RESUMO
Covert speech (CS) refers to speaking internally to oneself without producing any sound or movement. CS is involved in multiple cognitive functions and disorders. Reconstructing CS content by brain-computer interface (BCI) is also an emerging technique. However, it is still controversial whether CS is a truncated neural process of overt speech (OS) or involves independent patterns. Here, we performed a word-speaking experiment with simultaneous EEG-fMRI. It involved 32 participants, who generated words both overtly and covertly. By integrating spatial constraints from fMRI into EEG source localization, we precisely estimated the spatiotemporal dynamics of neural activity. During CS, EEG source activity was localized in three regions: the left precentral gyrus, the left supplementary motor area, and the left putamen. Although OS involved more brain regions with stronger activations, CS was characterized by an earlier event-locked activation in the left putamen (peak at 262 ms versus 1170 ms). The left putamen was also identified as the only hub node within the functional connectivity (FC) networks of both OS and CS, while showing weaker FC strength towards speech-related regions in the dominant hemisphere during CS. Path analysis revealed significant multivariate associations, indicating an indirect association between the earlier activation in the left putamen and CS, which was mediated by reduced FC towards speech-related regions. These findings revealed the specific spatiotemporal dynamics of CS, offering insights into CS mechanisms that are potentially relevant for future treatment of self-regulation deficits, speech disorders, and development of BCI speech applications.
Assuntos
Eletroencefalografia , Imageamento por Ressonância Magnética , Fala , Humanos , Masculino , Imageamento por Ressonância Magnética/métodos , Feminino , Fala/fisiologia , Adulto , Eletroencefalografia/métodos , Adulto Jovem , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodosRESUMO
Portion size selection is an indicator of appetite and within younger adults, is predicted by factors such as expected satiety, liking and motivations to achieve an ideal sensation of fullness (i.e., implicit satiety goals). Currently, there is limited research available on the determinants of portion size selection within older adults. Therefore, the current study aimed to examine the relationship between individual differences in implicit satiety goals, food-related expectations, and portion size selection in older adults. Free-living older adult Singaporeans (N = 115; Nmales = 62; age: M = 66.21 years, SD = 4.78, range = 60-83 years) participated as part of the Brain, Ageing, Microbiome, Muscle, Bone, and Exercise Study (BAMMBE). Participants completed questionnaires on their subjective requirements for experiencing different states of satiety and food-related expectations (i.e., liking, how filling) as well as a computerised portion size selection task. Using a multiple regression, we found that goals to feel comfortably full (B = 3.08, SE = 1.04, t = 2.96, p = .004) and to stop hunger (B = -2.25, SE = 0.82, t = -2.75, p = .007) significantly predicted larger portion size selection (R2 = 0.24, F(4,87) = 6.74, p < .001). Larger portion sizes (R2 = 0.53, F(5,90) = 20.58, p < .001) were also predicted by greater expected satiety (B = 0.47, SE = 0.09, t = 5.15, p < .001) and lower perceptions of how filling foods are (B = -2.92, SE = 0.77, t = -3.79, p < .001) but not liking (B = -0.09, SE = 0.91, t = -0.10, p = .925) or frequency (B = -18.42, SE = 16.91, t = -1.09, p = .279) of consumption of target foods. Comparing our findings to results of studies conducted with younger adults suggests the influence of factors such as satiety related goals on portion size selection may change with ageing while the influence of other factors (e.g., expected satiety/fullness delivered by foods) may remain consistent. These findings may inform future strategies to increase/decrease portion size accordingly to ensure older adults maintain an appropriate healthy weight.
Assuntos
Exercício Físico , Humanos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Inquéritos e QuestionáriosRESUMO
Following the in vivo biodistribution of platelets can contribute to a better understanding of their physiological and pathological roles, and nuclear imaging methods, such as single photon emission tomography (SPECT), provide an excellent method for that. SPECT imaging needs stable labeling of the platelets with a radioisotope. In this study, we report a new method to label platelets with 99mTc, the most frequently used isotope for SPECT in clinical applications. The proposed radiolabeling procedure uses a membrane-binding peptide, duramycin. Our results show that duramycin does not cause significant platelet activation, and radiolabeling can be carried out with a procedure utilizing a simple labeling step followed by a size-exclusion chromatography-based purification step. The in vivo application of the radiolabeled human platelets in mice yielded quantitative biodistribution images of the spleen and liver and no accumulation in the lungs. The performed small-animal SPECT/CT in vivo imaging investigations revealed good in vivo stability of the labeling, which paves the way for further applications of 99mTc-labeled-Duramycin in platelet imaging.
Assuntos
Bacteriocinas , Tomografia Computadorizada de Emissão de Fóton Único , Camundongos , Humanos , Animais , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Peptídeos/metabolismo , Bacteriocinas/metabolismoRESUMO
Nutritional interventions may highly contribute to the maintenance or restoration of human health. Grapes (Vitis vinifera) are one of the oldest known beneficial nutritional components of the human diet. Their high polyphenol content has been proven to enhance human health beyond doubt in statistics-based public health studies, especially in the prevention of cardiovascular disease and cancer. The current review concentrates on presenting and classifying polyphenol bioactive molecules (resveratrol, quercetin, catechin/epicatechin, etc.) available in high quantities in Vitis vinifera grapes or their byproducts. The molecular pathways and cellular signaling cascades involved in the effects of these polyphenol molecules are also presented in this review, which summarizes currently available in vitro and in vivo experimental literature data on their biological activities mostly in easily accessible tabular form. New molecules for different therapeutic purposes can also be synthesized based on existing polyphenol compound classes available in high quantities in grape, wine, and grape marc. Therefore an overview of these molecular structures is provided. Novel possibilities as dendrimer nanobioconjugates are reviewed, too. Currently available in vitro and in vivo experimental literature data on polyphenol biological activities are presented in easily accessible tabular form. The scope of the review details the antidiabetic, anticarcinogenic, antiviral, vasoprotective, and neuroprotective roles of grape-origin flavonoids. The novelty of the study lies in the description of the processing of agricultural by-products (grape seeds and skins) of industrial relevance, and the detailed description of the molecular mechanisms of action. In addition, the review of the clinical therapeutic applications of polyphenols is unique as no summary study has yet been done.
Assuntos
Catequina , Dendrímeros , Vitis , Antioxidantes/farmacologia , Antivirais/análise , Flavonoides/farmacologia , Humanos , Hipoglicemiantes/análise , Polifenóis/análise , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Quercetina/análise , Resveratrol , Sementes/química , Vitis/químicaRESUMO
The development of a biomimetic neuronal network from neural cells is a big challenge for researchers. Recent advances in nanotechnology, on the other hand, have enabled unprecedented tools and techniques for guiding and directing neural stem cell proliferation and differentiation in vitro to construct an in vivo-like neuronal network. Nanotechnology allows control over neural stem cells by means of scaffolds that guide neurons to reform synaptic networks in suitable directions in 3D architecture, surface modification/nanopatterning to decide cell fate and stimulate/record signals from neurons to find out the relationships between neuronal circuit connectivity and their pathophysiological functions. Overall, nanotechnology-mediated methods facilitate precise physiochemical controls essential to develop tools appropriate for applications in neuroscience. This review emphasizes the newest applications of nanotechnology for examining central nervous system (CNS) roles and, therefore, provides an insight into how these technologies can be tested in vitro before being used in preclinical and clinical research and their potential role in regenerative medicine and tissue engineering.
Assuntos
Técnicas de Cultura de Células/métodos , Nanotecnologia/métodos , Rede Nervosa/metabolismo , Células-Tronco Neurais/metabolismo , Neurogênese , Engenharia Tecidual/métodos , Animais , Técnicas de Cultura de Células/instrumentação , Humanos , Nanotecnologia/instrumentação , Rede Nervosa/ultraestrutura , Células-Tronco Neurais/ultraestrutura , Neurogênese/fisiologia , Medicina Regenerativa , Engenharia Tecidual/instrumentaçãoRESUMO
Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [11C]PBR28 and [18F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [11C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [18F]flumazenil is a radioligand for GABAA-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [11C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [18F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [11C]PBR28 and [18F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.
Assuntos
Lesões Encefálicas Traumáticas/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Acetamidas , Animais , Lesões Encefálicas Traumáticas/etiologia , Lesões Encefálicas Traumáticas/patologia , Radioisótopos de Carbono , Modelos Animais de Doenças , Flumazenil , Radioisótopos de Flúor , Masculino , Percussão , Piridinas , Ratos , Ratos Sprague-DawleyRESUMO
Hepatitis C virus (HCV) infection is among the leading causes of hepatocellular carcinoma and liver cirrhosis globally, with a high economic burden. The disease progression is well established, but less is known about the spontaneous HCV infection clearance. This study tries to establish the relationship between codon biasness and expression of HCV clearance candidate genes in normal and HCV infected liver tissues. A total of 112 coding sequences comprising 151 679 codons were subjected to the computation of codon indices, namely relative synonymous codon usage, an effective number of codon (Nc), frequency of optimal codon, codon adaptation index, codon bias index, and base compositions. Codon indices report of GC3s, GC12, hydropathicity, and aromaticity implicates both mutational and translational selection in the candidate gene set. This was further correlated with the differentially expressed genes among the selected genes using BioGPS. A significant correlation is observed between the gene expression of normal liver and cancerous liver tissues with codon bias (Nc). Gene expression is also correlated with relative codon bias values, indicating that CCL5, APOA2, CD28, IFITM1, and TNFSF4 genes have higher expression. These results are quite encouraging in selecting the high responsive genes in HCV clearance. However, there could be additional genes which could also orchestrate the clearance role with the above mentioned first line of defensive genes.
Assuntos
Biomarcadores/metabolismo , Uso do Códon/genética , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C/virologia , Carga Viral , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/metabolismo , Apolipoproteína A-II/genética , Apolipoproteína A-II/metabolismo , Antígenos CD28/genética , Antígenos CD28/metabolismo , Quimiocina CCL5/genética , Quimiocina CCL5/metabolismo , Hepatite C/genética , Humanos , Ligante OX40/genética , Ligante OX40/metabolismoRESUMO
The rapid advancements in machine learning, graphics processing technologies and the availability of medical imaging data have led to a rapid increase in the use of deep learning models in the medical domain. This was exacerbated by the rapid advancements in convolutional neural network (CNN) based architectures, which were adopted by the medical imaging community to assist clinicians in disease diagnosis. Since the grand success of AlexNet in 2012, CNNs have been increasingly used in medical image analysis to improve the efficiency of human clinicians. In recent years, three-dimensional (3D) CNNs have been employed for the analysis of medical images. In this paper, we trace the history of how the 3D CNN was developed from its machine learning roots, we provide a brief mathematical description of 3D CNN and provide the preprocessing steps required for medical images before feeding them to 3D CNNs. We review the significant research in the field of 3D medical imaging analysis using 3D CNNs (and its variants) in different medical areas such as classification, segmentation, detection and localization. We conclude by discussing the challenges associated with the use of 3D CNNs in the medical imaging domain (and the use of deep learning models in general) and possible future trends in the field.
Assuntos
Aprendizado Profundo , Imageamento Tridimensional , Humanos , Aprendizado de Máquina , Redes Neurais de ComputaçãoRESUMO
In the present study pufferfish, Arothron immaculatus muscle methanol extract (AIME) was used to evaluate the antidiabetic activity against the high-fat diet (HFD) in streptozotocin (STZ) induced diabetic rat models. Initially, the In vitro antioxidant activity of the different muscle extract was evaluated which showed that AIME has higher efficiency to scavenge the free radicals. The animal study results revealed that the AIME could decrease the blood glucose level after 14â¯days of oral treatment and recover the animal from the severe progression of the disease. The LC-ESI/MS analysis of AIME extract revealed the presence of compounds such as docosahexaenoic acid, adrenic acid, docosanol, codeine and metoprolol. Among these compounds, docosahexaenoic acid, adrenic acid and docosanol are reported for its antidiabetic studies. Hence, the muscle is recommended to consume by humans as natural food in order to overcome the development of diabetes. This is the first study on the muscle extract of marine pufferfish which is used as antidiabetic agent to treat the diabetes-induced in the animal model.
Assuntos
Antioxidantes/farmacologia , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Hipoglicemiantes/farmacologia , Músculo Esquelético/química , Tetraodontiformes/fisiologia , Animais , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/patologia , Insulina/sangue , Masculino , Ratos , Ratos WistarRESUMO
Nanomaterials have gained tremendous significance as contrast agents for both anatomical and functional preclinical bio-imaging. Contrary to conventional medical practices, molecular imaging plays an important role in exploring the affected cells, thus providing precision medical solutions. It has been observed that incorporating nanoprobes improves the overall efficacy of the diagnosis and treatment processes. These nano-agents and tracers are therefore often incorporated into preclinical therapeutic and diagnostic applications. Multimodal imaging approaches are well equipped with nanoprobes to explore neurological disorders, as they can display more than one type of characteristic in molecular imaging. Multimodal imaging systems are explored by researchers as they can provide both anatomical and functional details of tumors and affected tissues. In this review, we present the state-of-the-art research concerning multimodal imaging systems and nanoprobes for neuroimaging applications.
Assuntos
Meios de Contraste , Imagem Multimodal , Nanoestruturas , Neoplasias/diagnóstico por imagem , Neuroimagem , Animais , Humanos , Imageamento por Ressonância Magnética , Imagem Multimodal/métodos , Neuroimagem/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Pesquisa , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Long gone is the time when tumors were thought to be insular masses of cells, residing independently at specific sites in an organ. Now, researchers gradually realize that tumors interact with the extracellular matrix (ECM), blood vessels, connective tissues, and immune cells in their environment, which is now known as the tumor microenvironment (TME). It has been found that the interactions between tumors and their surrounds promote tumor growth, invasion, and metastasis. The dynamics and diversity of TME cause the tumors to be heterogeneous and thus pose a challenge for cancer diagnosis, drug design, and therapy. As TME is significant in enhancing tumor progression, it is vital to identify the different components in the TME such as tumor vasculature, ECM, stromal cells, and the lymphatic system. This review explores how these significant factors in the TME, supply tumors with the required growth factors and signaling molecules to proliferate, invade, and metastasize. We also examine the development of TME-targeted nanotheranostics over the recent years for cancer therapy, diagnosis, and anticancer drug delivery systems. This review further discusses the limitations and future perspective of nanoparticle based theranostics when used in combination with current imaging modalities like Optical Imaging, Magnetic Resonance Imaging (MRI) and Nuclear Imaging (Positron Emission Tomography (PET) and Single Photon Emission Computer Tomography (SPECT)).
Assuntos
Neoplasias/diagnóstico , Neoplasias/terapia , Nanomedicina Teranóstica/métodos , Microambiente Tumoral , Animais , Diagnóstico por Imagem , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Humanos , Camundongos , Neoplasias/patologiaRESUMO
The auto-aggregating ability of a probiotic is a prerequisite for colonization and protection of the gastrointestinal tract, whereas co-aggregation provides a close interaction with pathogenic bacteria. Peptide pheromone mediated signaling has been studied in several systems. However, it has not yet been explored in prokaryotes, especially actinobacteria. Hence, in the present study, the diffusible aggregation promoting factor was purified from the culture supernatant of a potent actinobacterial probiont and characterized using 20 different actinobacterial cultures isolated from the gut region of chicken and goat. The results showed that the pheromone-like compound induces the aggregation propensity of treated isolates. The factor was found to be a heat stable, acidic pH resistant, low molecular weight peptide which enhances the biofilm forming ability of other actinobacterial isolates. The aggregation promoting factor represents a bacterial sex factor (pheromone) and its characterization confirms its usage in the probiotic formulation.
Assuntos
Actinobacteria , Biofilmes/crescimento & desenvolvimento , Trato Gastrointestinal/microbiologia , Interações Microbianas/fisiologia , Feromônios , Probióticos/metabolismo , Actinobacteria/isolamento & purificação , Actinobacteria/fisiologia , Animais , Galinhas , Cabras , Peptídeos/química , Peptídeos/metabolismo , Feromônios/química , Feromônios/metabolismo , Fatores de ProteçãoRESUMO
In this communication, we report the synthesis of small-sized (<10â nm), water-soluble, magnetic nanoparticles (MNPs) coated with polyhedral oligomeric silsesquioxanes (POSS), which contain either polyethylene glycol (PEG) or octa(tetramethylammonium) (OctaTMA) as functional groups. The POSS-coated MNPs exhibit superparamagnetic behavior with saturation magnetic moments (51-53â emu g(-1)) comparable to silica-coated MNPs. They also provide good colloidal stability at different pH and salt concentrations, and low cytotoxicity to MCF-7 human breast epithelial cells. The relaxivity data and magnetic resonance (MR) phantom images demonstrate the potential application of these MNPs in bioimaging.
Assuntos
Células Epiteliais/citologia , Compostos Férricos/química , Células MCF-7/química , Imageamento por Ressonância Magnética/métodos , Compostos de Organossilício/química , Polietilenoglicóis/química , Compostos de Amônio Quaternário/química , Dióxido de Silício/química , Dióxido de Silício/síntese química , Células Epiteliais/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas de Magnetita , PorosidadeRESUMO
Saliva is considered as the best source of biological material for biomarker discovery studies since it is noninvasive in comparison to other body sources. Usually buffalo cannot precisely express estrus signals. Hence, there is a need for concise methods to detect the time of estrus to ensure the success of artificial insemination. Therefore, we have established a reference proteome map on the whole saliva of buffalo during their estrous cycle with special reference to estrus. Nearly 12 bands have been observed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of whole saliva. Collectively, 179 proteins are identified with respect to different phases of the estrous cycle using mass spectrometry. On the whole, 37 proteins are exclusively expressed in the estrus phase, which include ß-enolase, Toll-like receptor (TLR) 4, clusterin, lactoperoxidase, serotransferrin, TGM3, UBA6, and transducin. Among the proteins, ß-enolase and TLR 4 were validated, and their specific expression was found during estrus as compared to other phases using immunoblot. The functional annotation reveals many as binding proteins in the estrus saliva when compared to the other phases. The present findings conclude that the proteomic approach adopted to identify the proteins from buffalo saliva around the estrous cycle may provide a new tool for screening the estrus phase. The results further conclude that the specific expression of ß-enolase and TLR 4 can be taken as the indicator of estrus in buffalo.
Assuntos
Ciclo Estral/metabolismo , Estro/metabolismo , Saliva/química , Proteínas e Peptídeos Salivares/análise , Animais , Biomarcadores/análise , Búfalos , Eletroforese em Gel de Poliacrilamida/métodos , Valor Preditivo dos Testes , Proteoma/metabolismoRESUMO
Perception of molecular mechanism would provide potent additional knowledge on mammalian membrane proteins involved in causing diseases. In human, syntaxin-3 (STX3) is a significant apical targeting protein in the epithelial membrane and in exocytosis process; it also acts as a vesicle transporter by cellular receptor in neutrophils, which is crucial for protein trafficking event. Structurally, syntaxin-3 has hydrophobic domain at carboxyl terminus that directs itself to intra-cellular compartments. In addition, the experimental structure of STX3 is not available and no mutational study has been carried out with natural variants of proteins. Moreover, there is no evidence so far for the natural variant Val286 of STX3 causing any diseases. Hence, in the present study, analyses of residue-based properties of the homology model STX3 were carried out along with mutations at carboxyl terminus of STX3 by implementing protein engineering and in silico approaches. The model structure of STX3 was constructed adopting Modeller v9.11 and the aggregation propensity was analyzed with BioLuminate tool. The results showed that there was reduction in aggregation propensity with point mutation at Val286, instead of Ile, resulting into increasing the structural stability of STX3. In conclusion, the Ccap exposed residue would be a suitable position for further mutational studies, particularly with Val286 of STX3 in human. This approach could gainfully be applied to STX3 for efficient drug designing which would be a valuable target in the cancer treatment.
Assuntos
Modelos Químicos , Modelos Genéticos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Proteínas Qa-SNARE/química , Proteínas Qa-SNARE/genética , Simulação por Computador , Humanos , Complexos Multiproteicos/química , Complexos Multiproteicos/genética , Complexos Multiproteicos/ultraestrutura , Mutação/genética , Ligação Proteica , Conformação Proteica , Dobramento de Proteína , Multimerização Proteica , Proteínas Qa-SNARE/ultraestrutura , Homologia de Sequência de AminoácidosRESUMO
Reactive oxygen species (ROS) contain at least one oxygen atom and one or more unpaired electrons and include singlet oxygen, superoxide anion radical, hydroxyl radical, hydroperoxyl radical, and free nitrogen radicals. Intracellular ROS can be formed as a consequence of several factors, including ultra-violet (UV) radiation, electron leakage during aerobic respiration, inflammatory responses mediated by macrophages, and other external stimuli or stress. The enhanced production of ROS is termed oxidative stress and this leads to cellular damage, such as protein carbonylation, lipid peroxidation, deoxyribonucleic acid (DNA) damage, and base modifications. This damage may manifest in various pathological states, including ageing, cancer, neurological diseases, and metabolic disorders like diabetes. On the other hand, the optimum levels of ROS have been implicated in the regulation of many important physiological processes. For example, the ROS generated in the mitochondria (mitochondrial ROS or mt-ROS), as a byproduct of the electron transport chain (ETC), participate in a plethora of physiological functions, which include ageing, cell growth, cell proliferation, and immune response and regulation. In this current review, we will focus on the mechanisms by which mt-ROS regulate different pathways of host immune responses in the context of infection by bacteria, protozoan parasites, viruses, and fungi. We will also discuss how these pathogens, in turn, modulate mt-ROS to evade host immunity. We will conclude by briefly giving an overview of the potential therapeutic approaches involving mt-ROS in infectious diseases.
Assuntos
Mitocôndrias , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Humanos , Mitocôndrias/metabolismo , Animais , Estresse Oxidativo , Infecções/metabolismo , Infecções/imunologia , ImunidadeRESUMO
Purpose: Development of SERS-based Raman nanoprobes can detect the misfolding of Amyloid beta (Aß) 42 peptides, making them a viable diagnostic technique for Alzheimer's disease (AD). The detection and imaging of amyloid peptides and fibrils are expected to help in the early identification of AD. Methods: Here, we propose a fast, easy-to-use, and simple scheme based on the selective adsorption of Aß42 molecules on SERS active gold nanoprobe (RB-AuNPs) of diameter 29 ± 3 nm for Detection of Alzheimer's Disease Biomarkers. Binding with the peptides results in a spectrum shift, which correlates with the target peptide. We also demonstrated the possibility of using silver nanoparticles (AgNPs) as precursors for the preparation of a SERS active nanoprobe with carbocyanine (CC) dye and AgNPs known as silver nanoprobe (CC-AgNPs) of diameter 25 ± 4 nm. Results: RB-AuNPs probe binding with the peptides results in a spectrum shift, which correlates with the target peptide. Arginine peak appears after the conjugation confirms the binding of Aß 42 with the nanoprobe. Tyrosine peaks appear after conjugated Aß42 with CC-AgNPs providing binding of the peptide with the probe. The nanoprobe produced a strong, stable SERS signal. Further molecular docking was utilized to analyse the interaction and propose a structural hypothesis for the process of binding the nanoprobe to Aß42 and Tau protein. Conclusion: This peptide-probe interaction provides a general enhancement factor and the molecular structure of the misfolded peptides. Secondary structural information may be obtained at the molecular level for specific residues owing to isotope shifts in the Raman spectra. Conjugation of the nanoprobe with Aß42 selectively detected AD in bodily fluids. The proposed nanoprobes can be easily applied to the detection of Aß plaques in blood, saliva, and sweat samples.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Ouro , Nanopartículas Metálicas , Simulação de Acoplamento Molecular , Fragmentos de Peptídeos , Prata , Análise Espectral Raman , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Análise Espectral Raman/métodos , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/química , Nanopartículas Metálicas/química , Ouro/química , Prata/química , Humanos , Biomarcadores/análise , Adsorção , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/químicaRESUMO
One of the major constituents of mitochondrial membranes is the phospholipids, which play a key role in maintaining the structure and the functions of the mitochondria. However, mitochondria do not synthesize most of the phospholipids in situ, necessitating the presence of phospholipid import pathways. Even for the phospholipids, which are synthesized within the inner mitochondrial membrane (IMM), the phospholipid precursors must be imported from outside the mitochondria. Therefore, the mitochondria heavily rely on the phospholipid transport pathways for its proper functioning. Since, mitochondria are not part of a vesicular trafficking network, the molecular mechanisms of how mitochondria receive its phospholipids remain a relevant question. One of the major ways that hydrophobic phospholipids can cross the aqueous barrier of inter or intraorganellar spaces is by apposing membranes, thereby decreasing the distance of transport, or by being sequestered by lipid transport proteins (LTPs). Therefore, with the discovery of LTPs and membrane contact sites (MCSs), we are beginning to understand the molecular mechanisms of phospholipid transport pathways in the mitochondria. In this review, we will present a brief overview of the recent findings on the molecular architecture and the importance of the MCSs, both the intraorganellar and interorganellar contact sites, in facilitating the mitochondrial phospholipid transport. In addition, we will also discuss the role of LTPs for trafficking phospholipids through the intermembrane space (IMS) of the mitochondria. Mechanistic insights into different phospholipid transport pathways of mitochondria could be exploited to vary the composition of membrane phospholipids and gain a better understanding of their precise role in membrane homeostasis and mitochondrial bioenergetics.
Assuntos
Mitocôndrias , Fosfolipídeos , Fosfolipídeos/metabolismo , Humanos , Animais , Mitocôndrias/metabolismo , Transporte Biológico , Membranas Mitocondriais/metabolismo , Proteínas de Transporte/metabolismoRESUMO
Semiconductor quantum dots (QDs) have been used in a variety of applications ranging from optoelectronics to biodiagnostic fields, primarily due to their size dependent fluorescent nature. CdSe nanocrystals (NCs) are generally synthesized via a hot injection method in an organic solvent. However, such NCs are insoluble in water and therefore preclude the direct usage toward biological systems. Thus, the preparation of more biocompatible water-soluble QDs with a high photoluminescent quantum yield (PLQY) is extremely important for imaging applications. Although previous literature has detailed on the synthesis of CdSe NCs in water, they suffer from poor size distribution and very low PLQY. The complex formation mechanism of CdSe NCs in an aqueous environment adversely affects the quality of NCs due to the presence of OH-, H+, and H2O moieties. Here in this article, we have presented the facile hydrothermal approach to obtain size tunable (2.9-5.1 nm), aqueous CdSe NCs with a narrow emission profile having â¼40 nm fwhm with 56% PLQY. Physicochemical properties of the synthesized water-soluble CdSe NCs were studied with the help of UV-vis, PL, XRD, FTIR, XPS, and HR-TEM analysis. Furthermore, the surface of the synthesized CdSe NCs was modified with d-glucosamine via EDC and NHS coupling to obtain a stable, biocompatible bioimaging probe. Furthermore, we demonstrated that their successful bioconjugation with glucosamine could facilitate effective internalization into the cellular matrix.
RESUMO
Functional metal nanomaterials, especially in the nanocluster (NC) size regime, with strong fluorescence, aqueous colloidal stability, and low toxicity, necessitate their application potential in biology and environmental science. Here, we successfully report a simple cost-effective method for red-/green-color-emitting protein/amino-acid-mediated Cu NCs in an aqueous medium. As-synthesized Cu NCs were characterized through UV-Vis absorption spectroscopy, fluorescence spectroscopy, time-resolved photoluminescence, dynamic light scattering, zeta potential, transmission electron microscopy and X-ray photoelectron spectroscopy. The optical properties of both Cu NCs responded linearly to the variation in pH in the neutral and alkaline ranges, and a robust pH reversible nature (between pH 7 and 11) was observed that could be extended to rapid, localized pH sensor development. However, a contrasting pH response nature between protein-Cu NCs and amino acid-Cu NCs was recorded. The alteration in protein secondary structure and strong binding nature of the surfactants were suggested to explain this behavior. Furthermore, we investigated their use as an efficient optical probe for fluoride ion detection. The limit of detection for protein-Cu NCs is 6.74 µM, whereas the limit of detection for amino acid-Cu NCs is 4.67 µM. Thus, it is anticipated that ultrasmall Cu NCs will exhibit promise in biological and environmental sensing applications.