Denervation does not induce muscle atrophy through oxidative stress

Denervation leads to the activation of the catabolic pathways, such as the ubiquitin-proteasome and autophagy, resulting in skeletal muscle atrophy and weakness. Furthermore, denervation induces oxidative stress in skeletal muscle, which is thought to contribute to the induction of skeletal muscle atrophy. Several muscle diseases are characterized by denervation, but the molecular pathways contributing to muscle atrophy have been only partially described. Our study delineates the kinetics of activation of oxidative stress response in skeletal muscle following denervation. Despite the denervation-dependent induction of oxidative stress in skeletal muscle, treatments with anti-oxidant drugs do not prevent the reduction of muscle mass. Our results indicate that, although oxidative stress may contribute to the activation of the response to denervation, it is not responsible by itself of oxidative damage or neurogenic muscle atrophy

Interactions between microRNAs and long non-coding RNAs in cardiac development and repair

Non-coding RNAs (ncRNAs) are emerging players in muscle regulation. Based on their length and differences in molecular structure, ncRNAs are subdivided into several categories including small interfering RNAs, stable non-coding RNAs, microRNAs (miRs), long non-coding RNAs (lncRNAs), and circular RNAs. miRs and lncRNAs are able to post-transcriptionally regulate many genes and bring into play several traits simultaneously due to a myriad of different targets. Recent studies have emphasized their importance in cardiac regeneration and repair. As their altered expression affects cardiac function, miRs and lncRNAs could be potential targets for therapeutic intervention. In this context, miR- and lncRNA-based gene therapies are an interesting field for harnessing the complexity of ncRNA-based therapeutic approaches in cardiac diseases. In this review we will focus on lncRNA- and miR-driven regulations of cardiac development and repair. Finally, we will summarize miRs and lncRNAs as promising candidates for the treatment of heart diseases.status: publishe

Interactions between microRNAs and long non-coding RNAs in cardiac development and repair

Non-coding RNAs (ncRNAs) are emerging players in muscle regulation. Based on their length and differences in molecular structure, ncRNAs are subdivided into several categories including small interfering RNAs, stable non-coding RNAs, microRNAs (miRs), long non-coding RNAs (lncRNAs), and circular RNAs. miRs and lncRNAs are able to post-transcriptionally regulate many genes and bring into play several traits simultaneously due to a myriad of different targets. Recent studies have emphasized their importance in cardiac regeneration and repair. As their altered expression affects cardiac function, miRs and lncRNAs could be potential targets for therapeutic intervention. In this context, miR- and lncRNA-based gene therapies are an interesting field for harnessing the complexity of ncRNA-based therapeutic approaches in cardiac diseases. In this review we will focus on lncRNA- and miR-driven regulations of cardiac development and repair. Finally, we will summarize miRs and lncRNAs as promising candidates for the treatment of heart diseases

Human dental pulp pluripotent-like stem cells promote wound healing and muscle regeneration

BACKGROUND: Dental pulp represents an easily accessible autologous source of adult stem cells. A subset of these cells, named dental pulp pluripotent-like stem cells (DPPSC), shows high plasticity and can undergo multiple population doublings, making DPPSC an appealing tool for tissue repair or maintenance. METHODS: DPPSC were harvested from the dental pulp of third molars extracted from young patients. Growth factors released by DPPSC were analysed using antibody arrays. Cells were cultured in specific differentiation media and their endothelial, smooth and skeletal muscle differentiation potential was evaluated. The therapeutic potential of DPPSC was tested in a wound healing mouse model and in two genetic mouse models of muscular dystrophy (Scid/mdx and Sgcb-null Rag2-null γc-null). RESULTS: DPPSC secreted several growth factors involved in angiogenesis and extracellular matrix deposition and improved vascularisation in all three murine models. Moreover, DPPSC stimulated re-epithelialisation and ameliorated collagen deposition and organisation in healing wounds. In dystrophic mice, DPPSC engrafted in the skeletal muscle of both dystrophic murine models and showed integration in muscular fibres and vessels. In addition, DPPSC treatment resulted in reduced fibrosis and collagen content, larger cross-sectional area of type II fast-glycolytic fibres and infiltration of higher numbers of proangiogenic CD206+ macrophages. CONCLUSIONS: Overall, DPPSC represent a potential source of stem cells to enhance the wound healing process and slow down dystrophic muscle degeneration.status: publishe

Aging affects the in vivo regenerative potential of human mesoangioblasts

Sarcopenia is the age-related loss of muscle mass, strength, and function. Although the role of human satellite cells (SCs) as adult skeletal muscle stem cells has been deeply investigated, little is known about the impact of aging on muscle interstitial stem cells. Here, we isolated the non-SC CD56- fraction from human muscle biopsies of young and elderly subjects. The elderly interstitial cell population contained a higher number of CD15+ and PDGFRα+ cells when compared to young samples. In addition, we found that the CD56- /ALP+ cells were well represented as a multipotent stem cell population inside the CD56- fraction. CD56- /ALP+ /CD15- cells were clonogenic, and since they were myogenic and expressed NG2, α-SMA and PDGFRβ can be considered mesoangioblasts (MABs). Interestingly, elderly MABs displayed a dramatic impairment in the myogenic differentiation ability in vitro and when transplanted in dystrophic immunodeficient Sgcb-null Rag2-null γc-null mice. In addition, elderly MABs proliferated less, but yet retained other multilineage capabilities. Overall, our results indicate that aging negatively impacted on the regenerative potential of MABs and this should be carefully considered for potential therapeutic applications of MABs

Making physics fun: key concepts, classroom activities, and everyday examples, grades K-8

In easy-to-understand language, this resource presents engaging, ready-to-use learning experiences that address the "big ideas" in K-8 science education and help students make larger, real-world connections

A New HRCT Score for Diagnosing SARS-CoV-2 Pneumonia: A Single-Center Study with 1153 Suspected COVID-19 Patients in the Emergency Department

The 2019 coronavirus disease (COVID-19) pandemic is affecting millions of people worldwide. Chest high-resolution computed tomography (HRCT) is commonly used as a diagnostic test for suspected COVID-19; however, despite numerous attempts, there is no single scoring system that is widely accepted and used in clinical practice to estimate the probability of SARS-CoV-2 pneumonia. The aim of this single-center retrospective study is to develop a radiological score to predict the probability of COVID-19 with HRCT. Patients admitted to the emergency department with symptoms suggestive of COVID-19 who underwent both HRCT and RT-PCR on nasopharyngeal swab to detect SARS-CoV-2 infection between 1 March and 30 April 2020 were included. A multivariable regression analysis was conducted to identify all HRCT signs independently associated with a positive RT-PCR assay for SARS-CoV-2 and build the HRCT score. A total of 1153 patients were enrolled in this study. The number of segments with ground glass opacities (OR 1.18, 95% CI 1.11–1.26), number of segments with linear opacities (OR 1.21, 95% CI 1.05–1.42), crazy paving patterns (OR 6, 95% CI 3.79–9.76), and vascular ectasia in each segment (OR 2.46, 95% CI 1.1.5–5.8) were included in the score. The HRCT score showed high discriminatory power (area under the ROC curve of 0.8267 [95% CI 0.8–0.85]) with 72.2% sensitivity, 86.6% specificity, 78% PPV, and 83% NPV for its best cut-off. In summary, the HRCT score has good diagnostic and discriminatory accuracy for COVID-19 and is easy and quick to perform

Additional file 1: Table S1. of Human dental pulp pluripotent-like stem cells promote wound healing and muscle regeneration

List of primers used for cDNA amplification in qRT-PCR analyses. (DOCX 11 kb

Additional file 2: Table S2. of Human dental pulp pluripotent-like stem cells promote wound healing and muscle regeneration

List of antibodies used for protein detection in immunofluorescence analyses. (DOCX 16 kb

Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions

: Skeletal muscle holds an intrinsic capability of growth and regeneration both in physiological conditions and in case of injury. Chronic muscle illnesses, generally caused by genetic and acquired factors, lead to deconditioning of the skeletal muscle structure and function, and are associated with a significant loss in muscle mass. At the same time, progressive muscle wasting is a hallmark of aging. Given the paracrine properties of myogenic stem cells, extracellular vesicle-derived signals have been studied for their potential implication in both the pathogenesis of degenerative neuromuscular diseases and as a possible therapeutic target. In this study, we screened the content of extracellular vesicles from animal models of muscle hypertrophy and muscle wasting associated with chronic disease and aging. Analysis of the transcriptome, protein cargo, and microRNAs (miRNAs) allowed us to identify a hypertrophic miRNA signature amenable for targeting muscle wasting, consisting of miR-1 and miR-208a. We tested this signature among others in vitro on mesoangioblasts (MABs), vessel-associated adult stem cells, and we observed an increase in the efficiency of myogenic differentiation. Furthermore, injections of miRNA-treated MABs in aged mice resulted in an improvement in skeletal muscle features, such as muscle weight, strength, cross-sectional area, and fibrosis compared to controls. Overall, we provide evidence that the extracellular vesicle-derived miRNA signature we identified enhances the myogenic potential of myogenic stem cells