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Objective To identify M1 macrophage-related genes in rejection after kidney transplantation and construct a risk prediction model for renal allograft survival. Methods GSE36059 and GSE21374 datasets after kidney transplantation were downloaded from Gene Expression Omnibus (GEO) database. GSE36059 dataset included the samples from the recipients with rejection and stable allografts. Using this dataset, weighted gene co-expression network analysis (WGCNA) and differential analysis were conducted to screen the M1 macrophage-related differentially expressed gene (M1-DEG). Then, GSE21374 dataset (including the follow-up data of graft loss) was divided into the training set and validation set according to a ratio of 7∶3. In the training set, a multivariate Cox's model was constructed using the variables screened by least absolute shrinkage and selection operator (LASSO), and the ability of this model to predict allograft survival was evaluated. CIBERSORT was employed to analyze the differences of infiltrated immune cells between the high-risk group and low-risk group, and the distribution of human leukocyte antigen (HLA)-related genes was analyzed between two groups. Gene set enrichment analysis (GSEA) was used to further clarify the biological process and pathway enrichment in the high-risk group. Finally, the database was employed to predict the microRNA (miRNA) interacting with the prognostic genes. Results In the GSE36059 dataset, 14 M1-DEG were screened. In the GSE21374 dataset, Toll-like receptor 8 (TLR8), Fc gamma receptor 1B (FCGR1B), BCL2 related protein A1 (BCL2A1), cathepsin S (CTSS), guanylate binding protein 2(GBP2) and caspase recruitment domain family member 16 (CARD16) were screened by LASSO-Cox regression analysis, and a multivariate Cox's model was constructed based on these 6 M1-DEG. The area under curve (AUC) of receiver operating characteristic of this model for predicting the 1- and 3-year graft survival was 0.918 and 0.877 in the training set, and 0.765 and 0.736 in the validation set, respectively. Immune cell infiltration analysis showed that the infiltration of rest and activated CD4+ memory T cells, γδT cells and M1 macrophages were increased in the high-risk group (all P < 0.05). The expression level of HLA I gene was up-regulated in the high-risk group. GSEA analysis suggested that immune response and graft rejection were enriched in the high-risk group. CTSS interacted with 8 miRNA, BCL2A1 and GBP2 interacted with 3 miRNA, and FCGR1B interacted with 1 miRNA. Conclusions The prognostic risk model based on 6 M1-DEG has high performance in predicting graft survival, which may provide evidence for early interventions for high-risk recipients.
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BACKGROUND: Although clinical studies have found that autologous adipose mesenchymal stem cells can effectively reduce facial fibrosis in patients with radiation-induced systemic sclerosis, but the mechanism of action has not been thoroughly analyzed. OBJECTIVE: To study the mechanism of action of adipose mesenchymal stem cells on bleomycin-induced systemic sclerosis in mice. METHODS: Forty SPF C57BL/6J female mice aged 6-8 weeks were randomly assigned to normal control group, adipose mesenchymal stem cells group, bleomycin group, and PBS group. Mice in the latter three groups were subjected to subcutaneous injection with bleomycin every other day for 28 days, and mouse models of systemic sclerosis were established. After successful model establishment, mice in the adipose mesenchymal stem cells group were subcutaneously injected with adipose mesenchymal stem cells; mice in the PBS group were subcutaneously injected with PBS; the treatments lasted for 14 days. Enzyme-linked immunosorbent assay was used to determine the levels of serum interleukin-17, transforming growth factor-β, interleukin-6, and tumor necrosis factor-α. Hematoxylin-eosin staining and Masson staining were utilized to measure histopathological changes in the skin and lung of systemic sclerosis mice. Immunofluorescence method was applied to examine collagen I, III, and V and CD31 expression levels in the skin and lung. RESULTS AND CONCLUSION: (1) Compared with the bleomycin group, the expression levels of interleukin-17, transforming growth factor-β, interleukin-6, and tumor necrosis factor-α were significantly decreased in the adipose mesenchymal stem cells group (P < 0.01). (2) Compared with the normal control group, the skin dermis of mice was thickened; inflammatory cells infiltrated; skin appendages reduced; the alveoli were atrophic and collapsed; with a lot of inflammatory cell infiltration, pulmonary arteriole wall thickening, microvascular basement membrane thickening, and fibrinoid necrosis, and the inflammatory symptoms improved after treatment in the adipose mesenchymal stem cells group. (3) Compared with the normal control group, the skin and lung tissues of bleomycin group mice showed a large aggregation of collagen fibers, and the collagen fibers were reduced after adipose mesenchymal stem cells treatment. (4) After treatment with adipose mesenchymal stem cells, the expression levels of collagen I, III, and V were decreased in the skin and lung tissue of mice, but the expression of CD31 in the skin tissues was increased in the bleomycin group (P < 0.01). (5) The results suggested that adipose mesenchymal stem cells can regulate the immune response of bleomycin mice and reduce fibrosis, inflammation and vascular lesions.
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Immune response is one of the main reasons causing neurological deficits in the patients with cere -brovascular diseases , which activates microglia , induces inflammatory reaction and finally results in serious neuronal and endothelial injury .MicroRNAs take part in the regulation of immunoreaction , and simultaneously regulates many target genes and induces faster post-transcriptional regulation to its target genes compared with the traditional transcriptional regu -lation.For providing a basis for the clinical use of microRNAs and applying new therapy , this review mainly focuses on the function and mechanism of microRNAs in the regulation of the immunoreaction caused by cerebrovascular diseases .
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Objective:To investigate the effect of HSM on the immunoreaction and renal fibrosis in mice with cecal ligation and puncture (CLP).Methods: Renal fibrosis was induced by CLP;mice were divided into three groups,including sham group (sham,n =5),model group (CLP,n =11),therapy group (HSM,n =11).HSM extract [200 mg/(kg?d)] was orally administered to HSM group2 hour before surgery and repeated everyday throughout 10 days,while sham group and model group were given the same dose of normalsaline.FACS assay was used to analyze the amount of macrophages ,neutrophils and Treg in PBMC,as well as macrophages in peritonealfluid;we used Q-PCR assay to analyze the expression of inflammatory molecules (IL-1βand TNF-α) and fibrogenic cytokines (TGF-β,MMP9 and TIMP1) from renal sections.Besides,renal sections were subjected to HE stain and immunohistochemical staining with α-SMA and fibronectin.Results: The amount of model group′s macrophages and neutrophils in PBMC,as well as macrophages in theperitoneal fluid were significantly higher than sham group ′s,whereas HSM succeeded in lowering them;contrast to sham group,Tregs′amount of CLP group and HSM group in PBMC had no significant changes .The expression of inflammatory molecules (IL-1βand TNF-α) and fibrogenic cytokines (TGF-β,MMP9 and TIMP1) from CLP group′s renal sections were remarkably improved ,whereas HSM inhibitedthat.The CLP group′s HE results showed obvious renal inflammatory damage ,whereas HSM reduced the histopathologicalterations;contrast to sham group,model group′s expression of α-SMA and fibronectin was remarkably improved,while HSM groupshowed lower expression.Conclusion: HSM extract could regulate immunity response and had effect in improving renal fibrosis .
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Summary: To explore the mechanism of epilepsy induced by IL-1β and IL-6, the changes of glutamic acid (Glu) and GABA immunoreaction in the cerebral cortex and hippocampus of rats with seizure induced by IL-1β or IL-6 were studied. Rats were randomly divided into 3 groups: control group (intracerebroventricular injection (icv) of NS), IL-1β group (icv injection of IL-1β) and IL-6 group (i.c.v. injection of IL-6). 120 min after the icv injection of reagents of IL-1β or IL-6, behavioral changes were observed and Glu and GABA in the cerebral cortex and hippocampus were examined by means of immunohistochemistry. Our results showed that no seizure developed in the control group, while moderate seizure was observed in IL-1β group and IL-6 group. Compared with the controls, the immunoreaction of Glu was significantly increased, while GABA was obviously decreased in IL-1β group and IL-6 group after 120 min. Our study suggested that the IL-1β and IL-6 might promote and induce epilepsy by increasing Glu and decreasing GABA in the cerebral cortex and hippocampus.
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Objective The changes of Glutamic acid(Glu) and GABA immunoreaction in the cerebral cortex and hippocampus of rats with seizure induced by IL-1? and IL-6 were studied.To explore the mechanism of IL-1? and IL-6 in epilepsy. Methods Experimental rats were randomly divided into 3 groups:control group,IL-1? group,and IL-6 group.After intracerebroventricular injection of relevant reagents for 120?min,behaviour changes were observed,Glu and GABA were examined by means of immunohistochemistry in the cerebral cortex and hippocampus of rats. Results The behaviour observation indicated that no seizure happened in control group,seizure in middle degree was observed in IL-1? group and IL-6 group.Compared with in control group,the immunoreaction of Glu showed that the expression was significantly increased in IL-1? group and IL-6 bgroup,while GABA was obviously decreased after intracerebroventricular injection IL-1? or IL-6 at 120?min.Conclusion The machanism of that IL-1? or IL-6 particpated in promotion and abduction epilepsy may be through increasing Glu and decreasing GABA in the cerebral cortex and hippocampus.The nerve excitation is enhanced and then epilepsy occurred.
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Objective To study the type Ⅰ,Ⅱ,Ⅲ and Ⅹcollag e n expression in meniscus and articular cartilage and immunoreactions post xenoge nic and allogenic meniscus transplantation. Methods After men iscectomy,30 adult New Zealand white rabbits were divded into two groups:group A undertook allogenic medial meniscus transplantation and group B undertook xenog enic meniscus transplantation with fitted meniscus tissues harvested from swine. 6, 12 and 24 weeks post transplantation, the histological and immunohistochemical analysis of type Ⅰ ,Ⅱ,Ⅲ and Ⅹ collagens monoclonal antibody were investigated in menisci and a rticular cartilage. Peripheral blood were obtained for immunoreactions study thr o ugh the methods of CDMT (Complement Dependent Microlymphocytotoxicity Test) and RIA (Radioimmunoassay)of IL-2 and IL-6. Results The meniscu s and articular cartilage were good post allogenic meniscus transplantation, but the transplanted xenogenic meniscus appeared to be dissolved and absorbed and c art ilage lesions were observed in 24 week post operation. No significant difference was found between two groups in type Ⅰ,Ⅱ and Ⅲ collagen expression during e xperiment. From 1～12 weeks, no significant diffe rence was found among type Ⅰ,Ⅱ and Ⅲ collagen expression in articular cartil age in two groups. However,24 weeks post operation, type Ⅹ collagen's expressio n in cartilage was abnormally increased. Neither allogenic nor xenogenic meniscu s transplantation caused fatal immunoreaction during the whole experiment. Con clusion The transplantation meniscus began to be dissolved and absorbed after half a year, but allogenic meniscus transplantation achieved good results . Type Ⅰ,Ⅱ and Ⅲ collagen expression in transplanted meniscus and articular cartilage showed no difference between two groups, but the expression of type Ⅹ collagen was abnormally increased in xenogenic group 24 weeks post operation. No fatal immunoreaction was found in both groups.
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Experiment Ⅰ. Twenty-eight rats were randomly assigned into Near-Infrared Information Radiation (NIIR) group and control group. Two weeks later each rat was innoculated intraperitoneally with Salmonella typhosa H antigen (HAg) and cyclophosphamide (CY). Peripheral lymphocyte counts in the NIIR group were significantly higher than those in the control group on the fifth day after administration of CY. Experiment Ⅱ, Fifty-four rats were randomly divided into NIIR group given CY and H Ag intraperitoneally, CY and H Ag group and H Ag group for treatment. By the end of the fourth week, the survival rate and serum IgG level in the NIIR group were significantly higher than those in the CY and HAg group. By the end of 2nd week, the titer of the anti-H antibody of the HAg group and NIIR group was significantly higher than that of the CY and HAg group. Experiment Ⅲ. Thirty rats were randomly allocated to NIIR group and control group. Spleen cells were taken and cultured with Con A for 24h to induce IL-2 and the activity of IL-2 in the NIIR group was significantly higher than that in the control group. The NK activity in NIIR group was higher but not significant and ADCC in the NIIR group was significantly higher than that in the control group. The results suggest that NIIR is capable of enhancing immunoreaction in immunosuppressive bodies by promoting the function recovery of T helper cells, therefore NIIR is effective to regulate the immunological function on chronic active hepatitis.
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Objective:To study the clinical and pathologic features of patients with lupus nephritis (LN) whose myeloperoxidase anti neutrophil cytoplasmic antibody (MPO ANCA) were positive. Methods:The clinical and pathological features were analyzed in 18 patients with LN whose MPO ANCA were positive. And the data of patients with different clinical outcomes were compared. Results:(1)The hematological abnormalities, hypertension and serositis in these patients were more common than general ones with LN. (2)Proteinuria and hematuria were common, the morbidities of gross hematuria and renal failure in these patients were higher than general ones with LN.(3)Various autoantibodies were positive in these patients.(4)Segmental necrosis crescentic nephritis accompanied by density of immunocomplex in glomeruli and vasculitis in intestitium were common.(5)The morbidity of ESRF and mortality of these patients were similar to general ones with LN. The morbidity of tubular atrophy in those with poor prognosis was significantly higher than those survived. Conclusion:The patients with LN whose MPO ANCA are positive have some difference from those with negative MPO ANCA, but positive MPO ANCA is not directly related to the prognosis. [