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Alzheimer's disease (AD) causes a decline in skeletal muscle function, which can further exacerbate the cognitive dysfunction of patients with AD. It has been widely established that exercise improves AD brain pathology, but the role of skeletal muscle in AD is still poorly understood. In this study, we investigated the effects of treadmill exercise on the exercise ability of APP/PS1 transgenic AD mice and explored potential gene expression changes in their skeletal muscle. The APP/PS1 mice were subjected to a treadmill exercise for 12 weeks, followed by the Morris water maze and the open field test. After behavioral experiments, the changes in morphology, area, collagen fiber deposition, and ultrastructure of the skeletal muscle were determined; the balance of skeletal muscle protein synthesis and decomposition was analyzed; and changes in gene expression were investigated using RNA-Seq. We found that this exercise strategy can promote the learning and memory abilities of AD mice, reduce their anxiety-like behavior, improve their exercise ability, alleviate skeletal muscle atrophy, and optimize the microstructure. It can also enhance skeletal muscle protein synthesis and decomposition and improve several signaling pathways, such as the JAK–STAT, Wnt, and NOD-like receptors while decreasing calcium, cAMP, cGMP–PKG, and other signaling pathways. Six KEGG enrichment signaling pathways were downregulated and five signaling pathways were upregulated in the AD mice compared with wild-type mice, and these pathways were precisely reversed after the treadmill exercise. The expression of transcription factors such as Fosb and Egr1 in the skeletal muscle of AD mice decreased, followed by a decrease in the regulated target genes Socs1, Srrm4, and Il1b, a trend that was reversed following the exercise intervention. After exercise, AD mice exhibited a similar gene expression to that of wild-type mice, indicating enhanced exercise ability. The potential regulatory pathways and related genes identified in this study provide valuable insights for the clinical management and treatment of AD. [ABSTRACT FROM AUTHOR]

Congenital heart defects (CHDs) are common human birth defects. Genetic mutations potentially cause the exhibition of various pathological phenotypes associated with CHDs, occurring alone or as part of certain syndromes. Zebrafish, a model organism with a strong molecular conservation similar to humans, is commonly used in studies on cardiovascular diseases owing to its advantageous features, such as a similarity to human electrophysiology, transparent embryos and larvae for observation, and suitability for forward and reverse genetics technology, to create various economical and easily controlled zebrafish CHD models. In this review, we outline the pros and cons of zebrafish CHD models created by genetic mutations associated with single defects and syndromes and the underlying pathogenic mechanism of CHDs discovered in these models. The challenges of zebrafish CHD models generated through gene editing are also discussed, since the cardiac phenotypes resulting from a single-candidate pathological gene mutation in zebrafish might not mirror the corresponding human phenotypes. The comprehensive review of these zebrafish CHD models will facilitate the understanding of the pathogenic mechanisms of CHDs and offer new opportunities for their treatments and intervention strategies. [ABSTRACT FROM AUTHOR]

Alcoholic myopathy is caused by chronic consumption of alcohol (ethanol) and is characterized by weakness and atrophy of skeletal muscle. Regular exercise is one of the important ways to prevent or alleviate skeletal muscle myopathy. However, the beneficial effects and the exact mechanisms underlying regular exercise on alcohol myopathy remain unclear. In this study, a model of alcoholic myopathy was established using zebrafish soaked in 0.5% ethanol. Additionally, these zebrafish were intervened to swim for 8 weeks at an exercise intensity of 30% of the absolute critical swimming speed (Ucrit), aiming to explore the beneficial effects and underlying mechanisms of regular exercise on alcoholic myopathy. This study found that regular exercise inhibited protein degradation, improved locomotion ability, and increased muscle fiber cross-sectional area (CSA) in ethanol-treated zebrafish. In addition, regular exercise increases the functional activity of mitochondrial respiratory chain (MRC) complexes and upregulates the expression levels of MRC complexes. Regular exercise can also improve oxidative stress and mitochondrial dynamics in zebrafish skeletal muscle induced by ethanol. Additionally, regular exercise can activate mitochondrial biogenesis and inhibit mitochondrial unfolded protein response (UPRmt). Together, our results suggest regular exercise is an effective intervention strategy to improve mitochondrial homeostasis to attenuate alcoholic myopathy. [ABSTRACT FROM AUTHOR]

Based on the concept of Xingfa teaching for pursuing a complete and well-rounded life, and for the sake of arousing and stimulating students' inner intention of active learning and also realizing the internal relationship between physical education and students' life growth, this paper uses the thinking way of hermeneutics to systematically discuss the Xingfa teaching of physical education. The conclusions are as follows: firstly, Xingfa teaching of physical education examines the releasing value of Xingfa teaching in the duality of students' individual life, and its purpose is to promote the development of students from the rise of prosperity and meet the dual needs of the complete integration of body and soul of students' individual life. Secondly, the three dimensions of students' desire, interest and mind should be gradually open. Among them, the original sexual desire of individual life should burst out through physical movement to mobilize physiological hormones and stimulate the pleasure of direct feedback from life senses; to promote students' interest, it is necessary to set up an appropriate, cultural, root and spiritual teaching methods for sports development; to cultivate students' studious life mind, it is necessary to feel the joy of life in the whole field of Xingfa teaching of physical education. Thirdly, it is proposed to explore the promotion path of Xingfa teaching of physical education in three artistic conceptions, such as activating the diachronic improvement of individual life, to make the potential energy of individual life become the characteristics of reality; fostering individual lives' independent personality, making the independence, autonomy and creativity of individual life become the characteristics of life; cultivating the self-perception of individual life, making the experience, happiness and significance of individual life become the essence of flow. In conclusion, the Xingfa teaching of physical education aims to make students' individual life open to three dimensions in the triple artistic conception, so as to release the duality. Therefore, Xingfa teaching will be applied to the teaching conditions of physical education teaching in order to achieve the integrity of life. [ABSTRACT FROM AUTHOR]

A growing body of clinical data has shown that patients with Alzheimer's disease (AD) have symptoms such as liver dysfunction and microbial-gut-brain axis dysfunction in addition to brain pathology, presenting a systemic multisystemic pathogenesis. Considering the systemic benefits of exercise, here, we first observed the effects of long-term treadmill exercise on liver injuries in APP/PS1 transgenic AD mice and explored the potential mechanisms of the gut-liver-brain axis's role in mediating exercise's ability to reduce bacterial lipopolysaccharide (LPS) pathology in the brain. The results showed that the livers of the AD mice were in states of oxidative stress, while the mice after long-term treadmill exercise showed alleviation of their oxidative stress, their intestinal barriers were protected, and the ability of their Kupffer cells to hydrolyze LPS was improved, in addition to the accumulation of LPS in their brains being reduced. Notably, the livers of the AD mice were in immunosuppressed states, with lower pro-oxidative and antioxidative levels than the livers of the wild-type mice, while exercise increased both their oxidative and antioxidative levels. These results suggest that long-term exercise modulates hepatic redox homeostasis in AD mice, attenuates oxidative damage, and reduces the accumulation of LPS in the brain through the combined action of the intestine-liver-Kupffer cells.

This study elucidated the role of CaN-NFAT signaling and neurotrophins on the transformation of myosin heavy chain isoforms in the rat soleus muscle fiber following aerobic exercise training. To do so, we examined the content and distribution of myosin heavy chain (MyHC) isoforms in the rat soleus muscle fiber, the activity of CaN and expression of NFATc1 in these fibers, and changes in the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neutrophin-3 (NT-3) in the soleus and striatum following high-and medium-intensity aerobic treadmill training. Specific pathogen-free 2 month old male Sprague-Dawley (SD) rats were randomly divided into three groups: Control group (Con, n = 8), moderate-intensity aerobic exercise group (M-Ex, n = 8) and high-intensity aerobic exercise group (H-Ex, n = 8). We used ATPase staining to identify the muscle fiber type I and II, SDS-PAGE to separate and analyze the isoforms MyHCI, MyHCIIA, MyHCIIB and MyHCIIx, and performed western blots to determine the expression of NFATc1, NGF, BDNF and NT-3. CaN activity was measured using a colorimetric assay. In the soleus muscle, 8 weeks of moderate-intensity exercise can induce transformation of MyHC IIA and MyHC IIB to MyHC IIX and MyHC I (p < 0.01), while high-intensity treadmill exercise can induce transform MyHC IIx to MyHC IIB, MyHC IIA and MyHC I (p < 0.01). In comparison to the control group, CaN activity and NFATcl protein level were significantly increased in both the M-Ex and H-Ex groups (p < 0.05, p < 0.01), with a more pronounced upregulation in the M-Ex group (p < 0.05). Eight weeks of moderate- and high-intensity aerobic exercise induced the expression of NGF, BDNF and NT-3 in the soleus muscle and the striatum (p < 0.01), with the most significant increase in the H-Ex group (p < 0.01). In the rat soleus muscle, (1) CaN-NFATcl signaling contributes to the conversion of MyHC I isoform in response to moderate-intensity exercise; (2) Neurotrophins NGF, BDNF and NT-3 might play a role in the conversion of MyHC II isoform in response to high-intensity treadmill exercise. Key pointsEight weeks of moderate-intensity treadmill training induces the transformation MyHC IIA and MyHC IIB to MyHC IIX and MyHC I in the soleus muscles, while high-intensity exercise leads to transformation of MyHC IIX to MyHC IIA, MyHC IIB and MyHC I.MyHC I conversion in response to moderate-intensity aerobic exercise is mediated by calcineurin-NFATcl signaling.Eight weeks of moderate- and high-ntensity aerobic exercise induces the expression of NGF, BDNF and NT-3 in expression noted in rats subjected to high-intensity training. NGF and NT-3 expression in the striatum is lower than in the soleus muscle, while BDNF levels are similar. Neurotrophins may be involved in mediating MyHC II conversion in response to high-intensity aerobic exercise.