1.Protection of neurons in vitro and improvement of learning and memory in mice by 2-phenoxy-indan-1-one derivatives
Fengyang CHEN ; Xiaoliang ZHENG ; Rong SHENG ; Zhong CHEN ; Hong SHI
Chinese Pharmacological Bulletin 1987;0(03):-
Aim To study the effect of novel AChE inhibitors, 2-phenoxy-indan-1-one derivatives (YKY-1~7), against glutamatic acid-induced neurotoxicity in PC12 cells and on learning & memory impairment in dementia model mice induced by A?25~35 icv Methods The PC12 cells were preincubated with different concentrations of YKY-1~7 for 24 h and subsequently treated by glutamatic acid, at the high concentration of 2 mmol?L-1 for 15 min to induce cytotoxicity. The cell viability was assessed with MTT method.. Dementia model mice were made by intracerebroventricular injection (icv) of aggregated A?25~35. From the next day, the model mice were administered YKY-7 (2.5, 5, 10 mg?kg-1, ig) for 10 consecutive days and sham control mice or A? model control mice received daily ig saline. After the final treatment, the passive avoidance learning was tested, regional cerebral blood flow at cerebral cortex was assessed, and the activity of AChE in the cerebral cortex, hippocampus and blood serum were determined. Results Six out of the seven YKY compounds appeared to be effective against glutamatic acid-induced neurotoxicity in PC12 cells, with YKY-7 demonstrating the most activity. YKY-7 significantly ameliorated the learning and memory ability in dementia model mice induced by A?25-35 icv, slightly and selectively inhibited the cortical and hippocampal AChE, and gently increased the blood flow at cerebral cortex. Conclusion Some of 2-phenoxy-indan-1-one derivatives reported here have protective effects against glutamatic acid induced neurotoxicity in PC12 cells, and improve the learning and memory impairment induced by A?25-35, which may be partly attributable to its selective inhibition of AChE activity in the cerebral cortex and hippocampus.
2.Density and hydrostatic settling velocity of Biomphalaria straminea
Fengyang MIN ; Jiasheng WANG ; Xingjian XU ; Jianyin ZHOU ; Lizhen CHEN
Chinese Journal of Schistosomiasis Control 2017;29(3):338-339,341
Objective To understand the eco-hydraulics characteristics of Biomphalaria straminea,the intermediate host of Schistosoma mansoni. Methods The drainage method and settlement tube method were applied to measure B. straminea's den-sity and hydrostatic settling velocity respectively. Results The density of B. straminea was 1.04-1.16 g/cm3,and the average value was 1.08 g/cm3. The hydrostatic settling velocity was 2.32-12.92 cm/s. Conclusions The eco-hydraulics characteristics of B. straminea is different from Oncomelania hupensis,and more attention should be paid to the hydraulic measures for the con-trol of B. straminea.
3.Whether autologous bone marrow mesenchymal stem cell transplantation is safe, feasible, and effective to the treatment of intracerebral hemorrhage: A 32-case analysis
Jianxin ZHU ; Zhongmin LI ; Taiwu XIAO ; Shuangfeng CHEN ; Fengyang GENG ; Qiang FU ; Chuanjun GUO
Chinese Journal of Tissue Engineering Research 2010;14(6):1097-1100
BACKGROUND: Previous animal studies demonstrated that bone marrow mesenchymal stem cells could differentiate into nerve cells under a certain condition; however, the clinical application for treating nervous system disease has been less reported. OBJECTIVE: To observe a short-term effect of autologous bone marrow mesenchymal stem cell transplantation on treating cerebral hemorrhage.METHODS: A total of 32 patients with cerebral hemorrhage who were selected from the Department of Neurosurgery, Liaocheng Brain Hospital between November 2007 and January 2009 were considered as a treatment group. According to general data and the amount of hematoma, they were treated by drilling drainage or hematoma evacuation. Drainage tubes were detained into hematoma cavity, and 3.5 mL autologous bone marrow mesenchymal stem cell suspension was injected through drainage tube. A total of 40 additional patients who did not treated with stem cell transplantation were considered as a control group. Neurologic impairment (NIHSS) and activities of daily living (Barthel index) were performed before and 6 months after transplantation; meanwhile, the brain MRI, serum biochemical and tumor marker were evaluated to detect security of stem cell transplantation. RESULTS AND CONCLUSION: The NIHSS score and Barthel index in the treatment group were similar to those in the control group before transplantation. Compared with control group, NIHSS scores were significantly decreased in the treatment group (P < 0.01), but Barthel index was significantly increased 6 months after transplantation (P < 0.01). Compared with before transplantation, NIHSS score were significantly decreased (P < 0.01), but Barthel index was significantly increased in the treatment group 6 months after transplantation (P < 0.01). Two patients in the treatment group had febrile, which was recovered after treatment. The following-up 6 months after transplantation demonstrated that brain MRI and biochemical indicators were normal except an increasing of CA-153 caused by lung cancer in one patient. The autologous bone marrow mesenchymal stem cell transplantation for treatment of cerebral hemorrhage is safe and effective in a short-term period; however the long-term effect still needs to be further studied.
4.Observation on the effect of autologous bone marrow stem cells transplantation in treatment of early spinal cord injury
Jianxin ZHU ; Zhongmin LI ; Li LI ; Yanhui LI ; Shuangfeng CHEN ; Fengyang GENG ; Qiang FU ; Chuanjun GUO
Journal of Chinese Physician 2010;12(8):1056-1059
Objective To investigate the recent efficacy and safety of autologous bone marrow stem cells transplantation in treatment of early spinal cord injury. Methods 51 cases of early spinal cord injury admitted to Liaocheng People Hospital from 2007.11 to 2009.8 were enrolled in this study. In transplantation group, 24 patients were treated by subarachnoid space injection with autologous bone marrow stem cell transplantation. The patients who were not transplanted in the same period of hospitalization were selected as control group. Motor and sensory function ( AISA score) was assessed at 1, 3, 6 months before and after transplantation in two groups patients. And blood routine, clotting mechanisms, biochemical items andtunor markers were determined in followed up. Results After one month of transplantation, two groups ofpatients had recovered in motor and sensory function to some degree. After three months of transplantation,there was significant different between transplantation group and control group in sensory function recovery (P < 0. 05 ). After 6 months of transplantation, there were significant different between transplant group and control group in motor and sensory function recovery (P<0.05). Blood examination results did not show markedly abnormal in followed -up patientsConclusion The safety and recent effect of autologous bone marrow stem cells transplantation in treatment of early spinal cord injury were satisfied, but the long - term effect was still unclear.
5.Molecular characterization of Cryptosporidium species in sheep and goats in Anhui Province and neighboring provinces
Wen-Chao LI ; Kai WANG ; Li TANG ; Miao CHEN ; Hui LI ; Zhen-Zhen KAN ; You-Fang GU
Chinese Journal of Schistosomiasis Control 2019;31(5):474-478
Objective To investigate the prevalence and molecular features of Cryptosporidium in sheep and goats from Anhui Province and neighboring provinces. Methods A total 832 and 781 fresh fecal samples were collected from seven large-scale sheep farms and ten large-scale goat farms in Anhui Province and neighboring provinces of Henan, Jiangsu and Shandong. The prevalence and species of Cryptosporidium were investigated in the fecal samples from the sheep and goats in the study areas using nested PCR assay based on the Cryptosporidium-specific SSU rDNA gene, and the subgenotypes of C. parvum and C. ubiquitum were characterized by amplification and sequencing of the 60 kDa glycoprotein (gp60) gene. Results The overall prevalence of Cryptosporidium was 5.8% (48/832) in sheep and 8.7% (68/781) in goats in Anhui Province and neighboring provinces, respectively. The SSU rDNA gene-based PCR assay identified C. xiaoi and C. ubiquitum in sheep and C. parvum in goats, and subtyping revealed that all C. ubiquitum subgenotypes belonged to XIIa subtype 2 and C. parvum subgenotypes belonged to IIdA19G1. Conclusion The identification of zoonotic C. ubiquitum XIIa subtype 2 and C. parvum subtype IIdA19G1 suggests that sheep and goats may serve as a potential source for human Cryptosporidium infections.
6.Prevalence of Cryptosporidium spp. infections in large - scale pig farms in north of Yangtze River in Anhui Province
Wen-Chao LI ; Hui-Hui YANG ; Zhen-Zhen KAN ; Yun-Long YANG ; Yue-Yang SUN ; You-Fang GU ; Hui-Liang CHEN
Chinese Journal of Schistosomiasis Control 2018;30(4):420-423
7.Treatment of rheumatoid arthritis with flavonoids of Echinps latifolius Tausch in rat model.
Cheng-Gui MIAO ; Guo-Liang ZHOU ; Mei-Song QIN ; Jian-Zhong CHEN ; Cheng-Feng LI ; Bing ZHANG
Journal of Zhejiang University. Medical sciences 2015;44(1):43-48
OBJECTIVETo investigate the effect of Flavonoids extracted from Echinps latifolius Tausch(FELT) on rheumatoid arthritis (RA) in rat model.
METHODFifty SD rats were randomly divided into model group, control group, and low, medium, and high-dose FELT groups (n=10 in each group). Complete Freund's adjuvant (0.1 mL) was used to induce RA in rats. FELT in doses of 50 mg/kg, 100 mg/kg, 150 mg/kg was given to rats in low, medium and high-dose FELT groups by gavage, and same volume of PBS was given to rats in control group. The arthritis score and the paw swelling score were measured to evaluate the therapeutic effect of FELT. Real time qPCR was used to detect the mRNA expression of fibronectin and MMP3 in synovial tissue and the mRNA expression of caspase 3, Bcl-2 and Bcl-2 associated X protein (Bax) in fibroblast-like synoviocytes (FLS).
RESULTSThe arthritis score and the paw swelling score were significantly decreased in three FELT groups compared to RA model rats (P <0.05). The relative expression levels of FN and MMP3 mRNA in synovium of three FELT-treatment groups were significantly lower than those in model group (1.80, 1.76 and 1.67 vs 2.53; 1.69, 1.46 and 1.45 vs 2.67, respectively, all P <0.05). The relative expression levels of Bax and caspase 3 mRNA in FLSs of three FELT groups were higher than those in model group (0.56, 0.58 and 0.60 vs 0.30; 0.54, 0.56 and 0.59 vs 0.29, respectively, all P <0.05); while the relative expression levels of Bcl-2 mRNA in FELT groups were lower than that in model group (2.20, 2.08 and 2.08 vs 4.04, respectively, P <0.05).
CONCLUSIONFELT may inhibit the synovium proliferation in RA model rats through promoting the FLS apoptosis.
Animals ; Apoptosis ; Arthritis, Rheumatoid ; drug therapy ; Caspase 3 ; metabolism ; Disease Models, Animal ; Echinops Plant ; chemistry ; Fibroblasts ; metabolism ; Flavonoids ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Synovial Membrane ; cytology ; bcl-2-Associated X Protein ; metabolism
8.Molecular mechanism of total flavonoids in Isodon amethystoides on adjuvant arthritis in rats.
Cheng-Gui MIAO ; Wei-Jing SHI ; Wei WEI ; Mei-Song QIN ; Hao CHEN ; Bing ZHANG
China Journal of Chinese Materia Medica 2017;42(17):3411-3416
Our preliminary study showed that the total flavonoids in Isodon amethystoides(TFIA), a local medicinal herb in Suzhou, had a certain therapeutic effect on adjuvant arthritis, and this therapeutic effect may be achieved through the up-regulation of miR-152 expression. In this paper, the molecular mechanism of TFIA on the pathogenesis of adjuvant arthritis(AA) rats was further studied. AA rats were prepared with complete Freund's adjuvant, and then treated with TFIA by intragastric administration. Real-time qPCR was used to detect the effects of TFIA on the negative regulatory loop of miR-152, methylase DNMT1 and methyl-CpG binding protein MeCP2 in fibroblast like synoviocytes(FLS) of AA rats, as well as the effects of TFIA on the classic Wnt signaling pathway and the expression of fibronectin gene in AA rats. Intragastric administration of TFIA significantly inhibited the expression of DNMT1 and reversed the negative regulatory loop composed of miR-152, DNMT1 and MeCP2 in the pathology of AA rats. After transfection of miR-152 inhibitors into the FLS in treatment group, DNMT1 expression was significantly restored. TFIA significantly up-regulated the expression of SFRP4 and inhibited the expression of β-catenin, C-myc and ccnd1, the key genes of canonical Wnt signaling pathway. TFIA also significantly inhibited the expression of fibronectin, an AA gene. The effect of TFIA on the expression of SFRP4, β-catenin, C-myc, ccnd1 and fibronectin was reversed after transfection with miR-152 inhibitors in the treatment group FLS. TFIA may inhibit the DNMT1 expression, up-regulate the SFRP4 expression, inhibit the expression of classical Wnt signaling genes β-catenin, C-myc, and ccnd1 as well as the RA gene fibronectin expression through the up-regulation of miR-152 expression.
9.Effect of geniposidic acid on hepato-enteric circulation in cholestasis rats through Sirt1-FXR signaling pathway.
Hao CHEN ; Jia LI ; Lei HU ; Wei ZHAO ; Hao YU ; Han-Zhen LIU ; Shi-Tang MA
China Journal of Chinese Materia Medica 2019;44(4):787-795
To investigate the effects of geniposidic acid( GPA) on hepato-enteric circulation in cholestasis rats,and to explore the mechanism based on the sirtuin 1( Sirt1)-farnesol X receptor( FXR) pathway,sixty SD rats were randomly divided into 6 groups:blank control group,ANIT model group,ursodeoxycholic acid group( 100 mg·kg~(-1)·d-1 UDCA),and GPA high,medium and low( 100,50 and 25 mg·kg~(-1)·d-1) dosage groups,10 rats in each group. Corresponding drugs were intragastrically( ig) administered for10 days. After administration on day 8,all rats except blank rats were administered with 65 mg·kg~(-1)α-naphthalene isothiocyanate( ANIT) once. After the last administration,the serum levels of alanine aminotransferase( ALT),glutamine oxalacetate aminotransferase( AST),gamma-glutamyltransferase( γ-GGT),alkaline phosphatase( ALP),total bilirubin( TB) and total bile acid( TBA)were measured,and the mRNA transcription levels of Sirt1,FXR,multidrug resistant associated protein 2( MRP2),bile salt export pump( BSEP),sodium taurocholate contractible polypeptide( NTCP) in liver and apical sodium bile acid transporter( ASBT),ileum bile acid binding protein( IBABP) in ileum were detected by reverse transcription-polymerase chain reaction( RT-PCR). The protein expression levels of Sirt1,FXR and NTCP were detected by Western blot; the expression of MRP2,BSEP in liver and ASBT,IBABP in ileum were determined by immunofluorescence three staining. Primary rat hepatocytes were cultured in vitro to investigate the inhibitory effect of GPA on a potent and selective Sirt1 inhibitor( EX 527),and the mRNA and protein expression levels of Sirt1 and FXR were detected by RT-PCR and Western blot. GPA significantly decreased the levels of ALT,AST,γ-GGT,ALP,TB,TBA in serum( P<0.01) and improved the pathological damage of liver tissues in ANIT-induced cholestasis rats; significantly increased the mRNA and protein expression levels of Sirt1,FXR,MRP2,BSEP,NTCP in liver and ASBT,IBABP in ileum( P< 0.01). In vitro primary hepatocytes experiment indicated that the gene and protein expression levels of FXR and Sirt1 were noticeably improved by GPA in primary hepatocytes inhibited by EX-527( P<0.01). It was found that the improvement of GPA was in a dose-dependent manner. GPA could improve bile acid hepatointestinal circulation and play a liver protection and cholagogu role in cholestasis rats induced by ANIT.The mechanism may be that GPA activated FXR by regulating Sirt1,a key regulator of oxidative stress injury,and then the activated FXR could regulate protein of bile acid hepato-enteric circulation.
Animals
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Cholestasis
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Iridoid Glucosides
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Liver
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Rats
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Rats, Sprague-Dawley
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Receptors, Cytoplasmic and Nuclear
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Signal Transduction
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Sirtuin 1
10.Mechanism of Gardenia jasminoides against cholestasis based on network pharmacology.
Hao CHEN ; Xuan GAO ; Wei ZHAO ; Hao YU ; Ning-Sheng WANG ; Han-Zhen LIU ; Shi-Tang MA
China Journal of Chinese Materia Medica 2019;44(13):2709-2718
To screen the active ingredients of Gardenia jasminoides and potential targets,and investigate the mechanisms against cholestasis based on network pharmacology technology. Twenty-one active components of G. jasminoides were retrieved and the target sites were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform( TCMSP). Cytoscape3. 2. 1 was used to construct the component-target network. Two hundred and eight targets related to cholestasis were searched and screened through Dis Ge NET,KEGG and OMIM databases. The key targets of G. jasminoides components and cholestasis were integrated and screened,and the component-target-disease network was constructed with Cytoscape 3. 2. 1 software to screen out the core network whose freedom degree was greater than the average value. The Clue GO plug-in of Cytoscape 3. 2. 1 software was used to analyze the biological processes and pathway enrichment of G. jasminoides in regulation of cholestasis. GO biological process analysis revealed 17 biological processes,involving 3 signaling biological processes related to cholestasis,i.e. acute inflammatory response,positive regulation of reactive oxygen species metabolic process,and nitric oxide biosynthetic process. KEGG-KEEG-305 terms and REACTOME pathways analysis revealed 17 regulatory pathways,involving 4 signaling pathways related to cholestasis,i.e. metabolism of xenobiotics by cytochrome P450,nuclear receptor transcription pathway,GPVI-mediated activation cascade and platelet activation. It was found that aqueous extract of G. jasminoides could improve serum biochemical abnormalities in ANIT-induced cholestasis rats. Aqueous extract of G. jasminoides could decrease the protein and mRNA expression levels of ESR1 in liver tissues,and increase the protein and mRNA expression levels of PPARG,NOS2,F2 R,NOS3,and NR3 C1. To sum up,the possible mechanisms of G. jasminoides against cholestasis may be related with the above three processes and four pathways.
Animals
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Cholestasis
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drug therapy
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Drugs, Chinese Herbal
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pharmacology
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Gardenia
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chemistry
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Medicine, Chinese Traditional
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Plant Extracts
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pharmacology
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Rats
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Signal Transduction