Objective To investigate the association between DNA methylation of matrix metallo-proteinase 9(MMP-9) gene and cognitive function including continuous attention,cognitive flexibility and visuospatial memory in patients with chronic schizophrenia.Methods 71 male schizophrenia patients and 69 healthy controls were recruited and detected their cognitive function.Pyrosequencing was used to determine DNA methylation at CpG site in exon 4 and exon 5 of MMP-9 gene.RT-qPCR was used to detect MMP-9 gene expression.Clinical symptoms were assessed by BPRS.Results (1) Cognitive function including Trail Making Test A,Trail Making Test B,Stroop words only,Stroop colors only,Stroop interference,Spatial Processing Block design and Block Design all scores were significantly lower in schizophrenia patients with schizophrenia than those in health controls (P＜0.01);(2) The MMP-9 gene expression in PBMCs was significantly higher in schizophrenia patients (1.31± 0.48) than that in health control (1.11 ± 0.45,P＜ 0.05).The DNA methylation of CpG4-1,CpG4-2,CpG4-3,CpG4-4,CpG4-5,CpG5-1,CpG5-2,CpG5-4 of MMP-9 gene in schizophrenia patients were lower than those in health controls (P＜0.01).(3)DNA methylation of CpG4-3 was positive correlated with Stroop interference (r=0.324,P＜0.01) in health controls.Correlation analysis showed that DNA methylation of CpG4-1 was negatively correlated with sustained attention function (r =-0.329,P＜0.01),cognitive flexibility (r =-0.337,P＜ 0.01) and visuospatial memory (r =-0.308,P＜ 0.05) in schizophrenia patients.There were positive correlations between DNA methylation of CpG4-5 (r=0.305,P＜0.05),CpG5-1 (r=0.262,P＜0.05),CpG5-3 (r=0.260,P＜0.05),average DNA methylation at exon 5 (r=0.288,P＜0.05) and visuospatial memory.DNA methylation of CpG5-4 was positive correlated with sustained attention function (r=0.251,P＜0.05) and visuospatial memory (r=0.350,P＜ 0.01) respectively.Conclusion Male patients with schizophrenia suffer from extensive cognitive impairment,and methylation of MMP-9 gene may be associated with cognitive impairment of schizophrenia.

Objective:To explore the role of macrophage polarization on pericyte-to-myofibroblast transition and renal allograft fibrosis after kidney transplantation(KT).Methods:Allograft tissues were harvestedfrom recipients with chronic allograft dysfunction(CGD)and normal kidney tissues.The expression and distribution of M1/M2 macrophages in kidney tissues were detected by routine and immunofluorescent staining; mRNA of CD68, CD206 and iNOS detected by polymerase chain reaction(PCR); Murine vascular pericytes subjected to TGF-β1 in vitro and the expressions of α-SMA and PDGFR-β in perivascular cells detected by immunoblotting and cellular fluorescence; The co-culturing models of vascular pericytes and M1/M2 macrophages were constructed.The expressions of α-SMA and PDGFR-β in pericytes were detected by immunoblotting, cellular fluorescence and PCR.Results:A marked infiltration of CD68+ iNOS+ M1 macrophages was present in allograft tissues of recipients with CGD while no obvious infiltration of CD68 + CD206 + was observed.The mRNA levels of CD68, iNOS and CD206 were significantly higher in CGD group than those in control group( P<0.05); In CGD allograft tissues, protein expressions of α-SMA and PDGFR-β spiked markedly( P<0.05)while cells with double staining of α-SMA and PDGFR-β were markedly infiltrated in interstitial area of CGD allograft.TGF-β1 could induce a marked elevation of PMT-related markers in a time-dependent manner( P<0.05); Immunoblotting and cellukar fluorescence indicated that M1 macrophages could promote the elevations of α-SMA and PDGFR-β in pericytes in vitro while M2 macrophages showed no effect on pericyte-to-myofibroblast transition in pericytes. Conclusions:M1 macrophage polarization may promote the formation of renal allograft interstitial fibrosis through promoting PMT.

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses