Personalized medicine promises to revolutionize cancer therapy by matching the most effective treatment to the individual patient. Using a nanoparticle-based system, we predict the therapeutic ...potency of anticancer medicines in a personalized manner. We carry out the diagnostic stage through a multidrug screen performed inside the tumour, extracting drug activity information with single cell sensitivity. By using 100 nm liposomes, loaded with various cancer drugs and corresponding synthetic DNA barcodes, we find a correlation between the cell viability and the drug it was exposed to, according to the matching barcodes. Based on this screen, we devise a treatment protocol for mice bearing triple-negative breast-cancer tumours, and its results confirm the diagnostic prediction. We show that the use of nanotechnology in cancer care is effective for generating personalized treatment protocols.
•Polylactic acid (PLA) is a biocompatible polymer that is used widely for biomedical applications.•PLA biodegrades into lactic acid (LA) or to carbon dioxide and water.•PLA degradation products are ...metabolized intracellularly or excreted in the urine and breath.•Adverse reactions or foreign body response to PLA are extremely rare.
Polylactic acid (PLA) is the most commonly used biodegradable polymer in clinical applications today. Examples range from drug delivery systems, tissue engineering, temporary and long-term implantable devices; constantly expanding to new fields. This is owed greatly to the polymer’s favorable biocompatibility and to its safe degradation products. Once coming in contact with biological media, the polymer begins breaking down, usually by hydrolysis, into lactic acid (LA) or to carbon dioxide and water. These products are metabolized intracellularly or excreted in the urine and breath. Bacterial infection and foreign-body inflammation enhance the breakdown of PLA, through the secretion of enzymes that degrade the polymeric matrix.
The biodegradation occurs both on the surface of the polymeric device and inside the polymer body, by diffusion of water between the polymer chains.
The median half-life of the polymer is 30 weeks; however, this can be lengthened or shortened to address the clinical needs. Degradation kinetics can be tuned by determining the molecular composition and the physical architecture of the device. For example, using L- or D-chirality of the LA will greatly lengthen or shorten the degradation rates, respectively.
Despite the fact that this polymer is more than 150 years old, PLA remains a fertile platform for biomedical innovation and fundamental understanding of how artificial polymers can safely coexist with biological systems.
Oropouche virus detection in saliva and urine Nascimento, Valdinete Alves do; Santos, João Hugo Abdalla; Monteiro, Dana Cristina da Silva ...
Memórias do Instituto Oswaldo Cruz,
01/2020, Letnik:
115
Journal Article
Recenzirano
Odprti dostop
Oropouche virus (OROV) is an arthropod-borne virus of the Peribunyaviridae family, transmitted to humans primarily by Culicoides paraensis. It is one of the main arboviruses infecting humans in ...Brazil, primarily in the Amazon Region. Here, we report the detection of OROV in the saliva and urine of a patient whose samples were collected five days after the onset of symptoms. Nucleotide sequencing and phylogenetic analysis further confirmed the results. To our knowledge, this is the first study reporting the detection of OROV in the saliva and urine of an infected patient. In addition, the results of our study expand the current knowledge pertaining to the natural history of Oropouche fever.
Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis.
To define ...the immunologic biomarkers that correlate with acute ZIKV infection.
We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining.
ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues.
Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application.
Lipid nanoparticles are used widely as anticancer drug and gene delivery systems. Internalizing into the target cell is a prerequisite for the proper activity of many nanoparticulate drugs. We show ...here, that the lipid composition of a nanoparticle affects its ability to internalize into triple-negative breast cancer cells. The lipid headgroup had the greatest effect on enhancing cellular uptake compared to other segments of the molecule. Having a receptor-targeted headgroup induced the greatest increase in cellular uptake, followed by cationic amine headgroups, both being superior to neutral (zwitterion) phosphatidylcholine or to negatively-charged headgroups. The lipid tails also affected the magnitude of cellular uptake. Longer acyl chains facilitated greater liposomal cellular uptake compared to shorter tails, 18:0 > 16:0 > 14:0. When having the same lipid tail length, unsaturated lipids were superior to saturated ones, 18:1 > 18:0. Interestingly, liposomes composed of phospholipids having 14:0 or 12:0-carbon-long-tails, such as DMPC and DLPC, decreased cell viability in a concertation dependent manner, due to a destabilizing effect these lipids had on the cancer cell membrane. Contrarily, liposomes composed of phospholipids having longer carbon tails (16:0 and 18:0), such as DPPC and HSPC, enhanced cancer cell proliferation. This effect is attributed to the integration of the exogenous liposomal lipids into the cancer-cell membrane, supporting the proliferation process. Cholesterol is a common lipid additive in nanoscale formulations, rigidifying the membrane and stabilizing its structure. Liposomes composed of DMPC (14:0) showed increased cellular uptake when enriched with cholesterol, both by endocytosis and by fusion. Contrarily, the effect of cholesterol on HSPC (18:0) liposomal uptake was minimal. Furthermore, the concentration of nanoparticles in solution affected their cellular uptake. The higher the concentration of nanoparticles the greater the absolute number of nanoparticles taken up per cell. However, the efficiency of nanoparticle uptake, i.e. the percent of nanoparticles taken up by cells, decreased as the concentration of nanoparticles increased. This study demonstrates that tuning the lipid composition and concentration of nanoscale drug delivery systems can be leveraged to modulate their cellular uptake.
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Despite advances in cancer therapy, treating cancer after it has metastasized remains an unmet clinical challenge. In this study we demonstrate that 100 nm liposomes target triple-negative murine ...breast-cancer metastases post intravenous administration. Metastatic breast cancer was induced in BALB/c mice either experimentally, by a tail vein injection of 4T1 cells, or spontaneously, after implanting a primary tumor xenograft. To track their biodistribution in vivo the liposomes were labeled with multi-modal diagnostic agents, including indocyanine green and rhodamine for whole-animal fluorescent imaging, gadolinium for magnetic resonance imaging (MRI), and europium for a quantitative biodistribution analysis. The accumulation of liposomes in the metastases peaked at 24 h post the intravenous administration, similar to the time they peaked in the primary tumor. The efficiency of liposomal targeting to the metastatic tissue exceeded that of a non-liposomal agent by 4.5-fold. Liposomes were detected at very early stages in the metastatic progression, including metastatic lesions smaller than 2 mm in diameter. Surprisingly, while nanoparticles target breast cancer metastasis, they may also be found in elevated levels in the pre-metastatic niche, several days before metastases are visualized by MRI or histologically in the tissue. This study highlights the promise of diagnostic and therapeutic nanoparticles for treating metastatic cancer, possibly even for preventing the onset of the metastatic dissemination by targeting the pre-metastatic niche.
Measles is a human infectious disease of global concern that is caused by the measles virus. In this study, we report the complete genome sequencing of one measles virus isolate, genotype D8, that ...was obtained directly from a urine sample in Boa Vista city, the capital of Roraima state in Brazil. Phylogenetic reconstruction grouped the genome described in this study with that of samples from Australia, South Korea, and Italy. To our knowledge, this is the first complete genome sequence of a wild-type measles virus reported from Latin America. Therefore, the present data strengthen the current knowledge on the molecular epidemiology of measles worldwide.
Music can change the world Da Silva, Dana
Africa renewal,
12/2013, Letnik:
27, Številka:
13
Journal Article
Odprti dostop
Do you ever listen to a song and find yourself moved so deeply you are almost in tears? Have you ever been to a live performance that turned your worst day into your best? Have you ever heard a song ...that inspired you? Music has the power to move us and to change us. Yet today’s music mostly does not seem to have the same earth-moving, society-shaping effects as that of the past.
Objetivos: analisar o perfil epidemiológico e clínico dos casos notificados de sífilis congênita em região de alta incidência. Metodologia: estudo descritivo, com dados do Sistema de Informação de ...Agravos de Notificação e Sistema de Informação de Nascidos Vivos, para o período de 2015 a 2017. Foram identificadas as notificações de mulheres que residiam na região Norte do Espírito Santo. Resultados: foram analisados 99 casos de sífilis congênita, 97% foram notificados até 29 dias de vida, 76,5% eram assintomáticos, 89,9% estavam vivas no momento da notificação, e 49% foram tratados com penicilina. A maioria das gestantes realizaram o pré-natal (92,9%) e 56,1% realizaram sete ou mais consultas. O tratamento da sífilis gestacional foi inadequado em 55,6% dos casos. A realização do pré-natal e o diagnóstico precoce influencia significativamente no desfecho da criança nascer viva (p=<0,001). Conclusão: Existe uma possível falha na assistência ao pré-natal e na detecção precoce da doença, fatores que influenciam na ocorrência de sífilis congênita. Necessitando de treinamento das equipes, com base nos protocolos do Ministério da Saúde.
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