Ergosta-7,9(11),22-trien-3ß-ol Alleviates Intracerebral Hemorrhage-Induced Brain Injury and BV-2 Microglial Activation.

Intracerebral hemorrhage (ICH) is a devastating neurological disorder characterized by an exacerbation of neuroinflammation and neuronal injury, for which few effective therapies are available at present. Inhibition of excessive neuroglial activation has been reported to alleviate ICH-related brain injuries. In the present study, the anti-ICH activity and microglial mechanism of ergosta-7,9(11),22-trien-3ß-ol (EK100), a bioactive ingredient from Asian medicinal herb Antrodia camphorate, were evaluated. Post-treatment of EK100 significantly attenuated neurobehavioral deficit and MRI-related brain lesion in the mice model of collagenase-induced ICH. Additionally, EK100 alleviated the inducible expression of cyclooxygenase (COX)-2 and the activity of matrix metalloproteinase (MMP)-9 in the ipsilateral brain regions. Consistently, it was shown that EK100 concentration-dependently inhibited the expression of COX-2 protein in Toll-like receptor (TLR)-4 activator lipopolysaccharide (LPS)-activated microglial BV-2 and primary microglial cells. Furthermore, the production of microglial prostaglandin E2 and reactive oxygen species were attenuated by EK100. EK100 also attenuated the induction of astrocytic MMP-9 activation. Among several signaling pathways, EK100 significantly and concentration-dependently inhibited activation of c-Jun N-terminal kinase (JNK) MAPK in LPS-activated microglial BV-2 cells. Consistently, ipsilateral JNK activation was markedly inhibited by post-ICH-treated EK100 in vivo. In conclusion, EK100 exerted the inhibitory actions on microglial JNK activation, and attenuated brain COX-2 expression, MMP-9 activation, and brain injuries in the mice ICH model. Thus, EK100 may be proposed and employed as a potential therapeutic agent for ICH.

Comparison of the effects between lasers applied to myofascial trigger points and to classical acupoints for patients with cervical myofascial pain syndrome.

BACKGROUND: To compare the immediate effectiveness of low-level laser therapy (LLLT) applied to classical acupoints versus trigger points for patients with cervical myofascial pain syndrome (MPS). METHODS: This was a single-blinded, randomized, placebo-controlled trial. This study was performed in a university-affiliated medical center. One hundred participants with cervical myofascial pain syndrome were randomly allocated to four treatment groups, including (1) acupoint therapy (AcuT), (2) acupoint control (AcuC), (3) trigger point therapy (TriT), and (4) trigger point control (TriC) groups. Low-level laser (810-nm) therapy was used in both therapy groups, while the same procedure was performed without laser in the acupoint control groups. The patients were evaluated based on visual analogue scale (VAS) pain score, pressure pain threshold, and cervical range of motion (ROM) before and after the therapy. RESULTS: Immediate pain relief was observed in the TriT group (p < 0.01). The TriT group showed improved cervical ROM in ipsilateral bending (p < 0.01), while the AcuT group did not. CONCLUSIONS: LLLT applied to trigger points could significantly relieve myofascial pain and was effective in relieving cervical ROM limitations. Considering the risk of pneumothorax, laser therapy at trigger points for patients with cervical MPS may be a choice when acupuncture therapy is unavailable. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01516502.

Effectiveness of Laser Acupuncture in Alleviating Chronic Insomnia: A Single-Blinded Randomized Controlled Trial.

STUDY OBJECTIVES: This study investigates the therapeutic effect of Low Level Laser Therapy (LLLT) acupuncture for chronic insomnia. METHODS: Thirty-seven adult subjects with chronic insomnia were recruited and randomly assigned to three groups, namely, Group A (6 pairs of acupoints: Ex-HN 22, HT 7, SP 6, KI 3, LR 3, and PC 6, bilaterally distributed); Group B (acupoints as for Group A other than PC 6, which was applied only on the left side [i.e., the dominant side of the PC meridian] and the addition of DU 20, which is the main tonic acupoint for integration of all the meridians); and a control group (sham LLLT). The subjects in the treatment groups (i.e., Groups A and B) received LLLT acupuncture and those in the control group received sham LLLT for 15 minutes per session twice a week for five weeks. The sleep quality of all the subjects was evaluated using the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Hospital Anxiety and Depression Scale (HADS), and a sleep diary. In addition, the sympathetic activity before and after every treatment sessions was measured using the Heart Rate Variability (HRV). RESULTS: All three groups showed an improved PSQI score. However, only Group A showed a significant reduction in the sleep onset latency and number of awakenings at night and a higher sleep efficiency and ESS score. Furthermore, Group B showed an increased low frequency power and normalized low frequency of the HRV signal and a lower normalized high frequency power, suggesting an increased sympathetic activity and decreased parasympathetic activity. CONCLUSIONS: For chronic insomnia insomniacs, LLLT appears to shorten the sleep latency, decrease the number of awakening events at night, and improve the sleep efficiency.

Biodegradable Polymer-Coated Multifunctional Graphene Quantum Dots for Light-Triggered Synergetic Therapy of Pancreatic Cancer.

In this work, we reported the synthesis of an engineered novel nanocarrier composed of biodegradable charged polyester vectors (BCPVs) and graphene quantum dots (GQDs) for pancreatic cancer (MiaPaCa-2 cells) therapy applications. Such a nanocarrier was utilized to co-load doxorubicin (DOX) and small interfering ribonucleic acid (siRNA), resulting in the formation of GQD/DOX/BCPV/siRNA nanocomplexes. The resulting nanocomplexes have demonstrated high stability in physiologically mimicking media, excellent K-ras downregulation activity, and effective bioactivity inhibition for MiaPaCa-2 cells. More importantly, laser light was used to generate heat for the nanocomplexes via the photothermal effect to damage the cells, which was further employed to trigger the release of payloads from the nanocomplexes. Such triggered release function greatly enhanced the anticancer activity of the nanocomplexes. Preliminary colony formation study also suggested that GQD/DOX/BCPV/siRNA nanocomplexes are qualified carrier candidates in subsequent in vivo tests.

The Novel HDAC8 Inhibitor WK2-16 Attenuates Lipopolysaccharide-Activated Matrix Metalloproteinase-9 Expression in Human Monocytic Cells and Improves Hypercytokinemia In Vivo.

Dysregulated human monocytes/macrophages can synthesize and secrete matrix metalloproteinases (MMPs), which play important roles in the progression of sepsis. In this study, we investigated the effects and mechanism of a novel histone deacetylase (HDAC8) inhibitor, (E)-N-hydroxy-4-methoxy-2-(biphenyl-4-yl)cinnamide (WK2-16), on MMP-9 production and activation in stimulated human monocytic THP-1 cells. Our results demonstrated that the acetylation level of structural maintenance of chromosomes 3 (SMC3) was up-regulated by WK2-16 in THP-1 cells. Consistently, an in vitro enzyme study demonstrated that WK2-16 selectively inhibited HDAC8 activity. Moreover, the WK2-16 concentration dependently suppressed MMP-9-mediated gelatinolysis induced by tumor necrosis factor-α (TNF-α) or lipopolysaccharide (LPS). Additionally, WK2-16 significantly inhibited both MMP-9 protein and mRNA expression without cellular toxicity. Nevertheless, WK2-16 suppressed the extracellular levels of interleukin (IL)-6 from LPS-stimulated THP-1 cells. For the signaling studies, WK2-16 had no effect on LPS/TLR4 downstream signaling pathways, such as the NF-κB and ERK/JNK/P38 MAPK pathways. On the other hand, WK2-16 enhanced the recruitment of acetylated Yin Yang 1 (YY1) with HDAC1. Finally, in vivo studies indicated that WK2-16 could reduce the serum levels of TNF-α and IL-6 in endotoxemic mice. These results suggested that HDAC8 inhibition might provide a novel therapeutic strategy of hypercytokinemia in sepsis.

Effects of combining robot-assisted therapy with neuromuscular electrical stimulation on motor impairment, motor and daily function, and quality of life in patients with chronic stroke: a double-blinded randomized controlled trial.

BACKGROUND: Robot-assisted therapy (RT) is a widely used intervention approach to enhance motor recovery in patients after stroke, but its effects on functional improvement remained uncertain. Neuromuscular electrical stimulation (NMES) is one potential adjuvant intervention approach to RT that could directly activate the stimulated muscles and improve functional use of the paretic hand. METHODS: This was a randomized, double-blind, sham-controlled study. Thirty-nine individuals with chronic stroke were randomly assigned to the RT combined with NMES (RT + ES) or to RT with sham stimulation (RT + Sham) groups. The participants completed the intervention 90 to 100 minutes/day, 5 days/week for 4 weeks. The outcome measures included the upper extremity Fugl-Meyer Assessment (UE-FMA), modified Ashworth scale (MAS), Wolf Motor Function Test (WMFT), Motor Activity Log (MAL), and Stroke Impact Scale 3.0 (SIS). All outcome measures were assessed before and after intervention, and the UE-FMA, MAL, and SIS were reassessed at 3 months of follow-up. RESULTS: Compared with the RT + Sham group, the RT + ES group demonstrated greater improvements in wrist flexor MAS score, WMFT quality of movement, and the hand function domain of the SIS. For other outcome measures, both groups improved significantly after the interventions, but no group differences were found. CONCLUSION: RT + ES induced significant benefits in reducing wrist flexor spasticity and in hand movement quality in patients with chronic stroke. TRIAL REGISTRATION: ClinicalTrials.gov. NCT01655446.

Sedative music facilitates deep sleep in young adults.

OBJECTIVES: To investigate the effect of sedative music on the different stages of the sleep cycle in young adults with various sleep latencies by using polysomnography (PSG). DESIGN: Prospective, randomized, controlled, crossover study. SETTING: Sleep center of a teaching hospital. PARTICIPANTS: Young adults with different sleep latencies. Poor sleepers (Pittsburgh Sleep Quality Index score ≥5) were excluded. INTERVENTIONS: Each participant stayed one night in the sleep center for adaptation and on each of the following two nights was assigned to (1) music and (2) control (without music) conditions in random order. In the music condition, sedative music composed by certified music therapists was played on a compact disc player for the first hour the participant was in bed. OUTCOME MEASURES: Sleep measures recorded with PSG, including sleep latency and durations of sleep stages. RESULTS: Twenty-four young adults (mean±standard deviation, 24.5±2.6 years) participated. They were classified into the short sleep latency (SL) group if the baseline SL of the adaptation night was shorter than 10 minutes or into the long SL group if the baseline SL was 10 minutes or longer. Sedative music did not alter the SL in either group. Sedative music reduced stage II sleep in both SL groups (main effect of music, p=0.03; interaction effect, p=0.87) but increased the duration of deep sleep (stages III and IV) only in the long SL group (main effect of music, p=0.15; interaction effect, p=0.02). CONCLUSIONS: In participants with long SL, sedative music improved the quality of sleep by prolonging the duration of deep sleep. This effect provides an alternative and noninvasive way to improve sleep in selected persons experiencing sleep problems.

Influence of magnetic knee wraps on joint proprioception in individuals with osteoarthritis: a randomized controlled pilot trial.

OBJECTIVE: To determine the effects of magnetic knee wraps (MKWs) on joint position sense (JPS) in individuals with mild-to-moderate knee osteoarthritis. DESIGN: Randomized, double-blind, placebo-controlled pilot trial. SETTING: Rehabilitation clinic of a tertiary hospital. SUBJECTS: Fifty volunteers with mild-to-moderate knee osteoarthritis participated and 33 (66%) completed the trial; only one (2%) withdrew due to study-related adverse effects. INTERVENTIONS: Knee wraps with a static magnetic field (35 mT) were compared with control knee wraps for 12 weeks. MAIN MEASURES: The main outcome measure was JPS at first, fourth, and twelfth week while applying of the knee wrap, quantified as the ability to replicate target knee joint angles. The secondary outcome was the Comprehensive Osteoarthritis Test (COAT) total score. RESULTS: In the intention-to-treat analysis with an alpha-level of 0.05, 12-week application of the MKWs did not significantly reduce the mean absolute error (MAE) of JPS (n = 18; P = 0.627); contrarily, the MAE was found to decrease significantly after wearing the sham MKWs (n = 20; P = 0.01). The COAT total score gradually improved in both groups (P < 0.05). When comparing the improvement of MAE and COAT total score at each follow-up between two groups, no significant differences were found; the maximal difference in the improvement of MAE between two groups was noted at week 12 (mean difference: 1.2°; 95% confidence interval -0.4 to 2.9; P = 0.144). In the per-protocol analysis, the study group showed better improvement in the COAT total score at week 12 (P = 0.033). CONCLUSION: The 35-mT MKWs could not significantly influence knee JPS in individuals with mild-to-moderate knee osteoarthritis.

Comparison of the effects of swimming and Tai Chi Chuan on body fat composition in elderly people.

BACKGROUND: Accumulation of fat and substantial loss of muscle mass are common phenomena in the elderly. In this study, we observed the effects of Tai Chi Chuan (TCC) and swimming, two exercises suitable for elderly people, on the percentage body fat and fat distribution by measuring subcutaneous adipose tissue thickness and body composition. METHODS: Subjects were divided into three groups: regular swimmers (n = 20), regular TCC practitioners (n = 32), and age-matched control subjects (n = 31). Subcutaneous adipose tissue thickness was taken using a Lange skinfold caliper at the chests, abdomens, and thighs in the men, and the triceps, suprailium, and thighs in the women. Mid-arm circumference (MAC) was measured on the non-dominant upper arm using fiberglass tape. Body composition was analyzed using the Inbody 3.0 logo, a bioelectrical impedance analysis (BIA) system. RESULTS: No significant differences were found between the three test groups in relation to total body adiposity and arm muscle circumference in the men and women. There was significantly less subcutaneous adipose tissue at the abdomen (p = 0.011) and thigh (p < 0.001) of TCC-group men and at the thighs (p < 0.001) of the swimming group compared with the control group. In women, only the thigh skinfold (p = 0.002) showed a decrease in the TCC group compared with the control group. CONCLUSION: Swimming and TCC may not decrease total fat adiposity in elderly men and women, however, they may change body fat distribution due to certain muscle group usage. The differences observed in the effects of exercise on body fat distribution between elderly women and men may be gender-related.