Parkinson's disease (PD) is a common neurodegenerative disorder that may increase the risk of falls, functional limitation, and balance deficits. Tai Chi was used as an option for improving balance in people with PD. The aim of this meta-analysis was to evaluate the effects of Tai Chi on falls, balance, and functional mobility in individuals with PD.

We conducted an observational study to investigate clinical predictors of cognitive decline in patients with mild cognitive impairment (MCI), with a focus on patients with Parkinson's disease (PD) and Alzheimer's disease (AD). The study was performed with detailed neuropsychological testing, a portable device for gait analysis, and a comprehensive geriatric assessment for patients with MCI. Cognitive decline was defined as subjective cognitive impairment with an objective decline in the Mini-Mental State Examination (MMSE) ≥2 points at the one-year follow-up. Participants (n = 74) had a median age of 70 (interquartile range 60-79) years, and 45.9% of them were women. At the end of the study, 17.6% of the patients with MCI had a cognitive decline. Although no differences were observed between groups at the baseline cognitive study, patients with PD-MCI demonstrated more cognitive decline than patients with AD-MCI (28.6% vs. 7.7% p = 0.03). Patients with PD-MCI had more physical disabilities, including scores of instrumental activities of daily living (IADL), Tinetti balance, and gait scores, and some Timed Up and Go components. Initial Clinical Dementia Rating-Sum of Boxes score was a better predictor of future cognitive decline than MMSE in PD-MCI. For predicting the occurrence of cognitive decline in PD-MCI, the prediction accuracy increased from the reduced model (AUC = 0.822, p < 0.001) to the full model (a total of five independent variables, AUC = 0.974, p < 0.001). Given the potentially modifiable predictor, our findings also highlight the importance of identifying sleep quality and the ability to perform IADL.

Lysyl oxidase-like 2 (LOXL2) is a matrix-remodeling enzyme that has recently been identified as an important regulator of tumor progression and metastasis. This study discovered that LOXL2 expression in oral squamous cell carcinoma (OSCC) tissues was significantly associated with tumor clinical stage, lymph node metastasis and patients' overall survival time. LOXL2-overexpressing human buccal SCC TW2.6 (TW2.6/LOXL2) and hypopharyngeal SCC FaDu (FaDu/LOXL2) cells exhibited enhanced migration, invasion, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) phenotypes, independently of its enzymatic activity. Moreover, TW2.6/LOXL2 significantly increased tumor-initiating frequency in SCID mice. We further demonstrated that LOXL2 increased the levels of interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) and IFIT3 in TW2.6/LOXL2 and FaDu/LOXL2 cells. We also identified IFIT1 and IFIT3 as key downstream components of LOXL2 action in migration, invasion, EMT, and CSC phenotypes in TW2.6 and FaDu cells. Furthermore, a significant positive correlation between LOXL2 expression and IFIT1 and IFIT3 overexpression in human OSCC tissues was observed. In addition, TW2.6/LOXL2 and FaDu/LOXL2 cells were 3.3- to 3.6-fold more susceptible to the epidermal growth factor receptor (EGFR) inhibitor gefitinib than were their respective control cells. The antitumor effect of gefitinib on orthotopic TW2.6/LOXL2 xenograft tumor was fourfold higher than that on controls. Our results indicate that LOXL2 expression is a strong prognostic factor for OSCC and may be used as a marker to identify patients most likely to respond to EGFR-targeted therapy.

Memory impairment is commonly noted in stroke survivors, and can lead to delay of functional recovery. Exercise has been proved to improve memory in adult healthy subjects. Such beneficial effects are often suggested to relate to hippocampal synaptic plasticity, which is important for memory processing. Previous evidence showed that in normal rats, low intensity exercise can improve synaptic plasticity better than high intensity exercise. However, the effects of exercise intensities on hippocampal synaptic plasticity and spatial memory after brain ischemia remain unclear. In this study, we investigated such effects in brain ischemic rats. The middle cerebral artery occlusion (MCAO) procedure was used to induce brain ischemia. After the MCAO procedure, rats were randomly assigned to sedentary (Sed), low-intensity exercise (Low-Ex), or high-intensity exercise (High-Ex) group. Treadmill training began from the second day post MCAO procedure, 30 min/day for 14 consecutive days for the exercise groups. The Low-Ex group was trained at the speed of 8 m/min, while the High-Ex group at the speed of 20 m/min. The spatial memory, hippocampal brain-derived neurotrophic factor (BDNF), synapsin-I, postsynaptic density protein 95 (PSD-95), and dendritic structures were examined to document the effects. Serum corticosterone level was also quantified as stress marker. Our results showed the Low-Ex group, but not the High-Ex group, demonstrated better spatial memory performance than the Sed group. Dendritic complexity and the levels of BDNF and PSD-95 increased significantly only in the Low-Ex group as compared with the Sed group in bilateral hippocampus. Notably, increased level of corticosterone was found in the High-Ex group, implicating higher stress response. In conclusion, after brain ischemia, low intensity exercise may result in better synaptic plasticity and spatial memory performance than high intensity exercise; therefore, the intensity is suggested to be considered during exercise training.

Coactivation of primary motor cortex ipsilateral to a unilateral movement (M1(ipsilateral)) has been observed, and the magnitude of activation is influenced by the contracting muscles. It has been suggested that the microstructural integrity of the callosal motor fibers (CMFs) connecting M1 regions may reflect the observed response. However, the association between the structural connectivity of CMFs and functional changes in M1(ipsilateral) remains unclear. The purpose of this study was to investigate the relationship between functional changes within M1(ipsilateral) during unilateral arm or leg movements and the microstructure of the CMFs connecting both homotopic representations (arm or leg).

This study investigated the effectiveness of Ai Chi compared to conventional water-based exercise on balance performance in individuals with chronic stroke. A total of 20 individuals with chronic stroke were randomly allocated to receive either Ai Chi or conventional water-based exercise for 60 min/time, 3 times/week, and a total of 6 weeks. Balance performance assessed by limit of stability (LOS) test and Berg balance scale (BBS). Fugl-Meyer assessment (FMA) and gait performance were documented for lower extremity movement control and walking ability, respectively. Excursion and movement velocity in LOS test was significantly increased in anteroposterior axis after receiving Ai Chi (p = 0.005 for excursion, p = 0.013 for velocity) but not conventional water-based exercise. In particular, the improvement of endpoint excursion in the Ai Chi group has significant inter-group difference (p = 0.001). Both groups showed significant improvement in BBS and FMA yet the Ai Chi group demonstrated significantly better results than control group (p = 0.025). Ai Chi is feasible for balance training in stroke, and is able to improve weight shifting in anteroposterior axis, functional balance, and lower extremity control as compared to conventional water-based exercise.

In daily life, mobility requires walking while performing a cognitive or upper-extremity motor task. Although previous studies have evaluated the effects of dual tasks on gait performance, few studies have evaluated cortical activation and its association with gait disturbance during dual tasks. In this study, we simultaneously assessed gait performance and cerebral oxygenation in the bilateral prefrontal cortices (PFC), premotor cortices (PMC), and supplemental motor areas (SMA), using functional near-infrared spectroscopy, in 17 young adults performing dual tasks. Each participant was evaluated while performing normal-pace walking (NW), walking while performing a cognitive task (WCT), and walking while performing a motor task (WMT). Our results indicated that the left PFC exhibited the strongest and most sustained activation during WCT, and that NW and WMT were associated with minor increases in oxygenation levels during their initial phases. We observed increased activation in channels in the SMA and PMC during WCT and WMT. Gait data indicated that WCT and WMT both caused reductions in walking speed, but these reductions resulted from differing alterations in gait properties. WCT was associated with significant changes in cadence, stride time, and stride length, whereas WMT was associated with reductions in stride length only. During dual-task activities, increased activation of the PMC and SMA correlated with declines in gait performance, indicating a control mechanism for maintaining gait performance during dual tasks. Thus, the regulatory effects of cortical activation on gait behavior enable a second task to be performed while walking.

Two different training strategies to improve turning performance in individuals with Parkinson's disease (PD) were designed and investigated in this study. Subjects were randomly assigned to a specific exercise group, turning-based training group, or control group to receive training that emphasized balance and strengthening, turning-based treadmill training, and general exercise training, respectively. A total of 12 30-min training sessions followed by 10 min of turning training on a level surface were administered over 4 to 6 weeks. The results (n = 12 for each group) showed that both the specific exercise and turning-based training group experienced improved turning performance, the primary outcome, compared with the control group (specific exercise, 33% change, p = 0.016; turning-based training, 35% change, p = 0.021). For the secondary outcomes, the specific exercise group performed better than the control group on the Tinetti balance scale, limit of stability test and lower extremity extensor and abductor strength. The turning-based training groups performed better than the control group in sensory organization and ankle plantar flexor strength. In summary, specific exercise training and turning-based treadmill training were both effective in improving turning performance in participants with PD. However, the improvements in turning performance of these two groups resulted from improving different aspects of impairment in individuals with PD.

Memory impairment is a frequent complication of brain ischemia. Neurogenesis is implicated in learning and memory and is regulated by the transcription factor c-Fos. Preconditioning intermittent hypoxia (IH) attenuates ischemia-related memory impairments, but it is not known whether post-ischemia IH intervention has a similar effect. We investigated the effects of post-ischemia IH on hippocampal neurogenesis and c-Fos expression as well as spatial learning and memory in rats.

To explore the effects of transcranial direct current stimulation followed by treadmill training on dual-task gait performance and contralesional cortical activity in chronic stroke patients.

Neurogenesis is a physiological response after cerebral ischemic injury to possibly repair the damaged neural network. Therefore, promoting neurogenesis is very important for functional recovery after cerebral ischemic injury. Our previous research indicated that hyperbaric oxygen therapy (HBOT) exerted neuroprotective effects, such as reducing cerebral infarction volume. The purposes of this study were to further explore the effects of HBOT on the neurogenesis and the expressions of cell migration factors, including the stromal cell-derived factor 1 (SDF1) and its target receptor, the CXC chemokine receptor 4 (CXCR4). Thirty-two Sprague-Dawley rats were divided into the control or HBO group after receiving transient middle cerebral artery occlusion (MCAO). HBOT began to intervene 24 h after MCAO under the pressure of 3 atmospheres for one hour per day for 21 days. Rats in the control group were placed in the same acrylic box without HBOT during the experiment. After the final intervention, half of the rats in each group were cardio-perfused with ice-cold saline followed by 4% paraformaldehyde under anesthesia. The brains were removed, dehydrated and cut into serial 20μm coronal sections for immunofluorescence staining to detect the markers of newborn cell (BrdU+), mature neuron cell (NeuN+), SDF1, and CXCR4. The affected motor cortex of the other half rats in each group was separated under anesthesia and used to detect the expressions of brain-derived neurotrophic factor (BDNF), SDF1, and CXCR4. Motor function was tested by a ladder-climbing test before and after the experiment. HBOT significantly enhanced neurogenesis in the penumbra area and promoted the expressions of SDF1 and CXCR4. The numbers of BrdU+/SDF1+, BrdU+/CXCR4+, and BrdU+/NeuN+ cells and BDNF concentrations in the penumbra were all significantly increased in the HBO group when compared with the control group. The motor functions were improved in both groups, but there was a significant difference between groups in the post-test. Our results indicated that HBOT for 21 days enhanced neurogenesis and promoted cell migration toward the penumbra area in transient brain ischemic rats. HBOT also increased BDNF expression, which might further promote the reconstructions of the impaired neural networks and restore motor function.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is the rate-limiting enzyme of ketogenesis. Growing evidence indicates that HMGCS2 may be involved in cancer progression, but its exact role is largely unknown. In this study, we demonstrate that HMGCS2 mRNA expression is associated with poor clinical prognosis and outcomes in patients with colorectal cancer (CRC) and oral squamous cell carcinoma (OSCC). In vitro, ectopic expression of HMGCS2 enhanced cancer cell motility in a ketogenesis-independent manner. Moreover, HMGCS2 promoted Src activity by directly binding to peroxisome proliferator-activated receptor alpha (PPARα), a transcriptional activator of Src. Taken together, these results suggest that HMGCS2 may serve as a useful prognostic marker and vital target for future therapeutic strategies against advanced cancer.

This study investigated effects of cognitive and motor dual task gait training on dual task gait performance in stroke. Participants (n = 28) were randomly assigned to cognitive dual task gait training (CDTT), motor dual task gait training (MDTT), or conventional physical therapy (CPT) group. Participants in CDTT or MDTT group practiced the cognitive or motor tasks respectively during walking. Participants in CPT group received strengthening, balance, and gait training. The intervention was 30 min/session, 3 sessions/week for 4 weeks. Three test conditions to evaluate the training effects were single walking, walking while performing cognitive task (serial subtraction), and walking while performing motor task (tray-carrying). Parameters included gait speed, dual task cost of gait speed (DTC-speed), cadence, stride time, and stride length. After CDTT, cognitive-motor dual task gait performance (stride length and DTC-speed) was improved (p = 0.021; p = 0.015). After MDTT, motor dual task gait performance (gait speed, stride length, and DTC-speed) was improved (p = 0.008; p = 0.008; p = 0.008 respectively). It seems that CDTT improved cognitive dual task gait performance and MDTT improved motor dual task gait performance although such improvements did not reach significant group difference. Therefore, different types of dual task gait training can be adopted to enhance different dual task gait performance in stroke.

Gait impairments in Parkinson's disease (PD) are aggravated under dual task conditions. Providing effective training to enhance different dual task gait performance is important for PD rehabilitation. This pilot study aimed to investigate the effects of cognitive and motor dual task gait training on dual task gait performance in PD. Eighteen PD participants (n = 6 per training group) were assigned to cognitive dual task gait training (CDTT), motor dual task gait training (MDTT), or general gait training (control) group randomly. The training was 30 min each session, 3 sessions per week for 4 weeks. Primary outcomes including gait performance during cognitive dual task, motor dual task, and single walking were assessed at pre- and post-training. The results showed decreased double support time during cognitive dual task walking after CDTT (-17.1±10.3%) was significantly more than MDTT (6.3±25.6%, p = .006) and control training (-5.6±7.8%, p = .041). Stride time variability during motor dual task walking decreased more after MDTT (-16.3±32.3%) than CDTT (38.6±24.0%, p = .015) and control training (36.8±36.4%, p = .041). CDTT also improved motor dual task walking performance especially on gait speed (13.8±10.71%, p = .046) stride length (10.5±6.6%, p = .046), and double support time (-8.0±2.0%, p = .028). CDTT improved single walking performance as well on gait speed (11.4±5.5%, p = .046), stride length (9.2±4.6%, p = .028), and double support time (-8.1±3.0%, p = .028). In summary, our preliminary data showed 12-session of CDTT decreased double support time during cognitive dual task walking, and MDTT reduced gait variability during motor dual task walking. Different training strategy can be adopted for possibly different training effects in people with PD.

Motoric cognitive risk syndrome (MCR) is defined by slow gait speed combined with subjective cognitive complaint. MCR is a predementia syndrome, similar to mild cognitive impairment (MCI). However, there is currently no study comparing the differences in cognitive performance and physical function between these two types of cognitive impairment. Thus, the aim of this study is to compare cognitive performance and physical function in individuals with MCR versus MCI.

The suppressive regulatory T cells (Treg) are frequently upregulated in cancer patients. This study aims to demonstrate the hypothesis that arecoline could induce the secretion of mitochondrial (mt) DNA D-loop and programmed cell death-ligand 1 (PD-L1) in extracellular vesicles (EVs), and attenuate T-cell immunity by upregulated Treg cell numbers. However, the immunosuppression could be reversed by whole glucan particle (WGP) β-glucan in oral squamous cell (OSCC) patients. Arecoline-induced reactive oxygen specimen (ROS) production and cytosolic mtDNA D-loop were analyzed in OSCC cell lines. mtDNA D-loop, PD-L1, IFN-γ, and Treg cells were also identified for the surgical specimens and sera of 60 OSCC patients. We demonstrated that higher mtDNA D-loop, PD-L1, and Treg cell numbers were significantly correlated with larger tumor size, nodal metastasis, advanced clinical stage, and areca quid chewing. Furthermore, multivariate analysis confirmed that higher mtDNA D-loop levels and Treg cell numbers were unfavorable independent factors for survival. Arecoline significantly induced cytosolic mtDNA D-loop leakage and PD-L1 expression, which were packaged by EVs to promote immunosuppressive Treg cell numbers. However, WGP β-glucan could elevate CD4+ and CD8+ T-cell numbers, mitigate Treg cell numbers, and promote oral cancer cell apoptosis. To sum up, arecoline induces EV production carrying mtDNA D-loop and PD-L1, and in turn elicits immune suppression. However, WGP β-glucan potentially enhances dual effects on T-cell immunity and cell apoptosis and we highly recommend its integration with targeted and immune therapies against OSCC.

Brain ischemia leads to muscle inactivity-induced atrophy and may exacerbate motor function deficits. Intramuscular insulin-like growth factor I (IGF-I) injection has been shown to alleviate the brain ischemia-induced muscle atrophy and thus improve the motor function. Motor function is normally gauged by the integrity and coordination of the central nervous system and peripheral muscles. Whether brain ischemic regions are adaptively changed by the intramuscular IGF-I injection is not well understood. In this study, the effect of intramuscular IGF-I injection was examined on the central nervous system of brain ischemic rats. Rats were divided into 4 groups: sham control, brain ischemia control, brain ischemia with IGF-I treatment, and brain ischemia with IGF-I plus IGF-I receptor inhibitor treatment. Brain ischemia was induced by right middle cerebral artery occlusion. IGF-I and an IGF-1 receptor inhibitor were injected into the affected calf and anterior tibialis muscles of the treated rats for 4 times. There was an interval of 2 days between each injection. Motor function was examined and measured at the 24 hours and 7 days following a brain ischemia. The affected hind-limb muscles, sciatic nerve, lumbar spinal cord, and motor cortex were collected for examination after euthanizing the rats. IGF-I expression in the central nervous system and affected muscles were significantly decreased after brain ischemia. Intramuscular IGF-I injection increased the IGF-I expression in the affected muscles, sciatic nerve, lumbar spinal cord, and motor cortex. It also increased the p-Akt expression in the affected motor cortex. Furthermore, intramuscular IGF-I injection decreased the neuronal apoptosis and improved the motor function. However, co-administration of the IGF-I receptor inhibitor eliminated these effects. Intramuscular IGF-I injection after brain ischemia attenuated or reversed the decrease of IGF-I in both central and peripheral tissues, and these effects could contribute to neuroprotection and improve motor function.

Neuromuscular electrical stimulation (NMES) has been used to improve muscle strength and decrease spasticity of the ankle joint in stroke patients. However, it is unclear how NMES could influence dynamic spasticity of ankle plantarflexors and gait asymmetry during walking. The study aimed to evaluate the effects of applying NMES over ankle dorsiflexors or plantarflexors on ankle control during walking and gait performance in chronic stroke patients. Twenty-five stroke participants with inadequate ankle control were recruited and randomly assigned to an experimental or a control group. The experimental group received 20 minutes of NMES on either the tibialis anterior muscle (NMES-TA) or the medial gastrocnemius muscle (NMES-MG). The control group received 20 minutes of range of motion and stretching exercises. After the 20 minutes of NMES or exercises, all participants received ambulation training for 15 minutes. Training sessions occurred 3 times per week for 7 weeks. The pre- and post-training assessments included spatio-temporal parameters, ankle range of motion, and dynamic spasticity of ankle plantarflexors during walking. Muscle strength of ankle dorsiflexors and plantarflexors as well as static spasticity of ankle plantarflexors were also examined. The results showed that the static and dynamic spasticity of ankle plantarflexors of the NMES-TA group were significantly decreased after training. Reduction in dynamic spasticity of ankle plantarflexors of the NMES-TA group was significantly greater than that of the NMES-MG group. When compared to the control group, the NMES-TA group had greater improvements in spatial asymmetry, ankle plantarflexion during push off, and muscle strength of ankle dorsiflexors, and the NMES-MG group showed a significant decrease in temporal asymmetry. In summary, NMES on ankle dorsiflexors could be an effective management to enhance gait performance and ankle control during walking in chronic stroke patients. NMES on ankle plantarflexors may improve gait symmetry.

Hyperbaric oxygen (HBO) has been suggested as a possible therapy for brain injury. However, the effects of HBO after transient brain ischemia are inconsistent and the underlying mechanisms are not fully known. The present study aimed to investigate the effects of repetitive HBO intervention in a transient middle cerebral artery occlusion (MCAO) animal model. Seventy-two Sprague-Dawley rats received MCAO and were randomly assigned to normal air control or HBO intervention groups. Each group was divided into 3 subgroups according to the intervention time period (7, 14, and 21 days). HBO was started 24 h post-MCAO for 1 h/day at 3.0 ATA with no-air breaks. After the final intervention, half of the rats in each subgroup were sacrificed and the right motor cortex was removed to examine levels of Akt phosphorylation and glutathione (GSH), as well as glutathione peroxidase (GPx) and reductase (GR) activity. The other half of the rats were used to examine infarct volume. At 24 h post-MCAO and the end of the final intervention, rats underwent tests to examine motor performance. We noted that 14- and 21-day HBO interventions significantly reduced infarct volume and increased Akt phosphorylation and GSH levels and GPx and GR activity. Motor performance was also significantly improved after 14- and 21-day interventions. No significant differences were observed between the controls and 7-day intervention groups. Repetitive HBO intervention starting 24 h post-MCAO and applied for at least 14 days, provided neuroprotective effects through modulating the cell survival pathway and antioxidative defense system.