The temporal expression of microRNA after spinal cord ischemia/reperfusion injury is not yet fully understood. In the present study, we established a model of spinal cord ischemia in Sprague-Dawley rats by clamping th...The temporal expression of microRNA after spinal cord ischemia/reperfusion injury is not yet fully understood. In the present study, we established a model of spinal cord ischemia in Sprague-Dawley rats by clamping the abdominal aorta for 90 minutes, before allowing reperfusion for 24 or 48 hours. A sham-operated group underwent surgery but the aorta was not clamped. The damaged spinal cord was removed for hematoxylin-eosin staining and RNA extraction. Neuronal degeneration and tissue edema were the most severe in the 24- hour reperfusion group, and milder in the 48-hour reperfusion group. RNA amplification, labeling, and hybridization were used to obtain the microRNA expression profiles of each group. Bioinformatics analysis confirmed tour differentially expressed microRNAs （miR-22-3p, miR-743b-3p, miR-201-5p and miR-144-5p） and their common target genes （Tmem69 and Cxcll0）. Compared with the sham group, miR- 22-3p was continuously upregulated in all three ischemia groups but was highest in the group with 11o reperfusion, whereas miR-743b-3p, miR-201-5p and miR-144-5p were downregulated in the three ischemia groups. We have successfully identified the key genes expressed at different stages of spinal cord ischemia/reperfusion injury, which provide a reference for future investigations into the mechanism of spinal cord injury.展开更多
AIM: To study KRAS/BRAF mutations in colorectal-cancer (CRC) that influences the efficacy of treatment. To develop strategies for overcoming combination of treatment.
Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis （ACD）. CXCR3 in the spinal cord also con- tribut...Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis （ACD）. CXCR3 in the spinal cord also con- tributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3-/- mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund＇s adjuvant-induced chronic inflammatory pain were reduced in Cxcr3-/- mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water （AEW）. Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Further- more, touch-elicited itch （alloknesis） after compound 48/80 or AEW treatment was suppressed in Cxcr3-/- mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3-/- mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.展开更多
OBJECTIVE:To investigate the effect of salvianolic acid A and C component molecules,which are involved in drug compatibility,on inflammatory cytokine expression that affects human chemokine ligand 5(CCL5) and chemokin...OBJECTIVE:To investigate the effect of salvianolic acid A and C component molecules,which are involved in drug compatibility,on inflammatory cytokine expression that affects human chemokine ligand 5(CCL5) and chemokine ligand 10(CXCL10)levels in rats with unilateral ureteral obstruction(UUO).METHODS:Fifty Sprague Dawley rats were randomly divided into five groups:normal,model,salvianolic acid A,salvianolic acid C and salvianolic acid A and C groups.The normal group was used as the control,and the other groups of rats had a UUO model established.The control group had free access to food and water,and the other groups received the corresponding drugs for 2 weeks.After the last administration,urine β_2-microglobulin(β_2-MG) and N-acetyl-β-D-glucosaminidase(NAG) levels were analyzed.After 24 h,all rats were sacrificed and the serum was analyzed for creatinine(Cr) and blood urea nitrogen(BUN) levels.Rat kidneys were removed,and CCL5 and CXCL10 inflammatory cytokine mRNA expression was measured using real-time fluorescent quantitative reverse transcription-polymerase chain reaction(RT-PCR).Kidney fibrosis was observed using hematoxylin-eosin(HE)staining and Masson trichrome staining.RESULTS:In the salvianolic acid A and salvianolic acid C treatment groups,serum Cr and urine NAG levels were significantly lower than in the model group(both P < 0.05).In all treatment groups,urine pYMG levels were significantly lower than in the model group(all P < 0.05).Compared with model group,the pathological changes and collagen deposition improved to varying degrees(both P <0.05).CCL5 and CXCL10 mRNA expression decreased to different degrees compared with the model group(both P < 0.05).CONCLUSION:Salvianolic acid A and C are component molecules of drug compatibility,and they may protect renal function and improve tubular function and renal pathology to a certain degree in UUO.This improvement may be related to a reduction in inflammatory cytokines CCL5 and CXCL10 secretion in the UUO rat kidney.展开更多
基金supported by a Grant from the National Natural Science Foundation of China,No.81350013,31572217,and 81672263
文摘The temporal expression of microRNA after spinal cord ischemia/reperfusion injury is not yet fully understood. In the present study, we established a model of spinal cord ischemia in Sprague-Dawley rats by clamping the abdominal aorta for 90 minutes, before allowing reperfusion for 24 or 48 hours. A sham-operated group underwent surgery but the aorta was not clamped. The damaged spinal cord was removed for hematoxylin-eosin staining and RNA extraction. Neuronal degeneration and tissue edema were the most severe in the 24- hour reperfusion group, and milder in the 48-hour reperfusion group. RNA amplification, labeling, and hybridization were used to obtain the microRNA expression profiles of each group. Bioinformatics analysis confirmed tour differentially expressed microRNAs （miR-22-3p, miR-743b-3p, miR-201-5p and miR-144-5p） and their common target genes （Tmem69 and Cxcll0）. Compared with the sham group, miR- 22-3p was continuously upregulated in all three ischemia groups but was highest in the group with 11o reperfusion, whereas miR-743b-3p, miR-201-5p and miR-144-5p were downregulated in the three ischemia groups. We have successfully identified the key genes expressed at different stages of spinal cord ischemia/reperfusion injury, which provide a reference for future investigations into the mechanism of spinal cord injury.
基金Supported by The German Research Foundation and the Open Access Publication Funds of the Gttingen University
文摘AIM: To study KRAS/BRAF mutations in colorectal-cancer (CRC) that influences the efficacy of treatment. To develop strategies for overcoming combination of treatment.
基金supported by Grants from the National Natural Science Foundation of China(31371121,81300954,and 31671091)the Priority Academic Program Development of Jiangsu Higher Education Institutions,China
文摘Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis （ACD）. CXCR3 in the spinal cord also con- tributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3-/- mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund＇s adjuvant-induced chronic inflammatory pain were reduced in Cxcr3-/- mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water （AEW）. Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Further- more, touch-elicited itch （alloknesis） after compound 48/80 or AEW treatment was suppressed in Cxcr3-/- mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3-/- mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.
基金Supported by the National Natural Science Foundation of China(Intervention Effect of Compatibility of Salvianolic Acid A,B,C on PDGF-C/PDGFR-A Signaling Pathway in Renal Fibrosis,No.81260603)
文摘OBJECTIVE:To investigate the effect of salvianolic acid A and C component molecules,which are involved in drug compatibility,on inflammatory cytokine expression that affects human chemokine ligand 5(CCL5) and chemokine ligand 10(CXCL10)levels in rats with unilateral ureteral obstruction(UUO).METHODS:Fifty Sprague Dawley rats were randomly divided into five groups:normal,model,salvianolic acid A,salvianolic acid C and salvianolic acid A and C groups.The normal group was used as the control,and the other groups of rats had a UUO model established.The control group had free access to food and water,and the other groups received the corresponding drugs for 2 weeks.After the last administration,urine β_2-microglobulin(β_2-MG) and N-acetyl-β-D-glucosaminidase(NAG) levels were analyzed.After 24 h,all rats were sacrificed and the serum was analyzed for creatinine(Cr) and blood urea nitrogen(BUN) levels.Rat kidneys were removed,and CCL5 and CXCL10 inflammatory cytokine mRNA expression was measured using real-time fluorescent quantitative reverse transcription-polymerase chain reaction(RT-PCR).Kidney fibrosis was observed using hematoxylin-eosin(HE)staining and Masson trichrome staining.RESULTS:In the salvianolic acid A and salvianolic acid C treatment groups,serum Cr and urine NAG levels were significantly lower than in the model group(both P < 0.05).In all treatment groups,urine pYMG levels were significantly lower than in the model group(all P < 0.05).Compared with model group,the pathological changes and collagen deposition improved to varying degrees(both P <0.05).CCL5 and CXCL10 mRNA expression decreased to different degrees compared with the model group(both P < 0.05).CONCLUSION:Salvianolic acid A and C are component molecules of drug compatibility,and they may protect renal function and improve tubular function and renal pathology to a certain degree in UUO.This improvement may be related to a reduction in inflammatory cytokines CCL5 and CXCL10 secretion in the UUO rat kidney.
