To determine the dose-response associations of sedentary behaviour with cardiovascular diseases (CVD), cancer, and all-cause mortality, and to examine whether the sedentary-associated all-cause mortality risk was affected by appearance of diabetes and hypertension, physical activity, and body mass index (BMI).

Neuroinflammation is a pathological hallmark of Alzheimer’s disease (AD), characterized by the stimulation of resident immune cells of the brain and the penetration of peripheral immune cells. These inflammatory processes facilitate the deposition of amyloid-beta (Aβ) plaques and the abnormal hyperphosphorylation of tau protein. Managing neuroinflammation to restore immune homeostasis and decrease neuronal damage is a therapeutic approach for AD. One way to achieve this is through exercise, which can improve brain function and protect against neuroinflammation, oxidative stress, and synaptic dysfunction in AD models. The neuroprotective impact of exercise is regulated by various molecular factors that can be activated in the same way as exercise by the administration of their mimetics. Recent evidence has proven some exercise mimetics effective in alleviating neuroinflammation and AD, and, additionally, they are a helpful alternative option for patients who are unable to perform regular physical exercise to manage neurodegenerative disorders. This review focuses on the current state of knowledge on exercise mimetics, including their efficacy, regulatory mechanisms, progress, challenges, limitations, and future guidance for their application in AD therapy.

The associations between sugar-sweetened beverage (SSB) consumption and the risk of stroke, depression, cancer, and cause-specific mortality have not been determined, and the quantitative aspects of this link remain unclear. This meta-analysis therefore conducted a systematic review and dose-response analysis to determine their causal links. The database searches were conducted in PubMed, Cochrane library, Embase, Web of Science up to 10 November 2021. The intervention effects were evaluated by relative risk (RR) with 95% confidences (CI). Thirty-two articles met the inclusion criteria. Higher levels of SSB consumption significantly increased the risk of stroke (RR 1.12, 95% CI 1.03–1.23), depression (1.25, 1.11–1.41), cancer (1.10, 1.03–1.17), and all-cause mortality (1.08, 1.05–1.11) compared with none or lower SSB intake. The associations were dose-dependent, with per 250 mL increment of SSB intake daily increasing the risk of stroke, depression, cancer, and all-cause mortality by RR 1.09 (1.03–1.15), 1.08 (1.06–1.10), 1.17 (1.04–1.32), and 1.07 (1.03–1.11), respectively. The link was curved for depression and cancer risk (p_non-linear < 0.05). Subgroup analysis suggested that higher SSB intake increased ischemic stroke by 10%, CVD-caused mortality by 13%, and cancer-caused mortality by 6.0% than none or lower SSB consumption. It is suggested that SSB accounts for a leading risk factor of stroke, depression, cancer, and mortality, and that the risk rises in parallel with the increment of SSB intake (and is affected by participant characteristics).

Background: Whether exercise prevents fall-related injuries in different health conditions and with different training protocols is still unclear. This study aimed to determine the effect of exercise on fall-related injuries by participant characteristics and divergent exercise protocols. The safety and compliance of exercise were also examined. Methods: Electronic database searches were conducted in PubMed, Web of Science, and EMBASE for randomised controlled trials that evaluated the influence of exercise on fall-induced injuries in older people. Results: Twenty-five trials met the inclusion criteria. Exercise significantly reduced the risk of fall-related injuries in older adults, risk ratio (RR) 0.879 [95% confidence interval (CI) 0.832–0.928]. Among the injuries, events needing medical care or resulting fractures were also decreased by exercise intervention, with RR 0.681 (0.562–0.825) and 0.561 (0.366–0.860), respectively. When analysis was stratified by participant characteristics and exercise protocols, we found that participants at high risk of falling, or with osteoporosis, were sensitive to exercise intervention. Combined exercise protocols and balance training were the most effective exercise types in reducing fall-related injuries. Exercise-associated beneficial effects were even significant in very old people (≥80 years) and across the duration of interventions (< 6 months, 6 to 12 months and ≥ 12 months). Exercise only generated a very low injury rate per participant year (0.002, 95% CI 0–0.05) and showed relatively good compliance of exercise (as reported in the included papers) (78.5, 95% CI 72.8–84.2%). Conclusions: Exercise is effective in preventing fall-induced injuries across a variety of baseline participant characteristics and exercise protocols. Exercise was associated with a low injury rate and had a good compliance, suggesting it is a feasible approach to managing fall-related injuries.

Persistent microglial inflammation is a detrimental contributor to the progression of Parkinson disease (PD) pathology and related issues such as impaired adult hippocampal neurogenesis (AHN) and cognition. We conducted a 10‐week exercise program with MPTP‐treated mice to determine whether neuroinflammation can be addressed by aerobic exercise and elucidate its underlying regulatory mechanisms. Ten weeks of exercise significantly reduced PD‐related pathology and enhanced AHN and memory. These changes were linked to a reduction in neuronal apoptosis, microglial inflammation, and NLRP3 inflammasome activation. In cultured microglia, fibril α‐synuclein reduced FNDC5/irisin protein levels and induced NLRP3 inflammasome formation and IL‐1β production, which could be diminished by recombinant irisin treatment. Interestingly, “runner serum” isolated from exercising rodents enhanced FNDC5/irisin expression and reduced NLRP3 inflammasome components and IL‐1β secretion in α‐synuclein‐treated microglia. These effects could be diminished by blocking irisin signaling with cyclo RGDyk or NLRP3 agonist, nigericin sodium salt. Exercise‐induced neuroprotective effects were weakened by treatment of MPTP‐treated mice with cyclo RGDyk. In contrast, systematic administration of irisin partially replicated the beneficial effects of exercise on PD pathology, AHN, and memory function. As a nonpharmacological strategy, aerobic exercise effectively addresses PD pathology and preserves adult neurogenesis and cognition by mitigating microglial inflammation via mediating irisin/NLRP3 inflammasome pathways.