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Objective: To investigate the ameliorating effect of ginsenoside Rg1 on the depression-like behaviors induced by chronic restraint stress (CRS) in rats and the underlying mechanisms. Methods: Forty male Wistar rats were divided into 4 groups according to their baseline sucrose preference: control group, model group, and Rg1-treated groups (5 and 10 mg/kg). Except for control group, the groups were exposed to CRS (6 h/day) for 28 days. All drugs were intraperitoneally administered once daily to CRS rats after restraint stress for 14 days. The behavioral tests were carried out via the open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and the Morris water maze (MWM) 4 weeks following CRS induction. The levels of serum corticosterone (CORT) and the activities of the antioxidant defense biomarkers (SOD, MDA and GSH-x) in the prefrontal cortex (PFC) were analyzed using commercial ELISA kits. The levels of the neurotransmitter (5-HT, 5-HIAA, Ach, NE, GABA and Glu) in the PFC were measured by ultra-performance liquid chromatography tandem mass spectrometry. The protein expression of BDNF, Trkb, Bax and Bcl-2 in the PFC was detected by western blotting. Results: Owing to increased sucrose consumption in the SPT, decreased immobility time in the FST, and the improved cognitive performance in MWM, chronic treatment with Ginsenoside Rg1 was found to significantly attenuate depression- like behaviors (anhedonia, behavioral despair and poor spatial memory) in rats. Moreover, CRS exposure caused evident alterations in the levels of the neurotransmitters (5-HT, 5-HIAA, Ach, GABA and Glu) and the activities of the antioxidant defense biomarkers (SOD, MDA and GSH-x) in the PFC and the levels of corticosterone in serum. However, Ginsenoside Rg1 treatment could restore these levels to normal values. Additionally, Ginsenoside Rg1 treatment significantly reverted the decreased expression of BDNF, Trkb and Bcl-2 and the increased expression of Bax in the PFC of CRS rats. Conclusions: Ginsenoside Rg1 could attenuate the CRS-induced depression-like behaviors, in part, by regulating neurotransmitter levels and HPA function, antagonizing oxidative stress and apoptosis, and restoring BDNF-TrkB signaling in PFC. Altogether, our results provide a novel basis regarding the potential therapeutic effects of Rg1 on depression. Keywords: Ginsenosides Rg1, Depression, Chronic restraint stress, Neurotransmitter, Oxidative stress, BDNF

Ethnopharmacological relevance Kai Xin San (KXS), a traditional formula of Chinese medicine, has been used to treat dementia. Aim of the study The present study aimed to investigate its ameliorating effects on Aβ 1-40 -induced cognitive impairment in rats using a series of novel reward-directed instrumental learning tasks, and to determine its possible mechanism of action. Materials and methods Rats were pretreated with KXS aqueous extract (0.72 and 1.44 g/kg, p.o.) for 10 days, and were trained to gain reward reinforcement by lever pressing at the meantime. Thereafter, rats received a bilateral microinjection of Aβ 1-40 in CA1 regions of the hippocampus. Cognitive performance was evaluated with the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning tasks, as well as on the levels of memory-related biochemical parameters and molecules. Results Our findings first demonstrated that KXS can improve Aβ 1-40 -induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior. Then, its ameliorating effects should be attributed to the modulation of memory-related molecules in the hippocampus. Conclusion In conclusion, KXS has the potential to prevent and/or delay the deterioration of cognitive impairment in AD.

It is vital for astronauts to develop effective countermeasures to prevent their decline of cognitive performance in microgravity to make space-flight missions successful. The traditional Chinese herbal formula Kai Xin San (KXS) has been used to treat amnesia for thousands years. It is a traditional complex prescription comprising of ginseng (Panax ginseng C. A. Meyer), hoelen (Poria cocos (Schw.) Wolf), polygala (Polygala tenaifolia Willd), and acorus (Acorus tatarinowii Schott). Previous study showed KXS could improve CMS-induced memory impairment in rats.In this paper, a unique environmental factor-microgravity (weightlessness) was simulated as hindlimb suspension (HLS) by tail in rats for two weeks as the HLS animal model. The KXS at the doses of 0.3 or 0.6g/kg p.o. daily was administrated to HLS rats for two weeks at the same time of HLS, the memory behavior tests were investigated with Morris water maze (MWM) and Shuttle Box (SB) test. The levels of ROS, 8-OHdG and 3-nitrotyrosine (3-NT) in the serum, and AChE and ChAT activity in the brain of rats were determined by ELISA or biochemical analysis.After HLS for two weeks, the escape latency and the swimming distance were significantly increased in the MWM test in rats in the HLS group, compared with control group. The percent of swimming distance in target quadrant and the number of target crossing was significantly decreased in rats in the HLS group compared with the control group. Performance in the SB test showed, the numbers and the distance of active avoidance was decreased from day 4 to day 7, the time spent in electric area was increased in rats in the HLS group compared with the control group. Administration of KXS 0.3 or 0.6g/kg to the HLS rats for two weeks significantly reduced the escape latency and the swimming distance, increased the percentage of swimming distance in target quadrant and the number of target crossings (P0.01, compared with the HLS group) in the MWM test. Similar treatment with KXS increased the numbers and the distance of active avoidance (P0.01, compared with the HLS group) and reduced the time spent in electric area after training 3 days in the SB test (P0.01, compared with the HLS group). The HLS induced the increase of the ROS, 8-OHdG and 3-NT in the serum of rats, but has little influence on the AChE, ChAT activity in the brain. Only the AChE activity in the cortex and the ChAT activity in the hippocampus had some changes in rats in the HLS model group. After administration of KXS 0.6g/kg for two weeks, the abnormal levels of ROS, 8-OHdG, 3-NT were found reversed in the serum of rats (P0.05, compared with HLS model group). And KXS 0.3g/kg was found reversed the increased AChE activity in the cortex.Experimental results from this study show that KXS may improve memory deficiency induced by HLS, its mechanisms are major related to antioxidant activities, rather than the central cholinergic system.

Cancer is a disease associated with the deregulation of multiple gene networks. Microarray data has permitted researchers to identify gene panel markers for diagnosis or prognosis of cancer but these are not sufficient to make specific mechanistic assertions about phenotype switches. We propose a strategy to identify putative mechanisms of cancer phenotypes by protein-protein interactions (PPI). We first extracted the logic status of a PPI via the relative expression of the corresponding gene pair. The joint association of a gene pair on a cancer phenotype was calculated by entropy minimization and assessed using a support vector machine. A typical predictor is “ If Src high-expression, and Cav-1 low-expression, then cancer.“ We achieved 90% accuracy on test data with a majority of predictions associated with the MAPK pathway, focal adhesion, apoptosis and cell cycle. Our results can aid in the development of phenotype discrimination biomarkers and identification of putative therapeutic interference targets for drug development.

Introductionn Advances in high-throughput technologies have generated diverse informative molecular markers for cancer outcome prediction. Long non-coding RNA (lncRNA) and DNA methylation as new classes of promising markers are emerging as key molecules in human cancers; however, the prognostic utility of such diverse molecular data remains to be explored.n Materials and Methodsn We proposed a computational pipeline (IDFO) to predict patient survival by identifying prognosis-related biomarkers using multi-type molecular data (mRNA, microRNA, DNA methylation, and lncRNA) from 3198 samples of five cancer types. We assessed the predictive performance of both single molecular data and integrated multi-type molecular data in patient survival stratification, and compared their relative importance in each type of cancer, respectively. Survival analysis using multivariate Cox regression was performed to investigate the impact of the IDFO-identified markers and traditional variables on clinical outcome.n Resultsn Using the IDFO approach, we obtained good predictive performance of the molecular datasets (bootstrap accuracy: 0.71-0.97) in five cancer types. Impressively, lncRNA was identified as the best prognostic predictor in the validated cohorts of four cancer types, followed by DNA methylation, mRNA, and then microRNA. We found the incorporating of multi-type molecular data showed similar predictive power to single-type molecular data, but with the exception of the lncRNA + DNA methylation combinations in two cancers. Survival analysis of proportional hazard models confirmed a high robustness for lncRNA and DNA methylation as prognosis factors independent of traditional clinical variables.n Conclusionn Our study provides insight into systematically understanding the prognostic performance of diverse molecular data in both single and aggregate patterns, which may have specific reference to subsequent related studies.

Background Tong Luo Jiu Nao (TLJN), a modern formula of Chinese medicine extracts on the basis of Traditional Chinese Medicine theory, has been used to treat dementia. The present study aimed to investigate its ameliorating effects on Aβ1–40-induced cognitive impairment in rats using a series of novel reward-directed instrumental learning (RDIL) tasks, and to determine its possible mechanism of action. Methods Rats were pretreated with TLJN extract (0.9 and 1.8 g/kg, p.o.) for 10 daysbefore surgery, and were trained to gain reward reinforcement by lever pressing at the meantime. Thereafter, rats received a bilateral microinjection of Aβ1–40 in CA1 regions of the hippocampus. Cognitive performance was evaluated with the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning tasks, as well as on the levels of biochemical parameters and molecules. Results Our findings first demonstrated that TLJN can improve Aβ1–40-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior. Then, its ameliorating effects should attribute to the modulation of ERK/CaMKII/CREB signaling in the hippocampus. Conclusion TLJN can markedly enhance cognitions of Aβ1–40 microinjection animal model in adaptive behavioral tasks. It has the potential, possibly as complementary and alternative therapy, to prevent and/or delay the deterioration of cognitive impairment in AD.

To study effective speech features which can represent different emotion styles in mandarin speech, nonlinear features based on Teager Energy Operator(TEO) are researched. Neutral state and 3 emotional states (i.e. happiness, anger and sadness) are classified from the mandarin speech database. MFCC extraction and HMM-based emotion recognition are used as baseline system to evaluate the emotional classification performance of TEO-based features. In comparison with MFCC, while text- dependent, improvements of classification capacity are obtained when using all 4 nonlinear features (i.e. NFD_Mel, AF_Mel, DAF_Mel, AM_SBCC). While text-independent, the performance of emotion classification are improved by using NFD_Mel, AF_Mel and DAF_Mel, but deteriorated by using AM_SBCC. The results of classification demonstrate that the nonlinear features based on TEO, when using NFD_Mel, AF_Mel and DAF_Mel, are better able to represent different emotion styles in speech than that of MFCC.

Background The automation of many common molecular biology techniques has resulted in the accumulation of vast quantities of experimental data. One of the major challenges now facing researchers is how to process this data to yield useful information about a biological system (e.g. knowledge of genes and their products, and the biological roles of proteins, their molecular functions, localizations and interaction networks). We present a technique called Global Mapping of Unknown Proteins (GMUP) which uses the Gene Ontology Index to relate diverse sources of experimental data by creation of an abstraction layer of evidence data. This abstraction layer is used as input to a neural network which, once trained, can be used to predict function from the evidence data of unannotated proteins. The method allows us to include almost any experimental data set related to protein function, which incorporates the Gene Ontology, to our evidence data in order to seek relationships between the different sets. Results We have demonstrated the capabilities of this method in two ways. We first collected various experimental datasets associated with yeast (Saccharomyces cerevisiae) and applied the technique to a set of previously annotated open reading frames (ORFs). These ORFs were divided into training and test sets and were used to examine the accuracy of the predictions made by our method. Then we applied GMUP to previously un-annotated ORFs and made 1980, 836 and 1969 predictions corresponding to the GO Biological Process, Molecular Function and Cellular Component sub-categories respectively. We found that GMUP was particularly successful at predicting ORFs with functions associated with the ribonucleoprotein complex, protein metabolism and transportation. Conclusion This study presents a global and generic gene knowledge discovery approach based on evidence integration of various genome-scale data. It can be used to provide insight as to how certain biological processes are implemented by interaction and coordination of proteins, which may serve as a guide for future analysis. New data can be readily incorporated as it becomes available to provide more reliable predictions or further insights into processes and interactions.

Accompanying the flourishing developments of China's manned spaceflight,space medicine has achieved great development during the past two years in China.In this paper,scientific research of space medicine and its application in China during 2010—2012 have been briefly introduced.