Inflammation is a major cause of neuronal injury after spinal cord injury. We hypothesized that inhibiting caspase-1 activation may reduce neuroinflammation after spinal cord injury, thus producing a protective effect...Inflammation is a major cause of neuronal injury after spinal cord injury. We hypothesized that inhibiting caspase-1 activation may reduce neuroinflammation after spinal cord injury, thus producing a protective effect in the injured spinal cord. A mouse model of T9 contusive spinal cord injury was established using an Infinite Horizon Impactor, and VX-765, a selective inhibitor of caspase-1, was administered for 7 successive days after spinal cord injury. The results showed that:(1) VX-765 inhibited spinal cord injury-induced caspase-1 activation and interleukin-1β and interleukin-18 secretion.(2) After spinal cord injury, an increase in M1 cells mainly came from local microglia rather than infiltrating macrophages.(3) Pro-inflammatory Th1 Th17 cells were predominant in the Th subsets. VX-765 suppressed total macrophage infiltration, M1 macrophages/microglia, Th1 and Th1 Th17 subset differentiation, and cytotoxic T cells activation;increased M2 microglia;and promoted Th2 and Treg differentiation.(4) VX-765 reduced the fibrotic area, promoted white matter myelination, alleviated motor neuron injury, and improved functional recovery. These findings suggest that VX-765 can reduce neuroinflammation and improve nerve function recovery after spinal cord injury by inhibiting caspase-1/interleukin-1β/interleukin-18. This may be a potential strategy for treating spinal cord injury. This study was approved by the Animal Care Ethics Committee of Bengbu Medical College(approval No. 2017-037) on February 23, 2017.展开更多
AIM： To determine whether Carbon （CO） liberated from CO-releasing molecules attenuates leukocyte infiltration in the small intestine of thermally injured mice. METHODS： Thirty-six mice were assigned to four groups...AIM： To determine whether Carbon （CO） liberated from CO-releasing molecules attenuates leukocyte infiltration in the small intestine of thermally injured mice. METHODS： Thirty-six mice were assigned to four groups. Mice in the sham group （n = 9） were underwent to sham thermal injury; mice in the burn group （n = 9） received 15% total body surface area full-thickness thermal injury; mice in the burn ＋ CORM-2 group （n = 9） were underwent to the same thermal injury with immediate administration of tricarbonyldichlororut henium （11） dimer CORM-2 （8 mg/kg, i.v.）; and mice in the burn＋DMSO group （n = 9） were underwent to the same thermal injury with immediate administration of 160 IJL bolus injection of 0.5% DMSO/saline. Histological alterations and granulocyte infiltration of the small intestine were assessed. Polymorphonuclear neutrophil （PMN） accumulation （myeloperoxidase assay） was assessed in mice mid-ileum. Activation of nuclear factor （NF）-KB, expression levels of intercellular adhesion molecule-1 （ICAM-1） and inducible heme oxygenase in mid-ileum were assessed. RESULTS： Treatment of thermally injured mice with CORM-2 attenuated PMN accumulation and prevented activation of NF-kB in the small intestine. This was accompanied by a decrease in the expression of ICAM-1. In parallel, burn-induced granulocyte infiltration in mid- ileum was markedly decreased in the burn mice treated with CORM-2. CONCLUSION： CORM-released CO attenuates leukocyteinfiltration in the small intestine of thermally injured mice by interfering with NF-KB activation and protein expression of ICAM-1, and therefore suppressing the pro-adhesive phenotype of endothelial cells.展开更多
Spontaneous term labour is associated with amplified inflammatory events in the myometrium including cytokine production and leukocyte infiltration; however, potential mechanisms regulating such events are not fully u...Spontaneous term labour is associated with amplified inflammatory events in the myometrium including cytokine production and leukocyte infiltration; however, potential mechanisms regulating such events are not fully understood. We hypothesized that mechanical stretch of the uterine wall by the growing fetus facilitates peripheral leukocyte extravasation into the term myometrium through the release of various cytokines by uterine myocytes. Human myometrial cells （hTERT-HM） were subjected to static mechanical stretch; stretch-conditioned media was collected and analysed using 48-plex Luminex assay and ELISA. Effect of stretch-conditioned media on cell adhesion molecule expression of human uterine microvascular endothelial cells （UtMVEC-Myo） was detected by quantitative polymerase chain reaction （qPCR） and flow cytometry; functional assays testing leukocyte-endothelial interactions： adhesion of leukocytes to endothelial cells and transendothelial migration of calcein-labelled primary human neutrophils as well as migration of THP-1 monocytic cells were assessed by fluorometry. The current in vitrostudy demonstrated that mechanical stretch （i） directly induces secretion of multiple cytokines and chemokines by hTERT-HM cells （IL-6, CXCL8, CXCL1, migration inhibitory factor （MIF）, VEGF, G-CSF, IL-12p70, bFGF and platelet-derived growth factor subunit B （PDGF-bb）, P〈0.05）; stretch-induced cytokines （ii） enhance leukocyte adhesion to the endothelium of the surrounding uterine microvasculature by （iii） inducing the expression of endothelial cell adhesion molecules and （iv） directing the transendothelial migration of peripheral leukocytes. （vi） Chemokine-neutralizing antibodies and broad-spectrum chemokine inhibitor block leukocyte migration. Our data provide a proof of mechanical regulation for leukocyte recruitment from the uterine blood vessels to the myometrium, suggesting a putative mechanism for the leukocyte infiltrate into the uterus during labour and postpartum involu展开更多
目的探讨外周血白细胞(WBC)、C反应蛋白(CRP)及胎盘白细胞检测与妊娠期高血压疾病的相关性。方法选择我院产科于2016年5月至2019年5月收治的50例妊娠期高血压孕妇作为观察组,另匹配选择我科同期收治规律产检的50例正常孕妇作为对照组。...目的探讨外周血白细胞(WBC)、C反应蛋白(CRP)及胎盘白细胞检测与妊娠期高血压疾病的相关性。方法选择我院产科于2016年5月至2019年5月收治的50例妊娠期高血压孕妇作为观察组,另匹配选择我科同期收治规律产检的50例正常孕妇作为对照组。比较两组外周血WBC、CRP和胎盘白细胞浸润情况,采用Spearman分析法对各指标与妊娠期高血压相关性进行分析。采用二元Logistic回归对妊娠期妇女发生高血压的危险因素进行多因素分析。结果观察组孕产妇外周血WBC(7.70±1.63 vs 5.71±2.02)、CRP(5.52±1.93 vs 2.90±1.32)水平及存在胎盘白细胞浸润比例(40.0%vs 82.0%)显著高于对照组,差异具有统计学意义(P<0.05)。Spearman分析发现,外周血WBC、CRP水平及胎盘白细胞浸润与妊娠期高血压的发生呈正相关(P<0.01),相关系数分别为0.813、0.864和0.761。二元Logistic回归分析表明,外周血WBC(OR=2.118,95%CI:1.370~3.273)、CRP(OR=2.616,95%CI:1.663~4.114)水平及胎盘白细胞浸润(OR=5.079,95%CI:1.419~18.176)是妊娠期高血压发生的独立危险因素。结论外周血WBC、CRP和胎盘白细胞浸润与妊娠期高血压的发生显著相关,全身炎症反应很可能是导致妊娠期妇女发生高血压的重要因素。展开更多
基金supported by the National Natural Science Foundation of China,Nos.81772321,82072416(both to HZL)。
文摘Inflammation is a major cause of neuronal injury after spinal cord injury. We hypothesized that inhibiting caspase-1 activation may reduce neuroinflammation after spinal cord injury, thus producing a protective effect in the injured spinal cord. A mouse model of T9 contusive spinal cord injury was established using an Infinite Horizon Impactor, and VX-765, a selective inhibitor of caspase-1, was administered for 7 successive days after spinal cord injury. The results showed that:(1) VX-765 inhibited spinal cord injury-induced caspase-1 activation and interleukin-1β and interleukin-18 secretion.(2) After spinal cord injury, an increase in M1 cells mainly came from local microglia rather than infiltrating macrophages.(3) Pro-inflammatory Th1 Th17 cells were predominant in the Th subsets. VX-765 suppressed total macrophage infiltration, M1 macrophages/microglia, Th1 and Th1 Th17 subset differentiation, and cytotoxic T cells activation;increased M2 microglia;and promoted Th2 and Treg differentiation.(4) VX-765 reduced the fibrotic area, promoted white matter myelination, alleviated motor neuron injury, and improved functional recovery. These findings suggest that VX-765 can reduce neuroinflammation and improve nerve function recovery after spinal cord injury by inhibiting caspase-1/interleukin-1β/interleukin-18. This may be a potential strategy for treating spinal cord injury. This study was approved by the Animal Care Ethics Committee of Bengbu Medical College(approval No. 2017-037) on February 23, 2017.
文摘AIM： To determine whether Carbon （CO） liberated from CO-releasing molecules attenuates leukocyte infiltration in the small intestine of thermally injured mice. METHODS： Thirty-six mice were assigned to four groups. Mice in the sham group （n = 9） were underwent to sham thermal injury; mice in the burn group （n = 9） received 15% total body surface area full-thickness thermal injury; mice in the burn ＋ CORM-2 group （n = 9） were underwent to the same thermal injury with immediate administration of tricarbonyldichlororut henium （11） dimer CORM-2 （8 mg/kg, i.v.）; and mice in the burn＋DMSO group （n = 9） were underwent to the same thermal injury with immediate administration of 160 IJL bolus injection of 0.5% DMSO/saline. Histological alterations and granulocyte infiltration of the small intestine were assessed. Polymorphonuclear neutrophil （PMN） accumulation （myeloperoxidase assay） was assessed in mice mid-ileum. Activation of nuclear factor （NF）-KB, expression levels of intercellular adhesion molecule-1 （ICAM-1） and inducible heme oxygenase in mid-ileum were assessed. RESULTS： Treatment of thermally injured mice with CORM-2 attenuated PMN accumulation and prevented activation of NF-kB in the small intestine. This was accompanied by a decrease in the expression of ICAM-1. In parallel, burn-induced granulocyte infiltration in mid- ileum was markedly decreased in the burn mice treated with CORM-2. CONCLUSION： CORM-released CO attenuates leukocyteinfiltration in the small intestine of thermally injured mice by interfering with NF-KB activation and protein expression of ICAM-1, and therefore suppressing the pro-adhesive phenotype of endothelial cells.
文摘Spontaneous term labour is associated with amplified inflammatory events in the myometrium including cytokine production and leukocyte infiltration; however, potential mechanisms regulating such events are not fully understood. We hypothesized that mechanical stretch of the uterine wall by the growing fetus facilitates peripheral leukocyte extravasation into the term myometrium through the release of various cytokines by uterine myocytes. Human myometrial cells （hTERT-HM） were subjected to static mechanical stretch; stretch-conditioned media was collected and analysed using 48-plex Luminex assay and ELISA. Effect of stretch-conditioned media on cell adhesion molecule expression of human uterine microvascular endothelial cells （UtMVEC-Myo） was detected by quantitative polymerase chain reaction （qPCR） and flow cytometry; functional assays testing leukocyte-endothelial interactions： adhesion of leukocytes to endothelial cells and transendothelial migration of calcein-labelled primary human neutrophils as well as migration of THP-1 monocytic cells were assessed by fluorometry. The current in vitrostudy demonstrated that mechanical stretch （i） directly induces secretion of multiple cytokines and chemokines by hTERT-HM cells （IL-6, CXCL8, CXCL1, migration inhibitory factor （MIF）, VEGF, G-CSF, IL-12p70, bFGF and platelet-derived growth factor subunit B （PDGF-bb）, P〈0.05）; stretch-induced cytokines （ii） enhance leukocyte adhesion to the endothelium of the surrounding uterine microvasculature by （iii） inducing the expression of endothelial cell adhesion molecules and （iv） directing the transendothelial migration of peripheral leukocytes. （vi） Chemokine-neutralizing antibodies and broad-spectrum chemokine inhibitor block leukocyte migration. Our data provide a proof of mechanical regulation for leukocyte recruitment from the uterine blood vessels to the myometrium, suggesting a putative mechanism for the leukocyte infiltrate into the uterus during labour and postpartum involu
文摘目的探讨外周血白细胞(WBC)、C反应蛋白(CRP)及胎盘白细胞检测与妊娠期高血压疾病的相关性。方法选择我院产科于2016年5月至2019年5月收治的50例妊娠期高血压孕妇作为观察组,另匹配选择我科同期收治规律产检的50例正常孕妇作为对照组。比较两组外周血WBC、CRP和胎盘白细胞浸润情况,采用Spearman分析法对各指标与妊娠期高血压相关性进行分析。采用二元Logistic回归对妊娠期妇女发生高血压的危险因素进行多因素分析。结果观察组孕产妇外周血WBC(7.70±1.63 vs 5.71±2.02)、CRP(5.52±1.93 vs 2.90±1.32)水平及存在胎盘白细胞浸润比例(40.0%vs 82.0%)显著高于对照组,差异具有统计学意义(P<0.05)。Spearman分析发现,外周血WBC、CRP水平及胎盘白细胞浸润与妊娠期高血压的发生呈正相关(P<0.01),相关系数分别为0.813、0.864和0.761。二元Logistic回归分析表明,外周血WBC(OR=2.118,95%CI:1.370~3.273)、CRP(OR=2.616,95%CI:1.663~4.114)水平及胎盘白细胞浸润(OR=5.079,95%CI:1.419~18.176)是妊娠期高血压发生的独立危险因素。结论外周血WBC、CRP和胎盘白细胞浸润与妊娠期高血压的发生显著相关,全身炎症反应很可能是导致妊娠期妇女发生高血压的重要因素。
