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Febuxostat, as a xanthine oxidase inhibitor, is a classic anti-gout drug with significant therapeutic effects and good tolerability. The structures of febuxostat and its derivatives can be divided into two parts: a substituted phenyl ring and a five-membered or six-membered heterocyclic ring with a carboxyl substitution. This paper reviewed the research progress of febuxostat derivatives in recent ten years and classified the structure-activity relationships of various febuxostat derivatives. Exploring the action mechanisms and structure-activity relationships of xanthine oxidase inhibitors might be significant for the rational design and development of new anti-gout chemical entities.
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The aim of this study was to investigate the effects of hirsutine on apoptosis of breast cancer cells and its possible mechanism. The MCF-10A, MCF-7 and MDA-MB-231 cells were treated with hirsutine at different concentrations for 48 h or incubated with 160 μmol/L hirsutine for 24, 48, and 72 h. The MCF-10A cell line is a non-tumorigenic epithelial cell line, and the MCF-7 and MDA-MB-231 are human breast adenocarcinoma cell lines. CCK-8 assay was employed to detect the cell viability. Flow cytometry was used to assay the apoptosis and mitochondrial membrane potential (MMP). The protein expressions of Bcl-2, Bax, cleaved-caspase 9, cleaved-caspase 3 and cytochrome C (Cyt C) in the MDA-MB-231 cells were detected by Western blotting. The results showed that hirsutine remarkably reduced the viability of MCF-7 and MDA-MB-231 cells in a time- and dose-dependent manner (P < 0.05) with IC50 values of 447.79 and 179.06 μmol/L, respectively. In the MDA-MB-231 cells, hirsutine induced apoptosis and depolarization of MMP (P < 0.05), released Cyt C from mitochondria (P < 0.05), and activated caspase 9 and caspase 3 (P < 0.05). However, these effects induced by hirsutine were all inhibited by cyclosporin A (CsA) (P < 0.05), a specific inhibitor of mitochondrial permeability transition pore (MPTP). In addition, hirsutine down-regulated the protein level of Bcl-2 and up-regulated the protein level of Bax (P < 0.05). These results suggest that hirsutine may induce apoptosis of human breast cancer MDA-MB-231 cells through decreasing the ratio of Bcl-2 to Bax, opening MPTP, releasing Cyt C from mitochondria, and activating caspase 9 and caspase 3.
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Objective To compare the clinical features between cryptogenic stoke(CS)with and without right-to-left shunt(RLS)so as to determine whether shunt severity determined by control-enhanced transcranial Doppler(c-TCD)is correlated with the risk of paradoxical embolism(RoPE)score.Methods We made a retrospective analysis of clinical characteristics of 138 CS patients with and without RLS admitted to our department between January 2014 and November 2016.For patients documented by c-TCD,we evaluated whether there was a correlation between RLS severity and RoPE score. RLS was diagnosed by c-TCD and contrast-enhanced transthoracic echocardiography(c-TTE).We compared every modality for detecting RLS with and without Valsalva maneuver.For patients found with RLS in c-TCD and c-TTE,we judged whether there was an agreement in grading RLS between two modalities.Results For patients with CS,shunt severity by c-TCD was positively correlated with RoPE score(r= 0.26,P= 0.05).The clinical features were different between CS patients with RLS and without RLS.Compared with the positive results of c-TCD and c-TTE at rest,the positive rate was higher in Valsalva maneuver,respectively(P＜0.01).There was a moderate agreement between shunt grades identified by the two techniques(Kappa=0.428).Conclusion There is a positive correlation between RoPE score and RLS severity determined by c-TCD in CS patients.Valsalva maneuver can significantly increase the positive rate of RLS detected by c-TCD and c-TTE.
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AIM:To investigate the effect of hirsutine on hypoxia-induced migration and invasion abilities of human breast cancer MCF-7 cells and its possible mechanism. METHODS:CCK-8 assay was employed to detect the cyto-toxic effect of hirsutine on the MCF-7 cells. Cell migration was observed by wound healing assay,and cell invasion ability was measured by Transwell invasion assay. Western blot was used to analyze the protein levels of hypoxia-inducible factor-1α(HIF-1α),Snail,E-cadherin and matrix metalloproteinase-9 (MMP-9). The mRNA levels of HIF-1α was detected by RT-PCR. RESULTS:Hirsutine remarkably reduced the cell viability from 32 μmol/L(P<0.05),and the IC50value was 62.82 μmol/L. In hypoxia state,MCF-7 cells showed more powerful capabilities of migration and invasion (P<0.05), higher protein levels of HIF-1α,Snail and MMP-9 (P<0.05),lower protein level of E-cadherin(P<0.05),and higher mRNA level of HIF-1α (P<0.05). These hypoxia-induced effects were all inhibited by hirsutine at 16 μmol/L (P<0.05),apart from the mRNA level of HIF-1α. CONCLUSION:Hirsutine inhibits hypoxia-induced migration and inva-sion in human breast cancer MCF-7 cells most likely via down-regulation of the protein levels of HIF-1α,Snail and MMP-9,and up-regulation of the protein level of E-cadherin.
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<p><b>OBJECTIVE</b>To compare agitated saline solution (AS) and the mixture of AS with blood (ASb) as the contrast agents in contrast transcranial Doppler (c-TCD) in the diagnosis of patent foramen ovale (PFO).</p><p><b>METHODS</b>We recruited 248 consecutive patients for c-TCD examination between November 2015 and January 2016, and the sequence of the use of AS (9 mL saline solution mixed with 1 mL air) and ASb (9 mL saline solution and a drop of the patient's blood mixed with 1 mL air) was determined by coin-tossing method. Before the examination, the contrast agent was injected with or without Valsalva maneuvers (VM), and the number of microbubbles within 25 s after the contrast agent injection and the time of first appearance of microbubbles were recorded by observing the TCD spectrum. Each injection was repeated twice and the interval between tests was at least 5 min. We classified PFO according to the number of microbubbles into negative (no microbubble), grade I (1-10 microbubbles), grade II (>10 microbubbles but no curtain), and grade III (with curtain).</p><p><b>RESULTS</b>s The positivity rates in diagnosis with AS without VM, AS with VM, ASb without VM, and ASb with VM tests were 10.9%, 23.8%, 12.1% and 25.8%, respectively. AS with VM test had a higher positive rate than AS without VM test (23.8% vs 10.9%, P=0.001), and ASb with VM test had a higher positive rate than ASb without VM test (25.8% vs 12.1%, P=0.001). The positive rates were similar between ASb without VM and AS without VM test (12.1% vs 10.9%, P=0.250) and between ASb with VM test and AS with VM test (25.8% vs 23.8%, P=0.125).</p><p><b>CONCLUSION</b>VM can improve the positive rate of PFO diagnosis in c-TCD examination, and the positive rates are comparable between examinations using the contrast agents AS and ASb.</p>
Subject(s)
Contrast Media , Chemistry , Foramen Ovale, Patent , Diagnostic Imaging , Microbubbles , Sensitivity and Specificity , Sodium Chloride , Ultrasonography, Doppler, Transcranial , Valsalva ManeuverABSTRACT
?AlM: To evaluate the relationship of early-life and childhood exposures and age-related cataract ( ARC ) , and provide a scientific evidence for early preventing, treating and detecting ARC. ?METHODS: A hospital-based case control study was conducted from April 2011 to October 2012. A total of 360 cases ( 360 eyes ) aged 41 ~ 60 years old for cataract extraction and 360 frequency-matched controls in the same hospital for various not related to ARC were included in the study. A structured interviewer -administrated questionnaire that included information on sociodemographic characteristics, early - life and childhood exposures was used. The risk factors of ARC were estimated with unconditioned logistic regression models. ?RESULTS:Early gestational age at birth sooner and lower birth weight was significantly associated with the risk of ARC(OR=1. 152,95%CI:1. 029~2. 235,P=0. 024;OR=1. 374, 95%CI:1. 156 ~2. 581,P=0. 037,respectively). The maternal pre-pregnancy diabetes ( OR=1. 587, 95%CI:1. 177~2. 915,P=0. 019),gestational diabetes (OR=1. 763, 95%CI:1. 375 ~ 2. 367,P= 0. 004), preeclampsia(OR=1. 581, 95%CI: 1. 139 ~1. 996,P=0. 021), and pregnancy induced hypertension (OR=1. 517, 95%CI:1. 032~1. 963,P=0. 024) could make the risk of ARC increased. Of the factors affecting the period of children, only shorter height relative to peers and overweight at age 10 were significantly associated with the risk of ARC( OR=1. 329, 95%CI:1. 072~2. 351,P=0. 038;OR=2. 302, 95%CI:1. 323~3. 196,P=0. 011, respectively). ?CONCLUSlON:Early gestational age at birth, low birth weight, the maternal pre - pregnancy diabetes, gestational diabetes, preeclampsia, and gestational hypertension, and shorter height and overweight relative to peers, at age 10 were risk factors of ARC. But lasted long large and prospective studies are needed to insure early risk factors for ARC in the Chinese population.
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<p><b>OBJECTIVE</b>To observe the protective effects of safflor Injection (SI) and extract of Ginkgo biloba (EGB) on lung ischemia-reperfusion injury (LIRI) and investigate its mechanism.</p><p><b>METHODS</b>In vivo rabbit model of LIRI was reconstructed. Forty rabbits were randomly and equally divided into four groups: sham-operation group (sham group), ischemia-reperfusion group (model group), ischemia-reperfusion plus SI group (safflor group) and ischemia-reperfusion plus EGB injection group (EGB group). Malondialdehyde (MDA) content, superoxide dismutase (SOD) and xanthine oxidase (XO) activity in serum were measured. The wet/dry weight ratio (W/D) of the lung tissue and activity of myeloperoxidase (MPO) were also tested. Ultrastructure change of the lung tissue was observed by the electron microscope. The expression of intercellular adhesion molecule-1 (ICAM-1) was measured by immunohistochemistry (IHC).</p><p><b>RESULTS</b>In the model group, MDA and XO increased and SOD decreased in serum compared with the sham group (P<0.01). The values of W/D, MPO and ICAM-1 of the model group were higher than those of the sham group (P<0.01), but those of the safflor group and EGB group were significantly lower than those of the model group (P<0.01). The IHC demonstrated that ICAM-1 expression in lung tissue of the model group was significantly higher than those of the safflor group (P<0.01). Compared with safflor group, in the EGB group MDA, XO, MPO decreased, SOD and ICAM-1 expression increased (P<0.05), but the change of W/D was not statistically significant (P>0.05).</p><p><b>CONCLUSIONS</b>SI and EGB may attenuate LIRI through antioxidation, inhibition of neutrophil aggregation and down-regulation of ICAM-1 expression. But EGB had more effect on the antioxidation, while SI did better on regulating ICAM-1 expression.</p>
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Animals , Female , Male , Rabbits , Ginkgo biloba , Chemistry , Immunohistochemistry , Injections , Intercellular Adhesion Molecule-1 , Metabolism , Lung , Pathology , Malondialdehyde , Metabolism , Plant Extracts , Pharmacology , Therapeutic Uses , Protective Agents , Pharmacology , Therapeutic Uses , Reperfusion Injury , Blood , Drug Therapy , Safflower Oil , Pharmacology , Therapeutic Uses , Superoxide Dismutase , Blood , Xanthine Oxidase , BloodABSTRACT
The efficiency of dendritic cell-activated and cytokine-induced killer cell (DC-CIK) therapy on children with acute myeloid leukemia (AML) after chemotherapy was investigated. Mononuclear cells were collected from children achieving complete remission after chemotherapy, cultured in vitro and transfused back into the same patient. Interleukin-2 (IL-2) was injected subcutaneously every other day 10 times at the dose of 1 × 10(6) units. Peripheral blood lymphocyte subsets and minimal residual disease (MRD) were detected by flow cytometry. Function of bone marrow was monitored by methods of morphology, immunology, cytogenetics and molecular biology. The side effects were also observed during the treatment. The average follow-up period for all the 22 patients was 71 months and relapse occurred in two AML patients (9.1%). The percentage of CD3(+)/CD8(+) cells in peripheral blood of 15 patients at the 3rd month after DC-CIK treatment (36.73% ± 12.51%) was dramatically higher than that before treatment (29.20% ± 8.34%, P < 0.05). The MRD rate was >0.1% in 5 patients before the treatment, and became lower than 0.1% 3 months after the treatment. During the transfusion of DC-CIK, side effects including fever, chills and hives appeared in 7 out of 22 (31.82%) cases but disappeared quickly after symptomatic treatments. There were no changes in electrocardiography and liver-renal functions after the treatment. MRD in children with AML can be eliminated by DC-CIK therapy which is safe and has fewer side effects.
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Adolescent , Child , Child, Preschool , Female , Humans , Male , Antineoplastic Agents , Therapeutic Uses , Bone Marrow , Allergy and Immunology , Pathology , Cytokine-Induced Killer Cells , Cell Biology , Allergy and Immunology , Transplantation , Dendritic Cells , Cell Biology , Allergy and Immunology , Transplantation , Immunotherapy, Adoptive , Methods , Injections, Subcutaneous , Interleukin-2 , Therapeutic Uses , Leukemia, Myeloid, Acute , Allergy and Immunology , Pathology , Therapeutics , Neoplasm, Residual , Primary Cell Culture , Recurrence , Remission Induction , Treatment OutcomeABSTRACT
The current 5 kinds of integrated solutions are analysed and compared to accomplish the connecting demand between laboratory small systems and LIS systems. According to different scenarios and specific needs, we have adopted suitable technical solution for the integration to complete connection requirements.
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Clinical Laboratory Information Systems , Computer Systems , Systems IntegrationABSTRACT
Objective To study the construction of the lentiviral-mediated RNA interference(RNAi) vector targering rat suppressors of cytokine signaling 3(SOCS3) gene.Methods Three target sequences were selected by on-line designer software on Ambion according to rat SOCS3 mRNA sequence(NM053565),the complementary DNA contained both sense and antisense oligonucleotides were designed and synthesized.After annealing,these double strands DNA were cloned to pRNA-Lenti-green fluorescent protein(GFP),which contained U6 promoter and GFP.The resulting Lentiviral vector containing SOCS3 shRNA was named pRNA-Lenti-SOCS3-GFP.After the rat glioma cells(C6)were transduced with the constructed 1entiviral vectors,real-time polymerase chain reaction was used to evaluate the level of SOCS3 expression(including siRNA1 group,siRNA2 group,siRNA3 group,vacuity group and siRNA-Negative group).The pRNA-Lenti-SOCS3-GFP and Lentivector Pakaging plasmid mix were cotransfected into 293T to package Lentivirus particles.Culture supematant was harvested,then the virus titer was determined by serial dilution assay.Results The SOCS3 mRNA sequence was successfully cloned to pRNA-Lenti-GFP,which was proved by PCR and DNA sequence.Compared with control group,the SOCS3 mRNA expressions were obviously suppressed in all 3 experimental groups,especially the expression rate in siRNA1 group was reduced by 80%.The Lentiviral particle titer was determined by serial dilution assay with 1.0?1010 TU?L-1.Conclusion The lentiviral-mediated RNAi vector of rat SOCS3 gene has been constructed successfully,this may provide a potential tool for studying and treating SOCS3-related diseases.