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[Display omitted] • A new snail shell structure is used as the prototype of the optimal design. • The multi-objectives are changed into one objective through the weight coefficient. • The designed labyrinth seal has good load-bearing and heat insulation performance. Labyrinth seals are widely used in turbomachinery devices to prevent the leakage of fluid medium in seal structures. Under high parametrical environments, the heat generated by frictional resistance of the turbulence between the stator and rotor walls not only increases the temperature of the fluid and the solid, but also reduces the operation efficiency of the device. Therefore, it is necessary to implement the fluid–solid-thermal multi-field analysis of labyrinth seals and propose a comprehensive optimization design of the load-bearing and heat insulation. In the present study, inspired by a bionic snail shell, a sandwich structure with load-bearing material on both upper and lower surfaces and the heat insulation material in the middle is obtained through the genetic algorithm optimization. Then, the luid-solid-thermal multi-field analysis of the labyrinth seal with the sandwich structure is carried out. It is verified that the layer arrangement and layer thickness ratio of the bionic structure ensured the optimal performance of load-bearing and heat insulation. After changing the layer arrangement or layer thickness ratio, the comprehensive performance of load-bearing and heat insulation is obviously weakened. The result shows that the bionic multilayer sandwich structure can be applied to the labyrinth seal to achieve optimal comprehensive performance of load-bearing and heat insulation. [ABSTRACT FROM AUTHOR]

Abstract: Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK), which plays a pivotal role in cell apoptosis. To determine the mechanism of ASK1 induction during reperfusion of ischemic spinal tissue, we used a model of rabbit spinal cord ischemia and reperfusion. To assess the role of ASK1 in spinal cord ischemia-reperfusion injuries, we examined alterations in spinal tissue morphology, protein–protein interactions, and activation of key members of the ASK1-mediated signaling pathway. Changes in spinal cord morphology were observed with hematoxylin and eosin (H&E) staining and electron microscopy. The phosphorylation levels of ASK1, JNK, and p38 were assessed by immunoblotting proteins from animals that received 30min of ischemia followed by 1 or 24h of reperfusion. We observed increased phosphorylation of ASK1, JNK, and p38 after reperfusing ischemic spinal cords. Immunohistochemical studies were performed to determine the cellular localization of phosphorylated ASK1 (pASK1) and 14-3-3. Following reperfusion for 24h, we observed increased cytoplasmic localization of pASK1 and decreased cytoplasmic localization of 14-3-3. Immunoprecipitation analyses suggested that 14-3-3 dissociates from ASK1 during reperfusion of ischemic spinal cords. These results indicate that activation of ASK1 may play an important role in the apoptotic signaling mechanisms that occur in reperfused spinal cord injuries. [Copyright &y& Elsevier]

Abstract: With a view to better understanding the role of oxidant/antioxidant variables in proliferation dynamics of somatic cells, we explored the relationships among superoxide dismutase (SOD) activity, glutathione peroxidase (Gpx) activity, reactive oxygen intermediates (ROI), and indices of cellular proliferation and senescence in cultured fibroblasts from Down syndrome and normal donors. We found that Down syndrome cells had a significantly slower proliferative rate, but attain replicative senescence at similar population doubling (PD) as control cells. Irrespective of donor origin, the number of PD until replicative senescence was positively correlated with Gpx activity (r = 0.784, P = 0.007). In addition, the presence of exogenous catalase in the growth medium significantly extended the number of PD until replicative senescence (P = 0.011). The loss of telomere repeats per PD was not different between Down syndrome cells and controls. However, SOD activity was inversely correlated with the loss of telomere repeats per PD. Collectively, these findings suggest that replicative senescence ultimately relates to mechanisms downstream to SOD (i.e., Gpx and catalase) and confirmed previous observations about inverse relationships between SOD activity and telomere repeat loss per cellular replication. [Copyright &y& Elsevier]

In order to explore high-viscosity, high-elasticity composite modified asphalt materials suitable for drainage pavements, different dosages of graphene-modified asphalt and graphene composite-modified asphalt were prepared. Elastic recovery efficiency and rotational viscosity as the main experimental indicators for modified asphalt are employed to determine the optimal dosage of graphene and help conduct a study on the viscoelastic properties, analyzing the fatigue performance of the modified asphalt through linear amplitude sweep (LAS). Based on molecular dynamics simulation (MD) to build an asphalt model, the study on viscoelastic properties uses calculated viscosity and the asphalt glass transition temperature range (Tg) obtained from simulation results as indicators to verify the optimal dosage of graphene. Scanning Electron Microscopy (SEM) is utilized to reveal the effects of different dosages of graphene modification. The research results indicate that the optimal dosages of graphene in graphene-modified asphalt and graphene composite-modified asphalt are 0.1 % and 0.2 %, respectively. At these concentrations, graphene significantly enhanced the elastic recovery properties of the matrix asphalt (113 % increase) and the composite-modified asphalt (28 % increase). In terms of rotational viscosity, the matrix asphalt saw a 54 % rise with the addition of graphene, while the composite-modified asphalt experienced a substantial 151 % increase. Notably, the incorporation of graphene also resulted in a rise in the glass transition temperature and a reduction in the length of the graphene-modified asphalt, signifying an improvement in its elastic properties. Furthermore, the calculated viscosity of the graphene-modified asphalt and composite-modified asphalt surged by 47.49 % and 64.01 %, respectively. Additionally, SEM results indicate that differences in the effects of graphene modification are primarily due to the dispersion and coating extent of graphene. • CWRB plays a central role in mining reinforcement projects and waste recycling. • IGO reinforces the CWRB microstructure via nucleation and pore-filling effects. • Optimized W/C ratio is significant for the modification effects of the IGO-FA hybrid on CWRB. • IGO enhances the integrity and toughness of the CWRB specimens. • IGO-FA hybrid can replace 20 % cement in CWRB without affecting its consolidation properties. [ABSTRACT FROM AUTHOR]

• Porosity and temperature-dependent material properties considered. • Slice model proposed for discretization. • Iteration algorithm developed for heat transfer analysis. • Exact 2-D thermoelasticity theory applied. • Effects of some key factors on the thermoelastic behaviors comprehensively studied. Porosity usually occurs in functionally graded materials (FGMs) during the fabrication process. Its effects on the thermomechanical behaviors of FGM structures are worth studying. In this work, heat transfer and thermoelastic behaviors of porous FGM sandwich beams with temperature-dependent material properties are examined. The effective material properties are approximately estimated by the modified Voigt mixture rule. Because of the continuously varied material properties across the thickness direction, it is impractical to seek exact solutions for the beam. By proposing a slice model in which the face and core layers are divided into numerous thin slices, the material properties of each slice can be treated as uniform. Based on the model, the through-thickness temperature distribution is first obtained by using an iteration algorithm. Then the two-dimensional (2-D) thermoelasticity equations are analytically solved by using the state space method and Fourier series expansion method. The correctness of the proposed model is checked through comparison with results reported in previous works. The effects of some key factors such as the temperature dependence of material properties, volume fraction, and porosity on the thermomechanical behaviors of the beam are comprehensively studied. It is shown that with the increase of porosity, the thermal resistance capacity of the beam is enhanced yet the bending stiffness is weakened. [ABSTRACT FROM AUTHOR]

To investigate the molecular mechanism of osteoclast-derived exosomes in osteoporosis. RANKL induced osteoclast model was screened for significantly differentially expressed lncRNAs and mRNAs by whole RNA sequencing. Exosomes were characterized using electron microscopy, western blotting and nanosight. Overexpression or knockdown of AW011738 was performed to explore its function. The degree of osteoporosis in an osteoporosis model was assessed by mirco-CT. The osteoclast model, osteoblast differentiation ability and the molecular mechanism of lncRNA AW011738/miR-24-2-5p/TREM1 axis in osteoporosis were assessed by dual luciferase reporter gene assay, Western blotting (WB), immunofluorescence and ALP staining. Bioinformatics was used to predict interactions of key osteoporosis-related genes with miRNAs, transcription factors, and potential drugs after upregulation of AW011738. To predict the protein-protein interaction (PPI) network associated with key genes, GO and KEGG analyses were performed on the key genes. The ssGSVA was used to predict changes in the immune microenvironment. Osteoclast-derived exosomes containing lncRNA AW011738 decreased the osteogenesis-related markers and accelerated bone loss in OVX mice. Osteoclast (si-AW011738)-derived exosomes showed a significant increase in biomarkers of osteoblast differentiation in vitro compared to the si-NC group. As analyzed by mirco-CT, tail vein injected si-AW011738 OVX mice were less osteoporotic than the control group. AW011738 inhibited osteoblast differentiation by regulating TREM1 expression through microRNA. Meanwhile, overexpression of miR-24-2-5p inhibited TREM1 expression to promote osteoblast differentiation. Osteoclast-derived exosomes containing lncRNA AW011738 inhibit osteogenesis in MC3T3-E1 cells through the lncRNA AW011738/miR-24-2-5p/TREM1 axis and exacerbate osteoporosis in OVX mice. [Display omitted] • Osteoclast-derived Exosomes transfer lncRNA AW011738 to osteoblasts. • The lncRNA AW011738/miR-24-2-5p/TREM1 axis affects osteoblast proliferation and differentiation. • AW011738 and TREM1 are potential therapeutic targets for osteoporosis. • AW011738 triggers up- or down-regulation of several osteoporosis and inflammation-related key genes. • Inhibition of AW011738 effectively prevents the progression of osteoporosis. [ABSTRACT FROM AUTHOR]

This paper mainly investigates the tensile behavior of fiber metal laminates (FMLs) under various temperatures ranged from 25 ℃ to 175 ℃ combined experimental measurement, theoretical model and numerical technique. Firstly, based on numerous tensile tests under various temperatures, different tensile load–displacement response and damage modes for FMLs can be obtained and compared. And in virtue of the scanning electron microscopy (SEM), microscopic damage modes are identified through the fracture surface scanning of FMLs subjected to different temperatures. Subsequently, in order to analyze the discreteness of experimental results and evaluate the theoretical tensile strength of FMLs under different temperatures, the two-parameter Weibull statistics model is established for engineering application of FMLs. Finally, the effect of layer direction on damage modes and progressive damage evolution process of FMLs is characterized numerically. These results indicate that the tensile strength of FMLs represents a nonlinear downward trend with the increase of temperature. The complex failure mechanisms under different temperatures can be captured from SEM observation, including fiber/matrix debonding, fiber pull-out, matrix microcrack, delamination damage and so on. The deeper understanding of tensile behavior and failure mechanisms of FMLs under thermal conditions can be provided for the design and utilization of FML structures. [ABSTRACT FROM AUTHOR]

Objective: Little is known about the relationship of telomere length among leukocyte subsets and cells up the hematopoietic hierarchy. This information is relevant because telomere dynamics in granulocytes were postulated to mirror those of hematopoietic stem cells (HSCs). Materials and Methods: In newborn umbilical cord blood (UCB), we examined the relationships of telomere length in hematopoietic progenitor cells (HPCs) (CD34+CD45−) with those in T lymphocytes and granulocytes. In addition, we correlated telomere length in granulocytes with those in whole leukocyte samples of individuals ranging in age from birth to 100 years. Results: In the UCB, we found strong correlations of telomere length in HPCs with telomere length in T lymphocytes (r ranging from 0.882 to 0.935; p ranging from 0.0038 to 0.0007) and in granulocytes (r = 0.930; p = 0.0072). At birth, strong correlations were also observed between telomere length in granulocytes and those in all leukocytes (r = 0.979; p = 0.0003). Throughout the human lifespan, the relationship between telomere length in granulocytes and that in all leukocytes was r > 0.980 and p < 0.0001. Conclusions: Robust synchrony exists among leukocyte subsets throughout the human lifespan; individuals with relatively long (or short) telomeres in one leukocyte subset have long (or short) telomeres in other leukocyte subsets. Moreover, telomere length in leukocytes reflects its length in cells up the hematopoietic hierarchy, i.e., HPCs and, by inference, HSCs. Strong links have been found by many studies between leukocyte telomere length and a host of aging-related diseases. Our findings suggest, therefore, that these links might be traced to telomere dynamics in HSCs. [Copyright &y& Elsevier]

This study explored diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) to assess the prognosis of thoracolumbar spinal cord injury (SCI). Twenty patients with acute traumatic thoracolumbar complete SCI (T1-L1, American Spinal Injury Association Impairment Scale [AIS] grade A) underwent conventional magnetic resonance imaging and DTI examinations. DTI measured the fractional anisotropy (FA) and apparent diffusion coefficient adjacent to the lesion epicenter. DTT was used to detect the white matter fiber morphology and measure the imaginary white matter fiber volume and connection rates of fiber tractography (CRFT). The patients' neurological functions were evaluated by the AIS grades. At the final-follow-up, among the 20 patients with AIS grade A, 15 maintained the AIS grade (group A), and 5 patients showed improvement of AIS grade (group B). Group A's mean FA value was significantly lower than that of group B, whereas the mean apparent diffusion coefficient value among the 2 groups showed no significant difference. The white matter fibers of most patients in group A were completely ruptured (11/15), but the white matter fibers of all patients in group B were retained in different number (5/5). The mean CRFT of group B was significantly higher than that of group A (P < 0.05). The improvement of AIS grade was slightly positively correlated with FA values and highly positively correlated with CRFT. The prognosis of complete thoracolumbar SCI may be related to the FA value and the CRFT. The application of DTI and DTT may optimize the diagnosis of thoracolumbar SCI. [ABSTRACT FROM AUTHOR]

Mitomycin C (MMC) is known to reduce epidural fibrosis, but the underlying mechanisms have not yet been elucidated. Aberrant miR-200b expressions have been reported in multiple types of fibrotic tissues from many diseases. The aim of this study was to clarify the mechanism by which MMC induces fibroblasts apoptosis and reduces epidural fibrosis. The expression of miR-200b in human fibroblasts was determined after MMC treatment, and the targeted association between miR-200b and RhoE was determined using the luciferase activity assay. The effects of MMC and miR-200b on human fibroblasts apoptosis were evaluated using flow cytometry and western blot analysis. The effects of MMC and miR-200b on epidural fibrosis were evaluated using the Rydell classification, hydroxyproline content, apoptotic cell count and histological analysis. The study revealed that MMC could significantly downregulate miR-200b expression and induce human fibroblasts apoptosis. The direct downregulation of miR-200b could induce human fibroblasts apoptosis. Furthermore, we identified the binding sequence for miR-200b within the 3′ untranslated region of RhoE. RhoE was confirmed to be a direct target of miR-200b, and RhoE itself acted as a promoter of fibroblasts apoptosis. The inhibition of miR-200b increased fibroblasts apoptosis and reduced epidural fibrosis in rats, which was in accordance with the effect of MMC. This study suggests that MMC induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-200b expression and its targeting of RhoE. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the effects of topical application mitomycin-C (MMC) on wound healing after laminectomy. 60 adult male SD rats were equally and randomly divided into five groups. Laminectomy was performed at the level of L1 in all rats. After hemostasis was achieved, cotton pads soaked with saline and MMC (0.1mg/ml, 0.3mg/ml, 0.5mg/ml and 0.7mg/ml) were directly subjected to the exposed dura for 5min in each group. Two weeks after laminectomy all the rats were killed. The vertebral column including the back scar tissue and muscles was obtained to make paraffin sections. The hematoxylin–eosin staining and Masson staining were performed with the obtained paraffin sections. The number of the fibroblast and the capillary density were counted by the hematoxylin–eosin staining slice. The extent of epidural fibrosis and the expression of vascular endothelial growth factor (VEGF) were evaluated by the immunohistochemical slice through a computer image analysis system. Our data showed that the number of fibroblast, capillary density and fibrotic tissue in the 0.5 and 0.7mg/ml MMC groups was significantly lower than the control, 0.1 and 0.3mg/ml MMC groups; while the expression of VEGF in control and 0.1mg/ml MMC groups was notably higher than 0.3, 0.5 and 0.7mg/ml MMC groups. Topical application of MMC above the concentration of 0.3mg/ml could affect all steps of the wound healing process via inhibiting the angiogenesis and fibroblast proliferation, thus delayed the wound healing after laminectomy. [Copyright &y& Elsevier]

Abstract: Astrocytes play an important role in protecting neurons during ischemia and reperfusion in the central nervous system. Although many studies have shown that oxygen–glucose deprivation (OGD) can induce astrocyte apoptosis, the role of PERK/eIF2α/ATF4 integrated stress response (ISR) in astrocyte apoptosis mediated by oxygen–glucose–serum deprivation (OGSD)/restoration remains uncertain. Astrocytes were subjected to a combination of oxygen, glucose, and serum deprivation for 8h followed by restoration. Hoechst 33342 staining was performed to quantify apoptotic astrocytes and cell viability was assessed with Cell Counting Kit-8 (CCK8). Immunocytochemical analysis and Western blotting for some related molecules, including pancreatic ER stress kinase (PERK), p-PERK, eukaryotic initiation factor 2 alpha (eIF2α), p-eIF2α, activating transcription factor 4 (ATF4), caspase-12, were examined. Caspase activation and apoptosis were detected in neonatal rat astrocytes from spinal cord subjected to OGSD/restoration. We also observed an increase in cytoplasmic staining of p-eIF2α in astrocytes (8h OGSD/15min restoration) compared with that of non-treated cells. In addition, we found the sequential activation of PERK, eIF2α, and ATF4 during OGSD/restoration by Western blotting. These results indicate that both the PERK/eIF2α/ATF4 ISR and activation of caspase-12 may be involved in apoptosis of spinal cord astrocytes induced by OGSD/restoration. [Copyright &y& Elsevier]

Abstract: Background context: Recovery from spine surgery is usually accompanied with the development of epidural scar adhesions from the abnormal proliferation of fibroblast and extracellular matrix–related metabolism. Polyethylene glycol (PEG) could alleviate the postsurgical adhesion formation with still leaving a gap between the sheet and the dura. However, PEG film could not function as a three-dimensional barrier to prevent adhesion completely. Mitomycin C (MMC) could also reduce the scar formation after surgery, but cytotoxicity and the administrative pathway prevent its application. Purpose: Our purpose was to design and attest the role of new delivery system MMC-PEG controlled-release film in preventing the epidural scar adhesions after laminectomy in the rat model. Study design/setting: A total laminectomy of L1 in the rat model was used to assess epidural fibrosis between and around the spinal nerves using a histochemistry assessment along with flow cytometry analysis. Patient sample: The sample comprises 64 adult male Sprague-Dawley rats. Outcome measures: The outcome measures are macroscopic evaluation, histological analysis, and flow cytometry analysis. Methods: Lumbar laminectomies at L1 and L2 with a L1–L2 disc injury were performed on 64 adult male Sprague-Dawley rats. The rats were then randomized into four groups. In Group I, 25 mg PEG film was applied on the dura mater in the laminectomy area before the layers were sutured. In Group II, a cotton pad soaked with 0.05% MMC solution was kept on the laminectomy area for 5 minutes. In Group III, 25 mg PEG film containing 0.01% MMC was implanted on the laminectomy area. In Group IV, the laminectomy area was flushed with saline before wound closure. The rats were sacrificed 4 weeks after the operation. Macroscopic evaluation and histological analysis of epidural scar adhesion with the hematoxylin and eosin stain and Masson stain were used followed by the quantification of hydroxyproline (Hyp) and flow cytometry analysis of the apoptosis of fibroblasts in the scar tissues. Results: The recovery of all rats was uneventful after the operations. In the laminectomy sites of rats treated with MMC or MMC-PEG, the dura mater was clean without any evident adhesion or membrane. Collagen tissue hyperplasia significantly decreased in the MMC- or MMC-PEG–treated models. Accordingly, Hyp concentration was significantly reduced in these two groups compared with saline-control group. In addition, the apoptosis of fibroblasts, however, was significantly elevated in the MMC or MMC-PEG group compared with the saline-control group. Conclusions: These results demonstrate that the treatment of postlaminectomy wounds with MMC-PEG film reduces the severity of adhesion by decreasing the concentration of Hyp and increasing the apoptosis of fibroblasts. [Copyright &y& Elsevier]

Abstract: Objective: This study examined the relationships of high-density lipoprotein cholesterol (HDL-C) with LTL and the rate of its shortening. Background: Diminished levels of HDL-C are associated with an increased risk for atherosclerosis. Shortened leukocyte telomere length (LTL) also entails an increased atherosclerotic risk. Methods: We studied 472 Whites and 190 African Americans (AfAs) enrolled in the Bogalusa Heart Study. Subjects were examined serially 3–13 times for HDL-C over an average period of 27.8 years from childhood through young adulthood. LTL was measured twice during adulthood at a mean age of 31.5 years (baseline exam) and 37.8 years (follow-up exam). HDL-C trajectories with age were constructed and the area under the curve (AUC) was used as a measure of cumulative HDL-C levels. Results: Multivariate regression analyses showed that LTL was positively associated with HDL-C in childhood (regression coefficient (bp per mg/dL) β =3.1, p =0.024), adulthood (β =4.4, p =0.058) and AUC from childhood to adulthood (β =12.2, p =0.0004) in the combined sample of AfAs and Whites. The association between LTL and HDL-C AUC was stronger in females (β =18.5, p <0.001) than in males (β =2.9, p =0.590) (difference in slopes p =0.037). A slower rate of LTL shortening per year was associated with higher HDL-C AUC in the total sample (p =0.033), adjusting for baseline LTL. Conclusions: As HDL-C exerts anti-oxidant and anti-inflammatory effects and LTL registers the accruing burden of oxidative stress and inflammation, the association between HDL-C and LTL might be explained by the lifelong status of oxidative stress and inflammation. [Copyright &y& Elsevier]

To determine the role of MICAL2 in myofibroblasts differentiation and epidural fibrosis. Epidural fibrosis (EF) may develop following laminectomy and aberrant myofibroblasts differentiation and excessive extracellular matrix (ECM) accumulation play key roles in the formation of EF. Dense epidural fibrosis results to the poor surgical outcomes and failed back surgery syndrome (FBSS), and there is no effective treatment available. Molecule interacting with Casl2 (MICAL2) has been demonstrated to participate in multiple cellular processes by regulating actin cytoskeleton dynamics. However, its role in epidural fibrosis remains totally unverified. The potential functions and mechanisms of MICAL2 were explored using western blotting, immunofluorescence and lentivirus infection. In our study, we determined that the MICAL2 expression was elevated in epidural fibrotic tissues and TGF-β1-stimulated fibroblasts. Moreover, knockdown of MICAL2 using MICAL2-specific short hairpin RNA attenuated TGF-β1-induced myofibroblasts differentiation and epidural fibrosis both in vitro and vivo, as indicated by decreased scar formation, reduced collagen production and down-regulated expression of α-SMA, collagen-1 and fibronectin. We also demonstrated that MICAL2 knockdown affected the migratory capability of fibroblasts in vitro. By further mechanistic research, we revealed that the MRTF-A nuclear translocation was inhibited in response to the knockdown of MICAL2 in fibroblasts and MICAL2 served as a pro-fibrotic factor in an SRF/MRTF-A-dependent manner. In conclusion, our results indicated that MICAL2 mediated myofibroblasts differentiation and promoted epidural fibrogenesis via SRF/MRTF-A signaling pathway, suggesting manipulation of MICAL2 activity as a novel alternative strategy for the prevention of epidural fibrosis. [ABSTRACT FROM AUTHOR]

Apoptosis of endothelial cells (ECs) is a crucial factor in blood-spinal cord barrier (BSCB) disruption post spinal cord injury (SCI). Insulin-like growth factor-1 (IGF-1) is a protective cytokine that plays an important role in multiple diseases, whereas the distinct role in SCI-induced remains critical questions to address. Here we designed to explore the role and underlying mechanism of IGF-1 in endothelial damage after SCI. In the current study, we established mouse microvascular endothelial cells (MVECs) injury model via LPS and cDNA of IGF-1 was transfected into MVECs. In vivo SCI mice, overexpression of IGF-1 (SCI-IGF-1) and its corresponding empty vehicle (SCI-NC) were conducted using lentivirus, then apoptosis degree, component of tight junction, and inflammatory damage were evaluated. IGF-1 treatment in MVECs displayed a milder apoptosis and cell damage under LPS insult. IGF-1 increased the level of PI3K/AKT pathway, which impeded the procedure of apoptosis. Blocking of PI3K/AKT pathway markedly neutralized the effect of IGF-1 treatment. Transfection of excess IGF-1 into SCI mice significantly corrected microenvironment of neural tissue repair, reduced area of injured core and improved functional recovery with greater activation of PI3K/AKT pathway. The results above argue that the promising roles played by IGF-1 is potentially vital for developing effective future therapies in SCI. Unlabelled Image [ABSTRACT FROM AUTHOR]

Osteosarcoma accounts for about 0.2% in human malignant solid tumors. The mortality and metastatic rates of osteosarcoma remain relatively high. MicroRNA (miRNA) is a kind of non-coding small-molecular RNA discovered in recent years. Various studies have identified the involvement of miRNA in the occurrence and development of tumor as an oncogene or tumor-suppressor gene. This study aims to investigate the effect of hsa-miR-889-3p on the progression of osteosarcoma and its underlying mechanism. Through the bioinformatics methods, we first found that hsa-miR-889-3p was upregulated in osteosarcoma, and it was a prognostic risk factor for osteosarcoma. Additionally, the gene set enrichment analysis (GSEA) revealed that hsa-miR-889-3p mainly affected cell cycle progression and proliferation of osteosarcoma. To verify the bioinformatics results, regulatory effects of hsa-miR-889-3p on osteosarcoma both in vitro and in vivo experiments were investigated. It is found that hsa-miR-889-3p could promote the proliferation of osteosarcoma cells though regulating cell cycle progression. Tumor size and growth rate of osteosarcoma were influenced by hsa-miR-889-3p in xenograft models. To further explore its potential mechanism, the target gene of hsa-miR-889-3p was predicted. Furthermore, hsa-miR-889-3p was confirmed to inhibit the expression of myeloid cell nuclear differentiation antigen (MNDA) in a targeted manner. In conclusion, hsa-miR-889-3p could promote the proliferation of osteosarcoma through inhibiting MNDA expression, which provides a potential therapeutic strategy in treatment for osteosarcoma. [ABSTRACT FROM AUTHOR]