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    An Update on Antipsychotic Drugs: New Targets and New Mechanisms
    GUO Lin, ZHEN Xue-chu
    2013, 3 (5):  2-12. 
    Abstract ( 2437 )   PDF (2653KB) ( 3046 )  
    Schizophrenia is a devastating disease affecting nearly 1% population worldwide. Since 1950s, both typical and atypical antipsychotic drugs have been introduced to treat the disease. Although great efforts and progress have been made, the challenge remains. The current paper will review the recent progress in developing novel anti-psychotic drugs and discuss the challenges and opportunities.
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    Development of Human Experimental Pain Models
    ZHANDSUN Dong-ting, LUO Su-lan
    2013, 3 (5):  13-26. 
    Abstract ( 2289 )   PDF (2778KB) ( 2056 )  
    Pain is the most common symptom of various diseases, which is a vexing worldwide problem that causes substantial disability and consumes significant medical resources. Limited analgesic medications were used in the clinic. The effects of these analgesics are often incomplete and complicated by serious side effects and/or tolerance. Thus, new types of analgesic drugs without addiction and serious side effects are desperately needed. It is hard to understand the basic biology of pain as well as to evaluate analgesic effects in human models. Therefore, animal models are widely used in the laboratory investigations to screen and identify new painkiller candidates. Animal pain models have shown low predictability for analgesic efficacy in humans, and clinical studies are confounded to interfere with the evaluation. Human experimental pain models may therefore help to evaluate mechanisms and effect of analgesics and bridge findings from basic studies to the clinic. The value of human experimental pain models is to link animal and clinical pain studies, providing new possibilities for designing successful clinical trials. The present review outlines the progress of human experimental pain models in healthy volunteers and addresses analgesic efficacy in patients, which would be helpful to speed up development of new types of analgesic drugs.
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    Depression and Inflammation
    WANG Zhen-zhen, CHEN Nai-hong
    2013, 3 (5):  27-37. 
    Abstract ( 3587 )   PDF (2160KB) ( 1997 )  
    Depression is the affective disorder characterized by a state of low mood, pessimism, cognitive and sleep disorders. Despite the widespread prescription of monoaminergic neurotransmitter modulators, the monoamine hypothesis cannot explain all the phenomena of depression. Moreover, limited drug efficacies, slow onset of action and undesirable side effects have made urgent the task of discovering novel therapeutics. Thus, several hypotheses other than the monoamine hypothesis have received much attention in recent years. The inflammatory hypothesis of depression is that inflammatory mechanisms play a crucial role in the pathophysiological mechanisms of major depression. This review will focus on progress of the (neuro)inflammatory hypothesis of depression.
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    Columns of research note and experimental methodology
    Temporal Changes of Wnt3a Protein Level in Rats after Focal Cerebral Ischemia Reperfusion
    LI Yan-fei, WANG Wen
    2013, 3 (5):  38-42. 
    Abstract ( 2014 )   PDF (1357KB) ( 1393 )  
    Objective: To investigate the dynamic change of Wnt3a in rats after focal cerebral ischemia reperfusion. Methods: 80 rats were induced by occlusion of middle cerebral artery with suture embolus and ischemia for 30 minutes, then randomly assigned into different groups to receive reperfusion for 3, 6, 12, 24 h, 3, 7, 14, 28 d. Sham operation group did not receive no suture embolus. The infarct side of the cortex of rats for each time group was harvested for the assessment of protein expression of activated Wnt3a using western blot staining. Results: Compared with the sham operation group (0.66±0.04), Wnt3a was slightly increased after 3 hours of focal cerebral ischemia reperfusion, and then reached the peak at 24 hours (1.57±0.18) and maintained a higher level within 7 days, declined after 2 weeks, but remained higher than the level of the sham operation group at 4 weeks (0.68±0.04). Conclusion: Wnt3a level of the cortex changed over time after reperfusion, suggesting that this signaling pathway may be activated in the regulation of neurogenesis.
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    Ginkgo Biloba Leaves and Depression
    ZHANG Hai-hong, WANG Shu
    2013, 3 (5):  43-49. 
    Abstract ( 3326 )   PDF (1234KB) ( 2082 )  
    Depression is a refractory mental disorder and exerts substantial challenge to public health. Ginkgo biloba extract can clear free radicals in the body and effectively improve the energy metabolism of the central nervous system, and also can protect the nerve function and improve cognitive function in patients with depression. This review summarized the combined therapy of depression by Ginkgo biloba extract and antidepressants, with a special focus on vascular depression.
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    The Relationship Between reactive oxygen species (ROS) and activation of neutrophilic alkaline phosphatase 3 (NALP3) Inflammasome
    ZHANG Nan, ZHANG Xiang-jian
    2013, 3 (5):  50-57. 
    Abstract ( 2791 )   PDF (1366KB) ( 1765 )  
    Inflammatory reaction has been proved to play an important role in the cerebral ischemia/reperfusion. Inflammasomes are a family of protein complexes that were recently identified as the cellular machinery responsible for recognizing pathogen-associated molecular patterns and reacting to these through activation of inflammatory processes, such as IL1b and IL18. Among different types of inflammasomes, the neutrophilic alkaline phosphatase-3 (NALP3) inflammasome is the most studied. It is characterized as a proteolytic complex mainly composed of the neutrophilic alkaline phosphatase-3 (NALP3), the adaptor protein apoptosis-associated speck-like protein (ASC), and caspase-1. However, little is known on the molecular mechanisms that mediate its assembly and activation. Recent evidence suggests that reactive oxygen species (ROS) are produced by NALP3 activators and are essential secondary messengers signaling NALP3 inflammasome activation. This paper discussed the relationship between ROS and activation of NALP3 inflammasome.
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    Progress on the Neuroprotective Mechanism of Gastrodin
    TIAN Hui, ZHANG Dan-shen
    2013, 3 (5):  58-64. 
    Abstract ( 3099 )   PDF (1249KB) ( 2350 )  
    Gastrodin is a main chemical constituent in Gastrodia elata blume and has been widely used in clinical application with various therapeutic effects. Current studies suggest that gastrodin has analgesic, sedative, hypnosis, anti- convulant, antiepileptic, antineurodegenerative diseases, and so on. Its mechanism of action is not fully understood, yet existing results suggest that its neuroprotective mechanism is closely related to inhibiting the activation of astrocytes, reducing the expression of CGRP, lowering DRG excitability, activating benzodiazepine receptor, reducding the amount of dopamine and norepinephrine, balancing the amino acid neurotransmitter, and inhibiting brain synaptic remodeling in the brain.
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