[Research progress on regulation of N6-adenylate methylation modification in lipid metabolism disorders].

Lipid metabolism is a complex physiological process, which is closely related to nutrient regulation, hormone balance and endocrine function. It involves the interactions of multiple factors and signal transduction pathways. Lipid metabolism disorder is one of the main mechanisms to induce a variety of diseases, such as obesity, diabetes, non-alcoholic fatty liver disease, hepatitis, hepatocellular carcinoma and their complications. At present, more and more studies have found that the "dynamic modification" of N6-adenylate methylation (m6A) on RNA represents a new "post-transcriptional" regulation mode. m6A methylation modification can occur in mRNA, tRNA, ncRNA, etc. Its abnormal modification can regulate gene expression changes and alternative splicing events. Many latest references have reported that m6A RNA modification is involved in the epigenetic regulation of lipid metabolism disorder. Based on the major diseases induced by lipid metabolism disorders, we reviewed the regulatory roles of m6A modification in the occurrence and development of those diseases. These overall findings inform further in-depth investigations of the underlying molecular mechanisms regarding the pathogenesis of lipid metabolism disorders from the perspective of epigenetics, and provide reference for health prevention, molecular diagnosis and treatment of related diseases.

Low-level laser therapy prevents endothelial cells from TNF-α/cycloheximide-induced apoptosis.

Low-level laser therapy (LLLT), widely used in physiotherapy, has been known to enhance wound healing and stimulate cell proliferation, including fibroblast and endothelial cells. Applying LLLT can increase cell proliferation in many kinds of cells including fibroblasts and endothelial cells. However, the protective mechanisms of LLLT on endothelial apoptosis remain unclear. We hypothesized LLLT can protect endothelial cells from inflammation-induced apoptosis. Human endothelial cell line, EA.hy926 cells, and TNF-α/cycloheximide (TNF/CHX) were used to explore the protective effects of LLLT (660 nm) on inflammation-induced endothelial apoptosis. Cell viability, apoptosis, caspase-3/7/8/9 activity, MAPKs signaling, NF-κB activity, and inducible/endothelial nitric oxide synthase (iNOS/eNOS) expression were measured. Our results showed that LLLT increased EA.hy926 cell proliferation, attenuated the TNF/CHX-induced apoptosis, and reduced the TNF/CHX-mediated caspase-3/7/8/9 activation. In addition, LLLT increased ERK MAPK phosphorylation and suppressed the TNF/CHX-increased p38 MAPK, JNK, IKK phosphorylation, NF-κB translocation, and iNOS expression. The caspases-3 cleavage and cell death were not increased in cells treating with ERK inhibitor U0126, which implicated that ERK is not to be responsible for the protective effects of LLLT. After treating with p38 mitogen-activated protein kinase (MAPK) activator, the protection of LLLT in cell apoptosis was no longer existed, showing that LLLT protected the endothelial cells by suppressing p38 MAPK signaling. Our results provide a new insight into the possible molecular mechanisms in which LLLT protects against inflammatory-induced endothelial dysfunction.

Action Research on Applying Compound Stimulus Approach to Improve Empathetic Communication: The Case of Physical Therapy Students.

(1) Background: Empathetic communicative skills are the first step in establishing a good therapeutic relationship. The purpose of this study is to understand the effectiveness of improving the empathetic communicative skills applied to obtain accurate and precise information from patients via compound stimulus-drama in education. (2) Methods: A cross-sectional, one-group, pre- and post-test design was used for this study. In the two-day workshop, four clinical physiotherapists acted as tutors for the "Compound Stimulus-Drama in Education" module and assessed students' performances. The Standard Patient Rating Scale (SPRS), Objective Structured Clinical Examination Scale (OSCES), Professional and Communication Self-Assessment Scale (PCSS), Patients' Information (PI), and the Jefferson Scale of Empathy (JSE) were used to assess the students' empathy scores and communication skills, before and after the course. (3) Results: Fifty-seven students participated in this study. The results showed that there were significant improvements in the SPRS, OSCES, PCSS, PI, and JSE (p < 0.05). Both the quantitative data and the participants' reflection feedback suggest that this novel module was more helpful than traditional clinical practice courses for improving clinical empathy communication skills. (4) Conclusions: This study provided an innovative teaching model and assessment tools for learning clinic empathetic communicative skills in future education training.

PDB-1 from Potentilla discolor Bunge induces apoptosis and autophagy by downregulating the PI3K/Akt/mTOR signaling pathway in A549 cells.

PDB-1 is a new C-27-carboxylated-lupane-triterpenoid derivative isolated from Potentilla discolor Bunge. In our previous research, PDB-1 was suggested to have an obvious selectivity for tumor cells. This study focused on clarifying PDB-1's anticancer mechanism in the inhibition of proliferation and in the induction of apoptosis and autophagy in A549 cells. In general, A549 cells were treated with PDB-1 for different times, and cell survival was assessed by a CCK8 assay. The assessment of intracellular reactive oxygen species, a mitochondrial membrane potential assay, a cell cycle assay, an annexin V-FITC/PI assay, and MDC staining were performed in A549 cells treated with PDB-1. Moreover, the mRNA and protein expression of cell cycle-, apoptosis- and autophagy-related factors were detected by RT-qPCR and western blotting. The results showed that PDB-1 inhibited A549 cell proliferation and colony formation in a dose- and time-dependent manner. The decrease in the viability of A549 cells was due to a G2/M cell cycle arrest. Moreover, PDB-1 induced cell apoptosis, accompanied by an increase in the Bax/Bcl-2 ratio and an increase in the expression levels of cleaved caspase-3/caspase-9. We also found that PDB-1 induced autophagy by increasing the conversion of LC3-I to LC3-II and elevating Beclin-1. In addition, further studies indicated that pretreatment with a specific PI3K inhibitor (LY294002) enhanced the effects of PDB-1 on the expression of proteins associated with apoptosis and autophagy, demonstrating that the PI3K/Akt/mTOR pathway was related to PDB-1-induced apoptosis and autophagy. These results indicated that PDB-1 may be considered a potential candidate for the future treatment of lung adenocarcinoma. These findings should benefit the development of the C14-COOH type of pentacyclic triterpenoids.

Intervention to enhance skilled arm and hand movements after stroke: A feasibility study using a new virtual reality system.

BACKGROUND: Rehabilitation programs designed to develop skill in upper extremity (UE) function after stroke require progressive practice that engage and challenge the learner. Virtual realty (VR) provides a unique environment where the presentation of stimuli can be controlled systematically for optimal challenge by adapting task difficulty as performance improves. We describe four VR tasks that were developed and tested to improve arm and hand movement skills for individuals with hemiparesis. METHODS: Two participants with chronic post-stroke paresis and different levels of motor severity attended 12 training sessions lasting 1 to 2 hours each over a 3-week period. Behavior measures and questionnaires were administered pre-, mid-, and post-training. RESULTS: Both participants improved VR task performance across sessions. The less impaired participant averaged more time on task, practiced a greater number of blocks per session, and progressed at a faster rate over sessions than the more impaired participant. Impairment level did not change but both participants improved functional ability after training. The less impaired participant increased the number of blocks moved on the Box & Blocks test while the more impaired participant achieved 4 more items on the Functional Test of the Hemiparetic UE. CONCLUSION: Two participants with differing motor severity were able to engage in VR based practice and improve performance over 12 training sessions. We were able to successfully provide individualized, progressive practice based on each participant's level of movement ability and rate of performance improvement.

A systematic review of voluntary arm recovery in hemiparetic stroke: critical predictors for meaningful outcomes using the international classification of functioning, disability, and health.

BACKGROUND AND PURPOSE: Stroke is the leading cause of long term disability in the United States. Most poststroke individuals experience difficulty in moving the contralesional limbs to perform daily activities. Studies were systematically reviewed to identify the best predictors of arm-specific motor recovery and further analyzed using the International Classification of Functioning, Disability, and Health to distinguish outcome measures that best reflected participation in life situations. METHODS: We used PubMed, CINAHL, the Cochrane Library, and EMBASE with the keywords stroke, upper extremity, recovery of function, and predictor. Inclusion and exclusion criteria were developed and applied to further refine the search. Finally, methodological quality was assessed. RESULTS: Fifty-six studies published between 1979 and 2008 met the criteria. There was a 317% increase in the frequency of articles on predictors of arm recovery over a nearly 30-year period. Thirty-six percent were of high methodological quality (score, >or=10 of 15). Early neurophysiologic and sensorimotor measures were the best predictors at follow-up of arm-specific outcomes. There was no outcome measure classified at the International Classification of Functioning, Disability, and Health participation level. Only one study provided information about an outcome-related minimal clinically important difference. DISCUSSION AND CONCLUSIONS: Initial measures of the integrity of neural connectivity and voluntary motor behavior were the best predictors of arm-specific functional recovery. The paucity of valid and reliable instruments to capture the more distal outcomes associated with activities and participation has likely limited the breadth of available evidence in this field. This suggests an urgent need for the development of direct measures of arm use in real-life environments.

Isokinetic characteristics of shoulder rotators in patients with adhesive capsulitis.

OBJECTIVE: To demonstrate the muscle strength characteristics of shoulder internal and external rotators and the effects of isokinetic exercise on muscle activity in patients with adhesive capsulitis. DESIGN: Cohort study with control subjects. PARTICIPANTS: Eight patients with adhesive capsulitis and 8 controls. METHODS: Maximal isometric and isokinetic strength tests of shoulder internal and external rotators in the scapular plane were carried out. Muscle activities of the rotators were recorded in resting and during maximal isometrics. Muscle strength variables (peak torque, total work and power) and myoelectric variables (resting root-mean-square amplitude pre- and post-tests and the external-internal rotator co-activity in resting and during isometric contractions) were recorded. A mixed repeated-measure analysis of variance test was used to examine the within-group and between-group differences. RESULTS: For affected shoulders, smaller isometric average torque of internal rotators and high-speed peak torque, total work and power of external rotator were observed. The external/internal rotator ratio of peak torque in high-speed testing also exhibited significant decrease. The myoelectric variables showed no significant changes. CONCLUSION: High-speed external rotator strength and isometric internal rotator strength of the affected shoulders were decreased significantly. Isokinetic exercise may not increase the resting muscle activities and co-activity. These results provide a reference in planning muscle strengthening programmes and goals for these patients.

Arthrographic and clinical findings in patients with hemiplegic shoulder pain.

OBJECTIVES: To identify the etiology of hemiplegic shoulder pain by arthrographic and clinical examinations and to determine the correlation between arthrographic measurements and clinical findings in patients with hemiplegic shoulder pain. DESIGN: Case series. SETTING: Medical center of a 1582-bed teaching institution in Taiwan. PARTICIPANTS: Thirty-two consecutive patients with hemiplegic shoulder pain within a 1-year period after first stroke were recruited. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Clinical examinations included Brunnstrom stage, muscle spasticity distribution, presence or absence of subluxation and shoulder-hand syndrome, and passive range of motion (PROM) of the shoulder joint. Arthrographic measurements included shoulder joint volume and capsular morphology. RESULTS: Most patients had onset of hemiplegic shoulder pain less than 2 months after stroke. Adhesive capsulitis was the main cause of shoulder pain, with 50% of patients having adhesive capsulitis, 44% having shoulder subluxation, 22% having rotator cuff tears, and 16% having shoulder-hand syndrome. Patients with adhesive capsulitis showed significant restriction of passive shoulder external rotation and abduction and a higher incidence of shoulder-hand syndrome (P=.017). Those with irregular capsular margins had significantly longer shoulder pain duration and more restricted passive shoulder flexion (P=.017) and abduction (P=.020). Patients with shoulder subluxation had significantly larger PROM (flexion, P=.007; external rotation, P<.001; abduction, P=.001; internal rotation, P=.027), lower muscle tone (P=.001), and lower Brunnstrom stages of the proximal upper extremity (P=.025) and of the distal upper extremity (P=.001). Muscle spasticity of the upper extremity was slightly negatively correlated with shoulder PROM. Shoulder joint volume was moderately positively correlated with shoulder PROM. CONCLUSIONS: After investigating the hemiplegic shoulder joint through clinical and arthrographic examinations, we found that the causes of hemiplegic shoulder pain are complicated. Adhesive capsulitis was the leading cause of shoulder pain, followed by shoulder subluxation. Greater PROM of the shoulder joint, associated with larger joint volume, decreased the occurrence of adhesive capsulitis. Proper physical therapy and cautious handling of stroke patients to preserve shoulder mobility and function during early rehabilitation are important for a good outcome.