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OBJECTIVE: This study introduces a novel methodology combining rapid stretch compound training with blood flow restriction (BFR) to investigate post activation performance enhancement (PAPE) in basketball players, a field that has been predominantly explored for lower limbs. We aimed to assess the efficacy of this combined approach on upper limb muscle performance in athletes. METHODS: We employed a randomized, self-controlled crossover trial with ten male basketball players. The bench press throw (BPT) served as the primary metric, with players undergoing four interventions post-baseline: (1) STR-plyometric training; (2) BFR-blood flow restriction; (3) COMB-STR integrated with BFR; and (4) CON-control. Innovatively, we utilized an intelligent tracking sensor to precisely measure peak power (PP), peak velocity (PV), mean power (MP), and mean velocity (MV) at 4, 8, and 12 min post-intervention, providing a detailed temporal analysis of PAPE. RESULTS: The COMB intervention demonstrated superior PAPE effects at 4 min, significantly outperforming STR and BFR alone and the control group across all measured indices (p < 0.05). Notably, the COMB group maintained these improvements for PV, PP, and H up to 12 min post-intervention, suggesting a prolonged effect. CONCLUSION: (1) The COMB stimulation has been shown to successfully induce PAPE more effectively than STR and BFR modality alone. (2) It appears that the optimal effects of PAPE are achieved within 4 min of exercising under this COMB. By the 12 min mark, only the COMB group continued to show significant improvements in PV, PP, and H compared to both the baseline and the CON group, while the effects in the STR and BFR groups further diminished. This suggests that although the PAPE effect is maintained over time, its optimal performance may peak at the 4 min mark and then gradually weaken as time progresses.
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Atletas , Basquetebol , Extremidade Superior , Humanos , Basquetebol/fisiologia , Masculino , Extremidade Superior/fisiologia , Adulto Jovem , Desempenho Atlético/fisiologia , Estudos Cross-Over , Adulto , Músculo Esquelético/fisiologia , Músculo Esquelético/irrigação sanguínea , Exercícios de Alongamento Muscular , Fluxo Sanguíneo Regional/fisiologiaRESUMO
Background: The aim of this study was to investigate the effects of different pressurization modes during high-load bench press training on muscle activation and subjective fatigue in bodybuilders. Methods: Ten bodybuilders participated in a randomized, self-controlled crossover experimental design, performing bench press training under three different pressurization modes: T1 (low pressure, high resistance), T2 (high pressure, high resistance), and C (non-pressurized conventional). Surface EMG signals were recorded from the pectoralis major, deltoid, and triceps muscles using a Delsys Trigno wireless surface EMG during bench presses. Subjective fatigue was assessed immediately after the training session. Results: (1) Pectoralis major muscle: The muscle activation degree of the T1 group was significantly higher than that of the blank control group during the bench press (p < 0.05). The muscle activation degree of the T2 group was significantly higher than that of the C group during the bench press (p < 0.05). In addition, the muscle activation degree of the T2 group was significantly higher than that of the T1 group during the first group bench press (p < 0.05). (2) Deltoid muscle: The muscle activation degree of the T2 group during the third group bench press was significantly lower than the index values of the first two groups (p < 0.05). The muscle activation degree in the experimental group was significantly higher than that in the C group (p < 0.05). The degree of muscle activation in the T2 group was significantly higher than that in the T1 group during the first bench press (p < 0.05). (3) Triceps: The muscle activation degree of the T1 group was significantly higher than the index value of the third group during the second group bench press (p < 0.05), while the muscle activation degree of the T2 group was significantly lower than the index value of the first two groups during the third group bench press (p < 0.05). The degree of muscle activation in all experimental groups was significantly higher than that in group C (p < 0.05). (5) RPE index values in all groups were significantly increased (p < 0.05). The RPE value of the T1 group was significantly higher than that of the C group after bench press (p < 0.05). The RPE value of the T1 group was significantly higher than that of the C group after bench press (p < 0.05). In the third group, the RPE value of the T1 group was significantly higher than that of the C and T2 groups (p = 0.002) (p < 0.05). Conclusions: The activation of the pectoralis major, triceps brachii, and deltoid muscles is significantly increased by high-intensity bench press training with either continuous or intermittent pressurization. However, continuous pressurization results in a higher level of perceived fatigue. The training mode involving high pressure and high resistance without pressurization during sets but with 180 mmHg occlusion pressure and pressurization during rest intervals yields the most pronounced overall effect on muscle activation.
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Músculos Peitorais , Extremidade Superior , Humanos , Eletromiografia , Terapia por Exercício , FadigaRESUMO
OBJECTIVES: Confirm that stem cells from human exfoliated deciduous teeth-derived exosomes (SHED-exos) can limit inflammation-triggered epithelial cell apoptosis and explore the molecular mechanism. METHODS: SHED-exos were injected into the submandibular glands (SMGs) of non-obese diabetic (NOD) mice, an animal model of Sjögren's syndrome (SS). Cell death was evaluated by western blotting and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining. RESULTS: SHED-exos treatment promoted the saliva flow rates of NOD mice, accompanied by decreased cleaved caspase-3 levels and apoptotic cell numbers in SMGs. SHED-exos inhibited autophagy, pyroptosis, NETosis, ferroptosis, necroptosis and oxeiptosis marker expression in SS-damaged glands. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis of exosomal miRNAs suggested that the rat sarcoma virus (RAS)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway might play an important role. In vivo, the expression of Kirsten RAS, Harvey RAS, MEK1/2 and p-ERK1/2 was upregulated in SMGs, and this change was blocked by SHED-exos treatment. In vitro, SHED-exos suppressed p-ERK1/2 activation and increased cleaved caspase-3 and apoptotic cell numbers, which were induced by IFN-γ. CONCLUSION: SHED-exos suppress epithelial cell death, which is responsible for promoting salivary secretion. SHED-exos inhibited inflammation-triggered epithelial cell apoptosis by suppressing p-ERK1/2 activation, which is involved in these effects.
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OBJECTIVES: To evaluate the effect of stem cellsâ fromâ exfoliatedâ deciduous âteeth on the hyposalivation caused by Sjögren syndrome (SS) and investigate the mechanism. METHODS: Stem cells were injected into the tail veins of non-obese diabetic mice, the animal model of SS. The saliva flow was measured after pilocarpine intraperitoneal injection. Apoptosis and autophagy were evaluated by TUNEL and Western blot. Lymphocyte proportions were detected by flow cytometer. RESULTS: Fluid secretion was decreased in 21-week-old mice. Stem cell treatment increased fluid secretion, alleviated inflammation in the submandibular glands and reduced inflammatory cytokine levels in the serum, submandibular glands and saliva. Stem cells decreased the apoptotic cell number and the expressions of ATG5 and Beclin-1 in the submandibular glands. Stem cells have no effect on other organs. Furthermore, the infused stem cells migrated to the spleen and liver, not the submandibular gland. Stem cells directed T cells towards Treg cells and suppressed Th1 and Tfh cells in spleen lymphocytes. CONCLUSION: Stem cellsâ fromâ exfoliatedâ deciduous âteeth alleviate the hyposalivation caused by SS via decreasing the inflammatory cytokines, regulating the inflammatory microenvironment and decreasing the apoptosis and autophagy. The stem cells regulated in T-cell differentiation are involved in the immunomodulatory effects.
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Transplante de Células-Tronco Mesenquimais , Síndrome de Sjogren/complicações , Xerostomia/etiologia , Animais , Diabetes Mellitus Experimental , Camundongos , Camundongos Endogâmicos NOD , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Síndrome de Sjogren/terapia , Células-Tronco , Glândula Submandibular , Dente DecíduoRESUMO
Circular RNAs(circRNA) are recently demonstrated to have a close relationship with tumors.To investigate the role of circular RNA in the pathogenesis of salivary adenoid cystic carcinoma(SACC), ten SACC tissues and paired normal submandibular gland(SMG) tissues were collected as the tumor group and the control group. Total RNA was extracted and then measured using ceRNA microarray (including mRNA, lncRNA, and circRNA) and miRNA microarray. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis were performed in order to investigate the function of the differential expressing genes. The ceRNA regulatory network was constructed to find the core circRNAs. Then the role of circRNA on proliferation was examined in the SACC cell line SACC-83 using CCK-8,qRT-PCR and western blotting, and its roles on migration and invasion were examined using wound healing assay and transwell assay. The results of the microarrays showed that 3792 mRNAs, 7649 lncRNAs, 11553 circRNAs, and 132 miRNAs expressed differentially. The ceRNA regulatory network analysis showed that hsa_circ_0059655 and other 14circRNAs derived from PYGB target on several similar genes by miR-338-3p.Among the 15 circRNAs derived from PYGB, hsa_circ_0059655has the most relationships in the ceRNA network. Furthermore, after hsa_circ_0059655 was knocked down in SACC-83 cells, the expression of hsa-miR-338-3p was up-regulated while CCND1was down-regulated. The proliferation, migration, and invasion of SACC-83 cells also decreased after hsa_circ_0059655 knock-downed.Taken together, the circRNAs derived from PYGB may regulate the tumorigenesis and development of SACC through competing with miR-338-3p.
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Carcinoma Adenoide Cístico/genética , MicroRNAs/metabolismo , RNA/genética , Neoplasias das Glândulas Salivares/genética , Sítios de Ligação/genética , Carcinoma Adenoide Cístico/patologia , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Ontologia Genética , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , Invasividade Neoplásica , RNA/metabolismo , RNA Circular , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Neoplasias das Glândulas Salivares/patologiaRESUMO
Chronic Obstructive Pulmonary Disease (COPD) is a global health concern. Mind-body exercises like Tai Chi and Yoga are suggested as non-pharmacological interventions for COPD management. This meta-analysis evaluates mind-body exercises' impact on lung function and exercise capacity in stable COPD patients, aiming to assess their effectiveness in rehabilitation. A systematic search across various databases identified relevant randomized controlled trials until April 2024. Primary outcomes included lung function tests (FEV1, FVC, FEV1/FVC, FEV1%) and Six-Minute Walk Test (6MWT) results. The Standardized Mean Difference (SMD) measured intervention effects. Fifteen studies with 1047 participants were analyzed. Mind-body exercises significantly improved FEV1 (SMD = 0.87), FEV1/FVC (SMD = 0.19), FEV1% (SMD = 0.43), and 6MWT (SMD = 1.21) compared to standard care. Sensitivity and subgroup analyses confirmed result stability despite some heterogeneity.In conclusion, Mind-body exercises enhance lung function and exercise capacity in stable COPD patients. Integrating them into comprehensive rehabilitation programs is advisable. Further research should explore the specific impacts of different exercise types and intensities.
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Doença Pulmonar Obstrutiva Crônica , Ensaios Clínicos Controlados Aleatórios como Assunto , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Humanos , Tolerância ao Exercício/fisiologia , Pulmão/fisiopatologia , Terapias Mente-Corpo/métodos , Testes de Função Respiratória , Tai Chi Chuan/métodos , Terapia por Exercício/métodos , YogaRESUMO
Background: Tai Chi is an excellent traditional Chinese physical fitness exercise, and its unique balancing movements are very important for improving human balance. In this study, the two most representative Tai Chi balance movements, "knee lift balance" and "leg stirrup balance", were selected to establish the lower limb bone muscle model of Tai Chi balance movements by using computer simulation modeling technology, aiming to analyze the characteristics of the lower limb movement mechanisms of typical balance movements, to provide a quantitative theoretical basis for improving the scientific level of Tai Chi. Method: A total of 16 subjects were recruited for this study. the BTS three-dimensional motion capture system and three-dimensional force platform were used for motion data acquisition, the physiological electromyographic signals were collected using BTS surface electromyography, and the lower limb bone muscle model of Tai Chi balance movements was established by AnyBody human simulation. Result: In the knee lift balancing movement, the balance leg hip abduction/adduction angle, hip flexion/extension moment, and the strength of the rectus femoris muscle, biceps femoris short capitis, and iliacus muscle of the amateur group was significantly smaller than that of the professional group (P < 0.01). In the leg stirrup balance movement, the knee flexion/extension angle of the balancing leg in the amateur group was significantly greater than that in the professional group (P < 0.01), and the hip flexion/extension angle, hip inversion/abduction angle, knee flexion/extension moment, hip flexion/extension moment, the strength iliacus, gluteus maximus, and obturator internus were significantly smaller than those in the professional group (P < 0.01). The integral EMG of the biceps femoris of the support leg in the amateur group was significantly smaller than that of the professional group (P < 0.01). The integral EMG of the lateral femoral muscle of the balance leg was significantly smaller than that of the professional group (P < 0.01). Conclusion: In this study, we found that the balancing leg of the balancing movement has a larger hip joint angle, the stirrup balancing knee joint angle is smaller, and the hip and knee joint moments are larger. This is related to joint activity and muscle activation, and amateurs should pay attention to increasing the range of motion of the hip joint and decreasing the range of motion of the knee joint when practicing to better stimulate exercise of the lower limb joints. In addition, the practice of balancing movements should strengthen the iliacus muscle, which plays an important role in maintaining the stable balance of the lower limbs, and strengthen the knee flexor and extensor muscles and hip adductor/abductor muscles of the balancing leg, thus promoting the stability of the balancing leg movements.
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Tai Chi Chuan , Humanos , Estudos Transversais , Simulação por Computador , Músculo Esquelético/fisiologia , NádegasRESUMO
Lymphocyte-activation gene 3 (LAG3) is a highly anticipated immune checkpoint in the context of cancer, exerting regulatory control over immune cell proliferation and function to reinforce the advancement of cancers. However, the comprehensive functional analysis of LAG3 across various cancer types remains undisclosed; thus, this study aims to investigate the pan-cancer expression profile of LAG3. We have investigated the expression profile, prognostic significance, and genetic alterations of LAG3 in various cancers while elucidating its characteristic in immune response regulation. Our findings demonstrated that elevated LAG3 expression is significantly associated with favorable prognosis in patients with cutaneous melanoma (SKCM), and it may be a potential biomarker for SKCM. Furthermore, multiple immune algorithms have highlighted the important regulatory role of LAG3 for the tumor-infiltrating immune cells including CD8 + T cells, B cells, dendritic cells (DCs), macrophages, and natural killer (NK) cells. We also examined the distribution of LAG3 at the single-cell level and explored its functional significance. A comprehensive and systematic analysis of LAG3 would facilitate a comprehensive evaluation of LAG3 in cancer biology and provide valuable insights for cancer management.
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Melanoma , Neoplasias Cutâneas , Humanos , Prognóstico , Antígenos CD/metabolismo , Melanoma/genética , Melanoma/terapia , Multiômica , Proteína do Gene 3 de Ativação de Linfócitos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , ImunoterapiaRESUMO
The positive impact of mind-body movement therapy on mental health has been confirmed, but the current effect of various mind-body movement-specific therapies on improving the negative psychology of college students is controversial. This study compared the effects of six mind-body exercise (MBE) therapies on improving negative psychological symptoms in college students. The study found that Tai Chi (standardized mean difference [SMD] = -0.87, 95% confidence interval [CI] (-1.59, -0.15), p < 0.05), yoga (SMD = -0.95, 95% CI (-1.74, -0.15), p < 0.05), Yi Jin Jing (SMD = -1.15, 95% CI (-2.36, -0.05), p=<0.05), Five Animal Play (SMD = -1.1, 95% CI (-2.09, -0.02), p < 0.05), and Qigong Meditation (SMD = -1.31, 95% CI (-2.2, -0.4), p < 0.05) improved depressive symptoms in college students (p < 0.05). Tai Chi (SMD = -7.18, 95% CI (-13.18, -1.17), p = 0.019), yoga (SMD = -6.8, 95% CI (-11.79, -1.81), p = 0.008), and Yi Jin Jing (SMD = -9.21, 95% CI (-17.55, -0.87), p = 0.03) improved college students' anxiety symptoms. It shows that the six MBE therapies are effective in improving anxiety and depression in college students.
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Developmental coordination disorder (DCD) is a motor development disorder that affects an individual's growth and development, and may persist throughout life. It is not caused by intellectual or physical disability. Studies have suggested DCD often occurs in childhood, resulting in a series of abnormal manifestations that hinder children's normal development; cohort studies suggest a higher incidence in boys than in girls. Early diagnosis and appropriate interventions can help relieve symptoms. Unfortunately, the relevant research still needs to be further developed. In this paper, we first start from the definition of DCD, systematically investigate the relevant research papers in the past decades and summarize the current research hotspots and research trends in this field. After summarizing, it is found that this research field has attracted more researchers to join, the number of papers published has increased year by year and has become a hot spot in multidisciplinary research, such as education, psychology, sports rehabilitation, neurobiology, and neuroimaging. The continuous development of the correlation between perinatal factors and DCD, various omics studies, and neuroimaging methods also brings new perspectives and working targets to DCD research. DCD-related research will continue to deepen along the research direction of multivariate, multidimensional, and multimodal.
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BACKGROUND: Sjögren's syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. The treatment is still challenging. This study aimed to explore the therapeutic role and mechanism of exosomes obtained from the supernatant of stem cells derived from human exfoliated deciduous teeth (SHED-exos) in sialadenitis caused by SS. METHODS: SHED-exos were administered to the submandibular glands (SMGs) of 14-week-old non-obese diabetic (NOD) mice, an animal model of the clinical phase of SS, by local injection or intraductal infusion. The saliva flow rate was measured after pilocarpine intraperitoneal injection in 21-week-old NOD mice. Protein expression was examined by western blot analysis. Exosomal microRNA (miRNAs) were identified by microarray analysis. Paracellular permeability was evaluated by transepithelial electrical resistance measurement. RESULTS: SHED-exos were injected into the SMG of NOD mice and increased saliva secretion. The injected SHED-exos were taken up by glandular epithelial cells, and further increased paracellular permeability mediated by zonula occluden-1 (ZO-1). A total of 180 exosomal miRNAs were identified from SHED-exos, and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway might play an important role. SHED-exos treatment down-regulated phospho-Akt (p-Akt)/Akt, phospho-glycogen synthase kinase 3ß (p-GSK-3ß)/GSK-3ß, and Slug expressions and up-regulated ZO-1 expression in SMGs and SMG-C6 cells. Both the increased ZO-1 expression and paracellular permeability induced by SHED-exos were abolished by insulin-like growth factor 1, a PI3K agonist. Slug bound to the ZO-1 promoter and suppressed its expression. For safer and more effective clinical application, SHED-exos were intraductally infused into the SMGs of NOD mice, and saliva secretion was increased and accompanied by decreased levels of p-Akt/Akt, p-GSK-3ß/GSK-3ß, and Slug and increased ZO-1 expression. CONCLUSION: Local application of SHED-exos in SMGs can ameliorate Sjögren syndrome-induced hyposalivation by increasing the paracellular permeability of glandular epithelial cells through Akt/GSK-3ß/Slug pathway-mediated ZO-1 expression.
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Exossomos , MicroRNAs , Síndrome de Sjogren , Xerostomia , Camundongos , Animais , Humanos , Síndrome de Sjogren/terapia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Junções Íntimas/metabolismo , Glicogênio Sintase Quinase 3 beta , Camundongos Endogâmicos NOD , Fosfatidilinositol 3-Quinases/metabolismo , Exossomos/metabolismo , Fosfatidilinositol 3-Quinase , MicroRNAs/genéticaRESUMO
It explores the roles of self-efficacy and self-control in physical activity and Internet addiction. And it further provides a theoretical basis for the treatment and improvement of Internet addiction among college students. This study employs the whole group sampling method. The questionnaire was conducted on 855 college students from five universities in three provinces using the Physical Activity Level Scale, the General Self-Efficacy Scale, the Self-Control Scale, and the Chinese Internet Addiction Scale (IAS). The analyses yielded three main findings. (1) A large amount of physical activity was helpful in reducing the symptoms of Internet addiction and the problematic status of each dimension among college students. (2) A large or moderate amount of physical activity was helpful in enhancing college students' self-efficacy. Besides, a large amount of physical activity was likely to enhance college students' self-control. (3) The condition of physical activity not only directly has the negative correlation with college students' Internet addiction but also influences college students' Internet addiction through two indirect ways: the mediating role of self-control and the chain mediating role of self-efficacy and self-control. These conclusions provide a deeper understanding of the protective factors of Internet addiction among Chinese college students.
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Background: Taijiquan, as a physical and mental exercise, can improve the negative psychology of college students. However, it is still controversial, and the optimal exercise dose of taijiquan to interfere with negative psychology has not been evaluated. Objective: This study is aimed at systematically evaluating the effect of taijiquan therapy on improving negative psychological symptoms of college students and its optimal intervention dose. Methods: Search databases such as Web of Science, Embase, PubMed, CNKI, WFSD, etc. Collect high-quality relevant RCT studies. After screening, extracting, coding and counting the data, a META analysis is done through Review Manage 5.3 and Stata 15.0 software. PICOS established the eligibility criteria to select the studies as follows: (i) population - non-clinical of college students; (ii) intervention - taijiquan intervention; (iii) comparison - taijiquan intervention group and regular physical activity group; (iv) outcomes - depression, anxiety; and (v) study design - randomized controlled trial. Results: A total of 12 articles and 1,000 samples were included. All of the participants are college students. Taijiquan therapy can significantly reduce the depression and anxiety symptoms of college students [SMD = -0.53, 95% CI (-0.82, -0.23)], [SMD = -0.49, 95% CI (-0.90, -0.09)], with statistical significance (P < 0.05). Subgroup analysis shows that: there is a precise focus on depression and anxiety symptoms. The intervention period is more than 12 weeks, and the best effect appears when people practice 3 times a week. The best single intervention time for depression symptoms is 60 min, and for anxiety symptoms 80-90 min. It is found that taijiquan combined with mindfulness intervention can significantly reduce negative psychological symptoms like depression and anxiety of college students than single taijiquan intervention. Funnel plot combined with sensitivity analysis, Begg, Egger test showed no publication bias. Conclusion: Taijiquan intervention can effectively improve the negative psychological symptoms of college students, and it has great promotion value in colleges and universities. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022314071.
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Tai Chi Chuan , Humanos , Depressão/terapia , Estudantes/psicologia , Ansiedade/terapia , Transtornos de AnsiedadeRESUMO
High-strength 7075 aluminum alloy is widely used in the aerospace industry. The forming performance of 7075 aluminum alloy is poor at room temperature. Therefore, hot forming is mainly adopted. Electromagnetic forming is a high-speed forming technology that can significantly improve the forming limit of difficult-to-deform materials. However, there are few studies on electromagnetic hot forming of 7075-T6 aluminum alloy. In this study, the deformation behavior of 7075-T6 aluminum alloy in the temperature range of 25 °C to 400 °C was investigated. As the temperature increased, the sheet forming height first decreased, then increased. When the forming temperature is between 200 °C and 300 °C, η phase coarsening leads to a decrease in stress and hardness of the material. When the forming temperature is between 300 °C and 400 °C, continuous dynamic recrystallization of 7075 aluminum alloy occurs, resulting in grain refinement and an increase in stress and hardness. The results of numerical simulations and experiments all show that the forming height and deformation uniformity of the sheet metal are optimal at 400 °C, compared to 200 °C.
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Cell-free based therapy is an effective strategy in regenerative medicine as it avoids controversial issues, such as immunomodulation and stability. Recently, exosomes have been explored as a favorable substitution for stem cell therapy as they exhibit multiple advantages, such as the ability to be endocytosed and innate biocompatibility. This study aimed to investigate the effects of stem cells from human exfoliated deciduous teeth (SHED)-derived exosomes (SHED-Exo) on bone marrow stromal cells (BMSCs) osteogenesis and bone recovery. SHED-Exo were isolated, characterized, and applied to the bone loss area caused by periodontitis in a mouse model. We found that the injection of SHED-Exo restored bone loss to the same extent as original stem cells. Without affecting BMSCs proliferation, SHED-Exo mildly inhibited apoptosis. Moreover, SHED-Exo specifically promoted BMSCs osteogenesis and inhibited adipogenesis compared with SHED-derived conditioned medium. The expression of osteogenic marker genes, alkaline phosphatase activity, and Alizarin Red S staining of BMSCs was significantly increased by co-culturing with SHED-Exo. Moreover, Western blot analysis showed that Runx2, a key transcriptional factor in osteogenic differentiation, and p-Smad5 were upregulated upon SHED-Exo stimulation. Expression of the adipogenic marker PPARγ and the amount of lipid droplets decreased when exosomes were present. Low doses of exosomes inhibited the expression of the inflammatory cytokines IL-6 and TNF-α. In conclusion, SHED-Exo directly promoted BMSCs osteogenesis, differentiation, and bone formation. Therefore, exosomes have the potential to be utilized in the treatment of periodontitis and other bone diseases.
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Reabsorção Óssea/terapia , Exossomos/fisiologia , Células-Tronco Mesenquimais/fisiologia , Osteogênese/fisiologia , Dente Decíduo/fisiologia , Adipogenia/fisiologia , Fosfatase Alcalina/metabolismo , Animais , Biomarcadores/metabolismo , Reabsorção Óssea/metabolismo , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Exossomos/metabolismo , Regulação da Expressão Gênica/fisiologia , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Células-Tronco/metabolismo , Células-Tronco/fisiologia , Dente Decíduo/metabolismoRESUMO
Lung metastasis is a major factor affecting long-term survival in patients with adenoid cystic carcinoma. Here, we showed that the long noncoding RNA (lncRNA) MRPL23 antisense RNA 1 (MRPL23-AS1) was highly expressed and correlated with lung metastasis and overall survival in patients with salivary adenoid cystic carcinoma (SACC). MRPL23-AS1 positively regulated epithelial-mesenchymal transition by forming an RNA-protein complex with enhancer of zeste homolog 2 (EZH2). MRPL23-AS1 increased the binding of EZH2 and H3K27me3 on the E-cadherin promoter region. Moreover, MRPL23-AS1 levels were higher in exosomes isolated from the blood plasma of patients with SACC, and exosomal MRPL23-AS1 affected pulmonary microvascular endothelial cells in an "exosomecrine" manner. MRPL23-AS1-enriched exosomes increased microvascular permeability and facilitated the metastasis of SACC in vivo. Collectively, these findings highlight a molecular mechanism of lung metastasis in SACC. MRPL23-AS1 may represent a biomarker and target for clinical intervention to control this intractable disease. SIGNIFICANCE: This study identifies a novel metastasis-promoting lncRNA MRPL23-AS1, which mediates the transcriptional silencing of E-cadherin through forming an RNA-protein complex with EZH2.
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Carcinoma Adenoide Cístico/genética , Neoplasias Pulmonares/genética , RNA Antissenso/genética , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética , Proteínas Ribossômicas/genética , Neoplasias das Glândulas Salivares/genética , Animais , Antígenos CD/biossíntese , Antígenos CD/genética , Caderinas/biossíntese , Caderinas/genética , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Exoma , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , RNA Antissenso/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Ribossômicas/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Microambiente Tumoral , Regulação para CimaRESUMO
Salivary adenoid cystic carcinoma (SACC) exhibits slow continuous growth, frequent local recurrences and a high incidence of blood metastasis, with advanced lung metastasis frequently occurring and being among the primary causes of mortality. MicroRNAs (miR) serve a significant role in the initiation and development of cancer and may be tumourspecific molecular targets. However, the role of miR103a3p in SACC remains largely unknown. In the present study, the expression levels of miR103a3p and tumour protein D52 (TPD52) were detected by reverse transcriptionquantitative PCR. In addition, woundhealing assays, Transwell assays and mouse models of lung metastasis were used to investigate the biological functions exerted by miR103a3p. The present results suggested that miR103a3p expression was significantly upregulated in SACC samples. Gainoffunction and lossoffunction studies in SACC cells demonstrated that miR103a3p acted as an oncogene by promoting tumour cell migration in vitro and lung metastasis in vivo. Dualluciferase reporter gene assays indicated that miR103a3p exerted its regulatory functions by binding to the 3' untranslated region of TPD52 mRNA. TPD52 overexpression rescued the effect of miR103a3p on promoting SACC cell migration, suggesting that miR103a3p acted as an oncogene to promote cancer metastasis by directly targeting TPD52. Thus, the newly identified miR103a3p/TPD52 axis contributes to the understanding of SACC pathogenesis, providing insights into the identification of novel biomarkers or potential therapeutic targets in SACC.
Assuntos
Carcinoma Adenoide Cístico/genética , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , Proteínas de Neoplasias/genética , Neoplasias das Glândulas Salivares/genética , Adulto , Idoso , Animais , Carcinoma Adenoide Cístico/secundário , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pulmão/patologia , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Cultura Primária de Células , Neoplasias das Glândulas Salivares/patologia , Glândula Submandibular/patologia , Análise Serial de Tecidos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The coil is the most important component in electromagnetic forming. Two important questions in electromagnetic forming are how to obtain the desired magnetic force distribution on the sheet and increase the service life of the coil. A uniform pressure coil is widely used in sheet embossing, bulging, and welding. However, the coil is easy to break, and the manufacturing process is complex. In this paper, a new uniform-pressure coil with a planar structure was designed. A three-dimensional (3D) finite element model was established to analyze the effect of the main process parameters on magnetic force distribution. By comparing the experimental results, it was found that the simulation results have a higher analysis precision. Based on the simulation results, the resistivity of the die, spacing between the left and right parts of the coil, relative position between coil and sheet, and sheet width significantly affect the distribution of magnetic force. Compared with the structure and magnetic force on a traditional uniform pressure coil, the planar uniform pressure coil can produce a uniform magnetic force distribution on the sheet, reduce the manufacturing difficulty, reduce manufacturing cost, and enhance the service life for the coil.
RESUMO
The incidence of recurrent t(6;9) translocation of the MYB protooncogene to NFIB (the gene that encodes nuclear factor 1 Btype) in adenoid cystic carcinoma (ACC) tumour tissues is high. However, MYB [the gene that encodes transcriptional activator Myb (MYB)] overexpression is more common, indicating that MYB serves a key role in ACC. The current study aimed to investigate the role of MYB in salivary (S)ACC growth and metastasis. A total of 50 freshfrozen SACC tissues and 41 freshfrozen normal submandibular gland (SMG) tissues were collected to measure MYB mRNA expression, and to analyse the associations between MYB and epithelialmesenchymal transition (EMT) markers. Compared with normal SMG tissue, SACC tissues demonstrated significantly increased MYB expression, with a high expression rate of 90%. Interestingly, MYB tended to be negatively correlated with CDH1 [the gene that encodes cadherin1 (Ecadherin)] and positively correlated with VIM (the gene that encodes vimentin), suggesting that MYB is associated with SACC metastasis. To explore the role of MYB in SACC, the authors stably overexpressed and knocked down MYB in SACC cells. The authors of the current study demonstrated that MYB overexpression promoted SACC cell proliferation, migration and invasion, whereas its knockdown inhibited these activities. Additionally, when MYB was overexpressed, CDH1 expression was downregulated, and CDH2 (the gene that encodes cadherin2), VIM and ACTA2 (the gene that encodes actin, aortic smooth muscle) expression was upregulated. Then, the effect of MYB on lung tumour metastasis was investigated in vivo in nonobese diabetic/severe combined immunodeficiency mice. MYB overexpressing and control cells were injected into the mice through the tail vein. The results revealed that MYB promoted SACC lung metastasis. Collectively, these results demonstrated that MYB is aberrantly overexpressed in SACC tissues, and promotes SACC cell proliferation and metastasis, indicating that MYB may be a novel therapeutic target for SACC.
Assuntos
Carcinoma Adenoide Cístico/patologia , Perfilação da Expressão Gênica/métodos , Neoplasias Pulmonares/secundário , Proteínas Proto-Oncogênicas c-myb/genética , Neoplasias das Glândulas Salivares/patologia , Regulação para Cima , Animais , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Proteínas Proto-Oncogênicas c-myb/metabolismo , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismoRESUMO
Adiponectin functions as a promoter of saliva secretion in rat submandibular gland via activation of adenosine monophosphate-activated protein kinase (AMPK) and increased paracellular permeability. Ca2+ mobilization is the primary signal for fluid secretion in salivary acinar cells. However, whether intracellular Ca2+ mobilization is involved in adiponectin-induced salivary secretion is unknown. Here, we found that full-length adiponectin (fAd) increased intracellular Ca2+ and saliva secretion in submandibular glands. Pre-perfusion with ethylene glycol-bis (2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) combined with thapsigargin (TG), an endoplasmic reticulum Ca2+-ATPase inhibitor, abolished fAd-induced salivary secretion, AMPK phosphorylation, and enlarged tight junction (TJ) width. Furthermore, in cultured SMG-C6 cells, co-pretreatment with EGTA and TG suppressed fAd-decreased transepithelial electrical resistance and increased 4-kDa FITC-dextran flux responses. Moreover, fAd increased phosphorylation of calcium/calmodulin-dependent protein kinase (CaMKKß), a major kinase that is activated by elevated levels of intracellular Ca2+, but not liver kinase B1 phosphorylation. Pre-perfusion of the isolated gland with STO-609, an inhibitor of CaMKKß, abolished fAd-induced salivary secretion, AMPK activation, and enlarged TJ width. CaMKKß shRNA suppressed, whereas CaMKKß re-expression rescued fAd-increased paracellular permeability. Taken together, these results indicate that adiponectin induced Ca2+ modulation in rat submandibular gland acinar cells. Ca2+-CaMKKß pathway is required for adiponectin-induced secretion through mediating AMPK activation and increase in paracellular permeability in rat submandibular glands.