Nicaraven Attenuates Postoperative Systemic Inflammatory Responses-Induced Tumor Metastasis

Zhang, Xu; Moriwaki, Toshikazu; Kawabata, Tsuyoshi; Goto, Shinji; Liu, Ke-Xiang; Guo, Chang‐Ying; Li, Tao‐Sheng

doi:10.1245/s10434-019-08076-2

Cited by 17 publications

(11 citation statements)

References 19 publications

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“…In this study, we found that the recruitment of monocytes/immune cells, including the M2 macrophages was significantly increased in the irradiated lungs. Consistent with previous reports [ 22 , 34 ], the administration of nicaraven inhibited significantly the recruitment of monocytes into the irradiated lungs. It will be better to understand the precise role of especial subpopulation of inflammatory cells, such as the M2 macrophages in lungs using genetically modified animals.…”

Section: Discussionsupporting

confidence: 92%

Nicaraven mitigates radiation-induced lung injury by downregulating the NF-κB and TGF-β/Smad pathways to suppress the inflammatory response

Zhai

Goto

et al. 2022

Journal of Radiation Research

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Radiation-induced lung injury (RILI) is commonly observed in patients receiving radiotherapy, and clinical prevention and treatment remain difficult. We investigated the effect and mechanism of nicaraven for mitigating RILI. C57BL/6 N mice (12-week-old) were treated daily with 6 Gy X-ray thoracic radiation for 5 days in sequences (cumulative dose of 30 Gy), and nicaraven (50 mg/kg) or placebo was injected intraperitoneally in 10 min after each radiation exposure. Mice were sacrificed and lung tissues were collected for experimental assessments at the next day (acute phase) or 100 days (chronic phase) after the last radiation exposure. Of the acute phase, immunohistochemical analysis of lung tissues showed that radiation significantly induced DNA damage of the lung cells, increased the number of Sca-1+ stem cells, and induced the recruitment of CD11c+, F4/80+ and CD206+ inflammatory cells. However, all these changes in the irradiated lungs were effectively mitigated by nicaraven administration. Western blot analysis showed that nicaraven administration effectively attenuated the radiation-induced upregulation of NF-κB, TGF-β, and pSmad2 in lungs. Of the chronic phase, nicaraven administration effectively attenuated the radiation-induced enhancement of α-SMA expression and collagen deposition in lungs. In conclusion we find that nicaraven can effectively mitigate RILI by downregulating NF-κB and TGF-β/pSmad2 pathways to suppress the inflammatory response in the irradiated lungs.

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Section: Discussionsupporting

confidence: 92%

Nicaraven mitigates radiation-induced lung injury by downregulating the NF-κB and TGF-β/Smad pathways to suppress the inflammatory response

Zhai

Goto

et al. 2022

Journal of Radiation Research

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“…In pathological conditions, the small intestine performs functions that influence all systems of the body (29). Previous studies have demonstrated that intestinal I/R injury is a universal pathophysiological process that occurs in patients suffering from shock, severe trauma and undergoing resuscitation, all of which cause a series of pathophysiological changes to occur in intestinal tissues (30,31). Intestinal I/R injury can also cause secondary damage to distant organs, in addition to intestinal tissue damage (32).…”

Section: Discussionmentioning

confidence: 99%

Remote ischemic post‑conditioning alleviates ischemia/reperfusion‑induced intestinal injury via the ERK signaling pathway‑mediated RAGE/HMGB axis

et al. 2021

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Intestinal ischemia reperfusion (I/R) injury is a tissue and organ injury that frequently occurs during surgery and significantly contributes to the pathological processes of severe infection, injury, shock, cardiopulmonary insufficiency and other diseases. However, the mechanism of intestinal I/R injury remains to be elucidated. A mouse model of intestinal I/R injury was successfully established and the model mice were treated with remote ischemic post-conditioning (RIPOC) and/or an ERK inhibitor (CC-90003), respectively. Histopathological changes of the intestinal mucosa were determined by hematoxylin and eosin staining. In addition, the levels of high-mobility group box 1 (HMGB1) and receptor for advanced glycation end products (RAGE) expression were confirmed by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry assays. The levels of antioxidants, oxidative stress markers (8-OHdG) and interleukin 1 family members were evaluated by ELISA assays and the levels of NF-κB pathway proteins were analyzed by western blotting. The data demonstrated that RIPOC could attenuate the histopathological features of intestinal mucosa in the intestinal I/R-injury mouse models via the ERK pathway. It was also revealed that HMGB1 and RAGE expression in the mouse models could be markedly reduced by RIPOC (P<0.05) and that these reductions were associated with inhibition of the ERK pathway. Furthermore, it was demonstrated that RIPOC produced significant antioxidant and anti-inflammatory effects following an intestinal I/R injury and that these effects were mediated via the ERK pathway (P<0.05). In addition, RIPOC was demonstrated to suppress the NF-κB (p65)/NLR family pyrin domain containing 3 (NLRP3) inflammatory pathways in the intestinal I/R injury mouse models via the ERK pathway. The findings of the present study demonstrated that RIPOC helped to protect mice with an intestinal I/R injury by downregulating the ERK pathway.

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“…To evaluate the overall changes in the levels of systemic cytokines/chemokines, we mixed the six plasma samples (50 µl collected from each mouse at 24 h after oxygen exposure for 60 min) and used 200 µl of the mixture for analysis. The average levels of cytokines/chemokines in plasma were compared with those in the control group using mouse cytokine Proteome Profiler TM array (ARY006, R&D Systems) per manufacturer's instructions (Zhang et al, 2020). Briefly, the membranes were blocked and then treated with plasma mixture/antibody cocktails overnight at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Prolonged oxygen exposure causes the mobilization and functional damage of stem or progenitor cells and exacerbates cardiac ischemia or reperfusion injury in healthy mice

Luo

Zhang

et al. 2021

Journal Cellular Physiology

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Oxygen is often administered to patients and occasionally to healthy individuals as well; however, the cellular toxicity of oxygen, especially following prolonged exposure, is widely known. To evaluate the potential effect of oxygen exposure on circulating stem/progenitor cells and cardiac ischemia/reperfusion (I/R) injury, we exposed healthy adult mice to 100% oxygen for 20 or 60 min. We then examined the c-kit-positive stem/progenitor cells and colony-forming cells and measured the cytokine/chemokine levels in peripheral blood. We also induced cardiac I/R injury in mice at 3 h after 60 min of oxygen exposure and examined the recruitment of inflammatory cells and the fibrotic area in the heart. The proportion of c-kit-positive stem/progenitor cells significantly increased in peripheral blood at 3 and 24 h after oxygen exposure for either 20 or 60 min (p < .01 vs. control). However, the abundance of colony-forming cells in peripheral blood conversely decreased at 3 and 24 h after oxygen exposure for only 60 min (p < .05 vs. control). Oxygen exposure for either 20 or 60 min resulted in significantly decreased plasma vascular endothelial growth factor levels at 3 h, whereas oxygen exposure for only 60 min reduced plasma insulin-like growth factor 1 levels at 24 h (p < .05 vs. control).Protein array indicated the increase in the levels of some cytokines/chemokines, such as CXCL6 (GCP-2) at 24 h after 60 min of oxygen exposure. Moreover, oxygen exposure for 60 min enhanced the recruitment of Ly6g-and CD11c-positive inflammatory cells at 3 days (p < .05 vs. control) and increased the fibrotic area at 14 days in the heart after I/R injury (p < .05 vs. control). Prolonged oxygen exposure induced the mobilization and functional impairment of stem/progenitor cells and likely enhanced inflammatory responses to exacerbate cardiac I/R injury in healthy mice.

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Nicaraven Attenuates Postoperative Systemic Inflammatory Responses-Induced Tumor Metastasis

Cited by 17 publications

References 19 publications

Nicaraven mitigates radiation-induced lung injury by downregulating the NF-κB and TGF-β/Smad pathways to suppress the inflammatory response

Nicaraven mitigates radiation-induced lung injury by downregulating the NF-κB and TGF-β/Smad pathways to suppress the inflammatory response

Remote ischemic post‑conditioning alleviates ischemia/reperfusion‑induced intestinal injury via the ERK signaling pathway‑mediated RAGE/HMGB axis

Prolonged oxygen exposure causes the mobilization and functional damage of stem or progenitor cells and exacerbates cardiac ischemia or reperfusion injury in healthy mice

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