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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 239: 118546, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32505107

RESUMO

In this paper, a label-free fluorescence nanoprobe is constructed based on poly(thymine) single strand DNA-templated Copper nanocluster (denote as: T-CuNCs) for the detection of hydrogen peroxide. In the assay, the fluorescent T-CuNCs will generate though the reaction of Cu2+, poly(thymine) and sodium ascorbate. However, the hydroxyl radical (.OH) will generated in the presence of H2O2, which is able to induced the oxidative lesions of poly(thymine) single chain DNA and lead to the poly(thymine) being splitted into shorter or single oligonucleotide fragments and lose the ability to template the fluorescent T-CuNCs again. Therefore, H2O2 can be detected by monitoring the fluorescence strength change of T-CuNCs. The experimental results show that the fluorescence intensity change of T-CuNCs has fantastic linearity versus H2O2 concentration in the range of 1-30 µM (R2 = 0.9947) and 30-80 µM (R2 = 0.9972) with the limit of detection (LOD) as low as 0.5 µM (S/N = 3). More important, the fluorescent nanoprobe was also successfully utilized on the detection of H2O2 in serum samples. Therefore, a label-free, costless and effective fluorescence method has been established for the detection of H2O2, the intrinsic properties of the nanoprobe endow its more potential applications in chemical and biological study.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 470-475, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32319381

RESUMO

OBJECTIVE: To explore the value of CpG-oligonucleotide(CpG-ODN) immunostimulatory method in chromosome culture of chronic lymphocytic leukemia (CLL) cells and to compare the differences between related studies at home and abroad, so as to improve the success rate of CLL karyotype culture and the detection rate of abnormal karyo-types. METHODS: Bone marrow samples from 82 CLL patients were collected and cultured with phytohemagglutinin (PHA), CpG-oligonucleotide plus interleukin-2 (CpG-ODN DSP30+IL-2) for 72 hours. Chromosomes were prepared and analyzed by conventional cytogenetics (CC). Meanwhile, D13S25, Rb1, ATM, p53 and CSP12 probes were used for interphase fluorescence in situ hybridization (iFISH) test. The differences of chromosome culture and iFISH test results between two cell stimulants were compared. RESULTS: The success rate of karyotype culture in PHA and CpG-ODN DSP30+IL-2 immunostimuli (analyzable mitotic t >20) was 90.2% (74 cases), 68.3% (56 cases) respectively, and the detection rate of abnormal karyotype was 13.5% (10 cases) and 46.4% (26 cases), respectively. The success rate of karyotype culture in PHA group was significantly higher than that in CpG-ODN DSP30+IL-2 group (P=0.01). The detection rate of abnormal karyotypes in CpG-ODN DSP30+IL-2 group was significantly higher than that in PHA group, and the difference was statistically significant (P=0.003). The detection rate of abnormal karyotypes in iFISH group was 74.4% (61 cases), which was significantly higher than that in CpG-ODN DSP30+IL-2 group (P=0.000). iFISH detection could verify the abnormalities detected by CC analysis. CONCLUSION: Application of CpG-ODN DSP30+IL-2 immunostimulation method in culture of CLL cells can enhance the detection rate of abnormal karyotypes, especially the detection of various translocations suggesting poor prognosis.


Assuntos
Leucemia Linfocítica Crônica de Células B , Aberrações Cromossômicas , Humanos , Imunização , Hibridização in Situ Fluorescente , Oligodesoxirribonucleotídeos
3.
Int J Mol Sci ; 21(5)2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32155790

RESUMO

Combretastatin-4 (CA-4) as a tubulin polymerization inhibitor draws extensive attentions. However, due to its weak stability of cis-olefin and poor metabolic stability, structure modifications on cis-configuration are being performed. In this work, we constructed a series of novel CA-4 analogues with linkers on olefin containing diphenylethanone, cis-locked dihydrofuran, α-substituted diphenylethanone, cyclobutane and cyclohexane on its cis-olefin. Cytotoxic activity of all analogues was measured by an SRB assay. Among them, compound 6b, a by-product in the preparation of diphenylethanone analogues, was found to be the most potent cytotoxic agents against HepG2 cells with IC50 values of less than 0.5 µM. The two isomers of 6b induced cellular apoptosis tested by Annexin V-FITC and propidium iodide (PI) double staining, arrested cells in the G2/M phase by PI staining analysis, and disrupted microtubule network by immunohistochemistry study in HepG2 cells. Moreover, 6b-(E) displayed a dose-dependent inhibition effect for tubulin assembly in in vitro tubulin polymerization assay. In addition, molecular docking studies showed that two isomers of 6b could bind efficiently at colchicine binding site of tubulin similar to CA-4.

4.
Biomolecules ; 9(9)2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31480670

RESUMO

Tannins biodegradation by a microorganism is one of the most efficient ways to produce bioproducts of high value. However, the mechanism of tannins biodegradation by yeast has been little explored. In this study, Aureobasidium melanogenum T9 isolated from red wine starter showed the ability for tannins degradation and had its highest biomass when the initial tannic acid concentration was 20 g/L. Furthermore, the genes involved in the tannin degradation process were analyzed. Genes tan A, tan B and tan C encoding three different tannases respectively were identified in the A. melanogenum T9. Among these genes, tan A and tan B can be induced by tannin acid simultaneously at both gene transcription and protein expression levels. Our assay result showed that the deletion of tanA and tanB resulted in tannase activity decline with 51.3 ± 4.1 and 64.1 ± 1.9 U/mL, respectively, which is much lower than that of A. melanogenum T9 with 91.3 ± 5.8 U/mL. In addition, another gene coding gallic acid decarboxylase (gad) was knocked out to better clarify its function. Mutant Δgad completely lost gallic acid decarboxylase activity and no pyrogallic acid was seen during the entire cultivation process, confirming that there was a sole gene encoding decarboxylase in the A. melanogenum T9. These results demonstrated that tanA, tanB and gad were crucial for tannin degradation and provided new insights for the mechanism of tannins biodegradation by yeast. This finding showed that A. melanogenum has potential in the production of tannase and metabolites, such as gall acid and pyrogallol.

5.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(5): 491-496, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31104669

RESUMO

OBJECTIVE: To study the effect of 280 nm-LED ultraviolet irradiation on the proliferation of acute promyelocytic leukemia (APL) HL-60 cells under hypoxic conditions and related mechanism. METHODS: HL-60 cells in the logarithmic growth phase were selected and divided into control, hypoxia, ultraviolet and hypoxia+ultraviolet groups. The cells in the hypoxia group were treated with cobalt chloride (with a final concentration of 150 µmol/L), those in the ultraviolet group were irradiated by 280 nm-LED ultraviolet with an energy intensity of 30 J/m2, and those in the hypoxia+ultraviolet group were treated with cobalt chloride and then irradiated by 280 nm-LED ultraviolet. After 48 hours of treatment, the cells were placed under an invert microscope to observe cell morphology. CCK-8 assay was used to measure the inhibition rate of cell proliferation. Annexin V-FITC/PI double staining flow cytometry was used to evaluate cell apoptosis. Quantitative real-time PCR was used to measure the mRNA expression of Bcl-2. Each experiment above was repeated three times independently. RESULTS: Compared with the control group, the experimental groups showed shrinkage, decreased brightness, and disordered arrangement of cells, and the number of cells decreased over the time of culture. There were significant differences in the inhibition rate of cell proliferation and cell apoptosis rate among the groups (P<0.01), and the hypoxia+ultraviolet group showed the strongest inhibition of cell proliferation and induction of cell apoptosis, followed by the ultraviolet group and the hypoxia group. Compared with the control group, the other three groups had a gradual reduction in the mRNA expression of Bcl-2, and the hypoxia+ultraviolet group had a significantly greater reduction than the hypoxia and ultraviolet groups (P<0.01). CONCLUSIONS: Both hypoxia and ultraviolet irradiation can inhibit the proliferation of HL-60 cells and induce cell apoptosis, and ultraviolet irradiation has a better effect on proliferation inhibition and cell apoptosis under hypoxic conditions than under normoxic conditions, possibly by downregulating the mRNA expression of Bcl-2.


Assuntos
Leucemia Promielocítica Aguda , Apoptose , Hipóxia Celular , Proliferação de Células , Humanos
6.
BioDrugs ; 33(4): 437-446, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31111423

RESUMO

BACKGROUND: Bridging studies are mandatory in the EU and USA if the reference biological product used in the biosimilar comparability exercise is foreign sourced. However, it has been argued that the duplication of bridging studies may limit biosimilar development. OBJECTIVE: The aim of the study was to explore whether it is necessary to conduct pharmacokinetic (PK)/pharmacodynamic (PD) bridging studies for biosimilars. This study examines similarities and differences between EU- and US-licensed reference biological products, based on literature-reported PK and/or PD data. METHODS: We searched PubMed, Drugs@FDA, and European Medicines Agency (EMA) databases to identify biosimilar bridging studies designed to evaluate similarities between EU- and US-licensed reference biological products. PK and/or PD parameters were retrieved; the ratio of the parameter value of the EU-licensed product to that of the US-licensed product and its corresponding 90% confidence intervals (CIs) were calculated. Similarity was declared if the 90% CIs for the ratios of the PK or PD parameters were within the range of 80-125%. RESULTS: Thirty-one bridging studies were identified for 11 biosimilars, including adalimumab (n = 10), bevacizumab (n = 4), epoetin alfa (n = 1), etanercept (n = 2), filgrastim (n = 1), infliximab (n = 3), insulin glargine (n = 1), insulin lispro (n = 1), PEGfilgrastim (n = 2), rituximab (n = 2), and trastuzumab (n = 4). Most studies showed PK and/or PD similarities between the EU- and US-licensed reference biological products. However, among the 31 studies, only three studies (accounting for two biologics, PEGfilgrastim and adalimumab) showed dissimilarity between the EU and US reference products. Although one bridging study on PEGfilgrastim (Sandoz) indicated dissimilar PKs (maximum observed plasma concentration [Cmax] and area under the concentration-time curve [AUC]) between the reference products, the other study (Mylan) demonstrated similar PK. Moreover, two of ten studies involving adalimumab failed to demonstrate similarities between the reference products. However, for both cases, PK similarities were later confirmed in the follow-up bridging studies with larger sample sizes. CONCLUSION: Our analysis reveals that, in most cases, the reference biological products originated from the EU and those from the USA are almost indistinguishable in terms of PK/PD properties. Additional in vivo bridging studies between reference products from different global regions may not be required if similar physicochemical and structural properties are evident in vitro.


Assuntos
Medicamentos Biossimilares/farmacologia , Ensaios Clínicos como Assunto/normas , Aprovação de Drogas , Ensaios Clínicos como Assunto/estatística & dados numéricos , Bases de Dados de Produtos Farmacêuticos/estatística & dados numéricos , Europa (Continente) , Humanos , Padrões de Referência , Equivalência Terapêutica , Estados Unidos
7.
Polymers (Basel) ; 11(1)2019 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-30960114

RESUMO

With the prestressed carbon fiber reinforced polymer (CFRP) strengthening technique widely used in reinforced concrete (RC) structures, it is more and more important to study the fatigue performance of RC structures. Since the fracture of a tensile steel bar at the main cracked section is the leading reason for the failure of RC beams reinforced by prestressed CFRP, a fatigue life prediction model of RC beams reinforced by prestressed CFRP was developed based on an accumulative damage model. Moreover, gradual degradation of the performance of the concrete was considered in the fatigue life prediction model. An experimental study was also conducted to research the fatigue behavior of RC beams reinforced by prestressed or non-prestressed carbon fiber laminate (CFL). During the tests, fatigue crack patterns were captured using a digital image correlation (DIC) technique, and the fatigue lives of a total of 30 beams were recorded. The results showed that the predicted main crack propagation curves and the fatigue lives were close to the experimental data. This study also exhibited that the prestressed CFRP could reduce the stress of main steel bars in RC beams and effectively improve the fatigue performance of the RC beams.

9.
Regul Toxicol Pharmacol ; 103: 174-180, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30711621

RESUMO

In principle, approval of a modified-release (MR) drug product is based on evidence from pharmacokinetic (PK) and/or pharmacodynamic studies and clinical efficacy/safety studies. The purpose of this survey is (i) to explore the number of new drug applications (NDAs) of MR drug products, approved by the FDA, employ the PK study as a bridge to already-approved immediate-release drug products without conducting their own clinical efficacy/safety studies; and (ii) to understand the type of PK studies are required for such NDAs. To this end, we surveyed the approved records of MR drug products from 2008 to 2017 from the Drug@FDA website, and filtered pertinent information from FDA's assessment reports. A total of five out of 79 products were found. A single dose PK study was conducted to investigate the underlying drug release mechanisms in four of these products. For these products, the applicants also performed multiple dose PK equivalence studies, but the PK parameters used to support the equivalence were different among studies. Information regarding the exposure-response relationship was available for all selected products, which is fundamental for such cases. Although the difference in PK curve shapes is recognized as being critical for the clinical effectiveness, this evaluation was not performed in all selected cases, as indicated in FDA's assessment reports.


Assuntos
Aprovação de Drogas , Preparações Farmacêuticas/análise , Inquéritos e Questionários , United States Food and Drug Administration/legislação & jurisprudência , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos
10.
Cell Death Differ ; 26(11): 2237-2252, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30728460

RESUMO

TP53 is the most frequently mutated gene in human cancer, whereas tumors with wild-type TP53 develop alternative strategies to survive. Identifying new regulators of p53 reactivation would greatly contribute to the development of cancer therapies. After screening the entire genome in liver cancer cells, we identified lysyl oxidase-like 4 (LOXL4) as a novel regulator for p53 activation. We found that 5-azacytidine (5-aza-CR) induces LOXL4 upregulation, with LOXL4 subsequently binding the basic domain of p53 via its low-isoelectric point region. The interaction between LOXL4 and p53 induces the reactivation of compromised p53, resulting in cell death. Furthermore, the nude mouse xenograft model showed that the 5-aza-CR-dependent LOXL4-p53 axis reduces tumor growth. A positive correlation between LOXL4 expression and overall survival in liver cancer patients with wild-type p53 tumors was observed. In conclusion, we found that 5-aza-CR-induced LOXL4 upregulation reactivates wild-type p53 and triggers cell death, which blocks liver cancer development.

11.
Int J Biol Macromol ; 121: 97-103, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30290260

RESUMO

Isomaltulose production by bacterial fermentation was limited, due to generation of undesirable products and reduced yields. Isomaltulose production using sucrose isomerase (SIase) catalyzed methods was expected to be more applicable, but was hampered by low SIase activity and lack of a secreted SIase producer. Here, we aimed to obtain high levels of secreted SIase by overexpressing the SIase gene from Pantoea dispersa UQ68J in Yarrowia lipolytica, a successful host for efficient secretory expression, with a newly characterized strong constitutive promoter. After optimization of the culture medium, the engineered strain JD secreted SIase with an activity of 49.3 U/mL. The recombinant SIase was effectively immobilized onto polyvinyl alcohol-alginate, and the enzymatic activity recovery rate was up to 82.4%. The stability of the SIase was significantly improved by immobilization. Batch production of isomaltulose catalyzed by the immobilized SIase was performed under optimal conditions, generating 620.7 g/L isomaltulose with a yield of 0.96 g/g. The conversion rate of sucrose after 13 batches remained above 90%. These results demonstrated that the proposed SIase expression and immobilization method was promising in the industrial production of isomaltulose.


Assuntos
Enzimas Imobilizadas/genética , Enzimas Imobilizadas/metabolismo , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Isomaltose/análogos & derivados , Yarrowia/genética , Biocatálise , Meios de Cultura/química , Enzimas Imobilizadas/química , Expressão Gênica , Glucosiltransferases/química , Isomaltose/biossíntese , Pantoea/enzimologia , Pantoea/genética , Álcool de Polivinil/química
12.
Oncotarget ; 9(31): 21687-21695, 2018 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-29774095

RESUMO

Dysregulation of long non-coding RNA (lncRNA) plays important roles in cancer development and progression. In this work, we attempted to develop a lncRNA signature to improve prognosis prediction of colorectal cancer. A comprehensive analysis for the lncRNA expression and corresponding clinical information of 344 colorectal patients has been performed based on the data from The Cancer Genome Atlas (TCGA). We randomly divided TCGA data into a training set (n = 172) and a testing set (n = 172). A four-lncRNA signature has been established which was significantly associated with the overall survival of colorectal cancer patients. Based on the four-lncRNA signature, the training set can be classified into high-risk and low-risk groups with significantly different survival. The result can be further validated in the testing dataset and another independent dataset. Further analyses suggested that the prognostic power of the four-lncRNA signature was independent of other clinical variables. The identification of lncRNA signature indicated that lncRNAs could be novel independent biomarkers for predicting the survival in patients with colorectal cancer.

13.
J Bone Miner Metab ; 36(1): 1-11, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28766139

RESUMO

Extracellular vesicles (EVs) are phospholipid membrane-enclosed entities containing specific proteins, RNA, miRNA, and lncRNA. EVs are released by various cells and play a vital role in cell communication by transferring their contents from the host cells to the recipient cells. The role of EVs has been characterized in a wide range of physiological and pathophysiological processes. In this context, we highlight recent advances in our understanding of the regulatory effects of EVs, with a focus on bone metabolism and the bone microenvironment. The roles of EVs in cell communication among bone-related cells, stem cells, tumor cells, and other cells under physiological or pathological conditions are also discussed. In addition, promising applications for EVs in treating bone-related diseases are proposed.


Assuntos
Osso e Ossos/metabolismo , Microambiente Celular , Vesículas Extracelulares/metabolismo , Animais , Doenças Ósseas/patologia , Humanos , Modelos Biológicos , Células-Tronco/metabolismo
15.
Shanghai Kou Qiang Yi Xue ; 26(4): 461-464, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-29199347

RESUMO

PURPOSE: To explore the factors affecting soft tissue infection after oral and maxillofacial debridement. METHODS: Fifty hundred patients with debridement were enrolled in this study from January 2013 to June 2016. The patients were divided into 2 groups according to soft tissue infection, 18 cases in infection group and 482 cases in non-infection group. Age, mean time to surgery, average length of stay, duration of antibiotics use, abbreviated injury scale (AIS), combined injuries, maxillofacial fractures, soft tissue injury, type of fracture, and history of diabetes were recorded and analyzed using SPSS 19.0 software package. RESULTS: The factors influencing soft tissue infection after oral and maxillofacial surgery were the aged, longer hospital stay, longer operation time, longer antibiotics use time, higher AIS score, Jaw bone injury and diabetes. CONCLUSIONS: The factors influencing soft tissue infection after oral and maxillofacial debridement are various. The aged, longer operation time, higher AIS score, jaw bone involvement lip and chin injury as well as diabetes might be the independent factors. Health care providers should give preventive measures to reduce the incidence of infection, according to specific factors.


Assuntos
Desbridamento , Traumatismos Maxilofaciais , Infecções dos Tecidos Moles , Humanos , Traumatismos Maxilofaciais/cirurgia , Estudos Retrospectivos , Lesões dos Tecidos Moles
16.
Oncotarget ; 8(34): 56168-56173, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28915581

RESUMO

Accumulating evidence suggested that long non-coding RNAs (lncRNAs) play essential roles in various biological processes, including tumorigenesis. Aberrant expression of LINC00161 has been reported in some cancer types, however, the association of LINC00161 and hepatocellular carcinoma (HCC) has not been evaluated. Here, we measured the expression of LINC00161 in HCC tissues and corresponding normal liver tissues using real-time PCR. The result showed that the expression level of LINC00161 was significantly higher in HCC tissues. Further analysis indicated that HCC patients with higher LINC00161 expression have shorter survival. Multivariate Cox regression analysis showed that LINC00161 expression was an independent prognostic factor for the overall survival. Furthermore, our result indicated that knock-down of LINC00161 can significantly inhibit liver cancer cell migration and invasion. The present work indicated that LINC00161 might serve as an oncogenic gene and play a pivotal role in promoting tumor migration and invasion in HCC. Our work implicates the promising effect of LINC00161 on the prognosis of HCC.

17.
Sci Rep ; 7(1): 5795, 2017 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-28724960

RESUMO

CRISPR/Cas9-mediated genome editing is a next-generation strategy for genetic modifications. Typically, sgRNA is constitutively expressed relying on RNA polymerase III promoters. Polymerase II promoters initiate transcription in a flexible manner, but sgRNAs generated by RNA polymerase II promoter lost their nuclease activity. To express sgRNAs in a tissue-specific fashion and endow CRISPR with more versatile function, a novel system was established in a polycistron, where miRNAs (or shRNAs) and sgRNAs alternately emerged and co-expressed under the control of a single polymerase II promoter. Effective expression and further processing of functional miRNAs and sgRNAs were achieved. The redundant nucleotides adjacent to sgRNA were degraded, and 5'- cap structure was responsible for the compromised nuclease capacity of sgRNA: Cas9 complex. Furthermore, this strategy fulfilled conducting multiplex genome editing, as well as executing neural- specific genome editing and enhancing the proportion of homologous recombination via inhibiting NHEJ pathway by shRNA. In summary, we designed a new construction for efficient expression of sgRNAs with miRNAs (shRNAs) by virtue of RNA polymerase II promoters, which will spur the development of safer, more controllable/regulable and powerful CRISPR/Cas9 system-mediated genome editing in a wide variety of further biomedical applications.


Assuntos
Proteína 9 Associada à CRISPR/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Edição de Genes/métodos , MicroRNAs/metabolismo , RNA Guia/metabolismo , Expressão Gênica , MicroRNAs/genética , Regiões Promotoras Genéticas , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , RNA Guia/genética
18.
Eur J Drug Metab Pharmacokinet ; 42(6): 935-942, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28283987

RESUMO

BACKGROUND AND OBJECTIVES: The adoption of a domestic reference product in bioequivalence (BE) studies for generic drug applications is required by some countries. The objective of this study is to assess the feasibility of this by investigating whether innovative products from different countries are bioequivalent. METHODS: Data were collected from all generic drug applications received by the Taiwan regulatory authority 2012-2016. If a submission package contained BE studies, that generic product was compared separately with different reference products, and the resulting data included in this analysis. A method of adjusted indirect comparison was used to evaluate the BE of reference products from different sources. The relationship between in vitro dissolution and in vivo BE was also explored. RESULTS: The present study included 10 drugs and a total of 11 comparisons. Seven comparisons for maximum concentration (C max) (63.6%) and all comparisons (100.0%) for area under the curve up to last measurable time point (AUC) complied with the BE criterion. Similar in vitro dissolution profiles were observed in all comparisons. Among the comparisons that failed to demonstrate BE, only one was considered to be possibly related to product difference, with point estimates of indirect comparison for C max significantly greater than unity (22%). Discordance between in vitro and in vivo observations was probably due to either drugs with highly variable properties or a lack of discriminatory dissolution testing method. CONCLUSIONS: Although this retrospective analysis only included a few drugs and product formulation types, i.e., immediate release, delayed release, and orally disintegrating tablet, these preliminary results suggest that using a foreign reference product in BE studies for generic drug applications could be a feasible approach, but with some restrictions: comparable dissolution profiles, same innovator company, same size, weight, and type of coating as the domestic reference product, etc. Further investigations for other complex formulations are required.


Assuntos
Medicamentos Genéricos/farmacocinética , Medicamentos Genéricos/normas , Padrões de Referência , Equivalência Terapêutica , Liberação Controlada de Fármacos , Humanos , Projetos Piloto , Estudos Retrospectivos
19.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 33(2): 185-188, 2017 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-29931929

RESUMO

OBJECTIVE: To investigate the relationship between oxidative stress and myocardial apoptosis, endoplasmic reticulum stress, apoptosis-inducing factors in the process of by researching the effect of oxidative stress on myocardial apoptosis, endoplasmic reticulum stress and apoptosis factor--chop, bax, bcl-2 in suckling mouse atria myocardium. METHODS: The primary cultured suckling mouse myocardium were randomly divided into control group and oxidative stress group. Firstly, the suckling mouse atria cardiomyocytes were treated with H2O2 at the concentration of 100 m µmol/L for 2 hours. Then, the index of oxidative stress and anti-oxidative stress superoxide dismutase (SOD), the con-tents of malondialdehyde (MDA) and glutathione (GSH) of this two groups were detected by ELISA. Myocardial apoptosis of the two groups was detected by TUNEL. The expressions of glucose-regulated protein 78 (GRP78), glucose-regulated protein 94 (GRP94), C/EBP homolo-gous protein (chop), Bcl-2 associated X protein (bax), B-cell leukemia 2 protein (bcl-2) mRNA were detected by real time PCR. RESULTS: Compared with the control group, the viability of SOD and the contents of MDA in oxidative stress group were reduced, the contents of MDA was increased (P < 0.01). Compared with the control group, the expression of myocardial apoptosis in oxidative stress group was increased(P < 0.01); the expressions of GRP78, GRP94, chop and bax mRNA were increased, while the expression of bcl-2 mRNA was reduced in ox-idative stress group. CONCLUSIONS: Oxidative stress may induce the endoplasmic reticulum stress, activate the expressions of apoptosis factors, and finally increase the myocardial apoptosis of atria cardiomyocytes. This may connected to the incident of atrial fibrillation.


Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Miocárdio/patologia , Miócitos Cardíacos/citologia , Estresse Oxidativo , Animais , Animais Lactentes , Glutationa/metabolismo , Proteínas de Choque Térmico/metabolismo , Peróxido de Hidrogênio , Malondialdeído/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Superóxido Dismutase/metabolismo , Fator de Transcrição CHOP/metabolismo , Proteína X Associada a bcl-2/metabolismo
20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 33(3): 222-225, 2017 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-29931936

RESUMO

OBJECTIVE: To study the effects of Caspase broad spectrum inhibitor Z-VAD-FMK on the expressions of calumenin,caspase-3, GRP78 and GRP94 in adriamycin-injured cardiomyocytes and to discuss whether there is a regulation relationship between calumenin and endo-plasmic reticulum stress and myocardial apoptosis. METHODS: The primary cultured suckling mouse myocardium were randomly divided into control group (cardiomyocyte), adriamycin group (3 mg/L adriamycin + cardiomyocyte) and z-VAD-fm group (3 mg/L adriamycin + 0.1 µmol/L Z-VAD-fmk + cardiomyocyte), each group of cardiomyocytes were cultured in CO2 incubator at 37℃ for 24 h (n=3). The expres-sion ofα -SMA protein in ventricular myocytes was detected by immunohistochemical method. The expressions of calumenin, GRP78, GRP94 and Caspase-3 in the myocardial cells were detected by Western blot. RESULTS: Compared with the control group, the expression of calumenin in adriamycin induced myocardial cells was significantly decreased (P < 0.01), while the expressions of GRP78, GRP94 and Caspase-3 ex-pression were increased (P < 0.01). Compared with adriamycin group, the expression of calumenin in z-VAD-fm group was increased (P < 0.01), while the expressions of GRP78, GRP94 and caspase-3 were decreased (P < 0.01). CONCLUSIONS: The caspase inhibitor z-VAD-fmk inhibited the expression of caspase and increased the expression of calumenin in adriamycin induced myocardial cells, and thus alleviated the endoplasmic reticulum stress.


Assuntos
Clorometilcetonas de Aminoácidos/farmacologia , Proteínas de Ligação ao Cálcio/metabolismo , Caspase 3/metabolismo , Inibidores de Caspase/farmacologia , Proteínas de Choque Térmico/metabolismo , Glicoproteínas de Membrana/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Animais , Apoptose , Doxorrubicina/efeitos adversos , Estresse do Retículo Endoplasmático , Camundongos
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