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1.
Int J Mol Sci ; 25(1)2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38203243

RESUMEN

Small extracellular vesicles (sEVs) contain microRNAs (miRNAs) which have potential to act as disease-specific biomarkers. The current study uses an established method to maintain human thyroid tissue ex vivo on a tissue-on-chip device, allowing the collection, isolation and interrogation of the sEVs released directly from thyroid tissue. sEVs were analysed for differences in miRNA levels released from benign thyroid tissue, Graves' disease tissue and papillary thyroid cancer (PTC), using miRNA sequencing and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to identify potential biomarkers of disease. Thyroid biopsies from patients with benign tissue (n = 5), Graves' disease (n = 5) and PTC (n = 5) were perfused with medium containing sEV-depleted serum for 6 days on the tissue-on-chip device. During incubation, the effluents were collected and ultracentrifuged to isolate sEVs; miRNA was extracted and sequenced (miRNASeq). Out of the 15 samples, 14 passed the quality control and miRNASeq analysis detected significantly higher expression of miR-375-3p, miR-7-5p, miR-382-5p and miR-127-3p in the sEVs isolated from Graves' tissue compared to those from benign tissue (false discovery rate; FDR p < 0.05). Similarly, miR-375-3p and miR-7-5p were also detected at a higher level in the Graves' tissue sEVs compared to the PTC tissue sEVs (FDR p < 0.05). No significant differences were observed between miRNA in sEVs from PTC vs. those from benign tissue. These results were supported by Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). The novel findings demonstrate that the tissue-on-chip technology is a robust method for isolating sEVs directly from the tissue of interest, which has permitted the identification of four miRNAs, with which further investigation could be used as biomarkers or therapeutic targets within thyroid disease.


Asunto(s)
Vesículas Extracelulares , Enfermedad de Graves , MicroARNs , Enfermedades de la Tiroides , Neoplasias de la Tiroides , Humanos , MicroARNs/genética , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/genética , Control de Calidad , Biomarcadores , Vesículas Extracelulares/genética , Cáncer Papilar Tiroideo
2.
Cytokine ; 152: 155836, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35219004

RESUMEN

BACKGROUND: Interferon-γ (IFN-γ) is a pleiotropic immunomodulatory cytokine. Because of its contradictory and even dualistic roles in malignancies, its potential as a biomarker remains to be unraveled. AIM: To evaluate the prognostic significance of serum IFN-γ in hormonally treated breast cancer patients. MATERIAL AND METHODS: The study included 72 premenopausal breast cancer patients with known clinicopathological characteristics. All patients received adjuvant hormonal therapy based on hormone receptor-positivity. The median follow-up period was 93 months. IFN-γ serum protein levels were determined by quantitative ELISA. Prognostic performance was evaluated by the receiver operating characteristic (ROC), Cox proportional hazards regression and Kaplan-Meier analyses. Classification of patients into IFN-γlow and IFN-γhigh subgroups was performed by the use of the outcome-oriented cut-off point categorization approach. RESULTS: The best prognostic performance was achieved by IFN-γ (AUC = 0.24 and p = 0.01 for distant events, AUC = 0.29 and p = 0.01 for local and distant events combined). Age and IFN-γ were prognostically significant in instances of all types of outcomes and IFN-γ was the independent prognostic parameter (Cox regression). There was a significant difference between IFN-γ values of patients without any events and those with distant metastases (Mann-Whitney test, p = 0.007). IFN-γ levels correlated significantly with nodal status and tumor stage (Spearman's rank order, r = -0.283 and r = -0.238, respectively). Distant recurrence incidence was 4% for the IFN-γhigh subgroup and 33% for the IFN-γlow subgroup (Kaplan-Meier analysis). CONCLUSIONS: Raised serum IFN-γ levels associate independently with favorable disease outcome in hormonally dependent breast cancer.


Asunto(s)
Neoplasias de la Mama , Biomarcadores de Tumor , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Humanos , Interferón gamma , Estimación de Kaplan-Meier , Pronóstico
3.
J Power Sources ; 520: 230875, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-35125632

RESUMEN

In recent years, bioelectrochemical systems have advanced towards upscaling applications and tested during field trials, primarily for wastewater treatment. Amongst reported trials, two designs of urine-fed microbial fuel cells (MFCs) were tested successfully on a pilot scale as autonomous sanitation systems for decentralised area. These designs, known as ceramic MFCs ( c -MFCs) and self-stratifying MFCs ( s -MFC), have never been calibrated under similar conditions. Here, the most advanced versions of both designs were assembled and tested under similar feeding conditions. The performance and efficiency were evaluated under different hydraulic retention times (HRT), through chemical oxygen demand measures and polarisation experiments. Results show that c -MFCs displayed constant performance independently from the HRT (32.2 ± 3.9 W m-3) whilst displaying high energy conversion efficiency at longer HRT (NER COD  = 2.092 ± 0.119 KWh.Kg COD -1, at 24h HRT). The s -MFC showed a correlation between performance and HRT. The highest performance was reached under short HRT (69.7 ± 0.4 W m-3 at 3h HRT), but the energy conversion efficiency was constant independently from the HRT (0.338 ± 0.029 KWh.Kg COD -1). The c -MFCs and s -MFCs similarly showed the highest volumetric efficiency under long HRT (65h) with NER V of 0.747 ± 0.010 KWh.m-3 and 0.825 ± 0.086 KWh.m-3, respectively. Overall, c -MFCs seems more appropriate for longer HRT and s -MFCs for shorter HRT.

4.
Amino Acids ; 53(4): 489-506, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33404912

RESUMEN

Despite intense research efforts, our pharmaceutical repertoire against high-grade brain tumours has not been able to increase patient survival for a decade and life expectancy remains at less than 16 months after diagnosis, on average. Inhibitors of protein arginine methyltransferases (PRMTs) have been developed and investigated over the past 15 years and have now entered oncology clinical trials, including for brain tumours. This review collates recent advances in the understanding of the role of PRMTs and arginine methylation in brain tumours. We provide an up-to-date literature review on the mechanisms for PRMT regulation. These include endogenous modulators such as alternative splicing, miRNA, post-translational modifications and PRMT-protein interactions, and synthetic inhibitors. We discuss the relevance of PRMTs in brain tumours with a particular focus on PRMT1, -2, -5 and -8. Finally, we include a future perspective where we discuss possible routes for further research on arginine methylation and on the use of PRMT inhibitors in the context of brain tumours.


Asunto(s)
Arginina/metabolismo , Neoplasias Encefálicas/metabolismo , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/enzimología , Inhibidores Enzimáticos/uso terapéutico , Humanos , Metilación , Procesamiento Proteico-Postraduccional , Proteína-Arginina N-Metiltransferasas/antagonistas & inhibidores , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo
5.
J Power Sources ; 506: 230004, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34539048

RESUMEN

Hygienic measures are extremely important to avoid the transmission of contagious viruses and diseases. The use of an electronic faucet increases the hygiene, encourages hand washing, avoids touching the faucet for opening and closing, and it saves water, since the faucet is automatically closed. The microbial fuel cell (MFC) technology has the capability to convert environmental waste into energy. The implementation of low cost ceramic MFCs into electronic interfaces integrated in toilets, would offer a compact powering system as well as an environmentally friendly small-scale treatment plant. In this work, the use of low cost ceramic MFCs to power an L20-E electronic faucet is presented for the first time. A single MFC was capable of powering an electronic faucet with an open/close cycle of 8.5 min, with 200 ml of urine. With a footprint of 360 cm3, the MFC could easily be integrated in a toilet. The possibility to power e-toilet components with MFCs offers a sustainable energy generation system. Other electronic components including an automatic flush, could potentially be powered by MFCs and contribute to the maintenance efficiency and hygiene of the public toilets, leading to a new generation of self-sustained energy recovering e-toilets.

6.
Int J Hydrogen Energy ; 46(67): 33594-33600, 2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34594062

RESUMEN

The aim of the present study is to enhance the performance of a microbial fuel cell (MFC) design by making simple interventions. Specifically, terracotta "t" and mullite "m" ceramics are tested as membranes while carbon veil and carbon cloth are used as electrodes. In the case of "m" cylinders different dimensions are examined (m: ID 30 mm x height 11.5 mm; sm: ID 18 mm x height 18 mm). The units operated continuously with urine as the feedstock. The best performing is the sm type (60-100 µW), followed by the t type (40-80 µW) and the m type (20-40 µW). Polarisation experiments indicated that activated carbon on the anode enhances the power output (t: 423 µW, sm: 288 µW). Similarly, the increase of the surface area and the addition of stainless steel mesh on the cathode improves the power performance for the "sm" and the "t" units. Furthermore, it is shown that the design with the smaller internal diameter, performs better and is more stable through time.

7.
Apoptosis ; 25(1-2): 29-41, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31654241

RESUMEN

Accumulation of tissue factor (TF) within cells leads to cellular apoptosis mediated through p38 and p53 pathways. In this study, the involvement of Src1 in the induction of TF-mediated cell apoptosis, and the mechanisms of Src1 activation were investigated. Human coronary artery endothelial cell (HCAEC) were transfected with plasmids to express the wild-type TF (TFWt-tGFP), or a mutant (Ser253 → Ala) which is incapable of being released from cells (TFAla253-tGFP). The cells were then activated with PAR2-agonist peptide (SLIGKV-NH) and the phosphorylation of Src and Rac, and also the kinase activity of Src were assessed. Transfected cells were also pre-incubated with pp60c Src inhibitor, FAK inhibitor-14, or a blocking anti-ß1-integrin antibody prior to activation and the phosphorylation of p38 as well as cellular apoptosis was examined. Finally, cells were co-transfected with the plasmids, together with a Src1-specific siRNA, activated as above and the cellular apoptosis measured. Activation of PAR2 lead to the phosphorylation of Src1 and Rac1 proteins at 60 min regardless of TF expression. Moreover, Src phosphorylation and kinase activity was prolonged up to 100 min in the presence of TF, with a significantly higher magnitude when the non-releasable TFAla253-tGFP was expressed in HCAEC. Inhibition of Src with pp60c, or suppression of Src1 expression in cells, reduced p38 phosphorylation and prevented cellular apoptosis. In contrast, inhibition of FAK had no significant influence on Src kinase activity or cellular apoptosis. Finally, pre-incubation of cells with an inhibitory anti-ß1-integrin antibody reduced both Src1 activation and cellular apoptosis. Our data show for the first time that the over-activation of Src1 is a mediator of TF-induced cellular apoptosis in endothelial cells through a mechanism that is dependent on its interaction with ß1-integrin.


Asunto(s)
Apoptosis , Células Endoteliales/metabolismo , Integrina beta1/metabolismo , Proteínas Proto-Oncogénicas pp60(c-src)/metabolismo , Tromboplastina/metabolismo , Células Endoteliales/citología , Humanos , Integrina beta1/genética , Fosforilación , Proteínas Proto-Oncogénicas pp60(c-src)/genética , Transducción de Señal , Tromboplastina/genética
8.
J Power Sources ; 446: 227328, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31956276

RESUMEN

Many studies have demonstrated that microbial fuel cells (MFC) can be energy-positive systems and power various low power applications. However, to be employed as a low-level power source, MFC systems rely on energy management circuitry, used to increase voltage levels and act as energy buffers, thus delivering stable power outputs. But stability comes at a cost, one that needs to be kept minimal for the technology to be deployed into society. The present study reports, for the first time, the use of a MFC system that directly and continuously powered a small application without any electronic intermediary. A cascade comprising four membrane-less MFCs modules and producing an average of 62  mA at 2550 mV (158 mW) was used to directly power a microcomputer and its screen (Gameboy Color, Nintendo®). The polarisation experiment showed that the cascade produced 164 mA, at the minimum voltage required to run the microcomputer (ca. 1.850 V). As the microcomputer only needed ≈70 mA, the cascade ran at a higher voltage (2.550 V), thus, maintaining the individual modules at a high potential (>0.55 V). Running the system at these high potentials helped avoid cell reversal, thus delivering a stable level of energy without the support of any electronics.

9.
Electrochim Acta ; 353: 136388, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32884154

RESUMEN

This work is presenting for the first time the use of inexpensive and efficient anode material for boosting power production, as well as improving electrofiltration of human urine in tubular microbial fuel cells (MFCs). The MFCs were constructed using unglazed ceramic clay functioning as the membrane and chassis. The study is looking into effective anodic surface modification by applying activated carbon micro-nanostructure onto carbon fibres that allows electrode packing without excessive enlargement of the electrode. The surface treatment of the carbon veil matrix resulted in 3.7 mW (52.9 W m-3 and 1626 mW m-2) of power generated and almost a 10-fold increase in the anodic current due to the doping as well as long-term stability in one year of continuous operation. The higher power output resulted in the synthesis of clear catholyte, thereby i) avoiding cathode fouling and contributing to the active splitting of both pH and ions and ii) transforming urine into a purified catholyte - 30% salt reduction - by electroosmotic drag, whilst generating - rather than consuming - electricity, and in a way demonstrating electrofiltration. For the purpose of future technology implementation , the importance of simultaneous increase in power generation, long-term stability over 1 year and efficient urine cleaning by using low-cost materials, is very promising and helps the technology enter the wider market.

10.
Electrochim Acta ; 353: 136530, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32884155

RESUMEN

In this work, a membraneless microbial fuel cell (MFC) with an empty volume of 1.5 mL, fed continuously with hydrolysed urine, was tested in supercapacitive mode (SC-MFC). In order to enhance the power output, a double strategy was used: i) a double cathode was added leading to a decrease in the equivalent series resistance (ESR); ii) the apparent capacitance was boosted up by adding capacitive features on the anode electrode. Galvanostatic (GLV) discharges were performed at different discharge currents. The results showed that both strategies were successful obtaining a maximum power output of 1.59 ± 0.01 mW (1.06 ± 0.01 mW mL-1) at pulse time of 0.01 s and 0.57 ± 0.01 mW (0.38 ± 0.01 mW mL-1) at pulse time of 2 s. The highest energy delivered at ipulse equal to 2 mA was 3.3 ± 0.1 mJ. The best performing SC-MFCs were then connected in series and parallel and tested through GLV discharges. As the power output was similar, the connection in parallel allowed to roughly doubling the current produced. Durability tests over ≈5.6 days showed certain stability despite a light overall decrease.

11.
Int J Hydrogen Energy ; 45(46): 25240-25248, 2020 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-32982026

RESUMEN

Self-stratifying microbial fuel cells with three different electrodes sizes and volumes were operated in supercapacitive mode. As the electrodes size increased, the equivalent series resistance decreased, and the overall power was enhanced (small: ESR = 7.2 Ω and P max  = 13 mW; large: ESR = 4.2 Ω and P max  = 22 mW). Power density referred to cathode geometric surface area and displacement volume of the electrolyte in the reactors. With regards to the electrode wet surface area, the large size electrodes (L-MFC) displayed the lowest power density (460 µW cm-2) whilst the small and medium size electrodes (S-MFC, M-MFC) showed higher densities (668 µW cm-2 and 633 µW cm-2, respectively). With regard to the volumetric power densities the S-MFC, the M-MFC and the L-MFC had similar values (264 µW mL-1, 265 µW mL-1 and 249 µW cm-1, respectively). Power density normalised in terms of carbon weight utilised for fabricating MFC cathodes-electrodes showed high output for smaller electrode size MFC (5811 µW g-1-C- and 3270 µW g-1-C- for the S-MFC and L-MFC, respectively) due to the fact that electrodes were optimised for MFC operations and not supercapacitive discharges. Apparent capacitance was high at lower current pulses suggesting high faradaic contribution. The electrostatic contribution detected at high current pulses was quite low. The results obtained give rise to important possibilities of performance improvements by optimising the device design and the electrode fabrication.

12.
J Environ Manage ; 258: 109992, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-31929046

RESUMEN

The Microbial fuel cell (MFC) technology harnesses the potential of some naturally occurring bacteria for electricity generation. Digested sludge is commonly used as the inoculum to initiate the process. There are, however, health hazards and practical issues associated with the use of digested sludge depending on its origin as well as the location for system deployment. This work reports the development of an efficient electroactive bacterial community within ceramic-based MFCs fed with human urine in the absence of sludge inoculum. The results show the development of a uniform bacterial community with power output levels equal to or higher than those generated from MFCs inoculated with sludge. In this case, the power generation begins within 2 days of the experimental set-up, compared to about 5 days in some sludge-inoculated MFCs, thus significantly reducing the start-up time. The metagenomics analysis of the successfully formed electroactive biofilm (EAB) shows significant shifts between the microbial ecology of the feeding material (fresh urine) and the developed anodic biofilm. A total of 21 bacteria genera were detected in the urine feedstock whilst up to 35 different genera were recorded in the developed biofilm. Members of Pseudomonas (18%) and Anaerolineaceae (17%) dominate the bacterial community of the fresh urine feed while members of Burkholderiaceae (up to 50%) and Tissierella (up to 29%) dominate the anodic EAB. These results highlight a significant shift in the bacterial community of the feedstock towards a selection and adaptation required for the various electrochemical reactions essential for survival through power generation.


Asunto(s)
Fuentes de Energía Bioeléctrica , Biopelículas , Electricidad , Electrodos , Aguas del Alcantarillado
13.
Molecules ; 25(16)2020 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-32785079

RESUMEN

Microbial Fuel Cells (MFCs) employ microbial electroactive species to convert chemical energy stored in organic matter, into electricity. The properties of MFCs have made the technology attractive for bioenergy production. However, a challenge to the mass production of MFCs is the time-consuming assembly process, which could perhaps be overcome using additive manufacturing (AM) processes. AM or 3D-printing has played an increasingly important role in advancing MFC technology, by substituting essential structural components with 3D-printed parts. This was precisely the line of work in the EVOBLISS project, which investigated materials that can be extruded from the EVOBOT platform for a monolithically printed MFC. The development of such inexpensive, eco-friendly, printable electrode material is described below. The electrode in examination (PTFE_FREE_AC), is a cathode made of alginate and activated carbon, and was tested against an off-the-shelf sintered carbon (AC_BLOCK) and a widely used activated carbon electrode (PTFE_AC). The results showed that the MFCs using PTFE_FREE_AC cathodes performed better compared to the PTFE_AC or AC_BLOCK, producing maximum power levels of 286 µW, 98 µW and 85 µW, respectively. In conclusion, this experiment demonstrated the development of an air-dried, extrudable (3D-printed) electrode material successfully incorporated in an MFC system and acting as a cathode electrode.


Asunto(s)
Fuentes de Energía Bioeléctrica , Impresión Tridimensional , Alginatos/química , Fuentes de Energía Bioeléctrica/economía , Carbono/química , Técnicas Electroquímicas , Electrodos , Diseño de Equipo
14.
Appl Energy ; 262: 114475, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-32201452

RESUMEN

The chemical energy contained in urine can be efficiently extracted into direct electricity by Microbial Fuel Cell stacks to reach usable power levels for practical implementation and a decentralised power source in remote locations. Herein, a novel type of the anode electrode was developed using powdered activated carbon (PAC) applied onto the carbon fibre scaffold in the ceramic MFC stack to achieve superior electrochemical performance during 500 days of operation. The stack equipped with modified anodes (MF-CV) produced up to 37.9 mW (21.1 W m-3) in comparison to the control (CV) that reached 21.4 mW (11.9 W m-3) showing 77% increase in power production. The novel combination of highly porous activated carbon particles applied onto the conductive network of carbon fibres promoted simultaneously electrocatalytic activity and increased surface area, resulting in excellent power output from the MFC stack as well as higher treatment rate. Considering the low cost and simplicity of the material preparation, as well as the outstanding electrochemical activity during long term operation, the resulting modification provides a promising anode electrocatalyst for high-performance MFC stacks to enhance urine and waste treatment for the purpose of future scale-up and technology implementation as an applied off-grid energy source.

15.
Appl Energy ; 277: 115514, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-33144751

RESUMEN

The microbial fuel cell (MFC) technology relies on energy storage and harvesting circuitry to deliver stable power outputs. This increases costs, and for wider deployment into society, these should be kept minimal. The present study reports how a MFC system was developed to continuously power public toilet lighting, with for the first time no energy storage nor harvesting circuitry. Two different stacks, one consisting of 15 and the other 18 membrane-less MFC modules, were operated for 6 days and fuelled by the urine of festival goers at the 2019 Glastonbury Music Festival. The 15-module stack was directly connected to 2 spotlights each comprising 6 LEDs. The 18-module stack was connected to 2 identical LED spotlights but going through 2 LED electronic controller/drivers. Twenty hours after inoculation the stacks were able to directly power the bespoke lighting system. The electrical energy produced by the 15-module stack evolved with usage from ≈280 mW (≈2.650 V at ≈105 mA) at the beginning to ≈860 mW (≈2.750 V at ≈300 mA) by the end of the festival. The electrical energy produced by the LED-driven 18-module stack increased from ≈490 mW at the beginning to ≈680 mW toward the end of the festival. During this period, illumination was above the legal standards for outdoor public areas, with the 15-module stack reaching a maximum of ≈89 Lx at 220 cm. These results demonstrate for the first time that the MFC technology can be deployed as a direct energy source in decentralised area (e.g. refugee camps).

16.
Biochim Biophys Acta Mol Cell Res ; 1865(1): 12-24, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28962834

RESUMEN

The exposure and release of TF is regulated by post-translational modifications of its cytoplasmic domain. Here, the potential of Pin1 to interact with the cytoplasmic domain of TF, and the outcome on TF function was examined. MDA-MB-231 and transfected-primary endothelial cells were incubated with either Pin1 deactivator Juglone, or its control Plumbagin, as well as transfected with Pin1-specific or control siRNA. TF release into microvesicles following activation, and also phosphorylation and ubiquitination states of cellular-TF were then assessed. Furthermore, the ability of Pin1 to bind wild-type and mutant forms of overexpressed TF-tGFP was investigated by co-immunoprecipitation. Additionally, the ability of recombinant or cellular Pin1 to bind to peptides of the C-terminus of TF, synthesised in different phosphorylation states was examined by binding assays and spectroscopically. Finally, the influence of recombinant Pin1 on the ubiquitination and dephosphorylation of the TF-peptides was examined. Pre-incubation of Pin1 with Juglone but not Plumbagin, reduced TF release as microvesicles and was also achievable following transfection with Pin1-siRNA. This was concurrent with early ubiquitination and dephosphorylation of cellular TF at Ser253. Pin1 co-immunoprecipitated with overexpressed wild-type TF-tGFP but not Ser258→Ala or Pro259→Ala substituted mutants. Pin1 did interact with Ser258-phosphorylated and double-phosphorylated TF-peptides, with the former having higher affinity. Finally, recombinant Pin1 was capable of interfering with the ubiquitination and dephosphorylation of TF-derived peptides. In conclusion, Pin1 is a fast-acting enzyme which may be utilised by cells to protect the phosphorylation state of TF in activated cells prolonging TF activity and release, and therefore ensuring adequate haemostasis.


Asunto(s)
Micropartículas Derivadas de Células/metabolismo , Peptidilprolil Isomerasa de Interacción con NIMA/fisiología , Tromboplastina/metabolismo , Células Cultivadas , Células Endoteliales/metabolismo , Hemostasis/genética , Humanos , Peptidilprolil Isomerasa de Interacción con NIMA/genética , Fosforilación , Estabilidad Proteica , Transporte de Proteínas , Vías Secretoras/genética
17.
BMC Cancer ; 19(1): 259, 2019 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-30902086

RESUMEN

BACKGROUND: Though the management of malignancies has improved vastly in recent years, many treatment options lack the desired efficacy and fail to adequately augment patient morbidity and mortality. It is increasingly clear that patient response to therapy is unique to each individual, necessitating personalised, or 'precision' medical care. This demand extends to thyroid cancer; ~ 10% patients fail to respond to radioiodine treatment due to loss of phenotypic differentiation, exposing the patient to unnecessary ionising radiation, as well as delaying treatment with alternative therapies. METHODS: Human thyroid tissue (n = 23, malignant and benign) was live-sliced (5 mm diameter × 350-500 µm thickness) then analysed or incorporated into a microfluidic culture device for 96 h (37 °C). Successful maintenance of tissue was verified by histological (H&E), flow cytometric propidium iodide or trypan blue uptake, immunohistochemical (Ki67 detection/ BrdU incorporation) and functional analysis (thyroxine [T4] output) in addition to analysis of culture effluent for the cell death markers lactate dehydrogenase (LDH) and dead-cell protease (DCP). Apoptosis was investigated by Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Differentiation was assessed by evaluation of thyroid transcription factor (TTF1) and sodium iodide symporter (NIS) expression (western blotting). RESULTS: Maintenance of gross tissue architecture was observed. Analysis of dissociated primary thyroid cells using flow cytometry both prior to and post culture demonstrated no significant change in the proportion of viable cells. LDH and DCP release from on-chip thyroid tissue indicated that after an initial raised level of release, signifying cellular damage, detectable levels dropped markedly. A significant increase in apoptosis (p < 0.01) was observed after tissue was perfused with etoposide and JNK inhibitor, but not in control tissue incubated for the same time period. No significant difference in Ki-67 positivity or TTF1/NIS expression was detected between fresh and post-culture thyroid tissue samples, moreover BrdU positive nuclei indicated on-chip cellular proliferation. Cultured thyroid explants were functionally viable as determined by production of T4 throughout the culture period. CONCLUSIONS: The described microfluidic platform can maintain the viability of thyroid tissue slices ex vivo for a minimum of four days, providing a platform for the assessment of thyroid tissue radioiodine sensitivity/adjuvant therapies in real time.


Asunto(s)
Antineoplásicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales/instrumentación , Dispositivos Laboratorio en un Chip , Técnicas de Cultivo de Tejidos/instrumentación , Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos , Humanos , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/patología , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología
18.
J Power Sources ; 429: 30-37, 2019 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-31379405

RESUMEN

Ceramic membranes for MFCs offer a low cost alternative to the expensive ion exchange membranes, whilst promoting catholyte accumulation. However, their physicochemical properties need to be optimised, in order to increase the power output and the catholyte quality from MFCs. Two compositions of fine fire clay (FFC) cured under three firing cycles were manufactured, analysed and tested as ion-exchange and structural material for MFCs. The samples were characterised by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The power and catholyte generated from the ceramic MFCs with different FFC types was also evaluated. The results show a direct correlation between the ohmic resistance, the MFC power generation and the water absorption of the ceramics, giving a maximum power of 1 mW from the MFC with the most absorptive FFC (16.37% water absorbance). A slightly more alkaline catholyte was synthesised from the MFCs with higher water absorption FFC.

19.
J Power Sources ; 412: 416-424, 2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30774187

RESUMEN

The anode and cathode electrodes of a microbial fuel cell (MFC) stack, composed of 28 single MFCs, were used as the negative and positive electrodes, respectively of an internal self-charged supercapacitor. Particularly, carbon veil was used as the negative electrode and activated carbon with a Fe-based catalyst as the positive electrode. The red-ox reactions on the anode and cathode, self-charged these electrodes creating an internal electrochemical double layer capacitor. Galvanostatic discharges were performed at different current and time pulses. Supercapacitive-MFC (SC-MFC) was also tested at four different solution conductivities. SC-MFC had an equivalent series resistance (ESR) decreasing from 6.00â€¯Ω to 3.42â€¯Ω in four solutions with conductivity between 2.5 mScm-1 and 40 mScm-1. The ohmic resistance of the positive electrode corresponded to 75-80% of the overall ESR. The highest performance was achieved with a solution conductivity of 40 mS cm-1 and this was due to the positive electrode potential enhancement for the utilization of Fe-based catalysts. Maximum power was 36.9 mW (36.9 W m-3) that decreased with increasing pulse time. SC-MFC was subjected to 4520 cycles (8 days) with a pulse time of 5 s (ipulse 55 mA) and a self-recharging time of 150 s showing robust reproducibility.

20.
Electrochim Acta ; 307: 241-252, 2019 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-31217626

RESUMEN

A self-stratified microbial fuel cell fed with human urine with a total internal volume of 0.55 ml was investigated as an internal supercapacitor, for the first time. The internal self-stratification allowed the development of two zones within the cell volume. The oxidation reaction occurred on the bottom electrode (anode) and the reduction reaction on the top electrode (cathode). The electrodes were discharged galvanostatically at different currents and the two electrodes were able to recover their initial voltage value due to their red-ox reactions. Anode and cathode apparent capacitance was increased after introducing high surface area activated carbon embedded within the electrodes. Peak power produced was 1.20 ±â€¯0.04 mW (2.19 ±â€¯0.06 mW ml-1) for a pulse time of 0.01 s that decreased to 0.65 ±â€¯0.02 mW (1.18 ±â€¯0.04 mW ml-1) for longer pulse periods (5 s). Durability tests were conducted over 44 h with ≈2600 discharge/recharge cycles. In this relatively long-term test, the equivalent series resistance increased only by 10% and the apparent capacitance decreased by 18%.

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