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
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
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
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
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
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
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
A marine bacterium, Pseudoalteromonas sp. BC228 was supplemented to feed in a feeding experiment aiming to determine its ability of enhancing the digestive enzyme activity and immune response of juvenile Apostichopus ...A marine bacterium, Pseudoalteromonas sp. BC228 was supplemented to feed in a feeding experiment aiming to determine its ability of enhancing the digestive enzyme activity and immune response of juvenile Apostichopus japonicus. Sea cucumber individuals were fed with the diets containing 0(control), 105, 107 and 109 CFU g-1 diet of BC228 for 45 days. Results showed that intestinal trypsin and lipase activities were significantly enhanced by 107 and 109 CFU g-1 diet of BC228 in comparison with control(P < 0.01). The phagocytic activity in the coelomocytes of sea cucumber fed the diet supplemented with 107 CFU g-1 diet of BC228 was significantly higher than that of those fed control diet(P < 0.05). In addition, 105 and 107 CFU g-1 diet of BC228 significantly enhanced lysozyme and phenoloxidase activities in the coelomic fluid of sea cucumber, respectively, in comparison with other diets(P < 0.01). Sea cucumbers, 10 each diet, were challenged with Vibrio splendidus NB13 after 45 days of feeding. It was found that the cumulative incidence and mortality of sea cucumber fed with BC228 containing diets were lower than those of animals fed control diet. Our findings evidenced that BC228 supplemented in diets improved the digestive enzyme activity of juvenile sea cucumber, stimulated its immune response and enhanced its resistance to the infection of V. splendidus.展开更多
We have modified the previously described one-pot peptide synthesis method. The modified method has been successfully applied to the synthesis of TP3. Furthermore, the immune regulatory activity of TP3 has been charac...We have modified the previously described one-pot peptide synthesis method. The modified method has been successfully applied to the synthesis of TP3. Furthermore, the immune regulatory activity of TP3 has been characterized. The results show that the modified one-pot method can be used to synthesize the biological active peptide with the advantages of low cost and high productivity. Moreover, TP3 has a higher immune regulatory activity than TP5.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
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
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
Chirality is pervasive and plays a crucial role in biological processes.Although amino acids possess inherent chirality,the stereochemical influence of this property on the regulation of immune cells remains insuffici...Chirality is pervasive and plays a crucial role in biological processes.Although amino acids possess inherent chirality,the stereochemical influence of this property on the regulation of immune cells remains insufficiently explored.To address this,the unimolecular chiral poly(amino acid)s were synthesized to evaluate their immunostimulatory effects and anti-cancer potential.Among the candidates,G0-P_(D)-Lys_(50)emerged as the most effective adjuvant through in vitro screening.When complexed with antigen ovalbumin(OVA)to form chiral nanovaccines,G0-P_(L)-Lys_(50)-OVA and G0-P_(D)-Lys_(50)-OVA exhibited similar morphology,particle size,and zeta potential.Despite these comparable physicochemical properties,G0-P_(D)Lys_(50)-OVA induced significantly stronger activation of dendritic cells(DCs).Specifically,it resulted in 1.38-and 1.34-fold increases in CD11c^(+)CD80^(+)DCs and CD11c^(+)SIINFEKL-H-2Kb^(+)DCs in lymph nodes,respectively.In the LLC-OVA cancer model,G0-P_(D)-Lys_(50)-OVA reduced tumor volume by 50%compared to its enantiomer.These results establish a unique approach to designing chiral nanovaccines and provide a foundational strategy for developing broadly applicable immunotherapies.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
Psychological stress is an important factor for the development of irritable bowel syndrome(IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brai...Psychological stress is an important factor for the development of irritable bowel syndrome(IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brain. In the present review we discuss the potential role of psychological stress in the pathogenesis of IBS and provide comprehensive approaches in clinical treatment. Evidence from clinical and experimental studies showed that psychological stresses have marked impact on intestinal sensitivity, motility, secretion and permeability, and the underlying mechanism has a close correlation with mucosal immune activation, alterations in central nervous system, peripheral neurons and gastrointestinal microbiota. Stress-induced alterations in neuro-endocrine-immune pathways acts on the gut-brain axis and microbiota-gut-brain axis, and cause symptom flare-ups or exaggeration in IBS. IBS is a stresssensitive disorder, therefore, the treatment of IBS should focus on managing stress and stress-induced responses. Now, non-pharmacological approaches and pharmacological strategies that target on stress-related alterations, such as antidepressants, antipsychotics, miscellaneous agents, 5-HT synthesis inhibitors, selective 5-HT reuptake inhibitors, and specific 5-HT receptor antagonists or agonists have shown a critical role in IBS management. A integrative approach for IBS management is a necessary.展开更多
According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence abou...According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence about the implications of sex hormones in IBS symptom modulation,data on mechanisms by which they influence disease development are sparse.This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS.The scientific bibliography was searched using the following keywords:irritable bowel syndrome,sex,gender,ovarian hormone,estradiol,progesterone,testosterone,symptoms,pain,sensitivity,motility,permeability,stress,immune system,brain activity,spinal,supraspinal,imaging.Ovarian hormones variations along themenstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations.They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception.These hormones can also modulate the susceptibility to stress,which is a pivotal factor in IBS occurrence and symptom severity.For instance,estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function.In conclusion,whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS,they arguably modulate IBS onset and symptomatology.However,our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender.Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS.Finally,investigation of brain-gut interactions is critical to decipher how stress,ovarian hormones,and female brain processing of pain can translate into gut dysfunctions.展开更多
Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs...Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism.We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy.Rat offspring were intranasally administe red hUC-MSCs on postnatal day 14.We found that polypyrimidine tract-binding protein-1(PTBP-1)participated in the regulation of lipopolysaccharide-induced maternal immune activation,which led to neonatal hypoxic/ischemic brain injury.Intranasal delive ry of hUC-MSCs inhibited PTBP-1 expression,alleviated neonatal brain injury-related inflammation,and regulated the number and function of glial fibrillary acidic protein-positive astrocytes,there by promoting plastic regeneration of neurons and im p roving brain function.These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.展开更多
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.
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 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.
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.
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.
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financially supported by the National High Technology Research and Development Program of China (863 Project) of China (2012AA10A412)
文摘A marine bacterium, Pseudoalteromonas sp. BC228 was supplemented to feed in a feeding experiment aiming to determine its ability of enhancing the digestive enzyme activity and immune response of juvenile Apostichopus japonicus. Sea cucumber individuals were fed with the diets containing 0(control), 105, 107 and 109 CFU g-1 diet of BC228 for 45 days. Results showed that intestinal trypsin and lipase activities were significantly enhanced by 107 and 109 CFU g-1 diet of BC228 in comparison with control(P < 0.01). The phagocytic activity in the coelomocytes of sea cucumber fed the diet supplemented with 107 CFU g-1 diet of BC228 was significantly higher than that of those fed control diet(P < 0.05). In addition, 105 and 107 CFU g-1 diet of BC228 significantly enhanced lysozyme and phenoloxidase activities in the coelomic fluid of sea cucumber, respectively, in comparison with other diets(P < 0.01). Sea cucumbers, 10 each diet, were challenged with Vibrio splendidus NB13 after 45 days of feeding. It was found that the cumulative incidence and mortality of sea cucumber fed with BC228 containing diets were lower than those of animals fed control diet. Our findings evidenced that BC228 supplemented in diets improved the digestive enzyme activity of juvenile sea cucumber, stimulated its immune response and enhanced its resistance to the infection of V. splendidus.
文摘We have modified the previously described one-pot peptide synthesis method. The modified method has been successfully applied to the synthesis of TP3. Furthermore, the immune regulatory activity of TP3 has been characterized. The results show that the modified one-pot method can be used to synthesize the biological active peptide with the advantages of low cost and high productivity. Moreover, TP3 has a higher immune regulatory activity than TP5.
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.
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financially supported by the National Natural Science Foundation of China(Nos.U23A20591,82472144,52273158,52273159,and W2421115)the Science and Technology Department Project of Jilin Province(No.20220204018YY)+3 种基金the Industrial Technology Research and Development Project of Jilin Province(No.2023C040-8)the Health Research Talent Special Project of Jilin Province(Nos.2023SCZ70 and 2024SCZ46)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.Y2023066)the Bethune Project of Jilin University(No.2023B01)。
文摘Chirality is pervasive and plays a crucial role in biological processes.Although amino acids possess inherent chirality,the stereochemical influence of this property on the regulation of immune cells remains insufficiently explored.To address this,the unimolecular chiral poly(amino acid)s were synthesized to evaluate their immunostimulatory effects and anti-cancer potential.Among the candidates,G0-P_(D)-Lys_(50)emerged as the most effective adjuvant through in vitro screening.When complexed with antigen ovalbumin(OVA)to form chiral nanovaccines,G0-P_(L)-Lys_(50)-OVA and G0-P_(D)-Lys_(50)-OVA exhibited similar morphology,particle size,and zeta potential.Despite these comparable physicochemical properties,G0-P_(D)Lys_(50)-OVA induced significantly stronger activation of dendritic cells(DCs).Specifically,it resulted in 1.38-and 1.34-fold increases in CD11c^(+)CD80^(+)DCs and CD11c^(+)SIINFEKL-H-2Kb^(+)DCs in lymph nodes,respectively.In the LLC-OVA cancer model,G0-P_(D)-Lys_(50)-OVA reduced tumor volume by 50%compared to its enantiomer.These results establish a unique approach to designing chiral nanovaccines and provide a foundational strategy for developing broadly applicable immunotherapies.
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.
文摘Psychological stress is an important factor for the development of irritable bowel syndrome(IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brain. In the present review we discuss the potential role of psychological stress in the pathogenesis of IBS and provide comprehensive approaches in clinical treatment. Evidence from clinical and experimental studies showed that psychological stresses have marked impact on intestinal sensitivity, motility, secretion and permeability, and the underlying mechanism has a close correlation with mucosal immune activation, alterations in central nervous system, peripheral neurons and gastrointestinal microbiota. Stress-induced alterations in neuro-endocrine-immune pathways acts on the gut-brain axis and microbiota-gut-brain axis, and cause symptom flare-ups or exaggeration in IBS. IBS is a stresssensitive disorder, therefore, the treatment of IBS should focus on managing stress and stress-induced responses. Now, non-pharmacological approaches and pharmacological strategies that target on stress-related alterations, such as antidepressants, antipsychotics, miscellaneous agents, 5-HT synthesis inhibitors, selective 5-HT reuptake inhibitors, and specific 5-HT receptor antagonists or agonists have shown a critical role in IBS management. A integrative approach for IBS management is a necessary.
文摘According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence about the implications of sex hormones in IBS symptom modulation,data on mechanisms by which they influence disease development are sparse.This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS.The scientific bibliography was searched using the following keywords:irritable bowel syndrome,sex,gender,ovarian hormone,estradiol,progesterone,testosterone,symptoms,pain,sensitivity,motility,permeability,stress,immune system,brain activity,spinal,supraspinal,imaging.Ovarian hormones variations along themenstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations.They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception.These hormones can also modulate the susceptibility to stress,which is a pivotal factor in IBS occurrence and symptom severity.For instance,estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function.In conclusion,whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS,they arguably modulate IBS onset and symptomatology.However,our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender.Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS.Finally,investigation of brain-gut interactions is critical to decipher how stress,ovarian hormones,and female brain processing of pain can translate into gut dysfunctions.
基金the National Natural Science Foundation of China,No.81471308(to JL)Stem cell Clinical Research Registry Program,No.CMR-20161129-1003(to JL)+2 种基金Liaoning Province Excellent Talent Program Project of China,No.XLYC1902031(to JL)Dalian Innovation Fund of China,No.2018J11CY025(to JL)National Defense Science and Technology New Special Zone Contract,No.19-163-00-kx-003-001-01(to JL)。
文摘Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism.We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy.Rat offspring were intranasally administe red hUC-MSCs on postnatal day 14.We found that polypyrimidine tract-binding protein-1(PTBP-1)participated in the regulation of lipopolysaccharide-induced maternal immune activation,which led to neonatal hypoxic/ischemic brain injury.Intranasal delive ry of hUC-MSCs inhibited PTBP-1 expression,alleviated neonatal brain injury-related inflammation,and regulated the number and function of glial fibrillary acidic protein-positive astrocytes,there by promoting plastic regeneration of neurons and im p roving brain function.These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.
