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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 detect the expressions of ovarian function-related proteins in the ovarian follicles in different development stages,and to explore their roles and significances in the regulation of follicular development and ovarian function. Methods:The ovarian tissue containing primordial,primary,secondary follicles,mature follicles, atretic follicles and corpus albicans of the woman in the childbearing age was selected. Immunohisto chemical analysis was used to detect the expressions of Glyoxal enzyme I (glyoxalase I),ubiquitin carboxy-terminal hydrolase L1 (UCH-L1),heat shock protein 27 (HSP27),serum amyloid P (SAP)proteins in the ovarian follicles in different stages.The expression intensities of these proteins were compared.Results:The expression intensities of Glyoxalase I and UCH-L1 in the granulosa cells and theca cells of secondary follicles and marure follicles were strong,which were higher than those in the cytoplasm of primordial and primary follicles.The expression intensities of HSP27 in the cytoplasm of primordial and primary follicles were strong,which were higher than those in the granulosa cells and theca cells of secondary follicles and marure follicles.The expression intensities of Glyoxalase I and HSP27 in the atretic follicles were strong,which were higher than that in the growth follicles. The expressions of SAP were positive in the primordial,primary follicles,secondary and mature follicles and the expression intensities were not different.The expressions of four proteins in the corpus albicans did not express. Conclusion:The high expression of UCH-L1 and low expression of HSP27 are associated with the mature and development of follicles;the high expressions of Glyoxalase I and HSP27 are associated with the follicular atresia and ovarian failure.
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Objective:To observe and compare the clinical effect of single-incision and two-incision posterior chamber phakic intraocularlens implantation in the correction of extreme myopia.Methods:40 cases(80 eyes) of patients with extreme myopia underwent conventional two-incision posterior chamber phakic intraocularlens implantation in our hospital from January 2011 to June 2013 were selected as the control group and 40 cases(80 eyes) underwent single-incision posterior chamber phakic intraocularlens implantation from July 2013 to January 2016 were selected as observation group.The open hole before and after operation,best corrected visual acuity of vision,operation safety,effectiveness index,diopter (column mirror,equivalent ball for eyeglasses),intraocular pressure,ECD,anterior chamber depth and occurrence of complications were compared between two groups.Results:The uncorrected visual acuity (UCVA) of both groups at 6 months after operation were significantly higher than those before operation (P＜0.05),which was significantly higher in the observation group than that of the control group (P＜0.05);The operation safety and effectiveness index of observation group were significantly higher than those of the control group (P＜0.05);The cylinder and spherical equivalent degree of both groups at 6 months after operation were significantly better than those before operation(P＜0.05),which was significantly better in the observation group than that of the control group(P＜0.05).The corneal endothelial cell counts(ECL) of control group after operation was significantly lower than that before operation (P＜0.05),and no significant difference was found in the ECL of observation group before and after operation (P＞0.05).The ECL of observation group after operation was significantly higher than that of the control group (P＜0.05);The incidence rate of complication in observation group was significantly lower than that of the control group (P＜0.05).Conclusion:Compared with two-incision operation,the single-incision posterior chamber phakic intraocularlens implantation had remarkable clinical effect in the correction of extreme myopia with higher security.
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BACKGROUND: BALB/c and C57BL/6 mice are two inbred strains, but after voluntary movement, there is no report on how to scientifical y reasonably select behavioral experiment methods and indicators and to evaluate the learning and memory abilities of mice. OBJECTIVE: To analyze and compare the behavioral indicators between BALB/c and C57BL/6 mice fol owing voluntary wheel running, to explore the effect of exercise on learning and memory, and to provide a reference for selecting reasonable behavioral indicators. METHODS: 2.5-month-old BALB/c and C57BL/6 mice were randomly divided into control and voluntary wheel running groups. Independent running wheel movement of mice was recorded with VitalView system. 4 weeks later, newborn neurons were labeled via DCX immunofluorescence. Spatial learning, memory and exploration abilities were compared through new arm test, new object recognition test and Morris water maze test. RESULTS AND CONCLUSION: (1) The mean spontaneous activity of BALB/c mice daily was 2.56 fold of that of C57BL/6 mice during wheel running (P < 0.001). (2) Hippocampal DCX-positive cel s in exercised BALB/c and C57BL/6 mice were more than those in control group. (3) Meantime, exhibited by higher frequencies to explore new arm or object, and longer time and distance of moving around them, the learning and exploring capability was improved after exercising (P < 0.001), especial y in BALB/c mice. (4) Wheel running C57BL/6 mice exhibited progressed spatial learning and memory abilities compared with control mice in Morris water maze test, characterized by decreased latency to target, elevated target crossings and longer time or distance in quadrant zone (P < 0.05). However, there was no significant difference between wheel running and control BALB/c mice. Taken these data together, voluntary wheel running contributed to hippocampal neurogenesis of BALB/c and C57BL/6 mice, accompanied by the change of learning and memory capability, which could be detected properly via both new arm test and new object recognition test, but for Morris water maze test, C57BL/6 mice might be superior to BALB/c mice.
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AIM:To investigate the effect of 18 alpha-glycyrrhetinic acid (18α-GA) on delaying the senescent progress and promoting the proliferation in late-passage bone marrow mesenchymal stem cells ( BMSCs ) .METHODS:Late-passage BMSCs were incubated with 2.0 mg /L 18α-GA or the same volume of DMSO for 30 d, and the cells were harvested to determine the proteasome activity .The expression of senescence-related proteins p53, p21 and p16 was detec-ted by senescence-associated β-galactosidase ( SA-β-Gal) staining and Western blot .The cell proliferation , the expression level of cell cycle-related proteins and cell cycle distribution of the cells were measured by CCK -8 assay, BrdU incorpora-tion, Western blot and flow cytometry.RESULTS:Compared with DMSO group, the proteasome activity in 18α-GA group increased significantly by about 0.2 times (P<0.01).SA-β-Gal-positive cells in 18α-GA group decreased, and cell stai-ning was lighter.The contents of p53 and p21 in 18α-GA group were decreased (P<0.05).The results of CCK-8 assay showed that the A value in 18α-GA group was 0.3 times higher than that in DMSO group (P<0.01).BrdU incorporation showed the increased proliferation in 18α-GA group compared with DMSO group ( P<0.05).The cells in G1 phase in 18α-GA group decreased significantly compared with DMSO group , while the cells in S phase increased significantly ( P<0.05).The expression level of cyclin D1 in 18α-GA group was 2.8 times higher than that in DMSO group (P<0.01), and the CDK4 level was 1.4 times higher than that in DMSO group (P<0.05).CONCLUSION:Activation of the pro-teasome activity by 18α-GA delays the aging process in the BMSCs and promotes the cell proliferation via up -regulation of the cell cycle-related proteins .
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BACKGROUND:It is not fuly understood that whetherp53 inhibitor can directly intervene in the viability of bone marrow mesenchymal stem cels and the possible mechanism. OBJECTIVE:To investigate the effect of p53 inhibitor, PFT-α, on the aging process of bone marrow mesenchymal stem cels in late-phase amplification and to discover the key target to delay the replicative senescence of human bone marrow mesenchymal stem cels. METHODS:The expression levels ofp53,p21, andp15 mRNA in human bone marrow mesenchymal stem cels in both early and late-phase amplification were detected by quantitative PCR assay. Then, human bone marrow mesenchymal stem cels in late-phase amplification were respectively treated with 20 μmol/L PFT-α or an equivalent amount of dimethyl sulfoxide for 2 weeks. The positive rate of aging cels was determined by SA-β-Gal staining. The apoptosis was detected by TUNEL staining. Human bone marrow mesenchymal stem cels were treated with 300 μmol/L H2O2 for 30 minutes, and then celular anti-oxidative stress capacity was detected by cel counting kit-8 assay. RESULTS AND CONCLUSION:The quantitative PCR assay showed that the mRNA expression level ofp15, p21 andp53 in human bone marrow mesenchymal stem cels in late-phase amplification was significantly increased (1.45±0.23), (1.51±0.14) and (1.78±0.14) times as much as that in early phase amplification (P < 0.05). The positive rate of aging cels in PFT-α group was significantly lower than that in the dimethyl sulfoxide group[(41±5)%vs. (63±7)%,P < 0.05)]. However, there was no significant difference in apoptosis rate between PFT-α group and dimethyl sulfoxide group. After treatment with H2O2, the absorbance value in the PFT-α group was(1.27±0.13) times as much as that in the dimethyl sulfoxide group (P < 0.001). The above results demonstrate that the activation ofp53 signaling pathway may be an important factor of causing aging of human bone marrow mesenchymal stem cels. Application ofp53 inhibitor PFT-αcan enhance the anti-oxidative stress capacity of human bone marrow mesenchymal stem cels in late phrase amplification.
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BACKGROUND:Cationic liposome-mediated celltransfection is reliable and repeatable. However the transfection efficiency is often low. OBJECTIVE:To study the optimized methods for gene transfection mediated by liposome into N2a cells (mouse neuroblastma cells). METHODS:Using traditional adherent method and improved suspension method, 500 ng recombinant plasmid pcDNA3-GFP carrying green fluorescence protein was transfected into N2a cells in 24-wel culture plate, which was mediated by 1.5μL Lipofectamine?LTX Reagent. The expression of green fluorescent protein was observed by inverted fluorescence microscope, and the transfection efficiencies at different transfection ways were calculated. By using improved suspension transfection method, 500 ng plasmid DNA was transfected with different doses of Lipofectamine?LTX Reagent (1.0, 1.5, 2.0, 2.5μL). The optimal ratio of liposome and DNA was explored. RESULTS AND CONCLUSION:The transfection efficiency of suspension transfection method was significantly higher than that of the tranditional adherent method (P<0.01) when using 1.5μL liposome/500 ng DNA. The transfection efficiency of the 1.0, 1.5, 2.0, 2.5μL Lipofectamine?LTX on 500 ng plasmid DNA was respectively (76.60±3.85)%, (80.00±4.17)%, (88.00±5.89)%, (54.96±4.23)%. It showed the 500 ng DNA and 2.0μL liposome achieve the highest transfection efficiency.
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Objective To determine whether pulmonary arterial hypertension(PAH) and pulmonary venous hypertension (PVH) can be differentiated noninvasively by echocardiography. Methods Fifty-six patients with pulmonary arterial systolic pressure(PASP) ≥40 mmHg by echocardiography were involved,and cardiac catheterization performed within 7 days of each other. Based on left ventricular end-diastolic pressure or pulmonary capillary wedge pressure(PCWP) ,30 patients were classified as PAH group and 26 patients as PVH group. The early(E) and late(A) diastolic mitral inflow velocities,E/A ratios,deceleration time(DT),early dastlic mitrial annular velocity(E') and E/E' ratios were measured by conventional and Doppler tissue imaging echocardiography in the two groups. Results Compared with PVH group,the PAH group had significantly higher A,DT,PASP and E',and significantly lower E,E/A ratio and E/E' ratio (P < 0. 01 or P <0. 001). E/E' and E/A ratio was optimal indexes for differentiation of PAH and PVH,the area under receiver operating characteristic curve was 97% and 91 %, respectively. Optimal cutoff for diagnosing PVH was E/E'>9.2 (sensitivity 95%, specificity 97%) and E/A> 1. 7 (sensitivity 75%,specificity 92%). Conclusions PAH and PVH imaging can be reliably differentiated by echocardiography.
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To observe the influence of the placental apoptosis on the expression of Bax,Bcl-2, Fas, FasLand TNF-α during the second trimester of pregnancy, mice of experimental group were intraperitoneal injected with 100 purified Toxoplasma gondii tachyzoites added in 0.2mL of PBS, while those of the control group were injected with 0.2 mL of sterile PBS (0.01 mol/L, pH 7.4) in the 8-th day of pregnancy. During the 12, 14, 16 and 18-th days of pregnancy, 5 mice both in experimental and control group were randomly killed and the expression levels of the apoptosis-related proteins Bax, Bcl-2, Fas, FasL and TNF-α in the placental tissues were determined by means of immunohistochemical methods. It was showed that the apoptosis-related protein expressed both in villus and decidua of the placenta, most of which were expressed in syneytiotrophoblast (ST). The positive cells with expression of Bax, Fas, FasL and TNF-α increased along with the increase of the pregnant days in both the experimental group and the control group, and the positive cells with expression of Bcl-2 decreased along with the increase of the pregnant days. It was also demonstrated that the positive cells with expression of Bax, Fas, FasL and TNF-α of the experimental group showed a higher percentage of expression than that of the control group on the same pregnant days, but the positive cells with Bcl-2 expression of the experimental group were fewer than that of the control group. It is concluded that the expression of apoptosis-related protein Bax, Bcl-2, Fas, FasL and TNF-α in the placenta were altered when the pregnant mice were infected with Toxoplasma gondii during the second trimester, which may induce the apoptosis through the endogenic and ectogenic pathway.
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OBJECTIVE Comparing and analyzing the use of antibacterial drugs in our hospital for nearly 10 years,to guide more standardized and more rational use of antibiotics in clinical pediatrics.METHODS The use of antimicrobial drugs among 3711 pediatric cases in our hospital from 1999 to 2008 was comparatively analyzed.RESULTS The usage rate of antibacterial drugs among them in our hospital for nearly 10 years was 93.45%.The use of top six kinds of antimicrobial drugs constantly changed every year,so did the use rate.The rate of combined application was more than 43%,except for 17.67% in 2004,and the kinds of combined application were increasing year by year.The usage rate of second-line antibiotics was increasing year by year,increased from 7.25% in 2000 up to 71.89% in 2008.The preventive drug use was reduced year by year.CONCLUSIONS Using the antimicrobial agents in pediatric is more reasonable than the other departments in our hospital.However,there are some unreasonable phenomena.Antimicrobial agents use should be strengthened in the field of guidance,supervision and management.
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Objective To evaluate the effect of external direct current shock on left atrial(LA) diamension and volumes after cardioversion for atrial fibrillation(AF) and the relation between LA size and function.Methods The initial study population included 68 patients with AF.According to cardioversion patterns, the patients were divided randomly into cardioversion with direct-current shock(36 patients) and cardioversion with drugs(32 patients). Echocardiographic evaluations included LA size and volume,LA passive and active emptying volumes were calculated,and LA function was measured as LA ejection force (LAEF).The correlation between LA diameters and volumes and LA systolic function was analyzed. Results LA was dilated in all the patients during AF and the superior-infra dimensions of LA decreased after restoration of sinus rhythm in the patients reverted with external direct current shock and the patients reverted with durgs (P