[Research progress of the impacts of acupuncture on programmed cell death in treatment of ischemic stroke].

The new progress has been made in the research of programmed cell death (e.g. autophagy, apoptosis, pyroptosis, necroptosis and ferroptosis) for the pathological mechanism of ischemic stroke. As an important non-pharmacological therapy, acupuncture is widely used in stroke patients and has achieved favorable effect. The researches in recent years have shown that acupuncture plays its neuroprotective role on ischemic stroke by modulation of autophagy, apoptosis, pyroptosis, necroptosis and ferroptosis of neurons. Acupuncture is effective in treatment of ischemic stroke by regulating programmed cell death.

The Beneficial Role of Exercise on Treating Alzheimer's Disease by Inhibiting ß-Amyloid Peptide.

Alzheimer's disease (AD) is associated with a very large burden on global healthcare systems. Thus, it is imperative to find effective treatments of the disease. One feature of AD is the accumulation of neurotoxic ß-amyloid peptide (Aß). Aß induces multiple pathological processes that are deleterious to nerve cells. Despite the development of medications that target the reduction of Aß to treat AD, none has proven to be effective to date. Non-pharmacological interventions, such as physical exercise, are also being studied. The benefits of exercise on AD are widely recognized. Experimental and clinical studies have been performed to verify the role that exercise plays in reducing Aß deposition to alleviate AD. This paper reviewed the various mechanisms involved in the exercise-induced reduction of Aß, including the regulation of amyloid precursor protein cleaved proteases, the glymphatic system, brain-blood transport proteins, degrading enzymes and autophagy, which is beneficial to promote exercise therapy as a means of prevention and treatment of AD and indicates that exercise may provide new therapeutic targets for the treatment of AD.

The involvement of NLRP3 inflammasome in the treatment of neurodegenerative diseases.

In an ageing society, neurodegenerative diseases have attracted attention because of their high incidence worldwide. Despite extensive research, there is a lack of conclusive insights into the pathogenesis of neurodegenerative diseases, which limit the strategies for symptomatic treatment. Therefore, better elucidation of the molecular mechanisms involved in neurodegenerative diseases can provide an important theoretical basis for the discovery of new and effective prevention and treatment methods. The innate immune system is activated during the ageing process and in response to neurodegenerative diseases. Inflammasomes are multiprotein complexes that play an important role in the activation of the innate immune system. They mediate inflammatory reactions and pyroptosis, which are closely involved in neurodegeneration. There are different types of inflammasomes, although the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is the most common inflammasome; NLRP3 plays an important role in the pathogenesis of neurodegenerative diseases. In this review, we will discuss the mechanisms that are involved in the activation of the NLRP3 inflammasome and its crucial role in the pathology of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis. We will also review various treatments that target the NLRP3 inflammasome pathway and alleviate neuroinflammation. Finally, we will summarize the novel treatment strategies for neurodegenerative disorders.

The Anti-apoptosis Effect of Single Electroacupuncture Treatment via Suppressing Neuronal Autophagy in the Acute Stage of Ischemic Stroke Without Infarct Alleviation.

The main purpose of the study was to investigate the antiapoptotic effect of electroacupuncture (EA) in the acute stage of ischaemic stroke in rats. The cerebral ischemia model was established by middle cerebral artery occlusion (MCAO)/reperfusion in rats. A single EA treatment was performed at the acute stage of ischaemic stroke. The neurological function, brain water content, apoptotic cell number, and cerebral infarct volume were assessed in stroke rats. The expression of autophagy-related proteins (LC3II/I, Beclin1, P62, and LAMP1), Sirtuin 1 (SIRT1), p-JNK, p-ERK1/2, and cleaved caspase-3 (CCAS3) were measured by Western blot, immunofluorescence, and immunohistochemistry. Rapamycin (RAP, an activator of autophagy) was used to confirm the antiapoptotic effect of EA via regulating autophagy. The brain edema infarct size and apoptotic cell number were increasing within 3 days following stroke, and brain edema reached its peak at 24 h after stroke. EA treatment at 24 h after ischaemic stroke obviously suppressed the number of apoptotic cells and brain edema. However, there were no significant differences in infarct volumes among EA-12 h, EA-24 h, and MCAO/R group. Moreover, EA treatment at 24 h after ischaemic stroke obviously suppressed the expression of CCAS3, LC3II/I, Beclin1 while increasing the level of P62 and LAMP1 and hence mediating autophagy, which was reversed by RAP. Meanwhile, the expression of SIRT1, p-ERK1/2, p-JNK were promoted by EA at 24 h after ischaemic stroke. In conclusion, EA treatment may suppress apoptosis possibly via regulating autophagy in the acute period after ischaemic stroke, hence reducing brain injury.

The involvement of NLRP3 inflammasome in the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, and it is characterised by progressive deterioration in cognitive and memory abilities, which can severely influence the elderly population's daily living abilities. Although researchers have made great efforts in the field of AD, there are still no well-established strategies to prevent and treat this disease. Therefore, better clarification of the molecular mechanisms associated with the onset and progression of AD is critical to provide a theoretical basis for the establishment of novel preventive and therapeutic strategies. Currently, it is generally believed that neuroinflammation plays a key role in the pathogenesis of AD. Inflammasome, a multiprotein complex, is involved in the innate immune system, and it can mediate inflammatory responses and pyroptosis, which lead to neurodegeneration. Among the various types of inflammasomes, the NLRP3 inflammasome is the most characterised in neurodegenerative diseases, especially in AD. The activation of the NLRP3 inflammasome causes the generation of caspase-1-mediated interleukin (IL)-1ß and IL-18 in microglia cells, where neuroinflammation is involved in the development and progression of AD. Thus, the NLRP3 inflammasome is likely to be a crucial therapeutic molecular target for AD via regulating neuroinflammation. In this review, we summarise the current knowledge on the role and regulatory mechanisms of the NLRP3 inflammasome in the pathogenic mechanisms of AD. We also focus on a series of potential therapeutic treatments targeting NLRP3 inflammasome for AD. Further clarification of the regulatory mechanisms of the NLRP3 inflammasome in AD may provide more useful clues to develop novel AD treatment strategies.

The role of exosomes in stroke.

Stroke is induced by a partial disruption of cerebral blood flow to the brain and is related to high morbidity and mortality. In the central nervous system, exosomes have been proven to exert neuroprotective effects, reducing brain damage following a stroke. This review was performed by searching the relevant articles in the SCIENCEDIRECT, PUBMED, and Web of Science databases from respective inception to November 2018. We review the relationship between exosomes and angiogenesis, neurogenesis, antiapoptosis, autophagy, and the blood-brain barrier in stroke. Moreover, exosomes are found to be a promising tool for the diagnosis and treatment of stroke. In summary, exosomes provide a novel way to alleviate brain damage following a stroke.

Electroacupuncture Inhibits Neuronal Autophagy and Apoptosis via the PI3K/AKT Pathway Following Ischemic Stroke.

Electroacupuncture (EA) is a safe and effective therapy for ischemic stroke in both clinical and laboratory settings. However, the underlying mechanism behind EA treatment for stroke remains unclear. Here, we aimed to evaluate whether EA treatment at the acupoints of Zusanli (ST36) and Quchi (LI11) exerted a neuroprotective effect on ischemic stroke rats by modulating autophagy and apoptosis via the PI3K/AKT/mTOR signaling pathway. EA was performed at 24 h following brain ischemia/reperfusion (I/R) for 30 min per day for 3 days. Our results indicated that EA treatment significantly decreased neurological deficits and cerebral infarct volume in ischemic stroke rats. Also, EA intervention markedly reduced neuronal apoptosis by suppressing the activation of cleaved caspase-3 (CCAS3) at 72 h following I/R, as shown by a Western blot analysis. Furthermore, EA treatment after ischemic stroke suppressed the ischemia activated expression level of LC3II/I and Atg7 and increased the ischemia inhibited expression level of PI3K, phosphorylation of mTOR, phosphorylation of AKT, P62 and LAMP1, hence mediating the autophagy level of the neurocyte, which was reversed by the PI3K inhibitor Dactolisib. In summary, our results indicate that the protective effects of EA treatment at points of Quchi (LI11) and Zusanli (ST36) in rats following cerebral I/R injury was associated with the inhibition of neuronal apoptosis and autophagy via activating the PI3K/AKT/mTOR signaling pathway.

Inhibition of NLRP3 Inflammasome: A Prospective Target for the Treatment of Ischemic Stroke.

Stroke is one of the major devastating diseases with no effective medical therapeutics. Because of the high rate of disability and mortality among stroke patients, new treatments are urgently required to decrease brain damage following a stroke. In recent years, the inflammasome is a novel breakthrough point that plays an important role in the stroke, and the inhibition of inflammasome may be an effective method for stroke treatment. Briefly, inflammasome is a multi-protein complex that causes activation of caspase-1 and subsequent production of pro-inflammatory factors including interleukin (IL)-18 and IL-1ß. Among them, the NLRP3 inflammasome is the most typical inflammasome, which can detect cell damage and mediate inflammatory response to tissue damage in ischemic stroke. The NLRP3 inflammasome has become a key mediator of post-ischemic inflammation, leading to a cascade of inflammatory reactions and cell death eventually. Thus, NLRP3 inflammasome is an ideal therapeutic target due to its important role in the inflammatory response after ischemic stroke. In this mini review article, we will summarize the structure, assembly, and regulation of NLRP3 inflammasome, the role of NLRP3 inflammasome in ischemic stroke, and several treatments targeting NLRP3 inflammasome in ischemic stroke. The further understanding of the mechanism of NLRP3 inflammasome in patients with ischemic stroke will provide novel targets for the treatment of cerebral ischemic stroke patients.

The Beneficial Role of Exercise Training for Myocardial Infarction Treatment in Elderly.

Worldwide, elderly people have a higher prevalence of myocardial infarction (MI), which is associated with body function aging and a sedentary lifestyle. In addition to medication, exercise training is a well-established supplementary method to prevent and treat cardiovascular diseases (CVDs). Substantial evidence has shown the value of different intensity exercise programs in the prevention and treatment of MI, and exercise rehabilitation programs are also applicable to elderly patients with MI. Although exercise rehabilitation programs could significantly improve function, quality of life (QoL), and lower mortality and morbidity for people with MI, such programs are underused because their mechanisms are not accurately elucidated. To promote the application of exercise therapy for MI, this review summarizes the benefits and mechanisms of exercise rehabilitation for post-MI patients and provides rationalized proposals for outpatient cardiac rehabilitation.

The benefits and mechanisms of exercise training for Parkinson's disease.

Parkinson's disease (PD) is a significantly progressive neurodegenerative disease characterised by both motor and nonmotor disorders. The main pathological characteristics of PD consist of the loss of dopaminergic neurons and the formation of alpha-synuclein-containing Lewy bodies in the substantia nigra. Currently, the main therapeutic method for PD is anti-Parkinson medications, including levodopa, madopar, sirelin, and so on. However, the effect of pharmacological treatment has its own limitations, the most significant of which is that the therapeutic effect of dopaminergic treatments gradually diminishes with time. Exercise training, as an adjunctive treatment and complementary therapy, can improve the plasticity of cortical striatum and increase the release of dopamine. Exercise training has been proven to effectively improve motor disorders (including balance, gait, risk of falls and physical function) and nonmotor disorders (such as sleep impairments, cognitive function and quality of life) in PD patients. In recent years, various types of exercise training have been used to treat PD. In this review, we summarise the exercise therapy mechanisms and the protective effects of different types of exercise training on PD patients.

Mechanisms involved in the arthrofibrosis formation and treatments following bone fracture.

Arthrofibrosis is a common complication for patients with bone fracture following external and internal fixation. In this review, we summarize the related factors and significant pathways for joint adhesion following fracture surgery. Moreover, the different types of treatments and related preventive measures are also discussed. Many factors related to the development and treatment of arthrofibrosis are discussed in this review in order to provide possible clues for the prospective targets to develop new medication or treatments for preventing or reducing the joint adhesion following orthopedic surgery.

The Relationship Between Autophagy and Brain Plasticity in Neurological Diseases.

Autophagy, a catabolic degradation system, is utilized for destroying and recycling the damaged or unnecessary cellular components. Brain plasticity refers to the remarkable characteristics of brain neurons that change their structure and function according to previous experience. This review was performed by searching the relevant articles in databases of SCIENCEDIRECT, PUBMED, and Web of Science, from respective inception to January 2019. Here, we review the neuroprotective effect of autophagy in neurological diseases and the mechanism of autophagy in brain plasticity. Moreover, the mechanism of autophagy in the process of brain plasticity can provide the possibility for the development of new treatment methods in the future, thus benefiting patients with neurological diseases. In summary, autophagy and brain plasticity play important roles in neurological diseases.

The beneficial roles of exercise training via autophagy in neurological diseases and possible mechanisms.

Autophagy is a conservative catabolism process, participating in delivering the cytosol and cytosolic components to the lysosome. Abnormal autophagy is related to human pathologies, for instance diabetes, neurodegeneration, cardiovascular, macular degeneration, pulmonary, and cancer. Enormous evidences indicate that autophagy may mediate the cellular pathological condition in the process of neurological diseases. Exercise as a form of physiological stress may cause an adaptation, and autophagy is a necessary process for adaptational response to exercise. Autophagy during exercise may improve neurological function, control tissue maintain tissue integrity, and activate different signals pathway for adaptation. In this review, we summarize the possible mechanisms of exercise training via autophagy in neurological diseases.

Possible Involvement of PTEN Signaling Pathway in the Anti-apoptotic Effect of Electroacupuncture Following Ischemic Stroke in Rats.

As a traditional therapeutic method, electroacupuncture (EA) has been adopted as an alternative therapy for stroke recovery. Here, we aimed to evaluate whether EA therapy at points of Quchi (LI11) and Zusanli (ST36) alleviated neuronal apoptosis by PTEN signaling pathway after ischemic stroke. A total of 72 male Sprague-Dawley rats were randomized into three groups, including sham group, MCAO group, and EA group. EA was initiated after 24 h of reperfusion for 3 consecutive days. At 72 h following ischemia/reperfusion, neurological deficits, infarct volumes, and TUNEL staining were evaluated and the PTEN pathway-related proteins together with apoptosis-related proteins were detected. The results indicated that EA treatment significantly decreased cerebral infarct volume, neurological deficits and alleviated proportion of apoptotic cells in cerebral ischemic rats. Furthermore, EA significantly up-regulated the phosphorylation levels of PDK1, Akt(Thr308), GSK-3ß, and down-regulated the phosphorylation levels of PTEN, Akt(Ser473) in the peri-infarct cortex. EA treatment significantly reduced the up-regulation of caspase-3, cleaved-caspase-3, Bim, and reversed the reduction of Bcl-2 induced by the ischemic stroke. These findings suggest that EA treatment at points of Quchi (LI11)- and Zusanli (ST36)-induced neuroprotection might involve inhibition of apoptosis via PTEN pathway.

Electroacupuncture Alleviated Neuronal Apoptosis Following Ischemic Stroke in Rats via Midkine and ERK/JNK/p38 Signaling Pathway.

This study aimed to evaluate the effects of electroacupuncture (EA) intervention administered at rats of middle cerebral artery occlusion (MCAO)/reperfusion. Fifty-four male Sprague-Dawley rats were divided into three groups, consisting of sham group, MCAO/R group, and EA group. EA treatment at Quchi and Zusanli acupoints was applied in rats of EA group at 24 h after MCAO once per day for 3 days. Our results indicated that EA treatment reduced infarct volumes and neurological deficits, as well alleviated the apoptotic cells in peri-infarct cortex, indicating that EA exerted neuroprotective effect in cerebral ischemic rats. Moreover, EA treatment may effectively reverse the upregulation of caspase-3 and Bim and alleviate the inhibition of Bcl-2 following 72-h ischemic stroke. EA may significantly reverse the promoted relative density level of p-ERK1/2, p-JNK, and p-p38 in the EA group compared with the MCAO/R group. In addition, the growth factor midkine (MK) was upregulated at 72 h after MCAO/R, and EA treatment may significantly prompt expression of MK. Our study demonstrated that EA exerted neuroprotective effect against neuronal apoptosis and the mechanism might involve in upregulation of MK and mediation of ERK/JNK/p38 signal pathway.

The beneficial role of early exercise training following stroke and possible mechanisms.

Exercise training is a regular therapy for stroke patients in clinic. However, whether the early exercise is beneficial for stroke patients is still controversial. The review was performed in databases of OVID, PUBMED, and ISI Web of Science, from respective inception to December 2017. In this review, we summarize the effect of different exercise intensity, initiation time, and style on ischemic stroke. Moreover, the possible mechanism is also discussed. The conclusion is that the voluntary exercise is better in promoting the functional recovery following stroke compared to forced exercise; too early initiated exercise might play a harmful role following stroke, while early initiated exercise might exert benefits after stroke; mild and moderate intensity exercise training could generate better neuroprotection in comparison with high intensity exercise training; early excise training could regulate the process of brain edema, cell apoptosis, oxidative damage, stem cells and other mechanisms in order to exert neuroprotection for brain.