ABSTRACT
Silent information regulator 1 (SIRT1) is one of the seven mammalian proteins of the sirtuin family of NAD+-dependent deacetylases. SIRT1 plays a pivotal role in neuroprotection and ongoing research has uncovered a mechanism by which SIRT1 may exert a neuroprotective effect on Alzheimer's disease (AD). Growing evidence demonstrates that SIRT1 regulates many pathological processes including amyloid-β precursor protein (APP) processing, neuroinflammation, neurodegeneration, and mitochondrial dysfunction. SIRT1 has recently received enormous attention, and pharmacological or transgenic approaches to activate the sirtuin pathway have shown promising results in the experimental models of AD. In the present review, we delineate the role of SIRT1 in AD from a disease-centered perspective and provides an up-to-date overview of the SIRT1 modulators and their potential as effective therapeutics in AD.
Subject(s)
Animals , Humans , Alzheimer Disease , Amyloid beta-Protein Precursor , Animals, Genetically Modified , Sirtuin 1 , SirtuinsABSTRACT
Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during 2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.
Subject(s)
Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Stomach Neoplasms/therapyABSTRACT
Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.
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Objective: To explore the mechanism of drug resistance in acute lymphoblastic leukemia and the anti-tumor effect of combination therapy of dehydroabietic acid and vincristine against acute lymphoblastic leukemia cells. Methods: Acute lymphoblastic leukemia cells REH and CCRF- CEM were employed to detect the anti-tumor effect of vincristine and doxorubicin on proliferation and apoptosis using EdU assay, human active caspase-3 Quantikine ELISA kit, and flow cytometry. Vincristine-resistant REH cells (REH-R), survivin knockdown and overexpressing REH cells were established to verify the role of survivin in drug resistance. Additionally, in vitro and in vivo assays were performed to determine the effect of dehydroabietic acid on the cytotoxicity of vincristine. Results: Vincristine and doxorubicin markedly suppressed proliferation and induced apoptosis of REH and CCRF-CEM cells. Survivin expression was upregulated in REH-R cells compared with REH cells. Knockdown of survivin expression obviously restored the sensitivity of REH-R cells to vincristine. Akt phosphorylation was also increased in REH-R cells compared to REH cells. In addition, LY294002, a PI3k/Akt pathway blocker, inhibited survivin expression and enhanced cytotoxicity of vincristine to REH-R cells. Dehydroabietic acid effectively reduced survivin expression in REH-R cells, thereby enhancing the therapeutic effect of vincristine on drug-resistant cells. Survivin overexpression markedly reduced the effect of dehydroabietic acid on enhancing the anti-proliferation and inducing apoptosis effect of vincristine. Moreover, the combination of dehydroabietic acid with vincristine significantly extended the survival rate in a mouse xenograft model of acute lymphoblastic leukemia, compared with vincristine treatment alone. Conclusions: Dehydroabietic acid may be used as a potential candidate for the treatment of acute lymphoblastic leukemia in combination with vincristine.
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Malignant tumor is a disease that severely threaten human health. Common chemotherapeutical drugs currently used in clinical practice have some problems in severe side effects and chemoresistance. In contrast, natural venom peptides and artificially designed targeting peptides have excellent biological activities and potential druggability due to their small molecular weights and high affinity to tumor tissues. Thus, the methods for the discovery of anti-tumor peptides have attracted much attention. In this paper, we summarized the types of anti-tumor peptides from recent literatures. Then, we systematically reviewed screening theories, methods and applications based on traditional chromatographic separation, peptidomics, phage display, phenotypic screening, and artificial intelligence. These strategies and technologies will provide a methodological reference for accelerating anti-tumor peptides research.
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Objective To observe the effect of the intensive training of core stabilization on the general function of patients with femoral neck fractures in old patients after hip arthroplasty. Methods From January, 2011 to December, 2012, 60 old patients accepted hip arthroplas-ty for femoral neck fractures were randomly divided into control group (n=30) and observation group (n=30). The control group received routine rehabilitation training 50 minutes each time, and the observation group received intensive training of core muscles 20 minutes each time based on the routine rehabilitation training 30 minutes each time, twice a day, five days a week for two weeks. Both groups were evalu-ated with Harris Hip Score (HHS), Charnley Hip Score (CHS) and modified Barthel Index (MBI) before training and one week, two weeks and three months after training. Results There was no significant difference in the scores of HHS, CHS and MBI before and one week after training (P>0.05). All the scores increased with time in both groups (F>248.165, P<0.001). The scores of HHS, CHS and MBI were signifi-cantly higher in the observation group than in the control group two weeks and three months after training (t>3.211, P<0.001). Conclusion Early intensive training of core stabilization may facilitate to recover hip function and activity of daily living in old patients after hip arthro-plasty.
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Objective To observe the effect of the intensive training of core stabilization on the general function of patients with femoral neck fractures in old patients after hip arthroplasty. Methods From January, 2011 to December, 2012, 60 old patients accepted hip arthroplas-ty for femoral neck fractures were randomly divided into control group (n=30) and observation group (n=30). The control group received routine rehabilitation training 50 minutes each time, and the observation group received intensive training of core muscles 20 minutes each time based on the routine rehabilitation training 30 minutes each time, twice a day, five days a week for two weeks. Both groups were evalu-ated with Harris Hip Score (HHS), Charnley Hip Score (CHS) and modified Barthel Index (MBI) before training and one week, two weeks and three months after training. Results There was no significant difference in the scores of HHS, CHS and MBI before and one week after training (P>0.05). All the scores increased with time in both groups (F>248.165, P<0.001). The scores of HHS, CHS and MBI were signifi-cantly higher in the observation group than in the control group two weeks and three months after training (t>3.211, P<0.001). Conclusion Early intensive training of core stabilization may facilitate to recover hip function and activity of daily living in old patients after hip arthro-plasty.
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Objective To explore the relationship between body mass index (BMI),waist circumference (WC)and adult hypertension in Gongshu District,as well as on hypertension prediction effect.Methods Age -stratified Logistic regression was used to analyze the correlation between BMI,WC and hypertension;ROC curve was used to compare hypertension prediction effect of BMI with that of WC among different gender and age people.Results BMI and WC of hypertension group were higher than that of normal group (P <0.05);the mean SBP and DBP of abdominal obesity group were higher than that of normal group (P <0.001);the mean SBP and DBP of BMI obesity group were higher than that of overweight group,and overweight group were higher than that of the normal group.With the increase of age,the mean SBP,DBP,WC,the prevalence rate of hypertension,abdominal obesity rate were increased,but the value of BMI and the rates of BMI overweight and obesity of the youths were lower than that of the middle aged.According to the results of adjusted Logistic regression analysis,the OR value of the youths'BMI obesity group with hypertension is 15.167 times than the normal group,the OR value of the youths'abdominal obesity group with hypertension is 6.995 times than the normal group;the βand OR value of BMI obesity group and abdominal obesity are decreased along with the increasing age.Both male and female,WC and BMI are good predictors of hypertension.Conclusion For adults,WC and BMI were good predictors of hypertension.Effect of youths'overall obesity and abdominal obesity on blood pressure is higher than that of the elderly;and it needs to be focused on.
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<p><b>OBJECTIVE</b>To observe the influence of different bonding process and three different root canal sealing materials on microstructure of root canal dentin bonding interface after fiber post and resin bonding, so as to improve clinical operation steps and to optimize fiber post resin bonding effect.</p><p><b>METHODS</b>Fifteen human single mandibular first premolars were selected. Three were bonded with fiber posts through Relyx Unicem conventional bonding steps after filled with root canal sealing materials of zinc oxide eugenol paste (Group A), and another three were bonded through the same steps after filled with sealing materials of Vitapex (Group B). The other nine were filled with sealing materials of AH Plus, randomly divided into three groups and bonded through different steps as follows: conventional bonding steps only (Group C), etching with 35% phosphoric acid before conventional bonding steps (Group D), and etching and coating with Singlebond 2 adhesive before conventional bonding steps (Group E). After immersed in saline solution for one week, all the roots were cut into three sections of 3 mm in thickness with emery chip and numbered as crown section, middle section and tip section respectively. The samples were observed the resin protrusion in mixed layer of dentin interface and dentinal tubules by scanning electron microscopy.</p><p><b>RESULTS</b>We observed the resin protrusion in microstructures of the roots bonded through Relyx Unicem after filled with three different root canal sealing materials (Group A, B, C, E): most obvious in the root crown sections, middle in the root middle sections and least in the root tip sections. Differences were observed in roots filled with different sealing materials: little resin protrusion were observed in crown sections only in Group A and B, but large number of resin protrusion were found in crown and middle sections in Group C-E. Compared with Group C, no more resin protrusion were found in Group D. More and elongated resin protrusions were found in Group E.</p><p><b>CONCLUSIONS</b>We recommend using AH Plus as root canal sealing materials for residual crown and root needed to strengthen by fiber post. It is no need to etch before Relyx Unicem conventional bonding steps. However, coating Singlebond 2 adhesive after acid etching has the potential to increase fiber post cementation.</p>