Effect of nuclear factor kappa B on intercellular adhesion molecule-1 expression and neutrophil infiltration in lung injury induced by intestinal ischemia/reperfusion in rats

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.

CD30-Positive Anaplastic Large Cell Lymphoma with Abundant Neutrophils (Report of a Case)

ObjectiveTo report a rare case of ALCL (Anaplastic Large Cell Lymphoma) with abundant neutrophils and necrosis and to analyse the histomorphologic subtypes and immunohistologic characteristics of ALCL. MethodsA biopsy of a painless tumor on a 26 year old male′s neck was taken for morphologic and immunohistochemical analyse. ResultsJudging from the morphologic feature of ALCL,the prognosis of the patient is good. ConclusionIt is necessary to do immunohistochemical staining in diagnosing an ALCL since p80 NPM/ALK or ALK is the best antibody to distinguish ALCL from other lymphomas.

Pretreatment with Danhong injection protects the brain against ischemia-reperfusion injury

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.

Effects of IL-17 on Expression of GRO-α and IL-8 in Fibroblasts from Nasal Polyps

Recent studies indicated that interleukin（IL）-17, growth-related oncogene（GRO）-α and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the production of GRO-α and IL-8 in human nasal polyp fibroblasts are not completely understood. This study aimed to determine the effects of the increased IL-17 on the changes of GRO-α and IL-8 expression in human nasal polyp fibroblasts and further investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp fibroblasts were isolated from six cases of human nasal polyps, and the cells were stimulated with five different concentrations of IL-17. Real-time fluorescence quantitative polymerase chain reaction（RT-PCR） was used to detect the mRNA expression of GRO-α and IL-8. The mRNA of GRO-α and IL-8 was expressed in unstimulated controls and remarkably increased by stimulation with IL-17. Moreover, the levels of GRO-α and IL-8 produced by fibroblasts were increased gradually with the increases in IL-17 concentrations. The present study showed that nasal fibroblasts can produce GRO-α and IL-8, and their production is remarkably enhanced by IL-17 stimulation, thereby clarifying the mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These findings might provide a rationale for using IL-17 inhibitors as a treatment for nasal inflammatory diseases such as nasal polyps.

Pretreatment with Tongxinluo protects porcine myocardium from ischaemia/reperfusion injury through a nitric oxide related mechanism

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.

Enhanced tumor homing of pathogen-mimicking liposomes driven by R848 stimulation: A new platform for synergistic oncology therapy

Although multifarious tumor-targeting modifications of nanoparticulate systems have been attempted in joint efforts by our predecessors,it remains challenging for nanomedicine to traverse physiological barriers involving blood vessels,tissues,and cell barriers to thereafter demonstrate excellent antitumor effects.To further overcome these inherent obstacles,we designed and prepared mycoplasma membrane(MM)-fused liposomes(LPs)with the goal of employing circulating neutrophils with the advantage of inflammatory cytokine-guided autonomous tumor localization to transport nanoparticles.We also utilized in vivo neutrophil activation induced by the liposomal form of the immune activator resiquimod(LPsR848).Fused LPs preparations retained mycoplasma pathogen characteristics and achieved rapid recognition and endocytosis by activated neutrophils stimulated by LPs-R848.The enhanced neutrophil infiltration in homing of the inflammatory tumor microenvironment allowed more nanoparticles to be delivered into solid tumors.Facilitated by the formation of neutrophil extracellular traps(NETs),podophyllotoxin(POD)-loaded MM-fused LPs(MM-LPs-POD)were concomitantly released from neutrophils and subsequently engulfed by tumor cells during inflammation.MM-LPs-POD displayed superior suppression efficacy of tumor growth and lung metastasis in a 4T1 breast tumor model.Overall,such a strategy of pathogen-mimicking nanoparticles hijacking neutrophils in situ combined with enhanced neutrophil infiltration indeed elevates the potential of chemotherapeutics for tumor targeting therapy.