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

Antigens, CD20 ; metabolism ; Female ; Follow-Up Studies ; Humans ; Interferon Regulatory Factors ; metabolism ; Leg ; pathology ; Lymphoma, Large B-Cell, Diffuse ; complications ; metabolism ; pathology ; surgery ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Skin Neoplasms ; complications ; metabolism ; pathology ; surgery ; Thrombocytopenia ; complications

Objective To investigate the effect of propofol on nNOS expression after focal cerebral ischemia-reperfusion in rats and the possible mechanism of protective effect of propofol on brain. Method Seventy-eight male Wistar rats, weighting 250 ~ 300 g, were randomly divided into 3 groups:(1)Sham operation group (S group, n=6) was performed with scham operation; (2) Ischemia-reperfusion group (group I-R, n=36) was subjected to 2-hour right middle cerebral artery occlusion and then reperfusion was followed, saline (1 mg/kg) was injected into the right lateral cerebral ventricle using microsyringe before reperfusion;(3) Propefol group (group P, n=36) was injected with propofol (1mg/kg) into the right lateral cerebral ventricle using microsyringe right after ischemia. Group I-R and group P were divided into 3 subgroups according to the reperfusion time: 1 h, 3 h and 6 h. The neurological function of all rats were tested before reperfusion. The cerebral infarction area of the whole brain was calculated with TIC staining (n=6). The pathological change of brain was observed from HE staining (n=6) and the nNOS protein expression was obtained by immuno- histochemical method (n=6). Results Compared with I-R group, the neurological function was better in group P(P

Objective To investigate the changes of hydrogen sulfide (H_2S) level in plasma in order to explore the role of H_2S in the development of pulmonary hypertension (PH) secondary to congenital heart disease (CHD).Methods There were 9 CHD patients and 9 normal children in this study. The plasma concentration of H_2S and pulmonary artery pressure (PAP) of each child were measured. Meanwhile, the relationship between H_2S level and PAP was analyzed.Results The plasma level of H_2S in the group of CHD significantly decreased compared with control group (32.13?2.25) ?mol/L vs [(43.69?2.05)?mol/L, P

Objective: To understand epidemiological characteristics of the pathogens and evolution of the genotype associated with infectious diarrhea epidemic caused by norovirus in Hebei Province. Methods: A total of 8 infectious diarrhea outbreaks caused by norovirus were reported from Jan 2015 to Dec 2016, of which epidemic treatment materials and specimens were collected at the same time. Norovirus nucleic acid was detected by using real-time PCR, and the partial ORF2 of the all positive specimens were amplified by RT-PCR and sequenced. Phylogenetic tree was constructed by using Mega5.2 based on partial ORF2 sequences of norovirus to perform phylogenetic analysis. Results: A total of 8 norovirus outbreaks, involving 265 cases who were mainly for residential inhabitents, children and students, were reported during this period, and the overall attack rate ranged from 0.70% to 8.13%. The overall positive detection rate of norovirus was 66.25%. The PCR products were sequenced, and sequencing result were obtained for 28 samples, which included GⅠ.3, GⅡ.2, GⅡ.4, GⅡ.13 and GⅡ.17. Conclusions Multiple genotypes of infectious diarrhea outbreaks caused by norovirus were found in Hebei province.

Carnosic acid (CA) is the main phenolic diterpenoid active ingredient in plants such as rosemary and sage, and has antiviral, antioxidant, anti-inflammatory effects and so on, however, its antiviral activity against influenza virus infections was not reported. In this study, antiviral activities against influenza A virus infections of three main bioactive ingredients from rosemary, including rosmarinic acid, CA and ursolic acid, were evaluated using virus titer titration assay, and CA showed remarkable inhibition on influenza H5N1 replication in A549 cells. The antiviral activity of CA was further confirmed and its mechanism of action was investigated using the indirect immunofluorescence assay (IFA), Western blot and real-time fluorescence quantification polymerase chain reaction (qRT-PCR). The results showed that the 50% effective concentration (EC₅₀) of CA against influenza H5N1 in A549 cells and MDCK cells were 4.30 and 3.64 μmol·L^-1, respectively. Meanwhile, CA also showed inhibition on influenza virus 2009panH1N1 (EC₅₀: 10.1 μmol·L^-1) and H3N2 (EC₅₀: 12.8 μmol·L^-1) replications in A549 cells. Mechanistic studies showed that antiviral activity of CA is related to its induction of heme oxygenase-1 (HO-1) in A549 cells and suppression on production of reactive oxygen in H5N1-infected cells.

Objective To investigate the association between the rs1130864 polymorphisms in C-reactive protein (CRP) gene and ischemic stroke (IS).Methods One hundred and twenty-eight patients with IS,admitted to our hospital from December 2010 to December 2011,another 112 healthy subjects without atherosclerotic vascular disease history were chosen in our study.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the genotype ofrs1130864 site.Logistic multivariate regression analysis was employed to analyze the IS risk factors.Results The ratio of male patients,having history of hypertension,diabetes,hyperlipidemia,smoking and familial stroke in the patient group was significantly higher than that in control group (P＜0.05).The allele frequency,genotype and dominant model of rs1130864 site showed no statistically significant difference between the 2 groups (P＞0.05),but the recessive model ofrs1130864 site showed significant difference between the 2 groups (P＜0.05).Logistic regression analysis showed that male and having history of hypertension,diabetes and smoking in patients with rs1130864 recessive model (TT+CT) are the independent risk factors for IS (P＜0.05).Conclusion Male and history of hypertension,diabetes and smoking history in patients with rs1130864 recessive model (TT+CT) are independent risk factor for IS.

To study the chemical constituents of the aerial parts of Pulsatilla chinensis (Bge.) Regel, various chromatography methods were used. Seven triterpene glycosides were isolated from the n-BuOH extract. Their structures were identified as bayogenin 28-O-alpha-L-rhamnopyranosyl (1 --> 4 ) -beta-D-glucopyranosyl (1 --> 6) -beta-D-glucopyranosyl ester (1), 3-O-alpha-L-arabinopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl (1 --> 4) -beta-D-glucopyranosyl (1 --> 6) -beta-D-glucopyranosyl ester (2), 3-O-alpha-L-rhamnopyranosyl (1 -->-2 ) -alpha-L-arabinopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl (1 --> 4 ) -beta-D-glucopyranosyl (1 --> 6 ) -beta-D-glucopyranosyl ester (3), 3-O-alpha-L-rhamnopyranosyl (1 --> 2 ) -[beta-D-glucopyranosyl (1 --> 4)] -alpha-L-arabinopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl (1 --> 4) -beta-D-glucopyranosyl (1 --> 6) -beta-D-glucopyranosyl ester (4), 3-O-alpha-L-rhamnopyranosyl (1 --> 2) -alpha-L-arabinopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl (1 --> 4) -beta-D-glucopyranosyl (1 --> 6 ) -beta-D-glucopyranosyl ester (5), hederagenin 28-O-alpha-L-rhamnopyranosyl (1 --> 4) -beta-D-glucopyranosyl (1 --> 6) -beta-D-glucopyranosyl ester (6) and pulsatilla saponin (7). Among them, compound 1 is a new compound. Compounds 2 -6 were isolated from this plant for the first time.
Glycosides ; chemistry ; isolation & purification ; Molecular Conformation ; Molecular Structure ; Plant Components, Aerial ; chemistry ; Plants, Medicinal ; chemistry ; Pulsatilla ; chemistry ; Saponins ; chemistry ; isolation & purification ; Triterpenes ; chemistry ; isolation & purification

In order to minimize the residual tert-butyl alcohol (TBA) level in cyclodextrin complex prepared by freeze drying TBA/water cosolvent system, the formulation and lyophilization procedure that may influence the residual TBA was studied. Residual TBA in freeze dried cyclodextrin complex was determined by gas chromatography. The significant formulation and processing factors that influence residual TBA were identified by adjusting the initial TBA concentration in cosolvent, selecting cyclodextrin type (beta-cyclodextrin or hydroxypropyl beta-cyclodextrin), changing sample volume in flasket, altering freezing mode (fast freezing or slow freezing) and modifying the duration of secondary drying. The results show that the amorphous cyclodextrin material (hydroxypropyl beta-cyclodextrin), initial low TBA concentration in cosolvent and fast freezing would lead to high TBA residue in cyclodextrin complex, annealing was effective in reducing the residual TBA. The duration of secondary drying had no distinct effect on residual TBA. It is concluded that in order to reduce residual TBA in cyclodextrin complex prepared by lyophilization monophase solution, the initial TBA concentration in cosolvent should be higher than the crystal formation concentration, the appropriate cyclodextrin type and freeze drying processing should be choosen.
2-Hydroxypropyl-beta-cyclodextrin ; Anti-Inflammatory Agents ; chemistry ; Budesonide ; chemistry ; Chromatography, Gas ; Drug Residues ; analysis ; chemistry ; Freeze Drying ; methods ; Solvents ; chemistry ; Water ; chemistry ; beta-Cyclodextrins ; chemistry ; tert-Butyl Alcohol ; analysis ; chemistry

OBJECTIVETo study the cleavage activity of specific deoxyribozyme to hepatitis C virus in vitro.

METHODSThree deoxyribozymes were designed to cleave at sites 157, 168, 173 in HCV 5'-noncoding region with the active region of 5'-GGCTAGCTACAACGA-3' respectively. Plasmid pCMV/T7-NCRC -Delta Luc was completely linearized with restriction endonuclease Xba I. HCV RNA5'-NCRC was transcribed in vitro from the linearized products and radiolabelled with [alpha-32P] UTP. Under the conditions of 37 degrees C, pH7.5, Mg2+ 10 mmol/L, the three deoxyribozymes were mixed with substrate RNA individually for 120 minutes and then the reactions were terminated. The cleavaged products were separated with 8% denaturated polyacrylamide gel electrophoresis and displayed by autoradiography. DRz3 was mixed with the substrate RNA at different Mg2+ concentrations. The cleavage efficiency was analyzed with a gel document action analyzing systems.

RESULTSUnder the adopted conditions the three deoxyribozymes efficiently cleaved to the target RNA in vitro and the cleavage activity of DRz3 was increased with the increase of Mg2+ concentration.

CONCLUSIONThe designed deoxyribozymes can cleave 5'-NCR mRNA of HCV efficiently in vitro and it is dose-respondent to Mg2+ concentration.

DNA, Catalytic ; genetics ; DNA, Single-Stranded ; genetics ; Genetic Therapy ; Hepacivirus ; genetics ; Hepatitis C ; therapy ; Humans ; RNA, Messenger ; genetics