Background:Maternal viral infection during pregnancy can lead to maternal immune activation(MIA),increasing the risk of neurodevelopmental disorders in offspring.Amantadine(AMA)exhibits antiviral activity and is widel...Background:Maternal viral infection during pregnancy can lead to maternal immune activation(MIA),increasing the risk of neurodevelopmental disorders in offspring.Amantadine(AMA)exhibits antiviral activity and is widely employed in the management of neurologic conditions.Nevertheless,the efficacy of AMA in treating MIA is currently not established.Methods:MIA was induced by polyinosinic acid-polycytidylic acid(poly(I:C));AMA was administered from embryonic(E)day 11.5 for 3 days.BV-2 cells were stimulated using poly(I:C)and treated with AMA.Behavior was assessed via open field test,elevated plus maze test,three-chamber sociability test,and marble burying test.Neuronal morphology was vizualized using Nissl stain;apoptosis via TUNEL(terminal deoxynucleotidyl transferase dUTP nick-end labeling)stain;protein expression(Iba1,NeuN,CD68,TNF-α[tumor necrosis factor-alpha],IL-1β[interleukin-1β])using immunofluorescence(IF);interleukin-6(IL-6)levels using enzyme-linked immunosorbent assay;reactive oxygen species using staining;Iba1,NeuN,Bcl-2,Bax,and cleaved caspase 3 using Western blot;and gene expression changes using RNA-seq.Results:AMA treatment reduced the levels of IL-6 in maternal blood,improved autism-like behaviors in MIA offspring,and effectively prevented neuronal damage and neuroinflammation.In vitro cellular studies have demonstrated that AMA effectively downregulates the expression levels of pro-inflammatory cytokines,including IL-6,TNF-α,and IL-1β.RNA-seq analysis indicated that AMA mitigates abnormal activation of microglia by modulating inflammatory pathways associated with IL-6.Conclusion:AMA can prevent the development of neuropsychiatric disorders in MIA offspring.This effect may be related to its ability to attenuate neuronal damage,reduce neuronal apoptosis,and inhibit neuroinflammation,indicating that the antiviral drug AMA may be a potential treatment for MIA.展开更多
Designing and synthesizing nanomedicines with multi-modal tumor therapeutic capabilities is the key to cancer treatment.Herein,we prepared MICG nanoparticles(NPs)by assembling glucose oxidase(GOx)and indocyanine green...Designing and synthesizing nanomedicines with multi-modal tumor therapeutic capabilities is the key to cancer treatment.Herein,we prepared MICG nanoparticles(NPs)by assembling glucose oxidase(GOx)and indocyanine green(ICG)with manganese carbonate(MnCO_(3))NPs for starvation therapy cascaded chemodynamic therapy,enhanced phototherapy and immune activation.In MICG NPs,the GOx consumes intratumoral glucose resulting in starvation therapy,and simultaneously produces H_(2)O_(2)and decreases p H in tumor.The intensified acidic tumor environment promotes the decomposition of MnCO_(3)NPs to release Mn^(2+).The Mn^(2+)further catalyzes H_(2)O_(2)to generate hydroxyl radical for chemodynamic therapy.While ICG can generate singlet oxygen(^(1)O_(2))and heat to kill cancer cells through phototherapy mechanism.The hydroxyl radical and ^(1)O_(2) will further accelerate the oxidative stress,intensify immunogenic cell death,induce dendritic cell maturation,and thus activate systemic immunity.This work provides a new therapeutic platform for combining therapy of tumor.展开更多
The occurrence of massive CD4+ T cell depletion is one of the most prominent characteristics of human immunodeficiency virus type 1 (HIV-1) infection during acute phase, resulting in unrestorable destruction to the im...The occurrence of massive CD4+ T cell depletion is one of the most prominent characteristics of human immunodeficiency virus type 1 (HIV-1) infection during acute phase, resulting in unrestorable destruction to the immune system. The infected host undergoes an asymptomatic period lasting several years with low viral load and ostensibly healthy status, which is presumably due to virus-specific adaptive immune responses. In the absence of therapy, an overwhelming majority of cases develop to AIDS within 8-10 years of latent infection. In this review, we discuss the roles in AIDS pathogenesis played by massive CD4+ T lymphocytes depletion in gut-associated lymphoid tissue (GALT) during acute infection and abnormal immune activation emerging in the later part of chronic phase.展开更多
Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive ...Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.展开更多
Background:Autism and schizophrenia are environmental risk factors associated with prenatal viral infection during pregnancy.It is still unclear whether behavior phenotypes change at different developmental stages in ...Background:Autism and schizophrenia are environmental risk factors associated with prenatal viral infection during pregnancy.It is still unclear whether behavior phenotypes change at different developmental stages in offspring following the activation of the maternal immune system.Methods:Sprague–Dawley rats received a single caudal vein injection of 10 mg/kg polyinosinic:polycytidylic acid(poly I:C)on gestational day 9 and the offspring were comprehensively tested for behaviors in adolescence and adulthood.Results:Maternal serum levels of interleukin(IL)-6,IL-1βand tumor necrosis factor-αwere elevated in poly I:C-treated dams.The offspring of maternal poly I:C-i nduced rats showed increased anxiety,impaired social approach,and progressive impaired cognitive and sensorimotor gating function.Conclusion:Maternal immune activation led to developmental specificity behavioral impairment in offspring.展开更多
Plants rely on membrane and cytosolic receptors to perceive and defend against pathogens.Membrane pattern recognition receptors recognize pathogen-associated molecular patterns(PAMPs)to activate immune signaling pathw...Plants rely on membrane and cytosolic receptors to perceive and defend against pathogens.Membrane pattern recognition receptors recognize pathogen-associated molecular patterns(PAMPs)to activate immune signaling pathways,known as pattern-triggered immunity(PTI).展开更多
Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation,and it has emerged as a promising strategy for cancer therapy.Enhanced ferroptosis could overcome the limitations of conventi...Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation,and it has emerged as a promising strategy for cancer therapy.Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities,particularly in difficult-to-treat tumors.In this study,we developed a dual-modality therapy in nanomedicine by combining paclitaxel(PTX)chemotherapy and pyropheophorbide-a(Ppa)phototherapy.Heparin(HP)was grafted with poly(N-(2′-hydroxy)propyl methacrylamide)(pHPMA)using reversible addition–fragmentation chain transfer polymerization to form HP-pHPMA(HH),which was utilized to deliver Ppa and PTX,yielding HP-pHPMA-Ppa(HH-Ppa)and HP-pHPMA-PTX(HH-PTX),respectively.The prodrug-based combinational nanomedicine(HH-PP)was formed by co-assembly of HH-PTX and HH-Ppa.It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer(TNBC)cells,induced extensive lipid oxidation,and promoted ferroptosis.In vivo,HH-PP intervention achieved a tumor growth inhibition rate of 86.63%and activated adaptive immunity with an elevated CD8^(+) cytotoxic T cell infiltration level.This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents.It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.展开更多
Background:Chimeric antigen receptor(CAR)-based immune cell therapies attack neighboring cancer cells after receptor recognition but are unable to directly affect distant tumor cells.This limitation may contribute to ...Background:Chimeric antigen receptor(CAR)-based immune cell therapies attack neighboring cancer cells after receptor recognition but are unable to directly affect distant tumor cells.This limitation may contribute to their inefficiency in treating solid tumors,given the restricted intratumoral infiltration and immunosuppressive tumor microenvironment.Therefore,cell–cell fusion as a cell-killing mechanism might develop a novel cytotherapy aimed at improving the efficacy against solid tumors.Methods:We constructed a fusogenic protein,fusion-associated small transmembrane(FAST)p14 of reptilian reovirus,into cancer cells and mesenchymal stem cells(MSCs),which cocultured with various colon cancer cells and melenoma cells to validate its ability to induce cell fusion and syncytia formation.RNA sequencing,quantitative reverse transcription polymerase chain reaction,and Western blot were performed to elucidate the mechanism of syncytia death.Cell viability assay was employed to assess the killing effects of MSCs carrying the p14 protein(MSCs-p14),which was also identified in the subcutaneous tumor models.Subsequently,the Tet-On system was introduced to enhance the controllability and safety of therapy.Results:Cancer cells incorporated with fusogenic protein p14 FAST from reovirus fused together to form syncytia and subsequently died through apoptosis and pyroptosis.MSCs-p14 cocultured with different cancer cells and effienctly induced cancer cell fusion and caused widespread cancer cell death in vitro.In mouse tumor models,mMSCs-p14 treatment markedly suppressed tumor growth and also enhanced the activity of natural killer cells and macrophages.Controllability and safety of MSCs-p14 therapy were further improved by introducing the tetracycline-controlled transcriptional system.Conclusion:MSC-based cytotherapy carrying viral fusogenic protein in this study kills cancer cells by inducing cell–cell fusion.It has demonstrated definite efficacy in treating solid tumors and is worth considering for clinical development.展开更多
Background The frequencies of regulatory T cells （Tregs） increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect ...Background The frequencies of regulatory T cells （Tregs） increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs. Methods Tregs were defined as CD4＋CD25＋CD127lo/-T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer. Results Compared to HIV-1 seronegative donors, the levels of HLA-DR on CD4＋CD25＋CD127lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads （r=0.3163, P=-0.004） and negatively with CD4 T-cell counts （r=-0.4153, P 〈0.0001）. In addition, significant associations between HLA-DR expression on CD4＋CD25＋CD127lo/- Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4＋ and CD8＋ T cells were also identified. Conclusion HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.展开更多
Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity ...Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment.The agonist cyclic dinucleotides(CDNs)of the stimulator of interferon gene(STING)are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity.However,the tumor immune efficacy of CDNs is limited by several factors,including relatively narrow cytokine production,inefficient delivery to STING,and rapid clearance.In addition,a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect.To address this problem,two or more agonist molecules are often used together to synergistically enhance immune efficacy.In this work,we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8(TLR7/8)agonist 522 produced a broader cytokine response.Subsequently,we developed multicomponent nanovaccines(MCNVs)consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules.These MCNVs activate bone marrow-derived dendritic cells(BMDCs)to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor Tcell responses.In in vivo experiments,we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes,resulting in significant tumor regression and,notably,a 100%survival rate in mice through 25 days without other partnering therapies.These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency.展开更多
Arsenic(II)sulfide is a stable inorganic arsenic compound with a different valence from arsenic trioxide,and has been widely applied to treat various diseases with low toxic side effects for a long time.However,its lo...Arsenic(II)sulfide is a stable inorganic arsenic compound with a different valence from arsenic trioxide,and has been widely applied to treat various diseases with low toxic side effects for a long time.However,its low solubility and complicated formulations restrict its further applications in modern medical industry.Meanwhile,as the tumour with the highest incidence rate among women,the low recurrence risk of breast cancer has been confirmed to be closely related to the high infiltration of immune cells.Herein,we synthesized and filtered novel biocompatible PEGylated arsenic(II)sulfide nanocrystals AsS@PEG with a size of 93.14±0.49 nm by the gel method,which displayed excellent anticancer and immune activation activity in breast cancer model.Proteomic analysis suggested that the AsS@PEG induce ferroptosis in cancer cells and further activate antitumour immune responses via B-cell lymphoma 9-like(BCL9L)protein inhibition.Furthermore,mechanism studies revealed notable glutathione peroxidase 4(GPX4)downregulation in cancer cells,dendritic cells(DCs)maturation and subsequent effector CD8^(+)T-cells production induced by the AsS@PEG in the tumour microenvironment.This study highlights biocompatible arsenic(II)sulfide nanocrystals that induce ferroptotic cell death and activate antitumour immune responses,providing insights into the path towards the immunotherapy assisted chemotherapy for breast cancer.展开更多
Although antiretroviral treatment lowers the burden of human immunodeficiency virus(HIV)-related disease,it does not always result in immunological recovery.This manifests as persistent chronic inflammation,immune act...Although antiretroviral treatment lowers the burden of human immunodeficiency virus(HIV)-related disease,it does not always result in immunological recovery.This manifests as persistent chronic inflammation,immune activation or exhaustion that can promote the onset of co-morbidities.As the exact function of regulatory T(Treg)cells in HIV remains unclear,this cross-sectional study investigated three expression markers(Forkhead box protein P3[FOXP3],glycoprotein A repetitions predominant[GARP],special AT-rich sequence binding protein 1[SATB1])and compared their expansion between CD4^(+)CD25^(-)and CD4^(+)CD25^(++)T cells.Age-matched study subjects were recruited(Western Cape,South Africa)and sub-divided:HIV-negative subjects(n=12),HIV-positive na(i|")ve treated(n=22),HIV-positive treated based on CD4 count cells/μL(CD4>500 and CD4<500)(n=34)and HIV-treated based on viral load(VL)copies/mL(VL<1000 and VL>1000)(n=34).Markers of immune activation(CD38)and coagulation(CD142)on T cells(CD8)were assessed by flow cytometry together with FOXP3,GARP and SATB1 expression on CD4^(+)CD25^(-)and CD4^(+)CD25^(++)T cells.Plasma levels of interleukin-10(IL-10;anti-inflammatory marker),IL-6(inflammatory marker)and D-dimer(coagulation marker)were assessed.This study revealed three major findings in immuno-compromised patients with virological failure(CD4<500;VL>1000):(1)the expansion of the unconventional Treg cell subset(CD4^(+)CD25^(-)FOXP3^(+))is linked with disease progression markers;(2)increased GARP expression in the CD4^(+)CD25^(-)and CD4^(+)CD25^(++)subsets;and(3)the identification of a strong link between CD4^(+)CD25^(-)SATB1+cells and markers of immune activation(CD8^(+)CD38^(+))and coagulation(CD8^(+)CD142^(+)and D-dimer).展开更多
Compressed blood and intratumoral lymphatic vessels induced by proliferated tumor cells and elevated interstitial fluid pressure produce regional hypoxic and necrotic region within tumors,which severely reduced the ac...Compressed blood and intratumoral lymphatic vessels induced by proliferated tumor cells and elevated interstitial fluid pressure produce regional hypoxic and necrotic region within tumors,which severely reduced the accessibility of immunogenic cell death(ICD)related drugs and immune-related cells.Herein,the strategy of self-oriented deep tumor delivery by circulating monocyte/macrophage was proposed.Briefly,CS-AI including an indoleamine 2,3-dioxygenase(IDO)inhibitor indoximod(IND)and hydrophilic chitosan(CSO)linked with alanine-alanine-asparagine(AAN)was prepared,which could be selectively cleaved by legumain overexpressed in macrophages and promote the collapse in structure.Then,CS-AI was modified with mannose on the surface and further encapsulated the ICD inducer doxorubicin(DOX)to obtain M-CS-AI/DOX.Upon intravenous injection,MCS-AI/DOX was specially recognized and internalized by circulating monocyte in vivo.The formed drugs/monocyte tend to distribute in hypoxia/necrosis region guided by the homing signals released by tumor.Accumulated monocytes then further differentiated into macrophages,up-regulating the expression of legumain and promoting the sensitive-release of chemo-drug DOX,IND,and the mannose-modified CSO(M-CSO).The released IND would specifically regulate immunosuppressive tumor microenvironment,and synergistically inhibit tumor growth with immune activation elements,ICD-induced DOX,and the favorable adjuvant M-CSO.In summary,the self-oriented deep tumor delivery of legumain-cleavable nanovesicles through circulating monocyte makes it possible for reaching tumor regions inaccessible for nanoparticles and provides a novel insight for precise tumor enrichment and immune activation.展开更多
The growing body of evidence associates infections during pregnancy and other inflammatory insults with developing neurodevelopmental and neurodevelopmental disorders in children,especially autism spectrum disorder.We...The growing body of evidence associates infections during pregnancy and other inflammatory insults with developing neurodevelopmental and neurodevelopmental disorders in children,especially autism spectrum disorder.We review the specific roles that maternal immune activation(MIA)plays in the pathogenesis of autism,the critical cytokines involved,epigenetic factors,maternal antibodies and gender bias,and how MIA affects fetal neurodevelopment in the immune and neurological pathways.A comprehensive understanding of the profound impact of MIA on fetal neurodevelopment is vital for developing diagnostic criteria and medical measures for high-risk maternity and the development of treatments for multiple offspring neurodevelopmental disorders caused by maternal inflammation.展开更多
This paper investigates the effects of graphene quantum dots and mesoporous silica as nanomaterial adjuvants on immune activity in mice both in vitro and in vivo.The two materials have distinct properties;graphene qua...This paper investigates the effects of graphene quantum dots and mesoporous silica as nanomaterial adjuvants on immune activity in mice both in vitro and in vivo.The two materials have distinct properties;graphene quantum dots possess unique optical and electrical characteristics,while mesoporous silica features a regular pore structure.In vitro experiments show differences in their effects on immune cell activation and cytokine secretion;in vivo experiments reveal varying performances in antibody production and immune cell function regulation.Their mechanisms of action and safety profiles also differ,offering distinct advantages in application prospects.These two nanomaterial adjuvants provide new directions for the development of immunology,warranting further exploration.展开更多
Objective:Grifola frondosa,a medicinal mushroom,is widely used to enhance immunity and treat cancer.Polysaccharides are its primary active components.We aimed to investigate the effects of the alkaloid G.frondosa poly...Objective:Grifola frondosa,a medicinal mushroom,is widely used to enhance immunity and treat cancer.Polysaccharides are its primary active components.We aimed to investigate the effects of the alkaloid G.frondosa polysaccharide(GFP)extract on immunity and gut microbiota.Methods:Alkaloid GFP was extracted using an alkaline extraction method,followed by hollow-fiber microfiltration.The molecular weight of alkaloid GFP was determined by high-performance gel permeation chromatography(HPGPC).Monosaccharide composition was analyzed by pre-column derivatization combined with high-performance liquid chromatography(HPLC).Methylation analysis was performed to characterize glycosidic linkages in alkaloid GFP.The immune function of alkaloid GFP was assessed in a cyclophosphamide(CTX)-induced immunosuppressive mouse model.Splenic lymphocyte proliferation,macrophage phagocytic capacity,and natural killer(NK)cell cytotoxicity were evaluated.The effect of alkaloid GFP on gut microbiota was assessed by 16S rRNA sequencing.Results:The molecular weight distribution of alkaloid GFP ranged from 17 to 18 kDa.The alkaloid GFP contained aβ-(1→6)-glucan backbone branched at O-3 byβ-1,3-D-Glcp.Oral administration of alkaloid GFP mitigated the effects of CTX on spleen index,splenic lymphocyte proliferation,and peritoneal macrophage phagocytosis.Additionally,alkaloid GFP improved the gut microbiota composition of immunosuppressed mice,increasing the relative abundances of Ligilactobacillus and Lactobacillus.Conclusions:Alkaloid GFP demonstrated immune-enhancing effects and gut microbiota regulatory activity,providing a basis for developing related health food ingredients.展开更多
Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted...Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors.Several genes have been implicated in the pathogenesis of ASD,most of them are involved in neuronal synaptogenesis.A number of environmental factors and associated conditions such as gastrointestinal(GI)abnormalities and immune imbalance have been linked to the pathophysiology of ASD.According to the March 2012 report released by United States Centers for Disease Control and Prevention,the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms.Although there is a strong genetic base for the disease,several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem.Many children suffering from ASD have GI problems such as abdominal pain,chronic diarrhea,constipation,vomiting,gastroesophageal reflux,and intestinal infections.A number of studies focusing on the intestinal mucosa,its permeability,abnormal gut development,leaky gut,and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas.GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children.Maternal infection or autoimmune diseases have been suspected.Activation of the immune system during early development may have deleterious effect on various organs including the nervous system.In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.展开更多
Survival, growth and immune response of the scallop, Chlamys farreri, cultured in lantern nets at five different depths (2, 5, 10, 15, and 20 m below the sea surface) were studied in Haizhou Bay during the hot season ...Survival, growth and immune response of the scallop, Chlamys farreri, cultured in lantern nets at five different depths (2, 5, 10, 15, and 20 m below the sea surface) were studied in Haizhou Bay during the hot season (summer and autumn) of 2007. Survival and growth rates were quantified bimonthly. Immune activities in hemolymph (superoxide dismutase (SOD) and acid phosphatase (ACP)) were measured to evaluate the health of scallops at the end of the study. Environmental parameters at the five depths were also monitored during the experiment. Mortalities mainly occurred during summer. Survival of scallops suspended at 15 m (78.0%) and 20 m (86.7%) was significantly higher than at 2 m (62.9%), 5 m (60.8%) or 10 m (66.8%) at the end of the study. Mean shell height grew significantly faster at 10 m (205.0 μm/d) and 20 m (236.9 μm/d) than at 2, 5 or 15 m in summer (July 9 to September 1); however, shell growth rate at 20 m was significantly lower than at the other four depths in autumn (September 2 to November 6). In contrast to summer, scallops at 5 m grew faster (262.9 μm/d) during autumn. The growth of soft tissue at different depths showed a similar trend to the shell. Growth rates of shell height and soft tissue were faster in autumn than in summer, with the exception of shell height at 20 m. SOD activity of scallops increased with depth, and ACP activity was significantly higher at 15 and 20 m than at other depths, which suggests that scallops were healthier near the bottom. Factors explaining the depth-related mortality and growth of scallops are also discussed. We conclude that the mass mortality of scallop, C. farreri, during summer can be prevented by moving the culture area to deeper water and yield can be maximized by suspending the scallops in deep water during summer and then transferring them to shallow water in autumn.展开更多
The killing effects of lymphocytes on Hela cells expressing interleukin-12 （IL-12） in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression...The killing effects of lymphocytes on Hela cells expressing interleukin-12 （IL-12） in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression of IL-12 in Hela cells was detected quantitatively by ELISA; Changes in killing effects of lymphocytes on Hela cells expressing IL-12 were observed by MTT. It was found that Hela cells could express IL- 12 between 24 h and 72 h after transfection. Killing activity of lymphocytes on Hela cells expressing IL-12 was significantly enhanced. It was concluded by cell transfection technique, Hela cells could express 1L-12 and were more easily killed by lymphocytes.展开更多
基金Collaborative Innovation Project of Zigong Medical Big Data and Artificial Intelligence Research Institute,Grant/Award Number:2023-YGY-1-02 and 2024-YGY-02-04National Natural Science Foundation of China,Grant/Award Number:31900950+4 种基金Project Supported by the Natural Science Basic Research Plan in Shaanxi Province of China,Grant/Award Number:2024JCYBMS-706National Key Research and Development Program of China,Grant/Award Number:2022YFC2009900Zigong Science and Technology Program,Grant/Award Number:2023YKY11Scientific Research Project of Zigong Health Commission,Grant/Award Number:22yb001 and 24zd008Key Science and Technology Plan Projects in Zigong,Grant/Award Number:2022ZCNKY07,2023-NKY-01-02,2023-NKY-02-13 and 2023-NKY-02-14。
文摘Background:Maternal viral infection during pregnancy can lead to maternal immune activation(MIA),increasing the risk of neurodevelopmental disorders in offspring.Amantadine(AMA)exhibits antiviral activity and is widely employed in the management of neurologic conditions.Nevertheless,the efficacy of AMA in treating MIA is currently not established.Methods:MIA was induced by polyinosinic acid-polycytidylic acid(poly(I:C));AMA was administered from embryonic(E)day 11.5 for 3 days.BV-2 cells were stimulated using poly(I:C)and treated with AMA.Behavior was assessed via open field test,elevated plus maze test,three-chamber sociability test,and marble burying test.Neuronal morphology was vizualized using Nissl stain;apoptosis via TUNEL(terminal deoxynucleotidyl transferase dUTP nick-end labeling)stain;protein expression(Iba1,NeuN,CD68,TNF-α[tumor necrosis factor-alpha],IL-1β[interleukin-1β])using immunofluorescence(IF);interleukin-6(IL-6)levels using enzyme-linked immunosorbent assay;reactive oxygen species using staining;Iba1,NeuN,Bcl-2,Bax,and cleaved caspase 3 using Western blot;and gene expression changes using RNA-seq.Results:AMA treatment reduced the levels of IL-6 in maternal blood,improved autism-like behaviors in MIA offspring,and effectively prevented neuronal damage and neuroinflammation.In vitro cellular studies have demonstrated that AMA effectively downregulates the expression levels of pro-inflammatory cytokines,including IL-6,TNF-α,and IL-1β.RNA-seq analysis indicated that AMA mitigates abnormal activation of microglia by modulating inflammatory pathways associated with IL-6.Conclusion:AMA can prevent the development of neuropsychiatric disorders in MIA offspring.This effect may be related to its ability to attenuate neuronal damage,reduce neuronal apoptosis,and inhibit neuroinflammation,indicating that the antiviral drug AMA may be a potential treatment for MIA.
基金supported by the National Key Research and Development Program of China(No.2022YFA1207600)the National Natural Science Foundation of China(Nos.62375289,62175262)+2 种基金the Science and Technology Innovation Program of Hunan Province(No.2022RC1201)the Scientific Research Fund of Hunan Provincial Education Department(No.22B0081)Postdoctoral Funding Project of Jiangsu Province(No.2019Z156)。
文摘Designing and synthesizing nanomedicines with multi-modal tumor therapeutic capabilities is the key to cancer treatment.Herein,we prepared MICG nanoparticles(NPs)by assembling glucose oxidase(GOx)and indocyanine green(ICG)with manganese carbonate(MnCO_(3))NPs for starvation therapy cascaded chemodynamic therapy,enhanced phototherapy and immune activation.In MICG NPs,the GOx consumes intratumoral glucose resulting in starvation therapy,and simultaneously produces H_(2)O_(2)and decreases p H in tumor.The intensified acidic tumor environment promotes the decomposition of MnCO_(3)NPs to release Mn^(2+).The Mn^(2+)further catalyzes H_(2)O_(2)to generate hydroxyl radical for chemodynamic therapy.While ICG can generate singlet oxygen(^(1)O_(2))and heat to kill cancer cells through phototherapy mechanism.The hydroxyl radical and ^(1)O_(2) will further accelerate the oxidative stress,intensify immunogenic cell death,induce dendritic cell maturation,and thus activate systemic immunity.This work provides a new therapeutic platform for combining therapy of tumor.
文摘The occurrence of massive CD4+ T cell depletion is one of the most prominent characteristics of human immunodeficiency virus type 1 (HIV-1) infection during acute phase, resulting in unrestorable destruction to the immune system. The infected host undergoes an asymptomatic period lasting several years with low viral load and ostensibly healthy status, which is presumably due to virus-specific adaptive immune responses. In the absence of therapy, an overwhelming majority of cases develop to AIDS within 8-10 years of latent infection. In this review, we discuss the roles in AIDS pathogenesis played by massive CD4+ T lymphocytes depletion in gut-associated lymphoid tissue (GALT) during acute infection and abnormal immune activation emerging in the later part of chronic phase.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81972761 and 82202837)the National Key R&D Program of China (Grant Nos. 2016YFC1303200 and 2022YFC2505100)。
文摘Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.
基金Xinxiang Medical UniversityGrant/Award Number:2017ZDCG-04+2 种基金National Natural Science Foundation of ChinaGrant/Award Number:81972152 and 82171498Health Commission of Henan Province,Grant/Award Number:201300310200,212102310589 and LHGJ20190482。
文摘Background:Autism and schizophrenia are environmental risk factors associated with prenatal viral infection during pregnancy.It is still unclear whether behavior phenotypes change at different developmental stages in offspring following the activation of the maternal immune system.Methods:Sprague–Dawley rats received a single caudal vein injection of 10 mg/kg polyinosinic:polycytidylic acid(poly I:C)on gestational day 9 and the offspring were comprehensively tested for behaviors in adolescence and adulthood.Results:Maternal serum levels of interleukin(IL)-6,IL-1βand tumor necrosis factor-αwere elevated in poly I:C-treated dams.The offspring of maternal poly I:C-i nduced rats showed increased anxiety,impaired social approach,and progressive impaired cognitive and sensorimotor gating function.Conclusion:Maternal immune activation led to developmental specificity behavioral impairment in offspring.
基金supported by China Scholarship Council(CSC)scholarships.
文摘Plants rely on membrane and cytosolic receptors to perceive and defend against pathogens.Membrane pattern recognition receptors recognize pathogen-associated molecular patterns(PAMPs)to activate immune signaling pathways,known as pattern-triggered immunity(PTI).
基金supported by the National Key Research and Development Program of China(2023ZD0502304,2023YFB3810004,2022YFC2009900)Natural Science Foundation of China(32271445,52073193)+2 种基金Department of Science and Technology of Sichuan Province(2024NSFJQ0050,China)National Guidance Fund on Developing Local Science and Technology for Sichuan Province(2023ZYD0167,China)1‧3‧5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD23026,China).
文摘Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation,and it has emerged as a promising strategy for cancer therapy.Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities,particularly in difficult-to-treat tumors.In this study,we developed a dual-modality therapy in nanomedicine by combining paclitaxel(PTX)chemotherapy and pyropheophorbide-a(Ppa)phototherapy.Heparin(HP)was grafted with poly(N-(2′-hydroxy)propyl methacrylamide)(pHPMA)using reversible addition–fragmentation chain transfer polymerization to form HP-pHPMA(HH),which was utilized to deliver Ppa and PTX,yielding HP-pHPMA-Ppa(HH-Ppa)and HP-pHPMA-PTX(HH-PTX),respectively.The prodrug-based combinational nanomedicine(HH-PP)was formed by co-assembly of HH-PTX and HH-Ppa.It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer(TNBC)cells,induced extensive lipid oxidation,and promoted ferroptosis.In vivo,HH-PP intervention achieved a tumor growth inhibition rate of 86.63%and activated adaptive immunity with an elevated CD8^(+) cytotoxic T cell infiltration level.This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents.It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.
基金supported by grants 82272813,82373027,and 82303488 from the National Natural Science Foundation of Chinagrant BK20220668 from the Natural Science Foundation of Jiangsu Province,China+1 种基金grant CXZX202234 from Jiangsu Province Capability Improvement Project through Science,Technology and Educationgrant KC22233 from the Key Development Project of Science and Technology Bureau in Xuzhou.
文摘Background:Chimeric antigen receptor(CAR)-based immune cell therapies attack neighboring cancer cells after receptor recognition but are unable to directly affect distant tumor cells.This limitation may contribute to their inefficiency in treating solid tumors,given the restricted intratumoral infiltration and immunosuppressive tumor microenvironment.Therefore,cell–cell fusion as a cell-killing mechanism might develop a novel cytotherapy aimed at improving the efficacy against solid tumors.Methods:We constructed a fusogenic protein,fusion-associated small transmembrane(FAST)p14 of reptilian reovirus,into cancer cells and mesenchymal stem cells(MSCs),which cocultured with various colon cancer cells and melenoma cells to validate its ability to induce cell fusion and syncytia formation.RNA sequencing,quantitative reverse transcription polymerase chain reaction,and Western blot were performed to elucidate the mechanism of syncytia death.Cell viability assay was employed to assess the killing effects of MSCs carrying the p14 protein(MSCs-p14),which was also identified in the subcutaneous tumor models.Subsequently,the Tet-On system was introduced to enhance the controllability and safety of therapy.Results:Cancer cells incorporated with fusogenic protein p14 FAST from reovirus fused together to form syncytia and subsequently died through apoptosis and pyroptosis.MSCs-p14 cocultured with different cancer cells and effienctly induced cancer cell fusion and caused widespread cancer cell death in vitro.In mouse tumor models,mMSCs-p14 treatment markedly suppressed tumor growth and also enhanced the activity of natural killer cells and macrophages.Controllability and safety of MSCs-p14 therapy were further improved by introducing the tetracycline-controlled transcriptional system.Conclusion:MSC-based cytotherapy carrying viral fusogenic protein in this study kills cancer cells by inducing cell–cell fusion.It has demonstrated definite efficacy in treating solid tumors and is worth considering for clinical development.
文摘Background The frequencies of regulatory T cells （Tregs） increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs. Methods Tregs were defined as CD4＋CD25＋CD127lo/-T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer. Results Compared to HIV-1 seronegative donors, the levels of HLA-DR on CD4＋CD25＋CD127lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads （r=0.3163, P=-0.004） and negatively with CD4 T-cell counts （r=-0.4153, P 〈0.0001）. In addition, significant associations between HLA-DR expression on CD4＋CD25＋CD127lo/- Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4＋ and CD8＋ T cells were also identified. Conclusion HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.
基金supported by the National Key R&D Program of China(Nos.2019YFA0904200 and 2018YFA0507600)Tsinghua University Spring Breeze Fund(No.2020Z99CFY042)the National Natural Science Foundation of China(No.92053108).
文摘Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment.The agonist cyclic dinucleotides(CDNs)of the stimulator of interferon gene(STING)are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity.However,the tumor immune efficacy of CDNs is limited by several factors,including relatively narrow cytokine production,inefficient delivery to STING,and rapid clearance.In addition,a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect.To address this problem,two or more agonist molecules are often used together to synergistically enhance immune efficacy.In this work,we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8(TLR7/8)agonist 522 produced a broader cytokine response.Subsequently,we developed multicomponent nanovaccines(MCNVs)consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules.These MCNVs activate bone marrow-derived dendritic cells(BMDCs)to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor Tcell responses.In in vivo experiments,we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes,resulting in significant tumor regression and,notably,a 100%survival rate in mice through 25 days without other partnering therapies.These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency.
基金This work was supported by the National Natural Science Foundation of China(Nos.22207053,91753121,21872069,51761135104,21731004 and 91953201)the Shenzhen Basic Research Program(Nos.JCYJ20170413150538897 and JCYJ20180508182240106)+2 种基金the National Key R&D Program of China(Nos.2017YFA0208200,2016YFB0700600 and 2015CB659300)the Natural Science Foundation of Jiangsu Province(Nos.BK20220764,BK20180008 and BK20202004)The Fundamental Research Funds for the Central Universities,2021 Strategic Research Project of the Science and Technology Commission of the Ministry of Education of China.
文摘Arsenic(II)sulfide is a stable inorganic arsenic compound with a different valence from arsenic trioxide,and has been widely applied to treat various diseases with low toxic side effects for a long time.However,its low solubility and complicated formulations restrict its further applications in modern medical industry.Meanwhile,as the tumour with the highest incidence rate among women,the low recurrence risk of breast cancer has been confirmed to be closely related to the high infiltration of immune cells.Herein,we synthesized and filtered novel biocompatible PEGylated arsenic(II)sulfide nanocrystals AsS@PEG with a size of 93.14±0.49 nm by the gel method,which displayed excellent anticancer and immune activation activity in breast cancer model.Proteomic analysis suggested that the AsS@PEG induce ferroptosis in cancer cells and further activate antitumour immune responses via B-cell lymphoma 9-like(BCL9L)protein inhibition.Furthermore,mechanism studies revealed notable glutathione peroxidase 4(GPX4)downregulation in cancer cells,dendritic cells(DCs)maturation and subsequent effector CD8^(+)T-cells production induced by the AsS@PEG in the tumour microenvironment.This study highlights biocompatible arsenic(II)sulfide nanocrystals that induce ferroptotic cell death and activate antitumour immune responses,providing insights into the path towards the immunotherapy assisted chemotherapy for breast cancer.
基金supported by South African Medical Research Council and Stellenbosch University(to M.F.Essop)。
文摘Although antiretroviral treatment lowers the burden of human immunodeficiency virus(HIV)-related disease,it does not always result in immunological recovery.This manifests as persistent chronic inflammation,immune activation or exhaustion that can promote the onset of co-morbidities.As the exact function of regulatory T(Treg)cells in HIV remains unclear,this cross-sectional study investigated three expression markers(Forkhead box protein P3[FOXP3],glycoprotein A repetitions predominant[GARP],special AT-rich sequence binding protein 1[SATB1])and compared their expansion between CD4^(+)CD25^(-)and CD4^(+)CD25^(++)T cells.Age-matched study subjects were recruited(Western Cape,South Africa)and sub-divided:HIV-negative subjects(n=12),HIV-positive na(i|")ve treated(n=22),HIV-positive treated based on CD4 count cells/μL(CD4>500 and CD4<500)(n=34)and HIV-treated based on viral load(VL)copies/mL(VL<1000 and VL>1000)(n=34).Markers of immune activation(CD38)and coagulation(CD142)on T cells(CD8)were assessed by flow cytometry together with FOXP3,GARP and SATB1 expression on CD4^(+)CD25^(-)and CD4^(+)CD25^(++)T cells.Plasma levels of interleukin-10(IL-10;anti-inflammatory marker),IL-6(inflammatory marker)and D-dimer(coagulation marker)were assessed.This study revealed three major findings in immuno-compromised patients with virological failure(CD4<500;VL>1000):(1)the expansion of the unconventional Treg cell subset(CD4^(+)CD25^(-)FOXP3^(+))is linked with disease progression markers;(2)increased GARP expression in the CD4^(+)CD25^(-)and CD4^(+)CD25^(++)subsets;and(3)the identification of a strong link between CD4^(+)CD25^(-)SATB1+cells and markers of immune activation(CD8^(+)CD38^(+))and coagulation(CD8^(+)CD142^(+)and D-dimer).
基金supported by Zhejiang Provincial Natural Science Foundation of China(No.D19H300001).
文摘Compressed blood and intratumoral lymphatic vessels induced by proliferated tumor cells and elevated interstitial fluid pressure produce regional hypoxic and necrotic region within tumors,which severely reduced the accessibility of immunogenic cell death(ICD)related drugs and immune-related cells.Herein,the strategy of self-oriented deep tumor delivery by circulating monocyte/macrophage was proposed.Briefly,CS-AI including an indoleamine 2,3-dioxygenase(IDO)inhibitor indoximod(IND)and hydrophilic chitosan(CSO)linked with alanine-alanine-asparagine(AAN)was prepared,which could be selectively cleaved by legumain overexpressed in macrophages and promote the collapse in structure.Then,CS-AI was modified with mannose on the surface and further encapsulated the ICD inducer doxorubicin(DOX)to obtain M-CS-AI/DOX.Upon intravenous injection,MCS-AI/DOX was specially recognized and internalized by circulating monocyte in vivo.The formed drugs/monocyte tend to distribute in hypoxia/necrosis region guided by the homing signals released by tumor.Accumulated monocytes then further differentiated into macrophages,up-regulating the expression of legumain and promoting the sensitive-release of chemo-drug DOX,IND,and the mannose-modified CSO(M-CSO).The released IND would specifically regulate immunosuppressive tumor microenvironment,and synergistically inhibit tumor growth with immune activation elements,ICD-induced DOX,and the favorable adjuvant M-CSO.In summary,the self-oriented deep tumor delivery of legumain-cleavable nanovesicles through circulating monocyte makes it possible for reaching tumor regions inaccessible for nanoparticles and provides a novel insight for precise tumor enrichment and immune activation.
基金National Key R&D Program of China(Grant Nos.2021YFA0805200 and 2017YFA0103500)the Chinese Academy of Sciences Science and Technology Service(STS)Network Program(Grant No.KFJ-STS-QYZD-187).
文摘The growing body of evidence associates infections during pregnancy and other inflammatory insults with developing neurodevelopmental and neurodevelopmental disorders in children,especially autism spectrum disorder.We review the specific roles that maternal immune activation(MIA)plays in the pathogenesis of autism,the critical cytokines involved,epigenetic factors,maternal antibodies and gender bias,and how MIA affects fetal neurodevelopment in the immune and neurological pathways.A comprehensive understanding of the profound impact of MIA on fetal neurodevelopment is vital for developing diagnostic criteria and medical measures for high-risk maternity and the development of treatments for multiple offspring neurodevelopmental disorders caused by maternal inflammation.
文摘This paper investigates the effects of graphene quantum dots and mesoporous silica as nanomaterial adjuvants on immune activity in mice both in vitro and in vivo.The two materials have distinct properties;graphene quantum dots possess unique optical and electrical characteristics,while mesoporous silica features a regular pore structure.In vitro experiments show differences in their effects on immune cell activation and cytokine secretion;in vivo experiments reveal varying performances in antibody production and immune cell function regulation.Their mechanisms of action and safety profiles also differ,offering distinct advantages in application prospects.These two nanomaterial adjuvants provide new directions for the development of immunology,warranting further exploration.
基金supported by Infinitus Co.,Ltd(2019009)the Scientific and Technologic Foundation of Jilin Province(No.20230202050NC).
文摘Objective:Grifola frondosa,a medicinal mushroom,is widely used to enhance immunity and treat cancer.Polysaccharides are its primary active components.We aimed to investigate the effects of the alkaloid G.frondosa polysaccharide(GFP)extract on immunity and gut microbiota.Methods:Alkaloid GFP was extracted using an alkaline extraction method,followed by hollow-fiber microfiltration.The molecular weight of alkaloid GFP was determined by high-performance gel permeation chromatography(HPGPC).Monosaccharide composition was analyzed by pre-column derivatization combined with high-performance liquid chromatography(HPLC).Methylation analysis was performed to characterize glycosidic linkages in alkaloid GFP.The immune function of alkaloid GFP was assessed in a cyclophosphamide(CTX)-induced immunosuppressive mouse model.Splenic lymphocyte proliferation,macrophage phagocytic capacity,and natural killer(NK)cell cytotoxicity were evaluated.The effect of alkaloid GFP on gut microbiota was assessed by 16S rRNA sequencing.Results:The molecular weight distribution of alkaloid GFP ranged from 17 to 18 kDa.The alkaloid GFP contained aβ-(1→6)-glucan backbone branched at O-3 byβ-1,3-D-Glcp.Oral administration of alkaloid GFP mitigated the effects of CTX on spleen index,splenic lymphocyte proliferation,and peritoneal macrophage phagocytosis.Additionally,alkaloid GFP improved the gut microbiota composition of immunosuppressed mice,increasing the relative abundances of Ligilactobacillus and Lactobacillus.Conclusions:Alkaloid GFP demonstrated immune-enhancing effects and gut microbiota regulatory activity,providing a basis for developing related health food ingredients.
基金This work was supported by the National Natural Science Foundation of China the Fund of Chinese National Educational Commissionhad been accepted by the International Symposium on New Drug Research and Development.October,1991.Beijing.
文摘Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors.Several genes have been implicated in the pathogenesis of ASD,most of them are involved in neuronal synaptogenesis.A number of environmental factors and associated conditions such as gastrointestinal(GI)abnormalities and immune imbalance have been linked to the pathophysiology of ASD.According to the March 2012 report released by United States Centers for Disease Control and Prevention,the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms.Although there is a strong genetic base for the disease,several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem.Many children suffering from ASD have GI problems such as abdominal pain,chronic diarrhea,constipation,vomiting,gastroesophageal reflux,and intestinal infections.A number of studies focusing on the intestinal mucosa,its permeability,abnormal gut development,leaky gut,and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas.GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children.Maternal infection or autoimmune diseases have been suspected.Activation of the immune system during early development may have deleterious effect on various organs including the nervous system.In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.
基金Supported by the National Key Technology R&D Program (No. 2006BAD09A02)the High Technology Research and Development Program of China (863 Program) (Nos. 2006AA100304, 2006AA100307)the Knowledge Innovation Program of Chinese Academy of Sciences (No. KZCX2-YW-Q07-03)
文摘Survival, growth and immune response of the scallop, Chlamys farreri, cultured in lantern nets at five different depths (2, 5, 10, 15, and 20 m below the sea surface) were studied in Haizhou Bay during the hot season (summer and autumn) of 2007. Survival and growth rates were quantified bimonthly. Immune activities in hemolymph (superoxide dismutase (SOD) and acid phosphatase (ACP)) were measured to evaluate the health of scallops at the end of the study. Environmental parameters at the five depths were also monitored during the experiment. Mortalities mainly occurred during summer. Survival of scallops suspended at 15 m (78.0%) and 20 m (86.7%) was significantly higher than at 2 m (62.9%), 5 m (60.8%) or 10 m (66.8%) at the end of the study. Mean shell height grew significantly faster at 10 m (205.0 μm/d) and 20 m (236.9 μm/d) than at 2, 5 or 15 m in summer (July 9 to September 1); however, shell growth rate at 20 m was significantly lower than at the other four depths in autumn (September 2 to November 6). In contrast to summer, scallops at 5 m grew faster (262.9 μm/d) during autumn. The growth of soft tissue at different depths showed a similar trend to the shell. Growth rates of shell height and soft tissue were faster in autumn than in summer, with the exception of shell height at 20 m. SOD activity of scallops increased with depth, and ACP activity was significantly higher at 15 and 20 m than at other depths, which suggests that scallops were healthier near the bottom. Factors explaining the depth-related mortality and growth of scallops are also discussed. We conclude that the mass mortality of scallop, C. farreri, during summer can be prevented by moving the culture area to deeper water and yield can be maximized by suspending the scallops in deep water during summer and then transferring them to shallow water in autumn.
文摘The killing effects of lymphocytes on Hela cells expressing interleukin-12 （IL-12） in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression of IL-12 in Hela cells was detected quantitatively by ELISA; Changes in killing effects of lymphocytes on Hela cells expressing IL-12 were observed by MTT. It was found that Hela cells could express IL- 12 between 24 h and 72 h after transfection. Killing activity of lymphocytes on Hela cells expressing IL-12 was significantly enhanced. It was concluded by cell transfection technique, Hela cells could express 1L-12 and were more easily killed by lymphocytes.
