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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 study and observe application value of 256 slice spiral CT coronary imaging (MSCT) for di‐agnosing coronary artery stenosis in aged patients .Methods :A total of 95 aged patients suspecting coronary artery stenosis treated in our hospital were selected .They received MSCT and coronary angiography (CAG) respectively . Inspecting outcomes of above two diagnostic methods were comprehensively compared .Results :(1) CAG identified 91 positive cases and four negative cases in diagnosing coronary artery stenosis ,while it＇s 89 positive cases and six negative cases for MSCT .The diagnostic outcomes of two methods were highly consistent (Kappa＝ 0.789 , P＝0.001 ) ,suggesting MSCT can achieve the diagnostic effect of CAG ; (2) Sensitivity ,specificity ,positive predictive value ,negative predictive value and accuracy of MSCT diagnosing coronary artery stenosis was 94. 51%,25.00%, 96. 63%,16.67% and 91.58% respectively ,suggesting diagnostic outcomes of MSCT possessed high accuracy ; (3) There was no significant difference in judgment of coronary artery stenosis degree between MSCT and CAG , P＝0.524. Conclusion :The diagnostic accuracy of 256 slice MSCT is high in aged patients with coronary artery stenosis , which is almost consistent with that of the gold standard‐CAG .The conduction is simple and it＇s noninvasive ,which can be extended in clinic ;but it′s specificity is compare less ,must pay suitable intension
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Using stakeholder involvement analysis to analyze the appeal,position,power and role of stakehold-ers involved in the creation of the no-fault compensation system of medical damage,this paper believes that the gov-ernment,including the health administrative department, is the concrete maker and the important facilitator of the policy implementation,which needs to take advantage of the public power to predominate the creation and trial opera-tion of the system;the medical staffs,patients and their families are the direct beneficiary of the policy,but it is nec-essary to ensure the good operation of the system by establishing diversified financing channels and setting reasonable compensation scope. The judicial appraisal institution and the expert group are the important guarantors of the policy implementation,but the authentication system should be unified and the expert group evaluation mechanism should be introduced. The insurance industry is an important propellant of policy implementation, but it needs to increase its participation by taking measures,such as expanding financing channels. The news media has an important influence on the making and implementation of the policy and should be properly guided to play its positive role.
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<p><b>OBJECTIVE</b>To find the signaling pathway of triptolide (TP)-induced liver injury and to reveal whether NF-E2-related factor 2 (Nrf2) plays an important role in cellular self-protection.</p><p><b>METHODS</b>The L-02 and HepG2 cells were cultured and treated with various concentrations of TP. The cell viability was observed, and the cell medium was collected for detecting the aspartate aminotransferase (ALT), alanine aminotransferase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and L-glutathione production (GSH) levels. Nrf2 and its downstream target NAD(P)H: quinine oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) expression, the nuclear translocation of Nrf2, and the binding ability of Nrf2 and antioxidant response element (ARE) were also identified. Meanwhile, shRNA was used to silence Nrf2 in L-02 cells to find out whether Nrf2 plays a protective role.</p><p><b>RESULTS</b>The viability of the L-02 and HepG2 cells treated with TP decreased in a doseand time-dependent manner, and TP (20-80 μg/mL) markedly induced the release of ALT, AST and LDH (P<0.05 or P<0.01), reduced the levels of SOD and GSH (P<0.01), and increased the intracellular reactive oxygen species. Meanwhile, TP augmented the Nrf2 expression in L-02 and HepG2 cells (P<0.05 or P<0.01), induced Nrf2 nuclear translocation, increased the Nrf2 ARE binding activity, and increased HO-1 and NQO1 expressions. Nrf2 knockdown revealed a more severe toxic effect of TP (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>Human hepatic cells treated with TP induced oxidative stress, and led to cytotoxicity. Self-protection against TP-induced toxicity in human hepatic cells might be via Nrf2-ARE-NQO1 transcriptional pathway.</p>
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Tripterygium wilfordii Hook. f. induced-hepatotoxicity was the main limitation for its usage in clinic. Qingluo Tongbi formulation showed obvious attenuation for hepatotoxicity in clinic and fundamental research in vivo. To explore the potential mechanism of the attenuation, we conducted a study on the plasma metabolomic profiles of T. wilfordii and Qingluo Tongbi formulation in rats by a sensitive gas chromatography-mass spectrometry (GC-MS/MS) method. In plasma samples, a total of 72 compounds were analyzed by EI source MS, and were successfully identified by matching NIST database. The semi-quantification results were then calculated by OPLS-DA model with SIMCA-P 13.0 software. The three groups were clearly distinguished in OPLS-DA score plot. In addition, the observation values of Qingluo Tongbi formulation showed the obvious trend towards the control levels, suggesting the detoxicity effect of the formulation. Variation metabolites were further analyzed by VIP and One Way ANOVAs, and the results showed a significant increase in compounds of glycogenic amino acids, such as alanine, proline, serine and glutamine after the administration of T. wilfordii, indicated that the tissue proteins were decomposed and amino acids were leakage into blood. Qingluo Tongbi formulation could reverse the amino acids into normal level. On the contrary, the levels of glucose, lactic acid and hydroxy butyrate decrease, and the formulation can relieve the disorder in the levels of lactic acid, suggesting the regulation of the energy metabolism. Additionally, the level of branched chain amino acid was decreased, suggested the toxicity was induced, but the formulation cannot increase it into the normal levels. Nevertheless, all the above results suggested that the classical Qingluo Tongbi formulation displayed the liver protection effect by adjusting the amino acid levels and regulating the energy metabolism. Qingluo Tongbi formulation was developed based on traditional Chinese medicine theory "detoxicity compatibility", and contained Panax notoginseng (Burk.) F. H. Chen to nourish blood and absorb clots. Modern pharmacology suggested that its liver protection effect was correlated with the promotion of protein synthesis. Another important herb is Rehmannia glutinosa Libosch., which can regulate the energy metabolism. Both were consistent with the metabolomic results in this study, which explained the potential mechanism of "detoxicity compatibility" theory. Therefore, the currently developed metabolomic approach and the obtained results would be highly useful for the comprehensive toxicity studies for other herbal medicines and various complex deoxicity formulations.
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<p><b>OBJECTIVE</b>To study the mechanism underlying the inhibitory effect of Qingluo Tongbi Granule (, QTG) on osteoclast differentiation in rheumatoid arthritis in rats.</p><p><b>METHODS</b>Fibroblast and monocyte co-culture were used to induce osteoclast differentiation in adjuvant-induced arthritic (AIA) rats. Serum containing QTG was prepared and added to the osteoclasts, and activation of the tumor necrosis factor receptor-associated factor 6/mitogen-activated protein kinase/nuclear factor of activated T cells, cytoplasmic1 (TRAF6/MAPK/NFATc1) pathways was examined.</p><p><b>RESULTS</b>The induced osteoclasts were multinucleated and stained positive for tartrate-resistant acid phosphatase (TRAP) staining. Serum containing QTG at 14.4, 7.2 or 3.6 g/kg inhibited the activation of TRAF6, extracellular regulated protein kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38 and decreased the percentage of cells with nuclear NFATc1 in a dose-dependent manner, the high and middle doses exhibited clear inhibitory activity (P<0.01 and P<0.05, respectively). After the addition of MAPK inhibitors, the NFATc1 expression showed no significant difference compared with the control group (P>0.05).</p><p><b>CONCLUSIONS</b>Serum containing QTG could generally inhibit the TRAF6/MAPK pathways and possibly inhibit the NFATc1 pathway. In addition, QTG may regulate other signaling pathways that are related to osteoclast differentiation and maturation.</p>
Subject(s)
Animals , Male , Rats , Adjuvants, Immunologic , Arthritis, Experimental , Pathology , Cell Differentiation , Cells, Cultured , Coculture Techniques , Down-Regulation , Drugs, Chinese Herbal , Pharmacology , Fibroblasts , Pathology , Monocytes , Pathology , Osteoclasts , Cell Biology , Physiology , Rats, Sprague-Dawley , Synovial Membrane , PathologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of heat shock protein 72 (Hsp72) on the expression of IL-6 and IL-8 and activation of NF-kappaB in synoviocytes from patients suffered from rheumatoid arthritis (RA).</p><p><b>METHODS</b>IL6 and IL8 concentrations in culture supernatants were measured using enzyme-linked immunosorbent assays (ELISA). Nuclear translocation of NF-kappaB and degradation of the inhibitory protein IkappaBalpha were examined using immunohistochemistry and Western blot.</p><p><b>RESULTS</b>Hsp72 down-regulated IL-6 and IL-8 production in RA synoviocytes induced by tumor necrosis factor-alpha (TNF-alpha). Hsp72 inhibited nuclear translocation of NF-kappaB and degradation of IkappaBalpha induced by TNF-alpha.</p><p><b>CONCLUSION</b>Hsp72 has an anti-inflammatory effect on RA by down-regulation of IL-6 and IL-8 in synoviocytes, which is mediated through inhibiting the activation of NF-KalphaB signal pathways.</p>
Subject(s)
Humans , Arthritis, Rheumatoid , Metabolism , Cells, Cultured , HSP72 Heat-Shock Proteins , Pharmacology , I-kappa B Proteins , Metabolism , Interleukin-6 , Metabolism , Interleukin-8 , Metabolism , NF-KappaB Inhibitor alpha , NF-kappa B , Metabolism , Signal Transduction , Synovial Membrane , Cell Biology , Metabolism , Tumor Necrosis Factor-alpha , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of Premarin and Kuntai capsule (a traditional Chinese patent medicine) on the quality of life (QOL) and their cost-utility in early postmenopausal women.</p><p><b>METHODS</b>Fifty-seven women with menopausal syndrome in the early postmenopausal stage were randomly allocated into Premarin group (0.3 mg/day and 0.6 mg/day alternately, n=29) and Kuntai group (4 g/day, n=28). The therapies lasted for one year and the patients were followed up every 3 months. The QOL of the patients was evaluated and the utility scores were obtained from rating scale to conduct a cost-utility analysis (CUA).</p><p><b>RESULTS</b>At each follow-up examination, no significant difference was found in the QOL between the two groups (P>0.05). The QOL obviously increased after the 1-year-long therapy in both the groups, and Kuntai required longer treatment time than Premarin to take effect. The cost-utility ratio of Premarin and Kuntai were 13581.45 yuan/QALY (quality adjusted life year) and 25105.12 yuan/QALY, respectively. Both incremental cost analysis and sensitivity analysis showed that Kuntai was more costly than Premarin. The result of per-protocol analysis was consistent with that of intention-to-treat analysis.</p><p><b>CONCLUSION</b>At early stage of menopause, the QOL of women with menopausal syndrome can be significantly improved by low-dose Premarin and Kuntai capsule, but the latter is more costly.</p>
Subject(s)
Female , Humans , Middle Aged , Cost-Benefit Analysis , Drug Therapy, Combination , Drugs, Chinese Herbal , Economics , Therapeutic Uses , Estrogens, Conjugated (USP) , Economics , Therapeutic Uses , Phytotherapy , Postmenopause , Quality of LifeABSTRACT
AIM: To investigate the effects of TGP on immunologic changes associated with CJ-S131-induced SLE-like model in mice. METHODS: SLE-like syndrome was induced by injection of CJ-S131 and CFA. Various doses of TGP were given by gavage once daily for 28 days. RESULTS: The levels of IgG anti single-stranded DNA(ssDNA) and histone autoantibodies were increased in sera four weeks after injection. The proliferation response of splencytes to ConA and LPS and the production of IL-1 were also increased. TGP(50,100,200 mg·kg-1·d-1, ig) inhibited the aboved changes of SLE-like mouse model partly or completely. CONCLUSION: The SLE mouse model was similar to idiopathic SLE in humans. TGP has modulating effects on alternations of immunity of SLE-like mouse model.