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1.
BMC Biotechnol ; 24(1): 22, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664752

RESUMO

BACKGROUND: The advancement of AAV vectors into clinical testing has accelerated rapidly over the past two decades. While many of the AAV vectors being utilized in clinical trials are derived from natural serotypes, engineered serotypes are progressing toward clinical translation due to their enhanced tissue tropism and immune evasive properties. However, novel AAV vectors require formulation and stability testing to determine optimal storage conditions prior to their use in a clinical setting. RESULTS: Here, we evaluated the thermal stability of AAV6.2FF, a rationally engineered capsid with strong tropism for lung and muscle, in two different buffer formulations; phosphate buffered saline (PBS), or PBS supplemented with 0.001% non-ionic surfactant Pluronic F68 (PF-68). Aliquots of AAV6.2FF vector encoding the firefly luciferase reporter gene (AAV6.2FF-ffLuc) were incubated at temperatures ranging from -20°C to 55°C for varying periods of time and the impact on infectivity and particle integrity evaluated. Additionally, the impact of several rounds of freeze-thaw treatments on the infectivity of AAV6.2FF was investigated. Vector infectivity was measured by quantifying firefly luciferase expression in HEK 293 cells and AAV particle integrity was measured by qPCR quantification of encapsidated viral DNA. CONCLUSIONS: Our data demonstrate that formulating AAV6.2FF in PBS containing 0.001% PF-68 leads to increased stability and particle integrity at temperatures between -20℃ to 21℃ and protection against the destructive effects of freeze-thaw. Finally, AAV6.2FF-GFP formulated in PBS supplemented with 0.001% PF-68 displayed higher transduction efficiency in vivo in murine lung epithelial cells following intranasal administration than vector buffered in PBS alone further demonstrating the beneficial properties of PF-68.


Assuntos
Dependovirus , Vetores Genéticos , Poloxâmero , Animais , Humanos , Células HEK293 , Poloxâmero/farmacologia , Poloxâmero/química , Camundongos , Dependovirus/genética , Vetores Genéticos/genética , Luciferases de Vaga-Lume/genética , Luciferases de Vaga-Lume/metabolismo , Temperatura , Genes Reporter
2.
Mol Ther ; 31(12): 3457-3477, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37805711

RESUMO

Surfactant protein B (SP-B) deficiency is a rare genetic disease that causes fatal respiratory failure within the first year of life. Currently, the only corrective treatment is lung transplantation. Here, we co-transduced the murine lung with adeno-associated virus 6.2FF (AAV6.2FF) vectors encoding a SaCas9-guide RNA nuclease or donor template to mediate insertion of promoterless reporter genes or the (murine) Sftpb gene in frame with the endogenous surfactant protein C (SP-C) gene, without disrupting SP-C expression. Intranasal administration of 3 × 1011 vg donor template and 1 × 1011 vg nuclease consistently edited approximately 6% of lung epithelial cells. Frequency of gene insertion increased in a dose-dependent manner, reaching 20%-25% editing efficiency with the highest donor template and nuclease doses tested. We next evaluated whether this promoterless gene editing platform could extend survival in the conditional SP-B knockout mouse model. Administration of 1 × 1012 vg SP-B-donor template and 5 × 1011 vg nuclease significantly extended median survival (p = 0.0034) from 5 days in the untreated off doxycycline group to 16 days in the donor AAV and nuclease group, with one gene-edited mouse living 243 days off doxycycline. This AAV6.2FF-based gene editing platform has the potential to correct SP-B deficiency, as well as other disorders of alveolar type II cells.


Assuntos
Doxiciclina , Edição de Genes , Camundongos , Animais , Dependovirus/genética , Vetores Genéticos/genética , RNA Guia de Sistemas CRISPR-Cas , Pulmão/metabolismo , Tensoativos/metabolismo , Sistemas CRISPR-Cas
3.
Sensors (Basel) ; 24(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38400442

RESUMO

Nanofiber technology is leading the revolution of wearable technology and provides a unique capability to fabricate smart textiles. With the novel fabrication technique of electrospinning, nanofibers can be fabricated and then manufactured into a durable conductive string for the application of smart textiles. This paper presents an electrospun nanofiber mesh-based (NF-Felt) string electrode with a conducting polymer coating for an electrochemical enzymatic glucose sensor. The surface area of a nanofiber matrix is a key physical property for enhanced glucose oxidase (GOx) enzyme binding for the development of an electrochemical biosensor. A morphological characterization of the NF-Felt string electrode was performed using scanning electron microscopy (SEM) and compared with a commercially available cotton-polyester (Cot-Pol) string coated with the same conducting polymer. The results from stress-strain testing demonstrated high stretchability of the NF-Felt string. Also, the electrochemical characterization results showed that the NF-Felt string electrode was able to detect a glucose concentration in the range between 0.0 mM and 30.0 mM with a sensitivity of 37.4 µA/mM·g and a detection limit of 3.31 mM. Overall, with better electrochemical performance and incredible flexibility, the NF-Felt-based string electrode is potentially more suitable for designing wearable biosensors for the detection of glucose in sweat.


Assuntos
Técnicas Biossensoriais , Nanofibras , Dispositivos Eletrônicos Vestíveis , Glucose/química , Nanofibras/química , Técnicas Biossensoriais/métodos , Polímeros , Eletrodos , Técnicas Eletroquímicas/métodos , Glucose Oxidase/metabolismo
4.
Sensors (Basel) ; 23(3)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36772646

RESUMO

Fiber electronics, such as those produced by the electrospinning technique, have an extensive range of applications including electrode surfaces for batteries and sensors, energy storage, electromagnetic interference shielding, antistatic coatings, catalysts, drug delivery, tissue engineering, and smart textiles. New composite materials and blends from conductive-semiconductive polymers (C-SPs) offer high surface area-to-volume ratios with electrical tunability, making them suitable for use in fields including electronics, biofiltration, tissue engineering, biosensors, and "green polymers". These materials and structures show great potential for embedded-electronics tissue engineering, active drug delivery, and smart biosensing due to their electronic transport behavior and mechanical flexibility with effective biocompatibility. Doping, processing methods, and morphologies can significantly impact the properties and performance of C-SPs and their composites. This review provides an overview of the current literature on the processing of C-SPs as nanomaterials and nanofibrous structures, mainly emphasizing the electroactive properties that make these structures suitable for various applications.

5.
Haemophilia ; 27 Suppl 3: 96-102, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32490595

RESUMO

Joint bleeds cause major morbidity in haemophilia patients. The synovial tissue is responsible for removal of blood remnants from the joint cavity. But blood components, especially iron, lead to a series of changes in the synovial tissue: inflammation, proliferation and neovascularization. These changes make the synovium vulnerable to subsequent bleeding and as such a vicious cycle of bleeding-synovitis-bleeding may develop leading to chronic synovitis. The initial step in the treatment is adequate clotting factor supplementation and immediate physiotherapeutic involvement. If these measures fail, synovectomy may be indicated. Non-surgical options are chemical and radioactive synovectomy. This is a relatively non-invasive procedure to do synovectomy, leading to a reduction in pain and joint bleeds. Radioactive synovectomy seems more effective than chemical synovectomy in larger joints. Surgical options are open and arthroscopic synovectomy. Open synovectomy has been found to decrease the incidence of breakthrough bleeds but at the cost of loss of joint motion. Use of arthroscopic synovectomy has been advocated to reduce bleeding episodes with less morbidity to extra-articular tissue and preservation of joint motion. Use of a continuous passive motion (CPM) machine and early mobilization can decrease the postoperative stiffness and promote early recovery. This review addresses the current understanding of synovitis and its treatment options with specific emphasis on chemical and radioactive synovectomy and surgical options.


Assuntos
Hemofilia A , Sinovite , Artroscopia , Hemofilia A/complicações , Humanos , Articulação do Joelho , Recidiva , Sinovectomia , Sinovite/cirurgia
6.
Haemophilia ; 26(6): 1072-1080, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33058441

RESUMO

INTRODUCTION: The Hemophilia Joint Health Score (HJHS) was developed to detect early changes in joint health in children and adolescents with haemophilia. The HJHS is considered by some to be too time consuming for clinical use and this may limit broad adoption. AIM: This study was a first step to develop a shorter and/or more convenient version of the HJHS for the measurement of joint function in children and young adults with haemophilia, by combining real-life data and expert opinion. METHODS: A cross-sectional multicenter secondary analysis on pooled data of published studies using the HJHS (0-124, optimum score 0) in persons with haemophilia A/B aged 4-30 was performed. Least informative items, scoring options and/or joints were identified. An expert group of 19 international multidisciplinary experts evaluated the results and voted on suggestions for adaptations in a structured meeting (consensus set at ≥ 80%). RESULTS: Original data on 499 persons with haemophilia from 7 studies were evaluated. Median age was 15.0 years [range 4.0-29.9], 83.2% had severe haemophilia and 61.5% received prophylaxis. Median (IQR) HJHS total was 6.0 (1.0-17.0). The items 'duration swelling' and 'crepitus' were identified as clinically less informative and appointed as candidates for reduction. CONCLUSION: Analysis of 499 children and young adults with haemophilia showed that the HJHS is able to discriminate between children and adults and different treatment regimens. Reduction of the items 'duration swelling' and 'crepitus' resulted in the HJHSshort , which had the same discriminative ability. Additional steps are needed to achieve a substantially shorter HJHS assessment.


Assuntos
Hemofilia A/complicações , Articulações/fisiopatologia , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino
7.
Haemophilia ; 25(5): 821-830, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322311

RESUMO

AIM: To compare subjective and objective measures of adherence to prophylaxis in haemophilia. METHODS: In this cross-sectional study, we compared participants' self-perceived adherence and their estimate of the number of clotting factor concentrates (CFCs) that had been missed over the last period of CFC dispensation with an objective measure of adherence based on counts of CFC vials returned by participants. RESULTS: We included 29 out of 31 eligible patients in the study. There was no significant correlation between self-perceived degree of adherence and the objective classification of adherence (Rho: 0.10, 95% CI: -028 to 0.46, P: 0.61) and between the classification of adherence based on the proportion of missed CFC doses assessed by participants' self-report and objectively (Rho: 0.32, 95% CI: -0.01 to 0.59, P: 0.11). Conversely, we found evidence of moderate correlation between the proportion of missed CFC doses as assessed by participants' self-report and objectively (Rho: 0.56, 95% CI: 0.24 to 0.77, P: 0.003). Participants' self-perceived adherence was 3 times more likely to be rated as very good or good than it was for the objective assessment to be classified as adherent or suboptimally adherent. CONCLUSION: Our results showed significant discrepancies between subjective and objective measures of adherence, which likely reflect the influence of social desirability bias in self-reported measures and different concepts of adherence between patients/caregivers and haemophilia experts. Additionally, our results allow us to hypothesize that studies on adherence to prophylaxis in haemophilia relying exclusively on information from self-reports and questionnaires may substantially overestimate adherence levels.


Assuntos
Hemofilia A/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Autorrelato , Adulto Jovem
8.
Haemophilia ; 25(3): 509-513, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30866133

RESUMO

One of the key features of good practice in medicine is the doctor-patient communication. Radiation protection standards for radiosynovectomy (RS) is limited. Yttrium-90 is a beta-emitting radioisotope used in RS to treat joint pain from haemophilic arthritis. ICRP 94 states that if a patient is treated with up to 200 MBq, there is no need for further precautions when it comes to public exposure, however, activities can go up to 370 MBq in RS for the knee. This study analysed 119 family members' safety (16.7% pregnant women). The ambient dose equivalent rate was measured within four distances. A survey was carried analysing risk groups and time spent next to patients. Results showed that family members should be advised to remain at 1.0 m from the patient to decrease accumulated dose by 97.6%. The dose per activity factors estimated in this study is also a useful tool during the risk assessment and doctor/patient communication. Pamphlets were distributed with radiation protection recommendations. Ambient dose equivalent was low enough to show that RS is a safe procedure for family members, which is essential to promote adherence to RS in countries where it is needed but not performed due to lack of information on radiation safety.


Assuntos
Artrite/complicações , Artrite/radioterapia , Família , Hemofilia A/complicações , Pacientes Ambulatoriais , Doses de Radiação , Sinovectomia/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Radiocirurgia/efeitos adversos , Segurança , Radioisótopos de Ítrio/uso terapêutico
10.
Sci Rep ; 13(1): 10694, 2023 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-37394523

RESUMO

According to data from the U.S. Center for Disease Control and Prevention, as of June 2020, a significant number of African Americans had been infected with the coronavirus disease, experiencing disproportionately higher death rates compared to other demographic groups. These disparities highlight the urgent need to examine the experiences, behaviors, and opinions of the African American population in relation to the COVID-19 pandemic. By understanding their unique challenges in navigating matters of health and well-being, we can work towards promoting health equity, eliminating disparities, and addressing persistent barriers to care. Since Twitter data has shown significant promise as a representation of human behavior and for opinion mining, this study leverages Twitter data published in 2020 to characterize the pandemic-related experiences of the United States' African American population using aspect-based sentiment analysis. Sentiment analysis is a common task in natural language processing that identifies the emotional tone (i.e., positive, negative, or neutral) of a text sample. Aspect-based sentiment analysis increases the granularity of sentiment analysis by also extracting the aspect for which sentiment is expressed. We developed a machine learning pipeline consisting of image and language-based classification models to filter out tweets not related to COVID-19 and those unlikely published by African American Twitter subscribers, leading to an analysis of nearly 4 million tweets. Overall, our results show that the majority of tweets had a negative tone, and that the days with larger numbers of published tweets often coincided with major U.S. events related to the pandemic as suggested by major news headlines (e.g., vaccine rollout). We also show how word usage evolved throughout the year (e.g., outbreak to pandemic and coronavirus to covid). This work also points to important issues like food insecurity and vaccine hesitation, along with exposing semantic relationships between words, such as covid and exhausted. As such, this work furthers understanding of how the nationwide progression of the pandemic may have impacted the narratives of African American Twitter users.


Assuntos
Negro ou Afro-Americano , COVID-19 , Análise de Sentimentos , Mídias Sociais , Humanos , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/psicologia , Pandemias/estatística & dados numéricos , Mídias Sociais/estatística & dados numéricos , Estados Unidos/epidemiologia
11.
Front Res Metr Anal ; 8: 1204801, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601534

RESUMO

The COVID-19 pandemic highlighted two critical barriers hindering rapid response to novel pathogens. These include inefficient use of existing biological knowledge about treatments, compounds, gene interactions, proteins, etc. to fight new diseases, and the lack of assimilation and analysis of the fast-growing knowledge about new diseases to quickly develop new treatments, vaccines, and compounds. Overcoming these critical challenges has the potential to revolutionize global preparedness for future pandemics. Accordingly, this article introduces a novel knowledge graph application that functions as both a repository of life science knowledge and an analytics platform capable of extracting time-sensitive insights to uncover evolving disease dynamics and, importantly, researchers' evolving understanding. Specifically, we demonstrate how to extract time-bounded key concepts, also leveraging existing ontologies, from evolving scholarly articles to create a single temporal connected source of truth specifically related to COVID-19. By doing so, current knowledge can be promptly accessed by both humans and machines, from which further understanding of disease outbreaks can be derived. We present key findings from the temporal analysis, applied to a subset of the resulting knowledge graph known as the temporal keywords knowledge graph, and delve into the detailed capabilities provided by this innovative approach.

12.
ACS Appl Mater Interfaces ; 15(39): 46571-46578, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37733934

RESUMO

In the contemporary world, wearable electronics and smart textiles/fabrics are galvanizing a transformation of the health care, aerospace, military, and commercial industries. However, a major challenge that exists is the manufacture of electronic circuits directly on fabrics. In this work, we addressed the issue by developing a sequential manufacturing process. First, the target fabric was coated with a customized ink containing lignin. Next, a desired circuit layout was patterned by laser burning lignin, converting it to carbon and establishing a conductive template on the fabric. At last, using an in-house-designed printer, a devised localized hydrogen evolution-assisted (HEA) copper electroplating method was applied to metalize the surface of the laser-burned lignin pattern to achieve a very low resistive circuit layout (0.103 Ω for a 1 cm long interconnect). The nanostructure and material composition of the different layers were investigated via scanning electron microscopy, energy-dispersive X-ray spectroscopy (EDX), Raman spectroscopy, and Fourier-transform infrared spectroscopy (FTIR). Monitoring the conductivity change before and after bending, rolling, stretching, washing, and adhesion tests presented remarkable mechanical stability due to the entanglement of the copper nanostructure to the fibers of the fabric. Furthermore, the HEA method was used to solder a light-emitting diode to a patterned circuit on the fabric by growing copper at the terminals, creating interconnects. The presented sequential printing method has the potential for fabricating reliable wearable electronics for various applications, particularly in medical monitoring.

13.
Materials (Basel) ; 16(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37109942

RESUMO

In this study, morphology and in vitro response of electroconductive composite nanofibers were explored for biomedical use. The composite nanofibers were prepared by blending the piezoelectric polymer poly(vinylidene fluoride-trifluorethylene) (PVDF-TrFE) and electroconductive materials with different physical and chemical properties such as copper oxide (CuO), poly(3-hexylthiophene) (P3HT), copper phthalocyanine (CuPc), and methylene blue (MB) resulting in unique combinations of electrical conductivity, biocompatibility, and other desirable properties. Morphological investigation via SEM analysis has remarked some differences in fiber size as a function of the electroconductive phase used, with a reduction of fiber diameters for the composite fibers of 12.43% for CuO, 32.87% for CuPc, 36.46% for P3HT, and 63% for MB. This effect is related to the peculiar electroconductive behavior of fibers: measurements of electrical properties showed the highest ability to transport charges of methylene blue, in accordance with the lowest fibers diameters, while P3HT poorly conducts in air but improves charge transfer during the fiber formation. In vitro assays showed a tunable response of fibers in terms of viability, underlining a preferential interaction of fibroblast cells to P3HT-loaded fibers that can be considered the most suitable for use in biomedical applications. These results provide valuable information for future studies to be addressed at optimizing the properties of composite nanofibers for potential applications in bioengineering and bioelectronics.

14.
Polymers (Basel) ; 14(23)2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36501468

RESUMO

In this work, the electrospinning technique is used to fabricate a polymer-polymer coaxial structure nanofiber from the p-type regioregular polymer poly(3-hexylthiophene-2,5-diyl) (P3HT) and the n-type conjugated ladder polymer poly(benzimidazobenzophenanthroline) (BBL) of orthogonal solvents. Generally, the fabrication of polymeric coaxial nanostructures tends to be troublesome. Using the electrospinning technique, P3HT was successfully used as the core, and the BBL as the shell, thus conceptually forming a p-n junction that is cylindrical in form with diameters in a range from 280 nm to 2.8 µm. The UV-VIS of P3HT/PS blend solution showed no evidence of separation or precipitation, while the combined solutions of P3HT/PS and BBL were heterogeneous. TEM images show a well-formed coaxial structure that is normally not expected due to rapid reaction and solidification when mixed in vials in response to orthogonal solubility. For this reason, extruding it by using electrostatic forces promoted a quick elongation of the polymers while forming a concise interface. Single nanofiber electrical characterization demonstrated the conductivity of the coaxial surface of ~1.4 × 10-4 S/m. Furthermore, electrospinning has proven to be a viable method for the fabrication of pure semiconducting coaxial nanofibers that can lead to the desired fabrication of fiber-based electronic devices.

15.
Viruses ; 15(1)2022 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-36680125

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19) that has caused a pandemic with millions of human infections. There continues to be a pressing need to develop potential therapies and vaccines to inhibit SARS-CoV-2 infection to mitigate the ongoing pandemic. Epidemiological data from the current pandemic indicates that there may be sex-dependent differences in disease outcomes. To investigate these differences, we proposed to use common small animal species that are frequently used to model disease with viruses. However, common laboratory strains of mice are not readily infected by SARS-CoV-2 because of differences in the angiotensin-converting enzyme 2 (ACE2), the cellular receptor for the virus. To overcome this limitation, we transduced common laboratory accessible strains of mice of different sexes and age groups with a novel a triple AAV6 mutant, termed AAV6.2FF, encoding either human ACE2 or luciferase via intranasal administration to promote expression in the lung and nasal turbinates. Infection of AAV-hACE2-transduced mice with SARS-CoV-2 resulted in high viral titers in the lungs and nasal turbinates, establishment of an IgM and IgG antibody response, and modulation of lung and nasal turbinate cytokine profiles. There were insignificant differences in infection characteristics between age groups and sex-related differences; however, there were significant strain-related differences between BALB/c vs. C57BL/6 mice. We show that AAV-hACE2-transduced mice are a useful for determining immune responses and for potential evaluation of SARS-CoV-2 vaccines and antiviral therapies, and this study serves as a model for the utility of this approach to rapidly develop small-animal models for emerging viruses.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Humanos , Camundongos , Enzima de Conversão de Angiotensina 2/genética , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Dependovirus/genética , Dependovirus/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , SARS-CoV-2/genética , SARS-CoV-2/metabolismo
16.
Mol Ther Methods Clin Dev ; 26: 505-518, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36092367

RESUMO

Filoviruses cause severe hemorrhagic fever with case fatality rates as high as 90%. Filovirus-specific monoclonal antibodies (mAbs) confer protection in nonhuman primates as late as 5 days after challenge, and FDA-approved mAbs REGN-EB3 and mAb114 have demonstrated efficacy against Ebola virus (EBOV) infection in humans. Vectorized antibody expression mediated by adeno-associated virus (AAV) can generate protective and sustained concentrations of therapeutic mAbs in animal models for a variety of infectious diseases, including EBOV. Here we demonstrate that AAV6.2FF-mediated expression of murine IgG2a EBOV mAbs, 2G4 and 5D2, protects from mouse-adapted (MA)-EBOV infection with none of the surviving mice developing anti-VP40 antibodies above background. Protective serum concentrations of AAV6.2FF-2G4/AAV6.2FF-5D2 did not alter endogenous antibody responses to heterologous virus infection. AAV-mediated expression of EBOV mAbs 100 and 114, and pan-ebolavirus mAbs, FVM04, ADI-15878, and CA45, as human IgG1 antibodies conferred protection against MA-EBOV at low serum concentrations, with minimum protective serum levels as low as 2 µg/mL. Vectorized expression of murine IgG2a or human IgG1 mAbs led to sustained expression in the serum of mice for >400 days or for the lifetime of the animal, respectively. AAV6.2FF-mediated mAb expression offers an alternative to recombinant antibody administration in scenarios where long-term protection is preferable to passive immunization.

17.
Biomedicines ; 10(2)2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35203573

RESUMO

Epithelial ovarian cancer is the deadliest gynecological malignancy. The lack of effective treatments highlights the need for novel therapeutic interventions. The aim of this study was to investigate whether sustained adeno-associated virus (AAV) vector-mediated expression of vascular normalizing agents 3TSR and Fc3TSR and the antiangiogenic monoclonal antibody, Bevacizumab, with or without oncolytic virus treatment would improve survival in an orthotopic syngeneic mouse model of epithelial ovarian carcinoma. AAV vectors were administered 40 days post-tumor implantation and combined with oncolytic avian orthoavulavirus-1 (AOaV-1) 20 days later, at the peak of AAV-transgene expression, to ascertain whether survival could be extended. Flow cytometry conducted on blood samples, taken at an acute time point post-AOaV-1 administration (36 h), revealed a significant increase in activated NK cells in the blood of all mice that received AOaV-1. T cell analysis revealed a significant increase in CD8+ tumor specific T cells in the blood of AAV-Bevacizumab+AOaV-1 treated mice compared to control mice 10 days post AOaV-1 administration. Immunohistochemical staining of primary tumors harvested from a subset of mice euthanized 90 days post tumor implantation, when mice typically have large primary tumors, secondary peritoneal lesions, and extensive ascites fluid production, revealed that AAV-3TSR, AAV-Fc3TSR+AOaV-1, or AAV-Bevacizumab+AOaV-1 treated mice had significantly more tumor-infiltrating CD8+ T cells than PBS controls. Despite AAV-mediated transgene expression waning faster in tumor-bearing mice than in non-tumor bearing mice, all three of the AAV therapies significantly extended survival compared to control mice; with AAV-Bevacizumab performing the best in this model. However, combining AAV therapies with a single dose of AOaV-1 did not lead to significant extensions in survival compared to AAV therapies on their own, suggesting that additional doses of AOaV-1 may be required to improve efficacy in this model. These results suggest that vectorizing anti-angiogenic and vascular normalizing agents is a viable therapeutic option that warrants further investigation, including optimizing combination therapies.

18.
IEEE Trans Nanobioscience ; 20(4): 577-580, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34310315

RESUMO

This work presents, silicon carbide nanoparticles (SiCNPs) embedded in a conductive polymer (CP) to be electrospun to fabricate a nanofibrous membrane and a thin-film. Electrochemical enzymatic glucose sensing mechanism of an electrospun nanofibrous membrane (ENFM) of SiCNPs in a CP compared to a spin-coated-thin-film (SCTF) of SiCNPs in a CP. Fiber alignment in the form of a matrix is a key factor that determines the physical properties of nanofiber membrane compared to thin-film. It is found that glucose sensing electrodes formed by a SiCNPs-ENFM has enhanced binding of the glucose oxidase (GOx) enzyme within the fibrous membrane as compared to a SiCNPs-SCTF. The SiCNPs-ENFM and SiCNPs-SCTF glucose sensing electrodes were characterized for morphology by using scanning electron microscopy (SEM) and for electrochemical activity by using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and chronoamperometry (CA) methods. SiCNPs-ENFM based glucose electrodes shown a detection range from a 0.5 mM to 20 mM concentration with a better sensitivity of [Formula: see text]/gmMcm2, and low limit of detection (LOD) 552.89 nM compared to SiCNPs-SCTF with sensitivity of [Formula: see text]/gmMcm2 and LOD of [Formula: see text]. The change in current level with SiCNPs-ENFM was ~14% contrast to ~75% with the SiCNPs-SCTF based glucose sensor over 50 days. The electrochemical analysis results demonstrated that the SiCNPs-ENFM electrode provides enhanced sensitivity, better limit of detection (LOD), and durability compared to SiCNPs-SCTF based glucose sensing electrode.


Assuntos
Técnicas Biossensoriais , Nanofibras , Nanopartículas , Compostos Inorgânicos de Carbono , Técnicas Eletroquímicas , Eletrodos , Glucose , Compostos de Silício
19.
Biosens Bioelectron ; 186: 113285, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34004507

RESUMO

This paper presents an electrospun-nanofibrous-membrane (ENFM) of silicon carbide nanoparticles (SiCNPs) with a conductive polymer (CP) for an electrochemical enzymatic glucose sensor. The surface area of a fiber matrix is a key physical property of a nanofiber membrane for enzyme binding. It is found that glucose sensing electrodes, having a SiCNPs-ENFM nanostructure, show enhanced binding of glucose oxidase (GOx) enzyme within the fibrous membrane. Morphological characterization of SiCNPs based ENFM was performed by using scanning electron microscopy (SEM) and using transmission electron microscopy (TEM) for SiC nanoparticles. The electrochemical analysis of SiCNPs-ENFM electrode was conducted by using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and chronoamperometry (CA) methods. Glucose concentration was detected at +0.6 V in a 5 mM potassium ferricyanide electrolyte. SiCNPs-ENFM based glucose electrodes show a detection range from 0.5 mM to 20 mM concentration with the sensitivity of 30.75 µA/mM cm2 and the detection limit was 0.56 µM. The lower change in current response for SiCNPs-ENFM based glucose sensing electrodes was observed for a 50 day period.


Assuntos
Técnicas Biossensoriais , Nanofibras , Nanopartículas , Compostos Inorgânicos de Carbono , Técnicas Eletroquímicas , Eletrodos , Enzimas Imobilizadas , Glucose , Glucose Oxidase , Compostos de Silício
20.
Z Med Phys ; 31(1): 16-22, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33191067

RESUMO

PURPOSE: We analyzed the effect of the use of Eye Protective Equipment (EPE) and the best position to use individual dosimeters to estimate the eye lens radiation dose to a medical staff that works with yttrium-90. METHODS: Three Alderson-Head-Phantoms were exposed to 58MBq of 90Y for 24h, in two different experiments: (1) at different dosimeter placements and (2) with and without the use of EPE. The measurements were carried on by thermoluminescent technique. RESULTS: Doses received by dosimeters on both lenses were more closely represented by the ones placed between the eyes than those on the temples, which underestimated the doses by a factor of 3. Also, the transmission factors showed that the EPE was able to reduce the Hp(3) values from about 78% to 92%. CONCLUSIONS: This study demonstrated that the use of EPE can optimize the 90Y eye lens dose. An individual dosimeter should be worn between the eyes for an appropriate estimate of this equivalent dose.


Assuntos
Análise Custo-Benefício , Cristalino/efeitos da radiação , Doses de Radiação , Compostos Radiofarmacêuticos , Radioisótopos de Ítrio
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