Cortactin controls bone homeostasis through regulating the differentiation of osteoblasts and osteoclasts.

Cortactin (CTTN), a cytoskeletal protein and substrate of Src kinase, is implicated in tumor aggressiveness. However, its role in bone cell differentiation remains unknown. The current study revealed that CTTN was upregulated during osteoblast and adipocyte differentiation. Functional experiments demonstrated that CTTN promoted the in vitro differentiation of mesenchymal stem/progenitor cells into osteogenic and adipogenic lineages. Mechanistically, CTTN was able to stabilize the protein level of mechanistic target of rapamycin kinase (mTOR), leading to the activation of mTOR signaling. In-depth investigation revealed that CTTN could bind with casitas B lineage lymphoma-c (c-CBL) and counteract the function of c-CBL, a known E3 ubiquitin ligase responsible for the proteasomal degradation of mTOR. Silencing c-Cbl alleviated the impaired differentiation of osteoblasts and adipocytes caused by CTTN siRNA, while silencing mTOR mitigated the stimulation of osteoblast and adipocyte differentiation induced by CTTN overexpression. Notably, transplantation of CTTN-silenced bone marrow stromal cells (BMSCs) into the marrow of mice led to a reduction in trabecular bone mass, accompanied by a decrease in osteoblasts and an increase in osteoclasts. Furthermore, CTTN-silenced BMSCs expressed higher levels of receptor activator of nuclear factor κB ligand (RANKL) than control BMSCs did and promoted osteoclast differentiation when cocultured with bone marrow-derived osteoclast precursor cells. This study provides evidence that CTTN favors osteoblast differentiation by counteracting the c-CBL-induced degradation of mTOR and inhibits osteoclast differentiation by downregulating the expression of RANKL. It also suggests that maintaining an appropriate level of CTTN expression may be advantageous for maintaining bone homeostasis.

Psychological training of soccer players at competition level / Capacitação psicológica de jogadores de futebol a nível de competição / Capacitación psicológica de jugadores de fútbol a nivel de competición

ABSTRACT Introduction: Competitive sports compete for technology, tactics and physical fitness. There is also competition for the psychological quality of athletes. There is an intrinsic connection between athletes' mental state in competition and their psychological characteristics. Objective: Explore the influence of soccer players' psychological characteristics on the level of competition. Methods: This paper investigates 220 soccer players using a questionnaire. In this database, variance analysis, multiple comparisons, factor analysis and other statistical analysis methods were used to ascertain the psychological status of Chinese soccer players. Finally, the factors affecting the psychological characteristics of soccer players were analyzed. Results: There were differences in the psychological characteristics of soccer players at different positions and levels. Conclusion: There are specific variations in psychological status among different types of players. The factors that influence the anxiety level of soccer players are a multidimensional system. It contains both subjective and objective content. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Os esportes de competição disputam pela tecnologia, tática e aptidão física. Há também uma concorrência pela qualidade psicológica dos atletas. Existe uma conexão intrínseca entre o estado mental dos atletas na competição e suas características psicológicas. Objetivo: Explorar a influência das características psicológicas dos jogadores de futebol no nível da competição. Métodos: Este trabalho investiga 220 jogadores de futebol utilizando um questionário. Nesta base de dados, utilizou-se a análise de variações, comparações múltiplas, análise de fatores e outros métodos de análise estatística para verificar o estado psicológico dos jogadores de futebol chineses. Finalmente, foram analisados os fatores que afetam as características psicológicas dos jogadores de futebol. Resultados: Houve diferenças nas características psicológicas dos jogadores de futebol em diferentes posições e níveis. Conclusão: Existem variações específicas no estado psicológico entre diferentes tipos de jogadores. Os fatores que influenciam o nível de ansiedade dos jogadores de futebol são um sistema multidimensional. Ele contém tanto um conteúdo subjetivo quanto objetivo. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: En los deportes de competición se compite por la técnica, la táctica y la forma física. También hay una competencia por la calidad psicológica de los atletas. Existe una conexión intrínseca entre el estado mental de los deportistas en competición y sus características psicológicas. Objetivo: Explorar la influencia de las características psicológicas de los futbolistas en el nivel de competición. Métodos: Este trabajo investiga a 220 jugadores de fútbol mediante un cuestionario. En esta base de datos se utilizaron el análisis de la varianza, las comparaciones múltiples, el análisis factorial y otros métodos de análisis estadístico para determinar el estado psicológico de los futbolistas chinos. Por último, se analizaron los factores que afectan a las características psicológicas de los futbolistas. Resultados: Se observaron diferencias en las características psicológicas de los futbolistas de diferentes posiciones y niveles. Conclusión: Existen variaciones específicas en el estado psicológico entre los diferentes tipos de jugadores. Los factores que influyen en el nivel de ansiedad de los futbolistas constituyen un sistema multidimensional. Este posee un contenido tanto subjetivo como objetivo. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Integrating Network Pharmacology and Transcriptomic Strategies to Explore the Pharmacological Mechanism of Hydroxysafflor Yellow A in Delaying Liver Aging.

Aging affects the structure and function of the liver. Hydroxysafflor yellow A (HSYA) effectively improves liver aging (LA) in mice, but the potential mechanisms require further exploration. In this study, an integrated approach combining network pharmacology and transcriptomics was used to elucidate the potential mechanisms of HSYA delay of LA. The targets of HSYA were predicted using the PharmMapper, SwissTargetPrediction, and CTD databases, and the targets of LA were collected from the GeneCards database. An ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation of genes related to HSYA delay of LA were performed using the DAVID database, and Cytoscape software was used to construct an HSYA target pathway network. The BMKCloud platform was used to sequence mRNA from mouse liver tissue, screen differentially expressed genes (DEGs) that were altered by HSYA, and enrich their biological functions and signaling pathways through the OmicShare database. The results of the network pharmacology and transcriptomic analyses were combined. Then, quantitative real-time PCR (qRT-PCR) and Western blot experiments were used to further verify the prediction results. Finally, the interactions between HSYA and key targets were assessed by molecular docking. The results showed that 199 potentially targeted genes according to network pharmacology and 480 DEGs according to transcriptomics were involved in the effects of HSYA against LA. An integrated analysis revealed that four key targets, including HSP90AA1, ATP2A1, NOS1 and CRAT, as well as their three related pathways (the calcium signaling pathway, estrogen signaling pathway and cGMP-PKG signaling pathway), were closely related to the therapeutic effects of HSYA. A gene and protein expression analysis revealed that HSYA significantly inhibited the expressions of HSP90AA1, ATP2A1 and NOS1 in the liver tissue of aging mice. The molecular docking results showed that HSYA had high affinities with the HSP90AA1, ATP2A1 and NOS1 targets. Our data demonstrate that HSYA may delay LA in mice by inhibiting the expressions of HSP90AA1, ATP2A1 and NOS1 and regulating the calcium signaling pathway, the estrogen signaling pathway, and the cGMP-PKG signaling pathway.

Safflower oil body nanoparticles deliver hFGF10 to hair follicles and reduce microinflammation to accelerate hair regeneration in androgenetic alopecia.

Androgenetic alopecia (AGA) affects physical and mental health with limited therapeutic options. Novel materials and delivery methods have considerable potential to improve the current paradigm of treatment. In this study, we used a novel plant nanoparticle of safflower oil body (SOB) loaded with human fibroblast growth factor 10 (hFGF10) to target hair follicles and accelerate hair regeneration in AGA mice with few adverse effects. Our data revealed that the average particle size of SOB-hFGF10 was 226.73 ± 9.98 nm, with a spherical and uniform structure, and that SOB-hFGF10 was quicker to preferentially penetrate into hair follicles than hFGF2 alone. Using a mouse model of AGA, SOB-hFGF10 was found to significantly improve hair regeneration without any significant toxicity. Furthermore, SOB-hFGF10 inhibited dihydrotestosterone (DHT)-induced TNF-α, IL-1ß, and IL-6 overproduction in macrophages in relation to hair follicle microinflammation, thereby enhancing the proliferation of dermal papilla cells. Overall, this study provides an applicable therapeutic method through targeting hair follicles and reducing microinflammation to accelerate hair regeneration in AGA.