Background:Periodontitis disease(PD)is associated with a systemic disorder of inflammatory bowel disease(IBD).The immune response is the common feature of the two conditions,but the more precise mechanisms remain uncl...Background:Periodontitis disease(PD)is associated with a systemic disorder of inflammatory bowel disease(IBD).The immune response is the common feature of the two conditions,but the more precise mechanisms remain unclear.Methods:Differential expressed genes(DEGs)analysis and weighted gene co-expression network analysis(WGCNA)were performed on PD and Crohn’s disease(CD)data sets to identify crosstalk genes linking the two diseases.The proportions of infiltrating immune cells were calculated by using Single-sample Gene Set Enrichment Analysis.In addition,a data set of isolated neutrophils from the circulation was performed via WGCNA to obtain PD-related key modules.Then,single-cell gene set enrichment scores were computed for the key module and grouped neutrophils according to score order in the IBD scRNA-seq data set.Single-cell gene enrichment analysis was used to further explore the biological process of the neutrophils.Results:A total of 13 crosstalk genes(IL1B,CSF3,CXCL1,CXCL6,FPR1,FCGR3B,SELE,MMP7,PROK2,SRGN,FCN1,TDO2 and CYP24A1)were identified via DEGs analysis and WGCNA by combining PD and CD data sets.The enrichment analysis showed that these genes were involved in interleukin-10 signaling and inflammatory response.The immune infiltration analysis showed a significant difference in the proportion of neutrophils in PD and CD compared with healthy patients.Neutrophils were scored based on the expression of a periodontitis-related gene set in the scRNA-seq data set of IBD.The enrichment analysis demonstrated that inflammatory response,TNFa signaling via NF-jB and interferon-gamma response were upregulated in the high-score group,which expressed more pro-inflammatory cytokines and chemokines compared with the low-score group.Conclusions:This study reveals a previously unrecognized mechanism linking periodontitis and IBD through crosstalk genes and neutrophils,which provides a theoretical framework for future research.展开更多
AIM： To investigate the role of nuclear factor kappa B （NF-κB） in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion （I/R）, and its effect on intercellular adhesion molecule-1 （ICAM-1） ...AIM： To investigate the role of nuclear factor kappa B （NF-κB） in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion （I/R）, and its effect on intercellular adhesion molecule-1 （ICAM-1） expression and neutrophil infiltration. METHODS： Twenty-four Wistar rats were divided randomly into control, I/R and pyrrolidine dithiocarbamate （PDTC） treatment groups, n = 8 in each. I/R group and PDTC treatment group received superior mysenteric artery （SMA） occluding for 1 h and reperfusion for 2 h. PDTC group was administrated with intraperitoneal injection of 2% 100 mg/kg PDTC 1 h before surgery. Lung histology and bronchia alveolus lung fluid （BALF） protein were assayed. Serum IL-6, lung malondialdehyde （MDA） and myeloperoxidase （MPO） as well as the expression level of NF-κB and ICAM-1 were measured.RESULTS： Lung injury induced by intestinal I/R, was characterized by edema, hemorrhage and neutrophil infiltration as well as by the significant rising of BALF protein. Compared to control group, the levels of serum IL-6 and lung MDA and MPO increased significantly in I/R group （P=0.001）. Strong positive expression of NF-κB p65 and ICAM-1 was observed. After the administration of PDTC, the level of serum IL-6, lung MDA and MPO as well as NF-κB and ICAM-1 decreased significantly （P〈 0.05） when compared to I/R group.CONCLUSION： The activation of NF-κB plays an important role in the pathogenesis of lung injury induced by intestinal I/R through upregulating the neutrophil infiltration and lung ICAM-1 expression. PDTC as an inhibitor of NF-κB can prevent lung injury induced by intestinal I/R through inhibiting the activity of NF-κB.展开更多
Background The traditional Chinese medicine injury, but the mechanism of its action is not we protective role of Tongxinluo. Tongxinluo can protect myocardium against documented. We examined the involvement schaemia/r...Background The traditional Chinese medicine injury, but the mechanism of its action is not we protective role of Tongxinluo. Tongxinluo can protect myocardium against documented. We examined the involvement schaemia/reperfusion of nitric oxide in the Methods Miniswine were randomized to four groups of seven： sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N^ωnitro-L-arginine （L-NNA, 10 mg/kg i.v.）. Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively. Results Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA. Conclusions Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.展开更多
Danhong injection （DHI）, a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is widely used in China for treating acute isch-emic stroke. In the pres...Danhong injection （DHI）, a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is widely used in China for treating acute isch-emic stroke. In the present study, we explored the neuroprotective efficacy of DHI in a rat model of temporary middle cerebral artery ocdusion, and evaluated the potential mechanisms under-lying its effects. Pretreatment with DHI （0.9 and 1.8 mL/kg） resulted in a significantly smaller infarct volume and better neurological scores than pretreatment with saline. Furthermore, DHI significantly reduced the permeability of the blood-brain barrier, increased occludin protein expression and decreased neutrophil infiltration, as well as profoundly suppressing the upreg-ulation of matrix metallopeptidase-9 expression seen in rats that had received vehicle. Matrix metallopeptidase-2 expression was not affected by ischemia or DHI. Moreover, DHI （1.8 mL/kg） administered 3 hours after the onset of ischemia also improved neurological scores and reduced infarct size. Our results indicate that the neuroprotective efficacy of DHI in a rat model of cerebral ischemia-reperfusion injury is mediated by a protective effect on the blood-brain barrier and the reversal of neutrophil infiltration.展开更多
基金supported by the National Natural Science Foundation of China[grant numbers 82070752 and 82170939]Guangdong Natural Science Foundation[grant number 2023A1515010519].
文摘Background:Periodontitis disease(PD)is associated with a systemic disorder of inflammatory bowel disease(IBD).The immune response is the common feature of the two conditions,but the more precise mechanisms remain unclear.Methods:Differential expressed genes(DEGs)analysis and weighted gene co-expression network analysis(WGCNA)were performed on PD and Crohn’s disease(CD)data sets to identify crosstalk genes linking the two diseases.The proportions of infiltrating immune cells were calculated by using Single-sample Gene Set Enrichment Analysis.In addition,a data set of isolated neutrophils from the circulation was performed via WGCNA to obtain PD-related key modules.Then,single-cell gene set enrichment scores were computed for the key module and grouped neutrophils according to score order in the IBD scRNA-seq data set.Single-cell gene enrichment analysis was used to further explore the biological process of the neutrophils.Results:A total of 13 crosstalk genes(IL1B,CSF3,CXCL1,CXCL6,FPR1,FCGR3B,SELE,MMP7,PROK2,SRGN,FCN1,TDO2 and CYP24A1)were identified via DEGs analysis and WGCNA by combining PD and CD data sets.The enrichment analysis showed that these genes were involved in interleukin-10 signaling and inflammatory response.The immune infiltration analysis showed a significant difference in the proportion of neutrophils in PD and CD compared with healthy patients.Neutrophils were scored based on the expression of a periodontitis-related gene set in the scRNA-seq data set of IBD.The enrichment analysis demonstrated that inflammatory response,TNFa signaling via NF-jB and interferon-gamma response were upregulated in the high-score group,which expressed more pro-inflammatory cytokines and chemokines compared with the low-score group.Conclusions:This study reveals a previously unrecognized mechanism linking periodontitis and IBD through crosstalk genes and neutrophils,which provides a theoretical framework for future research.
基金Supported by The Natural Science Foundation of Liaoning Province,No.20042135
文摘AIM： To investigate the role of nuclear factor kappa B （NF-κB） in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion （I/R）, and its effect on intercellular adhesion molecule-1 （ICAM-1） expression and neutrophil infiltration. METHODS： Twenty-four Wistar rats were divided randomly into control, I/R and pyrrolidine dithiocarbamate （PDTC） treatment groups, n = 8 in each. I/R group and PDTC treatment group received superior mysenteric artery （SMA） occluding for 1 h and reperfusion for 2 h. PDTC group was administrated with intraperitoneal injection of 2% 100 mg/kg PDTC 1 h before surgery. Lung histology and bronchia alveolus lung fluid （BALF） protein were assayed. Serum IL-6, lung malondialdehyde （MDA） and myeloperoxidase （MPO） as well as the expression level of NF-κB and ICAM-1 were measured.RESULTS： Lung injury induced by intestinal I/R, was characterized by edema, hemorrhage and neutrophil infiltration as well as by the significant rising of BALF protein. Compared to control group, the levels of serum IL-6 and lung MDA and MPO increased significantly in I/R group （P=0.001）. Strong positive expression of NF-κB p65 and ICAM-1 was observed. After the administration of PDTC, the level of serum IL-6, lung MDA and MPO as well as NF-κB and ICAM-1 decreased significantly （P〈 0.05） when compared to I/R group.CONCLUSION： The activation of NF-κB plays an important role in the pathogenesis of lung injury induced by intestinal I/R through upregulating the neutrophil infiltration and lung ICAM-1 expression. PDTC as an inhibitor of NF-κB can prevent lung injury induced by intestinal I/R through inhibiting the activity of NF-κB.
文摘Background The traditional Chinese medicine injury, but the mechanism of its action is not we protective role of Tongxinluo. Tongxinluo can protect myocardium against documented. We examined the involvement schaemia/reperfusion of nitric oxide in the Methods Miniswine were randomized to four groups of seven： sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N^ωnitro-L-arginine （L-NNA, 10 mg/kg i.v.）. Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively. Results Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA. Conclusions Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.
基金supported by the National Natural Science Foundation of China,No.81173592National Science and Technology Major Project of the Ministry of Science and Technology of China,No.2011ZX09201-201,2012ZX09101201-004,2012ZX09101202,NCET-130935,2013ZX09201020+1 种基金Tianjin Municipal Applied Basic Research and Cutting-Edge Technology Research Scheme of China,No.14JCYBJC28900Program for Innovation Team Training in Universities in Tianjin,No.TD12-5035
文摘Danhong injection （DHI）, a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is widely used in China for treating acute isch-emic stroke. In the present study, we explored the neuroprotective efficacy of DHI in a rat model of temporary middle cerebral artery ocdusion, and evaluated the potential mechanisms under-lying its effects. Pretreatment with DHI （0.9 and 1.8 mL/kg） resulted in a significantly smaller infarct volume and better neurological scores than pretreatment with saline. Furthermore, DHI significantly reduced the permeability of the blood-brain barrier, increased occludin protein expression and decreased neutrophil infiltration, as well as profoundly suppressing the upreg-ulation of matrix metallopeptidase-9 expression seen in rats that had received vehicle. Matrix metallopeptidase-2 expression was not affected by ischemia or DHI. Moreover, DHI （1.8 mL/kg） administered 3 hours after the onset of ischemia also improved neurological scores and reduced infarct size. Our results indicate that the neuroprotective efficacy of DHI in a rat model of cerebral ischemia-reperfusion injury is mediated by a protective effect on the blood-brain barrier and the reversal of neutrophil infiltration.
