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Effect of compound Yindan decoction on alpha-naphthylisothiocyanate-Induced acute intrahepatic cholestasis in rats
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作者 Sun Fengxia Li Xiaoling +3 位作者 Xu Chunjun Sui Jingli Li Pan Wu Jingjing 《中医杂志:英文版》 SCIE CAS CSCD 2019年第3期315-323,共9页
OBJECTIVE:To investigate the therapeutic mechanism of compound Yindan decoction (CYD) in a rat model of acute intrahepatic cholestatic (AIC).METHODS:A total of 108 adult male rats were randomly divided into control (n... OBJECTIVE:To investigate the therapeutic mechanism of compound Yindan decoction (CYD) in a rat model of acute intrahepatic cholestatic (AIC).METHODS:A total of 108 adult male rats were randomly divided into control (n =18) and AIC groups (n =90).AIC was induced in rats using alpha-naphthylisothiocyanate (ANIT)(75 mg/kg,10 mL/kg in corn oil,p.o.).Then,90 AIC rats were randomly divided into five groups:a control group (n =18),a CYD high dose group (n =18),a CYD middle dose group (n =18),a CYD low dose group (n =18),and a ursodeoxycholicacid (UDCA) group (n =18).According to sampling time,each group was subdivided into three subgroups:24 h (n =6),48 h (n =6),and 72 h groups (n =6).The CYD-high,-middle and-low groups were orally administered 24.48,12.24,and 6.12 g.kg-1.d-1 modified CYD,respectively,while the model group was given 20 mL/kg of body weight of distilled water once a day.The UDCA group was given 67.5 mg.kg-1.d-1 UDCA once a day.Radioimmunity assay was used to detect the activity of alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),gamma-glutamyl transpeptidase (GGT) and the levels of total bilirubin (TBil) and indirectbiliruin (DBil) in rats.Reverse transcription quantitative polymerase chain reaction (qRT-PCR),Western blot analysis,and immunohistochemistry were used to detect multidrug resistance-associated protein 2 (MRP2) expression.In vitro,HepG2 hepatocellular carcinoma cells were treated with CYD medicated serum at a concentration of 15 mol/L.MRP2 and retinoid X receptor alpha (RXRα) expression was analyzed by qRT-PCR and Western blotting.RESULTS:Serum levels of ALT,AST,GGT,ALP,TBil,and DBil were significantly reduced in the CYD and positive drug groups compared with the control group (P < 0.05 and P < 0.01,respectively).Pathological changes in rat liver tissues at 72 h in the CYD-high and-medium dose groups and positive drug group were not significant compared with the control group.CYD and UDCA treatment ameliorated ANIT-induced biliary epithelial cell pro 展开更多
关键词 Cholestasis intrahepatic MULTIDRUG resistance-associated proteins RETINOID X receptor alpha COMPOUND Yindan DECOCTION
Characterization and frequency of antibiotic resistance related to membrane porin and efflux pump genes among Acinetobacter baumannii strains obtained from burn patients in Tehran, Iran
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作者 Majid Noori Behzad Mohsenzadeh +3 位作者 Aghil Bahramian Fatemeh Shahi Habibollah Mirzaei Saeed Khoshnood 《急性病杂志(英文版)》 2019年第2期63-66,共4页
Objective: To explore the characterization and frequency of antibiotic resistance related to membrane porin and efflux pump genes among Acinetobacter baumannii (A. baumannii) strains obtained from burn patients in Teh... Objective: To explore the characterization and frequency of antibiotic resistance related to membrane porin and efflux pump genes among Acinetobacter baumannii (A. baumannii) strains obtained from burn patients in Tehran, Iran. Methods: In this cross-sectional descriptive study, 100 strains of A. baumannii isolated from burn patients visiting teaching hospitals of Tehran were collected from January 2016 to November 2017. After A. baumannii strains were confirmed, antimicrobial susceptibility testing was done via Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute guidelines. PCR amplification was performed for detection of β-lactamase adeR, OprD, adeS genes among A. baumannii strains. Results: All isolates (100%) were resistant to ceftazidime, cefotaxime, cefepime, ciprofloxacin, and piperacillin, and most isolates indicated high resistance (95%-97%) to meropenem, imipenem, gentamicin, ceftriaxone, trimethoprim-sulfamethoxazole, piperacillin-tazobactam, amikacin, and tetracycline. The most effective antibiotic against A. baumannii isolates was colistin (97% sensitivity), followed by tigecycline. The frequency of OprD, adeS, and adeR genes were 98%, 91%, and 77%, respectively. Conclusions: This study shows that the majority of A. baumannii isolates are highly resistant to the antibiotics most commonly used in burn patients. Also, high distribution of OprD and adeRS genes may be responsible for the observed resistances among A. baumannii isolates that demonstrate the possible role of both efflux pumps in simultaneous of carbapenemase production during antibiotic resistance. 展开更多
关键词 ACINETOBACTER BAUMANNII MULTIDRUG resistance Burn EFFLUX pump genes
Activities of Biapenem against Mycobacterium tuberculosis in Macrophages and Mice 预览
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作者 GUO Zhen Yong ZHAO Wei Jie +4 位作者 ZHENG Mei Qin LIU Shuo YAN Chen Xia LI Peng XU Shao Fa 《生物医学与环境科学:英文版》 SCIE CAS CSCD 2019年第4期235-241,共7页
Objective To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. Methods Biapenem/clavulanate(BP/CL) was evaluated for in vitro activity against Myc... Objective To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. Methods Biapenem/clavulanate(BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis(Mtb) multidrug-resistant(MDR) isolates, extensively drug-resistant(XDR) isolates, and the H37 RV strain. BP/CL activity against the H37 Rv strain was assessed in liquid cultures, in macrophages, and in mice. Results BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units(CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment(isoniazid + rifampin + pyrazinamide) after 2 months of treatment. Conclusion BP/CL may provide a new option to clinically treat MDR tuberculosis. 展开更多
关键词 BIAPENEM CLAVULANATE MULTIDRUG resistant EXTENSIVE DRUG-RESISTANT MYCOBACTERIUM tuberculosis Activity Macrophage Synergy
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Eight new cytotoxic annonaceous acetogenins from the seeds of Annona squamosa
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作者 MA Cheng-Yao LU Jia-Hui +2 位作者 LI Xiang LIU Xiao CHEN Jian-Wei 《中国天然药物:英文版》 SCIE CAS CSCD 2019年第4期291-297,共7页
Eight new annonaceous acetogenins, squamotin A–D(1–4), annosquatin IV–V(5 and 6), muricin O(7) and squamosten B(8), together with four known ones(9–12) were isolated from the seeds of Annona squamosa. Their struct... Eight new annonaceous acetogenins, squamotin A–D(1–4), annosquatin IV–V(5 and 6), muricin O(7) and squamosten B(8), together with four known ones(9–12) were isolated from the seeds of Annona squamosa. Their structures were elucidated by chemical methods and spectral data. The inhibitory activities of compound 1–9 against three multidrug resistance cell lines were evaluated. All tested compounds showed strong cytotoxicity. 展开更多
关键词 ANNONA SQUAMOSA Annonaceous ACETOGENINS Cytotoxicity MULTIDRUG resistance
Urban recreational water – potential breeding ground for antibiotic resistant bacteria?
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作者 Jing Yang Xu Connie Le +1 位作者 Baowei Chen Hongquan Zhang 《环境科学学报:英文版》 SCIE EI CAS CSCD 2019年第7期1-3,共3页
The emergence of multidrug-resistant bacteria, or'superbugs,' has become an urgent and worldwide concern.Antibiotic-resistant bacteria (ARB) cause significant morbidity and mortality (O’Neill, 2016). It has b... The emergence of multidrug-resistant bacteria, or'superbugs,' has become an urgent and worldwide concern.Antibiotic-resistant bacteria (ARB) cause significant morbidity and mortality (O’Neill, 2016). It has been estimated that ARB cause at least 23,000 deaths annually in the United States alone and hundreds of thousands of deaths in developing countries (Bougnom and Piddock, 2017). 展开更多
关键词 Antibiotic RESISTANCE genes (ARGs) MULTIDRUG RESISTANCE in bacteria MICROBIAL PATHOGENS LAKE water and sediment
Curcumin Reverses 5-Fluorouracil Resistance by Promoting Human Colon Cancer HCT-8/5-FU Cell Apoptosis and Down-regulating Heat Shock Protein 27 and P-Glycoprotein
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作者 HE Wen-ting ZHU Yan-hua +6 位作者 ZHANG Tong ABULIMITI Patima ZENG Fan-ye ZHANG Li-ping LUO Ling-juan XIE Xin-mei ZHANG Hong-liang 《中国结合医学杂志:英文版》 SCIE CAS CSCD 2019年第6期416-424,共9页
Objective: To investigate the potential mechanisms that curcumin reverses 5-fluorouracil(5-FU) multidrug resistance(MDR). Methods: Cell growth and the inhibitory rate of curcumin(2–25 μg/mL) and/or5-FU(0.05–1000 μ... Objective: To investigate the potential mechanisms that curcumin reverses 5-fluorouracil(5-FU) multidrug resistance(MDR). Methods: Cell growth and the inhibitory rate of curcumin(2–25 μg/mL) and/or5-FU(0.05–1000 μg/mL) on human colon cancer HCT-8 and HCT-8/5-FU(5-FU-resistant cel line) were determined using cel counting kit-8(CCK-8) assay. Apoptosis and cel cycle after 5-FU and/or curcumin treatment were detected by ?ow cytometry(FCM) and transmission electron microscopy(TEM). The expression of the multidrug resistance related factors p-glycoprotein(P-gp) and heat shock protein 27(HSP-27) genes and proteins were analyzed by reverse transcription polymerase chain reaction(RT-PCR) and Western blotting(WB), respectively. Results: The inhibitory rate of curcumin or 5-FU on HCT-8 and HCT-8/5-FU cells proliferation at exponential phase were in a dosedependent manner, HCT-8 cell line was more sensitive to curcumin or 5-FU when compared the inhibitory rate of HCT-8/5-FU. The 50% inhibitory concentration(IC50) of combination 5-FU and curcumin(4.0 μg/mL)in HCT-8/5-FU was calculated as 179.26 μg/mL, with reversal fold of 1.85. Another IC50 of combination 5-FU and curcumin(5.5 μg/mL) in HCT-8/5-FU was calculated as 89.25 μg/mL, with reversal fold of 3.71. Synergistic effect of 5-FU and curcumin on HCT-8 and HCT-8/5-FU cells were found. The cell cycle analysis performed by FCM showed that HCT-8 and HCT-8/5-FU cel s mostly accumulated at G0/G1 phase, which suggested a synergistic effect of curcumin and 5-FU to induce apoptosis. FCM analysis found that the percentage of apoptosis of cel s treated with curcumin, 5-FU and their combination were signi?cantly increased compared to the control group(P<0.05), and the percentage of apoptosis of the combination groups were slightly higher than other groups(P<0.05). The m RNA levels of P-gp(0.28±0.02) and HSP-27(0.28±0.09) in HCT-8/5-FU cel s treated with combination drugs were lower than cel s treated with 5-FU alone(P-gp, 0.48±0.07, P=0.009;HSP-27, 0.57±0.10, P=0.007). T 展开更多
关键词 CURCUMIN Chinese medicine 5-FLUOROURACIL MULTIDRUG RESISTANCE HCT-8 HCT-8/5-FU col on cancer P-gp HSP-27
Environmentally responsive dual-targeting nanotheranostics for overcoming cancer multidrug resistance
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作者 Caixia Yang Xin Pang +7 位作者 Weihai Chen Xiaoyong Wang Gan Lin Chengchao Chu Xianzheng Zhang Xianming Deng Xiaoyuan Chen Gang Liu 《科学通报:英文版》 SCIE EI CSCD 2019年第10期705-714,共10页
The development of multiple drug resistance(MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycop... The development of multiple drug resistance(MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycoprotein(P-gp) in tumor cells. Here, we report a novel chemosensitizing agent, XMD8-92,which can down-regulate P-gp. To enhance the specificity of MDR chemotherapy, a promising nanotheranostic micelle system based on poly(ethylene glycol)-blocked-poly(L-leucine)(PEG-b-Leu) was developed to simultaneously carry the anticancer drug doxorubicin, chemosensitizing agent XMD8-92, and superparamagnetic iron oxide nanoparticles(SPIOs). Featured with MDR environmentally responsive dual-targeting capability, controllable drug delivery, and efficient magnetic resonance(MR) imaging characteristics, the prepared nanotheranostics(DXS@NPs) showed outstanding in vitro cytotoxicity on MDR cells(SCG 7901/VCR) with only 53% of cells surviving compared to 90% of DOX-treated cells.Furthermore, efficient tumor inhibition and highly reduced systemic toxicity were exhibited by MDR tumor-bearing mice treated with DXS@NPs. Overall, the environmentally responsive dual-targeting nanotheranostics represent a promising approach for overcoming cancer MDR. 展开更多
关键词 CANCER CHEMOSENSITIZATION MULTIDRUG resistance P-GLYCOPROTEIN PH-RESPONSIVE Magnetic resonance imaging
Secalonic acid D induces cell apoptosis in both sensitive and ABCG2-overexpressing multidrug resistant cancer cells through upregulating c-Jun expression
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作者 Hong Zhang Liyan Huang +4 位作者 Liyang Tao Jianye Zhang Fang Wang Xu Zhang Liwu Fu 《药学学报:英文版》 CSCD 2019年第3期516-525,共10页
Secalonic acid D(SAD) could inhibit cell growth in not only sensitive cells but also multidrug resistant(MDR) cells. However, the molecular mechanisms need to be elucidated. Here, we identified that SAD possessed pote... Secalonic acid D(SAD) could inhibit cell growth in not only sensitive cells but also multidrug resistant(MDR) cells. However, the molecular mechanisms need to be elucidated. Here, we identified that SAD possessed potent cytotoxicity in 3 pairs of MDR and their parental sensitive cells including S1-MI-80 and S1,H460/MX20 and H460, MCF-7/ADR and MCF-7 cells. Furthermore, SAD induced cell G2/M phase arrest via the downregulation of cyclin B1 and the increase of CDC2 phosphorylation. Importantly, JNK pathway upregulated the expression of c-Jun in protein level and increased c-Jun phosphorylation induced by SAD, which was linked to cell apoptosis via c-Jun/Src/STAT3 pathway. To investigate the mechanisms of upregulation of c-Jun protein by SAD, the mR NA expression level and degradation of c-Jun were examined. We found that SAD did not alter the mR NA level of c-Jun but inhibited its proteasome-dependent degradation. Taken together, these results implicate that SAD induces cancer cell death through c-Jun/Src/STAT3 signaling axis by inhibiting the proteasome-dependent degradation of c-Jun in both sensitive cells and ATP-binding cassette transporter sub-family G member 2(ABCG2)-mediated MDR cells. 展开更多
关键词 MULTIDRUG resistance Secalonic ACID D Apoptosis C-JUN ABCG2
Specific and Selective Bacteriophages in the Fight against Multidrugresistant Acinetobacter baumannii
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作者 Natalia Baginska Anna Pichlak +1 位作者 Andrzej Gorski Ewa Jonczyk-Matysiak 《中国病毒学:英文版》 CAS CSCD 2019年第4期347-357,共11页
Acinetobacter baumannii causes serious infections especially in immunocompromised and/or hospitalized patients.Several A.baumannii strains are multidrug resistant and infect wounds,bones,and the respiratory tract.Curr... Acinetobacter baumannii causes serious infections especially in immunocompromised and/or hospitalized patients.Several A.baumannii strains are multidrug resistant and infect wounds,bones,and the respiratory tract.Current studies are focused on finding new effective agents against A.baumannii.Phage therapy is a promising means to fight this bacterium and many studies on procuring and applying new phages against A.baumannii are currently being conducted.As shown in animal models,phages against multidrug-resistant A.baumannii may control bacterial infections caused by this pathogen and may be a real hope to solve this dangerous health problem. 展开更多
关键词 ACINETOBACTER BAUMANNII BACTERIOPHAGES PHAGE therapy MULTIDRUG resistance(MDR)
Calculus Bovis Sativus up-regulates hepatic protein 2 (Mrp2) and Mrp4 in 17α-ethynylestradiol-induced cholestasis via a regulatory effect on ER signaling
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作者 Wu Tao Liu Dong Song Hongping 《中医杂志:英文版》 SCIE CAS CSCD 2019年第3期402-409,共8页
OBJECTIVE:To investigate the pathway through which Calculus Bovis Sativus (CBS) up-regulates hepatic multidrug resistance-associated protein 2 (Mrp2) and Mrp4 in 17α-ethynylestradiol (EE)-induced cholestasis.METHODS:... OBJECTIVE:To investigate the pathway through which Calculus Bovis Sativus (CBS) up-regulates hepatic multidrug resistance-associated protein 2 (Mrp2) and Mrp4 in 17α-ethynylestradiol (EE)-induced cholestasis.METHODS:Five groups of rats were designed:control group,EE+ICI182780 group,EE group,EE+CBS 50 mg/kg group and EE + CBS 150 mg/kg group.CBS (50 and 150 mg.kg-1· d-1) was orally given to rats by gavage for five consecutive days in coadministration with EE.The levels of cholestasis biomarkers,alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP) and total bilirubin (TBIL) were determined by biochemical methods.The bile flow was measured.The histopathology of the liver tissue was evaluated.The expression of Mrp2,Mrp3,Mrp4,estrogen receptor α(ERα) and ERβ was determined by Western blotting.RESULTS:CBS markedly improved EE-induced cholestasis.EE exposure significantly reduced hepatic Mrp2 and Mrp4 expression compared with the control group.EE also dramatically up-regulated the expression of Mrp3.Compared to the EE group,CBS notably up-regulated hepatic Mrp2 and Mrp4 but failed to influence the Mrp3 level significantly.ICI182780,an ER antagonist,showed similar beneficial effects as CBS.Decreased expression of Mrp2 and Mrp4 caused by EE was also restored by IC1182780.Additionally,EE significantly induced hepatic ERα expression,which was reversed by ICI182780 or CBS (150 mg/kg) treatment,suggesting that CB5 exerted a moderate regulatory effect on ER signaling.CONCLUSION:CBS up-regulated hepatic Mrp2 and Mrp4 expression in EE-induced cholestasis,which might be associated with its regulation of ER signaling. 展开更多
关键词 Calculus BOVIS Ethynylestradiol Receptors estrogen MULTIDRUG resistance-associated proteins ICI182780
MicroRNAs in the prognosis and therapy of colorectal cancer:From bench to bedside 预览
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作者 Kenneth KW To Christy WS Tong +1 位作者 Mingxia Wu William CS Cho 《世界胃肠病学杂志:英文版》 SCIE CAS 2018年第27期2949-2973,共25页
MicroRNAs(miRNAs)are small,single-stranded,noncoding RNAs that can post-transcriptionally regulate the expression of various oncogenes and tumor suppressor genes.Dysregulated expression of many miRNAs have been shown ... MicroRNAs(miRNAs)are small,single-stranded,noncoding RNAs that can post-transcriptionally regulate the expression of various oncogenes and tumor suppressor genes.Dysregulated expression of many miRNAs have been shown to mediate the signaling pathways critical in the multistep carcinogenesis of colorectal cancer(CRC).MiRNAs are stable and protected from RNase-mediated degradation,thereby enabling its detection in biological fluids and archival tissues for biomarker studies.This review focuses on the role and application of miRNAs in the prognosis and therapy of CRC.While stage II CRC is potentially curable by surgical resection,a significant percentage of stage II CRC patients do develop recurrence.MiRNA biomarkers may be used to stratify such high-risk population for adjuvant chemotherapy to provide better prognoses.Growing evidence also suggests that miRNAs are involved in the metastatic process of CRC.Certain of these miRNAs may thus be used as prognostic biomarkers to identify patients more likely to have micro-metastasis,who could be monitored more closely after surgery and/or given more aggressive adjuvant chemotherapy.Intrinsic and acquired resistance to chemotherapy severely hinders successful chemotherapy in CRC treatment.Predictive miRNA biomarkers for response to chemotherapy may identify patients who will benefit the most from a particular regimen and also spare the patients from unnecessary side effects.Selection of patients to receive the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers.Lastly,forced expression of tumor suppressor miRNA or silencing of oncogenic miRNA in tumors by gene therapy can also be adopted to treat CRC alone or in combination with other chemotherapeutic drugs. 展开更多
关键词 microRNA colorectal cancer MULTIDRUG resistance PROGNOSIS therapeutic target apoptosis metastasis recurrence risk STRATIFICATION
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Chemical Characterization and Biological Potential of the Essential Oil of Eucalyptus globulus Labill 预览
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作者 Nayara Soares de Mendonca Braga Monizy da Costa Silva +3 位作者 Amanda Lima Cunha Antonio Euzebio Goulart Sant’Ana Luana Luzia Santos Pires Aldenir Feitosa dos Santos 《药剂与药理学:英文版》 2018年第12期979-988,共10页
Oxidation of lipids in various products,along with the growth of medically important pathogens,has led to a search for medicinal plants with antioxidant and antimicrobial activities.As a result,the aim of this study w... Oxidation of lipids in various products,along with the growth of medically important pathogens,has led to a search for medicinal plants with antioxidant and antimicrobial activities.As a result,the aim of this study was to evaluate the antioxidant and antibacterial activity of the essential oil of Eucalyptus globulus(EO-Eg).Antioxidant activity was assessed by using the 2,2-diphenyl-1-picrylhydrazyl hydrate(DPPH)assay method.Existing components were identified through gas chromatography-mass spectrometry(GC-MS)analysis.Antibacterial activity and minimum inhibitory concentration(MIC)were assessed by using the broth microdilution method with standard multidrug-resistant bacterial strains.The main EO-Eg compounds identified by GC-MS were isopulegol,citronellal,and citronellol,which are primarily used in the industrial sectors.EO-Eg demonstrated excellent antioxidant activity with an effective concentration(EC50)of 4.48μL/mL owing to the presence of phenolic compounds.Regarding antibacterial activity,the EO-Eg displayed a broad antimicrobial spectrum of antimicrobial activity across the different resistance phenotypes analyzed.The most notable antibacterial activity was observed against Staphylococcus aureus 169 MRSA(MIC=0.0625%).As a result,our findings suggest that EO-Eg has antioxidant and antibacterial potential against hospital-acquired multidrug-resistant pathogens,which may be correlated with its major components. 展开更多
关键词 ESSENTIAL oil ANTIOXIDANT chemical identification MULTIDRUG resistance EUCALYPTUS GLOBULUS
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ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer:what is the way forward? 预览
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作者 Aleksandra Adamska Marco Falasca 《世界胃肠病学杂志:英文版》 SCIE CAS 2018年第29期3222-3238,共17页
Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive diseases and is characterized by high chemoresistance,leading to the lack of effective therapeutic approaches and grim prognosis.Despite increasing u... Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive diseases and is characterized by high chemoresistance,leading to the lack of effective therapeutic approaches and grim prognosis.Despite increasing understanding of the mechanisms of chemoresistance in cancer and the role of ATPbinding cassette(ABC)transporters in this resistance,the therapeutic potential of their pharmacological inhibition has not been successfully exploited yet.In spite of the discovery of potent pharmacological modulators of ABC transporters,the results obtained in clinical trials have been so far disappointing,with high toxicity levels impairing their successful administration to the patients.Critically,although ABC transporters have been mostly studied for their involvement in development of multidrug resistance(MDR),in recent years the contribution of ABC transporters to cancer initiation and progression has emerged as an important area of research,the understanding of which could significantly influence the development of more specific and efficient therapies.In this review,we explore the role of ABC transporters in the development and progression of malignancies,with focus on PDAC.Their established involvement in development of MDR will be also presented.Moreover,an emerging role for ABC transporters as prognostic tools for patients’survival will be discussed,demonstrating the therapeutic potential of ABC transporters in cancer therapy. 展开更多
关键词 PANCREATIC DUCTAL ADENOCARCINOMA MULTIDRUG resistance ATP-BINDING cassette transporters Targeted THERAPIES PANCREATIC DUCTAL ADENOCARCINOMA prognosis Predictive markers
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多药耐药基因MDR1和细胞自噬在肿瘤多重耐药机制中的研究进展 预览
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作者 柳丹 李珊 +7 位作者 赵红艳 柯镜 汤志明 白磊 牛成群 牟雪瑶 朱明明 武福云 《中国现代医学杂志》 2018年第24期38-42,共5页
肿瘤是威胁人类健康的恶性疾病。化疗是目前临床抗肿瘤最常用的治疗方法,化疗药物具有较广的抗瘤谱。但肿瘤多重耐药的发生是导致化疗疗效不佳的主要原因。肿瘤多重耐药机制非常复杂,与药物代谢、药物靶点改变、DNA修复增强、细胞周期... 肿瘤是威胁人类健康的恶性疾病。化疗是目前临床抗肿瘤最常用的治疗方法,化疗药物具有较广的抗瘤谱。但肿瘤多重耐药的发生是导致化疗疗效不佳的主要原因。肿瘤多重耐药机制非常复杂,与药物代谢、药物靶点改变、DNA修复增强、细胞周期改变及肿瘤微环境等均有密切联系。其中多药耐药基因MDR1表达的膜转运蛋白P-糖蛋白参与的化疗药物逆向转用是多药耐药发生的重要机制之一,但是针对MDR1的一些抑制剂并不能很好地解决肿瘤的耐药问题。近年来研究发现,细胞自噬直接参与肿瘤多药耐药,联合调控MDR1的表达及肿瘤细胞自噬水平将可能改善肿瘤细胞的多重耐药。该文主要从多药耐药基因MDR1的表达调控及细胞自噬水平改变两方面综述肿瘤细胞多重耐药机制的研究进展。 展开更多
关键词 肿瘤多药耐药 机制 耐药蛋白 自噬
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Management of bacterial and fungal infections in end stage liver disease and liver transplantation:Current options and future directions 预览
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作者 Elda Righi 《世界胃肠病学杂志:英文版》 SCIE CAS 2018年第38期4311-4329,共19页
Patients with liver cirrhosis are susceptible to infections due to various mechanisms,including abnormalities of humoral and cell-mediated immunity and occurrence of bacterial translocation from the intestine.Bacteria... Patients with liver cirrhosis are susceptible to infections due to various mechanisms,including abnormalities of humoral and cell-mediated immunity and occurrence of bacterial translocation from the intestine.Bacterial infections are common and represent a reason for progression to liver failure and increased mortality.Fungal infections,mainly caused by Candida spp.,are often associated to delayed diagnosis and high mortality rates.High level of suspicion along with prompt diagnosis and treatment of infections are warranted.Bacterial and fungal infections negatively affect the outcomes of liver transplant candidates and recipients,causing disease progression among patients on the waiting list and increasing mortality,especially in the early posttransplant period.Abdominal,biliary tract,and bloodstream infections caused by Gram-negative bacteria[e.g.,Enterobacteriaceae and Pseudomonas aeruginosa(P.aeruginosa)]and Staphylococcus spp.are commonly encountered in liver transplant recipients.Due to frequent exposure to broad-spectrum antibiotics,invasive procedures,and prolonged hospitalizations,these patients are especially at risk of developing infections caused by multidrug resistant bacteria.The increase in antimicrobial resistance hampers the choice of an adequate empiric therapy and warrants the knowledge of the local microbial epidemiology and the implementation of infection control measures.The main characteristics and the management of bacterial and fungal infections in patients with liver cirrhosis and liver transplant recipients are presented. 展开更多
关键词 LIVER cirrhosis LIVER transplant RECIPIENTS BACTERIAL INFECTIONS Fungal INFECTIONS MULTIDRUG resistant organisms MANAGEMENT
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多药耐药相关蛋白4过表达对脂多糖诱导血管内皮高渗透性的影响及其机制 被引量:1
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作者 夏文芳 张桓铭 +2 位作者 郑颜磊 周青山 苏镔 《中华危重病急救医学》 CSCD 北大核心 2017年第7期608-612,共5页
目的 探讨多药耐药相关蛋白4(MRP4)基因过表达对脂多糖(LPS)诱导大鼠肺微血管内皮细胞(PMVECs)渗透性的影响及其分子机制.方法 体外培养PMVECs细胞,待细胞传至3~6代后分为3组:LPS组无血清培养基培养24 h后,用10μg/mL LPS刺激细... 目的 探讨多药耐药相关蛋白4(MRP4)基因过表达对脂多糖(LPS)诱导大鼠肺微血管内皮细胞(PMVECs)渗透性的影响及其分子机制.方法 体外培养PMVECs细胞,待细胞传至3~6代后分为3组:LPS组无血清培养基培养24 h后,用10μg/mL LPS刺激细胞;Ad-shRNA组用腺病毒空白载体转染细胞2 h,无血清培养基培养24 h后,用10μg/mL LPS刺激细胞;Ad-MRP4组用携带MRP4的重组腺病毒载体转染细胞2 h,无血清培养基培养24 h后,用10μg/mL LPS刺激细胞.于LPS刺激2、6、12、24 h采用Transwell小室法检测单层细胞渗透性;采用酶联免疫吸附试验(ELISA)检测细胞内环磷酸腺苷(cAMP)水平;激光共聚焦荧光显微镜下观察细胞内纤维型肌动蛋白(F-actin)形态及分布情况.于LPS刺激12 h收集细胞,采用蛋白质免疫印迹试验(Western Blot)检测PMVECs中MRP4、β-连环蛋白(β-catenin)、血管内皮-钙黏蛋白(VE-cad)和紧密连接蛋白(ZO-1)的表达水平.结果 ①LPS刺激后PMVECs细胞渗透性及细胞内cAMP水平逐渐增加,12 h达到高峰,24 h开始下降.用携带MRP4的重组腺病毒载体转染PMVECs后,细胞渗透性较LPS组及Ad-shRNA组显著增加〔12 h渗透性(A值):1.88±0.06比1.12±0.17、1.10±0.18〕,细胞内cAMP水平显著降低〔12 h cAMP(μg/L):2.39±0.02比2.97±0.01、3.00±0.02,均P〈0.05〕;而LPS组与Ad-shRNA组各时间点各指标差异均无统计学意义(均P〉0.05).② 激光共聚焦荧光显微镜下显示,3组细胞均出现F-actin重构、应力纤维形成,但Ad-MRP4组细胞破坏程度较LPS组和Ad-shRNA组更加严重.③ 与LPS组和Ad-shRNA组比较,Ad-MRP4组PMVECs中MRP4蛋白表达显著上调(灰度值:0.76±0.03比0.44±0.02、0.43±0.02,均P〈0.05),β-catenin、VE-cad和ZO-1蛋白表达显著下调〔β-catenin(灰度值):0.14±0.03比0.23±0.04、0.23±0.03;VE-cad(灰度值):0.21±0.01比0.34±0.02、0.35±0.04;ZO-1(灰度值):0.14±0.02比0.37±0. 展开更多
关键词 脂多糖 多药耐药性关蛋白4 内皮通透性 环磷酸腺苷 MULTIDRUG resistance PROTEIN 4
Isolation and Identification of Serotype O101 Bovine Pathogenic Escherichia coli with Multidrug Resistance 预览
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作者 Li Shuguang Liu Xiaoyun +4 位作者 Wang Yumao Li Feng Lin Chuwen Shen Zhiqiang Li Jinlin 《动物与饲料科学:英文版》 CAS 2017年第5期303-305,共3页
[Objective] The paper was to isolate and identify a multidrug resistance bovine pathogenic Escherichia coli. [Method] The dead cases of calf diarrhea were collected from a large scale beef cattle farm, and the isolate... [Objective] The paper was to isolate and identify a multidrug resistance bovine pathogenic Escherichia coli. [Method] The dead cases of calf diarrhea were collected from a large scale beef cattle farm, and the isolated pathogen was conducted molecular identification, serological identification, drug sensitivity test, and mice pathogenicity test, respectively. Targeted therapy was undertaken thereafter to herds. [Result] One strain of bovine pathogenic E. coli, serotype O101 with strong multidrug resistance and high pathogenicity to mice, was successfully isolated. It was used to develop sensitive drug for timely treating follow up diarrhea calves, and successfully controlled calf diarrhea in the farm. [Conclusion]The results provide a basis for effective prevention and control of bovine colibacillosis. 展开更多
关键词 CALF DIARRHEA ESCHERICHIA coli MULTIDRUG resistance Clinical treatment
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Liver transplantation and the management of progressive familial intrahepatic cholestasis in children 预览
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作者 Ashley Mehl Humberto Bohorquez +2 位作者 Maria-Stella Serrano Gretchen Galliano Trevor W Reichman 《世界移植杂志》 2016年第2期278-290,共13页
Progressive familial intrahepatic cholestasis(PFIC)is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children.The accumulation of bile re... Progressive familial intrahepatic cholestasis(PFIC)is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children.The accumulation of bile results in progressive liver damage,and if left untreated leads to end stage liver disease and death.Patients often present with worsening jaundice and pruritis within the first few years of life.Many of these patients will progress to end stage liver disease and require liver transplantation.The role and timing of liver transplantation still remains debated especially in the management of PFIC1.In those patients who are appropriately selected,liver transplantation offers an excellent survival benefit.Appropriate timing and selection of patients for liver transplantation will be discussed,and the short and long term management of patients post liver transplantation will also be described. 展开更多
关键词 PEDIATRIC liver transplant Progressive FAMILIAL INTRAHEPATIC CHOLESTASIS FAMILIAL INTRAHEPATIC CHOLESTASIS PROTEIN 1 CHOLESTASIS Multidrug resistance PROTEIN 3 PEDIATRIC JAUNDICE Bile salt excretion PROTEIN
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Association between infections caused by multidrug-resistant gram-negative bacteria and mortality in critically ill patients 预览
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作者 Elisabeth Paramythiotou Christina Routsi 《世界重症医学杂志》 2016年第2期111-120,共10页
The incidence of gram-negative multidrug-resistant(MDR)bacterial pathogens is increasing in hospitals and particularly in the intensive care unit(ICU)setting.The clinical consequences of infections caused by MDR patho... The incidence of gram-negative multidrug-resistant(MDR)bacterial pathogens is increasing in hospitals and particularly in the intensive care unit(ICU)setting.The clinical consequences of infections caused by MDR pathogens remain controversial.The purpose of this review is to summarize the available data concerning the impact of these infections on mortality in ICU patients.Twenty-four studies,conducted exclusively in ICU patients,were identified through PubMed search over the years 2000-2015.Bloodstream infection was the only infection examined in eight studies,respiratory infections in four and variable infections in others.Comparative data on the appropriateness of empirical antibiotic treatment were provided by only seven studies.In ten studies the presence of antimicrobial resistance was not associated with increased mortality;on the contrary,in other studies a significant impact of antibiotic resistance on mortality was found,though,sometimes,mediated by inappropriate antimicrobial treatment.Therefore,a direct association between infections due to gram-negative MDR bacteria and mortality in ICU patients cannot be confirmed.Sample size,presence of multiple confounders and other methodological issues may influence the results.These data support the need for further studies to elucidate the real impact of infections caused by resistant bacteria in ICU patients. 展开更多
关键词 Critically ILL patients INFECTIONS MULTIDRUG resistance GRAM-NEGATIVE pathogens MORTALITY
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多药耐药蛋白1在人与小鼠角膜及不同糖尿病病程小鼠角膜中的表达 预览
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作者 辛萌 代春华 张玉茹 《滨州医学院学报》 2016年第3期169-172,共4页
目的本文拟以外排转运蛋白中的多药耐药蛋白1(multi-drug resistance protein 1,MDR1)为代表,研究其在人角膜上皮、C57BL/6小鼠角膜上皮、C57BL/6小鼠腹腔注射链尿佐菌素(Streptozocin,STZ)诱导Ⅰ型糖尿病动物模型不同糖尿病病程角... 目的本文拟以外排转运蛋白中的多药耐药蛋白1(multi-drug resistance protein 1,MDR1)为代表,研究其在人角膜上皮、C57BL/6小鼠角膜上皮、C57BL/6小鼠腹腔注射链尿佐菌素(Streptozocin,STZ)诱导Ⅰ型糖尿病动物模型不同糖尿病病程角膜上皮中的表达与分布差异,为眼部外排转运蛋白表达与功能调控研究提供基础数据。方法 PCR、免疫组化/免疫荧光、Western Blotting分别从基因与蛋白水平检测各组织内MDR1的表达,同时还检测了人角膜上皮细胞系(HCEC)中MDR1的表达。结果在基因水平,MDR1在人角膜上皮中表达仅为(9.11±2.33)Qty·ng-1 RNA,HCEC则未检测到表达,MDR1在C57BL/6小鼠角膜上皮中则有较强的表达,但是与正常组相比,STZ小鼠角膜上皮中的MDR1表达在建模4周、12周和24周均呈现显著下降(P〈0.05),正常小鼠和STZ模型小鼠随着鼠龄的增长,角膜上皮中的MDR1基因表达也均呈现出显著下降的趋势(P〈0.05)。Western Blotting结果表明MDR1在人角膜上皮组织内表达,但表达量很低,MDR1在HCEC细胞内明显表达,在Ⅰ型糖尿病动物模型小鼠角膜上皮中表达但是变化趋势同基因表达变化趋势一致;免疫组化/荧光检测结果表明MDR1人角膜全层部分上皮细胞细胞核核周表达,在HCEC细胞中有表达,其表达部位均位于整个胞浆,MDR1在小鼠角膜组织内表达,且与空白组相比,STZ组小鼠角膜MDR1表达下降。结论人角膜上皮组织中MDR1表达与C57BL/6小鼠存在较大差异,且随着鼠龄增长MDR1表达也呈下降趋势,如基于C57BL/6小鼠等动物进行MDR1外排转运蛋白的研究和调控有可能偏离人组织的实际表达情况而得到错误结论。 展开更多
关键词 外排转运蛋白 多药耐药蛋白1 角膜
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