Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
ACS Appl Mater Interfaces ; 16(13): 16687-16698, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38517362

RESUMO

Industrial emissions, environmental monitoring, and medical fields have put forward huge demands for high-performance and low power consumption sensors. Two-dimensional quasicrystal (2D QC) nanosheets of metallic multicomponent Al70Co10Fe5Ni10Cu5 have emerged as a promising material for gas sensors due to their excellent catalytic and electronic properties. Herein, we demonstrate highly sensitive and selective NO2 sensors developed by low-cost and scalable fabrication techniques using 2D QC nanosheets and α-Fe2O3 nanoparticles. The sensitivity (ΔR/R%) of the optimal amount of 2D QC nanosheet-loaded α-Fe2O3 sensor was 32%, which is significantly larger about 3.5 times than bare α-Fe2O3 sensors for 1 ppm of NO2 at 150 °C operating temperature. The sensors exhibited p-type conduction, and resistance was reduced when exposed to NO2, an oxidizing gas. The enhanced sensing characteristics are a result of the formation of nanoheterojunctions between 2D QC and α-Fe2O3, which improved the charge transport and provided a large sensing signal. In addition, the heterojunction sensor demonstrated excellent NO2 selectivity over other oxidizing and reducing gases. Furthermore, density functional theory calculation examines the adsorption energy and charge transfer between NO2 molecules on the α-Fe2O3(110) and QC/α-Fe2O3(110) heterostructure surfaces, which coincides well with the experimental results.

2.
Nanotechnology ; 35(24)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38467060

RESUMO

Mechanical energy harvesting performances of poly(vinylidene fluoride) (PVDF) based composites are most often correlated with their polar phase and the individual piezoelectricity of the used filler materials. Here we show that the significant enhancement of space charge polarization of the said composites can play the key dominant role in determining their mechanical energy harvesting performance regardless of their polar phase and individual piezoelectricity of the used fillers. For this purpose, ionic liquid has been incorporated into PVDF/0.5(Ba0.7Ca0.3)TiO3-0.5Ba(Ti0.8Zr0.2)O3(BCZT) composites which led to a huge enhancement in space charge polarization. The gradual addition of ionic liquid into 10 wt% BCZT loaded PVDF (PBCZT) has helped in extraordinarily enhancing the conductivity gradually which has confirmed the huge enhancement of space charge polarization. However, after a certain limit of ionic liquid addition, the polar phase of the composite films is decreased. Despite this, the output voltages from the piezoelectric and piezo-tribo hybrid nanogenerators (PENGs and HNGs, respectively) fabricated by using the developed films have been found to be increased gradually with the increase in the ionic liquid amount in PBCZT composite. As the amount of BCZT filler was kept fixed for all the films, this result has confirmed the key role of space charge polarization of PVDF-based composites in determining their mechanical energy harvesting performances compared to the effect of polar phase and individual piezoelectricity of filler. The optimized PENG and HNG devices have shown the output voltage as high as 52 and 167 V, respectively, with power densities ∼85 and 152µW cm-2which predicted their excellent usability in real life energy conversion devices. This work also shows that the effect of extraordinarily enhanced space charge polarization is effective in improving the performance of all types of mechanical energy harvesting devices regardless of their mechanisms (piezoelectric or hybrid).

4.
ACS Appl Mater Interfaces ; 15(39): 45812-45822, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37733300

RESUMO

A significant driving force for the fabrication of IoT-compatible smart health gear integrated with multifunctional sensors is the growing trend in fitness and the overall wellness of the human body. In this work, we present an autonomous motion and activity-sensing device based on the efficacious nucleation of the polar ß-phase in an electroactive polymer. Representatively, we investigate the nucleating effect of TiO2 nanoparticles on weight-modulated PVDF-HFP films (PT-5, PT-10, and PT-15) and subsequently prototype a sensing device with the film that demonstrates superior ß-phase nucleation. The PT-10 film, with an optimal polar ß-phase, shows the highest remnant polarization (2Pr) and energy density of 0.36 µC/cm2 and 22.3 mJ/cm3, respectively, at 60 kV/cm. The films mimic a high pass filter at frequencies above 10 KHz with very low impedance and high ac conductivity values. The frequency-dependent impedance studies reveal an effective interfacial polarization between TiO2 nanoparticles and PVDF-HFP, explicitly observed in the low-frequency region. Consequently, the sensor fabricated with PT-10 as the sensing layer exhibits ultralow frequency detection (25 Hz) resulting from the blood flow muscle oxygenation. The device successfully senses voluntary joint movements of the human body and actively tracks a range of motions, from brisk walking to running. Additionally, through repetitive human finger-tapping motion, the nanogenerator lights up multiple light-emitting diodes in series and charges capacitors of varying magnitudes under 50 s. The real-time human motion sensing and movement tracking modalities of the sensor hold promise in the arena of smart wearables, sports biomechanics, and contact-based medical devices.

5.
J Colloid Interface Sci ; 644: 397-414, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37126890

RESUMO

Manganese and phosphorus co-doped, graphitic carbon nitride (g-C3N4) nanosheet (Mn/P-g-C3N4) is prepared by facile and green calcination process of melamine (C3H6N6), manganese chloride tetrahydrate (MnCl2·4H2O), and ammonium dihydrogen phosphate ((NH4)H2PO4). The Mn/P co-doping significantly enhances magnetic values compared to pristine-g-C3N4, phosphorus-doped g-C3N4 (P-g-C3N4), and manganese-doped g-C3N4 (Mn-g-C3N4). We find that Mn/P-g-C3N4 is a half-metallic ferromagnetic material having a magnetic moment and Curie temperature of 4.51 µB and âˆ¼ 800 K, respectively. The ultraviolet-visible (UV-vis) absorption spectrum of Mn/P-g-C3N4 reveals superior absorption in broader wavelength compared to pristine-g-C3N4, P-g-C3N4, and Mn-g-C3N4. The methyl orange degradation efficiency of Mn/P-g-C3N4 photocatalyst is 94 %, which is three times more than that of pristine-g-C3N4 (29 %) and more significant than the P-g-C3N4 (46 %) and Mn-g-C3N4 (58 %). Furthermore, density functional theory (DFT) calculation explains the origin of high magnetic behavior, the boosted photocatalytic efficiency of Mn/P-g-C3N4, and the essential material properties like structure, bandgap, the density of states (DOS), and atomic level interaction. This work may be helpful for reasonably designing ferromagnetic material for spintronics devices and boosting visible-light (VL) photocatalytic performance for environmental remediation.

6.
ACS Appl Bio Mater ; 6(4): 1566-1576, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-36947679

RESUMO

Direct ink writing (DIW) additive manufacturing is a versatile 3D printing technique for a broad range of materials. DIW can print a variety of materials provided that the ink is well-engineered with appropriate rheological properties. DIW could be an ideal technique in tissue engineering to repair and regenerate deformed or missing organs or tissues, for example, bone and tooth fracture that is a common problem that needs surgeon attention. A critical criterion in tissue engineering is that inserts must be compatible with their surrounding environment. Chemically produced calcium-rich materials are dominant in this application, especially for bone-related applications. These materials may be toxic leading to a rejection by the body that may need secondary surgery to repair. On the other hand, there is an abundance of biowaste building blocks that can be used for grafting with little adverse effect on the body. In this work, we report a bioderived ink made entirely of calcium derived from waste animal bones using a benign process. Calcium nanoparticles are extracted from the bones and the ink prepared by mixing with different biocompatible binders. The ink is used to print scaffolds with controlled porosity that allows better growth of cells. DIW printed parts show better mechanical properties and biocompatibility that are important for the grafting application. Degradation tests and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay study were done to examine the biocompatibility of the extracted materials. In addition, discrete element modeling and computational fluid dynamics numerical methods are used in Rocky and Ansys software programs. This work shows that biowaste materials if well-engineered can be a never-ending source of raw materials for advanced application in orthopedic grafting.


Assuntos
Materiais Biocompatíveis , Cálcio , Animais , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Impressão Tridimensional , Porosidade
8.
Nanotechnology ; 33(33)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35533643

RESUMO

Poly (vinylidene fluoride) (PVDF) and its copolymers have piqued a substantial amount of research interest for its use in modern flexible electronics. The piezoelectricß-phase of the polymers can be augmented with the addition of suitable fillers that promoteß-phase nucleation. In this work, we report an improved output voltage response of poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) with the incorporation of 10 wt.% Titanium (IV) oxide nanoparticles into the polymer matrix. The nano-filler was dispersed in the polymer matrix to form nanocomposite films via the solution casting technique. X-ray Diffraction and Scanning Electron Microscopy measurements were performed to verify the structure and morphology of the films. Fourier Transform Infrared Spectroscopy revealed enhancement in theß-phase nucleation from ∼15% to ∼36% with the addition of 10 wt.% titania nanoparticles. Thermogravimetric analysis and Differential Scanning Calorimetry results show improved thermal stability of the nanocomposite film, up to 345 °C, as compared to pristine PVDF-HFP. We also demonstrate a facile method for the fabrication of a piezoelectric nanogenerator withß-PVDF-HFP/TiO2nanocomposite as an active layer. The outputs from the fabricated nanogenerator reached up to 8.89 V through human finger tapping motions, paving way for its potential use in the field of sensors, actuators, and self-sustaining flexible devices.

9.
J Am Chem Soc ; 143(20): 7655-7670, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-33988982

RESUMO

Aptamers, synthetic single-strand oligonucleotides that are similar in function to antibodies, are promising as therapeutics because of their minimal side effects. However, the stability and bioavailability of the aptamers pose a challenge. We developed aptamers converted from RNA aptamer to modified DNA aptamers that target phospho-AXL with improved stability and bioavailability. On the basis of the comparative analysis of a library of 17 converted modified DNA aptamers, we selected aptamer candidates, GLB-G25 and GLB-A04, that exhibited the highest bioavailability, stability, and robust antitumor effect in in vitro experiments. Backbone modifications such as thiophosphate or dithiophosphate and a covalent modification of the 5'-end of the aptamer with polyethylene glycol optimized the pharmacokinetic properties, improved the stability of the aptamers in vivo by reducing nuclease hydrolysis and renal clearance, and achieved high and sustained inhibition of AXL at a very low dose. Treatment with these modified aptamers in ovarian cancer orthotopic mouse models significantly reduced tumor growth and the number of metastases. This effective silencing of the phospho-AXL target thus demonstrated that aptamer specificity and bioavailability can be improved by the chemical modification of existing aptamers for phospho-AXL. These results lay the foundation for the translation of these aptamer candidates and companion biomarkers to the clinic.


Assuntos
Anticorpos/imunologia , Aptâmeros de Nucleotídeos/imunologia , Neoplasias/imunologia , Anticorpos/química , Aptâmeros de Nucleotídeos/química , Humanos , Neoplasias/terapia
10.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 4903-4908, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019088

RESUMO

Haptic feedback can render real-time force interactions with computer simulated objects. In several telerobotic applications, it is desired that a haptic simulation reflects a physical task space or interaction accurately. This is particularly true when excessive applied force can result in disastrous consequences, as with the case of robot-assisted minimally invasive surgery (RMIS) and tissue damage. Since force cannot be directly measured in RMIS, non-contact methods are desired. A promising direction of non-contact force estimation involves the primary use of vision sensors to estimate deformation. However, the required fidelity of non-contact force rendering of deformable interaction to maintain surgical operator performance is not well established. This work attempts to empirically evaluate the degree to which haptic feedback may deviate from ground truth yet result in acceptable teleoperated performance in a simulated RMIS-based palpation task. A preliminary user-study is conducted to verify the utility of the simulation platform, and the results of this work have implications in haptic feedback for RMIS and inform guidelines for vision-based tool-tissue force estimation. An adaptive thresholding method is used to collect the minimum and maximum tolerable errors in force orientation and magnitude of presented haptic feedback to maintain sufficient performance.


Assuntos
Robótica , Interface Usuário-Computador , Retroalimentação , Retroalimentação Sensorial , Palpação
12.
EBioMedicine ; 40: 290-304, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30655206

RESUMO

BACKGROUND: Inflammatory mediator prostaglandin E2-prostaglandin E2 receptor EP3 (PTGER3) signaling is critical for tumor-associated angiogenesis, tumor growth, and chemoresistance. However, the mechanism underlying these effects in ovarian cancer is not known. METHODS: An association between higher tumoral expression of PTGER3 and shorter patient survival in the ovarian cancer dataset of The Cancer Genome Atlas prompted investigation of the antitumor effects of PTGER3 downmodulation. PTGER3 mRNA and protein levels were higher in cisplatin-resistant ovarian cancer cells than in their cisplatin-sensitive counterparts. FINDINGS: Silencing of PTGER3 via siRNA in cancer cells was associated with decreased cell growth and less invasiveness, as well as cell-cycle arrest and increased apoptosis, mediated through the Ras-MAPK/Erk-ETS1-ELK1/CFTR1 axis. Furthermore, sustained PTGER3 silencing with multistage vector and liposomal 2'-F-phosphorodithioate-siRNA-mediated silencing of PTGER3 combined with cisplatin resulted in robust antitumor effects in cisplatin-resistant ovarian cancer models. INTERPRETATION: These findings identify PTGER3 as a potential therapeutic target in chemoresistant ovarian cancers expressing high levels of this oncogenic protein. FUND: National Institutes of Health/National Cancer Institute, USA.


Assuntos
Transformação Celular Neoplásica/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/metabolismo , Receptores de Prostaglandina E Subtipo EP3/genética , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Biomarcadores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Imuno-Histoquímica , Modelos Biológicos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Proteína Proto-Oncogênica c-ets-1/metabolismo , Receptores de Prostaglandina E Subtipo EP3/metabolismo
13.
EBioMedicine ; 38: 100-112, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30487062

RESUMO

BACKGROUND: Circulating miRNAs are known to play important roles in intercellular communication. However, the effects of exosomal miRNAs on cells are not fully understood. METHODS: To investigate the role of exosomal miR-1246 in ovarian cancer (OC) microenvironment, we performed RPPA as well as many other in vitro functional assays in ovarian cancer cells (sensitive; HeyA8, Skov3ip1, A2780 and chemoresistant; HeyA8-MDR, Skov3-TR, A2780-CP20). Therapeutic effect of miR-1246 inhibitor treatment was tested in OC animal model. We showed the effect of OC exosomal miR-1246 uptake on macrophages by co-culture experiments. FINDINGS: Substantial expression of oncogenic miR-1246 OC exosomes was found. We showed that Cav1 gene, which is the direct target of miR-1246, is involved in the process of exosomal transfer. A significantly worse overall prognosis were found for OC patients with high miR-1246 and low Cav1 expression based on TCGA data. miR-1246 expression were significantly higher in paclitaxel-resistant OC exosomes than in their sensitive counterparts. Overexpression of Cav1 and anti-miR-1246 treatment significantly sensitized OC cells to paclitaxel. We showed that Cav1 and multi drug resistance (MDR) gene is involved in the process of exosomal transfer. Our proteomic approach also revealed that miR-1246 inhibits Cav1 and acts through PDGFß receptor at the recipient cells to inhibit cell proliferation. miR-1246 inhibitor treatment in combination with chemotherapy led to reduced tumor burden in vivo. Finally, we demonstrated that when OC cells are co-cultured with macrophages, they are capable of transferring their oncogenic miR-1246 to M2-type macrophages, but not M0-type macrophages. INTERPRETATION: Our results suggest that cancer exosomes may contribute to oncogenesis by manipulating neighboring infiltrating immune cells. This study provide a new mechanistic therapeutic approach to overcome chemoresistance and tumor progression through exosomal miR-1246 in OC patients.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Caveolina 1/genética , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , MicroRNAs/genética , Neoplasias Ovarianas/genética , Animais , Apoptose/efeitos dos fármacos , Caveolina 1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Exossomos/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , MicroRNAs/metabolismo , Modelos Biológicos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Interferência de RNA , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais , Microambiente Tumoral
14.
Mol Ther Nucleic Acids ; 9: 251-262, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29246304

RESUMO

Despite substantial improvements in the treatment strategies, ovarian cancer is still the most lethal gynecological malignancy. Identification of drug treatable therapeutic targets and their safe and effective targeting is critical to improve patient survival in ovarian cancer. AXL receptor tyrosine kinase (RTK) has been proposed to be an important therapeutic target for metastatic and advanced-stage human ovarian cancer. We found that AXL-RTK expression is associated with significantly shorter patient survival based on the The Cancer Genome Atlas patient database. To target AXL-RTK, we developed a chemically modified serum nuclease-stable AXL aptamer (AXL-APTAMER), and we evaluated its in vitro and in vivo antitumor activity using in vitro assays as well as two intraperitoneal animal models. AXL-aptamer treatment inhibited the phosphorylation and the activity of AXL, impaired the migration and invasion ability of ovarian cancer cells, and led to the inhibition of tumor growth and number of intraperitoneal metastatic nodules, which was associated with the inhibition of AXL activity and angiogenesis in tumors. When combined with paclitaxel, in vivo systemic (intravenous [i.v.]) administration of AXL-aptamer treatment markedly enhanced the antitumor efficacy of paclitaxel in mice. Taken together, our data indicate that AXL-aptamers successfully target in vivo AXL-RTK and inhibit its AXL activity and tumor growth and progression, representing a promising strategy for the treatment of ovarian cancer.

15.
Cell Discov ; 3: 17029, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28904816

RESUMO

The regulation of microRNA (miRNA) biogenesis, function and degradation involves a range of mechanisms, including interactions with RNA-binding proteins. The potential contribution of regulatory miRNAs to the expression of these RNA interactor proteins that could control other miRNAs expression is still unclear. Here we demonstrate a regulatory circuit involving oncogenic and tumor-suppressor miRNAs and an RNA-binding protein in a chemotherapy-resistant ovarian cancer model. We identified and characterized miR-15a-5p and miR-25-3p as negative regulators of hnRNPA1 expression, which is required for the processing of miR-18a-3p, an inhibitor of the K-RAS oncogene. The inhibition of miR-25-3p and miR-15a-5p decreased the proliferation, motility, invasiveness and angiogenic potential and increased apoptosis when combined with docetaxel. Alteration of this regulatory circuit causes poor overall survival outcome in ovarian cancer patients. These results highlight miR-15a-5p and miR-25-3p as key regulators of miR-18a-3p expression and its downstream target K-RAS, through direct modulation of hnRNPA1 expression. Our results demonstrate the therapeutic potential of inhibiting miR-25-3p and miR-15a-5p and the use of miR-18a-3p/KRAS ratio as a prominent outcome prognostic factor.

16.
Oncotarget ; 8(12): 20145-20164, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28423620

RESUMO

Exosomes have emerged as important mediators of diverse biological functions including tumor suppression, tumor progression, invasion, immune escape and cell-to-cell communication, through the release of molecules such as mRNAs, miRNAs, and proteins. Here, we identified differentially expressed exosomal miRNAs between normal epithelial ovarian cell line and both resistant and sensitive ovarian cancer (OC) cell lines. We found miR-940 as abundant in exosomes from SKOV3-IP1, HeyA8, and HeyA8-MDR cells. The high expression of miR-940 is associated with better survival in patients with ovarian serous cystadenocarcinoma. Ectopic expression of miR-940 inhibited proliferation, colony formation, invasion, and migration and triggered G0/G1 cell cycle arrest and apoptosis in OC cells. Overexpression of miR-940 also inhibited tumor cell growth in vivo. We showed that proto-oncogene tyrosine-protein kinase (SRC) is directly targeted by miR-940 and that miR-940 inhibited SRC expression at mRNA and protein levels. Following this inhibition, the expression of proteins downstream of SRC, such as FAK, paxillin and Akt was also reduced. Collectively, our results suggest that OC cells secrete the tumor-suppressive miR-940 into the extracellular environment via exosomes, to maintain their invasiveness and tumorigenic phenotype.


Assuntos
Biomarcadores Tumorais/metabolismo , Exossomos/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Ovarianas/patologia , Quinases da Família src/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Feminino , Genes Supressores de Tumor , Humanos , Camundongos , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Proto-Oncogene Mas , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases da Família src/genética
17.
Mol Cancer Ther ; 16(6): 1114-1123, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28265009

RESUMO

To address the need for efficient and biocompatible delivery systems for systemic siRNA delivery, we developed 1,2-Dioleoyl-sn-Glycero-3-Phosphatidylcholine (DOPC) nanoliposomal EphA2-targeted therapeutic (EPHARNA). Here, we performed safety studies of EPHARNA in murine and primate models. Single dosing of EPHARNA was tested at 5 concentrations in mice (N = 15 per group) and groups were sacrificed on days 1, 14, and 28 for evaluation of clinical pathology and organ toxicity. Multiple dosing of EPHARNA was tested in mice and Rhesus macaques twice weekly at two dose levels in each model. Possible effects on hematologic parameters, serum chemistry, coagulation, and organ toxicity were assessed. Following single-dose EPHARNA administration to mice, no gross pathologic or dose-related microscopic findings were observed in either the acute (24 hours) or recovery (14 and 28 days) phases. The no-observed-adverse-effect level (NOAEL) for EPHARNA is considered >225 µg/kg when administered as a single injection intravenously in CD-1 mice. With twice weekly injection, EPHARNA appeared to stimulate a mild to moderate inflammatory response in a dose-related fashion. There appeared to be a mild hemolytic reaction in the female mice. In Rhesus macaques, minimal to moderate infiltration of mononuclear cells was found in some organs including the gastrointestinal tract, heart, and kidney. No differences attributed to EPHARNA were observed. These results demonstrate that EPHARNA is well tolerated at all doses tested. These data, combined with previously published in vivo validation studies, have led to an ongoing first-in-human phase I clinical trial (NCT01591356). Mol Cancer Ther; 16(6); 1114-23. ©2017 AACR.


Assuntos
Lipossomos , Nanopartículas , Fosfatidilcolinas , Interferência de RNA , RNA Interferente Pequeno/genética , Receptor EphA2/genética , Animais , Biomarcadores , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Macaca mulatta , Masculino , Camundongos , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/efeitos adversos , RNA Interferente Pequeno/farmacocinética , Distribuição Tecidual
18.
Cancer Res ; 76(24): 7194-7207, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27742688

RESUMO

Cancer cells actively promote their tumorigenic behavior by reprogramming gene expression. Loading intraluminal vesicles with specific miRNAs and releasing them into the tumor microenvironment as exosomes is one mechanism of reprogramming whose regulation remains to be elucidated. Here, we report that miR-6126 is ubiquitously released in high abundance from both chemosensitive and chemoresistant ovarian cancer cells via exosomes. Overexpression of miR-6126 was confirmed in healthy ovarian tissue compared with ovarian cancer patient samples and correlated with better overall survival in patients with high-grade serous ovarian cancer. miR-6126 acted as a tumor suppressor by directly targeting integrin-ß1, a key regulator of cancer cell metastasis. miR-6126 mimic treatment of cancer cells resulted in increased miR-6126 and decreased integrin-ß1 mRNA levels in the exosome. Functional analysis showed that treatment of endothelial cells with miR-6126 mimic significantly reduced tube formation as well as invasion and migration capacities of ovarian cancer cells in vitro Administration of miR-6126 mimic in an orthotopic mouse model of ovarian cancer elicited a relative reduction in tumor growth, proliferating cells, and microvessel density. miR-6126 inhibition promoted oncogenic behavior by leading ovarian cancer cells to release more exosomes. Our findings provide new insights into the role of exosomal miRNA-mediated tumor progression and suggest a new therapeutic approach to disrupt oncogenic phenotypes in tumors. Cancer Res; 76(24); 7194-207. ©2016 AACR.


Assuntos
Exossomos/metabolismo , MicroRNAs/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Animais , Western Blotting , Feminino , Genes Supressores de Tumor , Xenoenxertos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Camundongos , Camundongos Nus , Reação em Cadeia da Polimerase , Transcriptoma , Transfecção
19.
ISRN Dermatol ; 2013: 739054, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24223310

RESUMO

Uncontrolled blood sugar is a major cause of vascular complications and delayed wound healing in diabetes mellitus. During wound healing process, normally, apoptosis is responsible for events such as removal of inflammatory cells and evolution of granulation tissue into scar which occur during the late phase of wound healing. Early apoptosis can lead to abnormal wound healing by removing granulation tissue including fibroblast, endothelial cell, and small vessels. To determine the role of apoptosis in association with hyperglycemia in diabetic wound healing, apoptosis-related intracellular marker such as expression of Bcl-2 protein by immunohistochemistry and normal histology has been studied. Histological findings show higher level of apoptosis and diminished granulation tissue formation in diabetic rats wounds along with minimal expression of Bcl-2 in diabetic rats wounds when compared with nondiabetic rats wounds. It can be concluded from this study that elevated blood sugar level may be associated with increased apoptosis and the least expression of Bcl-2 protein which might cause deregulation of the wound healing processes in streptozotocin-induced diabetic rats.

20.
ScientificWorldJournal ; 2013: 363652, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23509434

RESUMO

To aid the clinical diagnosis of typhoid fever in India, where most hospitals and primary health centres have no facilities for culture, we report on the development of a novel and rapid immunodiagnostic kit for the direct detection of Salmonella Typhi--specific IgG antibodies against S. Typhi flagellar H antigen. The disease often does not show a specific clinical picture, and can be confused with other febrile illness such as malaria, dengue fever and Staphylococcus aureus. To overcome the problem of cross reactivity specific epitope of the flagellar H antigen was immobilised on the testing kit strip eliminating chances of cross reactivity and false positive results thereby increasing the specificity of the test. Since the immunodiagnostic kit, uses the flagellar H antigen from bacteria present in our country, the antibodies present in the serum of patients of our country will have maximum binding affinity, enhancing the sensitivity of our test kit. The immunodiagnostic kit on analysis gave a positive result with clinically diagnosed typhoid positive patient serum and negative results were obtained with the sera of clinically diagnosed malaria, abscess of Staphylococcus aureus and Visceral leishmaniasis (Kala-azar) patients.


Assuntos
Antígenos de Bactérias/imunologia , Kit de Reagentes para Diagnóstico , Salmonella typhi/imunologia , Febre Tifoide/diagnóstico , Western Blotting , Reações Cruzadas , Eletroforese em Gel de Poliacrilamida , Epitopos/análise , Epitopos/imunologia , Flagelina/imunologia , Humanos , Soros Imunes , Testes Imunológicos/métodos , Índia , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/imunologia , Malária/diagnóstico , Malária/imunologia , Staphylococcus aureus/imunologia , Febre Tifoide/imunologia , Febre Tifoide/microbiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA