Knockdown of lncRNA HOXD-AS2 Improves the Prognosis of Glioma Patients by Inhibiting the Proliferation and Migration of Glioma Cells.

Objective: Increasing studies reported that long noncoding RNAs are involved in regulating glioma progression. However, the specific roles and mechanisms of lncRNAs in glioma remain unclear. Here, we sought to explore the functions of HOXD-AS2 in glioma progression. Methods: Gene expressions of lncRNAs in 5 normal brain tissue specimens and 5 glioblastoma tissue specimens were detected by gene expression profile chip technology. Bioinformatic analysis was performed to see whether differential expression of lncRNAs played any significant role in glioma occurrence and progression. The relationship between HOXD-AS2 level and clinical prognosis of the patients was analyzed. HOXD-AS2 was specifically interfered with by siRNA technology to observe its effects on U251 cell growth, proliferation, apoptosis, and invasion. Results: The expression level of HOXD-AS2 gene in glioma was significantly higher than that in the normal brain tissue, which was related to the tumor grade. The level of HOXD-AS2 gene in patients with high-grade glioma was higher than that in patients with low-grade glioma. High expression of HOXD-AS2 gene was a risk factor for poor prognosis of glioma patients. Knocking down the expression of HOXD-AS2 in glioma cell line U251 arrested the cell cycle and reduced the cell proliferation. Furthermore, it could significantly reduce the migration ability of the cells but had no significant effect on the invasion. Conclusion: HOXD-AS2 is an oncogenic lncRNA associated with the poor prognosis of glioma. Knockdown of HOXD-AS2 may reduce the growth of glioma, which may provide a new avenue for treatment.

[Warming acupuncture combined with "three steps and seven methods" of tuina for chronic nonspecific low back pain of yang deficiency and cold-dampness blockage: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy and possible mechanism of warming acupuncture combined with "three steps and seven methods" of tuina and simple "three steps and seven methods" of tuina in treatment of chronic nonspecific low back pain (NLBP) of yang deficiency and cold-dampness blockage. METHODS: A total of 138 patients were randomized into an observation group (69 cases, 5 cases dropped off) and a control group (69 cases, 7 cases dropped off). In the control group, "three steps and seven methods" of tuina was applied. On the basis of the treatment in the control group, warming acupuncture was applied at Shenshu (BL 23), Yaoyangguan (GV 3), Mingmen (GV 4), Weizhong (BL 40) and ashi points. The treatment was given once a day, 6 times a week for 3 weeks in both groups. Before and after treatment, the short form of McGill pain questionnaire (SF-MPQ) score, Oswestry disability index (ODI) score, finger-to-floor distance (FFD), Schober test distance, fear-avoidance beliefs questionnaire (FABQ) score and yang deficiency and cold-dampness blockage score were observed, the serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6 and thromboxane B2 (TXB2) were detected in both groups. The recurrence rate was evaluated in follow-up of 6 months after treatment. RESULTS: After treatment, the scores of PRI, PPI, VAS, ODI, FABQ and FFD, yang deficiency and cold-dampness blockage scores were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01); the Schober test distances were increased compared before treatment in both groups (P<0.01), and that in the observation group was larger than the control group (P<0.01). After treatment, the serum levels of TNF-α, IL-1ß, IL-6 and TXB2 were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01). In follow-up, the recurrence rate was 12.8% (6/47) in the observation group, which was lower than 34.3% (12/35) in the control group (P<0.05). CONCLUSION: Warming acupuncture combined with "three steps and seven methods" of tuina can effectively alleviate pain in patients with chronic NLBP of yang deficiency and cold-dampness blockage, improve activity and dysfunction of waist, the clinical efficacy is superior to simple "three steps and seven methods" of tuina, its mechanism may be relate to the inhibition of inflammatory reaction.

[Effects of biochar application patterns on soil nutrients and nitrogen- and phosphorus-related enzyme activities in Phaeozem and Luvisol]. / ç”Ÿç‰©ç‚­æ–½ç”¨æ–¹å¼å¯¹é»‘åœŸå’Œæ½®æ£•å£¤å »åˆ†åŠæ°®ç£·è½¬åŒ–ç›¸å ³é ¶æ´»æ€§çš„å½±å“.

We investigated the effects of different biochar application patterns on soil nutrient contents and element transformation, with soil samples being collected from two five-year field experiments in Phaeozem and Luvisol amended with biochar at annual low-rate (AL, 22.5 t·hm-2·a-1) and intervalic high-rate (IH, 112.5 t·hm-2·5 a-1). Changes of soil total carbon (C), nitrogen (N) and phosphorus (P) contents as well as the related enzyme activities were measured under different biochar application patterns to provide fundamental information for the straw utilization and soil fertility improvement in agroecosystem. Results showed that total C and organic N contents in AL treatment were significantly higher than those in IH treatment in Phaeozem soil. Compared with the control, the decreases of dehydrogenase activity in AL treatment was more pronounced than that in IH treatment in Phaeozem soil, and the increases of protease activity in IH treatment was pronounced than that in AL treatment in Luvisol. Compared with Luvisol soil, the application of biochar had stronger effect on total soil C and organic N contents in Phaeozem soil. Application of biochar significantly increased the activities of soil dehydrogenase and protease in Luvisol soil, but decreased the activity of soil dehydrogenase. Soil types and biochar application patterns interacted to affect soil C and N contents, microbial metabolic activity, N- and P-related enzyme activities. In summary, soil types and biochar addition affected soil properties and microbial characteristics, which would provide important information for straw application and soil management.

[Effect of nitrogen additions on soil pH, phosphorus contents and phosphatase activities in grassland]. / æ°®æ·»åŠ å¯¹è‰åœ°ç”Ÿæ€ç³»ç»ŸåœŸå£¤pHã€ç£·å«é‡å’Œç£·é ¸é ¶æ´»æ€§çš„å½±å“.

Phosphorus is a key nutrient for all plant species and a limiting factor for grassland ecosystem function. In recent years, in response to the rapid increase of global nitrogen deposition, soil phosphorus contents and phosphatase activities changed to varying degrees in grassland ecosystems. We conducted a meta-analysis to examine the responses of soil pH, total phosphorus (TP), available phosphorus (AP), as well as activities of alkaline phosphatase (AlP) and acid phosphatase (AcP) in soils to nitrogen addition amount, nitrogen type, experimental duration, and sampling depth. The correlation between soil pH and phosphatase response ratio was investigated. The results showed that nitrogen addition significantly reduced soil pH, TP and AlP activity, while significantly increased AcP activity, but had no significant effect on AP. Soil pH and AlP activity significantly decreased under nitrogen addition >5 g·m-2·a-1, and AcP activity significantly increased under high nitrogen addition (>10 g·m-2·a-1). The contents of TP and AP significantly decreased when nitrogen addition was 5-10 g·m-2·a-1. NH4NO3 treatment significantly reduced soil TP and increased AcP activity, while urea treatment significantly reduced soil pH and AlP activity. Across all nitrogen addition amounts, when the experiment duration was 3 to 10 years, soil TP content and AlP activity were significantly reduced. Soil pH was significantly reduced after three years nitrogen addition, and AcP activitiy was significantly increased after 10 years nitrogen addition. In the 0-10 cm soil layer, the TP content and AlP activity significantly decreased, while the AP content significantly increased. In >10 cm soil layer, the AP content was significantly decreased. The significant negative correlation between soil pH and AcP activity indicated that change in soil pH caused by nitrogen addition may be an important factor for the variation of soil phosphatase activity.

circRNA circAF4 functions as an oncogene to regulate MLL-AF4 fusion protein expression and inhibit MLL leukemia progression.

BACKGROUND: Circular RNAs (circRNAs) represent a type of endogenous noncoding RNAs that are generated by back-splicing events and favor repetitive sequences. Recent studies have reported that cancer-associated chromosomal translocations could juxtapose distant complementary repetitive intronic sequences, resulting in the aberrant formation of circRNAs. However, among the reported fusion genes, only a small number of circRNAs were found to originate from fusion regions during gene translocation. We question if circRNAs could also originate from fusion partners during gene translocation. METHODS: Firstly, we designed divergent primers for qRT-PCR to identify a circRNA circAF4 in AF4 gene and investigated the expression pattern in different types of leukemia samples. Secondly, we designed two small interfering RNAs specially targeting the back-spliced junction point of circAF4 for functional studies. CCK8 cell proliferation and cell cycle assay were performed, and a NOD-SCID mouse model was used to investigate the contribution of circAF4 in leukemogenesis. Finally, luciferase reporter assay, AGO2 RNA immunoprecipitation (RIP), and RNA Fluorescent in Situ Hybridization (FISH) were performed to confirm the relationship of miR-128-3p, circAF4, and MLL-AF4 expression. RESULTS: We discovered a circRNA, named circAF4, originating from the AF4 gene, a partner of the MLL fusion gene in MLL-AF4 leukemia. We showed that circAF4 plays an oncogenic role in MLL-AF4 leukemia and promotes leukemogenesis in vitro and in vivo. More importantly, knockdown of circAF4 increases the leukemic cell apoptosis rate in MLL-AF4 leukemia cells, while no effect was observed in leukemia cells that do not carry the MLL-AF4 translocation. Mechanically, circAF4 can act as a miR-128-3p sponge, thereby releasing its inhibition on MLL-AF4 expression. We finally analyzed most of the MLL fusion genes loci and found that a number of circRNAs could originate from these partners, suggesting the potential roles of fusion gene partner-originating circRNAs (named as FP-circRNAs) in leukemia with chromosomal translocations. CONCLUSION: Our findings demonstrate that the abnormal elevated expression of circAF4 regulates the cell growth via the circAF4/miR-128-3p/MLL-AF4 axis, which could contribute to leukemogenesis, suggesting that circAF4 may be a novel therapeutic target of MLL-AF4 leukemia.

Postoperative adjuvant sorafenib improves survival outcomes in hepatocellular carcinoma patients with microvascular invasion after R0 liver resection: a propensity score matching analysis.

BACKGROUND: Microvascular invasion (MVI) is a major determinant of survival outcome for hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy of postoperative adjuvant Sorafenib (PA-Sorafenib) in HCC patients with MVI after R0 liver resection (LR). METHODS: The data of patients who underwent R0 LR for HCC with histologically confirmed MVI at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-Sorafenib were compared with those who underwent R0 LR alone. Propensity score matching (PSM) analysis was performed. RESULTS: 728 HCC patients had MVI in the resected specimens after R0 resection, with 581 who underwent LR alone and 147 patients who received in additional adjuvant sorafenib. PSM matched 113 patients in each of these two groups. The overall survival (OS) and recurrence free survival (RFS) were significantly better for patients in the PA-sorafenib group (for OS: before PSM, P = 0.003; after PSM, P = 0.007), (for RFS: before PSM, P = 0.029; after PSM, P = 0.001), respectively. Similar results were obtained in patients with BCLC 0-A, BCLC B and Child-Pugh A stages of disease. CONCLUSIONS: PA-Sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI.

Responses of soil nutrients and biological characteristics to nitrogen deposition in Hulun Buir Grassland, China.

Studies on effects of nitrogen deposition were mainly focused on temperate grasslands in Inner Mongolia of China. In addition, there are substantial differences between the present simulation methods and the natural nitrogen deposition. A three-year experiment was carried out to compare the effects of simulation methods (common urea and slow-released urea) and nitrogen deposition rates (0, 25, 50, 75, 100, 150, 200 and 300 kg N·hm-2·a-1) on soil nutrients and biological characteristics in Hulun Buir Grassland. We found that simulated nitrogen deposition had significant influences on soil chemical properties, biological properties and enzyme activities. With the increases of nitrogen deposition, soil pH declined with the greatest extent of 0.2 units, while the highest concentrations of total dissolved nitrogen (TDN) and dissolved organic carbon (DOC) increased by 5-7 times and 12%-36%, respectively. There was a decline trend for soil total phosphorus (TP) and organic phosphorus (TOP). Microbial biomass and metabolic activity increased firstly and then decreased. Moderate simulated nitrogen deposition rates significantly increased soil carbon, nitrogen and phosphorus related enzyme activities. Compared to common urea, using slow-released urea to simulate nitrogen deposition decelerate the decline of soil pH and the increase of dissolved nutrients, and smoothed the change of microbial biomass, metabolic activity, and nitrogen hydrolyzed enzyme activities. Overall, the results confirmed that continuous nitrogen input caused the decline of soil pH and the increase of bioavailable carbon and nitrogen, and then changed microbial biomass and activity.

[Effects of carbon and nitrogen additions on soil organic C, N, P contents and their catalyzed enzyme activities in a grassland.] / ç¢³æ°®æ·»åŠ å¯¹è‰åœ°åœŸå£¤æœ‰æœºç¢³æ°®ç£·å«é‡åŠç›¸å ³é ¶æ´»æ€§çš„å½±å“.

Soil organic C, N, P contents and their catalyzed enzyme activities play an important role in maintaining and supplying energy and nutrient in grasslands. There is no consensus on the effects of N deposition on soil organic nutrients and enzyme activities in grassland ecosystems. It remains unclear whether C addition will retard the negative effects of N deposition. We carried out an experiment in Hulun Buir grassland of Inner Mongolia to examine the effects of C and N additions on soil organic C, N, P and relative enzyme activities after three years treatments. The experiment was conducted with N treatments at five levels (0, 25, 50, 100 and 200 kg·hm-2·a-1) and with C treatments at three levels (0, 250 and 500 kg·hm-2·a-1). The results showed that higher levels of N addition significantly decreased dehydrogenase (DHA) and ß-1,4-N-acetylglucosaminidase (NAG) activities by 22.3% and 12.5%, respectively. Nitrogen addition had no significant effect on soil organic N and decreased the organic C and P contents by 6.6% and 14.5%, respectively. High C addition significantly increased DHA, ß-glucosidase (BG) activities and increased soil organic N and organic P by 15.1%, 12.2%, 1.9%, 2.6%, respectively. The results suggested that continuous N inputs inhibited microbial activities and caused losses of soil organic C and organic P. Carbon addition could enhance microbial activities and promote the secretion of enzymes and increase soil organic N and P. The combined C and N addition could play an important role in maintaining the balance and supply of soil C, N, and P in grassland ecosystem.

Effect of Exogenous Phytase Addition on Soil Phosphatase Activities: a Fluorescence Spectroscopy Study.

The utilization of organic phosphorus (P) has directly or indirectly improved after exogenous phytase was added to soil. However, the mechanism by which exogenous phytase affected the soil phosphatases (phosphomonoesterase and phosphodiesterase) activities was not clear. The present work was aimed to study red soil, brown soil and cinnamon soil phosphomonoesterase (acid and alkaline) (AcP and AlP) and phosphodiesterase (PD) activities responding to the addition of exogenous phytase (1 g phytase/50 g air dry soil sample) based on the measurements performed via a fluorescence detection method combined with 96 microplates using a TECAN Infinite 200 Multi-Mode Microplate Reader. The results indicated that the acid phosphomonoesterase activity was significantly enhanced in red soil (p≤0. 01), while it was significantly reduced in cinnamon soil; alkaline phosphomonoesterase activity was significantly enhanced in cinnamon soil (p≤ 0. 01), while it was significantly reduced in red soil; phosphodiesterase activity was increased in three soils but it was significantly increased in brown soil (p≤0. 01) after the addition of exogenous phytase. The activities still remained strong after eight days in different soils, which indicated that exogenous phytase addition could be enhance soil phosphatases activities effectively. This effect was not only related to soil properties, such as pH and phosphorus forms, but might also be related to the excreted enzyme amount of the stimulating microorganism. Using fluorescence spectroscopy to study exogenous phytase addition influence on soil phosphatase activities was the first time at home and abroad. Compared with the conventional spectrophotometric method, the fluorescence microplate method is an accurate, fast and simple to use method to determine the relationships among the soil phosphatases activities.

Bioactive C21 Steroidal Glycosides from the Roots of Cynanchum otophyllum That Suppress the Seizure-like Locomotor Activity of Zebrafish Caused by Pentylenetetrazole.

Six new C21 steroidal glycosides, cynotophyllosides A-F (1-6), together with 16 known compounds, were isolated from the roots of Cynanchum otophyllum. The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. The three major components, otophylloside F (15), otophylloside B (17), and rostratamine 3-O-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside (18), suppressed the seizure-like locomotor activity caused by pentylenetetrazole in zebrafish. Preliminary structure-activity relation studies revealed that a pregnene skeleton with a C-12 ester group (ikemaoyl > cinnamoyl > hydroxy > p-hydroxybenzoyl) and a C-3 sugar chain consisting of three 2,6-dideoxysaccharide units is essential for this suppressive activity.

[Intestinal absorption of pulchinenosides from Pulsatilla chinensis in rats].

HPLC-ELSD was applied to explore the absorption mechanism of pulchinenosides (B3, BD, B7, B10, B11) in rats. The experimental results showed that the absorption rate constant, Ka value (B3, BD) and Permeability coefficient, Peff value (B3, B7) displayed significant difference (P <0.05) in various intestinal segments, The Ka value and Peff value of PRS was different from each other with the highest absorption in duodenum (duodenum > jejunum > colon > ileum); The PRS displayed excessive satuation as the concentration increased over 0.05-2.5 g · L(-1). There were no obvious linear correlations between Peff values and concentrations in duodenum (0.6007 ≤ R2 ≤ 0.7727); Ka and Peff value declined when the PRS was perfused with P-glycoprotein promoter digoxin, on the other hand, inclined when perfused with P-glycoprotein inhibitor verapamil with significant difference among PRS B3, BD, B7, B11 (P <0.05). All the above results demonstrated that B3, BD, B7 were greatly influenced by absorption sites, duodenum was the main absorption site; PRS didn't entirely transported in a concentration dependent manner, and the transporter-protein involved the transportation, so the intestinal absorption of the five pulchinenosides was not entirely passive diffusion; and PRS might be the substrates of P-glycoprotein.

Lithocarpic acids O-S, five homo-cycloartane derivatives from the cupules of Lithocarpus polystachyus.

Chemical investigation of the cupules of Lithocarpus polystachyus resulted in the identification of four 3,4-seco-homo-cycloartane and one homo-cycloartane derivatives named lithocarpic acids O-S. Their structures were determined based on extensive 1D/2D NMR, IR, MS spectroscopic analyses and chemical methods. Lithocarpic acid O (1) exhibited inhibitory activities on mouse and human isozymes of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) with IC50 values of 0.49 and 1.1 µM, respectively.

[Rapid identification for fruit drugs of rosaceae based on electrochemical oscillation reaction].

OBJECTIVE: To establish a rapid identification method for fruit drugs of Rosaceae, according to the influence of Chinese traditional medicine on the electrochemical oscillation reaction. METHODS: The experiments were carried out in H2SO4-Ce (SO4)2-CH2 (COOH)2-KBrO3 electrochemical oscillation system. The graphs and characteristic parameters which were formed by the disturbance of Rosaceous fruit drugs to the electrochemical oscillation reaction were studied. RESULTS: There were obvious distinction on the electrochemical fingerprints of five kinds of medicinal materials, and the characteristic parameters of oscillation life were significant different. CONCLUSION: The electrochemical fingerprints of five kinds of Rosaceous fruit drugs can be used to identify those medicinal materials. The method is simple, rapid, economic and reliable.

[Study on solubilization effect of solid dispersion technology and inclusion technology on pulsatillae total saponins].

OBJECTIVE: To study the effect of solid dispersion technology and inclusion technology on dissolution performance of Pulsatillae total saponins, and preliminarily investigate its mechanism. METHOD: The solid dispersion of Pulsatillae total saponins-PEG 4000 was prepared by the melting method. The inclusion compound of Pulsatillae total saponins-hydroxypropyl-beta-cyclodextrin ( HP-beta-CD) was prepared by the freeze-drying method. The properties of solid dispersion and inclusion compound were identified by using IR, DSC and NMR. And the dissolution of solid dispersion and inclusion compound were also determined by the small glass method. RESULT: IR, DSC and NMR results showed the formation of solid dispersion and inclusion compound. In terms of the dissolution, the inclusion compound ranked first, which was followed by solid dispersion and bulk pharmaceutical chemicals. CONCLUSION: The inclusion technology could significantly increase the dissolution of Pulsatillae total saponins, whereas the solid dispersion showed no notable solubilization effect.

[Preparation of colon target pellets of Pulsatilla total saponins-hydroxypropyl-beta-cyclodextrin inclusion].

OBJECTIVE: To prepare colon target pellets of Pulsatilla total saponins. METHOD: Pulsatilla total saponins-hydroxypropyl-beta-cyclodextrin inclusion was prepared by the water solution-mixing method. Then plain pills of inclusion were prepared by the granulation-spheronization method, and coated by Glatt fluid bed. RESULT: The dissolution of plain pills of Pulsatilla total saponins at 2 h was 16.0%, while that of plain pills of inclusion at 0.5 h was 91.9%. With Eudragit S100 as the coating material, TEC as the plasticizer and talcum power as the anti-adherent, when the coating weight was 12%, the coating efficiency was high, with almost no bonding and drug release of coated pellets in artificial gastric juice for 2 h. The accumulated drug release in artificial intestinal fluid for 4 h was less than 15%, and that in artificial colon fluid for 4 h was more than 90%. CONCLUSION: Coated pellets of Pulsatilla total saponins-hydroxypropyl-beta-cyclodextrin inclusion showed a good colon targeted drug release in vitro, thus could be further developed to be oral colon targeted preparations.

Structural revision of periplocosides and periperoxides, natural immunosuppressive agents from the genus Periploca.

The structures of a series of peroxy function containing pregnane glycosides isolated from Periploca sepium and Periploca forrestii were revised to be orthoester group bearing ones using 2D NMR spectroscopic techniques, as well as chemical transformations and X-ray crystallographic diffraction analysis. The orthoester function appears to be an essential structural feature for immunosuppressive activity.

Large-scale synthesis and phase transformation of CuSe, CuInSe2, and CuInSe2/CuInS2 core/shell nanowire bundles.

Facile chemical approaches for the controllable synthesis of CuSe, CuInSe2 nanowire, and CuInSe2/CuInS2 core/shell nanocable bundles were developed. Hexagonal CuSe nanowire bundles with lengths up to hundreds of micrometers, consisting of many aligned nanowires with a diameter of about 10-15 nm, were prepared by reacting cubic Cu(2-x)Se nanowire bundles with a sodium citrate solution at room temperature. The CuSe nanowire bundles were then used as self-sacrificial templates for making bundles of tetragonal chalcopyrite CuInSe2 nanowires by reacting with InCl3 via a solvothermal process. Furthermore, bundles of CuInSe2/CuInS2 core/shell nanocables were obtained by adding sulfur to the reaction system, and the shell thickness of the polycrystalline CuInS2 in the nanocables increased with increasing S/Se molar ratios. It was found that the small radius of copper ions allows their fast outward diffusion from the interior to the surface of nanowires to react with sulfur atoms/anions and indium ions to form a CuInS2 shell. Enhanced optical absorption in the vis-NIR region of CuInSe2/CuInS2 core/shell nanocable bundles is demonstrated, which is considered beneficial for applications in optoelectronic devices and solar energy conversion.

Effect of Warm-Supplementing Kidney Yang (WSKY) added to risperidone on quality of life in patients with schizophrenia: a randomized controlled trial.

OBJECTIVE: To evaluate the quality of life, efficacy and safety of Warm-Supplementing Kidney Yang (WSKY) added to risperidone in patients with schizophrenia. DESIGN: A randomized controlled trial. SETTING: The outpatient and inpatient departments of three hospitals. SUBJECTS: One hundred and twenty patients with clinically diagnosed schizophrenia with predominantly negative symptoms were included in the study. INTERVENTION: All 120 patients were randomly assigned to double-blind treatment with WSKY group (n = 60) or placebo group (n = 60) added to risperidone for eight weeks. MAIN MEASURE: The efficacy measures included the World Health Organization Quality of Life Scale (WHOQOL-100), the Positive and Negative Syndrome Scale (PANSS), the Social Disability Screening Schedule and the Hamilton Rating Scale for Depression. Safety and tolerability were assessed throughout the trial. RESULTS: The scores of quality of life in the WSKY group showed statistically significant improvement at the end-point of treatment compared with those in the placebo group (WSKY, increasing 40.5 (29.4); placebo, increasing 14.4 (27.1); F =24.900, P<0.001), while the scores of social function and depression symptoms also showed statistically significant improvement. The response rates for the WHOQOL-100 total scores were 50.0% for the WSKY group versus 31.7% for placebo group (chi( 2) = 4.172, P=0.041). There were no significant differences in the safety/tolerability measures between the WSKY group and the placebo group during treatment. CONCLUSIONS: The results suggest that WSKY added to risperidone significantly improved the quality of life, social function, depression symptom compared with placebo added to risperidone.

Periplocoside A prevents experimental autoimmune encephalomyelitis by suppressing IL-17 production and inhibits differentiation of Th17 cells.

AIM: The aim of this study was to determine the therapeutic effect of Periplocoside A (PSA), a natural product isolated from the traditional Chinese herbal medicine Periploca sepium Bge, in MOG(35-55) (myelin oligodendrocyte glycoprotein 35-55)-induced experimental autoimmune encephalomyelitis (EAE). METHODS: Female C57BL/6 mice immunized with MOG(35-55) were treated with (50 mg/kg or 25 mg/kg) or without PSA following immunization and continuously throughout the study. The degree of CNS inflammation was evaluated by H&E staining. Anti-MOG-specific recall responses were analyzed by [3H]-Thymidine incorporation, ELISA, and RT-PCR. The proportion of IL-17-producing T cells was measured by flow cytometry. RESULTS: Oral administration of PSA significantly reduced the incidence and severity of EAE, which closely paralleled the inhibition of MOG(35-55)-specific IL-17 production. Importantly, PSA inhibited the transcription of IL-17 mRNA and RORgammat. Further studies examining intracellular staining and adoptive transfer EAE validated the direct suppressive effect of PSA on Th17 cells. In vitro studies also showed that PSA significantly inhibited the differentiation of Th17 cells from murine purified CD4+ T cells in a dose-dependent manner. CONCLUSION: PSA ameliorated EAE by suppressing IL-17 production and inhibited the differentiation of Th17 cells in vitro. Our results provide new insight into the potential mechanisms underlying the immunosuppressive and anti-inflammatory effects of PSA.