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Glioblastoma (GBM) is the most aggressive tumor type whose resistance to conventional treatment is mediated, in part, by the angiogenic process. New treatments involving the application of nanoformulations composed of encapsulated drugs coupled to peptide motifs that direct drugs to specific targets triggered in angiogenesis have been developed to reach and modulate different phases of this process. We performed a systematic review with the search criterion (Glioblastoma OR Glioma) AND (Therapy OR Therapeutic) AND (Nanoparticle) AND (Antiangiogenic OR Angiogenesis OR Anti-angiogenic) in Pubmed, Scopus, and Cochrane databases, in which 312 articles were identified; of these, only 27 articles were included after selection and analysis of eligibility according to the inclusion and exclusion criteria. The data of the articles were analyzed in five contexts: the characteristics of the tumor cells; the animal models used to induce GBM for antiangiogenic treatment; the composition of nanoformulations and their physical and chemical characteristics; the therapeutic anti-angiogenic process; and methods for assessing the effects on antiangiogenic markers caused by therapies. The articles included in the review were heterogeneous and varied in practically all aspects related to nanoformulations and models. However, there was slight variance in the antiangiogenic effect analysis. CD31 was extensively used as a marker, which does not provide a view of the effects on the most diverse aspects involved in angiogenesis. Therefore, the present review highlighted the need for standardization between the different approaches of antiangiogenic therapy for the GBM model that allows a more effective meta-analysis and that helps in future translational studies.
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Inibidores da Angiogênese/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Glioblastoma/tratamento farmacológico , Nanopartículas/química , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/química , Animais , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Glioblastoma/irrigação sanguínea , Glioblastoma/patologia , Humanos , Nanopartículas/administração & dosagem , Neovascularização Patológica/patologiaRESUMO
OBJECTIVE: To evaluate the in vitro and in vivo toxicities of polyethylene glycol-coated gold nanoparticles synthesized using a one-step process. METHODS: Gold nanoparticles were prepared via a co-precipitation method using polyethylene glycol, and the synthesis product was characterized. For the in vitro evaluation, a flow cytometry analysis with Annexin V and iodide propidium staining was used to assess cytotoxicity in MG-63 cells labeled with 10, 50, and 100µg/mL of nanoparticle concentration. For the in vivo evaluation, nanoparticles were administered intraperitoneally at a dose of 10mg/kg dose in 10-week-old mice. Toxicity was assessed 24 hours and 7 days after administration via histopathological analysis of various tissues, as well as through renal, hepatic, and hematopoietic evaluations. RESULTS: Synthesized nanoparticles exhibited different hydrodynamic sizes depending on the medium: 51.27±1.62nm in water and 268.12±28.45nm (0 hour) in culture medium. They demonstrated a maximum absorbance at 520nm and a zeta potential of -8.419mV. Cellular viability exceeded 90%, with less than 3% early apoptosis, 6% late apoptosis, and 1% necrosis across all labeling conditions, indicating minimal cytotoxicity differences. Histopathological analysis highlighted the accumulation of nanoparticles in the mesentery; however, no lesions or visible agglomeration was observed in the remaining tissues. Renal, hepatic, and hematopoietic analyses showed no significant differences at any time point. CONCLUSION: Polyethylene glycol-coated gold nanoparticles exhibit extremely low toxicity and high biocompatibility, showing promise for future studies.
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Ouro , Nanopartículas Metálicas , Polietilenoglicóis , Polietilenoglicóis/toxicidade , Polietilenoglicóis/química , Ouro/toxicidade , Ouro/química , Animais , Nanopartículas Metálicas/toxicidade , Camundongos , Sobrevivência Celular/efeitos dos fármacos , Citometria de Fluxo , Apoptose/efeitos dos fármacos , Humanos , Tamanho da Partícula , Masculino , Rim/efeitos dos fármacos , Rim/patologia , Fatores de TempoRESUMO
Introduction: Inflammatory bowel diseases (IBDs) disrupt the intestinal epithelium, leading to severe chronic inflammation. Current therapies cause adverse effects and are expensive, invasive, and ineffective for most patients. Annexin A1 (AnxA1) is a pivotal endogenous anti-inflammatory and tissue repair protein in IBD. Nanostructured compounds loading AnxA1 or its active N-terminal mimetic peptides improve IBD symptomatology. Methods: To further explore their potential as a therapeutic candidate, the AnxA1 N-terminal mimetic peptide Ac2-26 was incorporated into SBA-15 ordered mesoporous silica and covered with EL30D-55 to deliver it by oral treatment into the inflamed gut. Results: The systems SBA-Ac2-26 developed measurements revealed self-assembled rod-shaped particles, likely on the external surface of SBA-15, and 88% of peptide incorporation. SBA-15 carried the peptide Ac2-26 into cultured Raw 264.7 macrophages and Caco-2 epithelial cells. Moreover, oral administration of Eudragit-SBA-15-Ac2-26 (200 µg; once a day; for 4 days) reduced colitis clinical symptoms, inflammation, and improved epithelium recovery in mice under dextran-sodium sulfate-induced colitis. Discussion: The absorption of SBA-15 in gut epithelial cells is typically low; however, the permeable inflamed barrier can enable microparticles to cross, being phagocyted by macrophages. These findings suggest that Ac2-26 is successfully delivered and binds to its receptors in both epithelial and immune cells, aligning with the clinical results. Conclusion: Our findings demonstrate a simple and cost-effective approach to delivering Ac2-26 orally into the inflamed gut, highlighting its potential as non-invasive IBD therapy.
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Colite , Doenças Inflamatórias Intestinais , Dióxido de Silício , Humanos , Camundongos , Animais , Células CACO-2 , Inflamação/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Peptídeos/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológicoRESUMO
Breast cancer (BC) presents a growing global concern, mainly for the female population of working age. Their pathophysiology shows challenges when attempting to ensure conventional treatment efficacy without adverse effects. This study aimed to evaluate the efficacy of magneto-hyperthermia (MHT) therapy associated with supplementation with omega-3 polyunsaturated fatty acid (w-3 PUFA) and engagement in physical training (PT) for the triple-negative BC (TNBC) model. First, we assessed the physicochemical properties of iron oxide nanoparticles (ION) in biological conditions, as well as their heating potential for MHT therapy. Then, a bioluminescence (BLI) evaluation of the best tumor growth conditions in the TNBC model (the quantity of implanted cells and time), as well as the efficacy of MHT therapy (5 consecutive days) associated with the previous administration of 8 weeks of w-3 PUFA and PT, was carried out. The results showed the good stability and potential of ION for MHT using 300 Gauss and 420 kHz. In the TNBC model, adequate tumor growth was observed after 14 days of 2 × 106 cells implantation by BLI. There was a delay in tumor growth in animals that received w-3 and PT and a significant decrease associated with MHT. This pioneering combination therapy approach (MHT, omega-3, and exercise) showed a positive effect on TNBC tumor reduction and demonstrated promise for pre-clinical and clinical studies in the future.
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Magnetic nanoparticles (MNPs) have been widely used for their potential applications, mainly for the diagnosis and/or therapy (theranostic) of several diseases in the field of nanomedicine, as passive contrast agents, through the opsonization process, or active contrast agents, after their functionalization and the subsequent capture of the signal using various techniques such as magnetic resonance imaging (MRI), optical imaging, nuclear imaging, and ultrasound [...].
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BACKGROUND: Induced pluripotent stem cells (iPSCs) show great ability to differentiate into any tissue, making them attractive candidates for pathophysiological investigations. The rise of organ-on-a-chip technology in the past century has introduced a novel way to make in vitro cell cultures that more closely resemble their in vivo environments, both structural and functionally. The literature still lacks consensus on the best conditions to mimic the blood-brain barrier (BBB) for drug screening and other personalized therapies. The development of models based on BBB-on-a-chip using iPSCs is promising and is a potential alternative to the use of animals in research. AIM: To analyze the literature for BBB models on-a-chip involving iPSCs, describe the microdevices, the BBB in vitro construction, and applications. METHODS: We searched for original articles indexed in PubMed and Scopus that used iPSCs to mimic the BBB and its microenvironment in microfluidic devices. Thirty articles were identified, wherein only 14 articles were finally selected according to the inclusion and exclusion criteria. Data compiled from the selected articles were organized into four topics: (1) Microfluidic devices design and fabrication; (2) characteristics of the iPSCs used in the BBB model and their differentiation conditions; (3) BBB-on-a-chip reconstruction process; and (4) applications of BBB microfluidic three-dimensional models using iPSCs. RESULTS: This study showed that BBB models with iPSCs in microdevices are quite novel in scientific research. Important technological advances in this area regarding the use of commercial BBB-on-a-chip were identified in the most recent articles by different research groups. Conventional polydimethylsiloxane was the most used material to fabricate in-house chips (57%), whereas few studies (14.3%) adopted polymethylmethacrylate. Half the models were constructed using a porous membrane made of diverse materials to separate the channels. iPSC sources were divergent among the studies, but the main line used was IMR90-C4 from human fetal lung fibroblast (41.2%). The cells were differentiated through diverse and complex processes either to endothelial or neural cells, wherein only one study promoted differentiation inside the chip. The construction process of the BBB-on-a-chip involved previous coating mostly with fibronectin/collagen IV (39.3%), followed by cell seeding in single cultures (36%) or co-cultures (64%) under controlled conditions, aimed at developing an in vitro BBB that mimics the human BBB for future applications. CONCLUSION: This review evidenced technological advances in the construction of BBB models using iPSCs. Nonetheless, a definitive BBB-on-a-chip has not yet been achieved, hindering the applicability of the models.
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The Scientists of Tomorrow/ Cientistas do Amanhã project is an immersive science training program developed by the Program of Post-Graduation in Health Sciences at Hospital Israelita Albert Einstein. This program was conducted in partnership with Volunteering and Escola Municipal de Ensino Fundamental Professor Paulo Freire in Paraisópolis, São Paulo, Brazil. The Scientists of Tomorrow Program comprised a short training period conducted in May 2022 involving 37 students, and a long training period from August to December 2022, which included 15 students. It aimed to popularize science through practical activities; transfer knowledge to young students; sensitize and guide them to pursue academic-scientific careers; reduce stereotypes about scientific work and scientists; and help students understand the social, political, and ethical roles of science within society. All activities were led by postgraduate students and professors from our postgraduate program, physicians, nurses, physiotherapists, biomedicals, and veterinarians from Hospital Israelita Albert Einstein, as well as medical students from Faculdade Israelita de Ciências da Saúde Albert Einstein . Activities in the short training included lectures on cinema and science, strategies to combat fake news, non-violent communication, innovation, design-thinking framework, and developing a scientific project. During the long training period, discussions were focused on nanotechnology, animal research, big data, bioinformatics, meditation, blood and bone marrow donation, telemedicine, sex and sexually-transmitted infections, rehabilitation, career opportunities, and scientific integrity. In addition, practical activities were further expanded using optical and confocal microscopy, cytometry, and basic concepts regarding the structure and function of living cells. The program also included the launching of the open-air outreach Education E-natureza activity, which turned students into ambassadors of nature. In conclusion, the Scientists of Tomorrow Program was innovative and enabled young students to learn that science is a collective activity that can enhance public health. In Brief Rangel et al. enumerated the Scientists of Tomorrow/Cientistas do Amanhã program, an immersive science initiative conducted in collaboration with a public school. The program, which involved 15 students, aimed to promote science, share knowledge, inspire academic paths, and underscore societal impacts. Led by postgraduates, professors, and healthcare experts, the program included diverse lectures and practical laboratory activities. Highlights Every research endeavor commences with a fundamental question. Sharing of findings by researchers and students contributes toward the expansion of knowledge. Teaching scientific methodology is a pivotal step in nurturing critical thinking skills. Science permeates our daily lives and plays a crucial role in addressing societal issues.
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Pessoal de Educação , Estudantes de Medicina , Humanos , Brasil , Instituições Acadêmicas , Atenção à SaúdeRESUMO
The treatment of bone cancer involves tumor resection followed by bone reconstruction of the defect caused by the tumor using biomaterials. Additionally, post-surgery protocols cover chemotherapy, radiotherapy, or drug administration, which are employed as adjuvant treatments to prevent tumor recurrence. In this work, we reviewed new strategies for bone cancer treatment based on bioactive glasses as carriers of cancer-targeted and other drugs that are intended for bone regeneration in conjunction with adjuvant treatments. Drugs used in combination with bioactive glasses can be classified into cancer-target, osteoclast-target, and new therapies (such as gene delivery and bioinorganic). Microparticulated, nanoparticulated, or mesoporous bioactive glasses have been used as drug-delivery systems. Additionally, surface modification through functionalization or the production of composites based on polymers and hydrogels has been employed to improve drug-release kinetics. Overall, although different drugs and drug delivery systems have been developed, there is still room for new studies involving kinase inhibitors or antibody-conjugated drugs, as these drugs have been poorly explored in combination with bioactive glasses.
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BACKGROUND: Bone marrow transplantation (BMT) can be applied to both hematopoietic and nonhematopoietic diseases; nonetheless, it still comes with a number of challenges and limitations that contribute to treatment failure. Bearing this in mind, a possible way to increase the success rate of BMT would be cotransplantation of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) to improve the bone marrow niche and secrete molecules that enhance the hematopoietic engraftment. AIM: To analyze HSC and MSC characteristics and their interactions through cotransplantation in murine models. METHODS: We searched for original articles indexed in PubMed and Scopus during the last decade that used HSC and MSC cotransplantation and in vivo BMT in animal models while evaluating cell engraftment. We excluded in vitro studies or studies that involved graft versus host disease or other hematological diseases and publications in languages other than English. In PubMed, we initially identified 555 articles and after selection, only 12 were chosen. In Scopus, 2010 were identified, and six were left after the screening and eligibility process. RESULTS: Of the 2565 articles found in the databases, only 18 original studies met the eligibility criteria. HSC distribution by source showed similar ratios, with human umbilical cord blood or animal bone marrow being administered mainly with a dose of 1 × 107 cells by intravenous or intrabone routes. However, MSCs had a high prevalence of human donors with a variety of sources (umbilical cord blood, bone marrow, tonsil, adipose tissue or fetal lung), using a lower dose, mainly 106 cells and ranging 104 to 1.5 × 107 cells, utilizing the same routes. MSCs were characterized prior to administration in almost every experiment. The recipient used was mostly immunodeficient mice submitted to low-dose irradiation or chemotherapy. The main technique of engraftment for HSC and MSC cotransplantation evaluation was chimerism, followed by hematopoietic reconstitution and survival analysis. Besides the engraftment, homing and cellularity were also evaluated in some studies. CONCLUSION: The preclinical findings validate the potential of MSCs to enable HSC engraftment in vivo in both xenogeneic and allogeneic hematopoietic cell transplantation animal models, in the absence of toxicity.
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The objective of this study was to highlight the global scientific effort to fight the SARS-CoV-2, addressing the preliminary results of passive immunization through convalescent plasma. We performed a search at the major databases of interventional clinical trial protocols about the transfusion of convalescent plasma in patients with COVID-19, as well as, published articles (n≥25), using the following search strategy: [(COVID-19 OR SARS-CoV-2 OR nCoV-2019) AND (Convalescent plasma OR Plasma exchange) AND (Treatment OR Therapy)]. A total of 24 interventional clinical trial protocols (advanced in phases II-III, III, and IV) were included in this review, as well as three studies that had enough outcomes to evaluate the efficacy of convalescent plasma therapy for patients with COVID-19. All interventional clinical trial protocols applied approximately 500mL of convalescent plasma (from single or more donations) in hospitalized patients, mainly in patients with severe disease associated with standard therapy for COVID-19, and compared to placebo or standard therapy plus specific drugs. Most of interventional clinical trial protocols are multicenter, and the phase IV studies are recruiting at intercontinental centers of North America, Oceania, Europe, but most are recruiting center inside their own county. The three studies published reported similar approach of convalescent plasma intervention with decrease in length of stay, mortality, with less than 4% of adverse events, mainly for treating critical cases with life-threatening disease. All advanced clinical trials focused on convalescent plasma therapy in patients with COVID-19 hospitalized in severe conditions, and the preliminary results provide strong evidence for therapy for the COVID-19 patients.
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COVID-19 , COVID-19/terapia , Estado Terminal , Humanos , Imunização Passiva , Estudos Multicêntricos como Assunto , Plasma , SARS-CoV-2 , Resultado do Tratamento , Soroterapia para COVID-19RESUMO
BACKGROUND: Stroke is the second leading cause of death worldwide. There is a real need to develop treatment strategies for reducing neurological deficits in stroke survivors, and stem cell (SC) therapeutics appear to be a promising alternative for stroke therapy that can be used in combination with approved thrombolytic or thrombectomy approaches. However, the efficacy of SC therapy depends on the SC homing ability and engraftment into the injury site over a long period of time. Nonetheless, tracking SCs from their niche to the target tissues is a complex process. AIM: To evaluate SC migration homing, tracking and therapeutic efficacy in the treatment of stroke using nanoparticles. METHODS: A systematic literature search was performed to identify articles published prior to November 2019 that were indexed in PubMed and Scopus. The following inclusion criteria were used: (1) Studies that used in vivo models of stroke or ischemic brain lesions; (2) Studies of SCs labeled with some type of contrast agent for cell migration detection; and (3) Studies that involved in vivo cellular homing and tracking analysis. RESULTS: A total of 82 articles were identified by indexing in Scopus and PubMed. After the inclusion criteria were applied, 35 studies were selected, and the articles were assessed for eligibility; ultimately, only 25 studies were included. Most of the selected studies used SCs from human and mouse bone marrow labeled with magnetic nanoparticles alone or combined with fluorophore dyes. These cells were administered in the stroke model (to treat middle cerebral artery occlusion in 74% of studies and for photothrombotic induction in 26% of studies). Fifty-three percent of studies used xenogeneic grafts for cell therapy, and the migration homing and tracking evaluation was performed by magnetic resonance imaging as well as other techniques, such as near-infrared fluorescence imaging (12%) or bioluminescence assays (12%). CONCLUSION: Our systematic review provided an up-to-date evaluation of SC migration homing and the efficacy of cellular therapy for stroke treatment in terms of functional and structural improvements in the late stage.
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OBJECTIVE: To evaluate the magnetic hyperthermia therapy in glioblastoma tumor-on-a-Chip model using a microfluidics device. METHODS: The magnetic nanoparticles coated with aminosilane were used for the therapy of magnetic hyperthermia, being evaluated the specific absorption rate of the magnetic nanoparticles at 300 Gauss and 305kHz. A preculture of C6 cells was performed before the 3D cells culture on the chip. The process of magnetic hyperthermia on the Chip was performed after administration of 20µL of magnetic nanoparticles (10mgFe/mL) using the parameters that generated the specific absorption rate value. The efficacy of magnetic hyperthermia therapy was evaluated by using the cell viability test through the following fluorescence staining: calcein acetoxymethyl ester (492/513nm), for live cells, and ethidium homodimer-1 (526/619nm) for dead cells dyes. RESULTS: Magnetic nanoparticles when submitted to the alternating magnetic field (300 Gauss and 305kHz) produced a mean value of the specific absorption rate of 115.4±6.0W/g. The 3D culture of C6 cells evaluated by light field microscopy imaging showed the proliferation and morphology of the cells prior to the application of magnetic hyperthermia therapy. Fluorescence images showed decreased viability of cultured cells in organ-on-a-Chip by 20% and 100% after 10 and 30 minutes of the magnetic hyperthermia therapy application respectively. CONCLUSION: The study showed that the therapeutic process of magnetic hyperthermia in the glioblastoma on-a-chip model was effective to produce the total cell lise after 30 minutes of therapy.
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Técnicas de Cultura de Células/métodos , Glioblastoma/terapia , Hipertermia Induzida/métodos , Dispositivos Lab-On-A-Chip , Nanopartículas de Magnetita/uso terapêutico , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Fluorescência , Campos Magnéticos , Ratos , Reprodutibilidade dos Testes , Temperatura , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the potential of magnetic hyperthermia using aminosilane-coated superparamagnetic iron oxide nanoparticles in glioblastoma tumor model. METHODS: The aminosilane-coated superparamagnetic iron oxide nanoparticles were analyzed as to their stability in aqueous medium and their heating potential through specific absorption rate, when submitted to magnetic hyperthermia with different frequencies and intensities of alternating magnetic field. In magnetic hyperthermia in vitro assays, the C6 cells cultured and transduced with luciferase were analyzed by bioluminescence in the absence/presence of alternating magnetic field, and also with and without aminosilane-coated superparamagnetic iron oxide nanoparticles. In the in vivo study, the measurement of bioluminescence was performed 21 days after glioblastoma induction with C6 cells in rats. After 24 hours, the aminosilane-coated superparamagnetic iron oxide nanoparticles were implanted in animals, and magnetic hyperthermia was performed for 40 minutes, using the best conditions of frequency and intensity of alternating magnetic field tested in the in vitro study (the highest specific absorption rate value) and verified the difference of bioluminescence before and after magnetic hyperthermia. RESULTS: The aminosilane-coated superparamagnetic iron oxide nanoparticles were stable, and their heating capacity increased along with higher frequency and intensity of alternating magnetic field. The magnetic hyperthermia application with 874kHz and 200 Gauss of alternating magnetic field determined the best value of specific absorption rate (194.917W/g). When these magnetic hyperthermia parameters were used in in vitro and in vivo analysis, resulted in cell death of 52.0% and 32.8%, respectively, detected by bioluminescence. CONCLUSION: The magnetic hyperthermia was promissing for the therapeutical process of glioblastoma tumors in animal model, using aminosilane-coated superparamagnetic iron oxide nanoparticles, which presented high specific absorption rate.
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Neoplasias Encefálicas/terapia , Compostos Férricos/uso terapêutico , Glioblastoma/terapia , Hipertermia Induzida/métodos , Magnetoterapia/métodos , Nanopartículas de Magnetita/uso terapêutico , Análise de Variância , Animais , Temperatura Corporal , Linhagem Celular Tumoral , Modelos Animais de Doenças , Compostos Férricos/química , Medições Luminescentes , Nanopartículas de Magnetita/química , Masculino , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: With application of 3T magnetic resonance imaging (MRI) to functional neurosurgery procedures and given the inherent requirement of millimetric precision, the need to develop a method for correction of geometric image distortion emerged. The aim of this study was to demonstrate clinical safety and practical viability of a correction protocol in patients scheduled to undergo stereotactic procedures using 3T MRI. METHODS: This prospective study comprised 20 patients scheduled to undergo computed tomography (CT) stereotactic functional procedures or encephalic brain lesion biopsies. The CT images were references for MRI geometric accuracy calculations. For each scan, 2 images were obtained: normal and reversed images. Eight distinct points on CT and MRI were selected summing 152 points that were based on a power analysis calculation value >0.999. One patient was excluded because of the inability to find reliable common landmark points on CT and MRI. RESULTS: The distortion range was 0-5.6 mm and increased proportionally with stereotactic isocenter distance, meaning the distortion was greater in the periphery. After correction, the minimum and maximum distortion found was 0 mm and 3.5 mm, respectively. There was no significant difference between CT and MRI corrected x-coordinates (P > 0.05). CONCLUSIONS: The proposed method can satisfactorily correct geometric distortions in clinical 3T MRI studies. Clinical use of the technique can be practical and efficient after software automation of the process. The method can be applied to all spin-echo MRI sequences.
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Imageamento Tridimensional/normas , Imageamento por Ressonância Magnética/normas , Doenças do Sistema Nervoso/diagnóstico por imagem , Técnicas Estereotáxicas/normas , Tomografia Computadorizada por Raios X/normas , Adolescente , Adulto , Idoso , Feminino , Humanos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios X/métodos , Adulto JovemRESUMO
The hippocampus is one of the earliest sites involved in the pathology of Alzheimer's disease (AD). Therefore, we specifically investigated the sensitivity and specificity of hippocampal volume and glucose metabolism in patients being evaluated for AD, using automated quantitative tools (NeuroQuant - magnetic resonance imaging [MRI] and Scenium - positron emission tomography [PET]) and clinical evaluation.This retrospective study included adult patients over the age of 45 years with suspected AD, who had undergone fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) and MRI. FDG-PET-CT images were analyzed both qualitatively and quantitatively. In quantitative volumetric MRI analysis, the percentage of the total intracranial volume of each brain region, as well as the total hippocampal volume, were considered in comparison to an age-adjusted percentile. The remaining brain regions were compared between groups according to the final diagnosis.Thirty-eight patients were included in this study. After a mean follow-up period of 23â±â11 months, the final diagnosis for 16 patients was AD or high-risk mild cognitive impairment (MCI). Out of the 16 patients, 8 patients were women, and the average age of all patients was 69.38â±â10.98 years. Among the remaining 22 patients enrolled in the study, 14 were women, and the average age was 67.50â±â11.60 years; a diagnosis of AD was initially excluded, but the patients may have low-risk MCI. Qualitative FDG-PET-CT analysis showed greater accuracy (0.87), sensitivity (0.76), and negative predictive value (0.77), when compared to quantitative PET analysis, hippocampal MRI volumetry, and specificity. The positive predictive value of FDG-PET-CT was similar to the MRI value.The performance of FDG-PET-CT qualitative analysis was significantly more effective compared to MRI volumetry. At least in part, this observation could corroborate the sequential hypothesis of AD pathophysiology, which posits that functional changes (synaptic dysfunction) precede structural changes (atrophy).
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Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Fluordesoxiglucose F18/metabolismo , Hipocampo/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Disfunção Cognitiva/metabolismo , Diagnóstico Precoce , Feminino , Glucose/metabolismo , Hipocampo/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
ABSTRACT Objective To evaluate the in vitro and in vivo toxicities of polyethylene glycol-coated gold nanoparticles synthesized using a one-step process. Methods Gold nanoparticles were prepared via a co-precipitation method using polyethylene glycol, and the synthesis product was characterized. For the in vitro evaluation, a flow cytometry analysis with Annexin V and iodide propidium staining was used to assess cytotoxicity in MG-63 cells labeled with 10, 50, and 100µg/mL of nanoparticle concentration. For the in vivo evaluation, nanoparticles were administered intraperitoneally at a dose of 10mg/kg dose in 10-week-old mice. Toxicity was assessed 24 hours and 7 days after administration via histopathological analysis of various tissues, as well as through renal, hepatic, and hematopoietic evaluations. Results Synthesized nanoparticles exhibited different hydrodynamic sizes depending on the medium: 51.27±1.62nm in water and 268.12±28.45nm (0 hour) in culture medium. They demonstrated a maximum absorbance at 520nm and a zeta potential of -8.419mV. Cellular viability exceeded 90%, with less than 3% early apoptosis, 6% late apoptosis, and 1% necrosis across all labeling conditions, indicating minimal cytotoxicity differences. Histopathological analysis highlighted the accumulation of nanoparticles in the mesentery; however, no lesions or visible agglomeration was observed in the remaining tissues. Renal, hepatic, and hematopoietic analyses showed no significant differences at any time point. Conclusion Polyethylene glycol-coated gold nanoparticles exhibit extremely low toxicity and high biocompatibility, showing promise for future studies.
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BACKGROUND: Mesenchymal stem cells (MSCs) have been widely tested for their therapeutic efficacy in the ischemic brain and have been shown to provide several benefits. A major obstacle to the clinical translation of these therapies has been the inability to noninvasively monitor the best route, cell doses, and collateral effects while ensuring the survival and effective biological functioning of the transplanted stem cells. Technological advances in multimodal imaging have allowed in vivo monitoring of the biodistribution and viability of transplanted stem cells due to a combination of imaging technologies associated with multimodal nanoparticles (MNPs) using new labels and covers to achieve low toxicity and longtime residence in cells. AIM: To evaluate the sensitivity of triple-modal imaging of stem cells labeled with MNPs and applied in a stroke model. METHODS: After the isolation and immunophenotypic characterization of human bone marrow MSCs (hBM-MSCs), our team carried out lentiviral transduction of these cells for the evaluation of bioluminescent images (BLIs) in vitro and in vivo. In addition, MNPs that were previously characterized (regarding hydrodynamic size, zeta potential, and optical properties), and were used to label these cells, analyze cell viability via the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and BLI analysis, and quantify the internalization process and iron load in different concentrations of MNPs via magnetic resonance imaging (MRI), near-infrared fluorescence (NIRF), and inductively coupled plasma-mass spectrometry (ICP-MS). In in vivo analyses, the same labeled cells were implanted in a sham group and a stroke group at different times and under different MNP concentrations (after 4 h or 6 d of cell implantation) to evaluate the sensitivity of triple-modal images. RESULTS: hBM-MSC collection and isolation after immunophenotypic characterization were demonstrated to be adequate in hBM samples. After transduction of these cells with luciferase (hBM-MSCLuc), we detected a maximum BLI intensity of 2.0 x 108 photons/s in samples of 106 hBM-MSCs. Analysis of the physicochemical characteristics of the MNPs showed an average hydrodynamic diameter of 38.2 ± 0.5 nm, zeta potential of 29.2 ± 1.9 mV and adequate colloidal stability without agglomeration over 18 h. The signal of iron load internalization in hBM-MSCLuc showed a close relationship with the corresponding MNP-labeling concentrations based on MRI, ICP-MS and NIRF. Under the highest MNP concentration, cellular viability showed a reduction of less than 10% compared to the control. Correlation analysis of the MNP load internalized into hBM-MSCLuc determined via the MRI, ICP-MS and NIRF techniques showed the same correlation coefficient of 0.99. Evaluation of the BLI, NIRF, and MRI signals in vivo and ex vivo after labeled hBM-MSCLuc were implanted into animals showed differences between different MNP concentrations and signals associated with different techniques (MRI and NIRF; 5 and 20 µg Fe/mL; P < 0.05) in the sham groups at 4 h as well as a time effect (4 h and 6 d; P < 0.001) and differences between the sham and stroke groups in all images signals (P < 0.001). CONCLUSION: This study highlighted the importance of quantifying MNPs internalized into cells and the efficacy of signal detection under the triple-image modality in a stroke model.
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The primary objective of this study is to monitor tumor growth by using image techniques and behavioral testing through general and specific motor activities (spontaneous movements and gait). Our sample includes male Wistar rats, 2 months old and weighing 250-300 g, that is categorized into three groups: control, sham, and experimental. The experimental group was anesthetized; the C6 cells with luciferase expression that were suspended in a culture medium were implanted into the right frontoparietal cortex of the rats. The sham group received implant only with culture medium without cells. Images and behavioral tests were evaluated at base time and at 7, 14, 21, and 28 days after induced tumor growth analysis. The tumor volume measured by magnetic resonance imaging (MRI) and quantitative bioluminescence imaging (BLI) signal showed a correlation coefficient of r = 0.96. The MRI showed that the mean tumor volume increased by approximately 10, 26, and 49 times according to a comparison of tumor volume on the seventh day with 14, 21, and 28 days, respectively. The quantification of the BLI signal was (4.12 ± 2.01) x 10(8), (8.33 ± 3.12) x 10(8), (28.43 ± 6.32) x 10(8), and (63.02 ± 10.53) x 10(8) photons/s at the seventh, fourteenth, twenty-first, and twenty-eighth day, respectively. After 14 days of tumor induction, both behavioral tests showed significant differences between tumor and sham or control groups. Our study showed a high correlation between MRI and BLI for tumor growth monitoring with complement aspects analysis in tumor volume. In addition, functional behavioral analysis displayed sensitivity to monitor tumor growth, as well as to detect early significant changes between groups, primarily in the tumor group. The results of gait analysis were more sensitive than general motor analysis.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/fisiopatologia , Glioma/diagnóstico por imagem , Glioma/fisiopatologia , Locomoção , Animais , Encéfalo/fisiopatologia , Linhagem Celular Tumoral , Marcha , Análise da Marcha , Medições Luminescentes/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Ratos WistarRESUMO
ABSTRACT The Scientists of Tomorrow/ Cientistas do Amanhã project is an immersive science training program developed by the Program of Post-Graduation in Health Sciences at Hospital Israelita Albert Einstein. This program was conducted in partnership with Volunteering and Escola Municipal de Ensino Fundamental Professor Paulo Freire in Paraisópolis, São Paulo, Brazil. The Scientists of Tomorrow Program comprised a short training period conducted in May 2022 involving 37 students, and a long training period from August to December 2022, which included 15 students. It aimed to popularize science through practical activities; transfer knowledge to young students; sensitize and guide them to pursue academic-scientific careers; reduce stereotypes about scientific work and scientists; and help students understand the social, political, and ethical roles of science within society. All activities were led by postgraduate students and professors from our postgraduate program, physicians, nurses, physiotherapists, biomedicals, and veterinarians from Hospital Israelita Albert Einstein, as well as medical students from Faculdade Israelita de Ciências da Saúde Albert Einstein . Activities in the short training included lectures on cinema and science, strategies to combat fake news, non-violent communication, innovation, design-thinking framework, and developing a scientific project. During the long training period, discussions were focused on nanotechnology, animal research, big data, bioinformatics, meditation, blood and bone marrow donation, telemedicine, sex and sexually-transmitted infections, rehabilitation, career opportunities, and scientific integrity. In addition, practical activities were further expanded using optical and confocal microscopy, cytometry, and basic concepts regarding the structure and function of living cells. The program also included the launching of the open-air outreach Education E-natureza activity, which turned students into ambassadors of nature. In conclusion, the Scientists of Tomorrow Program was innovative and enabled young students to learn that science is a collective activity that can enhance public health.
RESUMO
The use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of commonly used compounds in cancer diagnosis and treatment. Advances in the surface engineering of nanoparticles to accommodate targeting ligands turned nanocarriers attractive candidates for future work involving targeted drug delivery. Although not targeted, several nanocarriers have been approved for clinical use and they are currently used to treat and/or diagnosis various types of cancers. Furthermore, there are several formulations, which are now in various stages of clinical trials. This review examined some approved formulations and discussed the advantages of using nanocarriers in cancer therapy.