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Breast cancer is one of the most common cancers in women. One of the best therapeutic methods against breast cancer is gene therapy, while having an appropriate gene carrier is the biggest challenge of gene therapy. Hence, developing carriers with low cytotoxicity and high gene transfection efficiency, and preferentially with the selective function of gene delivery is a critical demand for this method. In the present study, we introduce a novel targeted carrier to deliver the inducible caspase-9 suicide gene (pLVSIN-iC9) into breast cancer cells. The carrier is composed of graphene oxide quantum dots decorated with polyethyleneimine, and S2.2; an aptamer with high affinity to MUC1 (GOQD-PEI/S2.2). Due to the overexpression of MUC1 in breast cancer cells, the designed GOQD-PEI/S2.2/pLVSIN-iC9 can selectively target cancer cells. Moreover, to better mimic solid tumor conditions, and to evaluate the selective effect of the GOQD-PEI/S2.2/pLVSIN-iC9, an organoid model derived from human dermal fibroblasts (HDF) and MCF-7 cells (coculture organoid) was generated and characterized. The results demonstrate that the coculture organoid model adapts the tissue structure of luminal breast cancer, as well. Therefore, the organoids were subjected to treatment with targeted gene therapy using GOQD-PEI/S2.2/pLVSIN-iC9. Our evidence supports the targeted killing effect of iC9 on the breast cancer cells of the organoids and suggests the good potential of the newly introduced carriers in targeted gene delivery.
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Aptámeros de Nucleótidos , Neoplasias de la Mama , Genes Transgénicos Suicidas , Terapia Genética , Grafito , Organoides , Puntos Cuánticos , Humanos , Grafito/química , Puntos Cuánticos/química , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Terapia Genética/métodos , Aptámeros de Nucleótidos/genética , Organoides/metabolismo , Células MCF-7 , Caspasa 9/metabolismo , Caspasa 9/genética , Polietileneimina/química , Técnicas de Transferencia de Gen , Mucina-1/genética , Mucina-1/metabolismoRESUMEN
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), also known as APO2L, has emerged as a highly potential anticancer agent because of its capacity to effectively trigger apoptosis in tumor cells by specifically binding to either of its death receptors (DR4 or DR5) while having no adverse effects on normal cells. Nevertheless, its practical use has been hindered by its inefficient pharmacokinetics characteristics, the challenges involved in its administration and delivery to targeted cells, and the resistance exhibited by most cancer cells towards TRAIL. Gene therapy, as a promising approach would be able to potentially circumvent TRAIL-based cancer therapy challenges mainly through localized TRAIL expression and generating a bystander impact. Among different strategies, using nanoparticles in TRAIL gene delivery allows for precise targeting, and overcoming TRAIL resistance by combination therapy. In this review, we go over potential mechanisms by which cancer cells achieve resistance to TRAIL and provide an overview of different carriers for delivering of the TRAIL gene to resistant cancer cells, focusing on different types of nanoparticles utilized in this context. We will also explore the challenges, and investigate future perspectives of this nanomedicine approach for cancer therapy.
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Many studies show that ortho-phenylenediamine (OPD) produces an oxidized fluorescent product when exposed to an oxidizing agent that enables the direct or indirect fluorescence detection of a range chemical and biochemical analytes. However, there is no report on this unique optical behavior for other two isomers of phenylenediamine. This study demonstrates that a simple hydrothermal treatment of para-phenylenediamine (PPD) in the presence of sulfuric acid results in the formation of fluorescent N, S-doped carbon dots (CDs) with triple functionalities including the reduction of Au3+ into gold nanoparticles (AuNPs), the stabilization of the produced AuNPs, and the determination of Au3+ concentration through an intrinsic ratiometric fluorescence signal. In the presence of Au3+, the blue emission of CDs at 437 nm quenched, and a green emission at 540 nm emerged. The linear concentration range for the determination of Au3+ was 20 nM-16 µM with a detection limit of 16 nM. Additionally, the dual emissive CDs-AuNPs hybrid probe showed potential for the indirect fluorescence ratiometric determination of cysteine and sulfide ions. The linear concentration range for cysteine and sulfide ions were 0.25-8 µM and 0.1-6 µΜ, with detection limits of 0.095 µM and 0.041 µM, respectively. Accordingly, CDs were applied to detect Au3+ and S2- in real water samples. Moreover, the synthesized CDs showed no cytotoxicity for HeLa cells up to 300 µg mL-1, as determined by the MTT assay. Therefore, their potential for intracellular imaging of Au3+ in living cells was also investigated.
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Carbono , Espacio Extracelular , Oro , Carbono/química , Fluorescencia , Oxidación-Reducción , Cationes/química , Oro/análisis , Oro/química , Humanos , Células HeLa , Dicroismo Circular , Espacio Extracelular/química , Nanopartículas del Metal/química , Supervivencia Celular , Fenilendiaminas/química , Cisteína/química , Sulfuros/química , Límite de DetecciónRESUMEN
Manganese dioxide (MnO2) nanoenzymes/nanozymes (MnO2-NEs) are 1-100 nm nanomaterials that mimic catalytic, oxidative, peroxidase, and superoxide dismutase activities. The oxidative-like activity of MnO2-NEs makes them suitable for developing effective and low-cost colorimetric detection assays of biomolecules. Interestingly, MnO2-NEs also demonstrate scavenging properties against reactive oxygen species (ROS) in various pathological conditions. In addition, due to the decomposition of MnO2-NEs in the tumor microenvironment (TME) and the production of Mn2+, they can act as a contrast agent for improving clinical imaging diagnostics. MnO2-NEs also can use as an in situ oxygen production system in TME, thereby overcoming hypoxic conditions and their consequences in the progression of cancer. Furthermore, MnO2-NEs as a shell and coating make the nanosystems smart and, therefore, in combination with other nanomaterials, the MnO2-NEs can be used as an intelligent nanocarrier for delivering drugs, photosensitizers, and sonosensitizers in vivo. Moreover, these capabilities make MnO2-NEs a promising candidate for the detection and treatment of different human diseases such as cancer, metabolic, infectious, and inflammatory pathological conditions. MnO2-NEs also have ROS-scavenging and anti-bacterial properties against Gram-positive and Gram-negative bacterial strains, which make them suitable for wound healing applications. Given the importance of nanomaterials and their potential applications in biomedicine, this review aimed to discuss the biochemical properties and the theranostic roles of MnO2-NEs and recent advances in their use in colorimetric detection assays of biomolecules, diagnostic imaging, drug delivery, and combinatorial therapy applications. Finally, the challenges of MnO2-NEs applications in biomedicine will be discussed.
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Nanoestructuras , Neoplasias , Humanos , Especies Reactivas de Oxígeno/metabolismo , Óxidos/uso terapéutico , Óxidos/química , Medicina de Precisión , Compuestos de Manganeso/química , Neoplasias/tratamiento farmacológico , Nanoestructuras/química , Microambiente TumoralRESUMEN
Disease-related tau protein in Alzheimer's disease is hyperphosphorylated and aggregates into neurofibrillary tangles. The cis-proline isomer of the pSer/Thr-Pro sequence has been proposed to act as a precursor of aggregation ('Cistauosis' hypothesis), but this aggregation scheme is not yet entirely accepted. Hence to investigate isomer-specific-aggregation of tau, proline residues at the RTPPK motif were replaced by alanine residues (with permanent trans configuration) employing genetic engineering methods. RTPAK, RTAPK, and RTAAK mutant variants of tau were generated, and their in vitro aggregation propensity was investigated using multi-spectroscopic techniques. Besides, the cell toxicity of oligomers/fibrils was analyzed and compared to those of the wild-type (WT) tau. Analyses of mutant variants have shown to be in agreement (to some degree) to the theory of the 'cistauosis' hypothesis. The results showed that the trans isomer in the 232-rd residue (P232A mutant rather than P233A) had reduced aggregation propensity. However, this study did not illustrate any statistically significant difference between the wild and the mutant protein aggregations concerning cell toxicity.
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Enfermedad de Alzheimer , Proteínas tau , Alanina , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Humanos , Proteínas Mutantes , Prolina/química , Agregado de Proteínas , Proteínas tau/químicaRESUMEN
The photo-physical properties of metal nano clusters are sensitive to their surrounding medium. Fluorescence enhancement, quenching, and changes in the emitted photon properties are usual events in the sensing applications using these nano materials. Combining this sensitivity with unique properties of self-assembled structures opens new opportunities for sensing applications. Here, we synthesized gold nanoclusters by utilizing phenylalanine amino acid as both capping and reducing molecule. Phenylalanine is able to self-assemble to rod-shaped nano structure in which the π-π interaction between the aromatic rings is a major stabilizing force. Any substance as iodide anion or molecule that is able to weaken this interaction influence the fluorescence of metal nano-clusters. Since the building blocks of the self-assembled structure are made through the reaction of gold ions and phenylalanine, the oxidized products and their effect of sensing features are explored.
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BACKGROUND: Parkinson's disease (PD) is a long-term, degenerative, and neurological disease in which a person loses control of certain body functions. The formulation of novel effective therapeutics for PD as a neurodegenerative disease requires accurate and efficient diagnosis at the early stages. OBJECTIVE: Analyzing data gathered by measurable signals converted from biological reactions allows for qualitative and quantitative evaluations. Among various approaches reported so far, biosensors are powerful analytical tools that have been used in detecting the biomarkers of PD. METHODS: Biosensor's biological recognition components include antibodies, receptors, microorganisms, nucleic acids, enzymes, cells and tissues, and biomimetic structures. This review introduces electrochemical, optical, and optochemical detection of PD biomarkers based on recent advances in nanotechnology and material science, which resulted in the development of high-performance biosensors in this field. RESULTS: PD biomarkers such as α-synuclein protein, dopamine (DA), urate, ascorbic acid, miRNAs, and their biological roles are summarized. Additionally, the advantages and disadvantages of the usual standard methods are reviewed. We compared electrochemical, optical, and optochemical biosensors' properties and novel strategies for higher sensitivity and selectivity. CONCLUSION: The development of novel biosensors is required for the early diagnosis of PD as sensitive, rapid, reliable, and cost-effective systems.
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Técnicas Biosensibles , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Biomarcadores , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Humanos , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/metabolismoRESUMEN
A variety of organic nanomaterials and organic polymers are used for enzyme immobilization to increase enzymes stability and reusability. In this study, the effects of the immobilization of enzymes on organic and organic-inorganic hybrid nano-supports are compared. Immobilization of enzymes on organic support nanomaterials was reported to significantly improve thermal, pH and storage stability, acting also as a protection against metal ions inhibitory effects. In particular, the effects of enzyme immobilization on reusability, physical, kinetic and thermodynamic parameters were considered. Due to their biocompatibility with low health risks, organic support nanomaterials represent a good choice for the immobilization of enzymes. Organic nanomaterials, and especially organic-inorganic hybrids, can significantly improve the kinetic and thermodynamic parameters of immobilized enzymes compared to macroscopic supports. Moreover, organic nanomaterials are more environment friendly for medical applications, such as prodrug carriers and biosensors. Overall, organic hybrid nanomaterials are receiving increasing attention as novel nano-supports for enzyme immobilization and will be used extensively.
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Enzimas Inmovilizadas , Nanoestructuras , Biocatálisis , Estabilidad de Enzimas , Enzimas Inmovilizadas/metabolismo , CinéticaRESUMEN
Tau protein (Tau) is a proline-rich protein and in this work, we have developed a very interesting strategy based on combination of electrochemistry with chemometric methods to investigate proline cis/trans isomeration effect on the Tau aggregation. To achieve this goal, the proline residues at RTPPK motif have been replaced by alanine to generate RTPAK, RTAPK and RTAAK mutants of the Tau. Then, cyclic voltammetric (CV) responses of the Tau and RTPAK, RTAPK and RTAAK as its mutants in the presence of heparin (HEP) as an anionic inducing agent which could trigger aggregation of the Tau were recorded at physiological conditions every hour during 12 h. Therefore, 48 data sets of titrations were obtained which were handled by chemometric methods to extract useful information about aggregation of the Tau. The data were hard-modeled by EQUISPEC, SQUAD, REACTLAB and SPECFIT to extract useful quantitative information. Our results confirmed that the strength of the binding of the HEP with proteins was obeyed from Tau > RTPAK ~ RTAPK > RTAAK which confirmed that the aggregation of the proteins was obeyed from this order as well. Therefore, aggregation of the Tau is decreased by transforming Cis isomer to Trans even in the presence of an anionic inducing agent such as HEP which may have value for the treatment of Alzheimer's disease.
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Modelos Químicos , Agregado de Proteínas , Proteínas tau/química , Técnicas Electroquímicas , Humanos , Prolina/químicaRESUMEN
Metallic materials made of rather precious alloys are widely used in orthopedic surgery, circulatory system, and dentistry fields. Stainless steel coated by alloys with a variety of physiochemical properties can be an excellent candidate for making economical devices with superior biomedical compatibility. In this study, a Fe- based metallic glass alloy was applied on 316L stainless steel (316L SS) using the electro-spark deposition (ESD) method as an economic and easy handling method. The coated samples were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and atomic force microscopy (AFM). It was found that a metallic glass coating was uniformly formed on the stainless steel substrate. Cytocompatibility (MTT assay), hemocompatibility, and cell attachment assays of the fabricated biomaterials were carried out using bone and connective tissue cell lines. The samples with optimized coating were shown to exert lower cytotoxicity, better cell attachment, and higher blood compatibility than the stainless steel substrates.
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Vidrio , Acero Inoxidable , Materiales Biocompatibles/farmacología , Corrosión , Ensayo de MaterialesRESUMEN
α-Synuclein (αS) aggregates plays a pivotal role in the pathogenesis of synucleinopathies including Parkinson's Disease. The toxicity of αS aggregates has been broadly studied and variant defects have been reported through which these aggregates lead in cell death. Although cell death through apoptosis pathway has been proposed in many studies, the molecular details underlying in this pathway have not been uncovered. To shed a light on the relationships between αS aggregates and apoptotic cell death, changes in levels and behavior of molecular indicators of the intrinsic apoptotic pathway was investigated in HEK-293T cells overexpressing wild-type α-synuclein and A53T-α-synuclein. Overexpression of both WT-αS and A53T-αS resulted in the increase of caspase-9 activity, and rise in Cytochrome c (Cyt c) and PARC content, concurrently. We assume that rising in PARC level may result in Cyt c degradation, and consequently suppressing/attenuating intrinsic apoptosis pathway. Besides, increasing of Casp-9 activity can be related to αS aggregates and subsequent degradation of Cyt c. To understand the mechanisms behind this using theoretical model, molecular dynamic simulation was also applied to investigate the possible interaction of Casp-9 with α-synuclein aggregates. The results showed that the interaction between Casp-9 with αS aggregates could activate Casp-9 by changing the conformation of some crucial residues.
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Apoptosis , Citocromos c/metabolismo , alfa-Sinucleína/metabolismo , Sitios de Unión , Caspasa 9/química , Caspasa 9/metabolismo , Células HEK293 , Humanos , Simulación de Dinámica Molecular , Mutación Missense , Unión Proteica , Proteolisis , Transferasas/metabolismo , alfa-Sinucleína/química , alfa-Sinucleína/genéticaRESUMEN
Today, Alzheimer's disease (AD) as the most prevalent type of dementia turns into one of the most severe health problems. Neurofibrillary tangle (NFT), mostly comprised of fibrils formed by Tau, is a hallmark of a class of neurodegenerative diseases. Tau protein promotes assembly and makes stable microtubules that play a role in the appropriate function of neurons. Polyanionic cofactors such as heparin, and azo dyes, can induce aggregation of tau protein in vitro. Sunset Yellow is a food colorant used widely in food industries. In the current work, we introduced degradation product (DP) of Sunset Yellow as an effective inducer of Tau aggregation. Two Tau aggregation inducers were produced, and then the aggregation kinetics and the structure of 1N4R Tau amyloid fibrils were characterized using ThT fluorescence spectroscopy, X-Ray Diffraction (XRD), circular dichroism (CD) and atomic force microscopy (AFM). Also, the toxic effects of the induced aggregates on RBCs and SH-SY5Y cells were demonstrated by hemolysis and LDH assays, respectively. Both inducers efficiently accelerated the formation of the amyloid fibril. Along with the confirmation of the ß-sheets structure in Tau aggregates by Far-UV CD spectra, X-ray diffractions revealed the typical cross-ß diffraction pattern. The oligomer formation in the presence of DPs was also confirmed by AFM. The possible in vivo effect of artificial azo dyes on Tau aggregation should be considered seriously as a newly opened dimension in food safety and human health.
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Péptidos beta-Amiloides/antagonistas & inhibidores , Compuestos Azo/farmacología , Colorantes de Alimentos/farmacología , Proteínas tau/antagonistas & inhibidores , Péptidos beta-Amiloides/metabolismo , Compuestos Azo/química , Relación Dosis-Respuesta a Droga , Colorantes de Alimentos/química , Colorantes de Alimentos/metabolismo , Humanos , Estructura Molecular , Agregado de Proteínas/efectos de los fármacos , Solubilidad , Espectrometría de Fluorescencia , Relación Estructura-Actividad , Células Tumorales Cultivadas , Agua/química , Proteínas tau/aislamiento & purificación , Proteínas tau/metabolismoRESUMEN
Known as a main neural MAP (microtubule associated protein), tau protein contributes to stabilizing microtubules involved in cellular transmission. Tau dysfunction is mainly associated with neurodegenerative diseases, particularly Alzheimer's disease (AD). In these patients, all the six tau isoforms, which are in hyperphosphorylated form, are first aggregated and then polymerized into neurofibrillary tangles inside the brain. Tau protein detected in cerebrospinal fluid (CSF) is significantly correlated with AD and is well recognized as a hallmark of the disease. Served for detection of analytes of interest, biosensor device comprises a physical transducer and a keen biological recognition component. Qualitative and quantitative evaluations may be performed through analyzation of the data, which is gathered by measurable signals converted from biological reaction. Antibodies, receptors, microorganisms, nucleic acids, enzymes, cells and tissues, as well as some biomimetic structures, normally constitute the biosensor biological recognition part. Production of nanobiosensor, which was made possible through several accomplishments in nano- and fabrication technology, opens up new biotechnological horizons in diagnosis of multiple diseases. In recent years, many researches have been focused on developing novel and effective tau protein biosensors for rapid and accurate detection of AD. In this review, tau protein function and correlation with AD as well as the eminent research on developing nanobiosensor based on optical, electrochemical and piezoelectric approaches will be highlighted.
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Enfermedad de Alzheimer/líquido cefalorraquídeo , Técnicas Biosensibles , Proteínas tau/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , HumanosRESUMEN
Wound is among the most common injuries. A suitable wound dressing has a significant effect on the healing process. In this study, a porous wound dressing was prepared using poly (lactic acid) (PLA) and two plasticizers, polyethylene glycol (PEG) and triacetin (TA), through solvent casting method. For antibacterial activities, metronidazole was incorporated in the structure. The morphology was investigated by scanning electron microscopy (SEM). In addition, the effect of plasticizers ratio on porosity growth was evaluated. It was also observed that each had a unique effect on the structure's porosity. The mechanical properties confirmed the effect of both plasticizers on increasing polymer softness and flexibility, and the most similar formulations to human skin in terms of mechanical properties were introduced. According to the results, TA had stronger effect on mechanical properties. The differential scanning calorimetry (DSC) showed the effect of increasing plasticizer concentration on crystalline structure and Tm reduction of PLA. The water contact angle measurement showed that both plasticizers enhanced hydrophilic characteristics of PLA, and this effect was weaker in PEG-containing formulations. The in vitro degradation study showed biodegradability, as a desirable property in wound dressing. Results suggested that higher degradation can be obtained by both plasticizers at the same time. The results also showed that PEG was more effective in enhancing water absorbency. In vitro drug release study indicated an explosive release and the highest amount was 85% over 186 h. The antibacterial activity test confirmed the effectiveness of the drug in preventing bacterial growth in the drug-containing formulations, while it showed the antibacterial property of TA. MTT assay was performed and the cellular toxicity of the formulations was checked and those that revealed the least toxicity were introduced.
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Additive manufacturing techniques have evolved novel opportunities for the fabrication of highly porous composite scaffolds with well-controlled and interconnected pore structures which is notably important for tissue engineering. In this work, poly (ε-caprolactone) (PCL)-based composite scaffolds (average pore diameter of 450 µm and strut thickness of 400 µm) reinforced with 10 vol% bioactive glass particles (BG; â¼6 µm) or TiO2 nanoparticles (â¼21 nm), containing different concentrations of tetracycline hydrochloride (TCH) as an antimicrobial agent, were prepared by 3D printing. In order to investigate the effect of fabrication process and scaffold geometry on the biocompatibility, drug release kinetics, and antibacterial activity, polymer and composite films (2D structures) were also prepared by solvent casting method. We demonstrate that even without any additional coating layer, sustainable release can be attained on highly porous scaffolds prepared by 3D printing due to chemical interactions between functional groups of TCH and the bioactive particles. Herein, the effect of TiO2 nanoparticles on the release rate is substantially more pronounced than BG particles. Nevertheless, agar well-diffusion and MTT assays determine better cellular viability and higher antibacterial effect for PCL/BG composite. Although all the drug-eluting composite scaffolds exhibit acceptable hemocompatibility, in vitro cellular and bacterial studies also determine that the maximum amount of TCH that can inhibit gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) bacteria without cytotoxicity effect (≥95% viability) is 0.57 mg/ml. These findings may pave the way for designing structurally engineered composite scaffolds with sustainable drug release profile by additive manufacturing techniques for tissue engineering applications.
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Antibacterianos/administración & dosificación , Preparaciones de Acción Retardada/química , Poliésteres/química , Tetraciclina/administración & dosificación , Titanio/química , Antibacterianos/química , Antibacterianos/farmacología , Materiales Biocompatibles/química , Liberación de Fármacos , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Humanos , Porosidad , Impresión Tridimensional , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Tetraciclina/química , Tetraciclina/farmacología , Andamios del Tejido/químicaRESUMEN
Exosomes belong to extracellular vehicles that were produced and secreted from most eukaryotic cells and are involved in cell-to-cell communications. They are an effective delivery system for biological compounds such as mRNAs, microRNAs (miRNAs), proteins, lipids, saccharides, and other physiological compounds to target cells. In this way, they could influence on cellular pathways and mediate their physiological behaviors including cell proliferation, tumorigenesis, differentiation, and so on. Many research studies focused on their role in cancers and also on potentially therapeutic and biomarker applications. In the current study, we reviewed the exosomes' effects on cancer progression based on their cargoes including miRNAs, long noncoding RNAs, circular RNAs, DNAs, mRNAs, proteins, and lipids. Moreover, their therapeutic roles in cancer were considered. In this regard, we have given a brief overview of challenges and obstacles in using exosomes as therapeutic agents.
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Antineoplásicos , Sistemas de Liberación de Medicamentos , Exosomas/patología , Neoplasias/patología , Neoplasias/terapia , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Biomarcadores de Tumor/metabolismo , Resistencia a Antineoplásicos , Exosomas/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunoterapia/métodos , Neoplasias/genéticaRESUMEN
Tau protein, characterized as "natively unfolded", is involved in microtubule assembly/stabilization in physiological conditions. Under pathological conditions, Tau dysfunction leads to its accumulation of insoluble toxic amyloid aggregates and thought to be involved in the degeneration and neuronal death associated with neurodegenerative diseases. Trazodone (TRZ), a triazolopyridine derivative, is a selective serotonin reuptake inhibitor (SSRI) which increases serotonin levels in synaptic cleft and potentiating serotonin activity, with antidepressant and sedative properties. This drug is more effective and tolerable than other therapeutic agents. In this study, the 1N4R isoform of Tau protein was purified and the effect of TRZ on the protein fibrillation was investigated using multi-spectroscopic techniques as well as computational methods. The results showed that TRZ is not only able to affect formation of Tau amyloid fibrils in vitro but also attenuates Tau oligomerization within SH-SY5Y cell line resulting in more cells surviving. Moreover, membrane disrupting activity of Tau aggregates decreased upon TRZ treatment. The binding forces involved in TRZ-Tau interaction were also explored using both experimental as well as theoretical docking/molecular dynamics approaches. The results of the current work may open new insights for applying therapeutic potential of TRZ against Alzheimer's disease.
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Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/prevención & control , Antidepresivos/farmacología , Trazodona/farmacología , Proteínas tau/química , Enfermedad de Alzheimer/metabolismo , Antidepresivos/uso terapéutico , Línea Celular Tumoral , Humanos , Simulación de Dinámica Molecular , Agregado de Proteínas/efectos de los fármacos , Multimerización de Proteína/efectos de los fármacos , Estructura Cuaternaria de Proteína , Trazodona/uso terapéuticoRESUMEN
One of the major reasons for mortality throughout the world is cardiovascular diseases. Therefore, bio-markers of cardiovascular disease are of high importance to diagnose and manage procedure. Detecting biomarkers provided a promising procedure in developing bio-sensors. Fast, selective, portable, accurate, inexpensive, and sensitive biomarker sensing instruments will be necessary for detecting and predicting diseases. One of the cardiac biomarkers may be ordered as C-reactive proteins, lipoprotein-linked phospho-lipase, troponin I or T, myoglobin, interleukin-6, interleukin-1, tumor necrosis factor alpha, LDL and myeloperoxidase. The biomarkers are applied to anticipate cardio-vascular illnesses. Initial diagnoses of these diseases are possible by several techniques; however, they are laborious and need costly apparatus. Current researches designed various bio-sensors for resolving the respective issues. Electrochemical instruments and the proposed bio-sensors are preferred over other methods due to its inexpensiveness, mobility, reliability, repeatability. The present review comprehensively dealt with detecting biomarkers of cardiovascular disease through electro-chemical techniques.
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Técnicas Biosensibles , Enfermedades Cardiovasculares , Biomarcadores , Técnicas Electroquímicas , Humanos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Dynamic light scattering (DLS) and electron microscopy (EM) are the most practical techniques for nanoparticles (NPs) characterization. However, the impediments which involved the sample preparation method lead to failure in provided results of mentioned device analysis. These problems will be intensifying, if the examined samples are the soft nanocarriers such as organic ones or biological samples. OBJECTIVES: In order to achieve the appropriate results from DLS and EM analysis, an optimized protocol was introduced by this research which would prepare samples with high degree of quality and accuracy. MATERIALS AND METHODS: Morphological analysis of prepared polymeric nanocarriers (micelles, nanogels) by this protocol were done. Filtration, dilution and sonication as three crucial and effectiveness steps of sample preparation were assessed through DLS data and EM images. RESULTS: This research has tried to introduce a facile method with novelty of simplicity and rapidity. These triple steps could improve the quality of morphological data. The obtained results indicated that sample preparation methods have the most effective factors on sample size distribution and homogeneity of desired samples. CONCLUSION: The suggested optimized preparation method will be helpful for all soft nanomaterial's samples.
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Long noncoding RNAs (lncRNAs) constitute large portions of the mammalian transcriptome which appeared as a fundamental player, regulating various cellular mechanisms. LncRNAs do not encode proteins, have mRNA-like transcripts and frequently processed similar to the mRNAs. Many investigations have determined that lncRNAs interact with DNA, RNA molecules or proteins and play a significant regulatory function in several biological processes, such as genomic imprinting, epigenetic regulation, cell cycle regulation, apoptosis, and differentiation. LncRNAs can modulate gene expression on three levels: chromatin remodeling, transcription, and post-transcriptional processing. The majority of the identified lncRNAs seem to be transcribed by the RNA polymerase II. Recent evidence has illustrated that dysregulation of lncRNAs can lead to many human diseases, in particular, cancer. The aberrant expression of lncRNAs in malignancies contributes to the dysregulation of proliferation and differentiation process. Consequently, lncRNAs can be useful to the diagnosis, treatment, and prognosis, and have been characterized as potential cancer markers as well. In this review, we highlighted the role and molecular mechanisms of lncRNAs and their correlation with some of the cancers.