Reciprocal interaction of HOTAIR and SP1 together enhance the ability of Xiaoji decoction and gefitinib to inhibit EP4 expression.

ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese herbal prescription Xiaoji decoction (XJD) has long been used for cancer treatment. However, the molecular mechanisms underlying the effects of this medicine, particularly to enhance the efficiency of EGFR-TKI in the treatment of lung cancer have not been well elucidated. MATERIALS AND METHODS: Cell viability and cell cycle distribution were detected by MTT assay and flow cytometry, respectively. The phosphorylation of ERK1/2 and protein levels of SP1 and EP4 were determined by Western blot. The expression of the HOX transcript antisense RNA (HOTAIR) was measured by qRT-PCR. Transient transfection experiments were used to overexpress the HOTAIR, SP1 and EP4 genes. The interaction between HOTAIR and SP1 were further examined via RNA immunoprecipitation (RIP) assay. A tumor xenograft model was used to confirm the in vitro findings. RESULTS: We showed that XJD inhibited growth and induced cell arrest of human non-small cell lung cancer (NSCLC) cells. We also found that XJD increased the phosphorylation of ERK1/2 and inhibited levels of HOTAIR and SP1, EP4 proteins, which were blocked by inhibitor of MEK/ERK. There was reciprocal interaction between HOTAIR and SP1. Silencing of HOTAIR reduced EP4 protein levels and repressed the growth of NSCLC cells, while overexpression of HOTAIR and SP1 overcame XJD-reduced EP4 protein expression. Additionally, excessive expressed EP4 reversed the effect of XJD on cell growth. Importantly, there was synergy of XJD with another cancer treatment drug, EGFR-TKI gefitinib, in this process. We also found that XJD inhibited tumor growth in a xenograft nude mice model. CONCLUSIONS: Our results show that XJD inhibits NSCLC cell growth via ERK1/2-mediated reciprocal repression of HOTAIR and SP1 protein expression, followed by reduced EP4 gene expression. XJD and gefitinib exhibit synergy in this process. The in vitro and in vivo study provides a novel mechanism by which XJD enhances the growth inhibitory effect of gefitinib in gefitinib-resistant NSCLC cells.

Phenolic compounds and antioxidant activity in red- and in green-fleshed kiwifruits.

Red-fleshed kiwifruits are receiving increasing attention because of their high phenolic contents. However, detailed information on their phenolic compounds and antioxidant capacities remains scarce. Here, six red-fleshed and six green-fleshed kiwifruits were investigated to determine their contents of phenolic compounds and their antioxidant capacities. The results showed chlorogenic acid, p-coumaric acid and ferulic acid were the main phenolic compounds found in kiwifruit. Most of red-fleshed kiwifruits contain higher amounts of total phenolics and anthocyanins, as well as higher activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). Moreover, they exhibited stronger antioxidant capacities than green-fleshed kiwifruits in ABTS, DPPH and FRAP assays. Furthermore, the reactive oxygen species (ROS) inhibition assay showed the phenolics extracted from red-fleshed kiwifruit can better protect tobacco leaves against hydrogen peroxide (H2O2)-induced oxidative damage. This is because of their abundant anthocyanins which in vitro contribute more to H2O2 scavenging than the other phenolic compounds. Based on these findings, it is fair to conclude the red-fleshed kiwifruits are promising sources of antioxidants in human nutrition.

Potassium fertilization arrests malate accumulation and alters soluble sugar metabolism in apple fruit.

Effects of different potassium (K) levels, which were K0 (no fertilizer), K1 (71.5 g KCl plant-1 year-1), K2 (286.7 g KCl plant-1 year-1), and K3 (434 g KCl plant-1 year-1), were evaluated based on sugar and organic acid metabolism levels from 70-126 days after bloom (DAB) in the developing fruit of potted five-year-old apple (Malus domestica, Borkh.) trees. The results indicate that K fertilization promoted greater fruit mass, higher Ca2+ and soluble solid levels, and lower titratable acid levels, as well as increased pH values at harvest. With the application of different levels of K fertilizer, fructose, sorbitol, glucose and sucrose accumulation rates significantly changed during fruit development. Fruit in the K2 group had higher fructose, sucrose and glucose levels than those in other treatment groups at 126 DAB. These changes in soluble sugar are related to the activity of metabolic enzymes. Sucrose synthase (SS) and sorbitol dehydrogenase (SDH) activity in the K2 treated fruit was significantly higher than those in other treatment groups from 70-126 DAB. Malate levels in K-supplemented fruit were notably lower than those in non K-supplemented fruit, and K3 treated fruit had the lowest malate levels during fruit development. Cytosolic malic enzyme (ME) and phosphoenolpyruvate carboxykinase (PEPCK) activity significantly increased in fruit under the K2 treatment during 112-126 DAB and 98-126 DAB, respectively. In addition, Ca2+ concentration increased with increasing K fertilization levels, which promoted a maximum of 11.72 mg g-1 dry weight in apple fruit. These results show that K levels can alter soluble sugar and malate levels due to the interaction between sugars and acid-metabolic enzymes in fruit.

S100a8/NF-κB signal pathway is involved in the 800-nm diode laser-induced skin collagen remodeling.

The 800-nm diode laser is widely used for hair removal and also promotes collagen synthesis, but the molecular mechanism by which dermis responses to the thermal damage induced by the 800-nm diode laser is still unclear. Ten 2-month-old mice were irradiated with the 800-nm diode laser at 20, 40, and 60 J/cm(2), respectively. Skin samples were taken for PCR, Western blot analysis, and histological study at day 3 or 30 after laser irradiation. The expression of S100a8 and its two receptors (advanced glycosylation end product-specific receptor, RAGE and toll-like receptor 4, TRL4) was upregulated at day 3 after laser treatments. P-p65 levels were also elevated, causing the increase of cytokine (tumor necrosis factor, TNF-α and interleukin 6, IL-6) and MMPs (MMP1a, MMP9). At day 30, PCR and Western blot analysis showed significant increase of type I and III procollagen in the dermis treated with laser. Importantly, skin structure was markedly improved in the laser-irradiated skin compared with the control. Thus, it seemed that S100a8 upregulation triggered NF-κB signal pathway through RAGE and TLR4, responding to laser-induced dermis wound healing. The involvement of the NF-κB pathway in MMP gene transcription promoted the turnover of collagen in the skin, accelerating new collagen synthesis.

Discovering treatment pattern in Traditional Chinese Medicine clinical cases by exploiting supervised topic model and domain knowledge.

In Traditional Chinese Medicine (TCM), the prescription is the crystallization of clinical experience of doctors, which is the main way to cure diseases in China for thousands of years. Clinical cases, on the other hand, describe how doctors diagnose and prescribe. In this paper, we propose a framework which mines treatment patterns in TCM clinical cases by exploiting supervised topic model and TCM domain knowledge. The framework can reflect principle rules in TCM and improve function prediction of a new prescription. We evaluate our method on 3090 real world TCM clinical cases. The experiment validates the effectiveness of our method.

Comparison of telecommunication, community, and home-based Tai Chi exercise programs on compliance and effectiveness in elders at risk for falls.

OBJECTIVE: To compare the adherence to and effectiveness of Tai Chi exercise program through a live, interactive, telecommunication-based exercise (Tele-ex) with that of a similar program through a community center-based exercise (Comm-ex) and a home video-based exercise (Home-ex) among community-dwelling elders who are at risk for falls. DESIGN: Three groups randomized controlled trial with pretests and posttests. SETTING: Exercise programs were community-based, and the outcome measures were laboratory-based. PARTICIPANTS: Adults (N=64) age 65+ years with positive fall history in the previous year and/or significant fear of falling. INTERVENTION: A 24-form, Yang-style Tai Chi for 15 weeks, 3 hours a week. MAIN OUTCOME MEASURES: Exercise compliance, number of falls, fear of falling (Activities-specific Balance Confidence [ABC] score), self-perceived health (Medical Outcomes Study 36-Item Short Form Health Survey [SF-36]), Timed Up & Go (TUG), single leg stance (SLS), and body sway during quiet stance (medial-lateral foot center of pressure [ML-COP]). RESULTS: Tele-ex and Comm-ex groups demonstrated significantly higher exercise attendance and in-class practice time than the Home-ex group (P<.01) and significant reductions in the mean number of falls and injurious falls (P<.01). There were significant improvements posttraining in SLS, ABC, ML-COP, and Physical Health subscore of the SF-36 (P<.05). Both Tele-ex and Comm-ex groups demonstrated larger improvements than the Home-ex group in TUG, ML-COP, and the Social Function, Mental Health, and Physical Health subscores of the MOS SF-36. CONCLUSION: Compared with the Home-ex, the Tele-ex and Comm-ex groups are better in exercise compliance, fall reduction and balance and health improvements. Tele-ex is an effective, affordable, and acceptable choice of exercise for elders.

Speed effect of selected Tai Chi Chuan movement on leg muscle activity in young and old practitioners.

BACKGROUND: Tai Chi Chuan is becoming a popular exercise for improving balance and preventing falls in the elderly. To date, there is no quantitative study investigating the effect of Tai Chi Chuan movement speed on leg muscle function. This study investigated the effect of Tai Chi Chuan exercise performed at different speed on leg muscle activity characteristics in both young and old Tai Chi Chuan practitioners. METHODS: Surface electromyography of six leg muscles and kinematics of lower extremity joints were measured in young and old subjects during Tai Chi Chuan practice at fast, normal, and slow speed, respectively. The magnitude and duration of activation, and durations of isometric, concentric and eccentric actions of each muscle were compared among three speeds and between two groups. FINDINGS: The activation duration of all six leg muscles was significantly longer at slower speed than at faster speed (P<0.039). The durations of isometric, concentric and eccentric actions were either longer at the slower speed or did not change with speed for all six leg muscles. The action of knee extensor was primarily isometric at slower speed (P=0.004), and increased significantly to concentric and eccentric at faster speed (P<0.031). The activation magnitude of posterior leg muscles increased with speed (P<0.009). The old subjects had significantly shorter activation duration and lower activation magnitude in several leg muscles than the young, but similar speed effect as the young. INTERPRETATION: The activation duration and function of leg muscles, especially the knee extensor muscle, are significantly affected by the speed of the selected Tai Chi Chuan movement. Practicing Tai Chi Chuan at different speed may alter the role of muscular function in movement control.