Exercise and nutrition benefit skeletal muscle: From influence factor and intervention strategy to molecular mechanism.

Sarcopenia is a progressive systemic skeletal muscle disease induced by various physiological and pathological factors, including aging, malnutrition, denervation, and cardiovascular diseases, manifesting as the decline of skeletal muscle mass and function. Both exercise and nutrition produce beneficial effects on skeletal muscle growth and are viewed as feasible strategies to prevent sarcopenia. Mechanisms involve regulating blood flow, oxidative stress, inflammation, apoptosis, protein synthesis and degradation, and satellite cell activation through exerkines and gut microbiomes. In this review, we summarized and discussed the latest progress and future development of the above mechanisms for providing a theoretical basis and ideas for the prevention and treatment of sarcopenia.

Role of Irisin in exercise training-regulated endoplasmic reticulum stress, autophagy and myogenesis in the skeletal muscle after myocardial infarction.

Patients with heart failure (HF) are often accompanied by skeletal muscle abnormalities, which can lead to exercise intolerance and compromise daily activities. Irisin, an exercise training (ET) -induced myokine, regulates energy metabolism and skeletal muscle homeostasis. However, the precise role of Irisin in the benefits of ET on inhibiting skeletal muscle atrophy, particularly on endoplasmic reticulum (ER) stress, autophagy, and myogenesis following myocardial infarction (MI) remains unclear. In this study, we investigated the expression of Irisin protein in wild-type mice with MI, and assessed its role in the beneficial effects of ET using an Fndc5 knockout mice. Our findings revealed that MI reduced muscle fiber cross-sectional area (CSA), while downregulating the expression of Irisin, PGC-1α and SOD1. Concurrently, MI elevated the levels of ER stress and apoptosis, and inhibited autophagy in skeletal muscle. Conversely, ET mitigated ER stress and apoptosis in the skeletal muscle of infarcted mice. Notably, Fndc5 knockout worsened MI-induced ER stress and apoptosis, suppressed autophagy and myogenesis, and abrogated the beneficial effects of ET. In conclusion, our findings highlight the role of Irisin in the ET-mediated alleviation of skeletal muscle abnormalities. This study provides valuable insights into MI-induced muscle abnormalities and enhances our understanding of exercise rehabilitation mechanisms in clinical MI patients.

The Emerging Role of Exercise in Alzheimer's Disease: Focus on Mitochondrial Function.

Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by memory impairment and cognitive dysfunction, which eventually leads to the disability and mortality of older adults. Although the precise mechanisms by which age promotes the development of AD remains poorly understood, mitochondrial dysfunction plays a central role in the development of AD. Currently, there is no effective treatment for this debilitating disease. It is well accepted that exercise exerts neuroprotective effects by ameliorating mitochondrial dysfunction in the neurons of AD, which involves multiple mechanisms, including mitochondrial dynamics, biogenesis, mitophagy, transport, and signal transduction. In addition, exercise promotes mitochondria communication with other organelles in AD neurons, which should receive more attentions in the future.

Food wastewater treatment using a hybrid biofilm reactor: nutrient removal performance and functional microorganisms on filler biofilm and suspended sludge.

In this study, a laboratory-scale hybrid biofilm reactor (HBR) was constructed to treat food wastewater (FWW) before it is discharged into the sewer. The chemical oxygen demand (COD) of 29 860 mg L-1 in FWW was degraded to 200-350 mg L-1 using the HBR under the operating parameters of COD load 1.68 kg m-3 d-1, hydraulic retention time (HRT) of 426.63 h, dissolved oxygen (DO) of 8-9 mg L-1, and temperature of 22-23 °C. The biomass of biofilm on the surface of filler was 2.64 g L-1 for column A and 0.91 g L-1 for column O. Microbial analysis revealed richer and more diverse microorganisms in filler biofilms compared to those in suspended sludge. The hybrid filler was conducive to the development of functional microbial species, including phyla Firmicutes, Actinobacteriota, and Chloroflexi, and genus level norank_f_JG30-KF-CM45, which will improve FWW treatment efficiency. Moreover, the microorganisms on the filler biofilm had more connections and relationships than those in the suspended sludge. The combination of an up-flow anaerobic sludge bed (UASB) and HBR was demonstrated to be an economical strategy for practical applications as a shorter HRT of 118.34 h could be obtained. Overall, this study provides reliable data and a theoretical basis for the application of HBR and FWW treatments.

Resistance exercise upregulates Irisin expression and suppresses myocardial fibrosis following myocardial infarction via activating AMPK-Sirt1 and inactivating TGFß1-Smad2/3.

AIM: To reveal the contribution of Irisin in the beneficial effects of resistance exercise on myocardial fibrosis (MF) and cardiac function in the mice with myocardial infarction (MI). METHODS: The MI model was built by ligating the left anterior descending coronary artery in Fndc5 knockout mice (Fndc5-/-). Resistance exercise was started one week after surgery and continued for four weeks. In addition, H2O2, AICAR, recombinant human Irisin protein (rhIRISIN), and Sirt1 shRNA lentivirus (LV-Sirt1 shRNA) were used to intervene primary isolated cardiac fibroblasts (CFs). MF was observed through Masson staining, and apoptosis was assessed using TUNEL staining. MDA and T-SOD contents were detected by biochemical kits. The expression of proteins and genes was detected by Western blotting and RT-qPCR. RESULTS: Resistance exercise increased Fndc5 mRNA level, inhibited the activation of TGFß1-TGFßR2-Smad2/3 pathway, activated AMPK-Sirt1 pathway, reduced the levels of oxidative stress, apoptosis, and MF in the infarcted heart, and promoted cardiac function. However, Fndc5 knockout attenuated the protective effects of resistance exercise on the MI heart. Results of the in vitro experiments showed that AICAR and rhIRISIN intervention activated the AMPK-Sirt1 pathway and inactivated the TGFß1-Smad2/3 pathway, and promoted apoptosis in H2O2-treated CFs. Notably, these effects of rhIRISIN intervention, except for the TGFßR2 expression, were attenuated by LV-Sirt1 shRNA. CONCLUSION: Resistance exercise upregulates Fndc5 expression, activates AMPK-Sirt1 pathway, inhibits the activation of TGFß1-Smad2/3 pathway, attenuates MF, and promotes cardiac function after MI.

The mechanisms of exercise improving cardiovascular function by stimulating Piezo1 and TRP ion channels: a systemic review.

Mechanosensitive ion channels are widely distributed in the heart, lung, bladder and other tissues, and plays an important role in exercise-induced cardiovascular function promotion. By reviewing the PubMed databases, the results were summarized using the terms "Exercise/Sport", "Piezo1", "Transient receptor potential (TRP)" and "Cardiovascular" as the keywords, 124-related papers screened were sorted and reviewed. The results showed that: (1) Piezo1 and TRP channels play an important role in regulating blood pressure and the development of cardiovascular diseases such as atherosclerosis, myocardial infarction, and cardiac fibrosis; (2) Exercise promotes cardiac health, inhibits the development of pathological heart to heart failure, regulating the changes in the characterization of Piezo1 and TRP channels; (3) Piezo1 activates downstream signaling pathways with very broad pathways, such as AKT/eNOS, NF-κB, p38MAPK and HIPPO-YAP signaling pathways. Piezo1 and Irisin regulate nuclear localization of YAP and are hypothesized to act synergistically to regulate tissue mechanical properties of the cardiovascular system and (4) The cardioprotective effects of exercise through the TRP family are mostly accomplished through Ca2+ and involve many signaling pathways. TRP channels exert their important cardioprotective effects by reducing the TRPC3-Nox2 complex and mediating Irisin-induced Ca2+ influx through TRPV4. It is proposed that exercise stimulates the mechanosensitive cation channel Piezo1 and TRP channels, which exerts cardioprotective effects. The activation of Piezo1 and TRP channels and their downstream targets to exert cardioprotective function by exercise may provide a theoretical basis for the prevention of cardiovascular diseases and the rehabilitation of clinical patients.

Manipulation of Glutamatergic Neuronal Activity in the Primary Motor Cortex Regulates Cardiac Function in Normal and Myocardial Infarction Mice.

Cardiac function is under neural regulation; however, brain regions in the cerebral cortex responsible for regulating cardiac function remain elusive. In this study, retrograde trans-synaptic viral tracing is used from the heart to identify a specific population of the excitatory neurons in the primary motor cortex (M1) that influences cardiac function in mice. Optogenetic activation of M1 glutamatergic neurons increases heart rate, ejection fraction, and blood pressure. By contrast, inhibition of M1 glutamatergic neurons decreased cardiac function and blood pressure as well as tyrosine hydroxylase (TH) expression in the heart. Using viral tracing and optogenetics, the median raphe nucleus (MnR) is identified as one of the key relay brain regions in the circuit from M1 that affect cardiac function. Then, a mouse model of cardiac injury is established caused by myocardial infarction (MI), in which optogenetic activation of M1 glutamatergic neurons impaired cardiac function in MI mice. Moreover, ablation of M1 neurons decreased the levels of norepinephrine and cardiac TH expression, and enhanced cardiac function in MI mice. These findings establish that the M1 neurons involved in the regulation of cardiac function and blood pressure. They also help the understanding of the neural mechanisms underlying cardiovascular regulation.

Increased gene dosage of RFWD2 causes autistic-like behaviors and aberrant synaptic formation and function in mice.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions, communication deficits and repetitive behaviors. A study of autistic human subjects has identified RFWD2 as a susceptibility gene for autism, and autistic patients have 3 copies of the RFWD2 gene. The role of RFWD2 as an E3 ligase in neuronal functions, and its contribution to the pathophysiology of ASD, remain unknown. We generated RFWD2 knockin mice to model the human autistic condition of high gene dosage of RFWD2. We found that heterozygous knockin (Rfwd2+/-) male mice exhibited the core symptoms of autism. Rfwd2+/- male mice showed deficits in social interaction and communication, increased repetitive and anxiety-like behavior, and spatial memory deficits, whereas Rfwd2+/- female mice showed subtle deficits in social communication and spatial memory but were normal in anxiety-like, repetitive, and social behaviors. These autistic-like behaviors in males were accompanied by a reduction in dendritic spine density and abnormal synaptic function on layer II/III pyramidal neurons in the prelimbic area of the medial prefrontal cortex (mPFC), as well as decreased expression of synaptic proteins. Impaired social behaviors in Rfwd2+/- male mice were rescued by the expression of ETV5, one of the major substrates of RFWD2, in the mPFC. These findings indicate an important role of RFWD2 in the pathogenesis of autism.

Resistance training up-regulates Smyd1 expression and inhibits oxidative stress and endoplasmic reticulum stress in the heart of middle-aged mice.

Persistent oxidative stress and endoplasmic reticulum (ER) stress are the primary mechanisms of age-related cardiovascular diseases. Although exercise training is viewed as an effective anti-aging approach, further exploration is needed to identify the mechanisms and functional targets. In this study, the impact of resistance training (RT) on the expression of Smyd1, the levels of reactive oxygen species (ROS) and the expression of ER stress-related protein in the hearts of mice of different ages were assessed. In addition, the role of Smyd1 in the aging-induced oxidative stress and ER stress were evaluated in d-galactose (D-gal)-treated H9C2 cells. We demonstrated that RT in middle age increased the expression of Smyd1 and restricted heart aging-induced ER stress. Overexpression of Smyd1 restrained oxidative stress and ER stress in D-gal-treated H9C2 cells, while the inhibition of Nrf2 and Smyd1 escalated ER stress. These findings demonstrate that Smyd1 has significant impact in regulating age-related ER stress. RT in middle age can up-regulates Smyd1 expression and inhibits oxidative stress and ER stress in the heart.

[Progress on the role of Kalirin-7 in exercise intervention-mediated improvement of neurodegenerative diseases].

Guanine nucleotide exchange factor Kalirin-7 (Kal-7) is a key factor in synaptic plasticity and plays an important regulatory role in the brain. Abnormal synaptic function leads to the weakening of cognitive functions such as learning and memory, accompanied by abnormal expression of Kal-7, which in turn induces a variety of neurodegenerative diseases. Exercise can upregulate the expression of Kal-7 in related brain regions to alleviate neurodegenerative diseases. By reviewing the literature on Kal-7 and neurodegenerative diseases, as well as the research progress of exercise intervention, this paper summarizes the role and possible mechanism of Kal-7 in the improvement of neurodegenerative diseases by exercise and provides a new rationale for the basic and clinical research on the prevention and treatment of neurodegenerative diseases by exercise.

Resistance exercise alleviates the prefrontal lobe injury and dysfunction by activating SESN2/AMPK/PGC-1α signaling pathway and inhibiting oxidative stress and inflammation in mice with myocardial infarction.

OBJECTIVES: Myocardial infarction (MI) induces inflammatory response and oxidative stress in the brain, which would be one of the causes of cardiac dysfunction. Exercise training is viewed as a feasible strategy to improve cardiac function of the infarcted heart. The aim of this study was to investigate whether exercise training could alleviate MI-induced prefrontal lobe injury via activating Sestrin2 (SESN2) signaling and inhibiting oxidative stress and inflammation. METHODS: Male C57BL/6 mice were divided into five groups: control group (CON), aerobic exercise group (AE), resistance exercise group (RE), whole-body vibration group (WBV) and electrical stimulation group (ES); and three groups: sham-operated group (S), sedentary MI group (MI) and MI with resistance exercise group (MRE). After four weeks of training, sensorimotor function, spatial learning, long-term and spatial memory, and cardiac function were detected. Then, mice were euthanized, and the prefrontal areas were separated for HE, Nissl, SESN2, microtubule-associated protein 2 (MAP2), neuron-specific nucleoprotein (NeuN), and TUNEL staining. Activation of SESN2/adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) signaling pathway and expression of proteins related to oxidative stress, inflammation and apoptosis in the prefrontal lobe were detected by western blotting. RESULTS: Different types of exercise training all activated the SESN2/AMPK/PGC-1α signaling pathway, and the effect of RE is the best. RE improved sensorimotor, learning, and memory impairments, increased the expressions of antioxidant, anti-inflammatory and anti-apoptotic proteins, reduced oxidative stress, inflammation and apoptosis, ultimately alleviated the prefrontal lobe injury and dysfunction in mice with MI. CONCLUSION: RE alleviates MI-indued prefrontal lobe injury and dysfunction by inhibiting the levels of oxidative stress, inflammation and apoptosis, partially via activating SESN2/AMPK/PGC-1α signaling pathway.

Exercise mitigates age-related metabolic diseases by improving mitochondrial dysfunction.

The benefits of regular physical activity are related to delaying and reversing the onset of ageing and age-related disorders, including cardiomyopathy, neurodegenerative diseases, cancer, obesity, diabetes, and fatty liver diseases. However, the molecular mechanisms of the benefits of exercise or physical activity on ageing and age-related disorders remain poorly understood. Mitochondrial dysfunction is implicated in the pathogenesis of ageing and age-related metabolic diseases. Mitochondrial health is an important mediator of cellular function. Therefore, exercise alleviates metabolic diseases in individuals with advancing ageing and age-related diseases by the remarkable promotion of mitochondrial biogenesis and function. Exerkines are identified as signaling moieties released in response to exercise. Exerkines released by exercise have potential roles in improving mitochondrial dysfunction in response to age-related disorders. This review comprehensive summarizes the benefits of exercise in metabolic diseases, linking mitochondrial dysfunction to the onset of age-related diseases. Using relevant examples utilizing this approach, the possibility of designing therapeutic interventions based on these molecular mechanisms is addressed.

FGF21 promotes myocardial angiogenesis and mediates the cardioprotective effects of exercise in myocardial infarction mice.

The mechanism by which aerobic exercise promotes cardiac function after myocardial infarction (MI) is still not fully understand. In this study, we investigated the role of fibroblast growth factor 21 (FGF21) in exercise protecting the cardiac function of MI mice. In vivo, MI was induced by left anterior descending coronary artery ligation in wild-type and fgf21 knockout mice on the C57BL/6 background. One week after MI, the mice underwent aerobic exercise for 4 wk. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with H2O2, recombinant human FGF21 (rhFGF21), fibroblast growth factor receptor 1 (FGFR1) inhibitor (PD166866), and phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) to explore the potential mechanisms. Scratch wound healing and tubule formation analysis were used to detect the migration and tubule formation ability of HUVECs. Our results showed that aerobic exercise significantly promoted angiogenesis and cardiac function through enhancing the expression of FGF21 and activating FGFR1/PI3K/AKT/VEGF pathway. But such changes in cardiac from aerobic exercise were attenuated by fgf21 knockout mice. 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) enhanced angiogenesis and cell migration through FGF21/FGFR1/PI3K/AKT/VEGF signaling pathway. Under the intervention of H2O2, rhFGF21 also played the role of promoting angiogenesis and cell migration through the same mechanism. In conclusion, our results showed that FGF21 promoted the aerobic exercise-induced angiogenesis and improved cardiac function via FGFR1/PI3K/AKT/VEGF signal in MI mice.NEW & NOTEWORTHY FGF21 activated FGFR1/PI3K/AKT/VEGF signaling pathway mediated angiogenesis in MI mice. FGF21 deficiency attenuated aerobic exercise-induced cardiac angiogenesis in MI mice. FGF21/FGFR1/PI3K/AKT/VEGF signal played an important role in aerobic exercise to promote myocardial angiogenesis and improved cardiac function.

Step-feeding food waste fermentation liquid as supplementary carbon source for low C/N municipal wastewater treatment: Bench scale performance and response of microbial community.

Municipal wastewater treatment often lacks carbon source, while carbon-rich organics in food waste are deficiently utilized. In this study, the food waste fermentation liquid (FWFL) was step-fed into a bench-scale step-feed three-stage anoxic/aerobic system (SFTS-A/O), to investigate its performance in nutrients removal and the response of microbial community as a supplementary carbon source. The results showed that the total nitrogen (TN) removal rate increased by 21.8-109.3% after step-feeding FWFL. However, the biomass of the SFTS-A/O system was increased by 14.6% and 11.9% in the two phases of the experiment, respectively. Proteobacteria was found to be the dominant functional phyla induced by FWFL, and the increase of its abundance attributed to the enrichment of denitrifying bacteria and carbohydrate-metabolizing bacteria was responsible for the biomass increase. Azospira belonged to Proteobacteria phylum was the dominant denitrifying genera when step-fed with FWFL, its abundance was increased from 2.7% in series 1 (S1) to 18.6% in series 2 (S2) and became the keystone species in the microbial networks. Metagenomics analysis revealed that step-feeding FWFL enhanced the abundance of denitrification and carbohydrates-metabolism genes, which were encode mainly by Proteobacteria. This study constitutes a key step towards the application of FWFL as a supplementary carbon source for low C/N municipal wastewater treatment.

Effect of microbial network complexity and stability on nitrogen and sulfur pollutant removal during sediment remediation in rivers affected by combined sewer overflows.

Discovering the complexity and improving the stability of microbial networks in urban rivers affected by combined sewer overflows (CSOs) is essential for restoring the ecological functions of urban rivers, especially to improve their ability to resist CSO impacts. In this study, the effects of sediment remediation on the complexity and stability of microbial networks was investigated. The results revealed that the restored microbial community structure using different approaches in the river sediments differed significantly, and random matrix theory showed that sediment remediation significantly affected microbial networks and topological properties; the average path distance, average clustering coefficient, connectedness, and other network topological properties positively correlated with remediation time and weakened the small-world characteristics of the original microbial networks. Compared with other sediment remediation methods, regulating low dissolved oxygen (DO) shifts the microbial network module hubs from Actinobacteria and Bacteroidetes to Chloroflexi and Proteobacteria. This decreases the positive association of networks by 17%-18%, which intensifies the competitiveness among microorganisms, further weakening the influence and transmission of external pressure across the entire microbial network. Compared with that of the original sediment, the vulnerability of the restored network was reduced by more than 36%, while the compositional stability was improved by more than 12%, with reduced fluctuation in natural connectivity. This microbial network succession substantially increased the number of key enzyme-producing genes involved in nitrogen and sulfur metabolism, enhancing nitrification, denitrification, and assimilatory sulfate reduction, thereby increasing the removal rates of ammonia, nitrate, and acid volatile sulfide by 43.42%, 250.68% and 2.66%, respectively. This study comprehensively analyzed the succession patterns of microbial networks in urban rivers affected by CSOs before and after sediment remediation, which may provide a reference for reducing the impact of CSO pollution on urban rivers in the subsequent stages.

Biomanipulation as a strategy for minimizing ecological risks in river supplied with reclaimed water.

Reclaimed water is an effective method for addressing water pollution and shortages. However, its use may contribute to the collapse of receiving water (algal blooms and eutrophication) owing to its unique characteristics. A three-year biomanipulation project was conducted in Beijing to investigate the structural changes, stability, and potential risks to aquatic ecosystems associated with the reuse of reclaimed water in rivers. During the biomanipulation, the proportion of Cyanophyta in the community structure of phytoplankton density in river supplied with reclaimed water decreased, and the community composition shifted from Cyanophyta and Chlorophyta to Chlorophyta and Bacillariophyta. The biomanipulation project increased the number of zoobenthos and fish species and significantly increased fish density. Despite the significant difference in aquatic organisms community structure, diversity index and community stability of aquatic organisms remained stable during the biomanipulation. Our study provides a strategy for minimizing the hazards of reclaimed water through biomanipulation by reconstructing the community structure of reclaimed water, thereby making it safe for large-scale reuse in rivers.

ELABELA-APJ-Akt/YAP Signaling Axis: A Novel Mechanism of Aerobic Exercise in Cardioprotection of Myocardial Infarction Rats.

PURPOSE: The aim of this study was to investigate the function and mechanisms of ELABELA (ELA) in the aerobic exercise-induced antiapoptosis and angiogenesis of ischemic heart. METHODS: The myocardial infarction (MI) model of Sprague-Dawley rat was established by the ligation of the left anterior descending coronary artery. MI rats underwent 5 wk of Fc-ELA-21 subcutaneous injection and aerobic exercise training using a motorized rodent treadmill. Heart function was evaluated by hemodynamic measures. Cardiac pathological remodeling was evaluated by Masson's staining and the calculation of left ventricular weight index. Cell proliferation, angiogenesis, and Yes-associated protein (YAP) translocation were observed by immunofluorescence staining. Cell apoptosis was analyzed by TUNEL. Cell culture and treatment were used to elucidate the molecular mechanism of ELA. Protein expression was detected by Western blotting. Angiogenesis was observed by tubule formation test. One-way or two-way ANOVA and Student's t -test were used for statistical analysis. RESULTS: Aerobic exercise stimulated the endogenous ELA expression. Exercise and Fc-ELA-21 intervention significantly activated APJ-Akt-mTOR-P70S6K signaling pathway, kept more cardiomyocytes alive, and increased angiogenesis, so as to inhibit the cardiac pathological remodeling and improved the heart function of MI rats. Fc-ELA-32 also had the cellular and functional cardioprotective activities in vivo . In vitro , ELA-14 peptide regulated the phosphorylation and nucleoplasmic translocation of YAP and activated the APJ-Akt signaling pathway so as to increase the proliferation of H9C2 cells. Moreover, the antiapoptosis and the tubule formation of HUVECs were also enhanced by ELA-14, whereas the inhibition of Akt activity weakened such effects. CONCLUSIONS: ELA is a potential therapeutic member that plays a key role through APJ-Akt/YAP signaling axis in aerobic exercise-induced cardioprotection of MI rats.

FNDC5/Irisin Inhibits the Inflammatory Response and Mediates the Aerobic Exercise-Induced Improvement of Liver Injury after Myocardial Infarction.

Myocardial infarction (MI) causes peripheral organ injury, in addition to cardiac dysfunction, including in the liver, which is known as cardiac hepatopathy. Aerobic exercise (AE) can effectively improve liver injury, although the mechanism and targets are currently not well established. Irisin, mainly produced by cleavage of the fibronectin type III domain-containing protein 5 (FNDC5), is a responsible for the beneficial effects of exercise training. In this study, we detected the effect of AE on MI-induced liver injury and explored the role of irisin alongside the benefits of AE. Wildtype and Fndc5 knockout mice were used to establish an MI model and subjected to AE intervention. Primary mouse hepatocytes were treated with lipopolysaccharide (LPS), rhirisin, and a phosphoinositide 3-kinase (PI3K) inhibitor. The results showed that AE significantly promoted M2 polarization of macrophages and improved MI-induced inflammation, upregulated endogenous irisin protein expression and activated the PI3K/ protein kinase B (Akt) signaling pathway in the liver of MI mice, while knockout of Fndc5 attenuated the beneficial effects of AE. Exogenous rhirisin significantly inhibited the LPS-induced inflammatory response, which was attenuated by the PI3K inhibitor. These results suggest that AE could effectively activate the FNDC5/irisin-PI3K/Akt signaling pathway, promote the polarization of M2 macrophages, and inhibit the inflammatory response of the liver after MI.

Effects of different exercise modalities on inhibiting left ventricular pathological remodeling in patients with heart failure with reduced ejection fraction: A systematic review and network meta-analysis.

AIMS: To evaluate the effects of different exercise training modalities on inhibiting the left ventricular pathological remodeling in patients with heart failure with reduced ejection fraction (HFrEF) and screen out the optimal exercise modality. METHODS: We performed a network meta-analysis based on the Frequentist model. Random-effect meta-analyses were used to estimate mean differences (MD) and 95 % confidence intervals. KEY FINDINGS: 25 randomized controlled trials (1284 patients) were enrolled in this study. Results revealed that: high-intensity interval training had the best effect in improving left ventricular ejection fraction (p-score = 0.93, MD: 6.44 (3.61 to 9.28)), reducing left ventricular end-diastolic diameter (p-score = 0.97, MD: -6.73 (-10.27 to -3.19)) and left ventricular end-systolic diameter (p-score = 0.97, MD: -9.33 (-14.90 to -3.76)). Combined aerobic training with resistance training and inspiratory muscle training had the best effect in improving maximal oxygen consumption (p-score = 0.90, MD: 5.19 (3.12 to 7.25)). SIGNIFICANCE: Current evidence revealed that exercise training could effectively inhibit left ventricular pathological remodeling in patients with HFrEF. For efficacy, high-intensity interval training may have greater potential.