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1.
Eur J Cancer ; 134: 29-40, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32460179

RESUMO

PURPOSE: We conducted preclinical experiments and phase I clinical trial to investigate the safety, pharmacokinetics (PK) and antitumour effects of GT0918 in castration-resistant prostate cancer (CRPC). EXPERIMENTAL DESIGN: An androgen receptor (AR) competitive binding assay was performed, followed by evaluation of GT0918 on AR protein expression. The efficacy of GT0918 was investigated in a castration-resistant xenograft model. A phase I dose-escalation study of GT0918 in CRPC was also carried out to evaluate its safety, PK and antitumour efficacy. RESULTS: GT0918 was demonstrated to inhibit the binding of androgen to AR more potently than MDV3100, and to effectively reduce the AR protein level. GT0918 inhibited the transcriptional activity of wild-type AR and AR with clinically relevant ligand-binding domain mutations. Furthermore, GT0918 significantly inhibited the growth of prostate cancer. A total of 16 patients was treated with GT0918 at five dose levels. Among these 16 patients, 10 and 2 patients, respectively, completed a three-cycle and six-cycle treatment, in which MTD was not reached. All the treatment-related adverse events were grade I, including hypercholesterolemia, hypertriglyceridemia, fatigue and anaemia. PK parameters showed that drug exposure increased with dose proportionally from 50 to 300 mg and a saturation was observed between 300 and 400 mg. PSA declines of ≥30% and ≥50% were, respectively, observed in six and two cases. All the 12 patients with metastatic soft tissue lesions confirmed stable disease. CONCLUSIONS: GT0918, a full AR antagonist without agonist effect, has high binding affinity to AR with AR protein down-regulation activity. GT0918 is demonstrated to be well tolerated with a favourable PK profile and exhibits promising antitumour activity in CRPC. CLINICALTRIALS: gov identifier CTR20150501.

2.
Med Sci Monit ; 26: e921272, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32339160

RESUMO

BACKGROUND The aim of this study was to compare the clinical safety and effectiveness of transurethral bipolar plasmakinetic enucleation of the prostate (PKEP) vs. transurethral bipolar plasmakinetic resection of the prostate (PKRP) in the treatment of benign prostate hyperplasia (BPH) more than 80 ml. MATERIAL AND METHODS From June 2015 to February 2019, 179 BPH patients with prostate volume greater than 80 ml were enrolled and separated into a PKEP (n=81) group and a PKRP group (n=98). The patients in the 2 groups were followed up for 6 months. We collected and analyzed data from the international Prostate Symptom Score (IPSS), residual urine volume (RUV), quality of life (QOL), maximum urine flow rate (Qmax), and international erectile function index (ILEF-5). The clinical data collected during and after the operation and surgical complications were compared between the 2 groups. RESULTS The PKEP group had significantly shorter operation time, bladder flushing time, indwelling catheter time, and hospitalization time, and has less intraoperative blood loss, intraoperative blood transfusion, postoperative secondary hemorrhage, bladder neck contracture, capsule perforation, and retrograde ejaculation (P<0.05). Compared with the PKRP group, the postoperative IPSS and QOL scores were significantly lower in the PKEP group (P<0.05), while the excision glandular tissue weight and Qmax were significantly improved (P<0.05). There were no significant differences in ILEF-5 scores, RUV, urethral stricture, urinary incontinence, or erectile dysfunction between the 2 groups (p>0.05). CONCLUSIONS PKEP treatment of BPH with a large volume (>80 ml) has the advantages of complete gland resection, good surgical effect, improved surgical safety, and reduced intraoperative and postoperative complications.

3.
Biomater Sci ; 8(8): 2318-2328, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32187239

RESUMO

In the past decade, the development of gene carriers has been key in enhancing gene therapy. Gene therapy is associated with not only the delivery process but also gene expression as a prominent role. Herein, for the purpose of achieving a novel breakthrough in gene therapy, we creatively proposed a "strengthened gene expression" idea beyond the range of improving the gene carrier. We constructed three types of gene delivery systems, namely, single-pZNF580 delivery system, single-pVEGF165 delivery system, and dual-gene delivery system. These systems possessed approximate same sizes (∼120 nm) and zeta potentials (∼+20 mV), which indicated negligible differences in their cellular uptake. Interestingly, we found that the gene expression of dual-gene groups significantly increased at the level of both mRNA and protein at least 2 times and 1.5 times as high as single-gene groups, respectively. This "1 + 1 > 2" expression effect benefited from the coordinated expression of the angiogenesis-related genes of ZNF580 and VEGF165. Furthermore, the coordinated effect was also confirmed in HUVEC activities such as an obviously enhanced proliferation and migration of the dual-gene group. Rationally, we further evaluated the effects of coordinated interactions on neovascularization. We observed that the statistic tube number of dual-gene groups was approximately 1.44 times as high as that of single-gene groups. More importantly, this enhanced angiogenesis induced by the coordinated expression was also demonstrated in an in vivo environment. Therefore, we believed that the enhanced gene therapy via the gene expression pathway could provide a creative viewpoint for the design of gene delivery system and therapy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31893996

RESUMO

BACKGROUND: Prostate cancer remains one of both the most common and deadliest forms of cancer, which is still localized generally respond well to radical prostatectomy and associated interventions, up to 30% of these individuals will still suffer from disease relapse. BUB1B has been found to be essential for cell growth and proliferation, even in several kinds of tumor cells. But the specific importance and mechanistic role of BUB1B in prostate cancer remains unclear. METHODS: Quantitative Real-Time PCR and Western-blot were used in detection of mRNA and protein expression. Lentivirus infection was used to overexpression or knock down target gene. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett's posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis. RESULTS: In the present report, we found BUB1B expression to be highly increased in prostate cancer tissues relative to normal controls. We further found BUB1B to be essential for efficient tumor cell proliferation, and to correlate with poorer prostate cancer patient outcomes. From a mechanistic perspective, the ability of BUB1B to regulate MELK was found to be essential for its ability to promote prostate cancer cell proliferation. CONCLUSION: Altogether, our data suggests that BUB1B is up-regulated in prostate cancer, suggesting that growth of cancer cells may depend on BUB1B-dependent regulation of MELK transcription. BUB1B may serve as a clinical prognostic factor and a druggable target for prostate cancer.

5.
Curr Med Sci ; 39(5): 825-830, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612403

RESUMO

To explore the feasibility and superiority of iodine delivery rate (IDR) and tube voltage determined by patients' body mass index (BMI) in coronary CT angiography (CCTA), a total of 1567 patients undertaking CCTA during Feb. and Dec. 2016 were enrolled and divided into two groups. In the control group, the IDR and tube voltage were fixed, while in the experimental group, the IDR and tube voltage were determined by patients' BMI. The volume of iodinated contrast media (ICM), extravasation rate, extravasation volume, extravasation recovery interval, incidence rate of adverse reactions, effective dose (ED) and image quality of the two groups were compared. The experiments demonstrated that the ICM volume, extravasation rate, extravasation volume, extravasation recovery interval, incidence of adverse reactions and ED were lower or shorter in the experimental group than in the control group, and the differences were statistically significant (all P<0.05). However, there were no significant differences in the mean CT value, image noise, signal to noise ratio and contrast to noise ratio between the two groups (all P<0.05), which were consistent with the diagnosticians' subjective evaluation outcomes. Our findings suggested that in CCTA, it is feasible to determine the IDR and tube voltage based on patients' BMI; low tube voltage and IDR are superior to the fixed tube voltage and IDR and are worthy of clinical promotion.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Meios de Contraste/farmacocinética , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Extravasamento de Materiais Terapêuticos e Diagnósticos/diagnóstico por imagem , Iodo/farmacocinética , Índice de Massa Corporal , Doença da Artéria Coronariana/sangue , Extravasamento de Materiais Terapêuticos e Diagnósticos/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão Sinal-Ruído
6.
Adv Mater ; : e1903747, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31660670

RESUMO

Advanced scanning transmission electron microscopy (STEM) and its associated instruments have made significant contributions to the characterization of all-solid-state (ASS) Li batteries, as these tools provide localized information on the structure, morphology, chemistry, and electronic state of electrodes, electrolytes, and their interfaces at the nano- and atomic scale. Furthermore, the rapid development of in situ techniques has enabled a deep understanding of interfacial dynamic behavior and heterogeneous characteristics during the cycling process. However, due to the beam-sensitive nature of light elements in the interphases, e.g., Li and O, thorough and reliable studies of the interfacial structure and chemistry at an ultrahigh spatial resolution without beam damage is still a formidable challenge. Herein, the following points are discussed: (1) the recent contributions of advanced STEM to the study of ASS Li batteries; (2) current challenges associated with using this method; and (3) potential opportunities for combining cryo-electron microscopy and the STEM phase contrast imaging techniques.

7.
Nanoscale ; 11(27): 13007-13016, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31265036

RESUMO

The electrochemical properties of layered cathodes can be enhanced by doping with aluminium. However, understanding of the underlying mechanism of Al ion behaviour is deficient, which obstructs its further application. Herein, we adjusted the aluminium content in model LiNi0.85-xCo0.15AlxO2 (LNCA) materials; the sample with the optimum aluminium content (x = 0.05) exhibited excellent electrochemical performance (98.6% capacity retention at 275 mA g-1). Meanwhile, for the samples with excessive aluminium (x = 0.15, 0.30), fast decay of the cycling stability could be observed. Meanwhile, their reversible capacities in the initial cycles were also greatly inferior to the theoretical values. These abnormal phenomena can be attributed to structure cracking and the impedance of Li-ion migration in samples with higher aluminium content. According to the microstructure observations, an unexpected beneficial heterostructure was found to cover the samples with optimum aluminium content, while in the samples with higher aluminium content, this heterostructure was not present. Furthermore, as confirmed by activation barrier calculations, Al ions were found to prefer to thermodynamically occupy the tetrahedral interstices instead of the octahedral sites in Li layers in a high delithiation state. Due to this selective occupancy, proper aluminium content can improve the stability of layered cathodes during cycling. However, excessive aluminium content instead impedes the formation of beneficial surface heterogeneity during synthesis and deeply affects Li-ion migration during cycling. Therefore, the electrochemical performance of the samples with higher aluminium content suffered severe decay. These results and discoveries significantly advance the guidance of microstructural design for next-generation layered cathode materials.

8.
Biomater Sci ; 7(8): 3307-3319, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31204746

RESUMO

Small interfering RNA (siRNA)-based therapy is an emerging treatment to address serious cardiovascular disease. It is essential to construct highly efficient vehicles for therapeutic siRNA intracellular delivery. Extracellular signal-regulated kinase-2 (ERK2) siRNA (abbreviated as ERK2-siRNA) is known as a type of siRNA to selectively silence the expression of ERK2. Herein, a type of ternary delivery system characterized by an endosome-selective-self-accelerating-escape ability was designed and prepared for the purpose of inhibiting the migration of vascular smooth muscle cells (VSMCs) in vitro. This system was called ternary ERK2-siRNA complexes (abbreviated as TRCs-Aco), which were fabricated via sequential electrostatic self-assembly of a star-shaped cell-penetrating peptide based on polyhedral oligomeric silsesquioxane (POSS-(C-G-R8-G-W)16), ERK2-siRNA and a pH-sensitive anionic polymer of cis-aconitic anhydride grafted ε-poly(l-lysine). Importantly, TRCs-Aco could break down the obstacle of biocompatibility-silencing efficiency. In comparison with the parent binary siRNA complexes (abbreviated as BRCs), which are composed of POSS-(C-G-R8-G-W)16 and ERK2-siRNA, our designed TRCs-Aco revealed more excellent biocompatibility including hemocompatibility and cytocompatibility. Unexpectedly, TRCs-Aco exhibited stronger ERK2 silencing efficiency at the level of mRNA and protein, which was mainly due to its remarkable self-accelerating endosomal escape. Definitive evidence demonstrated that this ternary ERK2-siRNA delivery system significantly prevented the migration of VSMCs and decreased the dermal thickness in bleomycin-treated mice. In brief, this unique structured system could provide a valuable nanoplatform for highly efficient siRNA delivery in VSMCs, and it might hold great potential in guiding ERK2-siRNA-based proliferative disease therapy.


Assuntos
Portadores de Fármacos/química , Endossomos/metabolismo , Hiperplasia/genética , Proteína Quinase 1 Ativada por Mitógeno/genética , Nanoestruturas/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , Sequência de Aminoácidos , Animais , Transporte Biológico , Membrana Celular/metabolismo , Movimento Celular/genética , Feminino , Fibrose , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/deficiência , Músculo Liso Vascular/patologia , Peptídeos/química , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Eletricidade Estática
9.
Opt Express ; 27(12): A620-A628, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31252842

RESUMO

For the [0001] oriented AlGaN-based deep ultraviolet light-emitting diodes (DUV LEDs), the holes in the p-type electron blocking layer (p-EBL) are depleted due to the polarization induced positive sheet charges at the last quantum barrier (LQB)/p-EBL interface. The hole depletion effect significantly reduces the hole injection capability across the p-EBL. In this work, we propose inserting a thin AlN layer between the LQB and the p-EBL, which can generate the hole accumulation at the AlN/p-EBL interface. Meanwhile, the holes can obtain the energy when traveling from the p-EBL into the multiple quantum wells (MQWs) by intraband tunneling through the thin AlN layer. As a result, the hole injection and the external quantum efficiency (EQE) have been remarkably enhanced. Moreover, we point out that the thick AlN insertion layer can further generate the hole accumulation in the p-EBL and increase the hole energy which helps to increase the hole injection. We also prove that the intraband tunneling for holes across the thick AlN insertion layer is facilitated by using the optimized structure.

10.
Biotechnol J ; 14(6): e1800694, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31066190

RESUMO

With nearly three decades of development, Pichia pastoris (P. pastoris) has become a powerful eukaryotic protein expression system for the expression of thousands of proteins both on a laboratory and industrial scale. In addition, it has also been extensively used as a cell factory for the production of a variety of chemicals. This review summarizes the bottlenecks and solutions in achieving high-level secretory protein expression with P. pastoris and then outlines its applications on chemical production with an emphasis on its role as whole-cell biocatalyst. Furthermore, current challenges and future directions of this important system are also discussed.


Assuntos
Pichia/metabolismo , Proteínas/metabolismo , Pichia/enzimologia , Biologia Sintética/métodos
11.
Nanoscale ; 11(10): 4552-4561, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30806412

RESUMO

Reactive oxygen species (ROS) are powerful oxidants generated in both biological systems and natural environments. Though enzyme-mimic activity and Fenton-like reactions have been postulated to explain how ceria nanoparticles and ROS are involved in the catalytic decomposition of hydrogen peroxide (H2O2), the corresponding reaction kinetics for this reaction have not yet been completely resolved. Here we present our investigation of the structure-activity relationship of ceria nanostructures for the generation of hydroxyl radicals through the catalytic decomposition of H2O2. Different nanostructured ceria including nanorods (NR), nanocubes (NC), and nanooctahedra (NO), together with commercial ceria, were examined to elucidate the relationship between the morphology and reaction kinetics. The initial relative production rates of hydroxyl radicals over different ceria nanostructures were determined using fluorescence measurements and were applied to obtain the apparent activation energy for their intrinsic activity comparisons. The activity trend of the order: ceria NR > ceria NC > ceria NO > commercial ceria was observed. This trend was rationalized and assessed using activity descriptive factors including the intensity ratio of Raman bands of vibration modes due to atomic defects, the percentage of surface Ce3+ content, and the average coordination number of oxygen anions surrounding each cerium cation in the ceria samples.

12.
Gene ; 670: 63-69, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-29792948

RESUMO

Fruit rot caused mainly by Colletotrichum gloeosporioides is a major cause of pre- and/or post-harvest diseases, which seriously constrains production, marketing, and export of fruits. To infect the host, this fungus evolves a specialized infection structure called the appressorium. Extensive past studies have characterized many appressorium-related genes in C. gloeosporioides, separately. However, a comprehensive understanding of the genes contributing to appressorium formation is far from complete. Here, global changes in gene expression were analyzed between appressoria and hyphae using RNA-Seq. We identified 4071 genes that are up-regulated in appressorium and discovered 468 unigenes that are expressed only in appressoria, compared with the fungal hyphae. Differentially expressed genes between appressoria and hyphae were assigned to 107 KEGG pathways, including metabolic pathways, secondary metabolite biosynthesis, molecular transport and signal transduction. Fourteen putative ABC transporter genes are significantly up-regulated in appressoria, and in contrast, twenty-six down-regulated. One hundred and one transcription factor genes show more than a 2-fold up-regulation in appressoria compared to hyphae. The up-regulation of 39 secreted protein candidates is observed, suggesting they may play important roles in initial infection processes. Our data demonstrate that appressorium development of C. gloeosporioides is accompanied by significant changes in gene expression, which provides novel insights to elucidate how this fungus regulates its development, pathogenicity and immune evasion.


Assuntos
Proteínas Fúngicas/genética , Perfilação da Expressão Gênica/métodos , Saccharomycetales/patogenicidade , Análise de Sequência de RNA/métodos , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Hifas/genética , Hifas/crescimento & desenvolvimento , Mapas de Interação de Proteínas , Saccharomycetales/genética , Metabolismo Secundário
13.
Nanoscale ; 10(21): 9822-9829, 2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29770828

RESUMO

We report a rapid, room temperature methodology to synthesize fluorite-structured ceria nanoparticles using cerium(iii) salts and ozone in the presence of short chain primary, secondary, and tertiary alcohols. This simple technique produced nanoparticles with higher oxygen vacancy compared to that of bulk ceria.

14.
Biotechnol Lett ; 40(7): 1149-1156, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29785668

RESUMO

OBJECTIVES: To systematically explore the effects of overexpressing Hac1p homologues from different sources on protein secretion in Pichia pastoris system. RESULTS: Effects of Hac1p homologues encompassing P. pastoris (PpHac1p), S. cerevisiae (ScHac1p), Trichoderma reesei (TrHac1p) and Homo sapiens (HsXbp1), on secretion of three reporter proteins-ß-galactosidase, ß-mannanase and glucose oxidase were investigated. No individual Hac1p was optimal for all the enzymes. Rather, by testing a set of Hac1p, the secretory expression of each of the enzymes was improved. Notably, HsXbp1 overexpression improved ß-mannanase production from 73 to 108.5 U ß-mannanase mL-1 while PpHac1p had no impact in shake flask culture. Moreover, HsXbp1 led to 41 and 67% increases in ß-mannanase production in the single- and four-copy strain, respectively in 1-L laboratory fermenter. Transcription analysis of indicative chaperones suggested that HsXbp1 may cause a stronger and prolonged activation of the UPR target chaperone genes. CONCLUSION: Mammalian HsXbp1 worked better than yeast Hac1p in terms of improving ß-mannanase secretion in P. pastoris, and Hac1p screening may offer an effective strategy to engineer the secretion pathway of eukaryotic expression systems.


Assuntos
Chaperonas Moleculares/genética , Pichia/genética , Biossíntese de Proteínas/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biotecnologia , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Glucose Oxidase/química , Glucose Oxidase/genética , Glucose Oxidase/metabolismo , Humanos , Chaperonas Moleculares/química , Chaperonas Moleculares/metabolismo , Pichia/metabolismo , Conformação Proteica , Desdobramento de Proteína , Proteínas Recombinantes/química , Proteína 1 de Ligação a X-Box/química , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo , beta-Manosidase/química , beta-Manosidase/genética , beta-Manosidase/metabolismo
15.
J Colloid Interface Sci ; 524: 434-444, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29677612

RESUMO

Synthetic polymer fluid loss additive (FLA), an important type of admixture, was broadly applied in modern well cementation. However, the filter loss volume and fluidity of cement pastes containing polymer-FLA would deteriorate remarkably when sea water was used in mixing slurries instead of fresh water. In this study, a novel sustained-release-type fluid loss additive(S-FLA) was synthesized by means of anion-exchange intercalation reaction between an anionic type-copolymer and a calcium/aluminum type-Layered Double Hydroxide (Ca/Al-LDH). Based on the fluidity and compressive strength of experiments, it was found that in seawater mixing conditions, this composite material not only utilized its sustained release effect to significantly improve retention fluidity performance, but also the seed crystal effect of the Ca/Al-LDH effectively alleviated the declining in compressive strength of the slurries caused by the carboxyl group in the polymer. More interestingly, the realization of the slow release function increased actual adsorption capacity of the anionic polymer on the surface of cement hydrated particles, which made its controlling water loss effect was also better than that of the conventional FLA. The above advantages of this hybrid materials created the possibility to surmount the negative effect of electrolytes present in seawater, so as to provide some useful references for its practical application in the offshore well cement.

16.
Materials (Basel) ; 11(5)2018 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-29701653

RESUMO

Due to the wide potential application in the fields of sensing, lighting materials, and optical⁻electrical multifunctional devices, rare earth complex hybrid materials have been studied extensively over the past decades. A poly(ionic liquid)/mesoporous-based hybrid system which has been functionalized by the covalently linked europium complexes was reported here. Through surface modification with a coupling agent bearing an vinyl group, MCM-41 was chosen as the carrier matrix for poly(ionic liquids) (PILs) and europium compounds, and based on that, novel luminescent hybrid materials were prepared by confining the ionic liquid and europium complexes into the inorganic Si⁻O frameworks. The resulting organic/inorganic materials are chemically bonded hybrids which show good photoluminescent properties such as broad excitation spectra, line-like emission spectra, and long luminescence lifetimes. The PILs/MCM-41/Eu3+ hybrid reported here is a rare earth multifunctional material which is believed to have potential applications in the field of optical⁻electrical materials.

17.
Environ Technol ; 39(24): 3228-3237, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28866963

RESUMO

The biochemical oxygen demand (BOD) is widely used for the evaluation of water and wastewater quality. However, the conventional method to measure BOD is time-consuming and requires complicated processes. In this study, a Microbial fuel cell (MFC)-based BOD sensor was developed by using low-cost activated carbon as the cathode catalyst. The sensor was calibrated with an aerated nutrient medium containing sodium acetate as the BOD source. When the sensor was operated with an external resistance of 1 K Ω, linear correlation (R2 = 0.9965) was obtained for BOD concentrations ranging from 80 to 1280 mg/L in a reaction time of 50 h. Besides acetate, glucose/glutamic acid (GGA) and ethanol could also be analyzed by the sensor. In a low concentration range (200 mg/L), the relationship between GGA solution concentration and output voltage was in accord with Monod growth kinetics.


Assuntos
Fontes de Energia Bioelétrica , Técnicas Biossensoriais , Eletrodos , Oxigênio , Águas Residuárias
18.
Food Chem Toxicol ; 107(Pt A): 68-73, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28587984

RESUMO

Huperzine A has been used for improving symptoms of Alzheimer's disease. Its cholinergic side effect is thought to be an exaggerated pharmacological outcome linked to its high brain or CNS concentrations. Although Huperzine A is brain penetrable, its interaction with efflux transporters (ABCB1 and ABCG2) has not been fully investigated. The aim of the present study was to characterize roles of ABCB1 and ABCG2 in the transmembrane transport of Huperzine A and identify a rate limiting step in its brain distribution. Data obtained from stably transfected MDCK II cells showed that Huperzine A is a substrate of ABCB1 but not ABCG2. ABCB1 inhibitors significantly inhibited ABCB1 mediated efflux of Huperzine A. In Abcb1a-/- mice, the brain to plasma concentration ratio of Huperzine A was significantly increased as compared to the wild type mice, while there were no obvious differences between the wild type and Abcg2-/- mice. Taken together, the present study demonstrated that ABCB1 but not ABCG2 played a predominant role in the efflux of Huperzine A across BBB. The current finding is clinically relevant as changes in ABCB1 activity in the presence of ABCB1 inhibitors or genetic polymorphism may affect efficacy and safety of Huperzine A.


Assuntos
Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Alcaloides/farmacocinética , Encéfalo/metabolismo , Sesquiterpenos/farmacocinética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Transporte Biológico , Encéfalo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Distribuição Tecidual
19.
Microb Pathog ; 110: 85-92, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28645773

RESUMO

ATP-binding cassette (ABC) proteins are exclusively found in both prokaryotes and eukaryotes. In this study, we have characterized a gene from Glomerella leaf spot pathogen Colletotrichum gloeosporioides that encodes an ABC protein, whose function to date remains unknown. We designated this gene as CgABCF2. Deletion of CgABCF2 showed drastic reduction both growing rate and conidial production in C. gloeosporioides. The Δcgabcf2 mutant did not form the appressoria, lost the capability to infect apple and failed to form lesions on the wounded leaves and fruits. The C. gloeosporioides native CgABCF2 fully recovered defect of the Δcgabcf2 mutant. These data indicated that CgABCF2 was required for fungal development and invasion. The transcriptions of six pectolytic enzymes genes (CgPG1, CgPG2, pnl-1, pnl-2, pelA and pelB) significantly reduced in the Δcgabcf2 mutant, indicating that deletion of CgABCF2 impaired the fungal necrotrophic growth. In addition, CgABCF2 mediated sexual development through the positive regulation of the gene MAT1-2-1 expression. These results indicated that CgABCF2 underlies the complex process governing morphogenesis, sexual and asexual reproduction, appressorial formation and pathogenicity in C. gloeosporioides.


Assuntos
Colletotrichum/genética , Colletotrichum/patogenicidade , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Doenças das Plantas/microbiologia , Desenvolvimento Sexual , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Colletotrichum/citologia , Colletotrichum/crescimento & desenvolvimento , DNA Fúngico/genética , Frutas/microbiologia , Deleção de Genes , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Genes Fúngicos/genética , Vetores Genéticos , Hifas/crescimento & desenvolvimento , Malus/microbiologia , Morfogênese , Folhas de Planta/microbiologia , Reprodução Assexuada , Autofertilização , Análise de Sequência , Esporos Fúngicos/crescimento & desenvolvimento , Virulência/genética , Virulência/fisiologia , Fatores de Virulência/genética
20.
Transfusion ; 57(2): 273-279, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28194856

RESUMO

BACKGROUND: Transfusion transmission of hepatitis E virus (HEV) is an emerging health risk, yet blood donors are rarely screened for this pathogen. Many blood centers instituted screening of blood donors for elevated levels of alanine aminotransferase (ALT) levels to prevent hepatitis C virus, which has continued in China. We evaluated whether elevated ALT levels were associated with HEV among blood donors in China. STUDY DESIGN AND METHODS: Blood samples were collected from 9069 qualified volunteer blood donors from four blood centers in China. A total of 5023 had elevated ALT levels, that is, more than 40 IU/L, and 4046 samples had normal ALT. We tested all the 9069 samples for anti-HEV immunoglobulin (Ig)M, anti-HEV IgG, and HEV antigen. Those who were positive for anti-HEV IgM or HEV antigen were tested individually for HEV RNA by polymerase chain reaction. RESULTS: The prevalence of anti-HEV IgG in donors with elevated ALT levels (33.3%) was higher than those with normal ALT (24.9%; p < 0.01). The prevalence of anti-HEV IgM was similar in donations with increased ALT (1.41%) and normal ALT (1.46%). More ALT-elevated donations were HEV antigen positive, 62 of 5023 (1.23%), than were ALT-normal donations, seven of 4046 (0.17%; p < 0.01). Six donors with elevated ALT levels and acute HEV infection markers (anti-HEV IgM or HEV antigen) were HEV RNA positive. CONCLUSION: Markers of active infection including HEV antigen and HEV RNA are significantly more common among donors with elevated ALT levels in China. These data support the fact that ALT testing of donors to HEV antigen or HEV RNA would have greater specificity and exclude fewer acceptable donors.


Assuntos
Alanina Transaminase/sangue , Seleção do Doador , Vírus da Hepatite E , Hepatite E/sangue , Adolescente , Adulto , Anticorpos Antivirais/sangue , Antígenos Virais/sangue , Biomarcadores/sangue , Doadores de Sangue , China/epidemiologia , Feminino , Hepatite E/epidemiologia , Hepatite E/prevenção & controle , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Soroepidemiológicos
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