Regenerative Biomaterials
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2023
·
IF 6.7
Hua Xi,Hou Mingzhuang,Deng Lei,Lv Nanning,Xu Yong,Zhu Xuesong,Yang Huilin,Shi Qin,Liu Hao,He Fan
The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects. The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture site. However, the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of pro-osteogenic factors. In this study, a polylactic acid (PLLA)/hyaluronic acid (HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning technique. The incorporation of irisin into the core-shell structure of PLLA/HA nanofibers (PLLA/HA@Irisin) achieved its sustained release. In vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable biocompatibility. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was improved by PLLA/HA@Irisin, as evidenced by a significant increase in alkaline phosphatase (ALP) activity and matrix mineralization. Mechanistically, PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant pathway. To assess the therapeutic effectiveness, PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in rats. The results at four and eight 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 vessels. The 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.
研究领域:
组织工程
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再生医学
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生物材料科学
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DOI
PubMed
高影响因子
AQUACULTURE NUTRITION
·
2022
·
IF 3.781
Shaoyang Zhi,Liping Yang,Guokun Yang,Chaobin Qin,Xiao Yan,Mingming Niu,Wenlei Zhang,Mingyu Liu,Mengjuan Zhao,Guoxing Nie
Irisin plays a crucial role in the glucose metabolism of mammals and fish. However, the mechanism by which irisin regulates hepatic glucose metabolism is not entirely known. To clarify irisin’s function and underlying mechanisms in common carp glucose metabolism, the FNDC5 expression patterns were detected after insulin/glucagon injection, long-term high-glucose, and high-fat diet feeding. In vivo, the activity of PFK and the synthesis of liver glycogen were significantly increased, while the enzyme activity of PEPCK was reduced after intraperitoneal injection with irisin. In contrast, irisin siRNA attenuated the brain and liver FNDC5a and FNDC5b expression, and the serum glucose was increased. Glut2, gs, hk, and pfk were considerably downregulated in the brain and liver, while pygl, pepck, and g6pase were remarkably upregulated after siRNA treatment. In vitro, irisin activates the phosphorylation level of AMPK and PI3K/Akt in primary hepatocytes. Compound C and wortmannin inhibit AMPK and PI3K/Akt, reversing irisin-induced expression of g6pase, fbpase, pepck, gk, gs, pfk, hk, and gsk3b. At the same time, compound C attenuated irisin-induced expression of pi3k and akt. Our research reveals the mechanisms of irisinA and irisinB as glucose metabolism regulators in teleost for the first time.
研究领域:
分子生物学
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内分泌学
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代谢
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鱼类生理学
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DOI
高影响因子
Advanced Science
·
2024
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IF 14.3
Xia Zhang,Lijia Liang,Fengxian Wang,Pedro A. Jose,Ken Chen,Chunyu Zeng
Acute kidney injury (AKI) is the sudden decrease in renal function that can be attributed to dysregulated reactive oxygen species (ROS) production and impaired mitochondrial function. Irisin, a type I membrane protein secreted by skeletal muscles in response to physical activity, has been reported to alleviate kidney damage through regulation of mitochondrial biogenesis and oxidative metabolism. In this study, a macrophage membrane-coated metal-organic framework (MCM@MOF) is developed as a nanocarrier for encapsulating irisin to overcome the inherent characteristics of irisin, including a short circulation time, limited kidney-targeting ability, and low membrane permeability. The engineered irisin-mediated biomimetic nanotherapeutics have extended circulation time and enhanced targeting capability toward injured kidneys due to the preservation of macrophage membrane proteins. The irisin-encapsulated biomimetic nanotherapeutics effectively mitigate acute ischemia-reperfusion injury by protecting mitochondrial function and modulating SOD2 levels in renal tubular epithelial cells. The present study provides novel insights to advance the development of irisin as a potential therapeutic approach for AKI.
研究领域:
纳米技术
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药学
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肾脏生理学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Cellular Neuroscience
·
2021
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IF 5.505
Cheng Yao,Cui Yaru,Zhai Yujie,Xin Wenyu,Yu Yan,Liang Jia,Li Shucui,Sun Hongliu
Elevated reactive oxygen species (ROS) level is considered a crucial causative factor for neuronal damage in epilepsy. Irisin has been reported to ameliorate mitochondrial dysfunction and to reduce ROS levels; therefore, in this study, the effect of exogenous irisin on neuronal injury was evaluated in rats with kainic acid (KA)-induced status epilepticus (SE). Our results showed that exogenous irisin treatment significantly increased the expression of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), and reduced the levels of neuronal injury and mitochondrial oxidative stress. Additionally, an inhibitor of UCP2 (genipin) was administered to investigate the underlying mechanism of irisin-induced neuroprotection; in rats treated with genipin, the neuroprotective effects of irisin on KA-induced SE were found to be partially reversed. Our findings confirmed the neuroprotective effects of exogenous irisin and provide evidence that these effects may be mediated via the BDNF/UCP2 pathway, thus providing valuable insights that may aid the development of exogenous irisin treatment as a potential therapeutic strategy against neuronal injury in epilepsy.
研究领域:
神经科学
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药理学
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神经保护
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DOI
PubMed
高影响因子
Cardiovascular Diabetology
·
2024
·Vol. 23
·期 1
·1-19
·
IF 8.5
Tang Yuan-juan,Zhang Zhen,Yan Tong,Chen Ken,Xu Guo-fan,Xiong Shi-qiang,Wu Dai-qian,Chen Jie,Jose Pedro A.,Zeng Chun-yu,Fu Jin-juan
Background Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia–reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known. Methods and results T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose. Conclusion This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.
研究领域:
内分泌学
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心脏病学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
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IF 8.3
Chunyu Wang,Kunjing Liu,Jing Ji,Wenyuan Ma,Haojia Zhang,Kai Wang,Yukun Lin,Chongyang Ma,Xueqian Wang,Fafeng Cheng
Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is a major global chronic liver disorder, with metabolic dysfunction-associated steatohepatitis (MASH) representing its severe subtype. Liu-Jun-Zi Decoction (LJZD), a classical traditional Chinese medicine (TCM) formula, has shown clinical efficacy against MASH, however, its underlying mechanisms remain unclear. Purpose To investigate the molecular mechanism through which LJZD alleviates hepatic steatosis in MASH mice by restoring irisin secretion in skeletal muscle. Methods A MASH mouse model was established using a methionine and choline deficient (MCD) diet, followed by LJZD treatment. First, major chemical components of LJZD were identified via UHPLC-QE-MS. Subsequently, histopathological and biochemical analyses were performed to evaluate the effects of LJZD on MASH and skeletal muscle atrophy. Finally, the secretion of irisin in skeletal muscle was assessed, and bioinformatics analysis was used to screen downstream targets of irisin. Results LJZD significantly alleviated hepatic steatosis, injury, inflammation, and fibrosis in MASH mice while improving concomitant skeletal muscle atrophy. Furthermore, LJZD enhanced irisin secretion from skeletal muscle. Integrated transcriptomic analysis identified carboxylesterase 2A (CES2A) as a key hepatic downstream effector of irisin. Conclusion LJZD ameliorates MASH by promoting skeletal muscle irisin secretion, which upregulates hepatic CES2A to enhance lipid catabolism. In summary, current data extend the research scope on LJZD's pharmacological effects and suggest new approaches for clinical MASH treatment. LJZD alleviates hepatic steatosis by targeting skeletal muscle, indicating its potential as a therapeutic candidate for MASH.
研究领域:
中医药学
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药理学
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肝病学
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分子生物学
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代谢疾病
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生物信息学
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产品关联
DOI
PubMed
高影响因子
GENERAL AND COMPARATIVE ENDOCRINOLOGY
·
2020
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IF 2.428
Liping Yang,Shaoyang Zhi,Guokun Yang,Chaobin Qin,Wenli Zhao,Mingming Niu,Wenlei Zhang,Wenyu Tang,Xiao Yan,Yuru Zhang,Xiaolin Meng,Ronghua Lu,Guoxing Nie
Irisin, encoded by fibronectin type III domain-containing protein 5 (FNDC5) gene, plays a role in energy expenditure and insulin sensitivity in mice. In fish, the function of irisin related to glucose metabolism is less reported. It may increase glucose utilization in fish. The aim of the present study was to characterize the regulatory role of irisin in glucose metabolism in common carp ( Cyprinus carpio L.). In this study, FNDC5a and FNDC5b were isolated from common carp. The cDNA of FNDC5a and FNDC5b were 722 bp and 714 bp, encoding 221 and 207 amino acids, respectively. FNDC5a was abundantly expressed in the brain and gonad. FNDC5b was mainly expressed in brain. Different expression pattern of FNDC5a and FNDC5b under fasting/refeeding and OGTT experiment were identified. The recombinant common carp irisinA and irisinB were prepared by prokaryotic expression system. Glucose concentration was decreased in treatment with irisinA or irisinB in the in vitro and in vivo experiments. The mRNA expression levels of gluconeogenesis-related genes were significantly down-regulated, while the mRNA expression of glycolysis-related genes were significantly up-regulated after treatment with recombinant irisinA or irisinB in liver in vivo and in primary hepatocytes in vitro. Our research shows that irisin inhibits hepatic gluconeogenesis and promotes hepatic glycolysis. Taken together, this study for the first time revealed the two subtypes of FNDC5 and explored the function and mechanisms of irisinA and irisinB in fish glucose homeostasis.
研究领域:
分子生物学
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内分泌学
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水产养殖
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DOI
PubMed
高影响因子
Neuroscience Bulletin
·
2022
·Vol. 38
·期 11
·1347-1364
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IF 5.271
Yu Jie,Cheng Yao,Cui Yaru,Zhai Yujie,Zhang Wenshen,Zhang Mengdi,Xin Wenyu,Liang Jia,Pan Xiaohong,Wang Qiaoyun,Sun Hongliu
An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.
研究领域:
神经科学
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药理学
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分子生物学
·
癫痫研究
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Yan Chen,Zheng Xu,Yunmo Xue,Shanshan Liu,Xiang Zhang,Jingyao Guo,Minhui Yao,Yue Liu,Xiaolin Lu,Jieshu Qian,Qian Ma
Surgical removal of bacterial plaque and antibiotic therapy have been widely used for the clinical treatment of periodontitis, which is driven by microbial dysbiosis and usually causes the loss of alveolar bone. However, key restrictions including drug resistance, poor anti-inflammatory effects, and limited bone repair capacity exist in antibiotic therapy, presenting challenges for periodontitis treatment. Consequently, it is urgently required to develop novel systems to combat antimicrobial resistance and enhance bone regeneration ability. Here, a MOF-based multicomponent system is developed, containing a cationic antimicrobial peptide GF for antimicrobial purpose and the adipomyokine Irisin for anti-inflammation, antioxidation, and promoting bone regeneration. The obtained composite Irisin/GF@NH 2 -MIL-101(Fe) exhibits pH-responsive release of GF and irisin. In vitro and vivo experiments demonstrate this multicomponent system has robust antimicrobial activity and could attenuate inflammation while stimulating bone regeneration. Remarkably, the antimicrobial mechanism of GF is explored, revealing a distinct binding mode at the ribosomal A-site, which establishes more stable interactions than tetracycline, thereby disrupting protein synthesis and effectively reducing the risk of antibiotic resistance. This study not only reveals a novel antibacterial mechanism of antimicrobial peptide, but also provides a novel cascade therapy for the treatment of periodontitis with multiple functions.
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DOI
PubMed
高影响因子
Diabetology & Metabolic Syndrome
·
2023
·Vol. 15
·期 1
·1-13
·
IF 4.8
Li Tianrong,Yang Jingjing,Tan Anjun,Chen Hewen
Background Irisin plays a key role in metabolic diseases, including type 2 diabetes mellitus (T2DM). However, the mechanism underlying the link between irisin and the development of T2DM, particularly in pancreatic islet β-cells, remains unknown.Methods In vitro, Min6 cells were treated with high glucose (HG) to generate T2DM cell models. GSDMD-N staining, Western blotting assays, and ELISA were performed to measure the expression levels of GSDMD, caspase 1, IL-1β, and IL-18. Next, the NLRP3 stimulator, ATP, was used to assess the effect of irisin on NLRP3 inflammasome. To evaluate the function of the Nrf2-TrX/TXNIP signaling axis, the Nrf2 inhibitor ML385 was used. For in vivo assessment, we first established T2DM model mice. Then, hematoxylin and eosin (H&E) staining was performed to observe the islet morphology, and the immunofluorescence technique was used to examine the mass of α and β cells. To confirm the role of the Nrf2-TrX/TXNIP signaling axis, ML385 was injected into the mice. Immunofluorescence of Nrf2, caspase 1, and GSDMD was detected in the islet cells of the model mice to verify the results.Results We found that irisin treatment significantly decreased the expression of GSDMD-N (P31) and cleaved caspase-1 (p20), decreased caspase1 activity, and inhibited the secretion of IL-1β and IL-18 in HG-treated Min6 cells. We also found that irisin inhibited oxidative stress and NLRP3 expression by activating the Nrf2-TrX/TXNIP signaling axis. Additionally, in the T2DM model mice, irisin enhanced the function of islet cells, decreased insulin resistance, and preserved the morphology of pancreatic islets.Conclusion We showed in this study that irisin can be used for treating pyroptosis in HG-induced islet β-cells and T2DM model mice. We also found that irisin inhibits pyroptosis and oxidative stress by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis.
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高影响因子
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