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irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway

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Regenerative Biomaterials 2024年第1期3卷 44-57页

作者： Xi Hua Mingzhuang Hou Lei Deng Nanning Lv Yong Xu Xuesong Zhu Huilin Yang Qin Shi Hao Liu Fan He Department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Orthopaedic Institute Suzhou Medical CollegeSoochow UniversitySuzhou 215000China Department of Orthopedics Suzhou Wuzhong People’s HospitalSuzhouJiangsu Province 215128China Department of Orthopedic Surgery Lianyungang Clinical College of Xuzhou Medical UniversityLianyungang 222003China

The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone *** challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture ***,the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of proosteogenic *** this study,a poly(L-lactic acid)(PLLA)/hyaluronic acid(HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning *** incorporation of irisin into the core-shell structure of PLLA/HA nanofibers(PLLA/HA@irisin)achieved its sustained *** vitro experiments demonstrated that the PLLA/HA@irisin membranes exhibited favorable *** osteogenic differentiation of bone marrow mesenchymal stem cells(BMMSCs)was improved by PLLA/HA@irisin,as evidenced by a significant increase in alkaline phosphatase activity and matrix ***,PLLA/HA@irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant *** assess the therapeutic effectiveness,PLLA/HA@irisin membranes were implanted in situ into critical-sized calvarial defects in *** results at 4 and 8 weeks post-surgery indicated that the implantation of PLLA/HA@irisin exhibited superior efficacy in promoting vascularized bone formation,as demonstrated by the enhancement of bone matrix synthesis and the development of new blood *** results of our study indicate that the electrospun PLLA/HA@irisin nanofibers possess characteristics of a biomimetic periosteum,showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs.

关键词： periosteum irisin mitochondrial function critical-sized bone defect redox homeostasis

Anti-Seizure and Neuronal Protective Effects of irisin in Kainic Acid-Induced Chronic Epilepsy Model with Spontaneous Seizures

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Neuroscience Bulletin 2022年第11期38卷 1347-1364页

作者： Jie Yu Yao Cheng Yaru Cui Yujie Zhai Wenshen Zhang Mengdi Zhang Wenyu Xin Jia Liang Xiaohong Pan Qiaoyun Wang Hongliu Sun School of Pharmaceutical Sciences Binzhou Medical UniversityYantai 264003China The Sixth Scientifc Research Department Shandong Institute of Nonmetallic MaterialsJinan 250031China

An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic *** reportedly attenuates the apoptosis and injury induced by oxidative ***,we evaluated the effects of exogenous irisin in a kainic acid(KA)-induced chronic spontaneous epilepsy rat *** results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury,learning and memory defects,and *** treatment also increased the levels of brain-derived neurotrophic factor(BDNF)and uncoupling protein 2(UCP2),which were initially reduced following KA ***,the specific inhibitor of UCP2(genipin)was administered to evaluate the possible protective mechanism of *** reduced apoptosis,neurodegeneration,and spontaneous seizures in rats treated with irisin were significantly reversed by genipin *** findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and ***,our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous *** protective effects of irisin may be mediated through the BDNF-mediated UCP2 *** results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.

关键词： Epilepsy Seizure irisin Genipin Neuronal injury

irisin attenuates intestinal injury,oxidative and endoplasmic reticulum stress in mice with L-arginine-induced acute pancreatitis

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World Journal of Gastroenterology 2019年第45期25卷 6653-6667页

作者： Yi-Fan Ren Meng-Zhou Wang Jian-Bin Bi Jia Zhang Lin Zhang Wu-Ming Liu Sha-Sha Wei Yi Lv Zheng Wu Rong-Qian Wu National Local Joint Engineering Research Center for Precision Surgery&Regenerative Medicine Shaanxi Provincial Center for Regenerative Medicine and Surgical EngineeringFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Hepatobiliary Surgery First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina

BACKGROUND Acute pancreatitis(AP)is often associated with intestinal injury,which in turn exaggerates the progression of *** recent study has shown that a low level of serum irisin,a novel exercise-induced hormone,is associated with poor outcomes in patients with AP and irisin administration protects against experimental ***,the role of irisin in intestinal injury in AP has not been *** To investigate the effect of irisin administration on intestinal injury in experimental *** AP was induced in male adult mice by two hourly intraperitoneal injections of *** 2 h after the last injection of L-arginine,irisin(50 or 250μg/kg body weight)or 1 mL normal saline(vehicle)was administered through intraperitoneal *** animals were sacrificed at 72 h after the induction of *** injury,apoptosis,oxidative and endoplasmic reticulum(ER)stress were *** Administration of irisin significantly mitigated intestinal damage,reduced apoptosis,and attenuated oxidative and ER stress in AP *** addition,irisin treatment also effectively downregulated serum tumor necrosis factor-alpha and interleukin-6 levels and alleviated injury in the pancreas,liver and lung of AP *** irisin-mediated multiple physiological events attenuate intestinal injury following an episode of *** has a great potential to be further developed as an effective treatment for patients with AP.

关键词： irisin Intestinal injury Oxidative stress Endoplasmic reticulum stress Acute pancreatitis Mouse model

irisin/BDNF signaling in the muscle-brain axis and circadian system: A review

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The Journal of Biomedical Research 2024年第1期38卷 1-16页

作者： Alexey N.Inyushkin Vitalii S.Poletaev Elena M.Inyushkina Igor S.Kalberdin Andrey A.Inyushkin Department of Human&Animal Physiology Samara National Research UniversitySamara 443011Russia.

In mammals,the timing of physiological,biochemical and behavioral processes over a 24-h period is controlled by circadian *** entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus to a precise 24-h rhythm,environmental zeitgebers are used by the circadian *** is done primarily by signals from the retina via the retinohypothalamic tract,but other cues like exercise,feeding,temperature,anxiety,and social events have also been shown to act as non-photic *** recently identified myokine irisin is proposed to serve as an entraining non-photic signal of *** is a product of cleavage and modification from its precursor membrane fibronectin typeⅢdomain-containing protein 5(FNDC5)in response to *** from well-known peripheral effects,such as inducing the"browning"of white adipocytes,irisin can penetrate the blood-brain barrier and display the effects on the *** data suggest that FNDC5/irisin mediates the positive effects of physical activity on brain *** several brain areas,irisin induces the production of brain-derived neurotrophic factor(BDNF).In the master clock,a significant role in gating photic stimuli in the retinohypothalamic synapse for BDNF is ***,the brain receptor for irisin remains *** the current review,the interactions of physical activity and the irisin/BDNF axis with the circadian system are reconceptualized.

关键词： irisin brain-derived neurotrophic factor peroxisome proliferator-activated receptorγcoactivator 1α circadian rhythm circadian system muscle-brain axis

Interaction between inflammatory bowel disease,physical activity,and myokines:Assessment of serum irisin levels

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World Journal of Gastroenterology 2024年第22期30卷 2923-2926页

作者： Marwan SM Al-Nimer Department of Therapeutics and Clinical Pharmacology College of MedicineUniversity of DiyalaBaqubah 32001Iraq

Inflammatory bowel disease(IBD),including Crohn’s disease and ulcerative colitis,showed a wide spectrum of intestinal and extra-intestinal manifestations,which rendered the patients physically inactive and impaired their quality of *** has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those *** is one member of the myokines secreted by muscle contraction during exercise and could be used as an antiinflammatory biomarker in assessing the physical activity of IBD *** addition,experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental ***,irisin produces changes in the diversity of the ***,endogenous or exogenous irisin,via its anti-inflammatory effects,will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.

关键词： irisin Inflammatory bowel disease Physical activity Myokines Prognostic marker

Relationship between circulating irisin levels and overweight/obesity: A meta-analysis

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World Journal of Clinical Cases 2019年第12期7卷 1444-1455页

作者： Jue Jia Fan Yu Wei-Ping Wei Ping Yang Ren Zhang Yue Sheng Yong-Qin Shi Affiliated Hospital of Jiangsu University Zhenjiang 212001 Jiangsu Province China Department of Library of Jiangsu University Zhenjiang 212001 Jiangsu Province China

BACKGROUND Currently, the findings about irisin as a novel myokine related to obesity are inconsistent in overweight/obese people. To our knowledge, no systematic analysis has been conducted to evaluate the relationship between irisin levels and overweight/obesity. AIM To evaluate the association between circulating irisin levels and overweight/obesity. METHODS The Cochrane Library, MEDLINE, SCOPUS, and the ISI Web of Science were searched to retrieve all of the studies associated with circulating irisin levels and overweight/obesity. Standard mean difference values and 95% confidence intervals (CI) were estimated and pooled using meta-analysis methodology. RESULTS A total of 18 studies were included in our meta-analysis containing 1005 cases and 1242 controls. Our analysis showed that the circulating irisin level in overweight/obese people was higher than that in overall healthy controls (random effects MD = 0.63;95%CI: 0.22-1.05;P = 0.003). In the subgroup analysis by ethnicity, the irisin level was higher in overweight/obesity people than that in controls in Africa (random effects MD = 3.41;95%CI: 1.23-5.59;P irisin level than controls (random effects MD = 0.86;95%CI: 0.28-1.43;P irisin is higher in obese individuals compared to healthy controls and it is important to identify the relationship between circulating irisin levels and overweight/obesity in predicting overweight/obesity.

关键词： irisin Overweight/obesity Myokines Body mass index

irisin Attenuates Osteoarthritis by Inhibiting Apoptosis of Osteocytes Through Activating Erk Signaling Pathway

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医用生物力学 2019年第A1期34卷 51-52页

作者： Zihao He Hanjun Li Feng Zhou Jingke Du Shuhong Zhang Tingting Tang Zhifeng Yu Department of Orthopedics Shanghai Key Laboratory of Orthopedic ImplantShanghai Ninth People’s HospitalShanghai Jiao Tong University School of Medicine

Osteoarthritis(OA)is an inflammatory disease involving the joints that is prevalent in the global aging *** purpose of this study is to determine whether irisin can attenuate osteoarthritis(OA)progression in anterior cruciate ligament transection(ACLT)mice models and the mechanism of irisin therapy effect on OA by increase the resistance of apoptosis in MLO-Y4 cells induced by mechanical stretch in *** For in vivo study,3-month-old male C57BL/6 J mice were randomized to three groups,sham-operated,anterior cruciate ligament transection(ACLT)-operated treated with vehicle,and ACLT-operated treated with irisin by intraperitoneal injection once a *** erosion was observed by HE *** Research Society International(OARSI)scores were evaluated according to the safranin O *** microstructure of tibia cortical bone,trabecular bone,and subchondral bone was analyzed by micro-CT and the bone histomorphometry has been administrated including mineral apposition rate(MAR).Edu staining and cck-8 were used for the detection of the proliferation of MLO-Y4 *** mechanical stress,cells were seeded on the collagen-I coated chamber subjected with a peak biaxial stretch of 20%at 1 Hz for 16 hours to induce *** cytometry was used for the detection of apoptosis and cell *** was used for staining the apoptotic cells and rt-PCR was applied for quantifying the expression of mRNA such as Bax,Bcl-2,SOST,c-myc,*** blot was utilized to confirm the mechanism of how irisin decrease the osteocyte *** In vivo,irisin can attenuate articular cartilage *** maintains the proportion of hyaline cartilage and calcified cartilage and keep fewer cartilage erosions in ACLT-operated *** immunohistochemical(IHC)staining,irisin reduced the expression of caspase3,Bax and matrix metalloproteinase-13 in both cartilage and subchondral ***-treated ACLT group shows higher Trabecular numb

关键词： irisin Attenuates Osteoarthritis Inhibiting Apoptosis Osteocytes Activating Erk Signaling Pathway

Serum irisin:Pathogenesis and Clinical Research in Cardiovascular Diseases

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Cardiovascular Innovations and Applications 2020年第1期4卷 195-200页

作者： Lutfu Askin Kader Eliz Uze Okan Tanriverdi Serdar Turkmen Department of Cardiology Adiyaman Education and Research HospitalAdiyamanTurkey

Recently,muscular function/dysfunction has gained importance in the maintenance of metabolic homeostasis in cardiovascular *** muscle plays a vital role in coordinating the activity and metabolism of endocrine organs by secreting many myokines,especially *** is a polypeptide hormone consisting of 112 amino acids secreted into the blood from muscle and adipose *** irisin levels are associated with cardiometabolic risk factors such as obesity and insulin resistance as defi ned by homeostatic model *** reduces endothelial damage by inhibiting infl ammation and oxidative stress,thus playing a key role in maintaining endothelial cell ***,low irisin levels cause endothelial dysfunction and increase the incidence of *** aimed to summarize the studies on this issue since we have not found any review in the literature on the role of serum irisin levels in the process of atherosclerosis and other cardiovascular events in cardiovascular diseases.

关键词： insulin resistance irisin cardiovascular diseases body mass index

irisin通过Sirt1/UCP2拮抗二氯化钴诱导的心肌损伤作用

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中国药理学通报 2023年第6期39卷 1061-1066页

作者：李如利黄韵晓韩彬刘福川北医学院川北医学院附属医院四川南充637000 川北医学院附属医院药剂科四川南充637000 川北医学院附属医院检验科四川南充637000

目的探讨肌肉因子irisin调节胞内保护蛋白Sirt1和线粒体解偶联蛋白2(uncoupling protein 2,UCP2)在心肌缺氧过程中发挥的作用及具体机制。方法以CoCl_(2)作用H9c2心肌细胞24 h,构建心肌细胞体外缺氧模型。实验分为6组:control组、irisin... 详细信息

目的探讨肌肉因子irisin调节胞内保护蛋白Sirt1和线粒体解偶联蛋白2(uncoupling protein 2,UCP2)在心肌缺氧过程中发挥的作用及具体机制。方法以CoCl_(2)作用H9c2心肌细胞24 h,构建心肌细胞体外缺氧模型。实验分为6组:control组、irisin 10 nmol·L^(-1)组、irisin 20 nmol·L^(-1)组、CoCl_(2)模型组、CoCl_(2)+irisin 10 nmol·L^(-1)治疗组、CoCl_(2)+irisin 20 nmol·L^(-1)治疗组。CCK-8法检测细胞存活率,Flow cytometry测定细胞凋亡和线粒体膜电位,探针法指示细胞内活性氧(reactive oxygen species,ROS)高低水平,Western blot法检测细胞内Sirt1、UCP2、Bcl-2、Bax、cleaved-caspase3的表达水平。结果心肌细胞H9c2缺氧模型组细胞活力下降、细胞凋亡增多、ROS增加、线粒体膜电位明显下降,同时抗凋亡蛋白Bcl-2、Sirt1和UCP2表达下调,凋亡相关蛋白Bax、cleaved-caspase3表达上调;与模型组相比,irisin预保护治疗组发挥保护作用呈浓度依赖性,表现为能明显抑制细胞凋亡,改善细胞活力,同时抑制ROS水平,恢复线粒体膜电位,上调保护性蛋白Sirt1、UCP2、Bcl-2的表达,下调介导凋亡的Bax、cleaved caspase-3的表达。结论irisin通过激活Sirt1/UCP2,进而抑制CoCl_(2)诱导的线粒体膜电位下降,改善氧化应激介导的心肌细胞凋亡。

关键词： irisin 氧化应激凋亡线粒体膜电位 Sirt1 UCP2