Rational: Senescence of mesenchymal stem cells (MSCs) and the related functional decline of osteogenesis have emerged as the critical pathogenesis of osteoporosis in aging.Resveratrol (RESV), a small molecular compound that safely mimics the effects of dietary restriction, has been well documented to extend lifespan in lower organisms and improve health in aging rodents.However, whether RESV promotes function of senescent stem cells in alleviating age-related phenotypes remains largely unknown.Here, we intend to investigate whether RESV counteracts senescence-associated bone loss via osteogenic improvement of MSCs and the underlying mechanism.Methods: MSCs derived from bone marrow (BMMSCs) and the bone-specific, senescence-accelerated, osteoblastogenesis/osteogenesis-defective mice (the SAMP6 strain) were used as experimental models.In vivo application of RESV was performed at 100 mg/kg intraperitoneally once every other day for 2 months, and in vitro application of RESV was performed at 10 μM.Bone mass, bone formation rates and osteogenic differentiation of BMMSCs were primarily evaluated.Metabolic statuses of BMMSCs and the mitochondrial activity, transcription and morphology were also examined.Mitofilin expression was assessed at both mRNA and protein levels, and short hairpin RNA (shRNA)-based gene knockdown was applied for mechanistic experiments.Results: Chronic intermittent application of RESV enhances bone formation and counteracts accelerated bone loss, with RESV improving osteogenic differentiation of senescent BMMSCs.Furthermore, in rescuing osteogenic decline under BMMSC senescence, RESV restores cellular metabolism through mitochondrial functional recovery via facilitating mitochondrial autonomous gene transcription.Molecularly, in alleviating senescence-associated mitochondrial disorders of BMMSCs, particularly the mitochondrial morphological alterations, RESV upregulates Mitofilin, also known as inner membrane protein of mitochondria (Immt) or Mic60, which is the core component of the mitochondrial contact site and cristae organizing system (MICOS).Moreover, Mitofilin is revealed to be indispensable for mitochondrial homeostasis and osteogenesis of BMMSCs, and that insufficiency of Mitofilin leads to BMMSC senescence and bone loss.More importantly, Mitofilin mediates resveratrol-induced mitochondrial and osteogenic improvements of BMMSCs in senescence.Conclusion: Our findings uncover osteogenic functional improvements of senescent MSCs as critical impacts in anti-osteoporotic practice of RESV, and unravel Mitofilin as a novel mechanism mediating RESV promotion on mitochondrial function in stem cell senescence.
Osteonecrosis of the femoral head (ONFH) is a common refractory orthopedic disease with multiple etiologies that more frequently occurs in middle-aged and young people. ONFH is the main cause of hip replacement in young patients. Since Professor Hernigou first reported the use of stem cells in the treatment of early stage ONFH, a large number of studies have demonstrated the potential of stem cells in the treatment of adult patients with ONFH. With the rise of interdisciplinary stem cell therapy combined with platelet-rich plasma therapy, gene therapy or other methods have gradually attracted the attention of researchers. This article summarizes the current advances in stem cell therapy for ONFH, as well as the problems and challenges, which may provide reference for further research.
Inflammatory response plays a critical role in myocardial infarction (MI) repair. The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration, while the therapeutic strategy that simulates and enhances this natural process has not been established. Here, we constructed engineered neutrophil apoptotic bodies (eNABs) to simulate natural neutrophil apoptosis, which regulated inflammation response and enhanced MI repair. The eNABs were fabricated by combining natural neutrophil apoptotic body membrane which has excellent inflammation-tropism and immunoregulatory properties, and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride (HAL). The eNABs actively targeted to macrophages and the encapsulated HAL simultaneously initiated the biosynthesis pathway of heme to produce anti-inflammatory bilirubin after intracellular release, thereby further enhancing the anti-inflammation effects. In in vivo studies, the eNABs efficiently modulated inflammation responses in the infarcted region to ameliorate cardiac function. This study demonstrates an effective biomimetic construction strategy to regulate macrophage functions for MI repair.
Aims: Little information exists on the associations of cardiovascular health, a new metric proposed by the American Heart Association, and executive function, particularly in children. We aimed to explore this topic. Methods: We studied 3,798 children aged 6–12 years from 5 schools in Guangzhou, China. The executive function of children was evaluated using parent reports of the Behavioral Rating Inventory of Executive Function, which included 2 composite indexes and 8 subscale scores. We calculated the number of ideal cardiovascular health (range: 0–7) based on smoking, body mass index, physical activity (PA), diet, blood pressure, cholesterol, and glucose. A generalized linear mixed model was used to assess the association of the number of ideal cardiovascular health metrics and executive function. Results: Compared with children exhibiting 1–3 ideal cardiovascular health metrics, decreases of 1.37–2.63 points (indicating better performance) in metacognition index and its 5 subscale indexes (initiate, working memory, plan/organize, organization of materials, and monitor) were observed in children who attained 5 or 6–7 ideal metrics (all p for trend <0.001). Ideal diet and ideal PA were independently associated with lower indexes of behavioral regulation and metacognition. Conclusions: The number of ideal cardiovascular health was positively associated with performance of executive function in children.
Abstract The engineering management is not a simple equation, such as “engineering management=engineering technology + economic management”, since there is rich connotation and significance between them. Almost all entrepreneurs have simple technology and lack scientific management for entrepreneurial engineering, which leads to the difficulty to start a business. In this paper, it starts from the related theories of engineering management and entrepreneurial engineering to make specific analysis on some problems. As a result, it explores the management methods and measures of the entrepreneurial engineering of art design, so as to promote the development of entrepreneurship.
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