Exercise has been proposed as an effective non-pharmacological management for Parkinson’s disease (PD) patients. Irisin, a recently identified myokine, is increased by exercise and plays pivotal roles in energy metabolism. However, it remains unknown whether irisin has any protective effects on PD. Here, we found that serum irisin levels of PD patients were markedly elevated after 12-week regular exercise, which had a positive correlation with improved balance function scored by Berg Balance Scale. Treatment with exogenous irisin could improve motor function, and reduce dopaminergic neurodegeneration in PD models. Meanwhile, irisin could reduce cell apoptosis by renovating mitochondrial function in PD models, which was reflected in decreased oxidative stress, increased mitochondrial complex I activity and mitochondrial content, increased mitochondrial biogenesis, and repaired mitochondrial morphology. Furthermore, irisin regulated the aforementioned aspects by upregulating downstream Akt signaling pathway and ERK1/2 signaling pathway through integrin receptors rather than directly targeting mitochondria. With the use of small-molecule inhibitors, it was found that irisin can reduce apoptosis, restore normal mitochondrial biogenesis, and improve mitochondrial morphology and dynamic balance in PD models by activating Akt signaling pathway and ERK1/2 signaling pathway. And irisin reduced oxidative stress via activating ERK1/2 signaling pathway. The results revealed that exogenous irisin conferred neuroprotection relieving apoptosis and oxidative stress, restraining mitochondrial fragmentation, and promoting mitochondrial respiration and biogenesis in PD models, and irisin exerted the aforementioned effects by activating Akt signaling pathway and ERK1/2 signaling pathway. Thus, peripherally delivered irisin might be a promising candidate for therapeutic targeting of PD.

Previous research has used the brain-computer interface (BCI) to promote upper-limb motor rehabilitation. However, the results of these studies were variable, leaving efficacy unclear. This review aims to evaluate the effects of BCI-based training on post-stroke upper-limb rehabilitation and identify potential factors that may affect the outcome. A meta-analysis including all available randomized-controlled clinical trials (RCTs) that reported the efficacy of BCI-based training on upper-limb motor rehabilitation after stroke. We searched PubMed, Cochrane Library, and Web of Science before September 15, 2024, for relevant studies. The primary efficacy outcome was the Fugl-Meyer Assessment-Upper extremity (FMA-UE). RevMan 5.4.1 with a random effect model was used for data synthesis and analysis. Mean difference (MD) and 95% confidence interval (95%CI) were calculated. Twenty-one RCTs (n = 886 patients) were reviewed in the meta-analysis. Compared with control, BCI-based training exerted significant effects on FMA-UE (MD = 3.69, 95%CI 2.41–4.96, P < 0.00001, moderate-quality evidence), Wolf Motor Function Test (WMFT) (MD = 5.00, 95%CI 2.14–7.86, P = 0.0006, low-quality evidence), and Action Research Arm Test (ARAT) (MD = 2.04, 95%CI 0.25–3.82, P = 0.03, high-quality evidence). Additionally, BCI-based training was effective on FMA-UE for both subacute (MD = 4.24, 95%CI 1.81–6.67, P = 0.0006) and chronic patients (MD = 2.63, 95%CI 1.50–3.76, P < 0.00001). BCI combined with functional electrical stimulation (FES) (MD = 4.37, 95%CI 3.09–5.65, P < 0.00001), robots (MD = 2.87, 95%CI 0.69–5.04, P = 0.010), and visual feedback (MD = 4.46, 95%CI 0.24–8.68, P = 0.04) exhibited significant effects on FMA-UE. BCI combined with FES significantly improved FMA-UE for both subacute (MD = 5.31, 95%CI 2.58–8.03, P = 0.0001) and chronic patients (MD = 3.71, 95%CI 2.44–4.98, P < 0.00001), and BCI combined with robots was effective for chronic patients (MD = 1.60, 95%CI 0.15–3.05, P = 0.03). Better results may be achieved with daily training sessions ranging from 20 to 90 min, conducted 2–5 sessions per week for 3–4 weeks. BCI-based training may be a reliable rehabilitation program to improve upper-limb motor impairment and function. PROSPERO registration ID: CRD42022383390.

Background: Glioblastoma (GBM) is a universally lethal tumor with frequently overexpressed or mutated epidermal growth factor receptor (EGFR). NADPH quinone oxidoreductase 1 (NQO1) and glutathione-S-transferase Pi 1 (GSTP1) are commonly upregulated in GBM. NQO1 and GSTP1 decrease the formation of reactive oxygen species (ROS), which mediates the oxidative stress and promotes GBM cell proliferation. Methods: High-throughput screen was used for agents selectively active against GBM cells with EGFRvIII mutations. Co-crystal structures were revealed molecular details of target recognition. Pharmacological and gene knockdown/overexpression approaches were used to investigate the oxidative stress in vitro and in vivo. Results: We identified a small molecular inhibitor, “MNPC,” that binds to both NQO1 and GSTP1 with high affinity and selectivity. MNPC inhibits NQO1 and GSTP1 enzymes and induces apoptosis in GBM, specifically inhibiting the growth of cell lines and primary GBM bearing the EGFRvIII mutation. Co-crystal structures between MNPC and NQO1, and molecular docking of MNPC with GSTP1 reveal that it binds the active sites and acts as a potent dual inhibitor. Inactivation of both NQO1 and GSTP1 with siRNA or MNPC results in imbalanced redox homeostasis, leading to apoptosis and mitigated cancer proliferation in vitro and in vivo. Conclusions: Thus, MNPC, a dual inhibitor for both NQO1 and GSTP1, provides a novel lead compound for treating GBM via the exploitation of specific vulnerabilities created by mutant EGFR.

Background: Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that has been closely examined as a possible treatment for Parkinson’s disease (PD). Owing to various rTMS protocols and results, the optimal mode and suitable PD symptoms have yet to be established. Objectives: This study intends to systematically evaluate the efficacy of rTMS intervention and identify optimal stimulation protocol of rTMS for specific motor symptoms. Methods: PubMed and web of Science databases were searched before January 2022. Eligible studies included sham-controlled and randomized clinical trials of rTMS intervention for motor dysfunction in patients with PD. Standard mean difference (SMD) was calculated with random-effects models. The effects of rTMS on motor symptoms were mainly estimated by the UPDRS-III. Results: A total of 1172 articles were identified, of which 32 articles met the inclusion criteria for meta-analysis. The pooled evidence suggested that rTMS relieves motor symptoms of patients with PD (SMD 0.64, 95%CI [0.47, 0.80]). High frequency stimulation on M1 is the most effective mode of intervention (SMD 0.79, 95%CI [0.52, 1.07]). HF rTMS has significant therapeutic effects on limbs motor function (SMD 1.93, 95%CI [0.73, 3.12] for upper limb function and SMD 0.88, 95%CI [0.43, 1.33] for lower limb function), akinesia (SMD 1.17, 95%CI [0.43, 1.92), rigidity (SMD 1.02, 95%CI [0.12, 1.92]) and tremor(SMD 0.91, 95%CI [0.15, 1.67]). Conclusion: rTMS therapy is an effective treatment for motor symptoms of PD and the individualized stimulation protocols for different symptoms would further improve its clinical efficacy.