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Objective @#To search for new biomarkers to predict prognosis in colorectal cancer ( CRC) patients @*Methods@#A prognostic model was developed for colorectal cancer with immune-related genes from the cancer ge.nome atlas ( 'TCGA) database using one-way Cox regression analysis and least absolute shrinkage and selection op.erator ( L.ASS0) regression analysis. Moreover, the immune infiltration characteristics of patients in high and lowrisk groups was compared by sstimation of stromal and immune cells in malignant tumor tissues using expression data ( ESTIMATE) and cel-type identification by estimating relative subsets of RNA transcripts ( CIBERSORT). Inaddition , the expression levels of immune checkpoints were analyzed in patients from different risk groups. The sensitivity of patients in the two risk groups to chemotherapeutic agents was also compared based on genomics of drugsensitivity in cancer (GDSC). @*Results@#It was found that the prognostic model constructed based on immune genescould better predict the overall survival (OS) of CRC patients, and the results showed area under curve ( AUC)values of0.764(95% C1:0.751-0.793),0.773(95% C:0.761 -0.779), and 0.760(95% C:0.742 -0. 774 ) for 1-, 3-, and 5-year OS, respectively. Patients in the low-risk group had higher expression levels of immune checkpoints and more abundant immune cells such as T cells (P <0. 001), dendritic cells (P <0. 001 ),macrophages (P <0. 001), neutrophils ( P <0. 001 ). Patients in the high-risk group might be more sensitive tosome chemotherapeutic agents such as axitinib , imatinib, methotrexate, pazopanib , rapamycin, sunitinib and tasigarnib. @*Conclusion@#A prognostic model based on 19 immune genes was effective in predicting the prognosis ofCRC patients. The number and activity of immune cells in the immune microenvironment in different patients maybe an important factor influencing their response to immunocheck inhibitors and chemotherapeutic agents.
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Objective:To explore the correlation between differential immune-related genes(DIRGs)and immune cells in the progression of atherosclerosis(AS)and general rule of Chinese medicine for intervening DIRGs.Methods:Firstly,GSE28829 data set was obtained from GEO database,and immune-related genes were downloaded from ImmPort database and MSigDB database.Secondly,differentially expressed genes between early AS plaques(EAP)and advanced AS plaques(AAP)of GSE28829 were screened by limma package,and their intersections with immune-related genes were known as DIRGs.clusterProfiler package was used to enrich the DIRGs.Protein interaction network of DIRGs was constructed and Hub genes were screened.Then,the infiltration patterns of 22 kinds of immune cells were analyzed by CIBERSORT to screen differential immune cells,and the correlation between them and Hub genes were analyzed by Pearson method.Finally,Coremine Medical database was used to predict Chinese herbs for in-tervening DIRGs,the property and flavor of Chinese herbs were collected.Results:Total 63 DIRGs were obtained,and 10 Hub genes(CD86,TLR2,TYROBP,CCR1,ITGB2,CCL2,CCL4,CSF1R,CXCR4,CTSS)were screened out.Enrichment analysis results showed that the molecular functions,biological processes and signaling pathways of DIRGs were closely related to immune regulation.Analysis of immune cell infiltration showed that proportions of regulatory T cells,activated dendritic cells and resting mast cells in EAP were increased.Proportions of memory B cells,γδ T cells,M0 macrophages and M2 macrophages were increased in AAP.Correla-tion analysis showed that CD86 was positively correlated with M2 macrophages in EAP.In AAP,CD86,CTSS,CXCR4,CSF1R,ITGB2 and TYROBP were positively correlated with M0 macrophages,while CCL4 and CCL2 were negatively correlated with resting mast cells.Results of frequency showed that Chinese herbs for intervening DIRGs mainly distributed to liver and lung meridians,and their property and taste were cold and bitter.Conclusion:This study found that in the progression of AS,10 DIRGs were the most important,and 7 kinds of immune cells were dysregulated,among which CD86,CTSS,CXCR4,CSF1R,ITGB2,TYROBP,CCL4 and CCL2 were correlated with resting mast cells,M0 and M1 macrophages.At the same time,immune mechanism of AS progression was closely related to liver meridian,lung meridian,bitter,sweet,cold and warm.The results can provide reference and ideas for Chinese herbs clinical prescription to treat AS and further exploratory the immunological mechanism of AS progression.
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Objective:To investigate the changes of hippocampal gray matter volume and expression of candidate immune related genes in a rat model of schizophrenia established by repeated administration of dizocilpine(MK-801).Methods:Thirty SPF grade Sprague-Dawley male rats at postnatal day 28 were randomly divided into MK-801 medium-dose (0.25 mg/kg) group, MK-801 high-dose(0.50 mg/kg) group and normal saline (5 mL/kg) group according to random number table method, with 10 in each group.Rats were given continuous intraperitoneal administration according to grouping once a day for 14 days.Open field test, novel object recognition test and Y-maze test were used at postnatal day 60 to detect spontaneous activity, exploration ability, anxiety level, object recognition memory ability and spatial working memory of rats, respectively.At postnatal day 67, structural magnetic resonance imaging was used to detect the changes of hippocampal gray matter volume in rat.And at postnatal day 70, qRT-PCR was used to detect the expression of candidate immune-related genes in rat hippocampus.SPSS 25.0 was used for statistical analysis, one-way ANOVA was used for comparison among multiple groups, and Tukey test was used for further pairwise comparisons.Results:(1)The behavioral results showed that there were significant differences in the total movement distance, central area activity time, novel object recognition index, and spontaneous correct alternation rate among the three groups ( F=11.15, 10.11, 13.62, 11.99, all P<0.05). The total movement distances in MK-801 medium-dose group and MK-801 high-dose group ((21.44±2.17) m, (22.87±1.96)m) were higher than that in the normal saline group ((18.70±1.88) m) (both P<0.05). The activity time of the central area in the MK-801 medium-dose group and MK-801 high-dose group((3.24±1.58) s, (2.50±1.32) s) were lower than that of the normal saline group ((6.05±2.48)s) (both P<0.01). Novel object recognition indexes in the MK-801 medium-dose group and MK-801 high-dose group((56.10±3.99)%, (54.00±6.41)%) were both lower than that in the normal saline group ((65.90±5.65)%)(both P<0.01), and the rates of spontaneous correct alternation ((54.60±7.03)%, (51.60±8.84)%) in the two groups were lower than that of the normal saline group ((68.40±8.57)%) (both P<0.01). (2) The results of structural magnetic resonance imaging showed that there were significant differences in the volume of hippocampal gray matter among the three groups ( F=9.24, P<0.001). The volumes of hippocampal gray matter in MK-801 medium-dose group and MK-801 high-dose group were lower than that in normal saline group(both P<0.001). (3)By constructing protein-protein interaction network, four candidate immune related genes were screened out: neuropeptide Y (NPY), somatostatin (SST), cholecystokinin (CCK) and tachykinin 1 (TAC1). The results showed that the mRNA expression levels of NPY, SST and CCK in the hippocampus of the three groups were significantly different ( F=11.41, 10.43, 5.85, all P<0.05), but there was no statistical difference in the TAC1 mRNA expression level ( F=0.08, P>0.05). The mRNA levels of NPY, SST and CCK in the hippocampus of rats in the MK-801 high-dose group were lower than those in the normal saline group (all P<0.05). Conclusion:Both medium dose and high dose MK-801 administration can reduce the volume of hippocampal gray matter in schizophrenia model rats, but they have different effects on the expression of hippocampal immune related genes, of which high dose administration has a greater effect.
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Traditionally, bamboo has immense medicinal values owing to their rich bioactive compounds. On the other hand, scientific developments in global aquaculture have revealed the significance of dietary nutraceuticals in aquaculture. In this study, efforts have been made to evaluate the properties of shoot and leaf extracts of Melocanna baccifera (Roxb.) Kurz (Muli bamboo) and demonstrated its immunomodulatory potential. At first, four different extracts of bamboo leaf and shoot were prepared through water and ethanolic solvents followed by phytochemical profiling, antioxidant and antimicrobial activities of extracts. Based on the in vitro evaluation, BLAL (bamboo leaf alcoholic) extract was chosen for further in vivo evaluation. Second experiment was carried to assess the toxicity of BLAL extract on the Indian major carp, Labeo rohita (Hamilton), locally called ‘rohu’. No mortality was observed up to 20 g of extract kg-1 body weight. Additionally, haemolytic assay was also conducted to ascertain the cellular toxicity of extract. Third experiment was conducted to find out the effect of dietary BLAL extract [doses: control (0.0%), T1 (0.01%), T2 (0.1%) and T3 (1%) of extract kg-1 feed] on immune related genes (HSP70, IL-1? and TNF-?) expression in L. rohita. The present study confirms the presence of vital phytochemicals in bamboo extracts and immunomodulatory potential of ethanolic leaf extract in roh
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BACKGROUND: Bones are currently considered as an immune organ. A variety of immune cells that originate from the bone marrow can interact with the cells of the skeletal system to jointly regulate bone metabolism. Explorations on the pathogenesis of postmenopausal osteoporosis as well as treatment-related molecular targets and signal pathways can help prevention and treatment of the disease. OBJECTIVE: To investigate the expression profiles of immune-related genes in peripheral blood leukocytes of postmenopausal osteoporosis patients using RNA-Seq technology. METHODS: Forty female patients who had experienced menopause for 0 to 20 years and were hospitalized due to fractures were enrolled. They were divided into normal bone mass group (T >-1) and osteoporosis group (T 2), and 131 genes were up-regulated and 56 genes were down-regulated. We identified in total 29 differentially expressed immune-related genes including 25 up-regulated and 4 down-regulated ones. There was significant difference in expression between the osteoporosis and normal bone mass groups for genes, including KIR3DL1, KIR3DL2, KIR2DL4, KLRD1 and HSPA6 (P < 0.05). These differentially expressed genes are potentially important for the natural killer cell-mediated cytotoxicity by the KEGG pathway analysis. KIR3DL1, KIR3DL2, KIR2DL4, KLRD1 and HSPA6 may be closely related to the natural killer cell-mediated cytotoxicity during the occurrence of postmenopausal osteoporosis.
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Differential gene expression profiles in Balb/cJ mouse model of acute hepatic failure in- fected with MHV-3 virus intervened by anti-hepatic failure compound (AHFC) and the changes of cytokines regulated by genes were investigated. The Balb/cj mice were divided into AHFC-intervened group and control group randomly. Acute hepatic failure model of Balb/cJ mice infected with MHV-3 virus was established. The survival rate in the two groups was observed. It was found that the survival rate in the AHFC-intervened group and control group was 90% and 50% re- spectively 48 h after intrapefitoneal injection of MHV-3 (P<0.05). Before and after the experiment, the cytokines in peripheral blood of the survival mice were determined, and RNA was extracted from survival mouse liver tissue for the analysis of the differential gene expression by a 36 kb mouse oli- gonuleotide DNA array. In all the genes of microarray there were 332 genes expressed differently in the two groups, in which 234 genes were up-regulated and 78 genes down-regulated. Through clustering analysis, the differential expression of immune related genes, including TNF receptor superfamily, Kctd9, Bcl-2, Fg12, IL-8, IL-6, IFN-γ, TNF-α etc. might be related with the curative effectiveness of AHFC. It was suggested that AHFC can balance the immune state of mouse model of acute hepatic failure infected with MHV-3 virus mainly through regulating the expression of immune related genes, decrease the immune damage and inhibit liver cell apoptosis of mouse acute hepatic failure model obviously so as to increase the survival rate of mouse models of acute hepatic failure.