Neurodegenerative disease is characterized by progressive loss of neurons in specific brain regions that results in neuronal dysfunction of the central nervous system. Although the pathological mechanism is not fully established, the activation of glial cells mediated neuroinflammation appears to be involved. Heat shock protein 70 (HSP70) is originally described as intracellular chaperone, which plays an important role in protein quality control in cells. However, recent study showed that up-regulation of HSP70 had anti-inflammatory effects in the brain. HSP70 protected neurons from damage and improved neurological function by decreasing inflammatory response as indicated by inactivation of glial cells and inhibition of pro-inflammatory cytokine release. So it is of great significance to find new compounds targeting at HSP70 as neuroprotective agents to delay the progress of neurodegenerative disease. This review will focus on the role of HSP70 in neuroinflammation and the recent advances in using HSP70 as a target for the treatment of neurodegenerative disease.
Brain ; physiopathology ; Cytokines ; HSP70 Heat-Shock Proteins ; physiology ; Humans ; Inflammation ; pathology ; Neurodegenerative Diseases ; physiopathology ; Neurons ; pathology ; Neuroprotection ; Up-Regulation

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Emodin ; pharmacology ; Humans ; Neoplasms ; pathology ; Tumor Cells, Cultured

AlM:To investigate the changes of retinal histology and oxidative stress in diabetic retinopathy and its reversal by pyruvate in diabetic rats.
METHODS: Eighty Wistar rats were divided into 3 groups:control group ( 20 rats ) , model group ( 30 rats ) and treatment group ( 30 rats ) . After streptozotocin ( STZ) induced diabetes mellitus in the model group and the treatment group, the treatment group received 2%pyruvate in diet and drinking. The changes of body weight and blood glucose were observed and the changes of glutathione peroxidase ( GSH-PX ) , malonie dialdehyde ( MDA) , and Na+-K+-ATPase levels of retinal tissue and retinal ultrastructure were investigated in three groups at 12wk after occurrence of diabetes.
RESULTS: Compared with control group, the body weight of the model group were significantly decreased, the activities of GSH-PX and ATP in the retina of diabetic rats were significantly lower, the MDA was signigicantly higher and significant changes occurred in retinal ultrastructure. Compared with model group, the blood glucose of the treatment group had no significant changes. However, the activities of GSH and ATP in the retina of diabetic rats were higher, the MDA was lower and the retinal ultrastructure was comparatively mild.
CONCLUSlON:Pyruvate can alleviate oxidatie stress reaction, improve the energy metabolism of retina, and delay the development of retinopathy.

Objective To investigate the expression of phosphatase and tension homolog (PTEN) in adipose tissue of KKAy diabetic mice, a mouse model of type 2 diabetes.
Methods KKAy diabetic mice were fed with high fat diet for 4 weeks. After blood glucose met the criteria of diabetes (over 16.7 mmol/L), mice were randomly divided into 3 groups:a control group (without any treatment), a rosiglitazone group (treated with rosiglitazone 12.5 mg/kg·d once per day), and a metformin group (treated with metformin 3 g/kg·d twice daily). After 4 weeks, we then determined the expression of PTEN and phosphoserine 473-Akt (pS473-Akt) in the epididymal adipose tissue with Western blots. The mice in each group were further divided into the insulin (-) subgroup and insulin (+) subgroup, which were intraperitoneally injected with saline and insulin (5 mU/g body weight), respectively.
Results The expression of PTEN was elevated in the epididymal adipose tissue obtained from KKAy diabetic mice compared with that from the C57BL/6J mice (P<0.001). In accordance with the enhanced expression of PTEN, the level of pS473-Akt stimulated by insulin was decreased in the adipose tissue of KKAy mice compared to the C57BL/6J mice (P<0.001). Treatment with the insulin-sensitizing agents, rosiglitazone and metformin did not inhibit the elevated expression of PTEN in adipose tissue of KKAy diabetic mice.
Conclusion PTEN may play an important role in the development of insulin resistance in adipose tissue of type 2 diabetes mice model.

To clone the 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (TwMCT) full length cDNA from Tripterygium wilfordii, the specific primers were designed according to the transcriptome data and the LCPCR were carried out. After a series of bioinformatics analysis on the TwMCT, the MeJA induced expression content were investigated by real-time fluorescence quantification polymerase chain reaction (RT-qPCR). The result showed that the full of TwMCTcDNA was 1 318 bp nucleotides encoding 311 amino acids. The molecular weight of the deduced TwMCT protein was about 34.14 kDa and the theoretical isoelectric point was 8.65. Result of the RT-qPCR analysis indicated that the content of TwMCT mRNA expression in T. wilfordii suspension cell was rising after treating with MeJA and reached the maximum in 24 h. Cloning and analyzing TwMCT gene from T. wilfordii provided gene element for studying the function and expression regulation of secondary metabolites.
Amino Acid Sequence ; Cloning, Molecular ; Erythritol ; analogs & derivatives ; metabolism ; Gene Expression Regulation, Plant ; Molecular Sequence Data ; Nucleotidyltransferases ; chemistry ; genetics ; metabolism ; Phylogeny ; Plant Proteins ; chemistry ; genetics ; metabolism ; Protein Structure, Secondary ; Sequence Alignment ; Sugar Phosphates ; metabolism ; Tripterygium ; chemistry ; enzymology ; genetics

Objective To observe the effects of 75 gram glucose oral tolerance test (75 g OGTT) and standard mixed meal test (SMMT) on insulin secretion function of the islets of Langerhans and plasma free fatty acid (FFA) in patients with type 2 diabetes mellitus.Methods Seventy-six patients with type 2 diabetes without using insulin and with no obvious complications were recruited for 75 g OGTT following overnight fasting on the first day and SMMT (bread 50 g,egg 50 g and milk 250 ml) on the 7th day.Blood specimens were collected from each patients before the tests and 30 min,60 min,120 min and 180 min after glucose or meal load to measure their levels of plasma glucose,serum insulin,C peptide,FFA and lipids (total cholesterol,triglyceride,high-density and low-density lipoprotein cholesterol).Results No difference in fasting plasma glucose,serum insulin,C peptide,FFA and lipids between 75 g OGTT and SMMT was found.Postprandial plasma glucose 30 min,60 min,120 min and 180 min after 75 g OGTT was significantly higher than that after SMMT,with (15.3?3.5) vs (9.9?3.4) mmol/L,(18.2?4.8) vs (12.8?4.0) mmol/L,(16.3?5.8) vs (12.2?4.9) mmol/L and (10.6?5.4) vs (9.5?4.5) mmol/L (F=28.1,P

By reverse transcription-polymerase chain reaction (RT-PCR), an open reading frame of pathogenesis-related protein 1 (PR1) was isolated from Panax notoginseng and named as PnPR1. Molecular and bioinformatic analyses of PnPR1 revealed that an open reading frame of 501 bp was predicted to encode a 166-amino acid protein with a deduced molecular mass of 18.1 kD. Homology analysis showed that the deduced amino acid sequence of PR1 protein of Panax notoginseng had a high similarity with other higher plants had the same conservative structure domain of cysteine-rich secretory protein (CAP). The recombinant expressed plasmid pET28a(+)-PnPR1 was expressed in Escherichia coli BL21. The expression conditions were optimized by induction at different times, different temperatures, different IPTG concentrations and different giving times. The optimum expression condition was 0.4 mmol.L-1 IPTG at 28 degrees C for 20 h. The successful expression of PnPR1 provides some basis for protein purification and preparation of the monoclonal antibody.
Amino Acid Sequence ; Cloning, Molecular ; Escherichia coli ; metabolism ; Molecular Weight ; Open Reading Frames ; genetics ; Panax notoginseng ; chemistry ; Phylogeny ; Plant Proteins ; genetics ; metabolism ; Plants, Medicinal ; chemistry ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Alignment

A full-length cDNA of GGPPS gene from Tripterygium wilfordii suspension cells was obtained by use of RACE strategy (GeneBank: KM978333), and then analyzed by bioinformatics approaches. TwGGPPS cDNA has 1857 nucleotides and an open reading frame (ORF) encoding a protein of 514 amino acid residues. The deduced protein has isoelectric point (pI) of 7.85, a calculated molecular weight about 57.13 kD, 5 conserved domains and 2 functional domains. PSORT Prediction showed it was located at plasma membrane. Phylogenetic analysis demonstrated that TwGGPPS1 was similar to GGPPS from other species of plants. For the first time the cloning of geranylgeranyl diphosphate synthase gene from T. wilfordii was reported, it lays the foundation for further research of diterpenoids biosynthetic pathway.
Amino Acid Sequence ; Cloning, Molecular ; Farnesyltranstransferase ; chemistry ; genetics ; metabolism ; Molecular Sequence Data ; Phylogeny ; Plant Proteins ; chemistry ; genetics ; metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; Tripterygium ; chemistry ; enzymology ; genetics

AIMTo investigate the effects of extremely low magnetic field on acute and chronic arthritis of rats.

METHODSThe acute arthritis animal models were built by the right thenar hypodermic injection of carrageenan. Then they were exposed to magnetic field for 6 hours and 8 hours, respectively. The chronic arthritis animal models were built by the right thenar hypodermic injection of complete freund's adjuvant. They were exposed to magnetic field for 7 days and 6 hours each day after the secondary affection appeared 15 days later. The swelling and inflammatory cytokine were observed in both the acute and chronic arthritis models.

RESULTSThe ankle and thenar swellings decreased in both the acute and chronic arthritis models after different time exposure. The cytokine of serum and articular lixivium did not change in 6 hours exposed groups of acute arthritis models. The serum IL-6 and articular lixivium IL-6, TNF-alpha decreased compared with sham groups. Though the rest indexes were unchanged, they had the tendency of decrease.

CONCLUSIONThe extremely low magnetic field has the effects of restraining acute and chronic arthritis of rats, and can also partially restrain the cytokines when the rats were exposed for 8 hours. The mechanisms need to be further investigated.

Animals ; Arthritis, Experimental ; metabolism ; pathology ; Disease Models, Animal ; Edema ; prevention & control ; Freund's Adjuvant ; adverse effects ; Interleukin-6 ; metabolism ; Magnetic Fields ; Male ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

4-(Cytidine-5-diphospho) -2-C-methyl-D-erythritol kinase is a key enzyme in the biosynthesis pathway of terpenoids. According to the transcriptome database, the specific primers were designed and used in PCR. The bioinformatic analysis of the sequenced TwCMK gene was performed in several bioinformatics software. The Real-time fluorescence quantification polymerase chain reaction (RT-qPCR) were used to detect the expression levels of TwCMK from T. wilfordii after elicitor MeJA supplied. The results showed that the full length of TwCMK cDNA was 1 732 bp encoding 387 amino acids. The theoretical isoelectric point of the putative TwCMK protein was 5.79 and the molecular weight was about 42.85 kDa. MeJA stimulated the rising of TwCMK expression in suspension cell and signally impacted at 24 h. The research provides a basis for further study on the regulation of terpenoid secondary metabolism and biological synthesis.
Amino Acid Sequence ; Cloning, Molecular ; Computational Biology ; Gene Expression Regulation, Plant ; Models, Molecular ; Molecular Sequence Data ; Phosphotransferases (Alcohol Group Acceptor) ; chemistry ; genetics ; metabolism ; Phylogeny ; Plant Proteins ; chemistry ; genetics ; metabolism ; Sequence Alignment ; Tripterygium ; chemistry ; enzymology ; genetics