Cancer-testis Antigen OY-TES-1 Expression and Immunogenicity in Hepatocellular Carcinoma

Summary:Cancer testis(CT)antigens have received particular attention in cancer immunotherapy.OY-TES-1 is a member of CT antigens.This study was to evaluate OY-TES-1 expression and immunogenicity in hepatocelluar carcinoma(HCC).OY-TES-1 mRNA expression was detected in 56 HCC tissues and 5 normal liver tissues by reverse transcriptase PCR(RT-PCR).Of the 56 cases of HCC tissues tested,37 cases had tumor and matched adjacent non-cancer tissues and were subjected to both RT-PCR and quantitative real-time PCR.OY-TES-1 protein was subsequently observed on a panel of tissue microarrays.Sera from patients were tested for OY-TES-1 antibody by ELISA.To identify OY-TES-1 capable of inducing cellular immune response,OY-TES-1 protein was used to sensitize dentritic cells and the cytotoxicity effect was measured in vitro.The results showed that OY-TES-1 mRNA was highly expressed in 41 of the 56(73.21%)HCC tissues,whereas none in 5 normal liver tissues.OY-TES-1 mRNA was frequently expressed not only in HCC tissues(72.97%,27/37),but also in paired adjacent non-cancer tissues(64.86%,24/37).But the mean expression level of OY-TES-1 mRNA in HCC tissues was significantly higher than that in adjacent non-cancer tissues(0.76854 vs.0.09834,P=0.021).Immunohistochemistry showed that OY-TES-1 protein expression was detected in 6 of the 49 cases of HCC tissues,and absent in 9 cases of normal liver and 6 cases of cirrhosis tissues.Seropositivity was detected in 10 of the 45 HCC patients,but not detected in 17 cirrhosis patients and 76 healthy donors.The specific cytotoxic T cells elicited by OY-TES-1 could kill HLA-A2^+HCC cell line which expressed OY-TES-1.The target lysis was mainly HLA class I-dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecule.In summary,OY-TES-1 expression is upregulated in HCC tissues and can be recognized by humoral and cellular responses,which suggests that OY-TES-1 is an attractive target for tumor immunotherapy in HCC.

FMR1NB Involved in Glioma Tumorigenesis Is a Promising Target for Prognosis and Therapy

Objective:Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer,but not in normal tissues except for testis.This study aimed to investigate the expression and functional role of FMR1NB in glioma.Methods:The expression of FMR1NB mRNA and protein was determined using RT-PCR and immunohistochemistry,respectively,in glioma specimens from 83 patients at follow-up.The effects of siRNA-mediated FMR1NB silencing on malignant biological behaviors were evaluated in glioma cell lines Al 72 and U251.Results:FMR1NB mRNA and protein expression was detected in 58.8%(77/131)and 46.34%(57/123)of glioma tissues,respectively.FMR1NB protein was positively correlated with World Health Organization grade and found to be an independent prognostic marker for poor outcome.Knockdown of FMR1NB induced apoptosis and suppressed proliferation,adhesion,migration,and invasion by modulating the expression of cyclin A,CDK2,caspase-3,E-cadherin,and N-cadherin in A172 and U251 cells.Conclusion:Our findings suggest that FMR1NB contributes to the tumorigenesis of glioma cells and may represent a potential prognostic biomarker and an attractive therapeutic target in glioma.

Dopamine agonist responsive burning mouth syndrome:Report of eight cases

BACKGROUND Burning mouth syndrome(BMS)is characterized by burning sensation of the oral mucosa.There is a lack of effective treatment.In recent years,a special subtype of BMS has been reported,in which oral burning sensation is alleviated after chewing,speaking,or dopaminergic drug delivery.Currently,there are few reports about the subtype of BMS in China.This study was a retrospective analysis of the clinical data of BMS patients sensitive to dopamine agonist at our hospital,aiming to improve the recognition on this disease.CASE SUMMARY Eight patients diagnosed with dopamine agonist responsive BMS at the Liaocheng People's Hospital from January 1,2017 to June 30,2020 were recruited.The clinical manifestations,treatment,and prognosis were retrospectively analyzed.There were three male and five females in the eight patients.The median age was 56 years(range,46-65 years).All the eight patients showed burning pain in the mouth.The symptoms were mild in the morning and severe in the evening,and alleviated after chewing,talking,and other oral activities.Four patients were accompanied by restless legs syndrome(RLS).Family history of RLS was positive in two patients.All patients were treated with pramipexol,and symptoms were basically relieved after 2-8 wk.CONCLUSION Dopamine agonist responsive BMS is a special subtype of BMS,which is alleviated after oral activities.Dopamine receptor agonist is an effective treatment.

Identification of Dysregulated microRNAs in Glioma Using RNA sequencing

Glioma is the most common malignant brain tumor in central nervous system.Despite advances in the treatment of glioma such as surgery and chemoradiotherapy,most patients are easy to relapse,resulting in adverse clinical outcomes.Hence,effective molecular=targeting treatment may be one of attractive strategies for glioma therapy.The dysregulated microRNAs(miRNAs),one of the candidates of therapeutic targets,are believed to play an important role in the progression of glioma.In this study,we aimed to examine the expression profile of miRNAs in glioma and provide a reference for glioma therapy.Firstly,expression profile of miRNAs in 5 normal brain tissues,5 low-grade glioma(LGG)tissues and 5 glioblastoma(GBM)tissues was detected by RNA sequencing(RNA-seq).Next,the target genes of differentially expressed miRNAs(DEmiRNAs)were predicted and then GO enrichment and KEGG pathway analysis performed by bioinformatics.Finally,10 miRNAs which were significantly up-or down-regulated both in GBM and LGG were validated by real-time quantitative PCR(qRT-PCR).RNA-seq results indicated a number of DEmiRNAs in glioma.There were 64 up-regulated miRNAs and 17 down-regulated miRNAs n LGG,and 181 up-regulated miRNAs and 124 down-regulated miRNAs in GBM,respectively.Bioinformatics analysis showed that the target genes of these DEmiRNAs were enriched in various biological processes and signaling pathways such as cell metabolic and developmental process.Selected DEmiRNAs were further confirmed by qRT-PCR.miRNA-10b-5p,miRNA-92b-3p and miRNA-455-5p were significantly up-regulated in both GBM and LGG;while miRNA-542-3p was significantly up-regulated in LGG;miRNA-184 and miRNA-206 were significantly down-regulated in both GBM and LGG;miRNA-766-5p and miRNA-1-3p were significantly down-regulated in GBM.The subject of our study demonstrated several dysregulated miRNAs may serve as a potential therapeutic target for gl ioma.

Biotechnological Strategies of Riboflavin Biosynthesis in Microbes

Riboflavin is an essential micronutrient for humans and must be obtained exogenously from foods or sup-plements.Numerous studies have suggested a major role of riboflavin in the prevention and treatment of various diseases.There are mainly three strategies for riboflavin synthesis,including total chemical syn-thesis,chemical semi-synthesis,and microbial fermentation,the latter being currently the most promis-ing strategy.In recent years,flavinogenic microbes have attracted increasing attention.Fungi,including Eremothecium ashbyii and Ashbya gossypii,and bacteria,including Bacillus subtilis,Escherichia coli,and lac-tic acid bacteria,are ideal cell factories for riboflavin overproduction.Thus they are good candidates for enhancing the level of riboflavin in fermented foods or designing novel riboflavin bio-enriched foods with improved nutritional value and/or beneficial properties for human health.This review briefly describes the role of riboflavin in human health and the historical process of its industrial production,and then highlights riboflavin biosynthesis in bacteria and fungi,and finally summarizes the strategies for ribofla-vin overproduction based on both the optimization of fermentation conditions and the development of riboflavin-overproducing strains via chemical mutagenesis and metabolic engineering.Overall,this review provides an updated understanding of riboflavin biosynthesis and can promote the research and development of fermented food products rich in riboflavin.

Microrna-1224-5p Is a Potential Prognostic and Therapeutic Biomarker in Glioblastoma:Integrating Bioinformatics and Clinical Analyses

Objective Glioblastoma(GBM)is the most common,invasive,and malignant primary brain tumor with a poor prognosis and high recurrence rate.It’s known that some microRNAs(miRNAs)which are associated with tumorigenesis and progression can be considered as prognostic and therapeutic targets in tumors including GBM.This study aims to highlight the potential role of the core miRNAs in GBM and their potential use as a prognostic and therapeutic biomarker.Methods Differentially expressed miRNAs(DEmiRNAs)were identified in GBM by integrating miRNA-sequencing results and a GBM microarray dataset from the Gene Expression Omnibus(GEO)database through bioinformatics tools.The dysregulated miRNAs were identified by survival analysis through Chinese Glioma Genome Atlas(CGGA).Target genes of the dysregulated miRNAs were predicted on MiRWalk and miRTarBase database.TAM2.0 database,Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways analysis were used to analyze the function of the dysregulated miRNAs.Subsequently,protein-protein interaction(PPI)network analysis was used to identify the top 20 hub targets of the up-regulated and down-regulated miRNAs,respectively.Then,core miRNAs in GBM were identified by constructing dysregulated miRNA-differentially expressed hub gene networks.Validation of the core miRNAs expression was detected in 41 GBM tissues compared to 8 normal brain tissues.Furthermore,the potential biomarkers were identified by clinical correlation analysis and survival analysis.Results Totally,68 intersecting DEmiRNAs were identified,40 of which were upregulated and the other 28 miRNAs were downregulated.Two upregulated and 4 downregulated miRNAs showed prognostic significance.Most differentially expressed hub genes were regulated by the miR-28-5p and miR-1224-5p,which were respectively upregulated and downregulated in GBM.The correlation between miR-1224-5p level and recurrence was statistically significant(P=0.011).Survival analysis showed that high miR-28-5p level and high miR-1224-5p level were both associated with better prognosis.Moreover,high miR-1224-5p level was an independent prognosis factor for GBM patients according to the cox regression analysis.Conclusion MiRNA-1224-5p could be a potential target for the prognosis and treatment in GBM.

Possible effects of chemokine-like factor-like MARVEL transmembrane domain-containing family on antiphospholipid syndrome

Antiphospholipid syndrome(APS)is a systemic autoimmune disease defined by thrombotic or obstetrical events and persistent antiphospholipid antibodies(aPLs).Chemokine-like factor-like MARVEL transmembrane domain-containing family(CMTM)is widely expressed in the immune system and may closely related to APS.This review aimed to systematically summarize the possible effects of CMTM on APS.Publications were collected from PubMed and Web of Science databases up to August 2020.CKLF,CKLFSF,CMTM,antiphospholipid syndrome,immune cells,and immune molecules were used as search criteria.Immune cells,including neutrophil,dendritic cells(DCs),T-cells,B-cells,and inflammatory cytokines,play an important role in the development of APS.Chemokine-like factor 1(CKLF1)has a chemotactic effect on many cells and can affect the expression of inflammatory cytokines and adhesion molecules through the nuclear factor-kB(NF-kB)pathway or mitogen-activated protein kinase(MARK)pathway.CKLF1 can participate in the maturation of DCs,T lymphocyte activation,and the activation of neutrophils through the MAPK pathway.CMTM1 may act on Annexin A2 by regulating Ca^(2+) signaling.CMTM2 and CMTM6 are up-regulated in neutrophils of APS patients.Some CMTM family members influence the activation and accumulation of platelets.CMTM3 and CMTM7 are binding partners of B-cell linker protein(BLNK),thereby linking B cell receptor(BCR)and activating BLNK-mediated signal transduction in B cells.Moreover,CMTM3 and CMTM7 can act on DCs and B-1a cell development,respectively.CMTM may have potential effects on the development of APS by acting on immune cells and immune molecules.Thus,CMTM may act as a novel prognostic factor or immunomodulatory treatment option of APS.