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1.
Metab Eng ; 67: 53-66, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34098101

RESUMO

Bacterial outer membrane (OM), an asymmetric lipid bilayer functioning as a self-protective barrier with reduced permeability for Gram-negative bacteria, yet wasting nutrients and energy to synthesize, has not been studied for its effect on bioproduction. Here we construct several OM-defected halophile Halomonas bluephagenesis strains to investigate the effects of OM on bioproduction. We achieve enhanced chassis properties of H. bluephagenesis based on positive cellular properties among several OM-defected strains. The OM-defected H. bluephagenesis WZY09 demonstrates better adaptation to lower salinity, increasing 28%, 30% and 12% on dry cell mass (DCM), poly(3-hydroxybutyrate) (PHB) accumulation and glucose to PHB conversion rate, respectively, including enlarged cell sizes and 21-folds reduced endotoxin. Interestingly, a poly(3-hydroxybutyrate-co-21mol%4-hydroxybutyrate) (P(3HB-co-21mol%4HB)) is produced by H. bluephagenesis WZY09 derivate WZY249, increasing 60% and 260% on polyhydroxyalkanoate (PHA) production and 4HB content, respectively. Furthermore, increased electroporation efficiency, more sensitive isopropyl ß-D-1-thio-galactopyranoside (IPTG) induction, better oxygen uptake, enhanced antibiotics sensitivity and ectoine secretion due to better membrane permeability are observed if OM defected, demonstrating significant OM defection impacts for further metabolic engineering, synthetic biology studies and industrial applications.


Assuntos
Halomonas , Poli-Hidroxialcanoatos , Ácido 3-Hidroxibutírico , Halomonas/genética , Hidroxibutiratos , Engenharia Metabólica , Permeabilidade , Poliésteres
2.
Radiology ; 294(1): 149-157, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31714192

RESUMO

Background MRI performed with echo-planar imaging (EPI) sequences is sensitive to susceptibility artifacts in the presence of metallic objects, which presents a substantial barrier for performing functional MRI and diffusion tensor imaging (DTI) in patients with metallic orthodontic material and other head implants. Purpose To evaluate the ability to reduce susceptibility artifacts in healthy human participants wearing metallic orthodontic braces for two alternative approaches: T2-prepared functional MRI and diffusion-prepared DTI with three-dimensional fast gradient-echo readout. Materials and Methods In this prospective study conducted from February to September 2018, T2-prepared functional MRI and diffusion-prepared DTI were performed in healthy human participants. Removable dental braces with bonding trays were used so that MRI could be performed with braces and without braces in the same participants. Results were evaluated in regions with strong (EPI dropout regions for functional MRI and the inferior fronto-occipital fasciculus for DTI) and minimal (motor cortex for functional MRI and the posterior limb of internal capsule for DTI) susceptibility artifacts. Signal-to-noise ratio (SNR), contrast-to-noise ratio for functional MRI, apparent diffusion coefficient and fractional anisotropy for DTI, and degree of distortion (quantified with the Jaccard index, which measures the similarity of geometric shapes) were compared in regions with strong or minimal susceptibility effects between the current standard EPI sequences and the proposed alternatives by using paired t test. Results Six participants were evaluated (mean age ± standard deviation, 40 years ± 6; three women). In brain regions with strong susceptibility effects from the metallic braces, T2-prepared functional MRI showed significantly higher SNR (37.8 ± 2.4 vs 15.5 ± 5.3; P < .001) and contrast-to-noise ratio (0.83 ± 0.16 vs 0.29 ± 0.10; P < .001), whereas diffusion-prepared DTI showed higher SNR (5.8 ± 1.5 vs 3.8 ± 0.7; P = .03) than did conventional EPI methods. Apparent diffusion coefficient and fractional anisotropy were consistent with the literature. Geometric distortion was substantially reduced throughout the brain with the proposed methods (significantly higher Jaccard index, 0.95 ± 0.12 vs 0.81 ± 0.61; P < .001). Conclusion T2-prepared functional MRI and diffusion-prepared diffusion tensor imaging can acquire functional and diffusion MRI, respectively, in healthy human participants wearing metallic dental braces with less susceptibility artifacts and geometric distortion than with conventional echo-planar imaging. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Dietrich in this issue.


Assuntos
Artefatos , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Braquetes Ortodônticos , Adulto , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes
3.
Exp Cell Res ; 383(1): 111496, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306654

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide, and there is currently no effective therapeutic strategy in clinical practice. Gene therapy has great potential for decreasing tumor-induced mortality but has been clinically limited because of the lack of tumor-specific targets and insufficient gene transfer. The study of targeted transport of therapeutic genes in HCC treatment seems to be very important. In this study, we evaluated a gene therapy approach targeting HCC using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system in HCC cell lines and in an in vivo human HCC xenograft mouse model. GP73-modified liposomes targeted gene delivery to the tumor tissue, and the survivin promoter drove HSVtk expression in the HCC cells. Our results showed that the survivin promoter was specifically activated in tumor cells and HSVtk was expressed selectively in tumor cells. Combined with GCV treatment, HSVtk expression resulted in suppression of HCC cell proliferation via enhancing apoptosis. Moreover, tail vein injection of GP73-HSVtk significantly suppressed the growth of xenograft tumors through an apoptosis-dependent pathway and extended the survival of tumor-bearing mice without damaging the mice liver functions. Taken together, this study demonstrates an effective cancer-specific gene therapy strategy using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system for HCC that can be further developed for future clinical trials.


Assuntos
Carcinoma Hepatocelular/terapia , Terapia Genética , Lipossomos/administração & dosagem , Neoplasias Hepáticas/terapia , Proteínas de Membrana/química , Survivina/genética , Timidina Quinase/genética , Animais , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células , Feminino , Ganciclovir/administração & dosagem , Vetores Genéticos/administração & dosagem , Humanos , Lipossomos/química , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Regiões Promotoras Genéticas , Simplexvirus/enzimologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Bioprocess Biosyst Eng ; 42(8): 1273-1283, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31041517

RESUMO

High cost and high viscosity of ionic liquid restricted its commercial application in pretreatment of lignocellulose. Water and ethanol were used as additive in [EMIM][OAc] to pretreat corn cob at moderate temperature (< 100 °C). It was found that enzyme hydrolysis (EH) sugar yield was increased with the increase of IL content. The largest EH sugar yield of 68.8% was obtained when pure IL was used. However, for [EMIM][OAc]/ethanol, the EH sugar yield as high as 66.9% was gained when the IL content was 80%, which was comparable to that for pure IL pretreatment. In addition, Kamlet-Taft parameter was calculated to characterize the polarity solvency of binary liquid phase, to illustrate the underlying reason for the increase of EH sugar and the lignin removal. Finally, to demonstrate the crystalline and microstructure change after pretreatment, XRD and SEM were performed for the raw materials and the pretreated samples.


Assuntos
Celulase/química , Etanol/sangue , Líquidos Iônicos/química , Lignina/química , Água/química , Zea mays/química , Hidrólise
5.
BMC Pharmacol Toxicol ; 25(1): 64, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39267168

RESUMO

BACKGROUND: Numerous digestive system adverse events (dsAEs) have been observed during the use of anti-obesity medications (AOMs), leading to concerns about the safety of these medications. However, most current studies are limited to the association of one class of drugs with specific digestive disorders, and there is no cascading analysis of AOMs in the digestive system. This study aims to use data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) for a stratified analysis of the reported associations between AOMs and dsAEs. METHODS: We analyzed adverse event reports submitted to FAERS between January 2015 and December 2023 related to obesity treatment. It is important to note that FAERS data cannot establish causality or incidence rates. Pharmacovigilance (PV) signals were detected by disproportionate analyses through proportionate reporting ratio (PRR), reporting odds ratios (ROR), and information components (IC) to detect dsAEs associated with AOMs. Reporting rates, severity, and response outcomes of digestive adverse events were compared across AOMs by multivariate logistic regression analysis. RESULTS: Among 34,396 adverse events (AEs) related to obesity treatment, 8844 dsAEs were analyzed. Comparing with semaglutide and liraglutide, tirzepatide exhibited fewer reported dsAEs while semaglutide and liraglutide showed a high correlation with non-lethal pancreatitis reports. Bupropion-naltrexone (31.65%) reported the highest number of dsAEs, and a PV signal was detected in mouth and lips AEs (ROR = 2.97, 95% CI: 2.42-3.6). Orlistat (ROR = 3.30, 95% CI: 3.08-3.55) exhibited the highest association with gastrointestinal AEs compared to other AOMs. PV signal for hepatobiliary AEs (ROR = 6.13, 95% CI: 3.45-10.88) with phentermine-topiramate still needs further clarification. CONCLUSIONS: Tirzepatide may be considered for patients with a history of digestive system disease or an elevated risk of pancreatitis based on the pattern of reported dsAEs. Caution is needed for the orofacial AEs when using bupropion-naltrexone. Orlistat has a higher reporting rate of gastrointestinal AEs, but these events are typically less severe. Phentermine-topiramate's association with liver impairment requires further clinical investigation. This article provides insights into the reported associations between AOMs and dsAEs, which may aid clinicians in making more informed decisions about individualizing medication and managing potential adverse events.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Fármacos Antiobesidade , Farmacovigilância , United States Food and Drug Administration , Humanos , Estados Unidos/epidemiologia , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/uso terapêutico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Bases de Dados Factuais , Idoso , Adulto Jovem , Doenças do Sistema Digestório/induzido quimicamente , Doenças do Sistema Digestório/epidemiologia , Obesidade/epidemiologia , Liraglutida/uso terapêutico , Liraglutida/efeitos adversos , Adolescente
6.
EuroIntervention ; 20(13): e806-e817, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38742581

RESUMO

BACKGROUND: The treatment of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains challenging in current clinical practice. AIMS: The study was conducted to investigate a novel biolimus-coated balloon (BCB) for the treatment of coronary DES-ISR compared with the best-investigated paclitaxel-coated balloon (PCB). METHODS: This was a prospective, multicentre, randomised, non-inferiority trial comparing a novel BCB with a clinically proven PCB for coronary DES-ISR. The primary endpoint was in-segment late lumen loss (LLL) at 9 months assessed by an independent core laboratory. Baseline and follow-up optical coherence tomography were performed in a prespecified subgroup of patients. RESULTS: A total of 280 patients at 17 centres were randomised to treatment with a BCB (n=140) versus a PCB (n=140). At 9 months, LLL in the BCB group was 0.23±0.37 mm compared to 0.25±0.35 mm in the PCB group; the mean difference between the groups was -0.02 (95% confidence interval [CI]: -0.12 to 0.07) mm; p-value for non-inferiority<0.0001. Similar clinical outcomes were also observed for both groups at 12 months. In the optical coherence tomography substudy, the neointimal area at 9 months was 2.32±1.04 mm2 in the BCB group compared to 2.37±0.93 mm2 in the PCB group; the mean difference between the groups was -0.09 (95% CI: -0.94 to 0.76) mm2; p=non-significant. CONCLUSIONS: This head-to-head comparison of a novel BCB shows similar angiographic outcomes in the treatment of coronary DES-ISR compared with a clinically proven PCB. (ClinicalTrials.gov: NCT04733443).


Assuntos
Angioplastia Coronária com Balão , Reestenose Coronária , Stents Farmacológicos , Paclitaxel , Intervenção Coronária Percutânea , Sirolimo , Humanos , Masculino , Feminino , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Reestenose Coronária/etiologia , Reestenose Coronária/diagnóstico por imagem , Idoso , Pessoa de Meia-Idade , Sirolimo/análogos & derivados , Sirolimo/administração & dosagem , Sirolimo/uso terapêutico , Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/métodos , Estudos Prospectivos , Resultado do Tratamento , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/efeitos adversos , Tomografia de Coerência Óptica , Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/diagnóstico por imagem , Materiais Revestidos Biocompatíveis , Angiografia Coronária
7.
J Craniofac Surg ; 24(4): 1111-3, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23851750

RESUMO

UNLABELLED: The mandibular angle plays an important role in determining the Asian human facial attractiveness. Currently, mandibular angle osteotomy is often reported as the correction of square face appearance due to its prominence. However, no previous study has documented the long-term outcome of partial masseter muscle resection along with reduction of mandibular angle. OBJECTIVE: Our study aims to investigate the outcome and complications of partial masseter muscle resection along with reduction of mandibular angle in long-term follow-up. METHOD: One hundred fifty-one patients were subjected to the computed tomography scan before and 3 years after surgery. Morphometrical analysis was conducted on all parameters for clinical evaluation, so as to reveal the change of masseter muscle, the postsurgical result, and the complication. RESULTS: All patients were satisfied with the optimal outcome of the reduction of mandibular angle and masseter muscle. Morphometrical analysis indicated that the volume of masseter muscle changed statistically significantly before and after surgery (reduced 21.31 ± 7.64% on left, 20.77 ± 7.45% on right). Complications included swelling and low lip numbness, yet no patients reported infection or facial nerve injury. CONCLUSION: Partial masseter muscle resection along with reduction of mandibular angle can improve the appearance of the patients greatly, and only a few complications occurred.


Assuntos
Mandíbula/cirurgia , Músculo Masseter/cirurgia , Osteotomia/métodos , Adulto , Povo Asiático , Feminino , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Músculo Masseter/diagnóstico por imagem , Satisfação do Paciente , Complicações Pós-Operatórias , Tomografia Computadorizada por Raios X , Adulto Jovem
8.
Children (Basel) ; 9(7)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35883992

RESUMO

The study aimed to investigate the relationship between smoking, Sugar-Sweetened Beverage (SSB) consumption and tooth brushing among adolescents in China. A valid sample of 6084 middle school students from the Zhejiang province was included. Participants were questioned about smoking status, SSB consumption, tooth brushing, and oral health-related quality of life (OHRQoL). Among the participants, smoking prevalence was 1.9% and nearly half of the students consumed SSBs. The demographic factors associated with smoking were gender, place of residence, and parental level of education. There are co-variations between smoking status, SSB consumption, and tooth brushing. Logistic regression showed that smoking adolescents were more likely to brush their teeth less than once per day (OR = 1.74, p < 0.05), consume soft drinks once or more per day (OR = 2.18, p < 0.01) and have a higher score on the Child Oral Health Impact Profile (OR = 1.05, p < 0.05) after adjusting for demographic factors. The findings provide compelling evidence for governments and related stakeholders to intervene in the lifestyle of adolescents. Future studies are needed to understand the interaction effects of such behaviors, and should help to inform appropriate interventions.

9.
Chemosphere ; 308(Pt 2): 136383, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36088979

RESUMO

BACKGROUND: Phthalates are commonly used in variety of plastic products. Previously it has been revealed that di (2-ethylhexyl) phthalate (DEHP), as the most common member of the class of phthalates, may disturb cholesterol homeostasis and deregulate the inflammatory response, and leading to accelerate the atherosclerosis process. In this regard, the aim of the current study is to explore the underlying mechanism of DEHP-induced atherosclerosis through the increasing of foam cell formation and Vascular Smooth Muscle Cells (VSMCs) damage via the interaction of long-non coding RNA (GAS5) and miR-145-5p. METHODS: ApoE-/- mice were used to evaluate the in vivo study. RAW264.7 and VSMCs were used to evaluate the effect of DEHP on formation of foam cell, cell proliferation, and cell damage in vitro. Animals were treated with DEHP (5% w/w of food) orally and cells were treated with medium containing of 100 µM DEHP; qRT-PCR, Western blotting, flowcytometry, IHC, oil red O, BODIPY, and autophagic vacuoles assay were used to evaluate the effect of DEHP on formation of atherosclerosis. RESULTS: DEHP significantly accelerated the formation of atherosclerosis in mice and alter the lipid profile in mice. In addition, after treating VSMCs with DEHP, GAS5 was significantly up-regulated and miR-145-5p was down-regulated. In VSMCs treated with DEHP, we observed that GAS5 could be used as the competing endogenous RNA (ceRNA) of miR-145-5p to regulate the proliferation and apoptosis of VSMCs; and the expression of GAS5 was correlated with the expression of miR-145-5p. DEHP increased the ox-LDL uptake by macrophage and increasing the formation of foam cells. Besides, GAS5 knocking down reversed the effect of DEHP on foam cell formation and ox-LDL uptake. CONCLUSION: DEHP could accelerate the atherosclerosis process through increasing VSMCs damage and formation of macrophage foam cell by increasing lipid uptake though down regulating lncRNA GAS5 and altering in regulation of miR-145-5p.


Assuntos
Aterosclerose , Dietilexilftalato , MicroRNAs , RNA Longo não Codificante , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Apolipoproteínas E/farmacologia , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , Movimento Celular , Proliferação de Células , Colesterol/metabolismo , Dietilexilftalato/metabolismo , Células Espumosas/metabolismo , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacologia , Macrófagos/metabolismo , Camundongos , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Ácidos Ftálicos , Plásticos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
10.
Chemosphere ; 308(Pt 2): 136315, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36087728

RESUMO

Due to the use of agricultural film, the pollution of phthalate esters (PAEs) in plastic-shed soils has attracted increasing attention. In this study, we used watermelon as a planting system and investigated the effects of organic fertilizer and chemical fertilizer application on the degradation of PAEs by evaluating soil nutrients and soil bacterial communities in plastic-shed soil. The dibutyl phthalate (DBP) concentration in the organic fertilizer soil was only 58.2% in the zero-fertilization control (CK) soil, but the concentrations of monohexyl phthalate (MEHP) and mono-n-butyl ester (MBP), the metabolites of PAEs, were found to be higher. The concentration of MBP is ten times that of DBP. The results showed that fertilization, especially the application of organic fertilizers, had a significant effect on the degradation of PAEs. There were specific biomarkers in different fertilization treatments. Among the microbiome community, Planifilum had the highest relative abundance in the organic fertilizer (OF) soil, and the highest proportion of Thermodesulfovibrionia was detected in the chemical fertilizer (CF) soil. These biomarkers were significantly correlated with PAEs and their metabolites. The relative abundance of Thermomonosporaceae was significantly positively correlated with DBP. Planifilum and Thermaerobacter, which significantly increased in organic fertilizer soil, showed a significant negative correlation with DBP and a significant positive correlation with MBP. The relative abundances of Planifilum and Geobacillus were elevated in the OF soil and may be able to co-metabolize soil nitrogen and PAEs. PAEs and their metabolites in soils had significant effects on soil microbes, as did the soil nutrients including available phosphorus (AP), alkali-hydrolysable nitrogen (Alkali-N), and organic matter (OM). Our research provides scientific support for the use of fertilizers to reduce PAE contamination but also warns of the potential risks of PAE metabolites.


Assuntos
Microbiota , Poluentes do Solo , Álcalis , Bactérias/metabolismo , Dibutilftalato/metabolismo , Ésteres , Fertilizantes , Nitrogênio , Fósforo , Ácidos Ftálicos , Plásticos , Solo , Poluentes do Solo/análise
11.
ACS Biomater Sci Eng ; 8(1): 32-53, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-34851607

RESUMO

X-ray computed tomography (CT), as one of the most widely used noninvasive imaging modalities, can provide three-dimensional anatomic details with high resolution, which plays a key role in disease diagnosis and treatment assessment. However, although they are the most prevalent and FDA-approved contrast agents, iodinated water-soluble molecules still face some challenges in clinical applications, such as fast clearance, serious adverse effects, nonspecific distribution, and low sensitivity. Because of their high biocompatibility, tunable designability, controllable biodegradation, facile synthesis, and modification capability, the polymers have demonstrated great potential for efficient delivery of iodinated contrast agents (ICAs). Herein, we comprehensively summarized the applications of multifunctional polymeric materials for ICA delivery in terms of increasing circulation time, decreasing nephrotoxicity, and improving the specificity and sensitivity of ICAs for CT imaging. We mainly focused on various iodinated polymers from the aspects of preparation, functionalization, and application in medical diagnosis. Future perspectives for achieving better imaging and clinical translation are also discussed to motivate new technologies and solutions.


Assuntos
Meios de Contraste , Nanopartículas , Meios de Contraste/efeitos adversos , Polímeros , Tomografia Computadorizada por Raios X
12.
Chemosphere ; 307(Pt 2): 135887, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35931252

RESUMO

Microplastic exposure leads to various toxic effects in Daphnia magna; however, the effects of microplastics on the metabolic processes in D. magna and the corresponding molecular toxicity mechanisms remain unclear. In the present study, the effects of acute exposure to polyethylene microplastics with different particle sizes (20 µm [MPs-20] and 30 µm [MPs-30]) on metabolites in D. magna and the mechanisms of toxicity were investigated by combining metabolomics and traditional toxicology techniques. Exposure to both MPs-20 and MPs-30 resulted in significant accumulation of microplastics in the gut of D. magna and significantly reduced D. magna survival and heart rate. Metabolomics analysis revealed that MPs-20 and MPs-30 induced significant changes in up to 88 and 91 differential metabolites, respectively, and collectively induced significant changes in 75 metabolites in D. magna. Among lipid metabolites, MPs-20 specifically downregulated phosphatidylcholine and upregulated phosphatidylethanolamine, which mainly affected phospholipid metabolism, whereas MPs-30 specifically downregulated amino acid metabolites l-glutamine, l-glutamate and malic acid, which mainly interfered with energy metabolism. The results of this study provide novel insights into the mechanism of effects of microplastics on metabolic processes in D. magna.


Assuntos
Microplásticos , Poluentes Químicos da Água , Animais , Daphnia , Ácido Glutâmico , Glutamina/farmacologia , Fosfatidilcolinas/farmacologia , Fosfatidiletanolaminas/farmacologia , Plásticos/toxicidade , Polietileno/toxicidade , Poluentes Químicos da Água/análise
13.
Drug Dev Ind Pharm ; 36(7): 832-8, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20515404

RESUMO

BACKGROUND: Poloxamer 188 is a safe biocompatible polymer that can be used in protein drug delivery system. AIM: In this study, a new heparin-poloxamer 188 conjugate (HP) was synthesized and its physicochemical properties were investigated. HP structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and Hydrogen-1 nuclear magnetic resonance spectroscopy ((1)H-NMR). Content of the conjugated heparin was analyzed using Toluidine Blue. The critical micelle concentration (CMC) of the copolymer was determined by a fluorescence probe technique. The effect of HP on the gelation of poloxamer 188 was characterized by the rheological properties of the HP-poloxamer hydrogels. Solubility and viscosity of HP were also evaluated compared with poloxamer 188. RESULTS: From the results, the solubility of the conjugated heparin was increased compared with free heparin. The content of heparin in HP copolymer was 62.9%. The CMC of HP and poloxamer 188 were 0.483 and 0.743 mg/mL, respectively. The gelation temperature of 0.4 g/mL HP was 43.5 degrees C, whereas that of the same concentration of poloxamer 188 was 37.3 degrees C. With HP content in poloxamer 188 solution increasing, a V-shape change of gelation temperature was observed. CONCLUSION: Considering the importance of poloxamer 188 in functional material, HP may prove to be a facile temperature-sensitive material for protein drug-targeted therapy.


Assuntos
Heparina/química , Poloxâmero/química , Portadores de Fármacos , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Micelas , Solubilidade , Tecnologia Farmacêutica , Viscosidade
14.
J Microencapsul ; 27(2): 115-21, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19538032

RESUMO

This work was to compare the encapsulation efficiency and ultrasound-triggered release for protein between microbubbles and liposomes. Bovine serum albumin (BSA) was used as a model. Final ratios between BSA and HPC in microbubbles and liposomes were 1:5, 1:7 and 1:10, respectively. Morphologic characteristics and contrast enhancement of loaded microbubbles and liposomes were measured. Encapsulation efficiency and ultrasound-stimulated release profile were detected. The mean size of loaded microbubbles and liposomes was 3.4 microm and 1.7 microm, respectively. Encapsulation efficiency of microbubbles had an inverse relationship with the ratio between BSA and HPC, while loaded liposomes remained nearly unchanged in the designed range of the ratio between BSA and HPC. Microbubbles resulted in significant enhancement of CnTi images. After ultrasound, more than 90% of the entrapped BSA was released from microbubbles, but less than 5% of BSA released from liposomes. Microbubbles are a promising delivery system for proteins.


Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Lipossomos , Microbolhas , Fosfolipídeos , Soroalbumina Bovina/administração & dosagem , Animais , Bovinos , Desenho de Equipamento , Rim/ultraestrutura , Lipossomos/química , Masculino , Fosfolipídeos/química , Coelhos , Ultrassom
15.
Cancer Gene Ther ; 27(10-11): 754-767, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31645678

RESUMO

Hepatocellular carcinoma (HCC) is a prevalent malignant tumour with high global morbidity and mortality associated with its multiple aetiologies, poor prognosis, resistance to chemotherapeutic drugs and high rate of recurrence. Here, we evaluated a gene therapy strategy that targets HCC using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system in HCC cell lines and in an in vivo human HCC xenograft mouse model. Apolipoprotein E (ApoE)-modified liposomes were used for targeted gene delivery to the tumour tissue, and the survivin promoter was used to drive HSVtk expression in HCC cells. Our results showed that the survivin promoter was specifically activated in tumour cells, and HSVtk was expressed selectively in tumour cells. In combination with GCV treatment, HSVtk expression resulted in the inhibition of HCC cell proliferation via enhanced apoptosis. In addition, tail vein injection of ApoE-HSVtk significantly suppressed the growth of xenograft tumours through an apoptosis-dependent pathway and extended the survival time of tumour-bearing mice. In summary, this study illustrates an effective cancer-specific gene therapy strategy for HCC that can be further developed for future clinical trials.


Assuntos
Apolipoproteínas E/metabolismo , Carcinoma Hepatocelular/genética , Terapia Genética/métodos , Lipossomos/metabolismo , Neoplasias Hepáticas/genética , Simplexvirus/patogenicidade , Survivina/metabolismo , Animais , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Transfecção
16.
Colloids Surf B Biointerfaces ; 178: 412-420, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30903980

RESUMO

As zwitterionic polymers show great promise in drug delivery, hyaluronic acid (HA) was deacetylated and grafted with dodecylamine to prepare a pH-sensitive zwitterionic polymer dHAD used as a carrier for antitumor drugs. The polymer was negatively charged at pH 7.4 and became positive at pH 6.2. In vitro delivery of DOX against MCF-7 cells showed that the blank micelle dHAD had low cytotoxicity and the dHAD-DOX micelles could greatly prohibit the growth of the MCF-7 cells. In addition, the dHAD-DOX micelles had higher cellular uptake, indicating that the micelles were rapidly internalized into the cells via CD44 receptor-mediated endocytosis. The in vivo delivery of DOX to tumor-bearing mice confirmed that the dHAD-DOX micelles greatly inhibited the tumor growth and significantly reduced systemic toxicity of DOX. These results demonstrated that biocompatible pH-responsive zwitterionic dHAD micelles are promising carriers for the delivery of DOX.


Assuntos
Doxorrubicina/química , Ácido Hialurônico/química , Polímeros/química , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Endocitose/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Micelas
17.
Environ Sci Pollut Res Int ; 25(32): 32122-32129, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30218339

RESUMO

A series of Zr-Fe (Zr/Fe = 4:0, 3:1, 2:2, 1:3, 0:4) polymeric pillared interlayered montmorillonite loading 10 wt.% MnOx (Mn/Zr-Fe-PILM) were investigated for the selective catalytic reduction of NOx by NH3 (NH3-SCR) in metallurgical sintering flue gas. The X-ray diffraction (XRD), N2 adsorption-desorption isotherm, scanning electron microscope (SEM), and ammonia temperature-programmed desorption (NH3-TPD) were used to analyze the physicochemical property. The Fe polymerized with Zr exchanged to montmorillonite can improve the Mn/Zr-Fe-PILM low-temperature NOx conversion and N2 selectivity. The Mn/Zr-Fe-PILM (1:3) shows the highest NOx conversion between 140 and 180 °C. The XRD results suggest that the growth of crystalline ZrO2 phase is intensely restrained for the Fe2O3 migration into the ZrO2 lattice. The ZrO2 and MnOx have an excellent dispersion in montmorillonite. The N2 adsorption result illustrates that the increase of Fe molar content in the Zr-Fe-PILM support increases the catalyst-specific surface area. The NH3-TPD results elucidate that the Mn/Zr-Fe-PILM (1:3) has the most total acid sites. Therefore, the low-temperature catalytic activity of the Mn/Zr-Fe-PILM (1:3) has been assigned to the large specific surface area, abundant acid sites, and the dispersion of metallic oxides.


Assuntos
Amônia/química , Modelos Químicos , Óxido Nítrico/química , Adsorção , Bentonita , Catálise , Temperatura Baixa , Compostos Férricos , Íons , Manganês/química , Metalurgia , Oxirredução , Óxidos/química , Polímeros , Temperatura , Difração de Raios X
18.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 36(4): 441-446, 2018 Aug 01.
Artigo em Zh | MEDLINE | ID: mdl-30182574

RESUMO

Bone tissue engineering is a scientific field devoted to the development of materials that can repair or replace human bone tissue with biological and engineering methods. The stent, which provides structural support and adhesion sites for cell and tissue growth, is one of the key elements in tissue engineering. The scaffold may comprise metal, polymer, and ceramic biomaterial. The polymer scaffold is widely used due to its biocompatibility, biodegradability, and mechanical stability. Chitosan, as a natural polymer, is derived from chitin and has played a particularly important role in bone tissue engineering over the past two decades. In recent years, chitosan composites and their application in bone tissue engineering have received considerable attention due to their small foreign body reaction, excellent antibacterial properties, plasticity, suitability for inward cell growth, and bone conduction. This review will discuss the biocompatibility and osteogenesis research in vivo and in vitro of several common chitosan composites in bone tissue engineering.


Assuntos
Regeneração Óssea , Quitosana , Engenharia Tecidual , Alicerces Teciduais , Materiais Biocompatíveis , Osso e Ossos , Humanos
19.
JACC Cardiovasc Interv ; 11(23): 2368-2377, 2018 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-30522665

RESUMO

OBJECTIVES: The aim of the present study was to evaluate the angiographic efficacy, clinical safety, and effectiveness of the Restore paclitaxel-coated balloon in a randomized trial designed to enable the approval of the new device in China. BACKGROUND: Drug-coated balloon (DCB) angioplasty offers an effective treatment for in-stent restenosis. Restore is a new DCB with a SAFEPAX shellac-ammonium salt excipient that can avoid drug washing off during catheter delivery to the target lesion site. METHODS: In the noninferiority RESTORE ISR China (Compare the Efficacy and Safety of RESTORE DEB and SeQuent Please in Chinese Patient With Coronary In-stent Restenosis) trial, eligible patients with first occurrence of drug-eluting stent ISR were randomized to the Restore DCB or SeQuent Please DCB in a 1:1 ratio stratified by diabetes. Angiographic and clinical follow-up was planned at 9 months and 1 year, respectively, in all patients. The study was powered for the primary endpoint of 9-month in-segment late loss. RESULTS: Between May 2016 and July 2017, a total of 240 subjects at 12 sites were randomized to either the Restore group (n = 120) or the SeQuent Please group (n = 120). Nine-month in-segment late loss was 0.38 ± 0.50 mm with Restore versus 0.35 ± 0.47 mm with SeQuent Please; the 1-sided 97.5% upper confidence limit of the difference was 0.17 mm, achieving noninferiority of Restore compared with SeQuent Please (p for noninferiority = 0.02). Both DCBs had similar 1-year rates of target lesion failure (13.3% vs. 12.6%; p = 0.87). CONCLUSIONS: In this head-to-head randomized trial, the Restore DCB was noninferior to the SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. (Compare the Efficacy and Safety of RESTORE DEB and SeQuent Please in Chinese Patient With Coronary In-stent Restenosis; NCT02944890).


Assuntos
Angioplastia Coronária com Balão/instrumentação , Cateteres Cardíacos , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Doença da Artéria Coronariana/terapia , Reestenose Coronária/terapia , Stents Farmacológicos , Paclitaxel/administração & dosagem , Intervenção Coronária Percutânea/instrumentação , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , China , Constrição Patológica , Doença da Artéria Coronariana/diagnóstico por imagem , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
J Acoust Soc Am ; 122(6): 3230-41, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18247735

RESUMO

The surface velocity of sand inside a large PVC container, induced by the sound pressure from either a large loudspeaker radiating into an inverted cone and pipe or a Bruel and Kjaer point source loudspeaker mounted with its axis vertical, has been measured using accelerometers. Results of white noise and stepped frequency excitation are presented. Without any buried object the mass loading of an accelerometer creates resonances in the spectral ratio of sand surface velocity to incident acoustic pressure, i.e., the acoustic-to-seismic (A/S) admittance spectra. The A/S responses above a buried compliant object are larger and distinctive. The linear A/S admittance spectra in the presence of a buried electronic components box have been studied as a function of burial depth and sand state. The nonlinear responses above the buried box have been studied as a function of depth, sand state, and amplitude. Predictions of a modified one-dimensional lumped parameter model have been found to be consistent with the observed nonlinear responses. Also the modified model has been used to explain features of the A/S responses observed when using an accelerometer without any buried object.


Assuntos
Aceleração , Acústica/instrumentação , Geologia/instrumentação , Ruído , Cloreto de Polivinila , Dióxido de Silício , Amplificadores Eletrônicos , Calibragem , Geologia/normas , Modelos Lineares , Modelos Teóricos , Movimento (Física) , Dinâmica não Linear , Pressão , Espectrografia do Som , Fatores de Tempo , Vibração
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