CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
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2021
·Vol. 99
·期 12
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IF 2.273
Dongdong Zhang,Dongxu Qi,Yi Xu,Chunhe Hu,Xiao Zhang,Qingjian Yang,Zikun Shang,Guisheng Zhang
Skin flap transfer is an important method to repair and reconstruct various tissue defects; however, avascular necrosis largely affects the success of flap transfer. The sphingosine 1-phosphate receptor 1 (S1PR1) agonist SEW2871 has been proven to ameliorate ischemic injury; however, its effect on flap survival has not been reported. In this study, an experimental skin flap model was established in rats to investigate the roles of SEW2871. The results indicated that SEW2871 greatly increased the survival of the skin flap, alleviated pathological injury, promoted the angiogenesis, and inhibited cells apoptosis in skin flap tissues. SEW2871 activated S1PR1 downstream signaling pathways, including heat shock protein 27 (HSP27), extracellular regulated protein kinases (ERK), and protein kinase B (Akt). In addition, SEW2871 promoted the expression of S1PR1. These findings may provide novel insights for skin flap transfer.
研究领域:
药理学
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外科手术
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分子生物学
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DOI
PubMed
高影响因子
Applied Materials Today
·
2020
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IF 8.352
Ye He,Kun Xu,Ke Li,Zhang Yuan,Yao Ding,Maowen Chen,Chuanchuan Lin,Bailong Tao,Xuemin Li,Guanjun Zhang,Peng Liu,Kaiyong Cai
The main task for medical-used titanium researches is to improve the in vivo osteointegration. In addition to mesenchymal stromal cells (MSCs)-osteoblasts lineage, macrophages also undertake irreplaceable roles in the osteointegration process of a titanium implant. The timely recruitment and efficient immunomodulation of macrophages is important. In this work, to firstly endow macrophages recruitment ability and immunomodulation effects to titanium, we fabricated a micro-structured titanium via a double acid etching method. Then a gelatin-chitosan multilayer contained SEW2871 (a macrophage recruitment agent) was constructed on the micro-structured titanium by a layer-by-layer (LBL) self-assembly technique. According to our results, the prepared samples effectively induced macrophages migration when SEW2871 was slowly released . The anti-inflammatory response of macrophages was enhanced and the pro-inflammatory response was alleviated, which were attributed to the changed surface roughness and wettability. This immunomodulation effects of macrophages further improved the osteogenic differentiation of MSCs in vitro and obtained a better osteointegration in vivo after 6 weeks of implantation. Therefore, this study demonstrated that a favorable osteointegration of titanium materials could also be achieved by regulating macrophages recruitment and immunomodulation, which implying a potential strategy for titanium implants amelioration.
研究领域:
生物材料
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组织工程
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免疫学
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骨科
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产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Tingting Yang,Lin Li,Jiale Pang,Cai Heng,Chujing Wei,Xue Wang,Ziyin Xia,Xin Huang,Luyong Zhang,Zhenzhou Jiang
Bile acid (BA) homeostasis throughout the enterohepatic circulation system is a guarantee of liver physiological functions. BA circulation disorders is one of the characteristic clinical manifestations of cholestasis, and have a closely relationship with intestinal barrier function, especially ileum. Here, our in vivo and in vitro studies showed that intestinal tight junctions (TJs) were disrupted by α-naphthylisothiocyanate (ANIT), which also down-regulated the protein expression of sphingosine-1-phosphate receptor 1 (S1PR1) in the top of villus of mice ileum. Activating S1PR1 by specific agonist SEW2871 could improve TJs via inhibiting ERK1/2/LKB1/AMPK signaling pathway in the ileum of ANIT-treated mice and ANIT-cultured Caco-2 cells. SEW2871 not only regained ileum TJs by activating S1PR1 in the epithelial cells of ileum mucosa, but also recovered ileum barrier function, which was further verified by the recovered BA homeostasis in mice ileum (content and tissue) by using of high-performance liquid chromatographytandem mass spectrometry (LC-MS/MS). Subsequently, the improved intestinal injury and inflammation further strengthened that SEW2871 modulated intestinal barrier function in ANIT-treated mice. Finally, our data revealed that along with the down-regulated levels of serum lipopolysaccharides (LPS), SEW2871 improved liver function and relieved hepatitis via blocking TLR4/MyD88/NF-kB signaling pathway in ANIT-treated mice. In conclusion, these results demonstrated that activating intestinal S1PR1 by SEW2871 could modulate intestinal barrier function, leading to the improvement of cholestatic hepatitis in ANIT-treated mice via the “gut-liver” axis.
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产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
·
2022
·Vol. 18
·期 8
·1763
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IF 6.058
Yang Li-Xiang,Yao Yuan-Yuan,Yang Jiu-Rong,Cheng Hui-Lin,Zhu Xin-Jian,Zhang Zhi-Jun
Destruction of the blood-brain barrier is a critical component of epilepsy pathology. Several studies have demonstrated that sphingosine 1-phosphate receptor 1 contributes to the modulation of vascular integrity. However, its effect on blood-brain barrier permeability in epileptic mice remains unclear. In this study, we prepared pilocarpine -induced status epilepticus models and pentylenetetrazol -induced epilepsy models in C57BL/6 mice. S1P1 expression was increased in the hippocampus after status epilepticus, whereas tight junction protein expression was decreased in epileptic mice compared with controls. Intraperitoneal injection of SEW2871, a specific agonist of sphingosine-1-phosphate receptor 1, decreased the level of tight junction protein in the hippocampus of epileptic mice, increased blood-brain barrier leakage, and aggravated the severity of seizures compared with the control. W146, a specific antagonist of sphingosine-1-phosphate receptor 1, increased the level of tight junction protein, attenuated blood-brain barrier disruption, and reduced seizure severity compared with the control. Furthermore, sphingosine 1-phosphate receptor 1 promoted the generation of interleukin-1β and tumor necrosis factor-α and caused astrocytosis. Disruption of tight junction protein and blood-brain barrier integrity by sphingosine 1-phosphate receptor 1 was reversed by minocycline, a neuroinflammation inhibitor. Behavioral tests revealed that sphingosine 1-phosphate receptor 1 exacerbated epilepsy -associated depression-like behaviors. Additionally, specific knockdown of astrocytic S1P1 inhibited neuroinflammatory responses and attenuated blood-brain barrier leakage, seizure severity, and epilepsy -associated depression-like behaviors. Taken together, our results suggest that astrocytic sphingosine 1-phosphate receptor 1 exacerbates blood-brain barrier disruption in the epileptic brain by promoting neuroinflammation .
研究领域:
神经科学
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药理学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
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