Different Dual-Task Paradigm Reduce Postural Control Ability and Dynamic Stability of Healthy Young Adults during Stair Descent.

Objective: This study aimed to compare the impacts of different dual-task paradigms on the postural control ability and dynamic stability of the youth during stair descent. Method: Twenty young adults without regular exercise habits were randomly recruited to perform stair descent tasks with three different paradigms: single-task, cognitive dual-task, and manual dual-task. Kinematic and dynamic data were collected using an 8 Vicon motion analysis system and a Kistler force plate to evaluate postural control ability and dynamic stability during stair descent. Results: The variation trends of lower limb joint moment were similar under the three task models. Compared with a single-task, both dual-task paradigms significantly reduced the mechanical parameters and dynamic stability during stair descent. Conclusion: The dual-task paradigm increases the risk of stair-related falls. Both cognitive and manual tasks have similar impacts on postural control ability and dynamic stability during stair walking. It is recommended that people avoid performing dual tasks during stair descent.

Quality in balance sensitivity through martial arts applied to children / Qualidade na sensibilidade do equilíbrio pelas artes marciais aplicadas às crianças / Calidad en la sensibilidad del equilibrio a través de las artes marciales aplicadas a los niños

ABSTRACT Introduction: Martial arts training focuses on science, methodology, and practice. Martial arts are a symbol of physical fitness. The academic analysis of the influence of martial arts training on children's physical health is of great importance for promoting traditional Chinese culture. It can enrich sports intervention programs to improve children's physical health. Objective: Analyze the effect of sensory quality training on martial arts balance training in children. Methods: Children aged 8 to 12 years were selected as research subjects. After repeated deliberations, a children's martial arts set was designed and implemented. The pilot project analyzes the importance of sensory quality in the essential stage of children's martial arts training. Results: After the experiment, there was a significant difference in balance quality in the experimental group (p<0.01). After the experiment, the difference in balance sense between the experimental and control groups was significant (p<0.01). Conclusion: In the basic training phase of children's martial arts, coaches should require athletes to master basic martial arts skills more comprehensively. All movement combinations in martial arts require comprehensive physical fitness and balance sensitivity, including speed, flexibility, and coordination. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O treinamento em artes marciais concentra-se na ciência, na metodologia e na prática. As artes marciais são um símbolo de aptidão física. A análise acadêmica da influência do treinamento de artes marciais na saúde física das crianças é de grande importância para a promoção da cultura tradicional chinesa e pode enriquecer os programas de intervenção esportiva para melhorar a saúde física infantil. Objetivo: Analisar o efeito do treinamento de qualidade sensitiva no treinamento de equilíbrio das artes marciais em crianças. Métodos: Selecionou-se crianças de 8 a 12 anos como objetos de pesquisa. Após repetidas deliberações, foi elaborado e implementado um conjunto de artes marciais infantis. O projeto piloto analisa a importância da qualidade sensitiva na etapa essencial do treinamento das artes marciais infantis. Resultados: Após o experimento, houve uma diferença significativa na qualidade do equilíbrio no grupo experimental (p<0,01). Após o experimento, a diferença no sentido de equilíbrio entre os grupos experimental e de controle foi significativa (p<0,01). Conclusão: Na fase de treinamento básico das artes marciais infantis, os treinadores devem exigir que os atletas dominem as habilidades básicas das artes marciais de forma mais abrangente. Todas as combinações de movimentos nas artes marciais exigem aptidão física e sensibilidade de equilíbrio abrangentes, incluindo velocidade, flexibilidade e coordenação. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El entrenamiento de las artes marciales se centra en la ciencia, la metodología y la práctica. Las artes marciales son un símbolo de la condición física. El análisis académico de la influencia del entrenamiento de artes marciales en la salud física de los niños es de gran importancia para la promoción de la cultura tradicional china y puede enriquecer los programas de intervención deportiva para mejorar la salud física de los niños. Objetivo: Analizar el efecto del entrenamiento de la calidad sensorial en el entrenamiento del equilibrio en artes marciales en niños. Métodos: Se seleccionaron niños de 8 a 12 años como sujetos de la investigación. Tras repetidas deliberaciones, se diseñó y puso en marcha un conjunto de artes marciales para niños. El proyecto piloto analiza la importancia de la calidad sensorial en la etapa esencial del entrenamiento de artes marciales de los niños. Resultados: Después del experimento, hubo una diferencia significativa en la calidad del equilibrio en el grupo experimental (p<0,01). Tras el experimento, la diferencia en el sentido del equilibrio entre los grupos experimental y de control fue significativa (p<0,01). Conclusión: En la fase de formación básica de las artes marciales infantiles, los entrenadores deberían exigir a los deportistas un dominio más completo de las habilidades marciales básicas. Todas las combinaciones de movimientos en las artes marciales requieren una amplia aptitud física y sensibilidad al equilibrio, incluidas la velocidad, la flexibilidad y la coordinación. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Wushu Routine Movement and Diagnosis Based on Deep Learning and Symmetric Difference Algorithm.

Wushu is one of the traditional cultural symbols of the Chinese nation. It is also one of the most popular sports activities among the people. With the attention and love of contemporary people to sports activities, Wushu is also constantly developing and innovating. The requirements for professional martial arts routines of martial arts athletes are higher than ever. The development of martial arts has also made martial arts competitions more intense, and often a small detail of martial arts movements can determine the success or failure of the competition. Therefore, various Wushu teams pay more and more attention to the analysis and diagnosis of Wushu routines. It ensures that coaches and athletes can obtain more quantitative indicators of technical movement training. The analysis and diagnosis of martial arts routines are inseparable from the support of reliable science and technology and related algorithms. This article aims to study the analysis and diagnosis of martial arts routines based on deep learning and symmetric difference algorithm. It combines deep learning and symmetric difference algorithm to analyze and diagnose martial arts routines. The article concludes that the level of martial arts routines of martial arts athletes has the greatest influence on their martial arts competition performance, and its comprehensive influence index is as high as 4.3.

MiR­30e and miR­92a are related to atherosclerosis by targeting ABCA1.

Atherosclerosis is a chronic disease characterized by the accumulation of lipids and fibrous elements in the large arteries, which is the principal cause of coronary artery disease. Dysregulated exosomal microRNA (miRNA) levels in serum have been identified in patients with various diseases, including CAD. In the present study, nine candidate miRNAs were detected in the plasma exosome from 42 patients with coronary atherosclerosis, and a higher expression of miR­30e and miR­92a was identified in patients. Following bioinformatics analysis and confirmation through immunoblotting, it was demonstrated that ATP binding cassette (ABC)A1 is a direct target of miR­30e, and miR­92a. Furthermore, a negative correlation was identified between plasma miR­30e and ABCA1, or miR­30e and cholesterol. Thus, the results of the present study suggest that the miR­30e level in exosomes from serum may have the potential to be a novel diagnostic biomarker for coronary atherosclerosis.

Reduction of PKCbetaII activity in smooth muscle cells attenuates acute arterial injury.

OBJECTIVE: The ubiquitous enzyme protein kinase C (PKC) has been linked to the pathogenesis of vascular injury, but the cell-specific and discrete functions of the betaII isoform have yet to be discovered in this setting. Our previous findings demonstrated significantly increased PKCbetaII in the membrane fraction of injured femoral arteries in wild type (WT) mice and revealed reduction of neointimal expansion in PKCbeta(-/-) mice after acute vascular injury. As PKCbeta(-/-) mice are globally devoid of PKCbeta, we established novel transgenic (Tg) mice to test the hypothesis that the action of PKCbetaII specifically in smooth muscle cells (SMCs) mediates the formation of neointimal lesions in response to arterial injury. METHODS: Tg mice expressing SM22alpha promoter-targeted mouse carboxyl-terminal deletion mutant PKCbetaII were produced using standard techniques, subjected to femoral artery injury and compared with littermate controls. Smooth muscle cells (SMCs) were isolated from wild type (WT) and Tg mice and exposed to a prototypic stimulus, tumor necrosis factor (TNF)-alpha. Multiple strategies were employed in vivo and in vitro to examine the molecular mechanisms underlying the specific effects of SMC PKCbetaII in neointimal expansion. RESULTS: In vivo and in vitro analyses demonstrated that PKCbetaII activity in SMCs was critical for neointimal expansion in response to arterial injury, at least in part via regulation of ERK1/2, Egr-1 and induction of MMP-9. CONCLUSIONS: These data identify the SMC-specific regulatory role of PKCbetaII in neointimal expansion in response to acute arterial injury, and suggest that targeted inactivation of PKCbetaII may be beneficial in limiting restenosis via suppression of the neointima-mediating effects of Egr-1 and MMP-9.

Advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling and up-regulation of Egr-1 in hypoxic macrophages.

Receptor for advanced glycation end product (RAGE)-dependent signaling has been implicated in ischemia/reperfusion injury in the heart, lung, liver, and brain. Because macrophages contribute to vascular perturbation and tissue injury in hypoxic settings, we tested the hypothesis that RAGE regulates early growth response-1 (Egr-1) expression in hypoxia-exposed macrophages. Molecular analysis, including silencing of RAGE, or blockade of RAGE with sRAGE (the extracellular ligand-binding domain of RAGE), anti-RAGE IgG, or anti-AGE IgG in THP-1 cells, and genetic deletion of RAGE in peritoneal macrophages, revealed that hypoxia-induced up-regulation of Egr-1 is mediated by RAGE signaling. In addition, the observation of increased cellular release of RAGE ligand AGEs in hypoxic THP-1 cells suggests that recruitment of RAGE in hypoxia is stimulated by rapid production of RAGE ligands in this setting. Finally, we show that mDia-1, previously shown to interact with the RAGE cytoplasmic domain, is essential for hypoxia-stimulated regulation of Egr-1, at least in part through protein kinase C betaII, ERK1/2, and c-Jun NH(2)-terminal kinase signaling triggered by RAGE ligands. Our findings highlight a novel mechanism by which an extracellular signal initiated by RAGE ligand AGEs regulates Egr-1 in a manner requiring mDia-1.

RAGE-dependent signaling in microglia contributes to neuroinflammation, Abeta accumulation, and impaired learning/memory in a mouse model of Alzheimer's disease.

Microglia are critical for amyloid-beta peptide (Abeta)-mediated neuronal perturbation relevant to Alzheimer's disease (AD) pathogenesis. We demonstrate that overexpression of receptor for advanced glycation end products (RAGE) in imbroglio exaggerates neuroinflammation, as evidenced by increased proinflammatory mediator production, Abeta accumulation, impaired learning/memory, and neurotoxicity in an Abeta-rich environment. Transgenic (Tg) mice expressing human mutant APP (mAPP) in neurons and RAGE in microglia displayed enhanced IL-1beta and TNF-alpha production, increased infiltration of microglia and astrocytes, accumulation of Abeta, reduced acetylcholine esterase (AChE) activity, and accelerated deterioration of spatial learning/memory. Notably, introduction of a signal transduction-defective mutant RAGE (DN-RAGE) to microglia attenuates deterioration induced by Abeta. These findings indicate that RAGE signaling in microglia contributes to the pathogenesis of an inflammatory response that ultimately impairs neuronal function and directly affects amyloid accumulation. We conclude that blockade of microglial RAGE may have a beneficial effect on Abeta-mediated neuronal perturbation relevant to AD pathogenesis.-Fang, F., Lue, L.-F., Yan, S., Xu, H., Luddy, J. S., Chen, D., Walker, D. G., Stern, D. M., Yan, S., Schmidt, A. M., Chen, J. X., Yan, S. S. RAGE-dependent signaling in microglia contributes to neuroinflammation, Abeta accumulation, and impaired learning/memory in a mouse model of Alzheimer's disease.

Mice deficient in PKCbeta and apolipoprotein E display decreased atherosclerosis.

Endothelial activation is a central initiating event in atheroma formation. Evidence from our laboratory and others has demonstrated links between activation of early growth response-1 (Egr-1) and atherosclerosis and also has demonstrated that activated protein kinase C (PKC) betaII is a critical upstream regulator of Egr-1 in response to vascular stress. We tested the role of PKCbeta in regulating key events linked to atherosclerosis and show that the aortas of apoE(-/-) mice display an age-dependent increase in PKCbetaII antigen in membranous fractions vs. C57BL/6 animals with a approximately 2-fold increase at age 6 wk and a approximately 4.5-fold increase at age 24 wk. Consistent with important roles for PKCbeta in atherosclerosis, a significant decrease in atherosclerotic lesion area was evident in PKCbeta(-/-)/apoE(-/-) vs. apoE(-/-) mice by approximately 5-fold, in parallel with significantly reduced vascular transcripts for Egr-1 and matrix metalloproteinase (MMP)-2 antigen and activity vs. apoE(-/-) mice. Significant reduction in atherosclerosis of approximately 2-fold was observed in apoE(-/-) mice fed ruboxistaurin chow (PKCbeta inhibitor) vs. vehicle. In primary murine and human aortic endothelial cells, the PKCbeta-JNK mitogen-activated protein kinase pathway importantly contributes to oxLDL-mediated induction of MMP2 expression. Blockade of PKCbeta may be beneficial in mitigating endothelial perturbation and atherosclerosis.

Oxygen deprivation triggers upregulation of early growth response-1 by the receptor for advanced glycation end products.

Myocardial infarction, stroke, and venous thromboembolism are characterized by oxygen deprivation. In hypoxia, biological responses are activated that evoke tissue damage. Rapid activation of early growth response-1 in hypoxia upregulates fundamental inflammatory and prothrombotic stress genes. We probed the mechanisms mediating regulation of early growth response-1 and demonstrate that hypoxia stimulates brisk generation of advanced glycation end products (AGEs) by endothelial cells. Via AGE interaction with their chief signaling receptor, RAGE, membrane translocation of protein kinase C-betaII occurs, provoking phosphorylation of c-Jun NH(2)-terminal kinase and increased transcription of early growth response-1 and its downstream target genes. These findings identify RAGE as a master regulator of tissue stress elicited by hypoxia and highlight this receptor as a central therapeutic target to suppress the tissue injury-provoking effects of oxygen deprivation.

PKCbeta modulates ischemia-reperfusion injury in the heart.

Protein kinase C-betaII (PKCbetaII) is an important modulator of cellular stress responses. To test the hypothesis that PKCbetaII modulates the response to myocardial ischemia-reperfusion (I/R) injury, we subjected mice to occlusion and reperfusion of the left anterior descending coronary artery. Homozygous PKCbeta-null (PKCbeta(-/-)) and wild-type mice fed the PKCbeta inhibitor ruboxistaurin displayed significantly decreased infarct size and enhanced recovery of left ventricular (LV) function and reduced markers of cellular necrosis and serum creatine phosphokinase and lactate dehydrogenase levels compared with wild-type or vehicle-treated animals after 30 min of ischemia followed by 48 h of reperfusion. Our studies revealed that membrane translocation of PKCbetaII in LV tissue was sustained after I/R and that gene deletion or pharmacological blockade of PKCbeta protected ischemic myocardium. Homozygous deletion of PKCbeta significantly diminished phosphorylation of c-Jun NH(2)-terminal mitogen-activated protein kinase and expression of activated caspase-3 in LV tissue of mice subjected to I/R. These data implicate PKCbeta in I/R-mediated myocardial injury, at least in part via phosphorylation of JNK, and suggest that blockade of PKCbeta may represent a potent strategy to protect the vulnerable myocardium.

Host cell Ca2+ and protein kinase C regulate innate recognition of Toxoplasma gondii.

In healthy hosts, acute infection with the opportunistic pathogen Toxoplasma gondii is controlled by innate production of IL-12, a key cytokine crucial for the development of protective immunity. Previous work has established that the mitogen-activated protein kinases (MAPK), particularly p38 and ERK1/2, are important regulators of T. gondii-induced IL-12 synthesis. Here we report that host cell Ca(2+) is required for activation of MAPK by T. gondii, as well as LPS and CpG, and for parasite-induced synthesis of IL-12. In addition, pharmacological mobilization of Ca(2+) stores in macrophages treated with parasites or LPS enhanced MAPK phosphorylation initiated by these stimuli. Investigation of the upstream mechanism by which Ca(2+) regulates MAPK activation revealed that T. gondii induced acute activation of conventional, Ca(2+)-dependent PKCalpha and PKCbeta, which are required for infection-induced MAPK activation and production of IL-12. Despite these findings, neither acute parasite infection nor LPS initiated a measurable Ca(2+) response in macrophages, suggesting that low levels of Ca(2+) are permissive for initiation of pro-inflammatory signaling. Together these data identify host cell Ca(2+) and PKC as crucial regulators of the innate immune response to microbial stimuli, including T. gondii.

Protein kinase C beta/early growth response-1 pathway: a key player in ischemia, atherosclerosis, and restenosis.

Atherosclerosis, restenosis, and the consequences of ischemia are the major causes of morbidity and mortality worldwide. Elucidation of key contributing pathways in animal models of ischemia-reperfusion injury, atherosclerosis, and restenosis consequent to vascular injury may lead to great interest in determining if blocking these pathways could prevent vascular disease in human subjects. This review details the evidence that the protein kinase C (PKC) beta/early growth response-1 axis plays a central role in the response to both acute and chronic vascular stresses in animal models and also indicates the clinical implications of a specific inhibitor of PKCbeta, ruboxistaurin (LY333531).

Central role of PKCbeta in neointimal expansion triggered by acute arterial injury.

We tested the hypothesis that PKCbeta contributes to vascular smooth muscle cell (SMC) migration and proliferation; processes central to the pathogenesis of restenosis consequent to vascular injury. Homozygous PKCbeta null (-/-) mice or wild-type mice fed the PKCbeta inhibitor, ruboxistaurin, displayed significantly decreased neointimal expansion in response to acute femoral artery endothelial denudation injury compared with controls. In vivo and in vitro analyses demonstrated that PKCbetaII is critically linked to SMC activation, at least in part via regulation of ERK1/2 MAP kinase and early growth response-1. These data highlight novel roles for PKCbeta in the SMC response to acute arterial injury and suggest that blockade of PKCbeta may represent a therapeutic strategy to limit restenosis.

RAGE modulates peripheral nerve regeneration via recruitment of both inflammatory and axonal outgrowth pathways.

Axotomy of peripheral nerve stimulates events in multiple cell types that initiate a limited inflammatory response to axonal degeneration and simultaneous outgrowth of neurites into the distal segments after injury. We found that pharmacological blockade of RAGE impaired peripheral nerve regeneration in mice subjected to RAGE blockade and acute crush of the sciatic nerve. As our studies revealed that RAGE was expressed in axons and in infiltrating mononuclear phagocytes upon injury, we tested the role of RAGE in these distinct cell types on nerve regeneration. Transgenic mice expressing signal transduction-deficient RAGE in mononuclear phagocytes or peripheral neurons were generated and subjected to unilateral crush injury to the sciatic nerve. Transgenic mice displayed decreased functional and morphological recovery compared with littermate controls, as assessed by motor and sensory conduction velocities; and myelinated fiber density. In double transgenic mice expressing signal transduction deficient RAGE in both mononuclear phagocytes and peripheral neurons, regeneration was even further impaired, suggesting the critical interplay between RAGE-modulated inflammation and neurite outgrowth in nerve repair. These findings suggest that RAGE signaling in inflammatory cells and peripheral neurons plays an important role in plasticity of the peripheral nervous system.

PKCbeta regulates ischemia/reperfusion injury in the lung.

Activation of PKCbetaII is associated with the response to ischemia/reperfusion (I/R), though its role, either pathogenic or protective, has not been determined. In a murine model of single-lung I/R, evidence linking PKCbeta to maladaptive responses is shown in the following studies. Homozygous PKCbeta-null mice and WT mice fed the PKCbeta inhibitor ruboxistaurin subjected to I/R displayed increased survival compared with controls. In PKCbeta-null mice, phosphorylation of extracellular signal-regulated protein kinase-1 and -2 (ERK1/2), JNK, and p38 MAPK was suppressed in I/R. Expression of the immediate early gene, early growth response-1 (Egr-1), and its downstream target genes was significantly increased in WT mice in I/R, particularly in mononuclear phagocytes (MPs), whereas this expression was attenuated in PKCbeta-null mice or WT mice fed ruboxistaurin. In vitro, hypoxia/reoxygenation-mediated induction of Egr-1 in MPs was suppressed by inhibition of PKCbeta, ERK1/2, and JNK, but not by inhibition of p38 MAPK. These findings elucidate key roles for PKCbetaII activation in I/R by coordinated activation of MAPKs (ERK1/2, JNK) and Egr-1.

Early growth response-1 promotes atherogenesis: mice deficient in early growth response-1 and apolipoprotein E display decreased atherosclerosis and vascular inflammation.

Early growth response-1 (Egr-1) regulates expression of proinflammatory and procoagulant genes in acute cell stress. Experimental evidence suggested that Egr-1 transcripts were upregulated in human atherosclerotic plaques versus adjacent unaffected tissue. To test the impact of Egr-1 in chronic vascular stress, we examined its role in a murine model of atherosclerosis. Real-time PCR analysis of aortae retrieved from apoE-/- mice demonstrated increased Egr-1 transcripts in an age-dependent manner, compared with aortae retrieved from C57BL/6 control animals. Therefore, homozygous Egr-1-/- mice were bred into the apoE-/- background. Homozygous double-knockout mice (Egr-1-/-/apoE-/-) in the C57BL/6 background were maintained on normal chow diet. At age 14 and 24 weeks, atherosclerotic lesion area and complexity at the aortic root were strikingly decreased in mice deficient in both Egr-1 and apoE compared with mice deficient in apoE alone. In parallel, transcripts for genes regulating the inflammatory/prothrombotic response were diminished in Egr-1-/-/apoE-/- aortae versus apoE-/-. In vitro, oxidized low-density lipoprotein (OxLDL), a key factor inciting atherogenic mechanisms in the vasculature, upregulated Egr-1 expression in monocytes via the MEK-ERK1/2 pathway. We conclude that Egr-1 broadly regulates expression of molecules critically linked to atherogenesis and lesion progression.

RAGE and its ligands: a lasting memory in diabetic complications?

The complications of diabetes are myriad and represent a rising cause of morbidity and mortality, particularly in the Western world. The update of the Diabetes Control and Clinical Trials Group/Epidemiology of Diabetes Interventions and Complications Research Group (DCCT/EDIC) suggested that previous strict control of hyperglycaemia was associated with reduced carotid atherosclerosis compared to conventional treatment, even after levels of glycosylated haemoglobin between the two treatment groups became indistinguishable. These intriguing findings prompt the key question, why does the blood vessel 'remember'? This review focuses on the hypothesis that the ligand/RAGE axis contributes importantly to glycaemic 'memory'. Studies in rodent models of diabetes suggest that blockade or genetic modification of RAGE suppress diabetes-associated progression of atherosclerosis, exaggerated neointimal expansion consequent to acute arterial injury, and cardiac dysfunction. We propose that therapeutic RAGE blockade will intercept maladaptive diabetes-associated memory in the vessel wall and provide cardiovascular protection in diabetes.

Transcriptional control of cardiac allograft vasculopathy by early growth response gene-1 (Egr-1).

Expression of the zinc finger transcription factor early growth response gene-1 (Egr-1) is triggered rapidly after mechanical vascular injury or after a precipitous drop in ambient oxygen, whereupon it induces the expression of diverse gene families to elicit a pathological response. Initially characterized as an early response transcriptional activator, the role of Egr-1 in more chronic forms of vascular injury remains to be defined. Studies were designed to examine whether Egr-1 induction may serve as a causal link between early preservation injury and delayed vascular consequences, such as coronary allograft vasculopathy (CAV). The preservation and transplantation of heterotopic murine cardiac allografts strongly induce Egr-1 expression, leading to increased expression of its downstream target genes, such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and platelet-derived growth factor A chain. Expression of these Egr-1-inducible gene targets is virtually obliterated in homozygous Egr-1-null donor allografts, which also exhibit attenuated parenchymal rejection and reduced CAV as long as 60 days. Congruous data are observed by treating donor hearts with a phosphorothioate antisense oligodeoxyribonucleotide directed against Egr-1 before organ harvest, which blocks subsequent expression of Egr-1 mRNA and protein and suppresses the late development of CAV. These data indicate that Egr-1 induction represents a central effector mechanism in the development of chronic rejection characterized by CAV. Blocking the expression of this proximal transcription factor solely at the time of organ harvest elicits beneficial delayed consequences for the cardiac allograft.