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Neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) are a heterogeneous group of disorders characterized by progressive degeneration of neurons. NDDs threaten the lives of millions of people worldwide and regretfully remain incurable. It is well accepted that dysfunction of mitochondria underlies the pathogenesis of NDDs. Dysfunction of mitochondria results in energy depletion, oxidative stress, calcium overloading, caspases activation, which dominates the neuronal death of NDDs. Therefore, mitochondria are the preferred target for intervention of NDDs. So far various mitochondria-targeting drugs have been developed and delightfully some of them demonstrate promising outcome, though there are still some obstacles such as targeting specificity, delivery capacity hindering the drugs development. In present review, we will elaborately address 1) the strategy to design mitochondria targeting drugs, 2) the rescue mechanism of respective mitochondria targeting drugs, 3) how to evaluate the therapeutic effect. Hopefully this review will provide comprehensive knowledge for understanding how to develop more effective drugs for the treatment of NDDs.
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Objective To explore the correlation of EGFR and Ki-67 expressions in lung adenocarcino-ma with MSCT features and general clinical characteristics. Methods According to the differences in EGFR 19/21 gene mutation in the tumor tissues ,120 patients with lung adenocarcinoma were divided into positive group or wild type group. And Ki-67 expression in the tumor tissues was also detected. The test results were analyzed ,and the clinical data and theMSCT imaging features were examined by using the SPSS 19.0. Results The expression of EGFR differed statistically with lymphatic metastasis ,organ metastasis ,pleural indentation ,andnodule types (P < 0.05),but had no statistical significance with age ,sex ,degree of differentiation ,tumor size ,tumor-lung boundary ,burr ,lobulated sign ,vacuole sign and pleural effusion.The high expression of Ki-67 had statistical sig-nificance with lymphatic metastasis and tumor size(P < 0.05)while had no statistical significance with other in-dicators.Ki-67 expression was significantly positively correlated with EGFR(P < 0.05). Conclusions Tumor size ,pleural indentation ,lymphatic metastasis ,organ metastasis and nodular types of lung adenocarcinoma have guiding significance in judging EGFR mutation , proliferation activity ,prognosis and therapy.
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Objective To predict and verify the upstream regulatory microRNA (miRNA)of protein kinase D1 (PKD1),and to investigate its role in cerulein induced acute pancreatitis (AP)in rats. Methods Potential up-stream regulatory miRNA of PKD1 was predicted by using bioinformatics software. Dual luciferase reporter gene system and Western blot were applied to verify the regulation of PKD1 by the selected miRNA. Experimental AP was induced by 6 intraperitoneal injection of cerulein (20 μg/ kg)at hourly intervals after administration of the CY5 - labeled notar-get control (AP group,n = 20)or selected miRNA (treatment group,n = 20),respectively by intraperitoneal injection into rats. Other rats were divided randomly into a normal control group (n = 10)without any treatment. Besides 10 rats in either AP or treatment group were sacrificed 6 hours after the first injection of cerulein,and the rats were all sacri-ficed 24 hours after the first injection. The blood samples and pancreatic tissues of each rat were collected to test serum amylase and lipase activities,or to make hematoxylin - eosin stain for AP pathological scores as well as PKD1 immuno-histochemical staining,respectively. Results TargetScan 7. 1 software analysis showed that miR - 128 - 3p was the po-tential upstream regulatory miRNA of PKD1,which was verified by dual luciferase reporter gene system and Western blot detection. Compared to the normal control group,serum amylase and lipase activities after 6 h exposure to cerulein increased in both AP group and the treatment group[13313. 00(9424. 00 - 15995. 00)U/ L,13552. 00(10399. 50 -18408. 25)U/ L vs. 1430. 50(1214. 25 - 1543. 25)U/ L;547. 00 (515. 00 - 627. 00)U/ L,857. 50(522. 00 -1222. 25)U/ L vs. 34. 00(32. 50 - 34. 75)U/ L],and the differences were significant(χ2 = 8. 715,P < 0. 05;χ2 =9. 115,P < 0. 05),which indicated that the rat models of AP were successfully established. The immunohistochemical scores of PKD1 after 24 h exposure to cerulein decreased in the treatment group[0. 50(0 - 2. 75)scores],compared with the normal control group [4. 00(4. 00 - 8. 00)scores]and the AP group [4. 00(3. 75 - 8. 00)scores],and difference was significant(χ2 = 18. 302,P < 0. 05). Accordingly,the total pathological scores of HE staining decreased significantly in the treatment group,as compared to the AP group (3. 80 ± 0. 85 vs. 6. 90 ± 1. 15,t = 4. 481,P < 0. 01). The results showed that the inflammatory cell infiltration and tissue necrosis were significantly improved after miR -128 - 3p treatment. Conclusions miR - 128 - 3p is the upstream regulatory microRNA of PKD1 which protects pan-creata from necrotic injury and inflammatory cell infiltration in PKD1 - mediated acute pancreatitis.
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Objective To investigate the value of MR T2* in evaluation of liver iron overload caused by long term blood transfusion.Methods Thirty one patients with long term blood transfusion were collected.Both serum ferritin(SF)and CRP levels were measured and the adjusted serum ferritin(ASF)concentration was calculated.MRI of the maximum cross-sectional liver was performed using a 1.5T scanner (Siemens Avanto).The T2* value of the liver was measured,and the correlation analysis was carried out.Twenty one normal volunteers served as controls.The transfusion group was divided into iron overload group and non overload group,and differences between groups were analyzed.Results The correlation coefficient in 31 patients between liver T2* value and SF,ASF and blood transfusion volume was-0.695,-0.728 and -0.657 respectively,and the difference was statistically significant(P<0.05).The correlation coefficient between SF and blood transfusion volume was 0.518,and the difference was statistically significant(P<0.05).There was difference in T 2* value between three groups.Conclusion MR T2* has some practical value in the evaluation of liver iron overload in patients with long term blood transfusion.
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Objective To screen genes differentially expressed between dermal papilla cells from occipital and vertex scalp of patients with androgenic alopecia (AGA) through a 3D culture system.Methods Dermal papilla cells isolated from the occipital scalp tissue of patients with AGA were cultured in a 2D system for several days.Then,the third-passage dermal papilla cells were subjected to a 3D culture with the presence of dihydrotestosterone (DHT) for 72 hours (experimental group).The dermal papilla cells isolated from the vertex scalp tissue of patients with AGA,which were cultured in a 3D system with dimethyl sulfoxide,but not DHT,served as the control group.Subsequently,total RNA was extracted from the cells and reversely transcribed into cDNA followed by labeling with Cy3 and hybridization to a NimbleGen microarray.Gene ontology (GO) and pathway analysis was carried out to screen differentially expressed genes between the experimental and control group.Real time PCR was conducted to validate the results of microarray analysis.Results As the genome-wide expression profile analysis showed,there were 622 genes differentially expressed between the experimental group and control group,of which,359 were up-regulated and 263 were down-regulated in the experimental group compared with the control group.The above results were corffirmed by real time PCR.GO analysis revealed that the up-regulated genes,such as the CHEK1 and Tobl genes,were mainly involved in the inhibition of cell proliferation and promotion of cell apoptosis,while the down-regulated genes,such as the BAMBI,EFNA3,Dlx3 and UCGC genes,were associated with the acceleration of cell proliferation as well as the growth and development of epidermis.Pathway analysis showed that cell circle-controlling molecules were the most abundant molecules.Conclusions Numerous signalling molecules and pathways are involved in the development of AGA,which are mainly responsible for the modulation of cell circle,proliferation and apoptosis.
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Objective To explore the clinicopathological features,diagnosis and differential diagnosis of colonic muco-submucosal elongated polyp (CMSEP).Methods The clinical manifestations,endoscopic and histological features of three cases of CMSEP were analyzed.The literature was reviewed with regard to the diagnostic criteria and differential diagnosis.Results Three patients were male,and aged 25,45 and 75 years old.Two polyps were at transverse colon and one at rectum.Under colonoscope,all three cases showed the long pedunculated polyps.The surfaces of two polyps were smooth and the colors were similar to colonic mucosa while one polyp appeared mucosal erosion and congestion on the top.Under optical microscope,three cases had similar lesions.The axis of the lesions was expanded submucosa and the surface was the layer of colonic mucosa.The expanded and thick walled blood vessels were seen paralleled to the long axis in the submucosa of the axis of lesions.One polyp with mucosal erosion on the top presented with adenocarcinomal changes.Conclusions CMSEP is a kind of specific polypoid lesion,with characteristic colonoscopic and pathological features.Most are benign changes,however malignant changes occur in a few cases.In histology,CMSEP should be identified with mucosal prolapse syndrome associated inflammatory polyp.
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To investigate the protective effect of polyethylene glycol (PEG) modified recombinant cytoglobin (PEG-rCygb) on acute liver damage in mice. The acute liver injury model of KM mice was induced by CCl4 and then treated with PEG-rCygb, The liver and blood samples were collected for biochemical and histopathological analysis. The results showed that PEG-rCygb reduced the liver mass index and decreased significantly the levels of alanine amiotransferase (AST) and aspartate transaminase (ALT) in mouse serum. In liver tissues, the content of malondialdehyde (MDA) was decreased, whereas the content of glutathione (GSH) was increased in PEG-rCygb treated group. PEG-rCygb also elevated the activities of total super oxidedismutase (T-SOD) and catalase (CAT) in liver tissues. HE staining of liver tissue slices revealed that PEG-rCygb relieved fatty degeneration of liver, decreased inflammatory factors and reduced liver cell injury. Further in vitro experiments indicated that the protective effects of PEG-rCygb on hepatic stellate cell (HSC) against H2O2 were enhanced compared with that of rCygb. All results indicated that the PEG-rCygb promoted oxygen free radical scavenging ability and prevented acute liver injury in KM mice induced by CCl4.
Subject(s)
Animals , Male , Mice , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury , Free Radical Scavengers , Metabolism , Globins , Genetics , Therapeutic Uses , Liver , Polyethylene Glycols , Chemistry , Protective Agents , Therapeutic Uses , Recombinant Proteins , Genetics , Therapeutic UsesABSTRACT
OBJECTIVE:To study the factors influencing the stability of Chlorogenic acid in Marsdenia tenacissima extract.METHODS:The contents of Chlorogenic acid in Marsdenia tenacissima extract in different solvents,different lighting and different time under the heat were determined by HPLC.RESULTS:The Chlorogenic acid in Marsdenia tenacissima extract in organic solvents was more stable,in addition,lighting and heating temperature were important factors affecting the stability of the Chlorogenic acid.CONCLUSION:The stability of the Chlorogenic acid in Marsdenia tenacissima extract changes in different conditions;and the study results serve as a reference for the preparation,storage,analysis and production of Marsdenia tenacissima extract.
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OBJECTIVE:To upgrade the information management of the traditional Chinese medicine(TCM)pharmacy in our hospital.METHODS:The benefits and problems in implementing information management in our hospital's TCM pharmacy were discussed,and solutions for improvement were proposed.RESULT & CONCLUSION:The application of the information management system can help regulate the management of the TCM pharmacy,and establish a closer connection between traditional medicine and modern technology.