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BACKGROUND: Long non coding RNA (lncRNA) and microRNA (miRNA) are two types of small non-coding RNA that are involved in regulating cell proliferation, apoptosis and migration and other life activities, and lncRNA can also be used as a competitive endogenous RNA and miRNA target binding to regulate the expression of miRNA target genes and play an important role in the occurrence and development of tumors. LINC02532 is an lncRNA that can target miR-129- 5p and miR-490-5p to promote the proliferation, migration and invasion of gastric cancer cells, but its effect on the biological behavior of pancreatic cancer stem cells and the action mechanism are still unknown. OBJECTIVE: To investigate the effect and action mechanism of LINC02532 on the proliferation, migration, invasion and apoptosis of pancreatic cancer stem cells. METHODS: (1) Fifty-six patients with pancreatic cancer confirmed by pathological examination in North China University of Science and Technology Affiliated Hospital from January 2017 to June 2018 were selected as the research subjects. Real time fluorescent quantitative PCR was used to detect the expression levels of LINC02532 and miR-145 in pancreatic cancer tissues and adjacent tissues. (2) Using CD24+CD44+ESA+ as surface markers, pancreatic cancer stem cells were sorted from human pancreatic cancer cells PANC-1 by flow cytometry. Pancreatic cancer stem cells were divided into normal group, si-LINC02532 group (transfected with LINC02532 small interfering RNA), si-NC group (transfected with disorderly negative sequence), si-LINC02532+anti-miR-145 group (co-transfected with LINC02532 small interfering RNA and miR-145 inhibitor) and si-LINC02532+anti-miR-NC group (co-transfected with LINC02532 small interfering RNA and miR-145 inhibitor negative control sequence). At 12 hours after transfection, real time fluorescent quantitative PCR was used to detect the expression levels of LINC02532 and miR-145 in each group of cells. Cell counting kit-8 (CCK-8) assay was utilized to detect the cell survival rate. The colony formation test was applied to detect the number of cell clones formed. Transwell chamber was used to detect cell migration and invasion. Flow cytometry was utilized to detect cell apoptosis rate. Western blot assay was used to detect the expression levels of P21, Bax, Caspase-3, E-cadherin and MMP-2 protein. The double luciferase reporter gene experiment was utilized to verify the regulatory relationship between miR-145 and LINC02532. RESULTS AND CONCLUSION: (1) Compared with adjacent tissues, the expression level of LINC02532 increased in pancreatic cancer tissues (P < 0.05), while the expression level of miR-145 decreased (P < 0.05). (2) Compared with the si-NC group, the survival rate, colony formation, cell migration and invasion number, and MMP-2 protein expression level of pancreatic cancer stem cells reduced in the si-LINC02532 group (P < 0.05), while the apoptotic rate and the expression levels of P21 and Bax, Caspase-3 and E-cadherin protein increased (P < 0.05), but there was no significant difference between the si-NC group and the normal group (P > 0.05). (3) LINC02532 targeted negatively regulated miR-145 expression in pancreatic cancer stem cells. Compared with the si-LINC02532+antimiR- NC group, the survival rate, colony formation, cell migration and invasion number, and MMP-2 protein expression level of pancreatic cancer stem cells increased in the si-LINC02532+anti-miR-145 group (P < 0.05), while the apoptotic rate and the expression levels of P21 and Bax, Caspase-3 and E-cadherin protein reduced (P < 0.05). (4) The results show that LINC02532 was up-regulated in pancreatic cancer tissues, and down-regulating its expression may inhibit the proliferation, migration and invasion of pancreatic cancer stem cells by targeting up-regulation of miR-145 expression, and induce apoptosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that Bushen Huoxue Decoction has a very active role in treating osteonecrosis of the femoral head (ONFH), but the chemical ingredients contained in the compound are more complicated. The action mechanism and pharmacological mechanism of the compound underlying the treatment of ONFH at the molecular level are not yet clear. Therefore, network pharmacology and protein module analyses are used to explain the potential active ingredients and molecular mechanism of Bushen Huoxue Decoction, and provide a certain theoretical basis for the later development of new drugs and better clinical application in the treatment of ONFH. OBJECTIVE: Through network pharmacology and protein module analysis to explore the molecular targets and mechanisms of Bushen Huoxue Decoction in the treatment of ONFH. METHODS: The compounds and their targets in Carthamus tinctorius, Angelica sinensis, Cistanche deserticola, Cornus officinalis, Chinese wolfberry, dodder, Radix Rehmanniae, Eucommia ulmoides, myrrh, Fructus psoraleae and Fructus psoraleae in Bushen Huoxue Decoction were searched by TCMSP and TCMID databases, and the related targets of ONFH were predicted by GeneCards and CTD databases. The drug-meridian-compound-target network was constructed by Cytoscape3.7.2, the protein-protein interaction network was constructed and analyzed by STRING database, and the key protein modules were analyzed by Metascape database. Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out by using DAVID database. RESULTS AND CONCLUSION: A total of 167 active components and 151 action targets of Bushen Huoxue Decoction were screened, with peroxisome proliferator-activated receptor, vascular endothelial growth factor A, tumor necrosis factor and epidermal growth factor receptor as key targets. There were 8 817 related targets of ONFH, 128 proteins in the protein-protein interaction core network, and 5 protein modules. A total of 289 GO biological processes were obtained, and 110 related signal pathways were obtained by enrichment and screening of KEGG pathway, including estrogen, phosphoinositide-3 kinase/ protein kinase, cyclic adenosine phosphate, Wnt signaling, tumor necrosis factor and mitogen-activated protein kinase. These pathways were associated with the occurrence and development of ONFH. The results show that Bushen Huoxue Decoction may treat ONFH by regulating cell metabolism, proliferation and apoptosis, lipid metabolism and promoting angiogenesis, which is the result of the interaction of multi-components, multi-targets and multi-pathways. [ABSTRACT FROM AUTHOR]

BACKGROUND: Most studies have shown that MAPK, nuclear factor κB, and Wnt signaling pathways are the major signaling pathways associated with osteoarthritis. OBJECTIVE: To review the related literature at home and abroad, and to summarize the mechanism of inflammatory cytokines and related signaling pathways in osteoarthritis, in order to further understand the pathogenesis of osteoarthritis. METHODS: CNKI, WanFang, VIP, MEDLINE, and PubMed databases were searched for relevant articles addressing inflammatory cytokines and related signaling pathways in osteoarthritis using the keywords of “osteoarthritis, inflammatory cytokine, signal path, pathogenesis, interleukin, BMP, treatment ” in Chinese and English, respectively. After reading the titles and abstracts, 55 articles were included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION: Up to now, the mechanism of osteoarthritis is not clear. Previous studies have shown that inflammation and inflammatory cytokines play an important role in the occurrence and development of osteoarthritis. Strengthening the research on inflammatory cytokines may improve the therapeutic potential of osteoarthritis. Among these cytokines, interleukin-1β is considered to be the main inducer of osteoarthritis, which plays a key role in cartilage degradation and bone regeneration. Therefore, inhibiting the expression of interleukin-1β and inflammatory mediators induced by interleukin-1β may provide a promising method for the treatment of osteoarthritis. The development of osteoarthritis may involve the correlation and interaction between many cytokines and different signaling pathways, but the relationship between inflammatory cytokines and signaling pathways has not yet been clearly clarified, and the mechanism of changes between their molecules is still unclear. A full understanding of these signaling pathways will help us to find a more reliable treatment for osteoarthritis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that Huangqi Guizhi Wuwu Decoction can reduce cartilage damage, promote cartilage repair, and delay the disease development by inhibiting angiogenesis, but its mechanism of action is not yet clear. OBJECTIVE: To investigate the molecular mechanism of Huangqi Guizhi Wuwu Decoction in the treatment of osteoarthritis based on network pharmacology and molecular docking technology. METHODS: The active ingredients of Huangqi Guizhi Wuwu Decoction were screened by TCMSP database and corresponding targets were collected. The potential targets for treating osteoarthritis were obtained by OMIM, GeneCards, and TTD databases, and the intersected targets of Huangqi Guizhi Wuwu Decoction for treating osteoarthritis were obtained. The STRING database was used to construct the single drug-active ingredient-acting target network, followed by protein-protein interaction network analysis using Cytoscape software. David database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking of active ingredients and key targets was finally performed using PyMOL software. RESULTS AND CONCLUSION: Sixty-three compounds of Huangqi Guizhi Wuwu Decoction and 217 related targets were screened, and 130 targets were obtained after the intersection, mainly involving AGE−RAGE signaling pathway, MAPK signaling pathway, nuclear factor-κB signaling pathway, tumor necrosis factor signaling pathway, and interleukin-17 signaling pathway. Treatment of osteoarthritis might be achieved by the response to lipopolysaccharide, molecules of bacterial origin, nutrient level, and oxidative stress. ESR1, PRKDC, HSPA8, EP300 and HSP90AA1 were the hub targets in the protein-protein interaction network. A total of five key active ingredients were docked with five key targets. To conclude, Huangqi Guizhi Wuwu Decoction plays a role in the treatment of osteoarthritis through multi-component, multi-target and multi-channel regulations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that injury and scar of the Achilles tendon in rats with terminal disease are difficult to heal, and the early treatment of Achilles tendon micro-injury caused by exhaustive exercise can avoid the accumulation of injury and prevent the occurrence of terminal disease. Therefore, it is necessary to explore the mechanism of Achilles tendon micro-injury caused by acute exhaustive exercise. OBJECTIVE: Through the comparison of the changes of ultra-structure, transforming growth factor-β1 (TGF-β1), Collagen-I, Collagen-III, matrix metalloproteinases-1 (MMP-1) and tissue inhibitors of metalloproteinase-1 (TIMP-1) mRNA and protein expression in the Achilles tendon before and after exhaustive exercise, to discuss the mechanism of Achilles tendon micro-injury caused by acute exhaustive exercise in rats. METHODS: Wistar rats were randomly divided into a control group and an exhaustive exercise group. No intervention was performed in the control group. In the exhaustive exercise group, rats were subjected to treadmill running. After exhaustive exercise, the two groups of rats were immediately killed under anesthesia. Through the observation using hematoxylin-eosin staining and transmission electronic microscopy, Achilles tendons were measured by reverse transcription-polymerase chain reaction and double antibody sandwich ABC-ELISA to show the genetic expression and protein expression of TGF-β1, Collagen-I, III, MMP-1 and TIMP-1. RESULTS AND CONCLUSION: Compared with the control group, the acute exhaustive exercise group showed the disordered arrangement of collagen fibers in Achilles tendon and the partially damaged structure of tendon cells. The mRNA and protein expressions of TGF-β1, MMP-1 and TIMP-1 were significantly higher in the exhaustive exercise group than the control group (P < 0.05), whereas the mRNA and protein expressions of Collagen-I and Collagen-III were significantly decreased (P < 0.05). These findings indicate that the over-expression of TGF-β1 results from the gradual accumulation of Achilles tendon micro-injuries caused by acute exhaustive exercise. Collagen synthesis decreases while the degradation accelerates; the tendon function is impaired as the micro-injuries continue. There is a similar variation tendency of MMP-1 and TIPM-1, which reminds an irreversible damage do not occur. Micro-injuries of the Achilles tendon caused by acute exhaustive exercise should be treated and repaired in time, avoiding excessive damage and scar repair. [ABSTRACT FROM AUTHOR]

BACKGROUND: Islet cell transplantation is one of the most effective methods to treat diabetes. However, the shortage of transplanted cells has limited its clinical application. Direct reprogramming of hepatocytes to islet β cells in vitro is a new idea to solve this problem, but differentiation of hepatocytes to islet β cells is a complicated process. OBJECTIVE: Direct reprogramming hepatocytes into islet-like cells by efficient targeting and activating the endogenous genes of hepatocytes with Casilio system (constructed CRISPR/Cas9-Pumilio system) through modifying guide RNA sequence combined with the transcriptional activator PUFa-P65-HSF1. METHODS: The endogenous PNM (Pdx1, Ngn3, MafA) genes of hepatocytes were targeted and activated by using the Casilio system, which was transfected to the HEK293T cell line by liposome transfection. The expression of endogenous PNM was detected by real-time fluorescence quantitative PCR and immunofluorescence. The Ins-EGFP cell line with stable expression of enhanced green fluorescent protein was constructed by the lentivirus carrying Inspromoter-EGFP. The Ins-EGFP-HepG2-Cas9-PUFa-p65-HSF1 cell line (referred to as stable translocated cell lines) with stable expression of dCas9 and PUFa-P65-HSF1 in Ins-EGFP-HepG2 cell line was constructed by the PiggyBac(PB) transposon system. By using liposome, the gRNAs were transfected to stable translocated cell line, and the expression level of endogenous gene PNM was detected by real-time fluorescence quantitative PCR and immunofluorescence. Simultaneously, reprogramming efficiency was observed. RESULTS AND CONCLUSION: (1) The activation of endogenous genes by Casilio system was verified in 293T cell line. (2) The expression of EGFP, dCas9 and PUFa-P65-HSF1 in stable cell line was detected by RT-PCR, western blot assay and immunofluorescence. (3) The real-time fluorescence quantitative PCR results confirmed that this new Casilio system could target and activate the PNM which led to the up-regulation of the endogenous PNM gene expression. The efficiency of direct reprogramming was 10%-15%. (4) Based on CRISPR/dCas9, the new Casilio system can efficiently activate the endogenous PNM gene in hepatocytes, enabling the hepatocyte line to be directly reprogrammed as islet-like cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: The dynamic balance between bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts is the basis for maintaining the stability of the body’s bone tissue. The metabolic imbalance between them can cause bone loss and fine structure degeneration of the bone cells, leading to osteoporosis. OBJECTIVE: To review the role of DNA methylation in osteoporosis and to explore the mechanism of exercise affecting DNA methylation and DNA methylation regulating bone metabolism. METHODS: A computer-based search of PubMed and CNKI databases was performed for relevant articles published from January 2002 to April 2020 with “DNA methylation; Osteoporosis; Exercise intervention; Mechanical stress; Osteogenic differentiation” as key words in English and Chinese, respectively. Initially, finally 52 eligible articles were included for result analysis. RESULTS AND CONCLUSION: DNA methylation is a relatively conservative and stable apparent modification, which regulates gene expression, silencing and disease occurrence. Studies have shown that reduced methylation levels of genes such as β-catenin, Runx2, osteopontin (OPG) can promote their expression and activate Wnt Pathway, whereas the reduction of methylation level of Sclerosin, receptor activator of nuclear factor kappa B ligand (RANKL) and other genes can promote their expression, and inhibit Wnt pathway and reduce the ratio of OPG/RANKL, thereby affecting the proliferation, differentiation and function of osteoblasts and osteoclasts, and accordingly regulating dynamic equilibrium between bone formation and bone resorption. Osteoblasts and osteoclasts act as sensitive cells for mechanical stimulation. Bone can transform the mechanical load generated by exercise into biological stimulation that acts on the differentiation and function of related bone cells, thereby regulating bone metabolism. In vitro experiments have indicated that different forms of mechanical stress stimulations can change the methylation level of genes such as OPN and GNAS1 to regulate their expression, which has a positive effect on bone formation. Bone tissue is a mechanically sensitive tissue, and DNA methylation can regulate bone metabolism by regulating a variety of factors. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that cornuside I (Cor I) can promote the proliferation of osteoblasts and chondrocytes, but its role and mechanism in repairing early cartilage damage of knee osteoarthritis are not clear. OBJECTIVE: To investigate the effect of Cor I on knee osteoarthritis rats and its effect on interleukin-6 (IL-6)/JAK2/STAT3 signaling pathway. METHODS: Fifty healthy male Sprague-Dawley rats were randomly divided into sham operation group, knee osteoarthritis model group (model group), Cor I high-dose group (Cor I-H), and cornuside I low-dose group (Cor I-L) and positive control group (celecoxib), with 10 rats in each group. Except the sham operation group, the knee osteoarthritis rat model was prepared according to the Hulth method. The Cor I-L and Cor I-H groups were administrated with Cor I 1.25 and 5 g/kg once a day for 6 weeks after modeling. The positive control group was fed with 4 mg/kg celecoxib, and the sham operation and model groups were fed with the same amount of normal saline once a day. The rats were sacrificed by cervical dislocation 24 hours after the last administration. Hematoxylineosin staining was used to observe the pathological and morphological changes of articular cartilage tissue in rats, and the degree of cartilage degeneration was scored according to Mankin’s method. Interleukin-1β, tumor necrosis and matrix metalloproteinase-13 in rat cartilage tissue were detected by ELISA. Interleukin-6 and STAT3 protein expression in rat articular cartilage tissue were detected by immunohistochemistry. Relative expressions of JAK2, p-JAK2, STAT3, and p-STAT3 were detected by western blot. RESULTS AND CONCLUSION: The articular cartilage of rats was severely damaged in the model group, where obvious chondrocyte damage and disordered arrangement of chondrocytes were observed. The joint structure of the rats in the Cor I-H, Cor I-L and positive control groups tended to be normal, the chondrocytes were distributed uniformly, and the fissures were reduced. Compared with the model group, the relevant indicators in the Cor I-L and Cor I-H groups were significantly reduced, including the Mankin’s score of cartilage tissue, interleukin-1β, tumor necrosis factor α and matrix metalloproteinase-13 levels (P < 0.05), interleukin-6 and STAT3 immunoreactivities (P < 0.01) as well as the relative expression levels of p-JAK2 and p-STAT3 and ratios of p-JAK2/JAK2 and p-STAT3/STAT3 (P < 0.05). Compared with the positive control group, these indicators mentioned above were significantly increased in the Cor I-L group (P < 0.05); however, there was no significant difference between the positive control group and Cor I-H group. Results have confirmed that Cor I can delay knee osteoarthritis-induced cartilage tissue degeneration, and its mechanism may be related to reducing the were expression of inflammatory factors and inhibiting the inflammatory response mediated by interleukin-6/JAK2/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although extracellular signal-regulated kinase 5 (ERK5) is an essential transducer of external signals for osteoblasts growth, differentiation, and survival, the effects of ERK5 signaling on bone homeostasis in vivo have not yet been described. OBJECTIVE: To elucidate whether the inhibition of ERK5 activity and its downstream targets by XMD8-92 results in osteoporosis and aggravates dexamethasoneinduced osteoporosis. METHODS: In vivo experiment: A mouse model of osteoporosis was induced by dexamethasone. There were four groups: blank control group (PBS); XMD8-92 group (50 mg/kg); dexamethasone group (50 mg/kg); XMD8-92+dexamethasone group (50 mg/kg XMD8-92 plus 50 mg/kg dexamethasone). Administration was done for 5 continuous weeks. Cell experiment: There were four groups: blank control group; XMD8-92 group (5 μmol/L); dexamethasone group (10×10-6 mol/L); XMD8-92+dexamethasone group (treatment with 5 μmol/L XMD8-92 followed by 10×10-6 mol/L dexamethasone). Cells were incubated for 1 hour. In addition, ERK5 activation was induced using epidermal growth factor. ERK5 activity in mice and MC3T3-E1 cells were detected. We further detected bone mass, bone architecture and mechanical stress of the trabecular bone, measured the expression of receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) and observed the roles of XMD8-92 in osteoblast proliferation and apoptosis. The study protocol was approved by the Ethics Committee of the Second Hospital of Lanzhou University (No. 2016-D44). RESULTS AND CONCLUSION: XMD8-92 could block ERK5 phosphorylation, change the architecture of the trabecular bone, reduce bone mass and aggravate dexamethasone-induced osteoporosis. XMD8-92 could significantly reduce the biomechanical properties of bone tissues in mice. XMD8-92 could up-regulate RANKL/OPG rate, lower osteoblasts vitality by inhibiting Cyclin B1 and CDK1 expression, and promote osteoblast apoptosis by up-regulating the expression of FasL. The novel findings suggest that ERK5 activity plays an important role in maintenance of bone mass, and altered ERK5 activation in disease conditions such as osteoporosis or dexamethasone-induced osteoporosis should be considered as a potential mechanism for abnormal bone homeostasis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Osteoporotic fractures are the most common serious complications caused by osteoporosis, and their repair is more difficult, which seriously threatens the health and quality of life of patients. OBJECTIVE: To investigate the interventional effect of Panax Notoginsenosides in ovariectomized osteoporotic fracture rats and the relevant mechanism. METHODS: Fifty healthy female rats were selected. Ten of them were normal group, and the other 40 rats were used to make ovariectomized osteoporotic fracture models. Model rats were divided into model group, low, medium and high dose group. Normal group and model group rats were intragastrically administered normal saline, rats in the low, medium and high dose group were given intragastric administration of 10, 20 and 40 mg/kg Panax Notoginsenosides solution. The study protocol was approved by the Animal Ethic Committee of the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. (2019)58 on September 23, 2019. RESULTS AND CONCLUSION: The bone mineral density and bone cell index of the high dose group were higher than those of low and middle dose groups (P < 0.05). The bone volume fraction, the number of callus trabeculae and the thickness of trabeculae in the high dose group were all higher than those in the model group, the low dose group and the middle dose group, and the resolution of trabeculae was lower than that in these three groups (P < 0.05). The levels of glutathione peroxidase, bone morphogenetic protein 2, and vascular endothelial growth factor in the high dose group were lower than those in the normal group, but higher than those in the model group, low and medium dose groups. The levels of lipid peroxide, malondialdehyde, osteocalcin, type I procollagen carboxy terminal propeptide, bone-specific alkaline phosphatase in the high dose group were higher than those in the normal group, but lower than those in the model group, low and medium dose group (P < 0.05). The expression of PI3K, Akt and mTOR in the low, middle and high dose groups was lower than that in the normal group and higher than that in the model group; and the expression of PI3K, Akt and mTOR in the high dose group was higher than that in the low and middle dose groups (P < 0.05). Therefore, treatment with Panax Notoginsenosides can increase the bone miner density and bone cell index, promote the growth of bone trabecula at the callus, alleviate oxidative stress injury, regulate the PI3K / Akt / mTOR signal pathway, and accelerate the formation of new blood vessels in the callus and fracture healing in ovariectomized osteoporotic fracture rats. [ABSTRACT FROM AUTHOR]

BACKGROUND: Melatonin, a neuroendocrine hormone, is mainly secreted by the pineal gland, which can promote the proliferation of Schwann cells and the regeneration of peripheral nerve after injury. OBJECTIVE: To investigate the role of melatonin in the migratory activity of Schwann cells together with the molecular mechanism involved. METHODS: The rodent RSC96 Schwann cell line was cultured in vitro followed by identification. The CCK-8 assay was performed to detect the effect of melatonin on Schwann cells proliferation. The Transwell chamber was adopted to observe the efficacy of melatonin with a series of concentrations, which is 0, 100 nmol/L, 1 μmol/L and 10 μmol/L, on the migratory activity of Schwann cells following 20 hours. The expression of melatonin receptor 1 and 2 in Schwann cells was assessed using qRT-PCR and western blot assay. Transwell cell migration system was conducted to determine the influence of melatonin receptor antagonist luzindole or inhibitor IWR-1 of the canonical Wnt/β-catenin signaling on the enhanced migratory activity exerted by melatonin. Western blot assay was performed to investigate the regulatory effect of melatonin on the activity of Wnt/β-catenin signal cascades. RESULTS AND CONCLUSION: (1) The cultured RSC96 cells showed the typical morphology of Schwann cells, showing a spindle-like or triangular shape with thin and long processes on the two cell poles. The Schwann cells marker S-100 immunofluorescence staining was positive. (2) Compared with the blank control group, 1 μmol/L and 10 μmol/L melatonin could promote Schwann cell migration dramatically compared to the control group, and displayed a chemoattractive effect, with 1 μmol/L showing the most significant effect. (3) Melatonin receptor 1 was the dominating receptor of melatonin expressed in Schwann cells. The Transwell assay results displayed that the number of migratory cells that melatonin induced was not significantly changed with luzindole added, as compared with treatment with melatonin alone, showing no statistical significance. The number of Schwann cells treated with IWR-1 and melatonin was significantly lower than those treated with melatonin (P < 0.05). (4) Results of qRT-PCR and western blot assay showed that compared with the blank control group, the expression levels of P-Lrp6, LEF-1 and nuclear β-catenin protein in Schwann cells of melatonin group were significantly increased (P < 0.05). (5) The expression levels of LEF-1 and nuclear β-catenin protein in Schwann cells of melatonin group and IWR-1 + melatonin group were significantly higher than those of blank control group and IWR-1 group (P < 0.05), indicating that melatonin can antagonize the inhibition of IWR-1 on Wnt/β-catenin signaling pathway activity to some extent. (6) The above data confirm that melatonin can promote Schwann cell migration by activating Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]