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Background: The purpose of this study was to determine the effect of one-wall elimination of the abutment and also the surface treatment of the abutment on the retention of cement-retained, implant-supported zirconium oxide copings. Material and Methods: In this experimental study, four straight abutments were connected to four implant analogs (DIO, UF, Busan, Korea) with 35 Ncm torque. They are mounted vertically in resin blocks. Abutments were prepared as following groups: A) abutment was used in its intact standard form as a control group. B) 4 mm of the flat wall was removed to produce an abutment with 3 walls. C) The abutment surface was abraded with 50 µm AL2O3 powder. D) 4 mm of a flat wall of the abutment was removed, then the abutment surface was abraded with 50 µm AL2O3 airborne particle.10 zirconium oxide copings were made. Samples were cemented with temp bond NE to abutments. The retention of copings was measured before and after incubation using the universal testing machine. T-test, one-way ANOVA, and Post Hoc Tukey Test were used for statistical analysis of data. Results: In all groups, retention was decreased after thermocycling (P ≤0.001). 3 wall abutments had less retention than the control group before thermocycling. A significant difference was detected between 3 wall abutments and 4 walls of sandblasted abutments before thermocycling. After thermocycling, no difference in retention was seen between groups. Conclusions: Thermocycling significantly reduces the retention of implant-supported ceramic copings. Sandblasting abutments with 50 µm AL2O3 air-borne particles did not increase the retention of ziconium oxide copings which were cemented with temp bond NE. One wall elimination of abutment decreased the retention of zirconia copings. Key words:Retention, crown, abutment, zirconia coping, sandblasting.
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BACKGROUND: While the concept of angled screw channels has gained popularity, there remains a scarcity of research concerning the torque loss and fracture strength of monolithic zirconia restorations with various screw channel angulations when exposed to thermomechanical cycling. This in-vitro study aimed to evaluate the reverse torque value and fracture resistance of one-piece screw-retained hybrid monolithic zirconia restorations with angulated screw channels after thermomechanical cycling. METHODS: One-piece monolithic zirconia restorations, with angulated screw channels set at 0°, 15°, and 25° (n = 6 per angulation) were fabricated and bonded to titanium inserts using a dual-cure adhesive resin cement. These assemblies were then screwed to implant fixtures embedded in acrylic resin using an omnigrip screwdriver, and reverse torque values were recorded before and after thermomechanical cycles. Additionally, fracture modes were assessed subsequent to the application of compressive load. One-way ANOVA and Bonferroni post hoc test were used to compare the groups (α = 0.05). RESULTS: The study groups were significantly different regarding the fracture resistance (P = 0.0015), but only insignificantly different in the mean percentage torque loss (P = 0.4400). Specifically, the fracture resistance of the 15° group was insignificantly higher compared to the 0° group (P = 0.9037), but significantly higher compared to the 25° group (P = 0.0051). Furthermore, the fracture resistance of the 0° group was significantly higher than that of the 25° group (P = 0.0114). CONCLUSIONS: One-piece hybrid monolithic zirconia restorations with angulated screw channels can be considered an acceptable choice for angulated implants in esthetic areas, providing satisfactory fracture strength and torque loss.
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Coronas , Cementos Dentales , Circonio , Humanos , Torque , Ensayo de Materiales , Pilares Dentales , Titanio , Tornillos Óseos , Análisis del Estrés Dental , Fracaso de la Restauración DentalRESUMEN
Microelectrode Arrays (MEAs) neural interfaces are considered implantable devices that interact with the nervous system to monitor and/or modulate brain activity. Graphene-based materials are utilized to address some of the current challenges in neural interface design due to their desirable features, such as high conductance, large surface-to-volume ratio, suitable electrochemical properties, biocompatibility, flexibility, and ease of production. In the current study, we fabricated and characterized a type of flexible, ultrasmall, and implantable neurostimulator based on graphene fibers. In this procedure, wet-spinning was employed to create graphene fibers with diameters of 10 to 50 µm. A 10-channel polyimide Printed Circuit Board (PCB) was then custom-designed and manufactured. The fibers were attached to each channel by conductive glue and also insulated by soaking them in a polyurethane solution. The tips were subsequently exposed using a blowtorch. Microstructural information on the fibers was obtained using Scanning Electron Microscopy (SEM), and the measurements of Electrochemical Impedance Spectroscopy (EIS) were conducted for each electrode. Flexible MEAs were created using graphene fibers with diameters ranging from 10 to 50 microns with a spacing of 150 microns. This method leads to producing electrode arrays with any size of fibers and a variety of channel numbers. The flexible neural prostheses can replace conventional electrodes in both neuroscience and biomedical research.
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Purpose: We describe a diagnostic procedure suitable for scheduling (re-)vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) according to individual state of humoral immunization. Methods: To clarify the relation between quantitative antibody measurements and humoral ex vivo immune responsiveness, we monitored 124 individuals before, during and six months after vaccination with Spikevax (Moderna, Cambridge, MA, USA). Antibodies against SARS-CoV-2 spike (S1) protein receptor-binding domain (S1-AB) and against nucleocapsid antigens were measured by chemiluminescent immunoassay (Roche). Virus-neutralizing activities were determined by surrogate assays (NeutraLISA, Euroimmune; cPass, GenScript). Neutralization of SARS-CoV-2 in cell culture (full virus NT) served as an ex vivo correlate for humoral immune responsiveness. Results: Vaccination responses varied considerably. Six months after the second vaccination, participants still positive for the full virus NT were safely determined by S1-AB levels ≥1000 U/mL. The full virus NT-positive fraction of participants with S1-AB levels <1000 U/mL was identified by virus-neutralizing activities >70% as determined by surrogate assays (NeutraLISA or cPas). Participants that were full virus NT-negative and presumably insufficiently protected could thus be identified by a sensitivity of >83% and a specificity of >95%. Conclusion: The described diagnostic strategy possibly supports individualized (re-)vaccination schedules based on simple and rapid measurement of serum-based SARS-CoV-2 antibody levels. Our data apply only to WUHAN-type SARS-CoV-2 virus and the current version of the mRNA vaccine from Moderna (Cambridge, MA, USA). Adaptation to other vaccines and more recent SARS-CoV-2 strains will require modification of cut-offs and re-evaluation of sensitivity/specificity.
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The great clinical success of chimeric antigen receptor (CAR) T cells has unlocked new levels of immunotherapy for hematological malignancies. Genetically modifying natural killer (NK) cells as alternative CAR immune effector cells is also highly promising, as NK cells can be transplanted across HLA barriers without causing graft-versus-host disease. Therefore, off-the-shelf usage of CAR NK cell products might allow to widely expand the clinical indications and to limit the costs of treatment per patient. However, in contrast to T cells, manufacturing suitable CAR NK cell products is challenging, as standard techniques for genetically engineering NK cells are still being defined. In this study, we have established optimal lentiviral transduction of primary human NK cells by systematically testing different internal promoters for lentiviral CAR vectors and comparing lentiviral pseudotypes and viral entry enhancers. We have additionally modified CAR constructs recognizing standard target antigens for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) therapy-CD19, CD33, and CD123-to harbor a CD34-derived hinge region that allows efficient detection of transduced NK cells in vitro and in vivo and also facilitates CD34 microbead-assisted selection of CAR NK cell products to >95% purity for potential clinical usage. Importantly, as most leukemic blasts are a priori immunogenic for activated primary human NK cells, we developed an in vitro system that blocks the activating receptors NKG2D, DNAM-1, NKp30, NKp44, NKp46, and NKp80 on these cells and therefore allows systematic testing of the specific killing of CAR NK cells against ALL and AML cell lines and primary AML blasts. Finally, we evaluated in an ALL xenotransplantation model in NOD/SCID-gamma (NSG) mice whether human CD19 CAR NK cells directed against the CD19+ blasts are relying on soluble or membrane-bound IL15 production for NK cell persistence and also in vivo leukemia control. Hence, our study provides important insights into the generation of pure and highly active allogeneic CAR NK cells, thereby advancing adoptive cellular immunotherapy with CAR NK cells for human malignancies further.
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Neoplasias Hematológicas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Animales , Línea Celular Tumoral , Ingeniería Genética , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/terapia , Humanos , Inmunoterapia Adoptiva/métodos , Células Asesinas Naturales , Ratones , Ratones Endogámicos NOD , Ratones SCID , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMEN
Antibodies as ideal therapeutic and diagnostic molecules are among the top-selling drugs providing considerable efficacy in disease treatment, especially in cancer therapy. Limitations of the hybridoma technology as routine antibody generation method in conjunction with numerous developments in molecular biology led to the development of alternative approaches for the streamlined identification of most effective antibodies. In this regard, display selection technologies such as phage display, bacterial display, and yeast display have been widely promoted over the past three decades as ideal alternatives to traditional methods. The display of antibodies on phages is probably the most widespread of these methods, although surface display on bacteria or yeast have been employed successfully, as well. These methods using various sizes of combinatorial antibody libraries and different selection strategies possessing benefits in screening potency, generating, and isolation of high affinity antibodies with low risk of immunogenicity. Knowing the basics of each method assists in the design and retrieval process of antibodies suitable for different diseases, including cancer. In this review, we aim to outline the basics of each library construction and its display method, screening and selection steps. The advantages and disadvantages in comparison to alternative methods, and their applications in antibody engineering will be explained. Finally, we will review approved or non-approved therapeutic antibodies developed by employing these methods, which may serve as therapeutic antibodies in cancer therapy.
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Bacteriófagos , Biblioteca de Péptidos , Anticuerpos/uso terapéutico , Bacterias , Bacteriófagos/genética , Técnicas de Visualización de Superficie Celular/métodos , Saccharomyces cerevisiaeRESUMEN
Up-to-date diagnostics is globally improved by point-of-care testing (POCT) analysis and bedside research works. Development in POCT analysis has been provided mostly by forward-looking engineering technology for biosensing and sensing assessments. Lately, lateral flow assays (LFAs) have attracted a lot of interest as a result of their noteworthy benefits including cost-effectiveness, better portability, being operator friendly and rapid detection. This technique has been employed broadly for monitoring diverse biomarkers linked to ultrasensitive detection of pathogenic bacteria, ecological monitoring, consumer protection, and infectious diseases. LFA analyses established on qualitative and optical outcomes have boosted the objectivity and data efficiency of the assessments. Therefore, developing novel methods with the capability of providing reliable and quantitative information regarding a target analyte in a model and preserving the qualities of LFAs is of great necessity. In this review, the main principles of LFAs, challenges, and prospects for more development in this field in sensing pathogenic bacteria have been summarized. Subsequently, visually-read LFAs improvement to further progressive platforms have been explored by considering the prospects of this very flexible method for ultrasensitive detection of pathogenic bacteria. In addition, novel labeling methodologies, electrochemical and optical transducers are described. Also, recent developments in these detection methods elements in combination with other considered approaches have been highlighted.
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Enfermedades Transmisibles , Sistemas de Atención de Punto , Bacterias , Bioensayo , Enfermedades Transmisibles/diagnóstico , Humanos , Inmunoensayo/métodos , Pruebas en el Punto de AtenciónRESUMEN
Viruses are responsible for multiple infections in humans that impose huge health burdens on individuals and populations worldwide. Therefore, numerous diagnostic methods and strategies have been developed for prevention, management, and decreasing the burden of viral diseases, each having its advantages and limitations. Viral infections are commonly detected using serological and nucleic acid-based methods. However, these conventional and clinical approaches have some limitations that can be resolved by implementing other detector devices. Therefore, the search for sensitive, selective, portable, and costless approaches as efficient alternative clinical methods for point of care testing (POCT) analysis has gained much attention in recent years. POCT is one of the ultimate goals in virus detection, and thus, the tests need to be rapid, specific, sensitive, accessible, and user-friendly. In this review, after a brief overview of viruses and their characteristics, the conventional viral detection methods, the clinical approaches, and their advantages and shortcomings are firstly explained. Then, LFA systems working principles, benefits, classification are discussed. Furthermore, the studies regarding designing and employing LFAs in diagnosing different types of viruses, especially SARS-CoV-2 as a main concern worldwide and innovations in the LFAs' approaches and designs, are comprehensively discussed here. Furthermore, several strategies addressed in some studies for overcoming LFA limitations like low sensitivity are reviewed. Numerous techniques are adopted to increase sensitivity and perform quantitative detection. Employing several visualization methods, using different labeling reporters, integrating LFAs with other detection methods to benefit from both LFA and the integrated detection device advantages, and designing unique membranes to increase reagent reactivity, are some of the approaches that are highlighted.
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AIM: One of the main problems in dentistry is the injury caused by the long-term application of an ill-fitting denture. The existence of multiple microorganisms along with the susceptibility of the tissue conditioners to colonize them can lead to denture stomatitis. This study is aimed at developing a tissue conditioner incorporated with Carum copticum L. (C. copticum L.) for the effective treatment of these injuries. MATERIALS AND METHODS: The Carum copticum L. essential oil composition was determined by gas chromatography-mass (GC-mass) spectrometry. The antimicrobial activity of the essential oil against the standard strains of bacterial and fungal species was determined by broth microdilution methods as suggested by the Clinical and Laboratory Standards Institute (CLSI). The physical and chemical properties of the prepared tissue conditioner were investigated by viscoelasticity, FTIR assays, and the release study performed. Furthermore, the antibiofilm activity of the Carum copticum L. essential oil-loaded tissue conditioner was evaluated by using the XTT reduction assay and scanning electron microscopy (SEM). RESULTS: The main component of the essential oil is thymol, which possesses high antimicrobial activity. The broth microdilution assay showed that the essential oil has broad activity as the minimum inhibitory concentration was in the range of 32-128 µg mL-1. The viscoelasticity test showed that the essential oil significantly diminished the viscoelastic modulus on the first day. The FTIR test showed that Carum copticum L. essential oil was preserved as an independent component in the tissue conditioner. The release study showed that the essential oil was released in 3 days following a sustained release and with an ultimate cumulative release of 81%. Finally, the Carum copticum L. essential oil exhibited significant activity in the inhibition of microbial biofilm formation in a dose-dependent manner. Indeed, the lowest and highest amounts of biofilm formation on the tissue conditioner disks are exhibited in the Streptococcus salivarius and Candida albicans by up to 22.4% and 71.4% at the 64 µg mL-1 concentration of C. copticum L. with a statistically significant difference (P < 0.05). CONCLUSION: The obtained results showed that the Carum copticum L. essential oil-loaded tissue conditioner possessed suitable physical, biological, and release properties for use as a novel treatment for denture stomatitis.
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Antiinfecciosos/química , Bacterias/crecimiento & desarrollo , Carum/química , Hongos/crecimiento & desarrollo , Aceites Volátiles/química , Acondicionamiento de Tejidos Dentales/instrumentación , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Biopelículas/efectos de los fármacos , Preparaciones de Acción Retardada , Relación Dosis-Respuesta a Droga , Módulo de Elasticidad , Hongos/efectos de los fármacos , Cromatografía de Gases y Espectrometría de Masas , Humanos , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , Aceites Volátiles/farmacología , Aceites de Plantas/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Neural interfacing devices using penetrating microelectrode arrays have emerged as an important tool in both neuroscience research and medical applications. These implantable microelectrode arrays enable communication between man-made devices and the nervous system by detecting and/or evoking neuronal activities. Recent years have seen rapid development of electrodes fabricated using flexible, ultrathin carbon-based microfibers. Compared to electrodes fabricated using rigid materials and larger cross-sections, these microfiber electrodes have been shown to reduce foreign body responses after implantation, with improved signal-to-noise ratio for neural recording and enhanced resolution for neural stimulation. Here, we review recent progress of carbon-based microfiber electrodes in terms of material composition and fabrication technology. The remaining challenges and future directions for development of these arrays will also be discussed. Overall, these microfiber electrodes are expected to improve the longevity and reliability of neural interfacing devices.
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The tissue engineering of hard organs and tissues containing cartilage, teeth, and bones is a widely used and rapidly progressing field. One of the main features of hard organs and tissues is the mineralization of their extracellular matrices (ECM) to enable them to withstand pressure and weight. Recently, a variety of printing strategies have been developed to facilitate hard organ and tissue regeneration. Fundamentals in three-dimensional (3D) printing techniques are rapid prototyping, additive manufacturing, and layered built-up and solid-free construction. This strategy promises to replicate the multifaceted architecture of natural tissues. Nowadays, 3D bioprinting techniques have proved their potential applications in tissue engineering to construct transplantable hard organs/tissues including bone and cartilage. Though, 3D bioprinting methods still have some uncertainties to fabricate 3D hard organs/tissues. In the present review, most advanced technical improvements, experiments, and future outlooks of hard tissue engineering are discussed, as well as their relevant additive manufacturing techniques.
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Bioimpresión , Ingeniería de Tejidos , Nanotecnología , Impresión Tridimensional , Andamios del TejidoRESUMEN
The generation and expansion of functionally competent NK cells in vitro is of great interest for their application in immunotherapy of cancer. Since CD33 constitutes a promising target for immunotherapy of myeloid malignancies, NK cells expressing a CD33-specific chimeric antigen receptor (CAR) were generated. Unexpectedly, we noted that CD33-CAR NK cells could not be efficiently expanded in vitro due to a fratricide-like process in which CD33-CAR NK cells killed other CD33-CAR NK cells that had upregulated CD33 in culture. This upregulation was dependent on the stimulation protocol and encompassed up to 50% of NK cells including CD56dim NK cells that do generally not express CD33 in vivo. RNAseq analysis revealed that upregulation of CD33+ NK cells was accompanied by a unique transcriptional signature combining features of canonical CD56bright (CD117high, CD16low) and CD56dim NK cells (high expression of granzyme B and perforin). CD33+ NK cells exhibited significantly higher mobilization of cytotoxic granula and comparable levels of cytotoxicity against different leukemic target cells compared to the CD33- subset. Moreover, CD33+ NK cells showed superior production of IFNγ and TNFα, whereas CD33- NK cells exerted increased antibody-dependent cellular cytotoxicity (ADCC). In summary, the study delineates a novel functional divergence between NK cell subsets upon in vitro stimulation that is marked by CD33 expression. By choosing suitable stimulation protocols, it is possible to preferentially generate CD33+ NK cells combining efficient target cell killing and cytokine production, or alternatively CD33- NK cells, which produce less cytokines but are more efficient in antibody-dependent applications.
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Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Citocinas/inmunología , Células Asesinas Naturales/inmunología , Lectina 3 Similar a Ig de Unión al Ácido Siálico/inmunología , Antígeno CD56/inmunología , Antígeno CD56/metabolismo , Células Cultivadas , Citocinas/metabolismo , Citotoxicidad Inmunológica/inmunología , Citometría de Flujo/métodos , Perfilación de la Expresión Génica/métodos , Humanos , Células K562 , Células Asesinas Naturales/metabolismo , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/inmunología , Proteínas Proto-Oncogénicas c-kit/metabolismo , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Receptores de IgG/genética , Receptores de IgG/inmunología , Receptores de IgG/metabolismo , Lectina 3 Similar a Ig de Unión al Ácido Siálico/genética , Lectina 3 Similar a Ig de Unión al Ácido Siálico/metabolismo , Regulación hacia ArribaRESUMEN
According to reports of the international agency for cancer on research, although malignant melanoma shows less prevalence than nonmelanoma skin cancers, it is the major cause of skin cancer mortality. Given that, the production of effective vaccines to control melanoma is eminently required. In this regard, DNA-based vaccines have been extensively investigated for melanoma therapy. DNA vaccines are capable of inducing both cellular and humoral branches of immune responses. These vaccines possess some valuable advantages such as lack of severe side effects and high stability compared to conventional vaccination methods. The ongoing studies are focused on novel strategies in the development of DNA vaccines encoding artificial polyepitope immunogens based on the multiple melanoma antigens, the inclusion of molecular adjuvants to increase the level of immune responses, and the improvement of delivery approaches. In this review, we have outlined the recent advances in the field of melanoma DNA vaccines and described their implications in clinical trials as a strong strategy in the prevention and control of melanoma.
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Vacunas contra el Cáncer , Melanoma , Neoplasias Cutáneas , Vacunas de ADN , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Humanos , Melanoma/inmunología , Melanoma/terapia , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/terapia , Vacunas de ADN/inmunología , Vacunas de ADN/uso terapéutico , Melanoma Cutáneo MalignoRESUMEN
Gastric cancer (GC) is considered one of the most lethal malignancies worldwide due to poor prognosis. Aberrant methylation has been demonstrated to be involved in PD-L1 dysregulated expression in human cancers and possesses a great value as a diagnostic biomarker. Given that, in this study, we investigated the methylation status of PD-L1 as a promising biomarker in primary gastric tumors and identified functional CpG loci undergoing aberrant methylation through tumorigenesis of GC. PD-L1 methylation was initially evaluated in-silico using TCGA-STAD dataset. Pearson's correlation analysis was further employed to identify the most significant functional methylated CpG loci of PD-L1 gene in TCGA-STAD patient cohort. Methylation status and its correlation with PD-L1 expression were also validated using q-MSP and qRT-PCR in a set of internal samples, including 25 paired primary gastric tumors and adjacent normal tissues. The obtained results from TCGA-STAD showed that PD-L1 is significantly hypermethylated through gastric tumorigenesis, mostly in two CpG loci overlapping with cg19724470 and cg15837913 probes. Besides, PD-L1 DNA methylation was negatively correlated with PD-L1 expression in tumor samples. Furthermore, hypermethylation of cg19724470 and cg15837913 regions was validated in primary gastric tumors compared to adjacent normal samples. Also, ROC curve analysis illustrated the high diagnostic value of PD-L1 methylation for early detection of GC (AUC = 0.8110). In conclusion, the findings of this study suggested that PD-L1 expression is regulated by methylation in functional CpG loci and its methylation could be considered as a valuable diagnostic target for GC.
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Antígeno B7-H1/genética , Biomarcadores de Tumor/genética , Metilación de ADN , Neoplasias Gástricas/diagnóstico , Estudios de Cohortes , Islas de CpG , Regulación hacia Abajo , Detección Precoz del Cáncer , Epigénesis Genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Clasificación del Tumor , Regiones Promotoras Genéticas , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Análisis de SupervivenciaRESUMEN
Current tuberculosis (TB) vaccines have some disadvantages and many efforts have been undertaken to produce effective TB vaccines. As a result of their advantages, DNA vaccines are promising future vaccine candidates. This review focuses on the design and delivery of novel DNA-based vaccines against TB.
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Glioblastoma multiform (GBM) as the most frequent and lethal brain tumor is defined by aggressive invasiveness and considerable resistance to chemotherapy. The molecular mechanisms underlying GBM tumorigenesis still needs to be further investigated. Considering that, the current study was aimed to investigate the function of miR-181a in human glioblastoma cells in combination with carmustine. U373 cell line with the low expression levels of miR-181a was selected for functional investigations. MTT assay was used to determine cell viability and Annexin V/PI and DAPI staining were employed to evaluate apoptosis induction. Also, cell migration and cell cycle progression were investigated using wound healing test and flow cytometry, respectively. qRT-PCR was used for the quantification of gene expression. MTT assay results revealed that miR-181a replacement increased the sensitivity of U373 cells to low doses of carmustine. Moreover, miR-181a was shown to increase the sub G1 cell cycle arrest and apoptosis induction by carmustine via regulating the expression of related genes including caspase-9, Bcl-2, and SIRT1. Furthermore, this miRNA combined with carmustine suppressed cell migration via downregulation of MMP-2 and Bach1 and reduced the clonogenic ability of U373 cells. Additionally, miR-181a-mediated downregulation of AKT1 implied that this miRNA could inhibit cell proliferation by modulating PI3K/AKT signaling pathway. In conclusion, the findings of this study suggest that miR-181a replacement, regarding its tumor-suppressive effects and sensitization of glioblastoma cells to carmustine, could be considered as a potential therapeutic strategy to improve the efficiency of glioblastoma chemotherapy.
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Neoplasias Encefálicas/metabolismo , Carmustina/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Glioblastoma/metabolismo , MicroARNs/metabolismo , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Alquilantes/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Carmustina/uso terapéutico , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Relación Dosis-Respuesta a Droga , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Humanos , MicroARNs/genéticaRESUMEN
OBJECTIVE: Retinal prostheses aim to restore vision in patients with retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa. By implanting an array of microelectrodes, such a device creates percepts in patients through electrical stimulation of surviving retinal neurons. A challenge for retinal prostheses when trying to return high quality vision is the unintended activation of retinal ganglion cells through the stimulation of passing axon bundles, which leads to patients reporting large, elongated patches of light instead of focal spots. APPROACH: In this work, we used calcium imaging to record the responses of retinal ganglion cells to electrical stimulation in explanted retina using rectangular electrodes placed with different orientations relative to the axon bundles. MAIN RESULTS: We showed that narrow, rectangular electrodes oriented parallel to the axon bundles can achieve focal stimulation. To further improve the strategy, we studied the impact of different stimulation waveforms and electrode configurations. We found the selectivity for focal stimulation to be higher when using short (33 µs), anodic-first biphasic pulses, with long electrode lengths and at least 50 µm electrode-to-retinal separation. Focal stimulation was, in fact, less selective when the electrodes made direct contact with the retinal surface due to unwanted preferential stimulation of the proximal axon bundles. SIGNIFICANCE: When employed in retinal prostheses, the proposed stimulation strategy is expected to provide improved quality of vision to the blind.
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Células Ganglionares de la Retina , Prótesis Visuales , Axones , Estimulación Eléctrica , Electrodos , Humanos , Microelectrodos , RetinaRESUMEN
Micro RNAs (miRNAs) show a considerable promise as a therapeutic agent for combination therapy of colorectal cancer (CRC). Given that, the current study was purposed to explore the potential therapeutic role and underlying mechanism of miR-193a as a promising tumor suppressor in human CRC cell lines in combination with Taxol. Therefore, HT-29 cells with the lowest expression levels of miR-193a were treated with miR-193a mimics and Taxol, separately or in combination. Functional analyses showed that the combination therapy inhibited migration and colony formation of HT-29 cells and arrested the cell cycle at the G1 phase. Moreover, treatment with Taxol reduced cell survival with an increase in mRNA expression of metastasis-related genes caspase-3 and caspase-9, whereas miR-193a transfection alone didn't significantly influence cell viability and apoptosis induction. Quantitative reverse transcription polymerase chain reaction results also revealed that miR-193a replacement decreased the expression levels of c-Myc, MMP-9, vimentin, and ROCK in treatment groups compared to the controls. Therefore, it could be concluded miR-193a inactivates cell migration via suppression of metastasis pathways in CRC and through downregulation of c-Myc, acts as a negative regulator of cell cycle and growth. Then, our findings imply that miR-193a replacement combined with Taxol chemotherapy could be considered as a new potential therapeutic approach for improvement of CRC treatment.
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Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/terapia , Regulación Neoplásica de la Expresión Génica , MicroARNs/administración & dosificación , Paclitaxel/farmacología , Antineoplásicos Fitogénicos/farmacología , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Terapia Combinada , Humanos , MicroARNs/genética , Células Tumorales CultivadasRESUMEN
Implantable medical devices are now in regular use to treat or ameliorate medical conditions, including movement disorders, chronic pain, cardiac arrhythmias, and hearing or vision loss. Aside from offering alternatives to pharmaceuticals, one major advantage of device therapy is the potential to monitor treatment efficacy, disease progression, and perhaps begin to uncover elusive mechanisms of diseases pathology. In an ideal system, neural stimulation, neural recording, and electrochemical sensing would be conducted by the same electrode in the same anatomical region. Carbon fiber (CF) microelectrodes are the appropriate size to achieve this goal and have shown excellent performance, in vivo. Their electrochemical properties, however, are not suitable for neural stimulation and electrochemical sensing. Here, we present a method to deposit high surface area conducting diamond on CF microelectrodes. This unique hybrid microelectrode is capable of recording single-neuron action potentials, delivering effective electrical stimulation pulses, and exhibits excellent electrochemical dopamine detection. Such electrodes are needed for the next generation of miniaturized, closed-loop implants that can self-tune therapies by monitoring both electrophysiological and biochemical biomarkers.
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Diamante , Potenciales de Acción , Fibra de Carbono , Estimulación Eléctrica , MicroelectrodosRESUMEN
This paper presented a new sensor to detect and localize partial discharge (PD) in power transformers based on a fiber Bragg grating (FBG). The fundamental characteristics of the proposed sensor, as a PD detector, were temperature compensation and direction independence. The proposed high-resolution PD detector operated based on the FBG wavelength shift. It is necessary to evaluate the physical parameters of the sensor to achieve the best results. Therefore, in this paper, the detected signal strength was investigated for different angles and temperatures. A Teflon hollow mandrel and two FBGs attached to the inner and outer surfaces of the hollow mandrel were chosen as the inner transformer PD detector. The changes in the sensor output were less than 0.4 mV and 0.5 mV for direction variations and a temperature variation of 14 °C (degrees Celsius), respectively. Consequently, the proposed sensor could be successfully employed for the detection of a transformer PD signal.