Research progress of IDO1-mediated tryptophan metabolism in sepsis / 药学学报

Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.

Research progress of interleukin-17 in offspring autism spectrum disorder / 中华实用儿科临床杂志

Interleukin-17 (IL-17) plays an important role in the body′s immune response and inflammatory response.High levels of IL-17 are associated with a variety of autoimmune diseases, acute and chronic neurodegenerative diseases, and psychiatric disorders.Autism spectrum disorder (ASD) is a group of common neurodevelopmental disorders in childhood.Recent clinical and experimental studies have linked maternal immune activation (MIA) during pregnancy to the risk of ASD in offspring.Significantly increased IL-17 level is found in MIA-induced progeny ASD, which is the key factor leading to neurodevelopmental abnormalities in progeny mice.This article reviews the latest research progress on the relationship between IL-17 and progeny ASD, and provides new ideas for the prevention and treatment of ASD.

Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure. Recently, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3K/AKT in fibrotic processes is increasingly prominent, with PI3K/AKT inhibitors currently under clinical evaluation in IPF. Therefore, PI3K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.

Changes of inflammatory cytokines and T lymphocyte activation in the peripheral blood of human immunodeficiency virus infected patients during anti-retroviral therapy / 中华传染病杂志

Objective:To explore the dynamic changes of inflammatory cytokines and T lymphocyte activation in the peripheral blood of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients during anti-retroviral therapy (ART).Methods:Two hundred and six HIV/AIDS patients with ART at clinic of the Department of Infectious Diseases in Second Xiangya Hospital, Central-South University between January 2017 and December 2019 were selected as HIV infection group. They were followed up regularly and the blood samples before treatment and at month 6, month 12, month 24 of treatment were collected. Meanwhile, 52 healthy cases were enrolled in the healthy control group and their blood samples were collected. Enzyme-linked immunosorbent assay was used to detect the plasma concentrations of interleukin (IL)-6, hypersensitive C-reactive protein (hsCRP) and tumor necrosis factor (TNF)-α. Flow cytometry was used to detect the CD3 + CD4 + T lymphocytes count and the percentage of CD4 + CD38 + T lymphocytes and CD8 + CD38 + T lymphocytes in the peripheral blood mononuclear cells. Plasma HIV RNA viral load was determined using a quantitative real-time polymerase chain reaction technique. Statistical methods used paired t test and Pearson correlation analysis. Results:The concentrations of IL-6, hsCRP and TNF-α in HIV infection group were (13.42±2.35) pg/mL, (4 012.46±1 012.35) μg/L and (51.78±11.32) μg/L, respectively, which were higher than those in healthy control group ((6.14±0.78) pg/mL, (707.21±305.76) μg/L and (19.01±6.48) μg/L, respectively). The differences were all statistically significant ( t=12.56, 16.79 and 13.45, respectively, all P<0.001). They decreased gradually after initiation of ART in HIV infection group, and returned to normal levels at month 24 of ART. CD3 + CD4 + T cells count was (256.00±65.32)/μL and HIV RNA viral load was (4.467±4.244) lg copies/mL before ART in HIV infection group, which were negatively correlated ( r=-0.625, P=0.041). The percentages of CD8 + CD38 + T lymphocytes before treatment and at month 12 or month 24 of treatment in HIV infection group were higher than those in healthy control group. The differences were all statistically significant ( t=3.85, 6.84 and 2.57, respectively, all P<0.050). The percentage of CD8 + CD38 + T lymphocytes was positively correlated with HIV RNA viral load before ART ( r=0.768, P=0.026). The percentages of CD4 + CD38 + T lymphocytes before treatment and at month 12 or month 24 of treatment in the HIV infection group were lower than those in the healthy control group, and the differences were all statistically significant ( t=6.80, 1.10, and 2.11, respectively, all P<0.050). Conclusions:HIV infection could not only cause insufficiency in immune system, but also abnormal activation of immune system, which could get better gradually with ART.

Dual role of exosomes in viral infection: immune activation and immune escape / 中华微生物学和免疫学杂志

Exosomes are extracellular vesicles containing a variety of cell membrane molecules and related protein. They have been found to act as important intercellular messengers carrying functional RNAs, proteins and lipids that can induce phenotypic changes in recipient cells and promote cell activation or inhibition effect. In recent years, some studies have shown that exosomes can not only play an immune activation role to trigger antiviral immune response after viral infection, but also help to spread virus among cells, thus contributing to viral immune escape. Exosomes can either spread or limit an infection depending on the type of pathogen and the features of source cells, and can be studied as potential targets for development of antiviral drugs and vaccines. This review summarized the role of exosomes in viral infections with an emphasis on their potential contribution to pathogenesis.

Microarray profiling and functional analysis of differentially expressed plasma exosomal circular RNAs in Graves disease

BACKGROUND: Circulating RNA (circRNA) regulates various bioactivities in cells. A better understanding of the exosomal circRNA can provide novel insights into the pathogenesis and treatment of Graves' disease (GD). We aimed to profile the differentially expressed circRNAs (DEcRs) in plasma exosomes of patients with GD and speculate and probe the functions of the DEcR by comprehensive bioinformatics analyses. METHODS: Serum exosomes were isolated from five primary GD patients and five healthy controls via ultracentrifugation. After verification with transmission electron microscopy, exosome samples were subjected to microarray profiling using human circRNA microarrays. Two up-regulated and two down-regulated DEcRs were selected for validation in plasma exosomes from 20 GD and 20 healthy control participants using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The circRNA/microRNA/mRNA interaction network was then assembled and the analysis of the Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was utilized to predict the potential functions of the DEcR associated genes. RESULTS: There were 15 DEcRs revealed in primary GD cases. The intronic circRNA hsa_circRNA_000102 was confirmed as an up-regulated component in plasma exosomes from patients with GD. The circRNA/microRNA/mRNA interaction network unveiled the most potential targeting microRNAs of hsa_circRNA_000102 and its associated genes. The functional analyses predicted involvement of hsa_circRNA_000102 associated genes in pathways of immune system activation, such as viral infection and interferon-beta signaling. CONCLUSIONS: hsa_circRNA_000102 is a differentially up-regulated plasma exosomal circRNA in patients with GD. Our study highlights multiple pathways, particularly virus infection and interferon-beta signaling, for mediating immune activation in Graves' disease.

Activación inmune durante el embarazo y riesgo de Trastorno del Espectro Autista / Maternal immune activation and risk of Autism Spectrum Disorder

Resumen: En los últimos años se ha intentado comprender la etiología del Trastorno del Espectro Autista (TEA), evidenciandose que existe una compleja interacción entre factores genéticos y ambientales. Estudios epidemiológicos y en modelos animales sugieren que la activación inmune de la madre durante el embarazo puede asociarse un mayor riesgo de desarrollar TEA en los hijos, destacando el rol de las citoquinas proinflamatorias, los auto-anticuerpos y el rol de la microglia activada en la poda sináptica durante el desarrollo embrionario. Comprender mejor los factores asociados con los Trastornos del Neurodesarrollo permitirá en el futuro desarrollar estrategias de manejo y detección precoz en población de riesgo.

Abstract: Autism Spectrum Disorder (ASD) etiology has been related whit complex interaction between ge netic and environmental factors. In the last years, numerous studies have suggested that maternal immune activation during pregnancy could be related to ASD in the offspring. This relation could be explained by the effects of pro-inflammatory cytokines, autoantibodies and microglial synap tic pruning during early embryonic development. Better understanding of Neurodevelopmental Disorders risk factors will support appropriate strategies of screening and management of risk population.

Research progress on immunomodulatory effect of plant components on dendritic cells / 中草药

Dendritic cells (DCs) are the key to connecting innate and acquired immunity. In infections and allergic reactions, DCs, as full-time antigen-presenting cells, elicit a T-cell immune response and maintain the autoantigen immune tolerance. Mediated sarcoma immune responses are beneficial for the treatment of infectious diseases as well as cancers and the like, while the immune tolerance induced by DCs plays a role in the control of autoimmune diseases, allergies or inflammatory diseases. Studies have shown that a variety of plant components can regulate the phenotype and function of DCs and they are effective in the clinical use of immunotherapy. Therefore, the use of plant components which can regulate the immune function of DC will provide new ideas for developing effective and low-cost methods of cell therapy. This review summarizes the recent studies on the function of plant components in the regulation of DCs, the effects of plant components on the dendritic phenotypes and their regulatory roles in immune response and immunosuppression.

Microglia and Autism Spectrum Disorder: Overview of Current Evidence and Novel Immunomodulatory Treatment Options

Autism spectrum disorder is a rapidly increasing heterogeneous neurodevelopmental syndrome, remarked by persistent deficit in social communication, and restricted, repetitive patterns of behavior and interest. Lately, maternal immune activation and micgroglial dysfunction in the developing brain have been gaining mounting evidence and leading to studies of various novel agents as potential treatment options. A few immunomodulatory treatment options—luteolin, minocycline, suramin, vitamin D, gut microbiota—are discussed in the current article, regarding the current understanding of their mechanisms and evidence for potential clinical use. More studies are warranted to understand their exact mechanisms of action and to verify efficacy and safety in human subjects.

Phenotype analysis of γδ T cell and their subsets in acute HIV-infected patients / 中国免疫学杂志

Objective:To analyze the phenotypes of γδ T cell in acute HIV-infected patients,and to clarify the role of γδ T cell in acute HIV infection(AHI). Methods:The expressions of CD38,programmed cell death protein-1(PD-1),CD160,CD95 and tumor necrosis factor-related apoptosis inducing ligand-death receptor 5 ( TRAIL-DR5 ) were detected by using flow cytometry. Results:Compared with healthy controls,the frequencies of Vδ1 T cells were significantly increased and the frequencies of Vδ2 T cells were de-creased,however,the frequencies of total γδ T cells were not significantly changed in acute HIV-infected patients. The frequencies of CD38+γδ T cells,CD38+Vδ1 T cells and CD38+Vδ2 T cells were significantly increased compared with healthy controls. Moreover, compared with healthy controls,the frequencies of PD-1+γδ T cells and DR5+γδ T cells were increased,but the expression of PD-1 and DR5 on Vδ1 and Vδ2 T cells were not significantly changed. However,the frequencies of CD38+Vδ1 T cells,CD160+Vδ1 T cells,PD-1+Vδ1 T cells,CD95+Vδ1 T cells and DR5+Vδ1 T cells were significantly increased compared with Vδ2 T cells in acute HIV-infected patients. Conclusion:Activation,inhibitor and apoptosis markers are highly expressed on γδ T cells,especially on Vδ1 T cells in acute HIV-infected patients,suggest that Vδ1 T cells play more important roles in acute HIV infection and disease progression.

Natural killer cells in liver diseases / 医学前沿

The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct "killer" functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.

Maternal Murine Cytomegalovirus Infection during Pregnancy Up-regulates the Gene Expression of Toll-like Receptor 2 and 4 in Placenta / 华中科技大学学报（医学）（英德文版）

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,E14.5 and E18.5,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 μg/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 proinflammatory cytokine IL-6.High dose of LPS stimulation (50 tg/kg) during pregnancy can lead to down-regulation of IL-6 levels in the late stage.Imbalance ofIL-6 expression in placenta might be associated with the neurodevelopmental disorders in progeny.

Maternal Murine Cytomegalovirus Infection during Pregnancy Up-regulates the Gene Expression of Toll-like Receptor 2 and 4 in Placenta / 华中科技大学学报（医学）（英德文版）

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,E14.5 and E18.5,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 μg/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 proinflammatory cytokine IL-6.High dose of LPS stimulation (50 tg/kg) during pregnancy can lead to down-regulation of IL-6 levels in the late stage.Imbalance ofIL-6 expression in placenta might be associated with the neurodevelopmental disorders in progeny.

Activación inmunológica crónica en la patogénesis de la enfermedad por virus de inmunodeficiencia humana / Chronic immunological activation in the pathogenesis of human immunodeficiency virus

ResumenJustificación y objetivo: el virus de inmunodeficiencia humana induce una activación inmune crónica que lleva a la progresión de la enfermedad por VIH. Estudios en primates han demostrado que el desarrollo de una infección retroviral patológica está determinada tanto por la respuesta del sistema inmunitario al virus, como por sus propiedades citopáticas. Esta revisión pretende resumir los conocimientos actuales acerca de los principales mecanismos envueltos en la activación inmune crónica durante la infección por VIH y sus repercusiones en la inmunidad virus-específica.Metodología: las referencias bibliográficas se obtuvieron en la base de datos PubMed. Se incluyeron todos los artículos publicados en lengua inglesa entre 1990 y 2016, hallados bajo las palabras clave "immunopathology and hiv" e "immune activation and hiv".Revisión:se discute la influencia de la inflamación persistente sobre el establecimiento de la enfermedad por VIH y la generación de condiciones patológicas no relacionadas con la infección. Tratamientos dirigidos a modular la inflamación podrían retardar el progreso de la enfermedad y reducir los daños colaterales de la estimulación inmunológica inducida por VIH.Conclusión: la evidencia parece indicar que la activación inmune crónica es la principal causa de la depleción de células T CD4+, la pérdida de inmunidad específica contra el virus y el establecimiento de enfermedades no relacionadas directamente con la infección viral en pacientes que reciben terapia antiretroviral.

AbstractBackground and purpose: The human immunodeficiency virus (HIV) induces chronic immune activation that leads to the worsening of HIV infection. Studies in primates have shown the development of pathological retroviral infection by immune system's response against the virus and its cytopathic properties. This review summarizes current facts about the main mechanisms of HIV chronic immune activation and its virus-related impairment on immunity.Methods: The references were obtained in the PubMed database, under the keywords: "immunopathology and HIV" and "immune activation and HIV". Also, all papers reviewed are in English and were published between 1990 and 2016.Review: Discussion of the persistent inflammation that establish the development of HIV disease and pathological conditions not directly related to HIV infection. Therefore, the treatments aimed to modulate inflammation could slow the disease progression and minimize collateral damage from HIV immune stimulation.Conclusion: Evidence suggests that chronic immune activation is the major cause of CD4+ T-cell depletion, loss of virus-specific immunity and the establishment of diseases not directly related to viral infection in patients on antiretroviral treatment.

Increased Levels of C1q in the Prefrontal Cortex of Adult Offspring after Maternal Immune Activation: Prevention by 7,8-Dihydroxyflavone

OBJECTIVE: Prenatal infection is implicated in the etiology of schizophrenia. The objective of this paper is to study the role of complement protein C1q in the psychosis of adult offspring after maternal immune activation (MIA). In addition, effect of 7,8-dihydroxyflavone (7,8-DHF: a tropomyosin receptor kinase B [TrkB] agonist) was also examined. METHODS: Western blot analysis of C1q in the brain regions from adult offspring after prenatal poly(I:C) (5.0 mg/kg/day from E12 to E17) exposure was performed. 7,8-DHF or vehicle was given from 4 to 8-weeks old. RESULTS: Expression of C1q in the prefrontal cortex (PFC) of adult offspring from poly(I:C)-treated pregnant mice was significantly higher than that of control group. Early treatment with 7,8-DHF during juvenile and adolescent stages could prevent an increase of C1q in the PFC of adult offspring after MIA. CONCLUSION: Therefore, it is likely that increased C1q expression in the frontal cortex may play a role in the behavioral abnormalities of adult offspring after MIA. Furthermore, supplementation with a TrkB agonist such as 7,8-DHF during the prodromal stage may have prophylactic effects on the behavioral abnormalities after MIA.

Effects of postnatal enriched environment on schizophrenia-related behaviors induced by early prena-tal polynosinic-polycytidylic acid immune challenge in adult mice offspring / 中华行为医学与脑科学杂志

Objective To investigate if the positive postnatal environment could modify the schizo-phrenia-related behaviors caused by early maternal immune activation,and the interaction of this two pre-and postnatal factors.Methods The pregnant mice were randomly divided into experimental and control groups.The experimental groups were injected with polynosinic-polycytidylic acid(Poly I : C)(5mg/kg),via intra-venous route,at gestational day 9.The control groups were injected with the same volume of normal saline (NS)at the same gestational day.All offspring were housed in groups of littermates until postnatal day (PND)21 when they were weaned.Between PND22-PND60,offspring were divided into dull or enriched en-vironment(DE or EE)groups by sex and treatment.Different toys were put into the cages of enriched envi-ronment group every week,such as running wheels,climbing materials,swings and rollers.The dull environ-ment(DE)groups were kept the normal housing environment only with sawdust.At PND60,behavioral tests were conducted,such as prepulse inhibition(PPI),open field test,novel object/location recognition,social interaction test,as well as water maze test,were conducted to evaluate the performance of all offspring.After behavioral tests,all offspring were killed and the hippocampus were dissected.The western blot was used to analyze the expression of myelin basic protein in the hippocampus.Results (1)The percentage of PPI with early maternal immune activation of Poly I : C were significantly reduced when compared with control groups (female offspring:F=28.12,P<0.001;male offspring:F=14.76,P<0.01),suggesting the schizophrenia-like behavioral deficit in the offspring induced by early prenatal Poly I : C challenge.(2)In open field test,early maternal immune activation increased the moved distance and speed of the offspring compared with the con-trol groups(female offspring:distances,F=5.10,P<0.05,speed:F=5.19,P<0.05;male offspring:distances:F=6.76,P<0.05,velocity:F=6.85,P<0.05,vs each corresponding control).(3)Enriched environment in-creased the social interaction time of offspring with strange mouse in the social interaction test(female off-spring:EE group(101.30±6.83)s,DE group(76.50±5.59)s,F=9.41,P<0.01;male offspring:EE group(98. 52±6.82)s,DE group(75.82±3.95)s,F=7.95,P<0.01).(4)Enriched environment decreased the time for offspring to find the platform in water maze test(P<0.05).(5)The expression of myelin basic protein in hip-pocampus in offspring which received early maternal immune activation by Poly I : C was lower than that in the control groups(P<0.05).Conclusion The postnatal enriched environment increased the social interac-tion and the learning abilities of the offspring with early maternal immune activation by Poly I : C in water maze,and even more improved the perseveration behavior of the offspring induced by the early maternal im-mune activation.

Expression of B and T lymphocyte attenuation factor on regulatory T cell of HIV-infected patients with different diseases progression / 中国免疫学杂志

Objective:To detect the expression of BTLA on Treg cells of HIV-infected patients and investigate the role of BTLA in HIV infection.Methods: Forty-four HIV-1-infected patients (twenty-four early HIV infection,fourteen chronic HIV-infected patients with CD4+ T counts> 200 cells/μl,AIDS patients with CD4+T counts<200 cells/μl) and nine healthy people served as normal controls were selected to detect the expression of BTLA on Treg cells by flow cytometry.The correlations between BTLA expression on Treg cells and disease progression or immune activation were studied.Results: There was a higher percentage of BTLA on Treg cells in chronic HIV patients and AIDS patients than that in early HIV infected patients(P<0.05,P<0.01),and the expression of BTLA on Treg cells in AIDS patients was higher than that in normal controls(P<0.05).The expression of BTLA on Treg cells was negatively correlated with CD4+T lymphocyte counts and positively correlated with viral load (P<0.001,P<0.01).The percentage of BTLA on Treg cells was positively correlated with CD4+CD38+T lymphocytes and CD4+HLA-DR+T lymphocytes(P<0.001,P<0.001).Conclusion: Increased BTLA expression on HIV-infected Treg cells is associated with disease progression,suggesting that it may accelerate disease progression by enhancing Treg cells inhibitory function and may provide intervention information for HIV infection in the future.

Macrophage activation by low molecular weight saccharides from Cistanche deserticola / 中国中药杂志

To investigate the immune activation effect and mechanism of low molecular weight saccharides from Cistanche deserticola(LMSC) on mouse peritoneal macrophages, RAW264.7 cells. The RAW264.7 cells were divided into the normal control group, LPS positive control group, and LMSC treatment groups. The RAW264.7 cells were treated with various concentrations of LMSC from 3.91 to 62.5 g•L ⁻¹. The neutral red assay was employed to detect the phagocytic activity of macrophages. NO release was detected by using NO kit, and macrophage activation associated protein expression levels (TNF-α, IL-6, IKKβ, p-IKKβ, IκBα, p-IκBα, NF-κB, and p-NF-κB) were detected by Western blot. Results showed that LMSC had an activation effect on macrophages; it can significantly increase the release of NO in RAW264.7 cells and promote the expression of cytokines TNF-α and IL-6. Moreover, LMSC significantly increased the phosphorylation of IKKβ, IκBα, and NF-κB p65. Furthermore, mannitol's one of the main constituents in LMSC significantly enhanced the phagocytic activity of macrophages. These results showed that LMSC could activate macrophages by up-regulating the NF-κB signaling pathway, and mannitol may be one of the main active components in LMSC.

Maternal periodontitis induces intergenerational injuries on reproductive performance of adult female rat offspring / Periodontite materna induz prejuízos transgeracionais no desempenho reprodutivo da prole feminina na idade adulta

Substantial evidence suggests a direct link between periodontitis in pregnant women and subsequent adverse pregnancy outcomes. However, no studies have evaluated the transgenerational effects of periodontitis on the reproductive performance of subsequent generations. The present study investigated whether maternal periodontal disease exerts deleterious transgenerational effects on reproductive performance in F1 female rats. Rat female offspring from mothers that were subjected to experimentally induced periodontitis or sham operation were mated with sexually experienced male rats. The weight and reproductive performance of these F1 offspring were evaluated on gestation day 21, including maternal weight, litter weight, individual pup weight, number of pups, and number of resorptions. The percentage of dams with resorptions and the litter weight/number of pups were also calculated. Compared with the control group, an increase was observed in the percentage and number of resorptions and litter weight/number of pups, and a decrease was observed in the number of pups born in the experimental group. Maternal weight, litter weight, and individual pup weight were not different between the control and experimental groups. Maternal periodontitis impaired reproductive performance in the F1 generation. We showed that periodontitis may induce reproductive injury in adult offspring even if the offspring do not undergo any inflammatory/infectious process during their postnatal life or during gestation. These findings reinforce the importance of oral care during pregnancy.(AU)

Existem evidências substanciais de uma relação direta entre periodontite em mulheres grávidas com efeitos adversos reprodutivos. No entanto, nenhum estudo avaliou os efeitos intergeracionais da periodontite sobre o desempenho reprodutivo das gerações subsequentes. O presente estudo investigou se a doença periodontal materna exerce efeitos intergeracionais deletérios sobre o desempenho reprodutivo em ratos fêmeas da geração F1. Assim, filhas de ratas cujas mães foram submetidas a periodontite experimental ou falsamente operadas foram acasaladas com ratos machos sexualmente experientes. O peso corporal e desempenho reprodutivo da geração F1 foram avaliados no dia 21 de gestação, incluindo o peso materno, peso da ninhada, peso da individual dos filhotes, número de filhotes e de reabsorções. A percentagem de fêmeas com reabsorção e o peso da ninhada/número de filhotes também foram calculados. Comparados com o grupo controle, observou-se aumento na porcentagem e número de reabsorções e no peso da ninhada/ número de filhotes, e decréscimo no número de filhotes nascidos no grupo experimental. O peso materno, peso da ninhada e individual dos filhotes não foi diferente entre o controle e experimental. Estes resultados mostram que a periodontite experimental materna prejudica o desempenho reprodutivo da geração F1, mesmo que estes animais não tenham sido expostos diretamente a um processo inflamatório.(AU)

Immune hyper-activation of multiple lymphocyte subsets in acute coronary syn-drome / 中国免疫学杂志

Objective:The process of myocardial infarction is generally characterized by the activation of host immune cells and the occurrence of inflammation. However, it is unknown which immune cells are preferentially activated and participated into the progression of myocardial infarction. Methods:A total of 55 patients with myocardial ischemia including 13 of stable angina ( SA) ,25 of unstable angina (UA) and 17 of acute myocardial infarction (AMI) as well as 12 of healthy controls (HCs) were enrolled in the study. The frequency and the immune activation marker CD38 expression by peripheral CD3 T cells,CD4 T cells,CD8 T cells,CD4+NKT cells, CD4- NKT cells, CD3-CD56+ NK cells and B cells were comprehensively analyzed. Results:There was no significant difference in the frequencies of these immune cell subsets in peripheral blood among these four groups. Importantly,it was found that CD38 expression was significantly increased on CD8 T cells,NKT cells and NK cells in patients with acute coronary syndromes ( ACS) including UA and AMI patients as compared with those in SA and HC subjects. These data indicated that multiple immune cells were activated in ACS patients,which were possibly participated into the pathogenesis of ACS. Conclusion:The activation of multiple immune cells was closely associated with the progression and outcome in ACS patients. This study provides immune hyper-activation mechanism underlying the development of ACS and may favor for finding a novel immune marker to predict the progression of ACS.