Oxaliplatin(OXA)can be used as a palliative treatment for advanced hepatocellular carcinoma(HCC).While most patients still have rapid disease progression after OXA due to the drug resistance.The lactate dehydrogenase ...Oxaliplatin(OXA)can be used as a palliative treatment for advanced hepatocellular carcinoma(HCC).While most patients still have rapid disease progression after OXA due to the drug resistance.The lactate dehydrogenase A(LDHA)inhibitors can reduce the inflammation-induced effects,metastasis,and proliferation potential of cancer cells.Here,we adopt the water-in-oil attractive Pickering emulsion gel(APEG)to deliver OXA and LDHA inhibitor,GSK2837808A(GSK).OXA is dissolved in water and GSK is dissolved in iodized oil.This drugs-loaded APEG has good biocompatibility and can release OXA and GSK slowly.OXA+GSK@gel has significant anti-tumor effect on HCC model,which can effectively inhibit tumor cell proliferation and promote tumor cell apoptosis.Meanwhile,flow analysis confirm that it could activate the tumor immune microenvironment in HCC.The infiltration of CD8^(+)T cells is increased,thereby providing better anti-tumor effect.The results suggest that the APEGs loaded with OXA and GSK can effectively improve the delivery efficiency and enhance the anti-tumor therapy.展开更多
Tumor vascular normalization has emerged as a promising strategy for synergistic therapy recently.Based on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed b...Tumor vascular normalization has emerged as a promising strategy for synergistic therapy recently.Based on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed based on previous developed vascular normalization inducer QDAU5,which could self-assemble to form functional enzyme infrared QDAU5 nanoparticles(FEIRQ NPs).Subsequently,biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis,endoplasmic reticulum stress,and antigen pre-conditioning and maturation of dendritic cells and CD8^(+)T cells,leading to excellent antitumor efficacy in the absence of cytotoxic drugs.Additionally,FEIRQ NPs show high fluorescence intensity upon expo-sure to theβ-galactosidase(β-Gal)enzyme expressed in ovarian cancer,enabling real-time monitoring of therapeutic effects.Overall,our findings suggest a prospering strategy to early diagnosis and efficient therapy for ovarian cancer without cytotoxicity.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
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
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
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
Oats, frequently incorporated into skincare formulations for their anti-inflammatory, moisturizing, and barrier-repairing properties, may present an overlooked risk to individuals with celiac disease, particularly whe...Oats, frequently incorporated into skincare formulations for their anti-inflammatory, moisturizing, and barrier-repairing properties, may present an overlooked risk to individuals with celiac disease, particularly when applied to compromised skin. Although pure oats are inherently gluten-free, the widespread contamination with gluten-containing grains like wheat, barley, or rye during agricultural and processing stages introduces the potential for gluten exposure through topical application. This raises important questions about whether gluten proteins, when applied to damaged skin, might penetrate the epidermal barrier and contribute to immune responses in genetically predisposed celiac patients, given that even minute amounts of gluten can trigger systemic symptoms. Emerging evidence suggests that transdermal absorption of gluten peptides through impaired skin integrity might bypass the gastrointestinal route, yet the precise mechanisms and clinical significance of this pathway remain poorly understood. The role of compromised skin in facilitating gluten absorption and the possible activation of CD4+ T-cells, mimicking gastrointestinal pathways, warrants further investigation. Additionally, the ability of gluten peptides to reach deeper dermal layers and potentially enter the systemic circulation remains speculative, though theoretically possible in severely disrupted skin barriers. Without clinical and molecular studies to determine the risk of topical gluten exposure, particularly in celiac patients with skin injuries, there remains a potential for undetected immune activation and subsequent adverse health outcomes in this sensitive population.展开更多
Regulatory T cells （Treg） play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have pre...Regulatory T cells （Treg） play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previously reported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity and upregulated Thl responses in vivo. However, the underlying molecular mechanisms are not well understood. Here we show that Treg function was significantly downregulated in mice that received immunization of attenuated activated autologous T cells. We found that Foxp3 expression decreased in CD4＋CD25＋ T cells from the immunized mice. Moreover, CD4＋CD25＋Foxp3＋ Treg obtained from immunized mice exhibited diminished immunosuppression ability compared to those from naive mice. Further analysis showed that the serum of immunized mice contains a high level ofanti-CD25 antibody （about 30 ng/ml, p〈0.01 vs controls）. Consistent with a role ofanti-CD25 response in the downregulation of Treg, adoptive transfer of serum from immunized mice to naive mice led to a significant decrease in Treg population and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explained by the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Our results demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25 antibody production, which leads to impeded CD4＋CD25＋Foxp3＋ Treg expansion and function in vivo. We suggest that dampened Treg function likely contributes to enhanced Thl response in immunized mice and is at least part of the mechanism underlying the boosted anti-tumor immunity.展开更多
Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli.Accordingly,pregnancy is an important stage of physiological adaptations to the environmen...Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli.Accordingly,pregnancy is an important stage of physiological adaptations to the environment where the fetus becomes exposed and adapted to the maternal milieu.Maternal exposure to high-energy dense diets can affect motivated behavior in the offs p ring leading to addiction and impaired sociability.A high-energy dense exposure also increases the pro-inflammatory cytokines profile in plasma and brain and favors microglia activation in the offspring.While still under investigation,prenatal exposure to high-energy dense diets promotes structural abnormalities in selective brain regions regulating motivation and social behavior in the offspring.The current review addresses the role of energy-dense foods programming central and peripheral inflammatory profiles during embryonic development and its effect on motivated behavior in the offspring.We provide preclinical and clinical evidence that supports the contribution of prenatal programming in shaping immune profiles that favor structural and brain circuit disruption leading to aberrant motivated behaviors after birth.We hope this minireview encourages future research on novel insights into the mechanisms underlying maternal programming of motivated behavior by central immune networks.展开更多
Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME...Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME),play complex roles that have long been a research focus.The interactions between p DCs and other components of the TME,whether direct or indirect,can either promote or hinder tumor development;consequently,p DCs are an intriguing target for therapeutic intervention.This review provides a comprehensive overview of p DC crosstalk in the TME,including crosstalk with various cell types,biochemical factors,and microorganisms.An in-depth understanding of p DC crosstalk in TME should facilitate the development of novel p DC-based therapeutic methods.展开更多
Although monocytes and macrophages are key mediators of the innate immune system,the focus has largely been on the role of the adaptive immune system in the context of human immunodeficiency virus(HIV)infection.Thus m...Although monocytes and macrophages are key mediators of the innate immune system,the focus has largely been on the role of the adaptive immune system in the context of human immunodeficiency virus(HIV)infection.Thus more attention and research work regarding the innate immune system-especially the role of monocytes and macrophages during early HIV-1 infection-is required.Blood monocytes and tissue macrophages are both susceptible targets of HIV-1 infection,and the early host response can determine whether the nature of the infection becomes pathogenic or not.For example,monocytes and macrophages can contribute to the HIV reservoir and viral persistence,and influence the initiation/extension of immune activation and chronic inflammation.Here the expansion of monocyte subsets(classical,intermediate and non-classical)provide an increased understanding of the crucial role they play in terms of chronic inflammation and also by increasing the risk of coagulation during HIV-1 infection.This review discusses the role of monocytes and macrophages during HIV-1 pathogenesis,starting from the early response to late dysregulation that occurs as a result of persistent immune activation and chronic inflammation.Such changes are also linked to downstream targets such as increased coagulation and the onset of cardiovascular diseases.展开更多
Two hundred and seventy multiparous Chinese Yellow cattle (beef) were selected at 1 to 3 months postpartum and divided into three groups (90 cows for each). Animals were given both a primary and booster immunizations ...Two hundred and seventy multiparous Chinese Yellow cattle (beef) were selected at 1 to 3 months postpartum and divided into three groups (90 cows for each). Animals were given both a primary and booster immunizations with a total dose of 3 mg (Group Th) or 1.5 mg (Group Tl) of seminal preparation containing inhibin activity, emulsified with Freund's complete adjuvant and incomplete adjuvant (for booster) , at 3 or 4-week intervals. Other cows were treated with the same volume of seminal preparation without inhibin activity as procedures mentioned above to serve as a control (Group C). Artificial inseminations were given twice at 8 - 12 h intervals when the cow was in heat. Jugular venous blood samples were collected from each cow and used to assay the presence of antibody against seminal preparation by double-diffusion in agar precipitation test and to detect the titer of inhibin antibody by an ELISA method. Data from 247 cows showed that 83.9% (73/87) of cows were in estrus and ovulated 89 ova altogether, of which 19 cows ovulated twin ova and 15 cows produced twins in Group Th (n = 87). However, only 61.1% (44/72) of cows in Group TI (n = 72) and 62.5% (55/88) of cows in Group C were in estrus and ovulated 46 and 52 ova altogether respectively. The ovulation rate (1.27 ± 0.03), calving rate (126.3%) and twinning rate (26.3%) in Group Th were greater than those in Groups Tl or C (P<0.01). Furthermore, the ovulation rate was associated with antibody titer in sera of immunized animals (r = 0.7507, P<0.01). These results indicate that active immunization of postpartum cows against inhibin purified from porcine seminal plasma may increase the ovulation rate and induce twinning, suggesting the potential to develop a method to improve fertility in cows.展开更多
This study was to explore the immunity-promoting activity of porcine placenta as a potential raw material for functional foods.Porcine placenta was subjected to the analysis for its bioactive substances,and their immu...This study was to explore the immunity-promoting activity of porcine placenta as a potential raw material for functional foods.Porcine placenta was subjected to the analysis for its bioactive substances,and their immunity-promoting activity was determined in mice supplemented with porcine placenta extract(PPE)and freeze-dried porcine placenta powder at high(PPH)and low(PPL)dosage.Results showed that porcine placenta contained placental peptides and 15 free amino acids,and the amounts of estrogen and progesterone in products developed from porcine placenta were within the limit of national standard.Mice model experiment revealed that compared with the control,the PPH treatment significantly improved the spleen index(P<0.05)by increasing the phagocytic rate of macrophages from 20%to 60%and the conversion rate of T lymphocytes from 8%to 60%.The q PCR analysis disclosed that the porcine placenta powder enhanced mice immunity via promoting the expression of Th1 cytokines of interleukin-2(IL-2)and IFN-γ,especially the former,by almost 8 times in the spleens of male mice,while inhibited Th2 cytokines of IL-4 and IL-10.This investigation has provided a reference for the development of porcine placenta as a raw material applied in functional foods to improve human immunity.展开更多
Pesticide ecological safety continues to be a hot issue.The inherent biosafety and physiological functions of vanillin,a widely used natural flavor in food additives,have unlocked numerous applications in the medical ...Pesticide ecological safety continues to be a hot issue.The inherent biosafety and physiological functions of vanillin,a widely used natural flavor in food additives,have unlocked numerous applications in the medical field,leading to a plethora of pharmaceutically active derivatives and commercial drugs.Despite its extensive use in pharmaceutical discovery and the food industry,vanillin's potential in the domain of green pesticide development has only recently come to light.Significantly,its advantages of safety and low price make vanillin ideal for green pesticide research and development(R&D).In this context,this review illuminates the research on vanillin's transformation into a suite of innovative agrochemicals.By delving into the design,synthesis,action mechanisms,and bio-safety of these vanillin-derived compounds,we uncover novel pathways for sustainable agriculture.Further possible directions for the exploration of this substance are also outlined.We believe that this story about vanillin will serve as a source of inspiration for those seeking to derive innovative ideas from natural substances,particularly in the realm of green pesticide R&D.展开更多
Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and immunotherapy.Normalization of tumor vasculature as well as depletion of...Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and immunotherapy.Normalization of tumor vasculature as well as depletion of glutathione(GSH)can improve the TME.Here,we developed a novel therapeutic nanoparticle functional enzyme ultra QDAU5 nanoparticles(FEUQ Nps)based on a fluorescence-on and releasable strategy by combining a vascular normalization inducer,a GSH depleting agent,and an activated fluorophore.In which the cleavage of disulfide bonds releases active molecules that induce vascular normalization and improve the hypoxic microenvironment.In addition,it may deplete GSH in cancer cells,thus inducing the production of reactive oxygen species(ROS)and lipid peroxide(LPO)and promoting iron toxicity.It may also lead to endoplasmic stress and release of calmodulin,which activates the immune system.Meanwhile,quenched fluorophores are turned on in the presence of galactosidase(GLU)for tumor-specific labeling.In summary,we developed novel therapeutic agent nanoparticles with the function of vascular normalization inducers to achieve specific labeling of hepatocellular carcinoma while exerting efficient antitumor effects in vivo.展开更多
Background:We previously described the mortality associated with cardiac injury in patients with coronavirus dis-ease 2019(COVID-19).The activation of immune and thrombotic biomarkers at admission,and their ability to...Background:We previously described the mortality associated with cardiac injury in patients with coronavirus dis-ease 2019(COVID-19).The activation of immune and thrombotic biomarkers at admission,and their ability to predict cardiac injury and mortality patterns in COVID-19,remains unclear.Methods:This retrospective cohort study included 170 patients with COVID-19 with cardiac injury at the time of admis-sion to Tongji Hospital in Wuhan between January 29,2020,and March 8,2020.The temporal evolution of inflammatory cytokines,coagulation markers,clinical treatment,and mortality were analyzed.Continuous variables are expressed as median(interquartile range).The Mann-Whitney test was used for two-group comparisons,whereas the Kruskal-Wallis test was used for comparisons among three groups.Categorical variables are expressed as proportions and percentages,and Fisher’s exact test was used to compare differences.Amultivariate regression model was used to predict in-hospital death.A simple linear regression analysis was applied to examine the correlation between baseline biomarkers and peak cTnI levels.Results:Of the 170 patients,60(35.3%)died early(<21 d),and 61(35.9%)died after a prolonged stay.The admis-sion laboratory findings correlating with early death were elevated interleukin 6(IL-6)(P<0.0001),tumor necrosis factor-α(P=0.0025),and C-reactive protein(P<0.0001).We observed the trajectory of biomarker changes in patients after admission hospitalization,and determined that early mortality was associated with a rapidly increasing D-dimer level,and gradually decreasing platelet and lymphocyte counts.Multivariate and simple linear regression models indi-cated that the risk of death was associated with immune and thrombotic pathway activation.Elevated admission cTnI levels were associated with elevated IL-6(P=0.03)and D-dimer(P=0.0021)levels.Conclusion:In patients with COVID-19 with cardiac injury,IL-6 and D-dimer levels at admission predicted sub-sequently elevated cTnI levels and early death,thus highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury.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
Oncological hyperthermia is one of the most versatile forms of oncotherapy. It can complement every conventional treatment method and be applied to any tumorous cancer, irrespective of its stages and localization. Num...Oncological hyperthermia is one of the most versatile forms of oncotherapy. It can complement every conventional treatment method and be applied to any tumorous cancer, irrespective of its stages and localization. Numerous technical realizations are conventionally compared by their thermal effect, measured by temperature. However, nonthermal (mainly electric) excitation effects are more recognized nowadays. The technical variants alter the synergy between thermal and nonthermal energy components. Nonthermal energy absorption-induced molecular mechanisms include essential behaviors like selectivity and immunogenicity. The nonthermal electromagnetic effects excite molecular changes, intracellular signals, gene expressions, and many other chemical reactions. Their synergy with thermal conditions is based on the Arrhenius law, which describes the rapid growth of chemical reactions with temperature. A unique technical realization of hyperthermia, modulated electrohyperthermia (mEHT) tries to optimize the thermal and nonthermal effects. The results look very perspective, containing the high accuracy of targeting the tumor cells, the immunogenic cell death, and the activation of tumor-specific immune reactions restoring the healthy immune surveillance to destroy the cancer.展开更多
基金supported by Natural Science Foundation of Zhejiang Province(Nos.LY20H160033,LY22H160019)National Key Research and Development Program of China(No.YS2021YFC3000089)+1 种基金Zhejiang Province Science and Technology Plan Project(No.2024C03175)National Natural Science Foundation of China(Nos.82074208,22278352,82473004).
文摘Oxaliplatin(OXA)can be used as a palliative treatment for advanced hepatocellular carcinoma(HCC).While most patients still have rapid disease progression after OXA due to the drug resistance.The lactate dehydrogenase A(LDHA)inhibitors can reduce the inflammation-induced effects,metastasis,and proliferation potential of cancer cells.Here,we adopt the water-in-oil attractive Pickering emulsion gel(APEG)to deliver OXA and LDHA inhibitor,GSK2837808A(GSK).OXA is dissolved in water and GSK is dissolved in iodized oil.This drugs-loaded APEG has good biocompatibility and can release OXA and GSK slowly.OXA+GSK@gel has significant anti-tumor effect on HCC model,which can effectively inhibit tumor cell proliferation and promote tumor cell apoptosis.Meanwhile,flow analysis confirm that it could activate the tumor immune microenvironment in HCC.The infiltration of CD8^(+)T cells is increased,thereby providing better anti-tumor effect.The results suggest that the APEGs loaded with OXA and GSK can effectively improve the delivery efficiency and enhance the anti-tumor therapy.
基金supported by the National Natural Science Foundation of China(NSFC,Nos.82373793,82173742)the Science Fund for Distinguished Young Scholars of Shaanxi Province(No.2022JC-54)the Key Research and Development Program of Shaanxi Province(No.2023-YBSF-131).
文摘Tumor vascular normalization has emerged as a promising strategy for synergistic therapy recently.Based on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed based on previous developed vascular normalization inducer QDAU5,which could self-assemble to form functional enzyme infrared QDAU5 nanoparticles(FEIRQ NPs).Subsequently,biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis,endoplasmic reticulum stress,and antigen pre-conditioning and maturation of dendritic cells and CD8^(+)T cells,leading to excellent antitumor efficacy in the absence of cytotoxic drugs.Additionally,FEIRQ NPs show high fluorescence intensity upon expo-sure to theβ-galactosidase(β-Gal)enzyme expressed in ovarian cancer,enabling real-time monitoring of therapeutic effects.Overall,our findings suggest a prospering strategy to early diagnosis and efficient therapy for ovarian cancer without cytotoxicity.
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.
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.
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.
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.
文摘Oats, frequently incorporated into skincare formulations for their anti-inflammatory, moisturizing, and barrier-repairing properties, may present an overlooked risk to individuals with celiac disease, particularly when applied to compromised skin. Although pure oats are inherently gluten-free, the widespread contamination with gluten-containing grains like wheat, barley, or rye during agricultural and processing stages introduces the potential for gluten exposure through topical application. This raises important questions about whether gluten proteins, when applied to damaged skin, might penetrate the epidermal barrier and contribute to immune responses in genetically predisposed celiac patients, given that even minute amounts of gluten can trigger systemic symptoms. Emerging evidence suggests that transdermal absorption of gluten peptides through impaired skin integrity might bypass the gastrointestinal route, yet the precise mechanisms and clinical significance of this pathway remain poorly understood. The role of compromised skin in facilitating gluten absorption and the possible activation of CD4+ T-cells, mimicking gastrointestinal pathways, warrants further investigation. Additionally, the ability of gluten peptides to reach deeper dermal layers and potentially enter the systemic circulation remains speculative, though theoretically possible in severely disrupted skin barriers. Without clinical and molecular studies to determine the risk of topical gluten exposure, particularly in celiac patients with skin injuries, there remains a potential for undetected immune activation and subsequent adverse health outcomes in this sensitive population.
基金This work was supported by National Natural Science Foundation of China(No.30671945)Science and Technology Commission of Shanghai Municipality(Nos.06JC14044,05ZR14055,054319928,04DZ14902)+2 种基金Shanghai Municipal Education(No.05BZ26)Shanghai Leading Academic Discipline Project(T0206)Science Foundation of Shanghai Institute of Immunology(No.07-A04,to Ningli Li).
文摘Regulatory T cells （Treg） play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previously reported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity and upregulated Thl responses in vivo. However, the underlying molecular mechanisms are not well understood. Here we show that Treg function was significantly downregulated in mice that received immunization of attenuated activated autologous T cells. We found that Foxp3 expression decreased in CD4＋CD25＋ T cells from the immunized mice. Moreover, CD4＋CD25＋Foxp3＋ Treg obtained from immunized mice exhibited diminished immunosuppression ability compared to those from naive mice. Further analysis showed that the serum of immunized mice contains a high level ofanti-CD25 antibody （about 30 ng/ml, p〈0.01 vs controls）. Consistent with a role ofanti-CD25 response in the downregulation of Treg, adoptive transfer of serum from immunized mice to naive mice led to a significant decrease in Treg population and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explained by the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Our results demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25 antibody production, which leads to impeded CD4＋CD25＋Foxp3＋ Treg expansion and function in vivo. We suggest that dampened Treg function likely contributes to enhanced Thl response in immunized mice and is at least part of the mechanism underlying the boosted anti-tumor immunity.
基金supported by the National Council of Science and Technology in Mexico(CONACYT)708452 CONACYT to LMM855559 CONACYT to GCC+1 种基金573686 CONACYT to RMRPAICYT 2021 to ACM。
文摘Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli.Accordingly,pregnancy is an important stage of physiological adaptations to the environment where the fetus becomes exposed and adapted to the maternal milieu.Maternal exposure to high-energy dense diets can affect motivated behavior in the offs p ring leading to addiction and impaired sociability.A high-energy dense exposure also increases the pro-inflammatory cytokines profile in plasma and brain and favors microglia activation in the offspring.While still under investigation,prenatal exposure to high-energy dense diets promotes structural abnormalities in selective brain regions regulating motivation and social behavior in the offspring.The current review addresses the role of energy-dense foods programming central and peripheral inflammatory profiles during embryonic development and its effect on motivated behavior in the offspring.We provide preclinical and clinical evidence that supports the contribution of prenatal programming in shaping immune profiles that favor structural and brain circuit disruption leading to aberrant motivated behaviors after birth.We hope this minireview encourages future research on novel insights into the mechanisms underlying maternal programming of motivated behavior by central immune networks.
基金supported by grants from the China Postdoctoral Science Foundation(Grant No.2022M712880)the Program of the Major Research Plan of the National Natural Science Foundation of China(Grant No.91942314)the National Natural Science Foundation of China(Grant No.82001659).
文摘Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME),play complex roles that have long been a research focus.The interactions between p DCs and other components of the TME,whether direct or indirect,can either promote or hinder tumor development;consequently,p DCs are an intriguing target for therapeutic intervention.This review provides a comprehensive overview of p DC crosstalk in the TME,including crosstalk with various cell types,biochemical factors,and microorganisms.An in-depth understanding of p DC crosstalk in TME should facilitate the development of novel p DC-based therapeutic methods.
文摘Although monocytes and macrophages are key mediators of the innate immune system,the focus has largely been on the role of the adaptive immune system in the context of human immunodeficiency virus(HIV)infection.Thus more attention and research work regarding the innate immune system-especially the role of monocytes and macrophages during early HIV-1 infection-is required.Blood monocytes and tissue macrophages are both susceptible targets of HIV-1 infection,and the early host response can determine whether the nature of the infection becomes pathogenic or not.For example,monocytes and macrophages can contribute to the HIV reservoir and viral persistence,and influence the initiation/extension of immune activation and chronic inflammation.Here the expansion of monocyte subsets(classical,intermediate and non-classical)provide an increased understanding of the crucial role they play in terms of chronic inflammation and also by increasing the risk of coagulation during HIV-1 infection.This review discusses the role of monocytes and macrophages during HIV-1 pathogenesis,starting from the early response to late dysregulation that occurs as a result of persistent immune activation and chronic inflammation.Such changes are also linked to downstream targets such as increased coagulation and the onset of cardiovascular diseases.
基金supported by the National Natural Science Foundation of China(No.39370512)the Foundation of Doctor Degree Unit Authorized by China Education Ministry(No.960204)the National Key Research Progress(No.96030311)of Chinese Ministry of Science and Technology,respectively.
文摘Two hundred and seventy multiparous Chinese Yellow cattle (beef) were selected at 1 to 3 months postpartum and divided into three groups (90 cows for each). Animals were given both a primary and booster immunizations with a total dose of 3 mg (Group Th) or 1.5 mg (Group Tl) of seminal preparation containing inhibin activity, emulsified with Freund's complete adjuvant and incomplete adjuvant (for booster) , at 3 or 4-week intervals. Other cows were treated with the same volume of seminal preparation without inhibin activity as procedures mentioned above to serve as a control (Group C). Artificial inseminations were given twice at 8 - 12 h intervals when the cow was in heat. Jugular venous blood samples were collected from each cow and used to assay the presence of antibody against seminal preparation by double-diffusion in agar precipitation test and to detect the titer of inhibin antibody by an ELISA method. Data from 247 cows showed that 83.9% (73/87) of cows were in estrus and ovulated 89 ova altogether, of which 19 cows ovulated twin ova and 15 cows produced twins in Group Th (n = 87). However, only 61.1% (44/72) of cows in Group TI (n = 72) and 62.5% (55/88) of cows in Group C were in estrus and ovulated 46 and 52 ova altogether respectively. The ovulation rate (1.27 ± 0.03), calving rate (126.3%) and twinning rate (26.3%) in Group Th were greater than those in Groups Tl or C (P<0.01). Furthermore, the ovulation rate was associated with antibody titer in sera of immunized animals (r = 0.7507, P<0.01). These results indicate that active immunization of postpartum cows against inhibin purified from porcine seminal plasma may increase the ovulation rate and induce twinning, suggesting the potential to develop a method to improve fertility in cows.
基金supported by grants from the National Key Research and Development Projects(2019YFE0103800)Scientific Research Project of Sichuan Provincial Health Department(No.18PJ586)Research and Innovation Team Project of Chengdu Medical College(No.CYTD16-04)。
文摘This study was to explore the immunity-promoting activity of porcine placenta as a potential raw material for functional foods.Porcine placenta was subjected to the analysis for its bioactive substances,and their immunity-promoting activity was determined in mice supplemented with porcine placenta extract(PPE)and freeze-dried porcine placenta powder at high(PPH)and low(PPL)dosage.Results showed that porcine placenta contained placental peptides and 15 free amino acids,and the amounts of estrogen and progesterone in products developed from porcine placenta were within the limit of national standard.Mice model experiment revealed that compared with the control,the PPH treatment significantly improved the spleen index(P<0.05)by increasing the phagocytic rate of macrophages from 20%to 60%and the conversion rate of T lymphocytes from 8%to 60%.The q PCR analysis disclosed that the porcine placenta powder enhanced mice immunity via promoting the expression of Th1 cytokines of interleukin-2(IL-2)and IFN-γ,especially the former,by almost 8 times in the spleens of male mice,while inhibited Th2 cytokines of IL-4 and IL-10.This investigation has provided a reference for the development of porcine placenta as a raw material applied in functional foods to improve human immunity.
基金the National Natural Science Foundation of China(32330087 and 32272590)the National Key Research and Development Program of China(2022YFD1700300)for financial support。
文摘Pesticide ecological safety continues to be a hot issue.The inherent biosafety and physiological functions of vanillin,a widely used natural flavor in food additives,have unlocked numerous applications in the medical field,leading to a plethora of pharmaceutically active derivatives and commercial drugs.Despite its extensive use in pharmaceutical discovery and the food industry,vanillin's potential in the domain of green pesticide development has only recently come to light.Significantly,its advantages of safety and low price make vanillin ideal for green pesticide research and development(R&D).In this context,this review illuminates the research on vanillin's transformation into a suite of innovative agrochemicals.By delving into the design,synthesis,action mechanisms,and bio-safety of these vanillin-derived compounds,we uncover novel pathways for sustainable agriculture.Further possible directions for the exploration of this substance are also outlined.We believe that this story about vanillin will serve as a source of inspiration for those seeking to derive innovative ideas from natural substances,particularly in the realm of green pesticide R&D.
基金supported by the National Natural Science Foundation of China(NSFC,No.82173742)the Science Fund for Distinguished Young Scholars of Shaanxi Province(No.2022JC-54)the Key Research and Development Program of Shaanxi Province(No.2023-YBSF-131).
文摘Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and immunotherapy.Normalization of tumor vasculature as well as depletion of glutathione(GSH)can improve the TME.Here,we developed a novel therapeutic nanoparticle functional enzyme ultra QDAU5 nanoparticles(FEUQ Nps)based on a fluorescence-on and releasable strategy by combining a vascular normalization inducer,a GSH depleting agent,and an activated fluorophore.In which the cleavage of disulfide bonds releases active molecules that induce vascular normalization and improve the hypoxic microenvironment.In addition,it may deplete GSH in cancer cells,thus inducing the production of reactive oxygen species(ROS)and lipid peroxide(LPO)and promoting iron toxicity.It may also lead to endoplasmic stress and release of calmodulin,which activates the immune system.Meanwhile,quenched fluorophores are turned on in the presence of galactosidase(GLU)for tumor-specific labeling.In summary,we developed novel therapeutic agent nanoparticles with the function of vascular normalization inducers to achieve specific labeling of hepatocellular carcinoma while exerting efficient antitumor effects in vivo.
基金supported by grants from the National Natural Science Foundation of China(No.82100337)the General Project of Natural Science Foundation of Jilin Province(No.YDZJ202201ZYTS097)the Bethune Program of Jilin University(No.419161900105).
文摘Background:We previously described the mortality associated with cardiac injury in patients with coronavirus dis-ease 2019(COVID-19).The activation of immune and thrombotic biomarkers at admission,and their ability to predict cardiac injury and mortality patterns in COVID-19,remains unclear.Methods:This retrospective cohort study included 170 patients with COVID-19 with cardiac injury at the time of admis-sion to Tongji Hospital in Wuhan between January 29,2020,and March 8,2020.The temporal evolution of inflammatory cytokines,coagulation markers,clinical treatment,and mortality were analyzed.Continuous variables are expressed as median(interquartile range).The Mann-Whitney test was used for two-group comparisons,whereas the Kruskal-Wallis test was used for comparisons among three groups.Categorical variables are expressed as proportions and percentages,and Fisher’s exact test was used to compare differences.Amultivariate regression model was used to predict in-hospital death.A simple linear regression analysis was applied to examine the correlation between baseline biomarkers and peak cTnI levels.Results:Of the 170 patients,60(35.3%)died early(<21 d),and 61(35.9%)died after a prolonged stay.The admis-sion laboratory findings correlating with early death were elevated interleukin 6(IL-6)(P<0.0001),tumor necrosis factor-α(P=0.0025),and C-reactive protein(P<0.0001).We observed the trajectory of biomarker changes in patients after admission hospitalization,and determined that early mortality was associated with a rapidly increasing D-dimer level,and gradually decreasing platelet and lymphocyte counts.Multivariate and simple linear regression models indi-cated that the risk of death was associated with immune and thrombotic pathway activation.Elevated admission cTnI levels were associated with elevated IL-6(P=0.03)and D-dimer(P=0.0021)levels.Conclusion:In patients with COVID-19 with cardiac injury,IL-6 and D-dimer levels at admission predicted sub-sequently elevated cTnI levels and early death,thus highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury.
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.
文摘Oncological hyperthermia is one of the most versatile forms of oncotherapy. It can complement every conventional treatment method and be applied to any tumorous cancer, irrespective of its stages and localization. Numerous technical realizations are conventionally compared by their thermal effect, measured by temperature. However, nonthermal (mainly electric) excitation effects are more recognized nowadays. The technical variants alter the synergy between thermal and nonthermal energy components. Nonthermal energy absorption-induced molecular mechanisms include essential behaviors like selectivity and immunogenicity. The nonthermal electromagnetic effects excite molecular changes, intracellular signals, gene expressions, and many other chemical reactions. Their synergy with thermal conditions is based on the Arrhenius law, which describes the rapid growth of chemical reactions with temperature. A unique technical realization of hyperthermia, modulated electrohyperthermia (mEHT) tries to optimize the thermal and nonthermal effects. The results look very perspective, containing the high accuracy of targeting the tumor cells, the immunogenic cell death, and the activation of tumor-specific immune reactions restoring the healthy immune surveillance to destroy the cancer.
