Pivotal role of long non-coding ribonucleic acid-X-inactive specific transcript in regulating immune checkpoint programmed death ligand 1 through a shared pathway between miR-194-5p and miR-155-5p in hepatocellular carcinoma

BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway.

Effect of TCM Combined with Chemotherapy on Immune Function and Quality of Life of Patients with Non-small Cell Lung Cancer inStage Ⅲ-Ⅳ

Objective: To observe and compare the effect of traditional Chinese medicine (TCM) combined with chemotherapy (CT) on immune function and quality of life (QOL)of patients with non-small cell lung cancer (NSCLC) in stage Ⅲ-Ⅳ. Methods: One hundred cases with stage Ⅲ-Ⅳ NSCLC were randomly divided into two groups. The treated group (n=50) received CT combined with TCM, and the control group received CT alone. The percentage of T lymphocyte subset in peripheral blood and the change of natural killer (NK) cell count were observed after treatment. The QOL and tolerance of CT were also compared between the two groups after treatment. Results: In the treated group, CD3 cell count, CD4 cell count, CD4/ CDg ratio and NK cell activity were higher than those in control group, while CD8 cell count in the treated group was lower than that in the control group (P<0.05), and QOL and tolerance of CT in the treated group were also better (P<0.05). Conclusion: TCM combined with CT could raise the patients' ability in tolerating CT in stage Ⅲ-ⅣNSCLC.

Effects of concurrent chemoradiotherapy on immune function and tumor markers SCC-Ag and CYFRA21-1 in patients with esophageal carcinoma

Objective: To investigate the effects of concurrent chemoradiotherapy and radiotherapy alone on immune function and tumor markers SCC-Ag and CYFRA21-1 in patients with esophageal carcinoma. Method: A total of 84 patients with esophageal cancer treated in our hospital from June 2015 to April 2017 were selected and randomly divided into the observation group and the control group with 42 cases each. The control group received radiotherapy only and irradiated by medical electron linear accelerator, radiotherapy for 6 weeks. The observation group was given radiotherapy and chemotherapy concurrently, 3 weeks for 1 courses, 2 cycles of chemotherapy. The fasting venous blood of patients in two groups were collected in the morning when patients were hospitalized and after chemotherapy, using flow cytometry to detect the immune function indexes of two groups of patients with esophageal cancer before and after treatment, including natural killer cells (NK), T suppressor cells (Ts), T helper cells (Th), Th/Ts and T lymphocytes (T total). The levels of serum SCC-Ag and CYFRA21-1 were detected by electrochemiluminescence assay. Results: There were no significant differences in the indexes of immune function between the two groups before treatment. Total T, the proportion of Th and Th/Ts in the two groups both increased significantly;the proportion of Ts decreased significantly;the difference was statistically significant. NK was higher than treatment before but not significantly. After treatment, the levels of T total, Th, Th/Ts in the observation group were significantly higher than the control group;the levels of NK and Ts were not significantly different. Before treatment, there was no significant difference in serum SCC-Ag and CYFRA21-1 between the two groups. After treatment, the serum SCC-Ag and CYFRA21-1 levels of the two groups were both significantly decreased;the serum levels of SCC-Ag and CYFRA21-1 in the observation group were significantly lower than the control group. Conclusion: Radiotherapy combined with chemotherapy of cisplatin and paclitaxel can improve the immune function and reduce serum SCC-Ag and CYFRA21-1 levels of esophageal cancer patients. This therapeutic schemes can be beneficial to increase the survival rate of patients with esophageal cancer.

Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

Survival rates for metastatic lung cancer, including non-small cell lung cancer （NSCLC） and small cell lung cancer （SCLC）, are poor with S-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-- with its capacity for memory, exquisite specificity and central and universal role in human biology--immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

ANTITUMOR IMMUNITY AND VACCINE EFFECT INDUCED BY IL-12 SYNERGIZES B7-1 GENE TRANSFECTED CELLS

Objective: To study the synergic effects of IL-12 and B7-1 transfectant on antitumor immunity in vivo. Methods: The retrovirus vector encoding mIL-12 and mB7-1 gene was tranfected into EL-4 thymic lymphoma cells respectively.The cells were used as tumor vaccine and the therapeutic effect was observed. Results: In contrast to the miceimmunized with EL-4/Wt or EL-4/Neo groups, thetumorigenicity of EL-4/IL-12 transfectant was decreased(P<0.001). The EL-4/IL-12 and EL-4/B7-1 cells irradiatedwith 60Co showed significant systematic protective effectsagainst the rechallenge of EL-4/Wt. 60Co irradiatedEL-4/IL-12 cells delayed the occurrence of tumor andprolonged the survival period of tumor bearing mice.Combination of the vaccines of EL-4/IL-12 and EL-4/B7-1 resulted in the enhanced therapeutic effect compared witheach single transfectant group (P<0.001). Conclusion: The results showed that IL-12 transduced cells could enhancethe antitumor immunity of host as cancer vaccine.Combination of the EL-4/IL-12 and EL-4/B7-1 transfectant could improve immunity of host and is a prospect cancervaccine.

Isolation, chemical characteristics and immunity activity of an extracellular polysaccharide EPS I isolated from Antarctic bacterium Pseudoalteromonas sp.S-15-13

A new extracelluar polysaccharide （EPS） was isolated and purified from Antarctic bacterium S-15-13, identified as Pseudoalteromonas sp. After being separated and purified by DEAE-Sephadex A-50 ionexchange and Sephadex G-100 gel chromatography, two mains fractions （EPS I and EPS Ⅱ ） were ob-tained. EPS I was composed of mannose, glucose and galactose with a molecular weight of 23kDa and EPS Ⅱ was composed of mannose only with a molecular weight of 62kDa. The effect of the polysaccharide EPS I on the cellular immune response of mice was investigated. Results demonstrated that EPS I could markedly facilitate lymphocyte proliferation, and might be a strong immunomodulator.

Transcriptome Analysis Reveals the Regulation Role of miR-144-5p in Intestinal Immunity of Japanese Flounder(Paralichthys olivaceus)

MicroRNAs(miRNAs),22-nucleotide-long micromanagers that guide the post-transcriptional regulation of a wide range of target genes,can theoretically be used as a diagnostic or therapeutic target for inflammatory reaction.In fish,miR-144-5p expression varies dramatically in response to the different bacterial infections and can regulate immunity-related genes to reduce the occurrence of inflammation.In this research,the regulation function of miR-144-5p to the intestinal innate immunity was udied in flounder Paralichthys olivaceus.The flounders were interfered by 2μg g^(-1) miR-144-5p antagomir and their tissues(intestine,liver and spleen)were harvested from the fish at 12 h post-injection.More than 60 million high-quality reads were collected.At 24 hours after miR-144-5p or miR-NC interference,a total of 2704 and 1823 different-expresion genes(DEGs)were identified in comparison with control group,respectively.The DEGs were enriched in a variety of immunity-related signaling pathways,including NOD-like receptor,Wnt and Toll-like receptor signaling pathways,according to GO and KEGG analyses.A total of 503 highly interacting DEGs engaged in 33 immunity-related signaling pathways were discovered using KEGG analyses.Additionally,5 hub genes were found by protein-protein interaction networks,which formed an intricate immune regulation network.Meanwhile,these hub genes were mostly involved in focal adhesion,Wnt signaling pathway,as well as the Intestinal Immune Network for IgT(IgA)Production Pathway.In conclusion,the loss of miR-144-5p can affect immunity-related genes and downstream signaling pathways.Our findings suggest that miR-144-5p is a modulator of gene networks and signaling pathways associated with intestinal innate immunity.

Use of a Simple Fabrication Process to Produce a Biosensor： The 3-Hydroxybutyrate Dehydrogenase Case

This study was aimed to construct a biodegradable but reliable 3-β-hydroxybutymte biosensor. In this context a versatile paper based biosensor, quickly, easily and cheaply fabricated is reported. The procedure of fabrication is based on the assumption that the introduction of the enzyme in the carbon ink will allow enzyme stabilization and facilitate the study of the catalysis of enzymes and the detection of substrates. To prove this concept we use the enzyme 3-hydroxybutyrate dehydrogenase, in aqueous solution. This enzyme was chosen because it catalyzes the 3-β-hydroxybutyrate, which results from ketoacidosis. The quantification this substance in the diabetics＇ blood is very important as it can increase the reliability of the diagnosis of glycaemia. To prove the multi-use of this biosensor we not only study the redox process in steady state and during the catalytic process, but also detected and quantify the 3-β-hydroxybutyrate. Our results showed that it was possible to study the redox process that occurred during the catalysis and to confirm the amino acid residues that participate in it. It was also observed that glucose and ascorbic acid can interfere in the detection and quantification of the 3-β-hydroxybutyrate, what should be in mind when the quantification of the 3-β-hydroxybutyrate is made in blood samples.

Stator Winding Turn Faults Diagnosis for Induction Motor by Immune Memory Dynamic Clonal Strategy Algorithm

Quick detection of a small initial fault is important for an induction motor to prevent a consequent large fault.The mathematical model with basic motor equations among voltages,currents,and fluxes is analyzed and the motor model equations are described.The fault related features are extracted.An immune memory dynamic clonal strategy(IMDCS)system is applied to detecting the stator faults of induction motor.Four features are obtained from the induction motor,and then these features are given to the IMDCS system.After the motor condition has been learned by the IMDCS system,the memory set obtained in the training stage can be used to detect any fault.The proposed method is experimentally implemented on the induction motor,and the experimental results show the applicability and effectiveness of the proposed method to the diagnosis of stator winding turn faults in induction motors.

Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.

F_0F_1-ATPase生物传感器检测肠出血性大肠埃希菌O157:H7

目的研究F0F1-ATPase纳米生物传感器在肠出血性大肠埃希菌O157:H7检测中的应用,开发高灵敏、特异性强的快速检测技术。方法利用免疫技术构建信号识别元件,根据F0F1-ATPase酶学机制建信号转化系统,建立免疫生物传感器,最后通过荧光扫描仪进行信号检测。本研究以食品中常见的大肠埃希菌(Escherichiacoli)和沙门菌(Salmonellatyphi)为干扰菌株进行了该方法的特异性研究。结果检测时间为4.5h,102～104cfu呈现良好的梯度性和线性,R2=0.9818。空白对照组和102cfu/孔均与104cfu/孔组存在极显著性差异,P值分均为P=0.00<0.01。结论 F0F1-ATPase纳米生物传感器对O157:H7检测快速、灵敏、特异性好,有良好的应用前景。

Effects ofβ-1,3-glucan and ascorbic acid on the nutritional-immune response and antioxidant signaling pathways of live tiger grouper during simulated transport

Transport in water is the most common method for transporting live fish in China,however,transport is a strong stressor.Transport stress could lead to a reduced immune and antioxidant system function of tiger grouper,resulting in sickness and death.Besides,tiger grouper were continuously stressed during transport,which resulted in quality deterioration.It is necessary that find a way to relieve the stress of transportation of tiger grouper.Ascorbic acid is not only a good anti-stress agent,but it is also an effective immunostimulant.β-1,3-glucan is a feed additive that can enhance the immune response of fish.Therefore,this study evaluated the effects ofβ-1,3-glucan and ascorbic acid on the nutritional-immune response and antioxidant signaling pathways of live tiger grouper during simulated transport.Results indicated that addingβ-1,3-glucan and ascorbic acid in transport-water muted the increase of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activity.In addition,β-1,3-glucan and ascorbic acid activated Nrf2 and mediated TOR expression and then up-regulate related mRNA expression of antioxidant and immune enzymes.We concluded that the application ofβ-1,3-glucan and ascorbic acid inhibit the increase of metabolism enzymes and inflammatory factors and activate immune and antioxidant signaling pathways to relieve oxidant stress,immune response,and apoptosis.Reducing the loss of amino acids provided nutrients to relieve oxidative stress and immune response,which demonstrated immune-nutritional response in live tiger grouper during simulated transport.These results may provide a new solution for alleviating the decline of immune and antioxidant function of tiger grouper caused by transportation stress.

Pegylated interferon α-2b up-regulates specific CD8+ T cells in patients with chronic hepatitis B

AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density:1.077 g/L,Pharmingen) at weeks 0,4,8,12,and 24,respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay. RESULTS:The frequency of circulating HBV core or env-specific CD8 T cells was higher (P < 0.05),the number of HBV core specific CD8 T cells was greater at week 24 (P < 0.05),the level of Th1-type cytokines [interleukin (IL)-12,tumor necrosis factor-α,and IFN-γ] was higher,while that of Th2-type cytokines (IL-4,IL-6,and IL-10) was lower in responders than in nonresponders (P < 0.05) after pegylated IFN α-2b treatment. The IL-6 level was correlated with HBV DNA (r = 0.597,P = 0.04),while the inducible protein-10 (IP-10) level was correlated with serum alanine aminotransferase (ALT) (r = 0.545,P = 0.005). The IP-10 level at week 8 after pegylated IFN α-2b treatment could predict the normalization of ALT in CHB patients (positive predict value = 56%,negative predict value = 92%). CONCLUSION:Pegylated IFN α-2b can enhance the immune response of CHB patients by increasing the frequency of HBV specific CD8+ T cells and regulating the Th1/Th2 cytokines.

Multiplexed Biosensing Diagnostic Platforms Detecting Autoantibodies to Tumor-Associated Antigens from Exosomes Released by CRC Cells and Tissue Samples Showed High Diagnostic Ability for Colorectal Cancer

Colorectal cancer(CRC)is the second leading cause of cancer-related death worldwide.The five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early stages but lower than 10%when CRC is diagnosed in advanced stages.Autoantibodies against specific CRC autoantigens(tumor-associated antigens(TAAs))in the sera of patients have been widely demonstrated to aid in early diagnosis.Thus,we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid biopsy.To that end,we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis.A total of 103 proteins were identified as potential autoantigens specific to CRC.After bioinformatics and meta-analysis,we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot(WB)and immunohistochemistry(IHC).We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients,along with an association of nine of these proteins with CRC prognosis.After validation,all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals,either by luminescence Halotag-based beads,or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC detection.Taken together,our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases;they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here could be integrated into a point-of-care(POC)device for CRC detection with high diagnostic ability.

African swine fever virus MGF505-3R inhibits cGAS-STING-mediated IFN-βpathway activation by degrading TBK1

African swine fever virus(ASFV)is an important pathogen causing acute infectious disease in domestic pigs and wild boars that seriously endangers the global swine industry.As ASFV is structurally complex and encodes a large number of functional proteins,no effective vaccine has been developed to date.Thus,dissecting the mechanisms of immune escape induced by ASFV proteins is crucial.A previous study showed that the ASFV-encoded protein is an important factor in host immunity.In this study,we identified a negative regulator,MGF505-3R,that significantly downregulated cGAS/STING-and poly(dG:dC)-mediated IFN-βand interferon stimulation response element(ISRE)reporter activity and suppressed IFNB1 and IFIT2 mRNA levels.In addition,TBK1,IRF3 and IκBαphosphorylation levels were also inhibited.Mechanistically,MGF505-3R interacted with cGAS/TBK1/IRF3 and targeted TBK1 for degradation,thereby disrupting the cGAS-STING-mediated IFN-βsignaling pathway,which appears to be highly correlated with autophagy.Knockdown MGF505-3R expression enhanced IFN-βand IL-1βproduction.Taken together,our study revealed a negative regulatory mechanism involving the MGF505-3R-cGAS-STING axis and provided insights into an evasion strategy employed by ASFV that involves autophagy and innate signaling pathways.

Potential role of long noncoding RNA RP5-881L22.5 as a novel biomarker and therapeutic target of colorectal cancer

BACKGROUND The incidence of colorectal cancer in humans is high,and it is in the top five for cancer-related morbidity and mortality.It is one of the main threats to human health.The function of long noncoding RNAs in tumor occurrence and development has gradually gained attention in recent years.In increasing numbers of studies,researchers have demonstrated that it plays an important role in the pathogenesis of colorectal cancer.AIM To find out if long noncoding RNA RP5-881L22.5 played a role in the pathogenesis of colorectal cancer in relation to the tumor microenvironment.METHODS We analyzed the transcriptome data and clinical data in The Cancer Genome Atlas-colon adenocarcinoma.The CIRBERSORT algorithm was applied to evaluate these tumor-infiltrating immune cells in The Cancer Genome Atlas-colon adenocarcinoma cancer tissue samples.Using the“estimate”package in R,we assessed the tumor immune microenvironment.The expression level of RP5-881L22.5 in tumor tissue and adjacent normal tissue samples from 4 pairs of colorectal cancer patients was determined by quantitative reverse transcription PCR.Colorectal cancer cells were tested for invasiveness using a transwell invasion assay after RP5-881L22.5 expression was knocked down.RESULTS The expression of lncRNA RP5-881L22.5 was related to the clinical characteristics of the tumors,and it was negatively related to the infiltration level of immune cells in the tumor microenvironment and the expression of T cell inhibitory receptors.A major function of its coexpressed mRNA was to regulate tumor immunity,such as the immune response.When quantitative reverse transcription PCR was performed on tumor tissues from 4 pairs of colorectal cancer patients,the results showed that RP5-881L22.5 was highly expressed.Subsequently,knocking down the expression of RP5-881L22.5,the invasiveness of colorectal cancer cell lines was reduced,and the apoptosis rate was increased.CONCLUSION RP5-881L22.5 plays a crucial role in the microenvironment of tumors as well as in the pathogenesis of colorectal cancer.The relationship between RP5-881L22.5 and the tumor immune microenvironment deserves further study.

Expression and significance of B7-H1 in peripheral blood dendritic cells from patients with bladder cancer

Objective： The aim of this study was to study the expression and the clinical significance of B7-H1 on dendritic cells （DCs） in peripheral blood from patients with bladder cancer. Methods： Peripheral blood mononuclear cell were disparted from 30 bladder cancer patients and 7 healthy controls by density gradient centfifugation and then co-cultured. The expres- sion of B7-H1 on DCs were analyzed by flow cytometry. Results： Expression of BT-H1 on DCs in bladder cancer was higher than healthy controls （P 〈 0.01）. And the expression were strongly associated with the pathological grade and clinical stage of bladder cancer （P 〈 0,05）. Conclusion： The up-regulation of B7-H1 on DCs was strongly associated with neoplastic progres-sion of bladder cancer. B7-H1/programmed death （PD）-1 signal pathway may also play an important role in immune escape of bladder cancer during initial phase of T cell immune response.

Programmed Death Ligand-1 on Microglia Regulates Th1 Differentiation via Nitric Oxide in Experimental Autoimmune Encephalomyelitis

Microglia are considered to be potential anti- gen-presenting cells and have the ability to present antigen under pathological conditions. Nevertheless, whether and how microglia are involved in immune regulation are lar- gely unknown. Here, we investigated the suppressive activity of microglia during experimental autoimmune encephalomyelitis （EAE） induced by myelin oligodendro- cyte glycoprotein, with the goal of understanding their role in regulating the T cell reaction. Using flow cytometric analysis, we found that microglia were characterized by increased cell number and up-regulated programmed death ligand-1 （PD-L1） at the peak phase of EAE. Meanwhile, both the CD4＋ T cells and microglia that infiltrated the central nervous system expressed higher levels of PD1, the receptor for PD-L1, accompanied by a decline of Thl cells. In an ex vivo co-culture system, microglia from EAE mice inhibited the proliferation of antigen-specific CD4＋ T cells and the differentiation of Thl cells, and this was significantly inhibited by PD-L 1 blockade. Further, microglia suppressed Thl cells via nitric oxide （NO）, the production of which was dependent on PD-L1. Thus, these data suggest a scenario in which microglia are involved in the regulation of EAE by suppressing Thl-cell differenti- ation via the PD-L1-NO pathway.

Pathogenesis and clinical features of severe hepatitis E virus infection

The hepatitis E virus(HEV),a member of the Hepeviridae family,is a small,non-enveloped icosahedral virus divided into eight distinct genotypes(HEV-1 to HEV-8).Only genotypes 1 to 4 are known to cause diseases in humans.Genotypes 1 and 2 commonly spread via fecal-oral transmission,often through the consum-ption of contaminated water.Genotypes 3 and 4 are known to infect pigs,deer,and wild boars,often transferring to humans through inadequately cooked meat.Acute hepatitis caused by HEV in healthy individuals is mostly asymptomatic or associated with minor symptoms,such as jaundice.However,in immunosup-pressed individuals,the disease can progress to chronic hepatitis and even escalate to cirrhosis.For pregnant women,an HEV infection can cause fulminant liver failure,with a potential mortality rate of 25%.Mortality rates also rise amongst cirrhotic patients when they contract an acute HEV infection,which can even trigger acute-on-chronic liver failure if layered onto pre-existing chronic liver disease.As the prevalence of HEV infection continues to rise worldwide,highlighting the particular risks associated with severe HEV infection is of major medical interest.This text offers a brief summary of the characteristics of hepatitis developed by patient groups at an elevated risk of severe HEV infection.