Exercise preconditioning inhibits doxorubicin-induced cardiotoxicity via YAP/STAT3 signaling.

Doxorubicin (DOX) possesses strong anti-tumor effects but is limited by its irreversible cardiac toxicity. The relationship between exercise, a known enhancer of cardiovascular health, and DOX-induced cardiotoxicity has been a focus of recent research. Exercise has been suggested to mitigate DOX's cardiac harm by modulating the Yes-associated protein (YAP) and Signal transducer and activator of transcription 3 (STAT3) pathways, which are crucial in regulating cardiac cell functions and responses to damage. This study aimed to assess the protective role of exercise preconditioning against DOX-induced cardiac injury. We used Sprague-Dawley rats, divided into five groups (control, DOX, exercise preconditioning (EP), EP-DOX, and verteporfin + EP + DOX), to investigate the potential mechanisms. Our findings, including echocardiography, histological staining, Western blot, and q-PCR analysis, demonstrated that exercise preconditioning could alleviate DOX-induced cardiac dysfunction and structural damage. Notably, exercise preconditioning enhanced the nuclear localization and co-localization of YAP and STAT3. Our study suggests that exercise preconditioning may counteract DOX-induced cardiotoxicity by activating the YAP/STAT3 pathway, highlighting a potential therapeutic approach for reducing DOX's cardiac side effects.

The Best Exercise Modality and Dose for Reducing Pain in Adults With Low Back Pain: A Systematic Review With Model-Based Bayesian Network Meta-analysis.

OBJECTIVE: To quantify the dose-response relationship between overall and specific exercise modalities and pain, in patients with nonspecific chronic low back pain (LBP). DESIGN: Systematic review with Bayesian network meta-analysis. LITERATURE SEARCH: We searched the Medline, Embase, Web of Science, Cochrane Library, Scopus, and SPORTDiscus databases from inception to June 2023. STUDY SELECTION CRITERIA: We included randomized controlled trials of exercise interventions in adults with nonspecific chronic LBP and at least 1 pain outcome reported at the main trial end point. DATA SYNTHESIS: A random-effects network meta-analysis was conducted. We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0, and used the GRADE approach to judge the certainty of evidence for each outcome. RESULTS: Eighty-two trials were included (n = 5033 participants). We found a nonlinear dose-response relationship between total exercise and pain in patients with nonspecific chronic LBP. The maximum significant response was observed at 920 MET minutes (standardized mean difference = -1.74; 95% credible intervals: -2.43, -1.04). The minimal clinically important difference for achieving meaningful pain improvement was 520 MET minutes per week. The dose to achieve minimal clinically important difference varied by type of exercise; Pilates was the most effective. The certainty of the evidence was very low to moderate for all outcomes. CONCLUSION: The dose-response relationship of different exercise modalities to improve pain in patients with nonspecific chronic LBP had a U-shaped trajectory and low- to moderate-certainty evidence. The clinical effect was most pronounced with Pilates exercise. J Orthop Sports Phys Ther 2024;54(5):1-13. Epub 8 March 2024. doi:10.2519/jospt.2024.12153.

An updated review of YAP: A promising therapeutic target against cardiac aging?

The transcriptional co-activator Yes-associated protein (YAP) functions as a downstream effector of the Hippo signaling pathway and plays a crucial role in cardiomyocyte survival. In its non-phosphorylated activated state, YAP binds to transcription factors, activating the transcription of downstream target genes. It also regulates cell proliferation and survival by selectively binding to enhancers and activating target genes. However, the upregulation of the Hippo pathway in human heart failure inhibits cardiac regeneration and disrupts astrogenesis, thus preventing the nuclear translocation of YAP. Existing literature indicates that the Hippo/YAP axis contributes to inflammation and fibrosis, potentially playing a role in the development of cardiac, vascular and renal injuries. Moreover, it is a key mediator of myofibroblast differentiation and fibrosis in the infarcted heart. Given these insights, can we harness YAP's regenerative potential in a targeted manner? In this review, we provide a detailed discussion of the Hippo signaling pathway and consolidate concepts for the development and intervention of cardiac anti-aging drugs to leverage YAP signaling as a pivotal target.

Comparative efficacy of four exercise types on obesity-related outcomes in breast cancer survivors: A Bayesian network meta-analysis.

PURPOSE: Exercise training is associated with improving the prognosis of breast cancer survivors, but no studies have evaluated the optimal exercise intervention. We aimed to investigate the most effective exercise intervention to improve obesity-related outcomes in breast cancer survivors. METHODS: A comprehensive search strategy was conducted in Medline, Embase, Web of Science, Cochrane Library, and Chinese biomedical literature databases from the time of library construction to April 2, 2023. We included randomized controlled trials reporting the effects of four types of exercise interventions (aerobic exercise; aerobic combined with resitance exercise, resitstance exercise and mind-body exercise ) on obesity-related outcomes in breast cancer survivors. A Bayesian network meta-analysis was used to analyze and rank the effectiveness of four exercise types. RESULTS: A total of 76 randomized controlled trials that contained 5610 breast cancer survivors were included. The treatment effect of combined aerobic and resistance exercise (mean difference = -0.59; 95% credible interval: 1.15, -0.08) was significantly better than that of the control groups in terms of body mass index. For percentage of body fat, combined aerobic and resistance exercise (mean difference = -1.74; 95% credible interval: 0.87, -0.90) and aerobic exercise (mean difference = -1.16; 95% credible interval: 2.15, -0.16) were significantly better than controls. Subgroup analysis suggested that combined aerobic and resistance exercise significantly affected body mass index at an intervention duration >12 weeks or weekly time on exercise >150 min. CONCLUSION: Our network meta-analysis found combined aerobic and resistance exercise may be the most effective intervention to improve obesity-related outcomes in breast cancer survivors. In addition, intervention duration and participant adherence are important factors that influence the effectiveness of exercise interventions.

[Exercise preconditioning reduces exercise-induced risks of cardiovascular events in obese population].

Obesity is an independent risk factor of cardiovascular diseases. Epidemiological studies have shown that obesity induces the production of inflammatory factors and changes in cardiac hemodynamics, remodeling and function, leading to myocardial damage and heart diseases. The positive effect of exercise on the cardiovascular system has been widely confirmed, while the acute cardiovascular stress caused by exercise cannot be ignored. Compared with the general population, obese people were more prone to arrhythmia and have a higher risk of cardiovascular events during exercise, due to their abnormal cardiac function, myocardial pathological remodeling and low tolerance to corresponding stress. Studies have shown that the intervention of exercise preconditioning (EP) can effectively reduce such risks. EP increases myocardial oxygen consumption through short-term exercise, resulting in relative or absolute myocardial ischemia, inducing the intrinsic myocardial protective effect and reducing the continuous ischemia caused by subsequent long-term exercise. This article reviews the obesity-induced abnormal changes of cardiac function and structure, possible exercise- induced risks of cardiovascular events in obese people and the role of EP in reducing exercise-induced risks of cardiovascular events. We summarize the progress on EP models in obese people, EP prevention against adverse cardiovascular events in obese people, with the aim to provide a theoretical basis for the application of EP in obese people.

Association between sedentary behavior, physical activity, and cardiovascular disease-related outcomes in adults-A meta-analysis and systematic review.

Background: Sedentary behavior (SB) and physical activity (PA) are modifiable risk factors for cardiovascular disease (CVD); however, previous research on the effects of PA and SB on CVD has been relatively homogeneous. Our study investigated the association between PA, SB, and CVD-related outcomes. Methods: A comprehensive search strategy was conducted in the MEDLINE, Embase, Cochrane Library, and Web of Science databases from their inception to September 2022. We identified eligible studies according to PICOS: the populations comprised healthy adults, the interventions or exposures were PA or SB, the outcomes were CVD-related outcomes, and the study designs were randomized controlled trials (RCTs) and longitudinal studies (LS). Outcomes were pooled using fixed or random effects models, and the quality of individual studies was assessed by the Cochrane Risk of Bias Instrument and the Newcastle Ottawa Scale. Results: A total of 148 RCTs and 36 LS were included, comprising a total of 75,075 participants. The study quality was rated as low to moderate. We found an increased hazard ratio (HR) for CVD in the population with SB (HR = 1.34; 95% confidence interval [CI]: 1.26 to 1.43; I2 = 52.3%; Pheterogeneity < 0.001, random model) and a decreased HR for CVD in those who performed long-term PA (HR = 0.71; 95% CI: 0.66 to 0.77; I2 = 78.0%, Pheterogeneity < 0.001, random model). Long-term PA improved the lipid profiles in healthy adults; participants in this group exhibited increased high-density lipoprotein (weighted mean difference [WMD] = 2.38; 95% CI: 1.00 to 3.76; I2 = 84.7%; Pheterogeneity < 0.001, random model), decreased triglycerides (WMD = -7.27; 95% CI: -9.68 to -4.87; I2 = 0%, Pheterogeneity = 0.670, fixed model), and lower total-cholesterol (WMD = -6.84; 95% CI: -9.15 to -4.52; I2 = 38.4%, Pheterogeneity < 0.001, random model). Conclusions: Long-term SB increases the risk of CVD in healthy adults, whereas PA reduces the risk of CVD and improves indicators associated with CVD. However, the ability of PA to improve blood lipids appeared to be limited. The detailed association of SB and PA on CVD needs to be further investigated in the future.

Targeting NAD+: is it a common strategy to delay heart aging?

Heart aging is the main susceptible factor to coronary heart disease and significantly increases the risk of heart failure, especially when the aging heart is suffering from ischemia-reperfusion injury. Numerous studies with NAD+ supplementations have suggested its use in anti-aging treatment. However, systematic reviews regarding the overall role of NAD+ in cardiac aging are scarce. The relationship between NAD+ signaling and heart aging has yet to be clarified. This review comprehensively summarizes the current studies on the role of NAD+ signaling in delaying heart aging from the following aspects: the influence of NAD+ supplementations on the aging heart; the relationship and cross-talks between NAD+ signaling and other cardiac aging-related signaling pathways; Importantly, the therapeutic potential of targeting NAD+ in delaying heart aging will be discussed. In brief, NAD+ plays a vital role in delaying heart aging. However, the abnormalities such as altered glucose and lipid metabolism, oxidative stress, and calcium overload could also interfere with NAD+ function in the heart. Therefore, the specific physiopathology of the aging heart should be considered before applying NAD+ supplementations. We believe that this article will help augment our understanding of heart aging mechanisms. In the meantime, it provides invaluable insights into possible therapeutic strategies for preventing age-related heart diseases in clinical settings.

Tricholoma matsutake-derived peptide WFNNAGP protects against DSS-induced colitis by ameliorating oxidative stress and intestinal barrier dysfunction.

Inflammatory bowel disease (IBD) is a non-specific, chronic inflammatory disease of the intestine. The precise etiology and mechanism underlying the pathogenesis of IBD have not been elucidated. In this study, we investigated the mechanisms through which the Tricholoma matsutake-derived peptide, WFNNAGP, exerts protective effects on the inflammatory response and oxidative stress in a dextran sodium sulfate (DSS)-induced IBD mouse model. WFNNAGP significantly attenuated colitis symptoms in mice, including weight loss, diarrhea, shortened colon, bloody stools, and histopathological changes. WFNNAGP significantly ameliorated the DSS-induced oxidative damage, showing scavenging activity against hydroxyl and DPPH radicals (23.67 ± 4.11% and 34.53 ± 2.45%), increased SOD activity (191.48 ± 4.35 U per mg prot), and decreased MDA activity (1.61 ± 0.24 nmol per mg prot). In addition, WFNNAGP improved the inflammatory response by inhibiting MPO and pro-inflammatory cytokine expression and protected the barrier function by promoting the expression of occludin and ZO-1 in the colon. Western blotting showed that WFNNAGP reduced the inflammatory response by downregulating NF-κB expression and inhibiting the formation and activation of NLRP3 and caspase-1. Thus, WFNNAGP may reduce colonic inflammation in mice by enhancing oxidative defense systems and barrier function and may be a promising candidate for IBD intervention.

Nutrition, Physical Exercise, and the Prevalence of Sarcopenia in Elderly Residents in Nursing Homes in China.

BACKGROUND This study aimed to investigate the factors associated with sarcopenia in elderly residents in three nursing homes in Suzhou City, East China including the association with nutrition and physical exercise. MATERIAL AND METHODS Elderly residents (n=316) from three nursing homes included 112 men and 204 women. The appendicular skeletal muscle index (ASMI), grip strength, and movements were measured to diagnose sarcopenia. The correlation between sarcopenia with age, sex, body mass index (BMI), ASMI, upper arm circumference, calf circumference, muscle content, grip strength, dietary intake, degree and duration of movement were also assessed. RESULTS The prevalence of sarcopenia was 28.8% (30.4% for men and 27.9% for women). Patients with sarcopenia were older compared with controls. Height, BMI, upper arm circumference, calf circumference and arm muscle mass, lower limb muscle mass, limb skeletal muscle index and ASMI, grip strength, and pace of movement were lower than controls. The prevalence of sarcopenia correlated with the intake of meat, fish, eggs, and milk, and duration of weekly aerobic and resistance exercise. Logistic regression analysis showed a positive correlation between the prevalence of sarcopenia and age, and a negative correlation between BMI and consumption of meat, eggs, and milk. CONCLUSIONS The prevalence of sarcopenia in elderly residents in three nursing homes in Suzhou City was 28.8%. Increasing age was a risk factor for sarcopenia. Increased BMI and a diet containing meat, eggs, and milk were protective factors. The findings from this study provide support that adequate dietary protein can prevent sarcopenia in the elderly.