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Mitochondrial oxidative stress has been recognized as a preliminary and critical factor that aggravates the pathological cascade of Alzheimer's disease, which induces the production of β-amyloid protein, upregulates the expression of phosphorylated tau protein and triggers oxidative damage to lipids, proteins and mitochondrial deoxyribonucleic acid. Central neurons are more vulnerable to oxidative stress than non-neuronal cells due to their high oxygen demand, abundant unsaturated fatty acids and antioxidant enzymes deficiency. On this account, this review introduces the causes of mitochondrial oxidative stress, and analyzes the important role of mitochondrial oxidative stress in the pathogenesis of Alzheimer's disease. Meanwhile, the review focuses on the design and intervention strategies of drug delivery systems targeting mitochondrial oxidative stress in neurons, aiming to provide new ideas for the prevention and treatment of Alzheimer's disease.
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OBJECTIVE@#To investigate the effect of intra-articular injection of tranexamic acid on blood loss and blood transfusion rate after minimally invasive unicompartmental knee arthroplasty.@*METHODS@#From January 2015 to September 2017, 90 patients underwent minimally invasive unicompartmental knee arthroplasty were divided into tranexamic acid group and control group, 45 cases in each group. In the tranexamic acid group, there were 22 males and 23 females, aged 62 to 69 (66.1±2.4) years;in the control group, 20 males and 25 females, aged 63 to 71(68.5±5.2) years. The amount of bleeding in the drainage ball at 48 hours after operation was recorded, and the blood transfusion rate and hematocrit level duringthe perioperative period were recorded. The factors influencing perioperative blood loss included gender, age and body mass index (BMI).@*RESULTS@#All patients were followed up for 12.5 to 28.3 (22.8±7.9) months. During the follow-up, the wounds of the two groups healed well, and no deep vein thrombosis and pulmonary embolism occurred. There was no significant difference in postoperative blood loss between the tranexamic acid group and the control group. The postoperative bleeding volume in the tranexamic acid group was (110.0±52.1) ml, and that in the control group was (123.0±64.5) ml (P=0.39). There was no blood transfusion in the two groups.@*CONCLUSION@#Intra articular injection of tranexamic acid can not significantly reduce the postoperative blood loss in patients with minimally invasive unicompartment.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Antifibrinolytic Agents/therapeutic use , Arthroplasty, Replacement, Knee/adverse effects , Blood Loss, Surgical/prevention & control , Hemostatics , Injections, Intra-Articular , Postoperative Hemorrhage , Tranexamic AcidABSTRACT
Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood-brain barrier (BBB) penetration and QSH peptide for -amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against -site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of A production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the A deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as A and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.
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OBJECTIVE:To synthesize 4-hydroxyphenylacetic acid(PHPAA)molecular imprinted polymers(MIPs),and to provide reference for separation and enrichment of PHPAA in urine of cancer patients. METHODS:With PHPAA as template molecule and azobisisobutyronitrile as evocating agent,MIPs was synthesized by precipitation polymerization using 4-vinyl pyridine(4-V),acrylamide(AM),1-vinyl imidazole(1-V)and o-diaminobenzene as functional monomers,ethylene glycol dimethacrylate(EGDMA)and trimethylolpropane trimethacrylate(TRIM)as crosslinking agent. Using scanning electron microscope,infrared spectrum,static adsorption test and molecular recognition performance test used adopted to characterize the structure and performance of MIPs. RESULTS:MIPs1(4-V,EGDMA)microspheres adhered seriously,and MIPs2(AM, EGDMA)microspheres are aggregated. MIPs3(1-V,TRIM),MIPs4(o-diaminobenzene,TRIM)microspheresare were dispersed and had good sphericity. Characteristic absorption peak of PHPAA was not found in infrared spectrum of MIPs. The adsorption capacity of each MIPs was higher than that of blank imprinted polymer without the template molecule,and increased as the increase of template molecular concentration. The adsorption capacity of MIPs3 was significantly higher than that of other MIPs,and its static distribution coefficient(0.14)of PHPAA was higher than that of other structural analogues [PHPA(0.06),TA(0.01)],selective separation factors of PHPAA to PHPA,PHPAA to TA were 2.3,11.5,respectively. CONCLUSIONS:MIPs synthesized with 1-V as functional monomer and TRIM as crosslinking agent has the ability of specific adsorption and selective recognition. It can used as solid phase extractant to separate and enrich low content of PHPAA in the urine of tumor patients.
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·AIM: To investigate the anti - aging effect and its potential mechanisms of simvastatin on retinas of physiological aging rats.·METHODS:Totally 40 three-month old healthy SD rats which had no eye diseases, were randomly assigned into two groups: simvastatin group ( n = 20 ) and control group ( n=20 ) . All rats were cultivated under the same conditions until they were nine - month old when interventions started to be given. Simvastatin group was given intragastric administration of 5mg/kg simvastatin every day until 17-month old. Control group was given intragastric administration of same amount of saline gavage. Retinal thickness was measured by HE staining, while Cu - Zn - SOD, NOX2, Bcl - 2 and Bax were determined by immunohistochemistry ( IHC) .·RESULTS:HE staining showed that the retinal structure was clearer; the morphology of cell was more homogeneous;the number of cells was more stable and the structure of retinal pigment epithelium was more compact when compared with control group. Thickness of retinal neuroepithelium layer and retinal pigment epithelium increased significantly in the simvastatin group. Immunohistochemistry analysis showed that the expressions of Cu - Zn - SOD and Bax statistically increased while the NOX2, Bcl-2 as well as Bcl-2/Bax decreased in simvastatin group when compared with control group (P<0. 05).·CONCLUSION: Simvastatin plays a protective role in retinal aging by decreasing oxidative stress reaction and promoting cell apoptosis.
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[Objective]To establish a rat model of connective tissue disease associated interstitial pneumonia induced by bleomycin, and explore the effect of Qingfei Decoction on interstitial pneumonia and its effect on antifibrosis. [Methods]48 male SD rats , weight 180~200g. All the rats were fed adaptivelly for one week and the rat model of interstitial lung disease were established by means of pour 5mg·kg-1 BLM into trachea .Divided these rats into 4 groups:the normal control group, the interstitial pneumonia model group ,the predmisone group and the Qingfei Decoction group. In addition, each group 12 rats. After 28 days'medication, compare the pathological difference between Qingfei Decoction group with the interstitial pneumonia model group, the predmisone group and the normal control group, and the difference in the expressions of TNF-α, IL-6, TGF-β1 in lung tissue, and the expression of hydroxyproline in lung tissue. [Result]①Pathological staining showed that:compared with the normal control group, the destruction of lung tissue structure of rats pneumonia, severe inflammatory cell infiltration, fibrous tissue hyperplasia massive consolidation, alveolar distribution of collagen fiber lesions in model groups; compared with interstitial pneumonia model group, Qingfei Decoction group reduced lung tissue damage, reduce inflammation cell infiltration, fibrous tissue hyperplasia reduced collagen relative area decreased compared with model group. ②Compared with normal control group, the lung tissue of HYP rats was significantly increased, and the difference was statistically significant the model group( P<0.01); Compared with interstitial pneumonia in the model group, the content of HYP in lung tissue of rats Qingfei Decoction group decreased significantly, and the difference was statistically significant(P<0.01). ③Compared with normal control group, the model group of rat lung tissue IL-6, TNF- alpha, TGF- beta1 concentration increased significantly(P<0.05, P<0.01);compared with the model group, interstitial pneumonia, Qingfeifang lung tissue homogenate TNF-alpha, TGF-beta 1, IL-6 concentration decreased significantly(P<0.05, P<0.01). [Conclusion]1.Qingfei Decoction has inhibition effect to the bleomycin induced interstitial pneumonia.2.The treatment mechanism of Qingfei Decoction to BLM-ILD maybe related to TNF-α, IL-6, TGF-β1.
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[Objective]To establish a rat model of connective tissue disease associated interstitial pneumonia induced by bleomycin, and explore the effect of Qingfei Decoction on interstitial pneumonia and its effect on antifibrosis. [Methods]48 male SD rats , weight 180~200g. All the rats were fed adaptivelly for one week and the rat model of interstitial lung disease were established by means of pour 5mg·kg-1 BLM into trachea .Divided these rats into 4 groups:the normal control group, the interstitial pneumonia model group ,the predmisone group and the Qingfei Decoction group. In addition, each group 12 rats. After 28 days'medication, compare the pathological difference between Qingfei Decoction group with the interstitial pneumonia model group, the predmisone group and the normal control group, and the difference in the expressions of TNF-α, IL-6, TGF-β1 in lung tissue, and the expression of hydroxyproline in lung tissue. [Result]①Pathological staining showed that:compared with the normal control group, the destruction of lung tissue structure of rats pneumonia, severe inflammatory cell infiltration, fibrous tissue hyperplasia massive consolidation, alveolar distribution of collagen fiber lesions in model groups; compared with interstitial pneumonia model group, Qingfei Decoction group reduced lung tissue damage, reduce inflammation cell infiltration, fibrous tissue hyperplasia reduced collagen relative area decreased compared with model group. ②Compared with normal control group, the lung tissue of HYP rats was significantly increased, and the difference was statistically significant the model group( P<0.01); Compared with interstitial pneumonia in the model group, the content of HYP in lung tissue of rats Qingfei Decoction group decreased significantly, and the difference was statistically significant(P<0.01). ③Compared with normal control group, the model group of rat lung tissue IL-6, TNF- alpha, TGF- beta1 concentration increased significantly(P<0.05, P<0.01);compared with the model group, interstitial pneumonia, Qingfeifang lung tissue homogenate TNF-alpha, TGF-beta 1, IL-6 concentration decreased significantly(P<0.05, P<0.01). [Conclusion]1.Qingfei Decoction has inhibition effect to the bleomycin induced interstitial pneumonia.2.The treatment mechanism of Qingfei Decoction to BLM-ILD maybe related to TNF-α, IL-6, TGF-β1.
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<p><b>OBJECTIVE</b>To explore the clinical effect of antero-medial incision of knee joint in treating intercondylar fracture of femur.</p><p><b>METHODS</b>From September 2012 to March 2015, 24 patients with intercondylar fracture of femur were selected, including 17 males and 7 females, aged from 20 to 65 years old with an average of(38.3±9.5) years old. Among them, 12 cases were caused by traffic accident, 8 cases were caused by falling injury and 4 cases were caused by falling down. All patients were closed fractures. The time from injury to hospital was from 30 min to 8 h with an average of(2.2±0.3) h. According to AO classification, 4 cases were type B1, 3 type B2, 2 type B3, 5 type C1, 6 type C2 and 4 type C3. All patients were treated with antero-medial incision of knee joint. Operative time, blood loss and postoperative complications were observed and recovery of keen function was evaluated by Kolmert scoring.</p><p><b>RESULTS</b>All patients were followed-up from 6 to 12 months with average of (9.0±1.7) months. Operative time ranged from 50 to 90 min with an average of (70.0±8.2) min; blood loss ranged from 90 to 400 ml with an average of (180±36) ml; negative pressure flow was from 30 to 90 ml, with an average of (50.0±7.1) ml. All fracture were healed at stage I without loosening of internal fixator, fracture nonunion, and deep vein thrombosis. According to Kolmert scoring, 16 patients got excellent result, 5 patients good and 3 fair.</p><p><b>CONCLUSIONS</b>Antero-medial incision of knee joint in treating intercondylar fracture of femur, which has advantages of good fracture reduction, less injury of soft tissue and simple operation, could obtain good clinical results.</p>
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<p><b>OBJECTIVE</b>To investigate the role of EPHA2 in regulating apoptosis, proliferation and vasculogenic mimicry of osteosarcoma cells, by gene silencing through RNA interference.</p><p><b>METHODS</b>EPHA2-siRNA plasmids were achieved by gene cloning. The plasmids were transfected into human osteosarcoma cells (MG63). The expression level of EPHA2 protein was measured by Western blotting. The proliferation, apoptosis and vasculogenic mimicry features of osteosarcoma MG63cells were assessed by light microscopy, MTIP assay, flow cytometry, annexin V-FITC/PI and HE staining, respectively.</p><p><b>RESULTS</b>The EPHA2-siRNA plasmid was confirmed by DNA sequencing. After treatment with Sequence-specific siRNA targeted EPHA2, the protein level of the transfected group decreased significantly. As compared to non-siRNA transfected cells, the transfected group showed lower proliferation, higher and earlier apoptosis and less osteosarcoma-generated vasculogenic mimicry.</p><p><b>CONCLUSION</b>EPHA2 gene may be involoved in apoptosis and proliferation of osteosarcoma cells, and may be necessary for vasculogenic mimicry. Down-regulation of EPHA2 expression by sequence-specific siRNA may be considered as a new option in the treatment of EPHA2 over-expressing cancer including osteosarcoma in future.</p>
Subject(s)
Humans , Apoptosis , Bone Neoplasms , Metabolism , Pathology , Cell Line, Tumor , Cell Proliferation , Neovascularization, Pathologic , Pathology , Osteosarcoma , Metabolism , Pathology , Plasmids , RNA Interference , RNA, Small Interfering , Genetics , Receptor, EphA2 , Genetics , Metabolism , TransfectionABSTRACT
Objective:To explore the molecular mechanism of Gold Theragran in the protection of renal function,and the inhibition of renal local rennin angiotensin(RA)system in the early diabetic nephropathy(DN),and to provide the theoretical and experimental data for clinical application to prevent the DN.Methods:The experimental rats consisted of 64 healthy SD rats,average 180-220g,female and male both a half,rat model of DN was established by improved method of YANG Junwei,s method of intraperitoneal injection of STZ after nephrectomy.8 Rats was taken as normal group,the rest of them were randomly divided into 5 groups:high,middle and low dose groups of Gold Theragran,Valsartan group,model group.In each group,blood glucose,blood lipids,urine microalbumin per 24 hours,KW/BW,renal angiotensin converting enzyme,plasma and renal angiotensin Ⅱ,and its type 1 receptor were observsd and measured.Results:①Rat's general status in each treatment group was improved compared with the DN model group.②The levels of serum glucose decreased in all treatment groups,especially the high-dose group and mid-dose group were significant(P0.05).③The levels of abnormally high lever of TG,TC decreased in treatment groups,especially the high-dose group and mid-dose group were significant(P0.05).The high-dose group had further function to regulate the lipids in the 28th day than in the 7th day(P0.05).Conclusion:Firstly,Gold Theragran had a therapeutic effect of protecting the renal function on the experimental DN rats;Secondly,Gold Theragran can inhibit the abnormal state of activated rennin angiotensin system in diabetic nephropathy,delay the development of diabetic nephropathy;Thirdly,with the treatment course prolonged,the effective of Gold Theragran might be more obvious,and different dose groups show dose-effect-dependent relationship.