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
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
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
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
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
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
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
Autism spectrum disorder is a mental neurodevelopmental condition characterized by social deficits and repetitive behavior,and its development is influenced by genetic and environmental factors.Furthermore,an importan...Autism spectrum disorder is a mental neurodevelopmental condition characterized by social deficits and repetitive behavior,and its development is influenced by genetic and environmental factors.Furthermore,an important factor in etiology is the health status of the mother during pregnancy.Maternal health can critically affect the development of the offspring’s nervous system,including the central nervous system and enteric nervous system.Unfavorable maternal health can disrupt the normal development of the offspring’s nervous system in various ways,such as changes in microbiota composition.As one of the common comorbidities of autism spectrum disorder,no consistent conclusion has been drawn on how poor maternal health affects enteric nervous system and cen-tral nervous system development in offspring.From the perspective of maternal health,this review discusses how maternal status affects the gastrointestinal health of offspring and the development of mental systems to raise public awar-eness of maternal health and provide a new idea for eugenics and childbearing.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
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
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
Pure drug-assembled nanosystem provides a facile and promising solution for simple manufacturing of nanodrugs,whereas a lack of understanding of the underlying assembly mechanism and the inefficient and uncontrollable...Pure drug-assembled nanosystem provides a facile and promising solution for simple manufacturing of nanodrugs,whereas a lack of understanding of the underlying assembly mechanism and the inefficient and uncontrollable drug release still limits the development and application of this technology.Here,a simple and practical nanoassembly of DOX and DiR is constructed on basis of their co-assembly characteristics.Multiple interaction forces are found to drive the co-assembly process.Moreover,DOX release from the nanoassembly can bewell controlled by the acidic tumormicroenvironment and laser irradiation,resulting in favorable delivery efficiency of DiR and DOX in vitro and in vivo.As expected,the nanoassembly with high therapeutic safety completely eradicated the mice triple negative breast cancer cells(4T1)on BALB/c mice,owing to synergistic chemo-photothermal therapy.More interestingly,DiR and DOX synergistically induce immunogenic cell death(ICD)of tumor cells after treatment,enabling the mice to acquire immune memory against tumor growth and recurrence.Such a facile nanoassembly technique provides a novelmultimodal cancer treatment platform of chemotherapy/phototherapy/immunotherapy.展开更多
Approximately 8%of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue(MALT),also known as MALT lymphomas.These arise at a wide range of different extranodal si...Approximately 8%of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue(MALT),also known as MALT lymphomas.These arise at a wide range of different extranodal sites,with most cases affecting the stomach,the lung,the ocular adnexa and the thyroid.The small intestine is involved in a lower percentage of cases.Lymphoma growth in the early stages is associated with long-lasting chronic inflammation provoked by bacterial infections(e.g.,Helicobacter pylori or Chlamydia psittaci infections)or autoimmune conditions(e.g.,Sjögren’s syndrome or Hashimoto thyroiditis).While these inflammatory processes trigger lymphoma cell proliferation and/or survival,they also shape the microenvironment.Thus,activated immune cells are actively recruited to the lymphoma,resulting in either direct lymphoma cell stimulation via surface receptor interactions and/or indirect lymphoma cell stimulation via secretion of soluble factors like cytokines.In addition,chronic inflammatory conditions cause the acquisition of genetic alterations resulting in autonomous lymphoma cell growth.Recently,novel agents targeting the microenvironment have been developed and clinically tested in MALT lymphomas as well as other lymphoid malignancies.In this review,we aim to describe the composition of the microenvironment of MALT lymphoma,the interaction of activated immune cells with lymphoma cells and novel therapeutic approaches in MALT lymphomas using immunomodulatory and/or microenvironmenttargeting agents.展开更多
Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted...Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors.Several genes have been implicated in the pathogenesis of ASD,most of them are involved in neuronal synaptogenesis.A number of environmental factors and associated conditions such as gastrointestinal(GI)abnormalities and immune imbalance have been linked to the pathophysiology of ASD.According to the March 2012 report released by United States Centers for Disease Control and Prevention,the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms.Although there is a strong genetic base for the disease,several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem.Many children suffering from ASD have GI problems such as abdominal pain,chronic diarrhea,constipation,vomiting,gastroesophageal reflux,and intestinal infections.A number of studies focusing on the intestinal mucosa,its permeability,abnormal gut development,leaky gut,and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas.GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children.Maternal infection or autoimmune diseases have been suspected.Activation of the immune system during early development may have deleterious effect on various organs including the nervous system.In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.展开更多
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
Increasing evidence has revealed that maternal cytomegalovirus （CMV） infection may be associated with neurodevelopmental disorders in offspring. Potential relevance between the placental inflammation and CMV-related...Increasing evidence has revealed that maternal cytomegalovirus （CMV） infection may be associated with neurodevelopmental disorders in offspring. Potential relevance between the placental inflammation and CMV-related autism has been reported by clinical observation. Meanwhile, abnormal expression of Toll-like receptor 2 （TLR2） and TLR4 in placenta of patients with chorioamnionitis was observed in multiple studies. IL-6 and IL- 10 are two important maternal inflammatory mediators involved in neurodevelopmental disorders. To investigate whether murine CMV （MCMV） infection causes alterations in placental IL-6/10 and TLR2/4 levels, we analyzed the dynamic changes in gene expression of TLR2/4 and IL-6/10 in placentas following acute MCMV infection. Mouse model of acute MCMV infection during pregnancy was created, and pre-pregnant MCMV infected, lipopolysaccharide （LPS）-treated and uninfected mice were used as controls. At E13.5, E 14.5 and E 18.5, placentas and fetal brains were harvested and mRNA expression levels of placental TLR2/4 and IL-6/10 were analyzed. The results showed that after acute MCMV infection, the expression levels of placental TLR2/4 and IL-6 were elevated at E13.5, accompanied by obvious placental inflammation and reduction of placenta and fetal brain weights. However, LPS 50 ktg/kg could decrease the IL-6 expression at E13.5 and E14.5. This suggests that acute MCMV infection during pregnancy could up-regulate the gene expression of TLR2/4 in placental trophoblasts and activate them to produce more pro- inflammatory cytokine IL-6. High dose of LPS stimulation （50 gg/kg） during pregnancy can lead to down-regulation of IL-6 levels in the late stage. Imbalance of IL-6 expression in placenta might be associated with the neurodevelopmental disorders in progeny.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
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 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 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 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This paper investigates the effects of graphene quantum dots and mesoporous silica as nanomaterial adjuvants on immune activity in mice both in vitro and in vivo.The two materials have distinct properties;graphene quantum dots possess unique optical and electrical characteristics,while mesoporous silica features a regular pore structure.In vitro experiments show differences in their effects on immune cell activation and cytokine secretion;in vivo experiments reveal varying performances in antibody production and immune cell function regulation.Their mechanisms of action and safety profiles also differ,offering distinct advantages in application prospects.These two nanomaterial adjuvants provide new directions for the development of immunology,warranting further exploration.
基金Supported by the National Natural Science Foundation of China,No.82305035China Academy of Chinese Medical Sciences,Special Project for Cultivating Outstanding Young Scientific and Technological Talents,No.2217-YQ-029Institute of Acupuncture,China Academy of Chinese Medical Sciences,Special Project for Innovative Talents,No.ZZ-YC2023002.
文摘Autism spectrum disorder is a mental neurodevelopmental condition characterized by social deficits and repetitive behavior,and its development is influenced by genetic and environmental factors.Furthermore,an important factor in etiology is the health status of the mother during pregnancy.Maternal health can critically affect the development of the offspring’s nervous system,including the central nervous system and enteric nervous system.Unfavorable maternal health can disrupt the normal development of the offspring’s nervous system in various ways,such as changes in microbiota composition.As one of the common comorbidities of autism spectrum disorder,no consistent conclusion has been drawn on how poor maternal health affects enteric nervous system and cen-tral nervous system development in offspring.From the perspective of maternal health,this review discusses how maternal status affects the gastrointestinal health of offspring and the development of mental systems to raise public awar-eness of maternal health and provide a new idea for eugenics and childbearing.
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.
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.
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financially supported by the Liaoning Revitalization Talents Program (no. XLYC1907129)the National Natural Science Foundation of China (no. 82161138029)+1 种基金the Excellent Youth Science Foundation of Liaoning Province (no. 2020-YQ-06)the China Postdoctoral Science Foundation (no. 2020M670794 and no. 2021MD703858)
文摘Pure drug-assembled nanosystem provides a facile and promising solution for simple manufacturing of nanodrugs,whereas a lack of understanding of the underlying assembly mechanism and the inefficient and uncontrollable drug release still limits the development and application of this technology.Here,a simple and practical nanoassembly of DOX and DiR is constructed on basis of their co-assembly characteristics.Multiple interaction forces are found to drive the co-assembly process.Moreover,DOX release from the nanoassembly can bewell controlled by the acidic tumormicroenvironment and laser irradiation,resulting in favorable delivery efficiency of DiR and DOX in vitro and in vivo.As expected,the nanoassembly with high therapeutic safety completely eradicated the mice triple negative breast cancer cells(4T1)on BALB/c mice,owing to synergistic chemo-photothermal therapy.More interestingly,DiR and DOX synergistically induce immunogenic cell death(ICD)of tumor cells after treatment,enabling the mice to acquire immune memory against tumor growth and recurrence.Such a facile nanoassembly technique provides a novelmultimodal cancer treatment platform of chemotherapy/phototherapy/immunotherapy.
文摘Approximately 8%of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue(MALT),also known as MALT lymphomas.These arise at a wide range of different extranodal sites,with most cases affecting the stomach,the lung,the ocular adnexa and the thyroid.The small intestine is involved in a lower percentage of cases.Lymphoma growth in the early stages is associated with long-lasting chronic inflammation provoked by bacterial infections(e.g.,Helicobacter pylori or Chlamydia psittaci infections)or autoimmune conditions(e.g.,Sjögren’s syndrome or Hashimoto thyroiditis).While these inflammatory processes trigger lymphoma cell proliferation and/or survival,they also shape the microenvironment.Thus,activated immune cells are actively recruited to the lymphoma,resulting in either direct lymphoma cell stimulation via surface receptor interactions and/or indirect lymphoma cell stimulation via secretion of soluble factors like cytokines.In addition,chronic inflammatory conditions cause the acquisition of genetic alterations resulting in autonomous lymphoma cell growth.Recently,novel agents targeting the microenvironment have been developed and clinically tested in MALT lymphomas as well as other lymphoid malignancies.In this review,we aim to describe the composition of the microenvironment of MALT lymphoma,the interaction of activated immune cells with lymphoma cells and novel therapeutic approaches in MALT lymphomas using immunomodulatory and/or microenvironmenttargeting agents.
文摘Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors.Several genes have been implicated in the pathogenesis of ASD,most of them are involved in neuronal synaptogenesis.A number of environmental factors and associated conditions such as gastrointestinal(GI)abnormalities and immune imbalance have been linked to the pathophysiology of ASD.According to the March 2012 report released by United States Centers for Disease Control and Prevention,the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms.Although there is a strong genetic base for the disease,several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem.Many children suffering from ASD have GI problems such as abdominal pain,chronic diarrhea,constipation,vomiting,gastroesophageal reflux,and intestinal infections.A number of studies focusing on the intestinal mucosa,its permeability,abnormal gut development,leaky gut,and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas.GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children.Maternal infection or autoimmune diseases have been suspected.Activation of the immune system during early development may have deleterious effect on various organs including the nervous system.In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.
基金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.
文摘Increasing evidence has revealed that maternal cytomegalovirus （CMV） infection may be associated with neurodevelopmental disorders in offspring. Potential relevance between the placental inflammation and CMV-related autism has been reported by clinical observation. Meanwhile, abnormal expression of Toll-like receptor 2 （TLR2） and TLR4 in placenta of patients with chorioamnionitis was observed in multiple studies. IL-6 and IL- 10 are two important maternal inflammatory mediators involved in neurodevelopmental disorders. To investigate whether murine CMV （MCMV） infection causes alterations in placental IL-6/10 and TLR2/4 levels, we analyzed the dynamic changes in gene expression of TLR2/4 and IL-6/10 in placentas following acute MCMV infection. Mouse model of acute MCMV infection during pregnancy was created, and pre-pregnant MCMV infected, lipopolysaccharide （LPS）-treated and uninfected mice were used as controls. At E13.5, E 14.5 and E 18.5, placentas and fetal brains were harvested and mRNA expression levels of placental TLR2/4 and IL-6/10 were analyzed. The results showed that after acute MCMV infection, the expression levels of placental TLR2/4 and IL-6 were elevated at E13.5, accompanied by obvious placental inflammation and reduction of placenta and fetal brain weights. However, LPS 50 ktg/kg could decrease the IL-6 expression at E13.5 and E14.5. This suggests that acute MCMV infection during pregnancy could up-regulate the gene expression of TLR2/4 in placental trophoblasts and activate them to produce more pro- inflammatory cytokine IL-6. High dose of LPS stimulation （50 gg/kg） during pregnancy can lead to down-regulation of IL-6 levels in the late stage. Imbalance of IL-6 expression in placenta might be associated with the neurodevelopmental disorders in progeny.
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.
