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1.  Wen-Dan Decoction Improves Negative Emotions in Sleep-Deprived Rats by Regulating Orexin-A and Leptin Expression 
Wen-Dan Decoction (WDD), a formula of traditional Chinese medicine, has been clinically used for treating insomnia for approximately 800 years. However, the therapeutic mechanisms of WDD remain unclear. Orexin-A plays a key role in the sleep-wake cycle, while leptin function is opposite to orexin-A. Thus, orexin-A and leptin may be important factors in sleep disorders. In this study, 48 rats were divided into control, model, WDD-treated, and diazepam-treated groups. The model of insomnia was produced by sleep deprivation (SD) for 14 days. The expressions of orexin-A, leptin, and their receptors in blood serum, prefrontal cortex, and hypothalamus were detected by enzyme-linked immunosorbent assay, immunohistochemistry, and real time PCR. Open field tests showed that SD increased both crossing movement (Cm) and rearing-movement (Rm) times. Orexin-A and leptin levels in blood serum increased after SD but decreased in brain compared to the control group. mRNA expressions of orexin receptor 1 and leptin receptor after SD were decreased in the prefrontal cortex but were increased in hypothalamus. WDD treatment normalized the behavior and upregulated orexin-A, leptin, orexin receptor 1 and leptin receptor in brain. The findings suggest that WDD treatment may regulate SD-induced negative emotions by regulating orexin-A and leptin expression.
doi:10.1155/2014/872547
PMCID: PMC4016855  PMID: 24864160
2.  Acute and subacute IL-1β administrations differentially modulate neuroimmune and neurotrophic systems: possible implications for neuroprotection and neurodegeneration 
Background
In Alzheimer’s disease, stroke and brain injuries, activated microglia can release proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines may change astrocyte and neurotrophin functions, which influences neuronal survival and induces apoptosis. However, the interaction between neuroinflammation and neurotrophin functions in different brain conditions is unknown. The present study hypothesized that acute and subacute elevated IL-1β differentially modulates glial and neurotrophin functions, which are related to their role in neuroprotection and neurodegeneration.
Method
Rats were i.c.v. injected with saline or IL-1β for 1 or 8 days and tested in a radial maze. mRNA and protein expressions of glial cell markers, neurotrophins, neurotrophin receptors, β-amyloid precursor protein (APP) and the concentrations of pro- and anti-inflammatory cytokines were measured in the hippocampus.
Results
When compared to controls, memory deficits were found 4 days after IL-1 administrations, however the deficits were attenuated by IL-1 receptor antagonist (RA). Subacute IL-1 administrations increased expressions of APP, microglial active marker CD11b, and p75 neurotrophin receptor, and the concentration of tumor necrosis factor (TNF)-α and IL-1β, but decreased expressions of astrocyte active marker glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and TrK B. By contrast, up-regulations of NGF, BDNF and TrK B expressions were found after acute IL-1 administration, which are associated with the increase in both glial marker expressions and IL-10 concentrations. However, TrK A was down-regulated by acute and up-regulated by subacute IL-1 administrations. Subacute IL-1-induced changes in the glial activities, cytokine concentrations and expressions of BDNF and p75 were reversed by IL-1RA treatment.
Conclusion
These results indicate that acute and subacute IL-1 administrations induce different changes toward neuroprotection after acute IL-1 administrations but neurodegeneration after subacute ones.
doi:10.1186/1742-2094-10-59
PMCID: PMC3656796  PMID: 23651534
Acute and 8 day repeated IL-1β administration; Microglia; Astrocytes; Memory; Neurotrophins; Neurotrophin receptors; Cytokines
3.  Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways 
BMC Medicine  2012;10:66.
It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers.
doi:10.1186/1741-7015-10-66
PMCID: PMC3391987  PMID: 22747645
depression; sickness behavior; inflammation; oxidative stress; cytokines
4.  An efficient approach to finding Siraitia grosvenorii triterpene biosynthetic genes by RNA-seq and digital gene expression analysis 
BMC Genomics  2011;12:343.
Background
Siraitia grosvenorii (Luohanguo) is an herbaceous perennial plant native to southern China and most prevalent in Guilin city. Its fruit contains a sweet, fleshy, edible pulp that is widely used in traditional Chinese medicine. The major bioactive constituents in the fruit extract are the cucurbitane-type triterpene saponins known as mogrosides. Among them, mogroside V is nearly 300 times sweeter than sucrose. However, little is known about mogrosides biosynthesis in S. grosvenorii, especially the late steps of the pathway.
Results
In this study, a cDNA library generated from of equal amount of RNA taken from S. grosvenorii fruit at 50 days after flowering (DAF) and 70 DAF were sequenced using Illumina/Solexa platform. More than 48,755,516 high-quality reads from a cDNA library were generated that was assembled into 43,891 unigenes. De novo assembly and gap-filling generated 43,891 unigenes with an average sequence length of 668 base pairs. A total of 26,308 (59.9%) unique sequences were annotated and 11,476 of the unique sequences were assigned to specific metabolic pathways by the Kyoto Encyclopedia of Genes and Genomes. cDNA sequences for all of the known enzymes involved in mogrosides backbone synthesis were identified from our library. Additionally, a total of eighty-five cytochrome P450 (CYP450) and ninety UDP-glucosyltransferase (UDPG) unigenes were identified, some of which appear to encode enzymes responsible for the conversion of the mogroside backbone into the various mogrosides. Digital gene expression profile (DGE) analysis using Solexa sequencing was performed on three important stages of fruit development, and based on their expression pattern, seven CYP450s and five UDPGs were selected as the candidates most likely to be involved in mogrosides biosynthesis.
Conclusion
A combination of RNA-seq and DGE analysis based on the next generation sequencing technology was shown to be a powerful method for identifying candidate genes encoding enzymes responsible for the biosynthesis of novel secondary metabolites in a non-model plant. Seven CYP450s and five UDPGs were selected as potential candidates involved in mogrosides biosynthesis. The transcriptome data from this study provides an important resource for understanding the formation of major bioactive constituents in the fruit extract from S. grosvenorii.
doi:10.1186/1471-2164-12-343
PMCID: PMC3161973  PMID: 21729270
5.  (E)-N′-(3,4-Dimethoxy­benzyl­idene)-2,4-dihydroxy­benzohydrazide methanol solvate 
The title compound, C16H16N2O5·CH3OH, was obtained from a condensation reaction of 3,4-dimethoxy­benzaldehyde and 2,4-dihydroxy­benzohydrazide. The non-H atoms of the Schiff base mol­ecule are approximately coplanar (r.m.s. deviation = 0.043 Å) and the dihedral angle between the two benzene rings is 1.6 (1)°. The mol­ecule adopts an E configuration with respect to the C=N double bond. An intra­molecular O—H⋯O hydrogen bond is observed. The Schiff base and methanol mol­ecules are linked into a two-dimensional network parallel to (10) by inter­molecular N—H⋯O, O—H⋯N and O—H⋯O hydrogen bonds.
doi:10.1107/S1600536809035752
PMCID: PMC2970482  PMID: 21577856
6.  (Z)-N′-(4-Hydr­oxy-4-methyl­pentan-2-yl­idene)-2-(8-quinol­yloxy)acetohydrazide 
The title compound, C17H21N3O3, has a Z configuration about the N=N double bond. The molecular conformation is stabilized by intramolecular N—H⋯O and O—H⋯N hydrogen bonds.
doi:10.1107/S1600536809024957
PMCID: PMC2977343  PMID: 21583455

Results 1-6 (6)