RESUMO
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 To achieve this goal, the proline residues at RTPPK motif have been replaced by alanine to generate RTPAK, RTAPK and RTAAK mutants of the Tau.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.
Assuntos
Modelos Químicos , Agregados Proteicos , Proteínas tau/química , Técnicas Eletroquímicas , Humanos , Prolina/químicaRESUMO
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 Liberação de Medicamentos , Exossomos/patologia , Neoplasias/patologia , Neoplasias/terapia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Exossomos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia/métodos , Neoplasias/genéticaRESUMO
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.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Antidepressivos/farmacologia , Trazodona/farmacologia , Proteínas tau/química , Doença de Alzheimer/metabolismo , Antidepressivos/uso terapêutico , Linhagem Celular Tumoral , Humanos , Simulação de Dinâmica Molecular , Agregados Proteicos/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Estrutura Quaternária de Proteína , Trazodona/uso terapêuticoRESUMO
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.
Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Compostos Azo/farmacologia , Corantes de Alimentos/farmacologia , Proteínas tau/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Compostos Azo/química , Relação Dose-Resposta a Droga , Corantes de Alimentos/química , Corantes de Alimentos/metabolismo , Humanos , Estrutura Molecular , Agregados Proteicos/efeitos dos fármacos , Solubilidade , Espectrometria de Fluorescência , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Água/química , Proteínas tau/isolamento & purificação , Proteínas tau/metabolismoRESUMO
In recent years there has been much interest in development of multifunctional drug delivery systems. In this work, liposomes that contain doxorubicin (Dox), a potent anticancer drug, and graphene nanosheets (GNS) were prepared. The GNSs have excellent optical properties, such as photoluminescence which enables tracking of the liposomes, high absorption in ultra violet region of electromagnetic spectrum which can be exploited in photodynamic and photothermal therapy, and low toxicity to mammalian cells. Nanoliposomes were prepared using the thin film hydration method. Dox and GNSs were loaded to the liposomes during the hydration of the lipid film. Liposomes were characterized and the profile of in vitro drug release, cellular uptake, and cytotoxicity of the prepared liposomes on MCF-7 cells were determined. Despite the earlier reports, the liposomes have kept their spherical structures in the presence of GNSs. The cytotoxicity of liposomal Dox and GNSs were shown to be higher than the free forms of them. Novel nanoliposomes that contain GNSs have provided a multi-functional system with the potential of tracking, photodynamic and photothermal therapy. Further improvements of this versatile nanosystem would be promising for treatment of cancer.
Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/análogos & derivados , Portadores de Fármacos/química , Grafite/química , Lipossomos/química , Nanoestruturas/química , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Etanolaminas/química , Humanos , Células MCF-7 , Tamanho da Partícula , Fosforilcolina/química , Polietilenoglicóis/farmacologiaRESUMO
Parkinson's disease is characterized by accumulation of inclusion bodies in dopaminergic neurons, where insoluble and fibrillar α-synuclein makes up the major component of these inclusion bodies. So far, several strategies have been applied in order to suppress α-synuclein aggregation and toxicity in Parkinson's disease. In the present study, a new database has been established by segmentation of all the proteins deposited in protein Data Bank. The database data base was searched for the sequences which adopt ß structure and are identical or very similar to the regions of α-synuclein which are involved in aggregation. The adjacent ß strands of the found sequences were chosen as the peptide inhibitors of α-synuclein aggregation. Two of the predicted peptides, namely KISVRV and GQTYVLPG, were experimentally proved to be efficient in suppressing aggregation of α-synuclein in vitro. Moreover, KISVRV exhibited the ability to disrupt oligomers of α-syn which are assumed to be the pathogenic species in Parkinson's disease.
Assuntos
Amiloide/química , Materiais Biomiméticos/química , Peptídeos/química , alfa-Sinucleína/química , Sítios de Ligação , Desenho de Fármacos , Ligação Proteica , Análise de Sequência de ProteínaRESUMO
BACKGROUND: Providing equitable maternal care to migrants is a seriously challenging task for hosting countries. Iran, the second-most accessed country for refugees from Afghanistan, has achieved maternal health improvement. However, Afghan women with near-miss morbidity faced pre-hospital delays and disparity in maternal care at hospitals. This study explores experiences of maternal care among Afghan women surviving near-miss morbidity to increase insight into healthcare improvements for migrants. METHODS: A qualitative study was conducted at university hospitals in Tehran, from April 2013 to May 2014. A total of 11 Afghan women and 4 husbands were interviewed when women recovered from near-miss morbidity that occurred around the childbirth period. Mothers were identified prospectively using the WHO maternal near-miss approach. Thematic analysis was used along with a data-driven approach to organize data guided by the 'three delays model' theoretical framework. RESULTS: Mistreatment in the form of discrimination and insufficient medical attention were key experiences. Participants commonly perceived poor women-professional communication and delays in recognizing obstetric complications despite repeated care-seeking. Financial constraints, costly care, lack of health insurance, and low literacy were experienced barriers to accessing care to a lesser extent. Non-somatic consequences of near-miss morbidity affected mothers and families for extended periods. CONCLUSIONS: Near-miss survivors' experiences provided remarkable insights into maternal care of Afghans in Iran. The challenge for the health system and professionals is to provide equitable care with dignity and improve communication skills with caring attitudes toward ethnic minorities. Antenatal visits provide the best and most appropriate opportunities to tackle health illiteracy in Afghan women.
Assuntos
Parto Obstétrico , Emigrantes e Imigrantes , Disparidades em Assistência à Saúde , Serviços de Saúde Materna/normas , Mortalidade Materna/etnologia , Satisfação do Paciente , Complicações na Gravidez/mortalidade , Adolescente , Adulto , Afeganistão/etnologia , Feminino , Hospitais Universitários , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Morbidade , Mães , Gravidez , Pesquisa Qualitativa , Refugiados , Discriminação Social , Sobreviventes , Migrantes , Adulto JovemRESUMO
BACKGROUND: Women from low-income settings have higher risk of maternal near miss (MNM) and suboptimal care than natives in high-income countries. Iran is the second largest host country for Afghan refugees in the world. Our aim was to investigate whether care quality for MNM differed between Iranians and Afghans and identify potential preventable attributes of MNM. METHODS: An MNM audit study was conducted from 2012 to 2014 at three university hospitals in Tehran. Auditors evaluated the quality of care by reviewing the hospital records of 76 MNM cases (54 Iranians, 22 Afghans) and considering additional input from interviews with patients and professionals. Main outcomes were frequency of suboptimal care and the preventable attributes of MNM. Crude and adjusted odds ratios with confidence intervals for the independent predictors were examined. RESULTS: Afghan MNM faced suboptimal care more frequently than Iranians after adjusting for educational level, family income, and insurance status. Above two-thirds (71%, 54/76) of MNM cases were potentially avoidable. Preventable factors were mostly provider-related (85%, 46/54), but patient- (31%, 17/54) and health system-related factors (26%, 14/54) were also important. Delayed recognition, misdiagnosis, inappropriate care plan, delays in care-seeking, and costly care services were the main potentially preventable attributes of MNM. CONCLUSIONS: Afghan mothers faced inequality in obstetric care. Suboptimal care was provided in a majority of preventable near-miss events. Improving obstetric practice and targeting migrants' specific needs during pregnancy may avert near-miss outcomes.
Assuntos
Hospitais Universitários/estatística & dados numéricos , Auditoria Administrativa/métodos , Serviços de Saúde Materna/organização & administração , Near Miss/organização & administração , Complicações na Gravidez/etnologia , Cuidado Pré-Natal/métodos , Migrantes , Adulto , Estudos Transversais , Feminino , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Mortalidade Materna/tendências , Razão de Chances , Gravidez , Fatores de Risco , Adulto JovemRESUMO
INTRODUCTION: Cesarean section carries a substantial risk of maternal near-miss morbidity. The aim of this study was to determine the frequency, causes, risk factors, and perinatal outcomes of maternal near-miss at three university hospitals with a high rate of cesarean section in Tehran, Iran. MATERIAL AND METHODS: An incident case-control study was conducted from March 2012 to May 2014. The modified WHO near-miss criteria were used to identify cases. A control sample of 1024 women delivering at the study hospitals was recruited to represent the source population. Near-miss ratio, crude and adjusted odds ratios with confidence intervals were assessed. RESULTS: Among 12 965 live births, 82 mothers developed near-miss morbidities and 12 died. The maternal near-miss ratio was 6.3/1000 live births. Severe postpartum hemorrhage (35%, 29/82), severe preeclampsia (32%, 26/82), and placenta previa/abnormally invasive placenta (10%, 8/82) were the most frequent causes of maternal near-miss. Women with antepartum cesarean section (adjusted odds ratio 7.4, 95% confidence interval 3.7-15.1) and co-morbidity (adjusted odds ratio 2.3, 95% confidence interval 1.4-3.8), uninsured Iranians (adjusted odds ratio 3.4, 95% confidence interval 1.7-7.1) and uninsured Afghans (adjusted odds ratio 4.7, 95% confidence interval 2.4-9.2) had increased risks of near-miss morbidity. Stillbirth and extremely preterm birth were the most prominent adverse perinatal outcomes associated with maternal near-miss. CONCLUSIONS: Overutilization of cesarean section clearly influenced the causes of maternal near-miss. A lack of health insurance had a measurable impact on near-miss morbidity. Tailored interventions for reducing unnecessary cesarean section and unrestricted insurance cover for emergency obstetric care can potentially improve maternal and perinatal outcomes.
Assuntos
Cesárea/estatística & dados numéricos , Complicações na Gravidez/epidemiologia , Cuidado Pré-Natal , Adulto , Estudos de Casos e Controles , Cesárea/efeitos adversos , Feminino , Hospitais Universitários , Humanos , Incidência , Recém-Nascido , Irã (Geográfico)/epidemiologia , Mortalidade Materna , Avaliação de Resultados em Cuidados de Saúde , Mortalidade Perinatal , Gravidez , Complicações na Gravidez/mortalidade , Complicações na Gravidez/prevenção & controle , Fatores de Risco , Adulto JovemRESUMO
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.
Assuntos
Carbono , Espaço Extracelular , Ouro , Carbono/química , Fluorescência , Oxirredução , Cátions/química , Ouro/análise , Ouro/química , Humanos , Células HeLa , Dicroísmo Circular , Espaço Extracelular/química , Nanopartículas Metálicas/química , Sobrevivência Celular , Fenilenodiaminas/química , Cisteína/química , Sulfetos/química , Limite de DetecçãoRESUMO
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.
RESUMO
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.
Assuntos
Nanoestruturas , Neoplasias , Humanos , Espécies Reativas de Oxigênio/metabolismo , Óxidos/uso terapêutico , Óxidos/química , Medicina de Precisão , Compostos de Manganês/química , Neoplasias/tratamento farmacológico , Nanoestruturas/química , Microambiente TumoralRESUMO
OBJECTIVE: To investigate whether the introduction of clinical audits by the Safe Motherhood Committee of a general hospital in Tehran, Iran, influenced cesarean section (CS) rates, STUDY DESIGN: A retrospective study was performed. The number of deliveries before and after the institution of clinical audits (May to December 2005) were tabulated in the audited hospital and analyzed by Chi(2) test. Additionally, CS rates were measured in 3 other general hospitals during the same time period for comparison. RESULTS: A total of 3,494 deliveries were recorded during the study periods in 2004 and 2005 at the audited hospital. Subsequent to the audit, the overall CS rate decreased from 40% to 33% (p < 0.001) and the primary CS rate from 29% to 21% (p < 0.001), accounting for a 27% reduction in the risk of primary CS. In 2006 CS rates reverted to 42%. None of the other 3 general hospitals indicated a decline in CS rates in 2005. CONCLUSION: Our findings show a preventive association between the clinical audits and CS rates in a general hospital. The implementation of a clinical audit process can be an effective way to track care pathways and reduce unnecessary CS deliveries.
Assuntos
Cesárea/estatística & dados numéricos , Auditoria Médica/estatística & dados numéricos , Complicações do Trabalho de Parto/epidemiologia , Cuidado Pré-Natal/organização & administração , Adulto , Feminino , Hospitais Gerais/organização & administração , Humanos , Irã (Geográfico) , Auditoria Administrativa , Complicações do Trabalho de Parto/prevenção & controle , Gravidez , Qualidade da Assistência à Saúde , Estudos Retrospectivos , Adulto JovemRESUMO
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.
RESUMO
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.
Assuntos
Doença de Alzheimer , Proteínas tau , Alanina , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Humanos , Proteínas Mutantes , Prolina/química , Agregados Proteicos , Proteínas tau/químicaRESUMO
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.
Assuntos
Técnicas Biossensoriais , Doenças Neurodegenerativas , Doença de Parkinson , Biomarcadores , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/metabolismoRESUMO
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.
Assuntos
Apoptose , Citocromos c/metabolismo , alfa-Sinucleína/metabolismo , Sítios de Ligação , Caspase 9/química , Caspase 9/metabolismo , Células HEK293 , Humanos , Simulação de Dinâmica Molecular , Mutação de Sentido Incorreto , Ligação Proteica , Proteólise , Transferases/metabolismo , alfa-Sinucleína/química , alfa-Sinucleína/genéticaRESUMO
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.
Assuntos
Enzimas Imobilizadas , Nanoestruturas , Biocatálise , Estabilidade Enzimática , Enzimas Imobilizadas/metabolismo , CinéticaRESUMO
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.
Assuntos
Vidro , Aço Inoxidável , Materiais Biocompatíveis/farmacologia , Corrosão , Teste de MateriaisRESUMO
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.