Transcranial direct current stimulation combined with bodyweight support-tai chi footwork for motor function of stroke survivors: a study protocol of randomised controlled trial.

INTRODUCTION: Our previous studies have proposed the bodyweight support-t'ai chi (BWS-TC) footwork training for stroke survivors with severe motor dysfunction and fear of falling, and have proven its positive effects for motor function. Transcranial direct current stimulation (tDCS) provides a non-invasive and safe way to modulate neuronal activity and provoke neuroplastic changes and to improve the motor function of stroke survivors. However, it is unclear whether the integration of BWS-TC and tDCS has synergistic effects on improving motor function of the stroke survivors. METHODS AND ANALYSIS: This study will be an assessor-blinded randomised controlled trial involving 12-week intervention and 6-month follow-up. One hundred and thirty-five individuals with stroke will be randomly divided in a ratio of 1:1:1 into three groups. Control group A, control group B and intervention group C will receive tDCS and conventional rehabilitation programmes (CRPs), BWS-TC and CRP, tDCS-BWS-TC and CRP for 12 weeks, respectively. The primary outcome measures will include the efficacy (Fugl-Meyer Assessment), acceptability and safety of these interventions. The secondary outcome measures will include balance ability (ie, limits of stability and modified clinical test of sensory integration), walking function, brain structure and function, risk of falling, Barthel Index and 36-Item Short Form Survey. All outcomes will be assessed at baseline, 6 and 12 weeks during intervention, and 1, 3 and 6 months during the follow-up period. Two-way analysis of variance with repeated measures will be applied to examine the main effects of the group and the time factor and group-time interaction effects for all outcome measures. ETHICS AND DISSEMINATION: Ethics approval was obtained from the ethics committee of the Shanghai Seventh People's Hospital (2021-7th-HIRB-017). The results of the study will be published in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200059329.

Effects of Body Weight Support-Tai Chi Footwork Training on Balance Control and Walking Function in Stroke Survivors with Hemiplegia: A Pilot Randomized Controlled Trial.

BACKGROUND: Tai Chi (TC) is known to enhance balance control and walking function in stroke survivors. However, motor disorders in stroke patients may limit the implementation of TC exercise and increase the risk of falling. The body weight support (BWS) device can provide protection during the early rehabilitation of stroke survivors using an overhead suspension system. Theoretically, combining TC with BWS may be an effective intervention for stroke survivors. This study aimed to examine the effects of body weight support-Tai Chi training on balance control and walking function in stroke survivors with hemiplegia. METHODS: Seventy-one stroke survivors with hemiplegia aged 30-75 years were randomly allocated to the control group (N = 35) or the BWS-TC group (N = 36). During BWS-TC training, the subjects performed 7 Tai Chi footwork forms, and gradual easy-to-difficult progression (from 40% to 0% body weight) was followed. The subjects participated in 40 min rehabilitation sessions three times per week for 12 weeks. The primary outcome was dynamic balance in the limits-of-stability test. The secondary outcomes, which reflect improvements walking function, included spatiotemporal parameters, the joint range of motion in the affected limb during the swing phase, the Berg Balance Scale score, and the Fugl-Meyer Assessment score. Evaluations were performed at baseline and 12 weeks and compared between groups. RESULTS: After training, significant between-group differences were observed in the scores for overall, forward, left, right, forward-left, and forward-right directional control in the limits-of-stability test (P < 0.05). Furthermore, the scores for gait cycle time, step length, step velocity, and range of motion of the joints were better in the BWS-TC group than in the control group (P < 0.05). CONCLUSIONS: The 12-week BWS-TC training may enhance dynamic balance and walking function in stroke survivors with hemiplegia.

MicroRNAs' Involvement in Osteoarthritis and the Prospects for Treatments.

Osteoarthritis (OA) is a chronic disease and its etiology is complex. With increasing OA incidence, more and more people are facing heavy financial and social burdens from the disease. Genetics-related aspects of OA pathogenesis are not well understood. Recent reports have examined the molecular mechanisms and genes related to OA. It has been realized that genetic changes in articular cartilage and bone may contribute to OA's development. Osteoclasts, osteoblasts, osteocytes, and chondrocytes in joints must express appropriate genes to achieve tissue homeostasis, and errors in this can cause OA. MicroRNAs (miRNAs) are small noncoding RNAs that have been discovered to be overarching regulators of gene expression. Their ability to repress many target genes and their target-binding specificity indicate a complex network of interactions, which is still being defined. Many studies have focused on the role of miRNAs in bone and cartilage and have identified numbers of miRNAs that play important roles in regulating bone and cartilage homeostasis. Those miRNAs may also be involved in the pathology of OA, which is the focus of this review. Future studies on the role of miRNAs in OA will provide important clues leading to a better understanding of the mechanism(s) of OA and, more particularly, to the development of therapeutic targets for OA.

Stereoselective Regulation of P-gp Activity by Clausenamide Enantiomers in Caco-2, KB/KBv and Brain Microvessel Endothelial Cells.

The (-)- and (+)-clausenamide (CLA) enantiomers have different pharmacokinetic effects in animals, but their association with putative stereoselective regulation of P-glycoprotein (P-gp) remains unclear. Using three cells expressing P-gp-Caco-2, KBv and rat brain microvessel endothelial cells(RBMEC), this study investigated the association of CLA enantiomers with P-gp. The results showed that the rhodamine 123 (Rh123) accumulation, an indicator of P-gp activity, in Caco-2, KBv and RBMECs was increased by (-)CLA (1 or 5 µmol/L) at 8.2%-28.5%, but reduced by (+)CLA at 11.7%-25.9%, showing stereoselectivity in their regulation of P-gp activity. Following co-treatment of these cells with each CLA enantiomer and verapamil as a P-gp inhibitor, the (+)-isomer clearly antagonized the inhibitory effects of verapamil on P-gp efflux, whereas the (-)-isomer had slightly synergistic or additive effects. When higher concentrations (5 or 10 µmol/L) of CLA enantiomers were added, the stimulatory effects of the (+)-isomer were converted into inhibitory ones, leading to an enhanced intracellular uptake of Rh123 by 24.5%-58.2%; but (-)-isomer kept its inhibition to P-gp activity, causing 30.0%-63.0% increase in the Rh123 uptake. The biphasic effects of (+)CLA were confirmed by CLA uptake in the Caco-2 cells. (+)CLA at 1 µmol/L had significantly lower intracellular uptake than (-)CLA with a ratio[(-)/(+)] of 2.593, which was decreased to 2.167 and 1.893 after CLA concentrations increased to 2.5 and 5 µmol/L. Besides, in the non-induced KB cells, (+)CLA(5 µmol/L) upregulated P-gp expression at 54.5% relative to vehicle control, and decreased Rh123 accumulation by 28.2%, while (-)CLA(5 µmol/L) downregulated P-gp expression at 15.9% and increased Rh123 accumulation by 18.0%. These results suggested that (-)CLA could be a P-gp inhibitor and (+)CLA could be a modulator with concentration-dependent biphasic effects on P-gp activity, which may result in drug-drug interactions when combined with other P-gp substrate drugs.

Effect of cervus and cucumis peptides on osteoblast activity and fracture healing in osteoporotic bone.

Osteoporosis is associated with delayed and/or reduced fracture healing. As cervus and cucumis are the traditional Chinese treatments for rheumatoid arthritis, we investigated the effect of supplementation of these peptides (CCP) on bone fracture healing in ovariectomized (OVX) osteoporotic rats in vitro and in vivo. CCP enhanced osteoblast proliferation and increased alkaline phosphatase activity, matrix mineralization, and expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 4 (BMP4), and osteopontin. In vivo, female Sprague-Dawley rats underwent ovariectomy and the right femora were fractured and fixed by intramedullary nailing 3 months later. Rats received intraperitoneal injections of either CCP (1.67 mg/kg) or physiological saline every day for 30 days. Fracture healing and callus formation were evaluated by radiography, micro-CT, biomechanical testing, and histology. At 12 weeks after fracture, calluses in CCP-treated bones showed significantly higher torsional strength and greater stiffness than control-treated bones. Bones in CCP-treated rats reunified and were thoroughly remodeled, while two saline-treated rats showed no bone union and incomplete remodeling. Taken together, these results indicate that use of CCP after fracture in osteoporotic rats accelerates mineralization and osteogenesis and improves fracture healing.

[High-throughput screening of human soluble epoxide hydrolase inhibitors].

To screen potential human soluble epoxide hydrolase (hsEH) inhibitors, a high-throughput screening model in 384-well microplate with total volume of 50 microL was established. Recombinant hsEH was cloned and expressed in E. coli. and its specific substrate PHOME was synthesized. The HTS model was based on fluorescence analysis with enhanced sensitivity and specificity (Z' = 0.65). A total of 47 360 samples (including 25 040 compounds and 22 320 natural products) were screened, of which 950 samples with inhibition greater than 80% were selected for further rescreening. Finally, two compounds with high inhibitory activity were identified, whose IC50 value were 8.56 and 4.31 micromol x L(-1), separately. The results indicated that the method was stable, sensitive, reproducible and also suitable for high-throughput screening.