Direction-dependent differences in the quality and quantity of horizontal reaching in people after stroke.

Arm reaching is often impaired in individuals with stroke. Nonetheless, how aiming directions influence reaching performance and how such differences change with motor recovery over time remain unclear. Here, we elucidated kinematic parameters of reaching toward various directions in people with poststroke hemiparesis in the subacute phase. A total of 13 and 15 participants with mild and moderate-to-severe hemiparesis, respectively, performed horizontal reaching in eight directions with their more-affected and less-affected sides using an exoskeleton robotic device at the time of admission to and discharge from the rehabilitation ward of the hospital. The movement time, path length, and number of velocity peaks were computed for the mild group (participants able to reach toward all eight directions). In addition, the total amount of displacement (i.e., movement quantity) toward two simplified directions (mediolateral or anteroposterior) was evaluated for the moderate-to-severe group (participants who showed difficulty in completing the reaching task). Motor recovery was evaluated using the Fugl-Meyer assessment. The mild group showed worse values of movement parameters during reaching in the anteroposterior direction, irrespective of the side of the arm or motor recovery achieved. The moderate-to-severe group exhibited less movement toward the anteroposterior direction than toward the mediolateral direction at admission; however, this direction-dependent bias in movement quantity decreased, with the movement expanding toward the anteroposterior direction with motor recovery at discharge. These results suggest that direction-dependent differences in the quality and quantity of reaching performance exist in people after stroke, regardless of the presence or severity of hemiparesis. This highlights the need to consider the task work area when designing rehabilitative training.NEW & NOTEWORTHY Arm reaching, a fundamental function required for the upper extremities, is often impaired after stroke due to muscle weakness and abnormal synergies. Nonetheless, how aiming directions influence performance remains unclear. Here, we report that direction-dependent differences in the quality and quantity of reaching performance exist, surprisingly regardless of the presence or severity of hemiparesis. This result highlights the need to consider the task work area when designing rehabilitative training.

Effects of trunk neuromuscular electrical stimulation on the motor circuits of able-bodied individuals.

Upper- and lower-limb neuromuscular electrical stimulation (NMES) is known to modulate the excitability of the neural motor circuits. However, it remains unclear whether short-duration trunk muscle NMES could achieve similar neuromodulation effects. We assessed motor evoked potentials (MEPs) elicited through transcranial magnetic stimulation of the primary motor cortex representation of the trunk extensor muscles to evaluate corticospinal excitability. Moreover, cervicomedullary motor evoked potentials (CMEPs) were assessed through cervicomedullary junction magnetic stimulation to evaluate subcortical excitability. Twelve able-bodied individuals participated in the MEP study, and another twelve in the CMEP study. During the interventions, NMES was applied bilaterally to activate the erector spinae muscle and produce intermittent contractions (20 s ON/20 s OFF) for a total of 20 min while participants remained seated. Assessments were performed: (i) before; (ii) during (in brief periods when NMES was OFF); and (iii) immediately after the interventions to compare MEP or CMEP excitability. Our results showed that MEP responses were not affected by trunk NMES, while CMEP responses were facilitated for approximately 8 min during the intervention, and returned to baseline before the end of the 20 min stimulating period. Our findings therefore suggest that short-duration NMES of the trunk extensor muscles likely does not affect the corticospinal excitability, but it has a potential to facilitate subcortical neural circuits immediately after starting the intervention. These findings indicate that short-duration application of NEMS may be helpful in rehabilitation to enhance neuromodulation of the trunk subcortical neural motor circuits.

Corticospinal excitability and somatosensory information processing of the lower limb muscle during upper limb voluntary or electrically induced muscle contractions.

Neural interactions between upper and lower limbs underlie motor coordination in humans. Specifically, upper limb voluntary muscle contraction can facilitate spinal and corticospinal excitability of the lower limb muscles. However, little remains known on the involvement of somatosensory information in arm-leg neural interactions. Here, we investigated effects of voluntary and electrically induced wrist flexion on corticospinal excitability and somatosensory information processing of the lower limbs. In Experiment 1, we measured transcranial magnetic stimulation (TMS)-evoked motor evoked potentials (MEPs) of the resting soleus (SOL) muscle at rest or during voluntary or neuromuscular electrical stimulation (NMES)-induced wrist flexion. The wrist flexion force was matched to 10% of the maximum voluntary contraction (MVC). We found that SOL MEPs were significantly increased during voluntary, but not NMES-induced, wrist flexion, compared to the rest (P < .001). In Experiment 2, we examined somatosensory evoked potentials (SEPs) following tibial nerve stimulation under the same conditions. The results showed that SEPs were unchanged during both voluntary and NMES-induced wrist flexion. In Experiment 3, we examined the modulation of SEPs during 10%, 20% and 30% MVC voluntary wrist flexion. During 30% MVC voluntary wrist flexion, P50-N70 SEP component was significantly attenuated compared to the rest (P = .003). Our results propose that the somatosensory information generated by NMES-induced upper limb muscle contractions may have a limited effect on corticospinal excitability and somatosensory information processing of the lower limbs. However, voluntary wrist flexion modulated corticospinal excitability and somatosensory information processing of the lower limbs via motor areas.

Short-term facilitation effects elicited by cortical priming through theta burst stimulation and functional electrical stimulation of upper-limb muscles.

Non-invasive theta burst stimulation (TBS) can elicit facilitatory or inhibitory changes in the central nervous system when applied intermittently (iTBS) or continuously (cTBS). Conversely, neuromuscular electrical stimulation (NMES) can activate the muscles to send a sensory volley, which is also known to affect the excitability of the central nervous system. We investigated whether cortical iTBS (facilitatory) or cTBS (inhibitory) priming can affect subsequent NMES-induced corticospinal excitability. A total of six interventions were tested, each with 11 able-bodied participants: cortical priming followed by NMES (iTBS + NMES and cTBS + NMES), NMES only (iTBSsham + NMES and cTBSsham + NMES), and cortical priming only (iTBS + rest and cTBS + rest). After iTBS or cTBS priming, NMES was used to activate right extensor capri radialis (ECR) muscle intermittently for 10 min (5 s ON/5 s OFF). Single-pulse transcranial magnetic stimulation motor evoked potentials (MEPs) and maximum motor response (Mmax) elicited by radial nerve stimulation were compared before and after each intervention for 30 min. Our results showed that associative facilitatory iTBS + NMES intervention elicited greater MEP facilitation that lasted for at least 30 min after the intervention, while none of the interventions alone were effective to produce effects. We conclude that facilitatory iTBS priming can make the central nervous system more susceptible to changes elicited by NMES through sensory recruitment to enhance facilitation of corticospinal plasticity, while cTBS inhibitory priming efficacy could not be confirmed.

1'-Acetoxychavicol Acetate Increases Proteasome Activity by Activating cAMP-PKA Signaling.

Protein degradation systems are critical pathways for the maintenance of protein homeostasis. The age-dependent attenuation of the proteasome activity contributes to age-related neurodegenerative processes. The molecule 1'-acetoxychavicol acetate (ACA) is naturally obtained from the rhizomes and seeds of Zingiberaceae plants, such as Languas galangal and Alpinia galangal, and exhibits anti-carcinogenic effects. Recently, we have shown that ACA protected the age-related learning and memory impairments in senescence-accelerated mice and maintained cognitive performance. Therefore, we here examined the effects of ACA on the protein degradation systems and cell protection against neurotoxicity in differentiated PC12 cells. ACA increased proteasome activity in PC12 cells. Increased proteasome activity occurred during the initial stages of ACA treatment and lasted at least 9 h. The activity returned to control levels within 24 h. The increase in proteasome activity by ACA was suppressed by H-89, which is a cAMP-dependent protein kinase A inhibitor. ACA increased the adenylate cyclase activity and therefore the intracellular cAMP levels. Furthermore, ACA recovered the initial cell viability, which was reduced after the addition of the amyloid ß-protein fragment to neuronally differentiated PC12 cells. The effects of ACA on amyloid toxicity were reduced after treatment with MG132, a proteasome inhibitor. These results demonstrated a neuroprotective effect of ACA via activation of cAMP/cAMP-dependent protein kinase A signaling in neuronally differentiated PC12 cells.

Phosphonate-based irreversible inhibitors of human γ-glutamyl transpeptidase (GGT). GGsTop is a non-toxic and highly selective inhibitor with critical electrostatic interaction with an active-site residue Lys562 for enhanced inhibitory activity.

γ-Glutamyl transpeptidase (GGT, EC 2.3.2.2) that catalyzes the hydrolysis and transpeptidation of glutathione and its S-conjugates is involved in a number of physiological and pathological processes through glutathione metabolism and is an attractive pharmaceutical target. We report here the evaluation of a phosphonate-based irreversible inhibitor, 2-amino-4-{[3-(carboxymethyl)phenoxy](methoyl)phosphoryl}butanoic acid (GGsTop) and its analogues as a mechanism-based inhibitor of human GGT. GGsTop is a stable compound, but inactivated the human enzyme significantly faster than the other phosphonates, and importantly did not inhibit a glutamine amidotransferase. The structure-activity relationships, X-ray crystallography with Escherichia coli GGT, sequence alignment and site-directed mutagenesis of human GGT revealed a critical electrostatic interaction between the terminal carboxylate of GGsTop and the active-site residue Lys562 of human GGT for potent inhibition. GGsTop showed no cytotoxicity toward human fibroblasts and hepatic stellate cells up to 1mM. GGsTop serves as a non-toxic, selective and highly potent irreversible GGT inhibitor that could be used for various in vivo as well as in vitro biochemical studies.

Protective Effects of Hydrolyzed Nucleoproteins from Salmon Milt against Ethanol-Induced Liver Injury in Rats.

Dietary nucleotides play a role in maintaining the immune responses of both animals and humans. Oral administration of nucleic acids from salmon milt have physiological functions in the cellular metabolism, proliferation, differentiation, and apoptosis of human small intestinal epithelial cells. In this study, we examined the effects of DNA-rich nucleic acids prepared from salmon milt (DNSM) on the development of liver fibrosis in an in vivo ethanol-carbon tetrachloride cirrhosis model. Plasma aspartate transaminase and alanine transaminase were significantly less active in the DNSM-treated group than in the ethanol plus carbon tetrachloride (CCl4)-treated group. Collagen accumulation in the liver and hepatic necrosis were observed histologically in ethanol plus CCl4-treated rats; however, DNSM-treatment fully protected rats against ethanol plus CCl4-induced liver fibrosis and necrosis. Furthermore, we examined whether DNSM had a preventive effect against alcohol-induced liver injury by regulating the cytochrome p450 2E1 (CYP2E1)-mediated oxidative stress pathway in an in vivo model. In this model, CYP2E1 activity in ethanol plus CCl4-treated rats increased significantly, but DNSM-treatment suppressed the enzyme's activity and reduced intracellular thiobarbituric acid reactive substances (TBARS) levels. Furthermore, the hepatocytes treated with 100 mM ethanol induced an increase in cell death and were not restored to the control levels when treated with DNSM, suggesting that digestive products of DNSM are effective for the prevention of alcohol-induced liver injury. Deoxyadenosine suppressed the ethanol-induced increase in cell death and increased the activity of alcohol dehydrogenase. These results suggest that DNSM treatment represents a novel tool for the prevention of alcohol-induced liver injury.

Ecklonia cava Polyphenol Has a Protective Effect against Ethanol-Induced Liver Injury in a Cyclic AMP-Dependent Manner.

Previously, we showed that Ecklonia cava polyphenol (ECP) treatment suppressed ethanol-induced increases in hepatocyte death by scavenging intracellular reactive oxygen species (ROS) and maintaining intracellular glutathione levels. Here, we examined the effects of ECP on the activities of alcohol-metabolizing enzymes and their regulating mechanisms in ethanol-treated hepatocytes. Isolated hepatocytes were incubated with or without 100 mM ethanol. ECP was dissolved in dimethylsulfoxide. ECP was added to cultured cells that had been incubated with or without ethanol. The cells were incubated for 0-24 h. In cultured hepatocytes, the ECP treatment with ethanol inhibited cytochrome P450 2E1 (CYP2E1) expression and activity, which is related to the production of ROS when large quantities of ethanol are oxidized. On the other hand, ECP treatment with ethanol increased the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. These changes in activities of CYP2E1 and ADH were suppressed by treatment with H89, an inhibitor of protein kinase A. ECP treatment with ethanol enhanced cyclic AMP concentrations compared with those of control cells. ECP may be a candidate for preventing ethanol-induced liver injury via regulating alcohol metabolic enzymes in a cyclic AMP-dependent manner.

Gamified exercise for the distal upper extremity in people with post-stroke hemiparesis: feasibility study on subjective perspectives during daily continuous training.

INTRODUCTION: Dose (number of repetitions) has been suggested as a key element in the effectiveness of rehabilitation exercises to promote motor recovery of the hemiparetic upper limb. However, rehabilitation exercises tend to be monotonous and require significant motivation to continue, making it difficult to increase the exercise dose. To address this issue, gamification technology has been implemented in exercises to promote self-engagement for people with hemiparesis in continuing monotonous repetitive movements. This study aimed to investigate how subjective perspectives, specifically enjoyability, motivation to continue, and expectancy of effectiveness, change through continuous daily exercise using a developed gamified exercise system. MATERIALS AND METHOD: Ten people with stroke suffering upper limb dysfunction underwent daily gamified exercise for seven days. The gamified exercise consisted of an electromyography (EMG)-controlled operating system that enabled users to play virtual games using repetitive finger movements. The participants performed conventional self-exercise on the same day as the control exercise, and rated their subjective perspectives on both exercises on a numerical rating scale on each exercise day. RESULTS: Ratings for enjoyability and motivation to continue consistently showed significantly higher scores for the gamified exercise than for conventional self-exercise on all exercise days. A similar trend was observed in the ratings for the expectancy of effectiveness. No changes over time were found in any of the ratings throughout the exercise period. CONCLUSIONS: Exercise using the developed EMG-controlled gamified system may have the potential to maintain motivation and enjoyment in people with stroke to continue monotonous repetitive finger movements.

Although dose (number of repetitions) has been suggested as a key element in the effectiveness of rehabilitation exercises to promote motor recovery of the hemiparetic upper limb, rehabilitation exercises tend to be monotonous and require significant motivation to continue.Gamification technology has been implemented in exercises to promote self-engagement for people with hemiparesis in continuing monotonous repetitive movements.Exercises using the developed EMG-controlled gamified system may have the potential to maintain motivation and enjoyment in people with stroke to continue monotonous repetitive finger movements.

The thermal sensation threshold and its reliability induced by the exposure to 28 GHz millimeter-wave.

The application of 28 GHz millimeter-wave is prevalent owing to the global spread of fifth-generation wireless communication systems. Its thermal effect is a dominant factor which potentially causes pain and tissue damage to the body parts exposed to the millimeter waves. However, the threshold of this thermal sensation, that is, the degree of change in skin temperature from the baseline at which the first subjective response to the thermal effects of the millimeter waves occurs, remains unclear. Here, we investigated the thermal sensation threshold and assessed its reliability when exposed to millimeter waves. Twenty healthy adults were exposed to 28 GHz millimeter-wave on their left middle fingertip at five levels of antenna input power: 0.2, 1.1, 1.6, 2.1, and 3.4 W (incident power density: 27-399 mW/cm2). This measurement session was repeated twice on the same day to evaluate the threshold reliability. The intraclass correlation coefficient (ICC) and Bland-Altman analysis were used as proxies for the relative and absolute reliability, respectively. The number of participants who perceived a sensation during the two sessions at each exposure level was also counted as the perception rate. Mean thermal sensation thresholds were within 0.9°C-1.0°C for the 126-399 mW/cm2 conditions, while that was 0.2°C for the 27 mW/cm2 condition. The ICCs for the threshold at 27 and 126 mW/cm2 were interpreted as poor and fair, respectively, while those at higher exposure levels were moderate to substantial. Apart from a proportional bias in the 191 mW/cm2 condition, there was no fixed bias. All participants perceived a thermal sensation at 399 mW/cm2 in both sessions, and the perception rate gradually decreased with lower exposure levels. Importantly, two-thirds of the participants answered that they felt a thermal sensation in both or one of the sessions at 27 mW/cm2, despite the low-temperature increase. These results suggest that the thermal sensation threshold is around 1.0°C, consistent across exposure levels, while its reliability increases with higher exposure levels. Furthermore, the perception of thermal sensation may be inherently ambiguous owing to the nature of human perception.

Suppression of Ehrlich ascites tumor cell proliferation via G1 arrest induced by dietary nucleic acid-derived nucleosides.

The nucleic acids found in food play a crucial role in maintaining various bodily functions. This study investigated the potential anticancer effects of dietary nucleic acids, an area that is still not fully understood. By utilizing an in vivo mouse model and an in vitro cell model, we discovered an anti-proliferative impact of RNA in both systems. DNA exhibited anti-proliferative effects in the mouse model, while this phenomenon wasn't observed in the in vitro cell model using Ehrlich ascites tumor (EAT) cells. Conversely, DNA hydrolysate demonstrated distinct anti-proliferative effects in EAT cells, suggesting that nucleotides or nucleosides generated during nucleic acid digestion act as active constituents. Furthermore, we examined various nucleosides and two sodium-independent equilibrative nucleoside transporter inhibitors (ENTs), identifying guanosine and 2'-deoxyguanosine as pivotal in the anti-proliferative effect. We also found that the anti-proliferation activity with both nucleosides was suppressed by the treatment of dipyridamole, a non-selective inhibitor for ENT1 and ENT2, but not nitrobenzylthioinosine, a low inhibitor for ENT2. The uptake of these compounds into cells is likely facilitated by ENT2. These nucleotides impeded the progression of cancer cells from the G1 phase to the S phase in the cell cycle. Another significant finding is the increased expression of CCAAT/enhancer-binding protein (C/EBPß) induced by guanosine and 2'-deoxyguanosine. Furthermore, immunostaining revealed that C/EBPß diffuses into the nucleus, indicating its presence. This suggests that guanosine or 2-deoxyguanosine induces G1 arrest in cancer cells via the activation of C/EBPß. Encouraged by these promising results, guanosine and 2'-deoxyguanosine show potential applications in cancer prevention.

Ecklonia cava Polyphenols Have a Preventive Effect on Parkinson's Disease through the Activation of the Nrf2-ARE Pathway.

Parkinson's disease (PD) is a degenerative neurological disorder defined by the deterioration and loss of dopamine-producing neurons in the substantia nigra, leading to a range of motor impairments and non-motor symptoms. The underlying mechanism of this neurodegeneration remains unclear. This research examined the neuroprotective properties of Ecklonia cava polyphenols (ECPs) in mitigating neuronal damage induced by rotenone via the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway. Using human neuroblastoma SH-SY5Y cells and PD model mice, we found that ECP, rich in the antioxidant polyphenol phlorotannin, boosted the gene expression and functionality of the antioxidant enzyme NAD(P)H quinone oxidoreductase-1. ECP also promoted Nrf2 nuclear translocation and increased p62 expression, suggesting that p62 helps sustain Nrf2 activation via a positive feedback loop. The neuroprotective effect of ECP was significantly reduced by Compound C (CC), an AMP-activated protein kinase (AMPK) inhibitor, which also suppressed Nrf2 nuclear translocation. In PD model mice, ECPs improved motor functions impaired by rotenone, as assessed by the pole test and wire-hanging test, and restored intestinal motor function and colon tissue morphology. Additionally, ECPs increased tyrosine hydroxylase expression in the substantia nigra, indicating a protective effect on dopaminergic neurons. These findings suggest that ECP has a preventative effect on PD.

Ecklonia cava polyphenol protects the liver against ethanol-induced injury in rats.

BACKGROUND: The development of alcoholic liver disease is a complex process that involves both the parenchymal and non-parenchymal cells of the liver. We examined the effect of an Ecklonia cava extract on ethanol-induced liver injury. METHODS: Isolated hepatocytes and hepatic stellate cells (HSCs) were incubated with ethanol. Ecklonia cava polyphenol (ECP) was added to the cultures that had been incubated with ethanol. Male Wistar rats were fed a diet that included 0.02% or 0.2% ECP or no ECP. For a period of 3 weeks, the animals were given drinking water containing 5% ethanol and were also treated with carbon tetrachloride (CCl4) (0.1 ml/kg of body weight). RESULTS: In the cultured hepatocytes, the ECP treatment suppressed the ethanol-induced increase in cell death by maintaining intracellular glutathione (GSH) levels. In HSCs, ECP treatment suppressed the ethanol-induced increases in type I collagen and α-smooth muscle actin expression by maintaining intracellular levels of reactive oxygen species and GSH. We examined the effects of ECP on serum AST and ALT activity, as well as the progression of liver fibrosis in rats treated with ethanol and CCl4. ECP treatment suppressed plasma AST and ALT activities in the ethanol- and CCl4-treated rats. ECP treatment fully protected the rats against ethanol- and CCl4-induced liver injury. GENERAL SIGNIFICANCE: ECP may be a candidate for preventing ethanol-induced liver injury.

Characteristics of current perception produced by intermediate-frequency contact currents in healthy adults.

Introduction: Contact electrical currents in humans stimulate peripheral nerves at frequencies of <100 kHz, producing sensations such as tingling. At frequencies above 100 kHz, heating becomes dominant, resulting in a sensation of warmth. When the current amplitude exceeds the threshold, the sensation results in discomfort or pain. In international guidelines and standards for human protection from electromagnetic fields, the limit for the contact current amplitude has been prescribed. Although the types of sensations produced by contact current at low frequencies, i.e., approximately 50-60 Hz, and the corresponding perception thresholds have been investigated, there is a lack of knowledge about those in the intermediate-frequency band-particularly from 100 kHz to 10 MHz. Methods: In this study, we investigated the current-perception threshold and types of sensations for 88 healthy adults (range: 20-79 years old) with a fingertip exposed to contact currents at 100 kHz, 300 kHz, 1 MHz, 3 MHz, and 10 MHz. Results: The current perception thresholds at frequencies ranging from 300 kHz to 10 MHz were 20-30% higher than those at 100 kHz (p < 0.001). In addition, a statistical analysis revealed that the perception thresholds were correlated with the age or finger circumference: older participants and those with larger finger circumferences exhibited higher thresholds. At frequencies of ≥300 kHz, the contact current mainly produced a warmth sensation, which differed from the tingling/pricking sensation produced by the current at 100 kHz. Discussion: These results indicate that there exists a transition of the produced sensations and their perception threshold between 100 kHz and 300 kHz. The findings of this study are useful for revising the international guidelines and standards for contact currents at intermediate frequencies. Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000045660, identifier UMIN 000045213.

Glyoxylic Acid, an α-Keto Acid Metabolite Derived from Glycine, Promotes Myogenesis in C2C12 Cells.

α-Keto acids may help prevent malnutrition in patients with chronic kidney disease (CKD), who consume protein-restricted diets, because they serve as amino acid sources without producing nitrogenous waste compounds. However, the physiological roles of α-keto acids, especially those derived from non-essential amino acids, remain unclear. In this study, we examined the effect of glyoxylic acid (GA), an α-keto acid metabolite derived from glycine, on myogenesis in C2C12 cells. Differentiation and mitochondrial biogenesis were used as myogenesis indicators. Treatment with GA for 6 d resulted in an increase in the expression of differentiation markers (myosin heavy chain II and myogenic regulatory factors), mitochondrial biogenesis, and intracellular amounts of amino acids (glycine, serine, and alanine) and their metabolites (citric acid and succinic acid). In addition, GA treatment suppressed the 2.5-µM dexamethasone (Dex)-induced increase in mRNA levels of ubiquitin ligases (Trim63 and Fbxo32), muscle atrophy markers. These results indicate that GA promotes myogenesis, suppresses Dex-induced muscle atrophy, and is metabolized to amino acids in muscle cells. Although further in vivo experiments are needed, GA may be a beneficial nutrient for ameliorating the loss of muscle mass, strength, and function in patients with CKD on a strict dietary protein restriction.

Electromyography-controlled gamified exercise system for the distal upper extremity: a usability assessment in subacute post-stroke patients.

PURPOSE: Movement repetition is known to play a key role in promoting functional improvements or maintaining functional levels in post-stroke hemiparetic patients. However, repetitive movements tend to be monotonous, making it challenging for patients to continue. Here, we developed a new gamified system to allow patients perform repetitive movements with enjoyment. The present study aimed to examine the usability of the system in subacute stroke patients. METHOD: The exercise system comprised an electromyography-controlled operating system that enabled users to play a virtual game by repetitive finger and wrist movements on the affected side. A total of 13 patients with upper-limb hemiparesis underwent a single bout of exercise using the system and assessed its usability, satisfactoriness, enjoyability, etc. using the System Usability Scale (SUS), Quebec User Evaluation of Satisfaction with assistive Technology (QUEST)-like questionnaire, and numerical rating scale (NRS). RESULTS: All the participants, who had a wide range of paretic levels, were able to perform the exercise using the system. Participants scored the system a median of 85.0 for SUS and 4.2 for the QUEST-like questionnaire, with an "excellent" in usability and "satisfied" in user satisfaction with the system. The median NRS scores for enjoyability, potential for continuous use, and effectiveness were 8.0, 9.0, and 9.0, respectively, which were greater than the scores for usual rehabilitation training for the upper extremity. CONCLUSIONS: The novel electromyography-controlled gamified exercise system may have sufficient usability and enjoyability to motivate patients with a wide range of paretic levels to perform repetitive finger and wrist movements.IMPLICATIONS FOR REHABILITATIONThe electromyography-controlled gamified exercise system had overall positive perspectives on the usability of the system.This exercise system could help motivate patients with a wide range of paretic levels to perform repetitive finger and wrist movements.

Kaempferia galanga L. extract and its main component, ethyl p-methoxycinnamate, inhibit the proliferation of Ehrlich ascites tumor cells by suppressing TFAM expression.

Kaempferia galanga L. shows anti-cancer effects; however, the underling mechanism remains unclear. In this study, we explored the underlying mechanism of the anti-cancer effects of Kaempferia galanga L. Kaempferia galanga L. rhizome extracts (KGEs) suppressed Ehrlich ascites tumor cell (EATC) proliferation by inhibiting S-phase progression. The main component of KGE is ethyl p-methoxycinnamate (EMC), which exhibits the same anti-proliferative effect as KGE. Furthermore, EMC induced the downregulation of cyclin D1 and upregulation of p21. EMC also decreased the expression of mitochondrial transcription factor A (TFAM) but did not significantly change mitochondrial DNA copy number and membrane potential. Phosphorylation at Ser62 of c-Myc, a transcription factor of TFAM, was decreased by EMC treatment, which might be due to the suppression of H-ras expression. These results indicate that EMC is the active compound responsible for the anti-cancer effect of KGE and suppresses EATC proliferation by regulating the protein expression of cyclin D1 and p21; TFAM may also regulate the expression of these genes. In addition, we investigated the anticancer effects of KGE and EMC in vivo using EATC bearing mice. The volume of ascites fluid was significantly increased by intraperitoneal administration of EATC. However, the increase in the volume of ascites fluid was suppressed by oral administration of EMC and KGE. This study provides novel insights into the association between the anti-cancer effects of natural compounds and TFAM, indicating that TFAM might be a potential therapeutic target.

The suppression of the differentiation of adipocytes with Mallotus furetianus is regulated through the posttranslational modifications of C/EBPß.

Obesity is a major risk factor for various chronic diseases, especially lifestyle-related diseases. Therefore, finding a protective substance against obesity and elucidating its molecular mechanism is one of the most important problems for improving human health. In this study, we investigated the antiobesity effect of Mallotus furetianus extract (MFE). The aim of the study was to examine the in vivo and in vitro effects of MFE on lipid synthesis. We examined the effect using an in vivo experimental system with obesity model mice and an in vitro experimental system with 3T3-L1 preadipocytes. We found that the treatment of MFE significantly suppressed the increase in body weight and adipose tissue weight and morphological changes in the liver and adipose tissue of the obesity model mice. In the in vitro experimental system, we revealed that MFE treatment suppressed the expression of transcription factors such as C/EBPα, C/EBPß, and PPARγ, which are involved in the early differentiation of 3T3-L1 preadipocytes. As a result, the ability to synthesize triacylglycerol was suppressed. An interesting finding in this study was the clarification that MFE decreases the expression of C/EBPß through post-translation modifications (PTMs), followed by the transcriptional suppression of PPAR𝛾 and C/EBP𝛼.

The enhancement of phase 2 enzyme activities by sodium butyrate in normal intestinal epithelial cells is associated with Nrf2 and p53.

Dietary fiber fermentation by the colonic bacterial flora produces short-chain fatty acids, acetate, propionate and butyrate. Among them, butyrate is considered to be the major energy substrate for colonocytes and, at least in rats, seems to protect against colonic carcinogenesis. In this study, we examined the effect and the mechanisms of short-chain fatty acids on the activity of phase 2 enzymes. Sodium butyrate increased phase 2 enzyme activities in normal rat small intestine epithelial cells, Glutathione S-transferase and NAD(P)H:quinone oxidoreductase (NQO) in a dose-dependent manner(;) however, other short-chain fatty acids did not increase them. The mechanism of the induction of phase 2 enzymes with sodium butyrate sodium butyrate, but not other short-chain fatty acids was related to the increase of NF-E2-related factor 2 (Nrf2) nuclear translocation and the decrease in the levels of nuclear fraction p53. Sodium butyrate also caused enhancement of Nrf2 mRNA levels and suppression of p53 mRNA levels. Sodium butyrate enhances the activities of phase 2 enzymes via an increase in the Nrf2 protein levels in the nucleus and a decrease in the mRNA and protein levels of p53.

Systematic determination of muscle groups and optimal stimulation intensity for simultaneous TMS mapping of multiple muscles in the upper limb.

Transcranial magnetic stimulation has been used to assess plastic changes in the cortical motor representations of targeted muscles. The present study explored the optimal settings and stimulation intensity for simultaneous motor mapping of multiple upper-limb muscles across segments. In 15 healthy volunteers, we evaluated cortical representations simultaneously from one muscle in the shoulder, two in the upper arm, two in the forearm, and two intrinsic hand muscles, using five stimulation intensities, ranging from 40% to 100% of the maximum stimulator output. We represented the motor map area acquired at each intensity as a percentage of the maximum for each muscle. We defined a motor map area between 25% and 75% of the maximum as the optimal area size with sufficient scope for both up- and down-regulation, and stimulation intensities producing the map area size within this range as the optimal intensities. We found that motor maps with optimal area sizes could be produced simultaneously for the four distal muscles of the forearm and hand in most participants when the stimulation intensity was set at 120-140% of the resting motor threshold (RMT) of the first dorsal interosseous. For the remaining three proximal muscles, motor maps with optimal area sizes were produced only in a few participants, even when using a higher intensity (180-220% RMT). These findings suggest that cortical representations can be assessed simultaneously in a group of distal muscles using a relatively low stimulation intensity, while a separate operation is required to assess that of the proximal muscles.