompanied by a 17% increase in the number of intrahepatic natural killer T (NKT) cells. A similar effect was observed when Shiitake was administered to animals without disease induction. CONCLUSION: Shiitake extract affected liver-mediated immune regulation by altering the NKT lymphocyte distribution and increasing intrahepatic CD8+ T lymphocyte trapping,thereby leading to alleviation of immune-mediated colitis.
