Maize seedling blight caused by Fusarium verticillioides is a widely occurring maize disease,but the genetics and mechanisms of resistance are not well understood.In this study,GWAS performed by MLM and 3VmrMLM identi...Maize seedling blight caused by Fusarium verticillioides is a widely occurring maize disease,but the genetics and mechanisms of resistance are not well understood.In this study,GWAS performed by MLM and 3VmrMLM identified 40 and 20 QTNs,associated with seedling blight resistance.These methods identified 49 and 36 genes,respectively.Functional verification of candidate gene ZmSBR1 identified by both methods showed that the resistance of a mutant line to seedling blight decreased by 0.37 grade points after inoculation with F.verticillioides,compared with the WT.The length of the stem rot lesion caused by F.verticillioides increased by 86%in mutant seedlings,and the relative length of the adult plant stalk rot increased by 35%in mutant plants compared to the wild type after inoculation with Fusarium graminearum.Transcriptome analysis showed that expression of defense-related genes after inoculation was down-regulated in the mutant compared to the wild type,synthesis of secondary metabolites associated with resistance was reduced,and the immune response triggered by PAMP decreased,resulting in decreased resistance of mutant maize seedlings.Candidate gene association analysis showed that most maize inbred lines carried the susceptible haplotype.A functional PCR marker was developed.The results demonstrated that ZmSBR1 conferred resistance to multiple Fusarium diseases at the seedling and adult growth stages and had important application value in breeding.展开更多
The granular carbides formed from hot deformation in multiple alloying wear resistant cast iron were studied through the observation by means of optical microscope, SEM and TEM. The experimental results show that carb...The granular carbides formed from hot deformation in multiple alloying wear resistant cast iron were studied through the observation by means of optical microscope, SEM and TEM. The experimental results show that carbides with large size are formed from original short rhabdoid carbides existing in cast, those with small size directly nucleate in the matrix. Carbides with the size between the above are formed from precipitation induced by hot deformation. The bigger the deformation is, the larger the number of microsized granular carbides is. The mechanisms of nucleation and growth of granular carbides and the function of RE were discussed.展开更多
Summary: The expression and functional activity of multiple drug resistance (MDR1) gene in human normal bone marrow CD34+ cells was observed. Human normal bone marrow CD34+ cells were enriched with magnetic cell sorti...Summary: The expression and functional activity of multiple drug resistance (MDR1) gene in human normal bone marrow CD34+ cells was observed. Human normal bone marrow CD34+ cells were enriched with magnetic cell sorting (MACS) system, and then liposome-mediated MDR1 gene was transferred into bone marrow CD34+ cells. Fluorescence-activated cell sorter was used to evaluate the expression and functional activity of P-glycoprotein (P-gp) encoded by MDR1 gene. It was found that the purity of bone marrow CD34+ cells was approximately (91±4.56) % and recovery rate was (72.3±2.36) % by MACS. The expression of P-gp in the transfected CD34+cells was obviously higher than that in non-transfected CD34+ cells. The amount of P-gp in non-transfected CD34+ cells was (11.2±2.2) %, but increased to (23.6±2.34) % 48 h after gene transfection (P<0.0l). The amount of P-gp was gradually decreased to the basic level one week later. The accumulation and extrusion assays showed that the overexpression of P-gp could efflux Rh-123 out of cells and there was low fluorescence within the transfected cells. The functional activity of P-gp could be inhibited by 10 μg/ml verapamil. It was suggested that the transient and highly effective expression and functional activity of P-gp could be obtained by liposome-mediated MRD1 transferring into human normal bone marrow CD34+ cells.展开更多
BACKGROUND: Multidrug resistance is a major obstacle in cancer chemotherapy. We examined whether the antisense RNA of multidrug resistance gene 1 (mdr1) could reverse multidrug resistance in the human hepatocellular c...BACKGROUND: Multidrug resistance is a major obstacle in cancer chemotherapy. We examined whether the antisense RNA of multidrug resistance gene 1 (mdr1) could reverse multidrug resistance in the human hepatocellular carcinoma (HCC) cell line SMMC7721/ADM. METHODS: The recombinant adenoviruses pAdEasy- GFP-ASmdr1 product was produced by the adenoviral vector AdEasy system, which can express antisense RNA against the mdr1 gene. Following that, the recombinant adenovirus was transfected into the P-glycoprotein- producing multidrug resistance cell line, SMMC7721/ADM human HCC cells resistant to adriamycin (ADM) and daunorubicin (DNR). In order to investigate the reversal of multidrug resistance phenotype, we measured the expression of mdr1 mRNA by RT-PCR and the production of P-glycoprotein by flow cytometry. The sensitivities for ADM and DNR SMMC7721/ADM cells were examined by [3-(4, 5-dimethylthi-azol-2-yl)-2,5 diphenyl-terazolium bromide] (MTT) analysis. RESULTS: The low-level expression of mdr1 mRNA and P-glycoprotein production were observed in parental sensitive cells SMMC/7721 in addition to the overexpressionof mdr1 mRNA and P-glycoprotein in SMMC7721/ADM cells. The transfection of antisense-RNA into SMMC7721/ ADM cells resulted in decreases of mdr1 mRNA and P-glycoprotein, but increase of drug sensitivities. The sensitivities of transfected SMMC7721/ADM cells to ADM and DNR in IC50 reduced by 31.25% and 62.96% respectively. CONCLUSIONS: Mdr1 antisense RNA can increase the sensitivities of SMMC7721/ADM cells to anticancer drug by decreasing the expression of the mdr1 gene and inhibiting P-glycoprotein expression. This strategy may be applicable to cancer patients with P-glycoportein mediated multidrug resistance.展开更多
BACKGROUND: Cholecyst cholesterol lithiasis is a common disease of the digestive system; however, the cause of lithogenesis is still unclear. Although bile salt export pump (BSEP), multidrug resistance protein 2 (MRP2...BACKGROUND: Cholecyst cholesterol lithiasis is a common disease of the digestive system; however, the cause of lithogenesis is still unclear. Although bile salt export pump (BSEP), multidrug resistance protein 2 (MRP2), and multiple drug resistance 3 (MDR3 ) are 3 well-known transporting proteins, their effect on lithogenesis has not been elucidated. This study was undertaken to examine the relationship between BSEP, MRP2, MDR3, and cholesterol calculus formation. METHODS: Liver tissue specimens were taken from 20 patients with cholesterol calculus and from 10 patients with normal liver. mRNA and protein expressions of BSEP, MRP2, and MDR3 were determined by reverse tran-scriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively. This study was approved by the ethics committee of China Medical University and informed consent was obtained from all patients. RESULTS: mRNA and protein expressions of BSEP, MRP2, and MDR3 were significantly down-regulated in the liver tissue of the patients with cholesterol calculus compared with normal liver tissue of the controls. CONCLUSION: The down-regulation of BSEP, MRP2, and MDR3 may be correlated with the formation of cholesterol calculus.展开更多
BACKGROUND: The most common mechanisms of mul- tidrug resistance (MDR) in cancer cells is the expression of an energy-dependent exfflux pump. P-glycoprotein (P-gp) encoded by MDR1 gene and multidrug associated protein...BACKGROUND: The most common mechanisms of mul- tidrug resistance (MDR) in cancer cells is the expression of an energy-dependent exfflux pump. P-glycoprotein (P-gp) encoded by MDR1 gene and multidrug associated protein (MRP) are well known proteins associated with MDR. In human cancers, the MDR1 gene expression is common in patients with intrinsic and acquired MDR. It is a major therapeutic problem in cancer chemotherapy. Previously we found that the MDR of HCC is related to MRP gene ex- pression and initiates the intrinsic MDR. The aim of this study is to study the expression of MDR1 gene encoding P-gp and MDR1 mRNA in primary gallbladder carcinoma, and analyze its clinical significance. METHODS: Immunohistochemistry (IHC) S-P method and in situ polymerase chain reaction (ISPCR) were used to detect the expression of P-gp and MDR1 mRNA in 53 cases of untreated primary gallbladder carcinoma and 12 ca- ses of cholecystitis (archival paraffin-embedded tissues). RESULTS: The positive expression rates of P-gp and MDR1 mRNA in the 53 cases and 12 cases were 60.38%, 71.69% and 25.00%, 33.33%, respectively. There was a significant difference between the two groups (P<0.05). The positive expression rate of P-gp and MDRlmRNA were 69.44%, 83.33% and 41.18%, 47.06% respectively in tissues in stage of Nevin against Nevin , (P<0.05). In well, moderately differentiated gallbladder carcinoma tissues, their expressions were 79.49%, 69.23% against 50.00%, 35.71% in low, undifferentiated tissues (P<0.05). CONCLUSIONS: MDR to gallbladder carcinoma is closely related to the intrinsic MDR and it provides an important evidence to reverse the MDR by detection of the MDR1gene. Meanwhile, MDR1 gene expression in gallbladder carcinoma is correlated with some biological characteris- tics , takes part in the carcinogenesis of gallbladder tissues, and acts as a valuable biomarker of prognosis.展开更多
The expression of multidrug resistant proteins in bladder cancer and clinical implication was studied. Expression of multidrug associated protein (MRP), P glycoprotein (P gp), P53 and Bcl 2 proteins were detected ...The expression of multidrug resistant proteins in bladder cancer and clinical implication was studied. Expression of multidrug associated protein (MRP), P glycoprotein (P gp), P53 and Bcl 2 proteins were detected by using immunohistochemical method in 40 specimens of bladder transitional cell carcinoma. The results showed that the positive rate of MRP, P gp, P53 and Bcl 2 was 52.5 %, 57.5 %, 47.5 % and 62.5 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in the grade Ⅰ, Ⅱ and Ⅲ of tumors was 46.3 %, 38.5 %, 38.5 %, 23.1 %; 52.9 %, 39.8 %, 47.1 %, 76.4 %; 60.0 %, 80.0 %, 60.0 %, 90.0 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in 24 primary tumor specimens was 37.5 %, 41.7 %, 33.3 %, 45.8 % and that in 16 cases in recurrent specimens receiving chemotherapy 75.0 %, 81.3 %, 68.8 %, 87.5 % respectively. It was suggested the positive rate of MRP, P gp, P53 and Bcl 2 was increased with the advance of tumor grade. The positive rate of four proteins in all recurrent cases was significantly increased ( P <0.05). The expression of MRP, P gp, P53 and Bcl 2 proteins might be the important factors for chemotherapy failure.展开更多
AIM: To investigate the specific mechanisms of intrinsic and acquired resistance to taxotere (TXT) in pancreatic adenocarcinoma (PAC).METHODS: MTT assay was used to detect the sensitivity of PAC cell line SUIT-2 and ...AIM: To investigate the specific mechanisms of intrinsic and acquired resistance to taxotere (TXT) in pancreatic adenocarcinoma (PAC).METHODS: MTT assay was used to detect the sensitivity of PAC cell line SUIT-2 and its sublines (S-007, S-013, S-020,S-028 and TXT selected SUIT-2 cell line, S2/TXT) to TXT.Mdr1 (P-gp), multidrug resistance associated protein (MRP), lung resistance protein (LRP) and β-tubulin isotype gene expressions were detected by RT-PCR. The functionality of P-gp and MRP was tested using their specific blocker verapamil ( Ver ) and indomethacin ( IMC ),respectively. The transporter activity of P-gp was also confirmed by Rhodamine 123 accumulation assay.RESULTS: S-020 and S2/TXT were found to be significantly resistant to TXT(19 and 9.5-fold to their parental cell line SUIT-2, respectively ). RT-PCR demonstrated strong expression of Mdr1 in these two cell lines, but weaker expression or no expression in other cells lines. MRP and LRP expressions were found in most of these cell lines. The TXT-resistance in S2-020 and S2/TXT could be reversed almost completely by Ver, but not by IMC. Flow cytometry showed that Ver increased the accumulation of Rhodamine-123 in these two cell lines. Compared with S-020 and SUIT-2,the levels of β-tubulin isotype II, III expreesions in S-2/TXTwere increased remarkably.CONCLUSION: The both intrinsic and acquired TXT-related drugresistance in these PAC cell lines is mainly mediated by P-gp, but had no relationship to MRP and LRP expressions.The increases of β-tubulin isotype II, III might be collateral changes that occur when the SUIT-2 cells are treated with TXT.展开更多
Multiple drug resistance(MDR)is a tough problem in developing hepatocellular carcinoma(HCC)therapy.Here,we developed TPGS-coated cationic liposomes with Bcl-2 siRNA corona to load doxorubicin(Dox)i.e.,Bcl-2 siRNA/Dox-...Multiple drug resistance(MDR)is a tough problem in developing hepatocellular carcinoma(HCC)therapy.Here,we developed TPGS-coated cationic liposomes with Bcl-2 siRNA corona to load doxorubicin(Dox)i.e.,Bcl-2 siRNA/Dox-TPGS-LPs,to enhance anticancer effect of Dox in HCC-MDR.TPGS i.e.,d-α-tocopheryl polyethylene glycol 1000 succinate,inhibited Pglycoprotein(P-gp)efflux pump and Bcl-2 siRNA suppressed anti-apoptotic Bcl-2 protein.The Bcl-2 siRNA loaded in the liposomal corona was observed under transmission electron microscopy.The stability and hemolysis evaluation demonstrated Bcl-2 siRNA/Dox-TPGSLPs had good biocompatibility and siRNA-corona could protect the liposomal core to avoid the attachment of fetal bovine serum.In drug-resistant cells,TPGS effectively prolonged intracellular Dox retention time and siRNA-corona did improve the internalization of Dox from liposomes.In vitro and in vivo anticancer effect of this dual-functional nanostructure was examined in HCC-MDR Bel7402/5-FU tumor model.MTT assay confirmed the IC50 value of Dox was 20–50 fold higher in Bel7402/5-FU MDR cells than that in sensitive Bel7402 cells.Bcl-2 siRNA corona successfully entered the cytosol of Bel7402/5-FU MDR cells to downregulate Bcl-2 protein levels in vitro and in vivo.Bcl-2 siRNA/Dox-TPGS-LPs showed superior to TPGS-(or siRNA-)linked Dox liposomes in cell apoptosis and cytotoxicity assay in Bel7402/5-FU MDR cells,and 7-fold greater effect than free Dox in tumor growth inhibition of Bel7402/5-FU xenograft nude mice.In conclusion,TPGS-coated cationic liposomes with Bcl-2 siRNA corona had the capacity to inhibit MDR dual-pathways and subsequently improved the anti-tumor activity of the chemotherapeutic agent co-delivered to a level that cannot be achieved by inhibiting a MDR single way.展开更多
Summary: In order to provide a rational research basis for detection of resistance of Neisseria gonorrhoeae to antimierobial hydrophobie agents and study on the resistant mechanism of multiple transferable resistance...Summary: In order to provide a rational research basis for detection of resistance of Neisseria gonorrhoeae to antimierobial hydrophobie agents and study on the resistant mechanism of multiple transferable resistance (mtr) efflux system, plasmid pET-28a(+) encoding mtrC gene was constructed and the related target protein was expressed in Escherichia colt (E. cold DE3. The fragments of mtrC gene of Neisseria gonorrhoeae from the standard strains were amplified and cloned into prokaryotic expression plasmid pET-28a(+) with restriction endonuelease to construct recombinant pET-mtrC which was verified by restriction endonuelease and DNA sequencing. The recom- binant was transformed into E. coli DE3 to express the protein mtrC induced by IPTG. The results showed mtrC DNA fragment was proved correct through restriction endonuelease and DNA sequencing. hs sequence was 99.5 % homologus to that published on GeneBank (U14993). A 48.5 kD fusion protein which was induced by IPTG was detected by SDS-PAGE. It was concluded that the construction of prokaryotic expression plasmid of mtrC protein of Neisseria gonorrhoeae was correct and the fusion protein was successively expressed in E. coli.展开更多
The multi-radiation of X-rays was investigated with special attention to their energy spectrum in a Mather-type plasma focus device (operated with argon gas). The analysis is based on the effect of anomalous resista...The multi-radiation of X-rays was investigated with special attention to their energy spectrum in a Mather-type plasma focus device (operated with argon gas). The analysis is based on the effect of anomalous resistances. To study the energy spectrum, a four-channel diode X-ray spectrometer was used along with a special set of filters. The filters were suitable for detection of medium range X-rays as well as hard X-rays with energy exceeding 30 keV. The results indicate that the anomalous resistivity effect during the post pinch phase may cause multi-radiation of X-rays with a total duration of 300 ± 50 ns. The significant contribution of Cu-Kα was due to the medium range X-rays, nonetheless, hard X-rays with energies greater than 15 keV also participate in the process. The total emitted X-ray energy in the forms of Cu-K and Cu-K/3 was around 0.14 ± 0.02 (J/Sr) and 0.04 ±0.01 (J/Sr), respectively. The total energy of the emitted hard X-ray (〉 15 keV) was around 0.12± 0.02 (J/Sr).展开更多
Theperformanceof a structurally dissipating rock-shed(SDR)depends largely onthecapacityofitsenergy dissipators.At present,mostenergy dissipatorsare made of metals,which dissipateenergy by unrecoverable plastic deforma...Theperformanceof a structurally dissipating rock-shed(SDR)depends largely onthecapacityofitsenergy dissipators.At present,mostenergy dissipatorsare made of metals,which dissipateenergy by unrecoverable plastic deformation.Therefore,they are not able to recover their energy-dissipation capacity after deformation under rockfall impact.However,a rockfall usually disintegrates into pieces when it rolls down from a higher position and results in multiple rockfall impacts.An energy dissipator with self-recovery capability is therefore more suitable for ensuring the safety of SDRs.Replacing metal with polyurethane(a hyperelastic material with remarkable self-recovery capability)can provide self-recovery capability for energy dissipators,making them more suitable for resisting multiple rockfall impacts.In this work,polyurethane was manufactured into twotypes ofenergy dissipators:cylindrical and cubical.Full-scale falling rock impact testsand dynamic numerical simulationswereconducted to study the mechanical response of the energy dissipators.In addition,in order to ensure the accuracy of the simulation,the dynamic mechanical properties of the polyurethanewere tested and its dynamic constitutive model was established.The experimental and simulation tests have clarified the advantages of the polyurethane energy dissipator.We also summarized the practical considerations in the design of energy dissipators.展开更多
Objective: To investigate the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) and the relationship with cell cycle profiles in ovarian cancer SK-OV-3ip1 multicellular aggregates. ...Objective: To investigate the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) and the relationship with cell cycle profiles in ovarian cancer SK-OV-3ip1 multicellular aggregates. Methods: Liquid overlay system was employed to obtain multicellular aggregates. Expression of P-gp and MRP was detected with flow cytometry (FCM). Outer, intermediate and inner cells from multicellular aggregates were collected by layer-trypsinized method. Cell cycle profiles were also analyzed by FCM. Results: Compared with control cells, no expression of P-gp and MRP was detected in monolyer cells (P=0.128 and P=0.604), but expression of P-gp and MRP in aggregate cells was significantly elevated (P<0.01). P-gp expression in every layer cells was also obviously increased (P<0.01). Furthermore, P-gp expression in every layer cells was also obviously increased (P=0.071). Tendency to increased G0–G1 phase and reduced S phase cells existed from outer through intermediate to inner layers in multicellular aggregates but with no statistical difference. Cell percentages in G2-M phase also had no difference. However, compared with monolayer cells, cells in G0–G1 phase increased and cells in S and G2-M phases lowered significantly in every layer and in the whole multicellular aggregates. Expression elevation of P-gp and MRP was consistent with increased G0–G1 percentage in aggregate cells. Conclusion: Expression of P-gp and MRP increases in cells of SK-OV-3ip1 multicellular aggregates and is consistent with increased G0–G1 percentage, which implies the possible relationship between them and the possible role in multicellular-mediated drug resistance.展开更多
Objective: The objective is to study the antibacterial activity of six medicinal plants against two naso-pharyngeal pathogens and determination of total phenol contents in ethanol extracts of those plants. Methods: Di...Objective: The objective is to study the antibacterial activity of six medicinal plants against two naso-pharyngeal pathogens and determination of total phenol contents in ethanol extracts of those plants. Methods: Different serial concentrations (0.05 g/mL, 0.1 g/mL, 0.2 g/mL, 0.4 g/mL) of ethanolic and acetone extracts of Piper nigrum L. (Piperaceae), Ocimum sanctum Linn., Plectranthus amboinicus L. (Lamiaceae), Ayapana triplinervis M.Vahl. (Asteraceae), Cinnamomum zeylanicum L. (Lauraceae), Allium schoenoprasum Linn. (Liliaceace) were evaluated for the antibacterial activity using disc diffusion method against gram positive Streptococcus pyogenes and gram negative Pseudomonas aeruginosa. The extracts were prepared from different parts of the plants. The total phenol content was estimated using folin-ciocaltau reagent in catechol equivalents. Results: Majority of the extracts had inhibitory effect against the tested bacteria at different concentrations. In ethanol extracts, Plectranthus amboinicus exhibited the maximum zone of inhibition (14 mm) at 0.05 g/mL concentration against Streptococcus pyogenes, and Ocimum sanctum showed highest zone of bacterial inhibition (19 mm) at 0.05 g concentration against Pseudomonas aeruginosa. In acetone extracts, Piper nigrum had the maximum zone of bacterial inhibition (17 mm) in 0.4 g/mL concentration against Streptococcus pyogenes and Cinnamomum zeylanicum and Allium schoenoprasum exhibited the highest zone of bacterial inhibition (0.4 g/mL) against Pseudomonas aeruginosa. The ethanol extract of Plectranthus amboinicus contained the highest amount of phenol (0.8 mg/mL) and Allium schoenoprasum contained the lowest amount (0.62 mg/mL). In acetone, Cinnamomum zeylanicum contained highest phenol content (0.78 mg/mL). Conclusion: All these investigations pave way to the molecular modeling of the lead phyto compounds present in the studied plants, and also in finding out their biochemical action in various metabolic pathways and reactions of infection.展开更多
In order to investigate the relationship between the expression of cyclin A and drug resistance in adult patients with acute leukemia (AL), the mRNA expression of cyclin A, mdr1, TopⅡ α , bcl-2 was detected in 6...In order to investigate the relationship between the expression of cyclin A and drug resistance in adult patients with acute leukemia (AL), the mRNA expression of cyclin A, mdr1, TopⅡ α , bcl-2 was detected in 64 adult patients with AL and 20 normal controls by semi-reverse transcription polymerse chain reaction (semi-RT-PCR). It was found that the cyclin A and TopⅡ α mRNA expression levels in drug resistant group were significantly lower than in sensitive group ( P <0.01). Under the same experimental condition no cyclin A mRNA expression was detectable in all normal controls. The mdr1 and bcl-2 mRNA expression levels in resistant group were significantly higher than in sensitive group ( P <0.01). cyclin A and TopⅡ α gene expression levels were closely correlated ( r s =+0.794, P=0.000, n =64) in all AL patients, but cyclin A was not correlated with mdr1 and bcl-2 gene expression levels. In drug resistant group there was a negative correlation between the gene expression levels of cyclin A and mdr1 ( r s =-0.337, P=0.029 ). The 10 AL patients with positive lower expression of both cyclin A and TopⅡ α were all resistant to drugs. Logistic regression of Binary analysis showed the correlation between the lower expression of cyclin A and drug resistance. It was concluded that lower expression of cyclin A gene might be an unfavorable prognostic factor for patients with AL, and detection of both cyclin A and TopⅡ α gene expression would predict drug resistance in AL patients.展开更多
Background: Urinary tract infection is a common disease in Somaliland society. The predominant causative organism of Urinary tract infection is Escherichia coli. This research studies antibiotic resistance of uropatho...Background: Urinary tract infection is a common disease in Somaliland society. The predominant causative organism of Urinary tract infection is Escherichia coli. This research studies antibiotic resistance of uropathogenic E. coli in patients of Hargeisa Group Hospital. The study selected commonly prescribed antibiotics for urinary tract infection treatment. Methodology: Urine samples of patients were cultured to isolate causative organisms of the urinary tract infection. Chromo-agar media, CLED, and biochemical tests are applied to identify the type of bacteria. Antibiotic reactions to E. coli bacteria are measured to differentiate between sensitive and resistant drugs with the guidance of the Clinical and Laboratories Standard Institute (CLSI). Kirby Bauer disc diffusion method is applied to assess antimicrobial activity against E. coli. Data of patients such as age, sex, symptoms of UTI, previous UTI infection, and history of antibiotic use were recorded. SPSS and Microsoft Excel are applied to analyze and interpret data. Results: The predominant organism that caused urinary tract infection was Escherichia coli (55%), Klebsiella spp (15%), Candida spp (15%), Enterococcus spp (10%), Staph spp 2.5%, and Pseudomonas spp 2.5% while other 55% were negative. The study assessed antibiotic resistance of E. coli, which reported resistance to Tetracycline at (70%), Ampicillin (64%), and Cotrimoxazole (61%). The bacteria showed moderate resistance to Ceftriaxone (43.5%), Nalidixic acid (43%), and Ciprofloxacin (36%). The bacteria are sensitive to Amikacin (100%), Nitrofurantoin (96%), Levofloxacin (73%) and gentamicin (74%). Conclusion: The overall incidence of antibiotic resistance to E. coli is high because the bacteria show a percentage of resistance to each antibiotic except Amikacin which gives (100%) sensitivity. The research recommends public awareness of the risks associated with antibiotic use and periodic evaluation of antibiotic resistance to accomplish better managing urinary tract infections.展开更多
Natural alleles controlling multiple disease resistances (MDR) are valuable for crop breeding. However, only one MDR gene have been cloned in maize, and molecular mechanisms of MDR are not clear. By map-based cloning,...Natural alleles controlling multiple disease resistances (MDR) are valuable for crop breeding. However, only one MDR gene have been cloned in maize, and molecular mechanisms of MDR are not clear. By map-based cloning, we have cloned a teosinte-derived allele of a resistance gene, Mexicana lesion mimic 1 (ZmMM1), which has a lesion mimic phenotype and confers resistance to northern leaf blight (NLB), gray leaf spot (GLS) and southern corn rust (SCR). Strong MDR conferred by the teosinte allele is linked with the polymorphisms in the 3' untranslated region of the ZmMM1 gene that cause increased accumulation of ZmMM1 protein. ZmMM1 acts as a transcription repressor and negatively regulates transcription of specific target genes including ZmMM1-target gene 3 (ZmMT3), which functions as a negative regulator of plant immunity and associated cell death. The successful isolation of the ZmMM1 resistance gene will help not only in developing broad-spectrum and durable disease resistance but also in understanding the molecular mechanisms underlying MDR.展开更多
Background The multidrug resistance (MDR) associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell (HCC) patients treated w...Background The multidrug resistance (MDR) associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell (HCC) patients treated with chemotherapy. Our study was to establish a stable HCC MDR cell line where a de novo acquisition of multidrug resistance specifically related to overexpression of a transgenic mdr1. Methods The 4.5-kb mdrl cDNA obtained from the plasmid pHaMDR1-1 was cloned into the PCl-neo mammalian expression vector, later was transferred by liposome to human hepatocarcinoma cell line HepG2. Then the transfected HepG2 cells resisting G418 were clustered and cultured and the specific fragment of mdr1 cDNA, mRNA and the P-glycoprotein (Pgp) in these HepG2 cells were detected by PCR, RT-PCR and flow cytometry, respectively. The accumulation of the daunorubicin was determinated by flow cytometry simultaneously. The nude mice model of grafting tumour was established by injecting subcutaneously HepG2/mdr1 cells in the right axilla. When the tumour diameter reached 5 mm, adriamycin was injected into peritoneal cavity. The size and growth inhibition of tumour were evaluated. Results The mdr1 expression vector was constructed successfully and the MDR HCC line HepG2/mdr1 developed. The PCR analysis showed that the specific fragment of mdrl cDNA in HepG2/mdr1 cells, but not in the control group HepG2 cells. Furthermore, the content of the specific fragment of mdr1 mRNA and Pgp expression in HepG2/mdr1 cells were (59.7±7.9)% and (12.28±2.09)%, respectively, compared with (16.9±3.2)% and (3.07±1.06)% in HepG2 cells. In the nude mice HCC model, the tumour genes of both groups were identified. After ADM therapy, the mean size of HepG2 cell tumours was significantly smaller than HepG2/mdr1 cell tumours. Conclusion The approach using the transfer of mdr1 cDNA may be applicable to the development of MDR hepatocarcinoma cell line, whose MDR mechanism is known. This would provide the experimental basis of MDR research.展开更多
Background Gram-positive bacteria such as Staphylococcus aureus have been a common cause of infection among liver transplant (LT) recipients in recent decades. The understanding of local epidemiology and its evolvin...Background Gram-positive bacteria such as Staphylococcus aureus have been a common cause of infection among liver transplant (LT) recipients in recent decades. The understanding of local epidemiology and its evolving trends with regard to pathogenic spectra and antibiotic susceptibility is beneficial to prophylactic and empiric treatment for LT recipients. This study aimed to investigate etiology, timing, antibiotic susceptibility and risk factors for multidrug resistant (MDR) Gram-positive coccal bacteremia after LT.Methods A cohort analysis of prospectively recorded data was performed to investigate etiologies, timing, antibiotic susceptibility and risk factors for MDR Gram-positive coccal bacteremia in 475 LT recipients.Results In 475 LT recipients in the first six months after LT, there were a total of 98 episodes of bacteremia caused by Gram-positive cocci in 82 (17%) patients. Seventy-five (77%) bacteremic episodes occurred in the first post-LT month.The most frequent Gram-positive cocci were methicillin-resistant coagulase-negative staphylococcus (CoNS, 46 isolates),methicillin-resistant Staphylococcus aureus (MRSA, 13) and enterococcus (34, E. faecium 30, E. faecalis 4). In all Gram-positive bacteremic isolates, 59 of 98 (60%) were MDR. Gram-positive coccal bacteremia and MDR Gram-positive coccal bacteremia predominantly occurred in patients with acute severe exacerbation of chronic hepatitis B and with fulminant/subfulminant hepatitis. Four independent risk factors for development of bacteremia caused by MDR Gram-positive coccus were: LT candidates with encephalopathy grades Ⅱ-Ⅳ (P=0.013, OR: 16.253, 95% CI:1.822-144.995), pre-LT use of empirical antibiotics (P=0.018, OR: 1.029, 95% CI: 1.002-1.057), post-LT urinary tract infections (P 〈0.001, OR: 20.340, 95% CI: 4.135-100.048) and abdominal infection (P=0.004, OR: 2.820, 95% CI:1.122-10.114). The main infectious manifestations were coinfections due to gram-positive cocci and gram-negative bacilli.Conclusions Methicillin-resistant CoNS and enterococci are predominant pathogens among LT recipients with Gram-positive coccal bacteremia. Occurrences of Gram-positive coccal bacteremia may be associated with the severity of illness in the perioperative stage.展开更多
Background The prognosis is poor for patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). The main reason for poor prognosis is multidrug resistance (MDR), for which the main phenotype is overexpres...Background The prognosis is poor for patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). The main reason for poor prognosis is multidrug resistance (MDR), for which the main phenotype is overexpression of P-glycoprotein (P-gp). This study explored the efficacy of ligustrazine as a salvage agent in patients with relapsed or refractory NHL, and the relationship to P-gp expression. Methods Sixty patients were randomized to a reversal agent group, receiving ligustrazine plus chemotherapy, and a control group, receiving chemotherapy alone. Flow cytometry was performed to evaluate P-gp expression. Results In the 56 patients we were able to evaluate, there was no statistically significant difference in progression-free survival (PFS) in the two groups (P=0.0651), but the reversal agent group had a higher overall response rate (ORR) than did the control group (P=0.048). Forty-one of 56 patients had P-gp(+) tumor cells. Among these patients, six of eighteen patients in the reversal agent group and in the control group had complete remission or complete remission/unconfirmed (CR+CRu) reflecting a significant advantage in the reversal agent group (P=0.048). Patients with P-gp(+) tumor cells in the reversal agent group had a higher overall response rate (ORR) than did the control group (11/18 vs. 6/23, P=0.024). Kaplan-Meier Survival curve and log-rank test demonstrated that patients with P-gp(+) tumor cells in the reversal agent group had longer progression-free survival than did the control group (P=0.0464). A small number of patients who received ligustrazine had a decrease in blood pressure. Conclusion Ligustrazine as a salvage agent in combination with chemotherapy can elevate response rate, prolong PFS with manageable toxicity, and correlate with P-gp expression in relapsed or refractory NHL.展开更多
基金supported by grants from the National Key Research and Development Program Project of China(2022YFD1201803)Research on Resistance Genetics of Maize Root Rot Disease,State Key Laboratory of Agronomy College,Henan Agricultural University,China(39990073/111)。
文摘Maize seedling blight caused by Fusarium verticillioides is a widely occurring maize disease,but the genetics and mechanisms of resistance are not well understood.In this study,GWAS performed by MLM and 3VmrMLM identified 40 and 20 QTNs,associated with seedling blight resistance.These methods identified 49 and 36 genes,respectively.Functional verification of candidate gene ZmSBR1 identified by both methods showed that the resistance of a mutant line to seedling blight decreased by 0.37 grade points after inoculation with F.verticillioides,compared with the WT.The length of the stem rot lesion caused by F.verticillioides increased by 86%in mutant seedlings,and the relative length of the adult plant stalk rot increased by 35%in mutant plants compared to the wild type after inoculation with Fusarium graminearum.Transcriptome analysis showed that expression of defense-related genes after inoculation was down-regulated in the mutant compared to the wild type,synthesis of secondary metabolites associated with resistance was reduced,and the immune response triggered by PAMP decreased,resulting in decreased resistance of mutant maize seedlings.Candidate gene association analysis showed that most maize inbred lines carried the susceptible haplotype.A functional PCR marker was developed.The results demonstrated that ZmSBR1 conferred resistance to multiple Fusarium diseases at the seedling and adult growth stages and had important application value in breeding.
文摘The granular carbides formed from hot deformation in multiple alloying wear resistant cast iron were studied through the observation by means of optical microscope, SEM and TEM. The experimental results show that carbides with large size are formed from original short rhabdoid carbides existing in cast, those with small size directly nucleate in the matrix. Carbides with the size between the above are formed from precipitation induced by hot deformation. The bigger the deformation is, the larger the number of microsized granular carbides is. The mechanisms of nucleation and growth of granular carbides and the function of RE were discussed.
文摘Summary: The expression and functional activity of multiple drug resistance (MDR1) gene in human normal bone marrow CD34+ cells was observed. Human normal bone marrow CD34+ cells were enriched with magnetic cell sorting (MACS) system, and then liposome-mediated MDR1 gene was transferred into bone marrow CD34+ cells. Fluorescence-activated cell sorter was used to evaluate the expression and functional activity of P-glycoprotein (P-gp) encoded by MDR1 gene. It was found that the purity of bone marrow CD34+ cells was approximately (91±4.56) % and recovery rate was (72.3±2.36) % by MACS. The expression of P-gp in the transfected CD34+cells was obviously higher than that in non-transfected CD34+ cells. The amount of P-gp in non-transfected CD34+ cells was (11.2±2.2) %, but increased to (23.6±2.34) % 48 h after gene transfection (P<0.0l). The amount of P-gp was gradually decreased to the basic level one week later. The accumulation and extrusion assays showed that the overexpression of P-gp could efflux Rh-123 out of cells and there was low fluorescence within the transfected cells. The functional activity of P-gp could be inhibited by 10 μg/ml verapamil. It was suggested that the transient and highly effective expression and functional activity of P-gp could be obtained by liposome-mediated MRD1 transferring into human normal bone marrow CD34+ cells.
基金This study was supported by the grant from National Natural Science Foundation of China (No: 30170925).
文摘BACKGROUND: Multidrug resistance is a major obstacle in cancer chemotherapy. We examined whether the antisense RNA of multidrug resistance gene 1 (mdr1) could reverse multidrug resistance in the human hepatocellular carcinoma (HCC) cell line SMMC7721/ADM. METHODS: The recombinant adenoviruses pAdEasy- GFP-ASmdr1 product was produced by the adenoviral vector AdEasy system, which can express antisense RNA against the mdr1 gene. Following that, the recombinant adenovirus was transfected into the P-glycoprotein- producing multidrug resistance cell line, SMMC7721/ADM human HCC cells resistant to adriamycin (ADM) and daunorubicin (DNR). In order to investigate the reversal of multidrug resistance phenotype, we measured the expression of mdr1 mRNA by RT-PCR and the production of P-glycoprotein by flow cytometry. The sensitivities for ADM and DNR SMMC7721/ADM cells were examined by [3-(4, 5-dimethylthi-azol-2-yl)-2,5 diphenyl-terazolium bromide] (MTT) analysis. RESULTS: The low-level expression of mdr1 mRNA and P-glycoprotein production were observed in parental sensitive cells SMMC/7721 in addition to the overexpressionof mdr1 mRNA and P-glycoprotein in SMMC7721/ADM cells. The transfection of antisense-RNA into SMMC7721/ ADM cells resulted in decreases of mdr1 mRNA and P-glycoprotein, but increase of drug sensitivities. The sensitivities of transfected SMMC7721/ADM cells to ADM and DNR in IC50 reduced by 31.25% and 62.96% respectively. CONCLUSIONS: Mdr1 antisense RNA can increase the sensitivities of SMMC7721/ADM cells to anticancer drug by decreasing the expression of the mdr1 gene and inhibiting P-glycoprotein expression. This strategy may be applicable to cancer patients with P-glycoportein mediated multidrug resistance.
文摘BACKGROUND: Cholecyst cholesterol lithiasis is a common disease of the digestive system; however, the cause of lithogenesis is still unclear. Although bile salt export pump (BSEP), multidrug resistance protein 2 (MRP2), and multiple drug resistance 3 (MDR3 ) are 3 well-known transporting proteins, their effect on lithogenesis has not been elucidated. This study was undertaken to examine the relationship between BSEP, MRP2, MDR3, and cholesterol calculus formation. METHODS: Liver tissue specimens were taken from 20 patients with cholesterol calculus and from 10 patients with normal liver. mRNA and protein expressions of BSEP, MRP2, and MDR3 were determined by reverse tran-scriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively. This study was approved by the ethics committee of China Medical University and informed consent was obtained from all patients. RESULTS: mRNA and protein expressions of BSEP, MRP2, and MDR3 were significantly down-regulated in the liver tissue of the patients with cholesterol calculus compared with normal liver tissue of the controls. CONCLUSION: The down-regulation of BSEP, MRP2, and MDR3 may be correlated with the formation of cholesterol calculus.
文摘BACKGROUND: The most common mechanisms of mul- tidrug resistance (MDR) in cancer cells is the expression of an energy-dependent exfflux pump. P-glycoprotein (P-gp) encoded by MDR1 gene and multidrug associated protein (MRP) are well known proteins associated with MDR. In human cancers, the MDR1 gene expression is common in patients with intrinsic and acquired MDR. It is a major therapeutic problem in cancer chemotherapy. Previously we found that the MDR of HCC is related to MRP gene ex- pression and initiates the intrinsic MDR. The aim of this study is to study the expression of MDR1 gene encoding P-gp and MDR1 mRNA in primary gallbladder carcinoma, and analyze its clinical significance. METHODS: Immunohistochemistry (IHC) S-P method and in situ polymerase chain reaction (ISPCR) were used to detect the expression of P-gp and MDR1 mRNA in 53 cases of untreated primary gallbladder carcinoma and 12 ca- ses of cholecystitis (archival paraffin-embedded tissues). RESULTS: The positive expression rates of P-gp and MDR1 mRNA in the 53 cases and 12 cases were 60.38%, 71.69% and 25.00%, 33.33%, respectively. There was a significant difference between the two groups (P<0.05). The positive expression rate of P-gp and MDRlmRNA were 69.44%, 83.33% and 41.18%, 47.06% respectively in tissues in stage of Nevin against Nevin , (P<0.05). In well, moderately differentiated gallbladder carcinoma tissues, their expressions were 79.49%, 69.23% against 50.00%, 35.71% in low, undifferentiated tissues (P<0.05). CONCLUSIONS: MDR to gallbladder carcinoma is closely related to the intrinsic MDR and it provides an important evidence to reverse the MDR by detection of the MDR1gene. Meanwhile, MDR1 gene expression in gallbladder carcinoma is correlated with some biological characteris- tics , takes part in the carcinogenesis of gallbladder tissues, and acts as a valuable biomarker of prognosis.
文摘The expression of multidrug resistant proteins in bladder cancer and clinical implication was studied. Expression of multidrug associated protein (MRP), P glycoprotein (P gp), P53 and Bcl 2 proteins were detected by using immunohistochemical method in 40 specimens of bladder transitional cell carcinoma. The results showed that the positive rate of MRP, P gp, P53 and Bcl 2 was 52.5 %, 57.5 %, 47.5 % and 62.5 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in the grade Ⅰ, Ⅱ and Ⅲ of tumors was 46.3 %, 38.5 %, 38.5 %, 23.1 %; 52.9 %, 39.8 %, 47.1 %, 76.4 %; 60.0 %, 80.0 %, 60.0 %, 90.0 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in 24 primary tumor specimens was 37.5 %, 41.7 %, 33.3 %, 45.8 % and that in 16 cases in recurrent specimens receiving chemotherapy 75.0 %, 81.3 %, 68.8 %, 87.5 % respectively. It was suggested the positive rate of MRP, P gp, P53 and Bcl 2 was increased with the advance of tumor grade. The positive rate of four proteins in all recurrent cases was significantly increased ( P <0.05). The expression of MRP, P gp, P53 and Bcl 2 proteins might be the important factors for chemotherapy failure.
基金Supported in part by Phne-Poulenc Rorer Pharmaceuticals INC.
文摘AIM: To investigate the specific mechanisms of intrinsic and acquired resistance to taxotere (TXT) in pancreatic adenocarcinoma (PAC).METHODS: MTT assay was used to detect the sensitivity of PAC cell line SUIT-2 and its sublines (S-007, S-013, S-020,S-028 and TXT selected SUIT-2 cell line, S2/TXT) to TXT.Mdr1 (P-gp), multidrug resistance associated protein (MRP), lung resistance protein (LRP) and β-tubulin isotype gene expressions were detected by RT-PCR. The functionality of P-gp and MRP was tested using their specific blocker verapamil ( Ver ) and indomethacin ( IMC ),respectively. The transporter activity of P-gp was also confirmed by Rhodamine 123 accumulation assay.RESULTS: S-020 and S2/TXT were found to be significantly resistant to TXT(19 and 9.5-fold to their parental cell line SUIT-2, respectively ). RT-PCR demonstrated strong expression of Mdr1 in these two cell lines, but weaker expression or no expression in other cells lines. MRP and LRP expressions were found in most of these cell lines. The TXT-resistance in S2-020 and S2/TXT could be reversed almost completely by Ver, but not by IMC. Flow cytometry showed that Ver increased the accumulation of Rhodamine-123 in these two cell lines. Compared with S-020 and SUIT-2,the levels of β-tubulin isotype II, III expreesions in S-2/TXTwere increased remarkably.CONCLUSION: The both intrinsic and acquired TXT-related drugresistance in these PAC cell lines is mainly mediated by P-gp, but had no relationship to MRP and LRP expressions.The increases of β-tubulin isotype II, III might be collateral changes that occur when the SUIT-2 cells are treated with TXT.
基金financially supported by National Basic Research Program of China(973 Program,2015CB931802)Natural Science Foundation of China(31470968 and 81627901)。
文摘Multiple drug resistance(MDR)is a tough problem in developing hepatocellular carcinoma(HCC)therapy.Here,we developed TPGS-coated cationic liposomes with Bcl-2 siRNA corona to load doxorubicin(Dox)i.e.,Bcl-2 siRNA/Dox-TPGS-LPs,to enhance anticancer effect of Dox in HCC-MDR.TPGS i.e.,d-α-tocopheryl polyethylene glycol 1000 succinate,inhibited Pglycoprotein(P-gp)efflux pump and Bcl-2 siRNA suppressed anti-apoptotic Bcl-2 protein.The Bcl-2 siRNA loaded in the liposomal corona was observed under transmission electron microscopy.The stability and hemolysis evaluation demonstrated Bcl-2 siRNA/Dox-TPGSLPs had good biocompatibility and siRNA-corona could protect the liposomal core to avoid the attachment of fetal bovine serum.In drug-resistant cells,TPGS effectively prolonged intracellular Dox retention time and siRNA-corona did improve the internalization of Dox from liposomes.In vitro and in vivo anticancer effect of this dual-functional nanostructure was examined in HCC-MDR Bel7402/5-FU tumor model.MTT assay confirmed the IC50 value of Dox was 20–50 fold higher in Bel7402/5-FU MDR cells than that in sensitive Bel7402 cells.Bcl-2 siRNA corona successfully entered the cytosol of Bel7402/5-FU MDR cells to downregulate Bcl-2 protein levels in vitro and in vivo.Bcl-2 siRNA/Dox-TPGS-LPs showed superior to TPGS-(or siRNA-)linked Dox liposomes in cell apoptosis and cytotoxicity assay in Bel7402/5-FU MDR cells,and 7-fold greater effect than free Dox in tumor growth inhibition of Bel7402/5-FU xenograft nude mice.In conclusion,TPGS-coated cationic liposomes with Bcl-2 siRNA corona had the capacity to inhibit MDR dual-pathways and subsequently improved the anti-tumor activity of the chemotherapeutic agent co-delivered to a level that cannot be achieved by inhibiting a MDR single way.
文摘Summary: In order to provide a rational research basis for detection of resistance of Neisseria gonorrhoeae to antimierobial hydrophobie agents and study on the resistant mechanism of multiple transferable resistance (mtr) efflux system, plasmid pET-28a(+) encoding mtrC gene was constructed and the related target protein was expressed in Escherichia colt (E. cold DE3. The fragments of mtrC gene of Neisseria gonorrhoeae from the standard strains were amplified and cloned into prokaryotic expression plasmid pET-28a(+) with restriction endonuelease to construct recombinant pET-mtrC which was verified by restriction endonuelease and DNA sequencing. The recom- binant was transformed into E. coli DE3 to express the protein mtrC induced by IPTG. The results showed mtrC DNA fragment was proved correct through restriction endonuelease and DNA sequencing. hs sequence was 99.5 % homologus to that published on GeneBank (U14993). A 48.5 kD fusion protein which was induced by IPTG was detected by SDS-PAGE. It was concluded that the construction of prokaryotic expression plasmid of mtrC protein of Neisseria gonorrhoeae was correct and the fusion protein was successively expressed in E. coli.
文摘The multi-radiation of X-rays was investigated with special attention to their energy spectrum in a Mather-type plasma focus device (operated with argon gas). The analysis is based on the effect of anomalous resistances. To study the energy spectrum, a four-channel diode X-ray spectrometer was used along with a special set of filters. The filters were suitable for detection of medium range X-rays as well as hard X-rays with energy exceeding 30 keV. The results indicate that the anomalous resistivity effect during the post pinch phase may cause multi-radiation of X-rays with a total duration of 300 ± 50 ns. The significant contribution of Cu-Kα was due to the medium range X-rays, nonetheless, hard X-rays with energies greater than 15 keV also participate in the process. The total emitted X-ray energy in the forms of Cu-K and Cu-K/3 was around 0.14 ± 0.02 (J/Sr) and 0.04 ±0.01 (J/Sr), respectively. The total energy of the emitted hard X-ray (〉 15 keV) was around 0.12± 0.02 (J/Sr).
基金The research reported in this manuscript was funded by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA20030301)the International Partnership Program of the Chinese Academy of Sciences(Grant No.131551KYSB20180042)+1 种基金“Belt&Road”international cooperation team for the“Light of West”program of CAS(Su Lijun),Sichuan Science and Technology Program(Grant No.2021YJ0040)CAS“Light of West China”Program(Grant No.E0R2160).
文摘Theperformanceof a structurally dissipating rock-shed(SDR)depends largely onthecapacityofitsenergy dissipators.At present,mostenergy dissipatorsare made of metals,which dissipateenergy by unrecoverable plastic deformation.Therefore,they are not able to recover their energy-dissipation capacity after deformation under rockfall impact.However,a rockfall usually disintegrates into pieces when it rolls down from a higher position and results in multiple rockfall impacts.An energy dissipator with self-recovery capability is therefore more suitable for ensuring the safety of SDRs.Replacing metal with polyurethane(a hyperelastic material with remarkable self-recovery capability)can provide self-recovery capability for energy dissipators,making them more suitable for resisting multiple rockfall impacts.In this work,polyurethane was manufactured into twotypes ofenergy dissipators:cylindrical and cubical.Full-scale falling rock impact testsand dynamic numerical simulationswereconducted to study the mechanical response of the energy dissipators.In addition,in order to ensure the accuracy of the simulation,the dynamic mechanical properties of the polyurethanewere tested and its dynamic constitutive model was established.The experimental and simulation tests have clarified the advantages of the polyurethane energy dissipator.We also summarized the practical considerations in the design of energy dissipators.
基金This work was supported by the National Natural Science Foundation of China (No. 30000177).
文摘Objective: To investigate the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) and the relationship with cell cycle profiles in ovarian cancer SK-OV-3ip1 multicellular aggregates. Methods: Liquid overlay system was employed to obtain multicellular aggregates. Expression of P-gp and MRP was detected with flow cytometry (FCM). Outer, intermediate and inner cells from multicellular aggregates were collected by layer-trypsinized method. Cell cycle profiles were also analyzed by FCM. Results: Compared with control cells, no expression of P-gp and MRP was detected in monolyer cells (P=0.128 and P=0.604), but expression of P-gp and MRP in aggregate cells was significantly elevated (P<0.01). P-gp expression in every layer cells was also obviously increased (P<0.01). Furthermore, P-gp expression in every layer cells was also obviously increased (P=0.071). Tendency to increased G0–G1 phase and reduced S phase cells existed from outer through intermediate to inner layers in multicellular aggregates but with no statistical difference. Cell percentages in G2-M phase also had no difference. However, compared with monolayer cells, cells in G0–G1 phase increased and cells in S and G2-M phases lowered significantly in every layer and in the whole multicellular aggregates. Expression elevation of P-gp and MRP was consistent with increased G0–G1 percentage in aggregate cells. Conclusion: Expression of P-gp and MRP increases in cells of SK-OV-3ip1 multicellular aggregates and is consistent with increased G0–G1 percentage, which implies the possible relationship between them and the possible role in multicellular-mediated drug resistance.
文摘Objective: The objective is to study the antibacterial activity of six medicinal plants against two naso-pharyngeal pathogens and determination of total phenol contents in ethanol extracts of those plants. Methods: Different serial concentrations (0.05 g/mL, 0.1 g/mL, 0.2 g/mL, 0.4 g/mL) of ethanolic and acetone extracts of Piper nigrum L. (Piperaceae), Ocimum sanctum Linn., Plectranthus amboinicus L. (Lamiaceae), Ayapana triplinervis M.Vahl. (Asteraceae), Cinnamomum zeylanicum L. (Lauraceae), Allium schoenoprasum Linn. (Liliaceace) were evaluated for the antibacterial activity using disc diffusion method against gram positive Streptococcus pyogenes and gram negative Pseudomonas aeruginosa. The extracts were prepared from different parts of the plants. The total phenol content was estimated using folin-ciocaltau reagent in catechol equivalents. Results: Majority of the extracts had inhibitory effect against the tested bacteria at different concentrations. In ethanol extracts, Plectranthus amboinicus exhibited the maximum zone of inhibition (14 mm) at 0.05 g/mL concentration against Streptococcus pyogenes, and Ocimum sanctum showed highest zone of bacterial inhibition (19 mm) at 0.05 g concentration against Pseudomonas aeruginosa. In acetone extracts, Piper nigrum had the maximum zone of bacterial inhibition (17 mm) in 0.4 g/mL concentration against Streptococcus pyogenes and Cinnamomum zeylanicum and Allium schoenoprasum exhibited the highest zone of bacterial inhibition (0.4 g/mL) against Pseudomonas aeruginosa. The ethanol extract of Plectranthus amboinicus contained the highest amount of phenol (0.8 mg/mL) and Allium schoenoprasum contained the lowest amount (0.62 mg/mL). In acetone, Cinnamomum zeylanicum contained highest phenol content (0.78 mg/mL). Conclusion: All these investigations pave way to the molecular modeling of the lead phyto compounds present in the studied plants, and also in finding out their biochemical action in various metabolic pathways and reactions of infection.
文摘In order to investigate the relationship between the expression of cyclin A and drug resistance in adult patients with acute leukemia (AL), the mRNA expression of cyclin A, mdr1, TopⅡ α , bcl-2 was detected in 64 adult patients with AL and 20 normal controls by semi-reverse transcription polymerse chain reaction (semi-RT-PCR). It was found that the cyclin A and TopⅡ α mRNA expression levels in drug resistant group were significantly lower than in sensitive group ( P <0.01). Under the same experimental condition no cyclin A mRNA expression was detectable in all normal controls. The mdr1 and bcl-2 mRNA expression levels in resistant group were significantly higher than in sensitive group ( P <0.01). cyclin A and TopⅡ α gene expression levels were closely correlated ( r s =+0.794, P=0.000, n =64) in all AL patients, but cyclin A was not correlated with mdr1 and bcl-2 gene expression levels. In drug resistant group there was a negative correlation between the gene expression levels of cyclin A and mdr1 ( r s =-0.337, P=0.029 ). The 10 AL patients with positive lower expression of both cyclin A and TopⅡ α were all resistant to drugs. Logistic regression of Binary analysis showed the correlation between the lower expression of cyclin A and drug resistance. It was concluded that lower expression of cyclin A gene might be an unfavorable prognostic factor for patients with AL, and detection of both cyclin A and TopⅡ α gene expression would predict drug resistance in AL patients.
文摘Background: Urinary tract infection is a common disease in Somaliland society. The predominant causative organism of Urinary tract infection is Escherichia coli. This research studies antibiotic resistance of uropathogenic E. coli in patients of Hargeisa Group Hospital. The study selected commonly prescribed antibiotics for urinary tract infection treatment. Methodology: Urine samples of patients were cultured to isolate causative organisms of the urinary tract infection. Chromo-agar media, CLED, and biochemical tests are applied to identify the type of bacteria. Antibiotic reactions to E. coli bacteria are measured to differentiate between sensitive and resistant drugs with the guidance of the Clinical and Laboratories Standard Institute (CLSI). Kirby Bauer disc diffusion method is applied to assess antimicrobial activity against E. coli. Data of patients such as age, sex, symptoms of UTI, previous UTI infection, and history of antibiotic use were recorded. SPSS and Microsoft Excel are applied to analyze and interpret data. Results: The predominant organism that caused urinary tract infection was Escherichia coli (55%), Klebsiella spp (15%), Candida spp (15%), Enterococcus spp (10%), Staph spp 2.5%, and Pseudomonas spp 2.5% while other 55% were negative. The study assessed antibiotic resistance of E. coli, which reported resistance to Tetracycline at (70%), Ampicillin (64%), and Cotrimoxazole (61%). The bacteria showed moderate resistance to Ceftriaxone (43.5%), Nalidixic acid (43%), and Ciprofloxacin (36%). The bacteria are sensitive to Amikacin (100%), Nitrofurantoin (96%), Levofloxacin (73%) and gentamicin (74%). Conclusion: The overall incidence of antibiotic resistance to E. coli is high because the bacteria show a percentage of resistance to each antibiotic except Amikacin which gives (100%) sensitivity. The research recommends public awareness of the risks associated with antibiotic use and periodic evaluation of antibiotic resistance to accomplish better managing urinary tract infections.
基金This work was supported by the National Key Research and Development Program of China(2016YFD0101002)the National Natural Science Foundation of China(31571676,32072007,and 31761143008)+4 种基金the Ministry of Science and Technology of the People's Republic of China(2015BAD02B01)the Fundamental Research Funds for the Central Universities(2014PY054 and 2662015PY185)the University Student Research Fund(2016090)the Innovation Training Plan of University Student Fund(201510504023)the Higher Education Discipline Innovation Project(B20051).
文摘Natural alleles controlling multiple disease resistances (MDR) are valuable for crop breeding. However, only one MDR gene have been cloned in maize, and molecular mechanisms of MDR are not clear. By map-based cloning, we have cloned a teosinte-derived allele of a resistance gene, Mexicana lesion mimic 1 (ZmMM1), which has a lesion mimic phenotype and confers resistance to northern leaf blight (NLB), gray leaf spot (GLS) and southern corn rust (SCR). Strong MDR conferred by the teosinte allele is linked with the polymorphisms in the 3' untranslated region of the ZmMM1 gene that cause increased accumulation of ZmMM1 protein. ZmMM1 acts as a transcription repressor and negatively regulates transcription of specific target genes including ZmMM1-target gene 3 (ZmMT3), which functions as a negative regulator of plant immunity and associated cell death. The successful isolation of the ZmMM1 resistance gene will help not only in developing broad-spectrum and durable disease resistance but also in understanding the molecular mechanisms underlying MDR.
基金the grants from the National Natural Science Foundation of China(No.30170925)China Postdoctoral Science Foundation(No.20060390678)
文摘Background The multidrug resistance (MDR) associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell (HCC) patients treated with chemotherapy. Our study was to establish a stable HCC MDR cell line where a de novo acquisition of multidrug resistance specifically related to overexpression of a transgenic mdr1. Methods The 4.5-kb mdrl cDNA obtained from the plasmid pHaMDR1-1 was cloned into the PCl-neo mammalian expression vector, later was transferred by liposome to human hepatocarcinoma cell line HepG2. Then the transfected HepG2 cells resisting G418 were clustered and cultured and the specific fragment of mdr1 cDNA, mRNA and the P-glycoprotein (Pgp) in these HepG2 cells were detected by PCR, RT-PCR and flow cytometry, respectively. The accumulation of the daunorubicin was determinated by flow cytometry simultaneously. The nude mice model of grafting tumour was established by injecting subcutaneously HepG2/mdr1 cells in the right axilla. When the tumour diameter reached 5 mm, adriamycin was injected into peritoneal cavity. The size and growth inhibition of tumour were evaluated. Results The mdr1 expression vector was constructed successfully and the MDR HCC line HepG2/mdr1 developed. The PCR analysis showed that the specific fragment of mdrl cDNA in HepG2/mdr1 cells, but not in the control group HepG2 cells. Furthermore, the content of the specific fragment of mdr1 mRNA and Pgp expression in HepG2/mdr1 cells were (59.7±7.9)% and (12.28±2.09)%, respectively, compared with (16.9±3.2)% and (3.07±1.06)% in HepG2 cells. In the nude mice HCC model, the tumour genes of both groups were identified. After ADM therapy, the mean size of HepG2 cell tumours was significantly smaller than HepG2/mdr1 cell tumours. Conclusion The approach using the transfer of mdr1 cDNA may be applicable to the development of MDR hepatocarcinoma cell line, whose MDR mechanism is known. This would provide the experimental basis of MDR research.
文摘Background Gram-positive bacteria such as Staphylococcus aureus have been a common cause of infection among liver transplant (LT) recipients in recent decades. The understanding of local epidemiology and its evolving trends with regard to pathogenic spectra and antibiotic susceptibility is beneficial to prophylactic and empiric treatment for LT recipients. This study aimed to investigate etiology, timing, antibiotic susceptibility and risk factors for multidrug resistant (MDR) Gram-positive coccal bacteremia after LT.Methods A cohort analysis of prospectively recorded data was performed to investigate etiologies, timing, antibiotic susceptibility and risk factors for MDR Gram-positive coccal bacteremia in 475 LT recipients.Results In 475 LT recipients in the first six months after LT, there were a total of 98 episodes of bacteremia caused by Gram-positive cocci in 82 (17%) patients. Seventy-five (77%) bacteremic episodes occurred in the first post-LT month.The most frequent Gram-positive cocci were methicillin-resistant coagulase-negative staphylococcus (CoNS, 46 isolates),methicillin-resistant Staphylococcus aureus (MRSA, 13) and enterococcus (34, E. faecium 30, E. faecalis 4). In all Gram-positive bacteremic isolates, 59 of 98 (60%) were MDR. Gram-positive coccal bacteremia and MDR Gram-positive coccal bacteremia predominantly occurred in patients with acute severe exacerbation of chronic hepatitis B and with fulminant/subfulminant hepatitis. Four independent risk factors for development of bacteremia caused by MDR Gram-positive coccus were: LT candidates with encephalopathy grades Ⅱ-Ⅳ (P=0.013, OR: 16.253, 95% CI:1.822-144.995), pre-LT use of empirical antibiotics (P=0.018, OR: 1.029, 95% CI: 1.002-1.057), post-LT urinary tract infections (P 〈0.001, OR: 20.340, 95% CI: 4.135-100.048) and abdominal infection (P=0.004, OR: 2.820, 95% CI:1.122-10.114). The main infectious manifestations were coinfections due to gram-positive cocci and gram-negative bacilli.Conclusions Methicillin-resistant CoNS and enterococci are predominant pathogens among LT recipients with Gram-positive coccal bacteremia. Occurrences of Gram-positive coccal bacteremia may be associated with the severity of illness in the perioperative stage.
基金This study was supported by a grant from the Province Natural Science Foundation of Shandong (No. Y2007C 148).
文摘Background The prognosis is poor for patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). The main reason for poor prognosis is multidrug resistance (MDR), for which the main phenotype is overexpression of P-glycoprotein (P-gp). This study explored the efficacy of ligustrazine as a salvage agent in patients with relapsed or refractory NHL, and the relationship to P-gp expression. Methods Sixty patients were randomized to a reversal agent group, receiving ligustrazine plus chemotherapy, and a control group, receiving chemotherapy alone. Flow cytometry was performed to evaluate P-gp expression. Results In the 56 patients we were able to evaluate, there was no statistically significant difference in progression-free survival (PFS) in the two groups (P=0.0651), but the reversal agent group had a higher overall response rate (ORR) than did the control group (P=0.048). Forty-one of 56 patients had P-gp(+) tumor cells. Among these patients, six of eighteen patients in the reversal agent group and in the control group had complete remission or complete remission/unconfirmed (CR+CRu) reflecting a significant advantage in the reversal agent group (P=0.048). Patients with P-gp(+) tumor cells in the reversal agent group had a higher overall response rate (ORR) than did the control group (11/18 vs. 6/23, P=0.024). Kaplan-Meier Survival curve and log-rank test demonstrated that patients with P-gp(+) tumor cells in the reversal agent group had longer progression-free survival than did the control group (P=0.0464). A small number of patients who received ligustrazine had a decrease in blood pressure. Conclusion Ligustrazine as a salvage agent in combination with chemotherapy can elevate response rate, prolong PFS with manageable toxicity, and correlate with P-gp expression in relapsed or refractory NHL.