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1.
Proc Natl Acad Sci U S A ; 119(11)2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35217532

RESUMO

The impacts of interferon (IFN) signaling on COVID-19 pathology are multiple, with both protective and harmful effects being documented. We report here a multiomics investigation of systemic IFN signaling in hospitalized COVID-19 patients, defining the multiomics biosignatures associated with varying levels of 12 different type I, II, and III IFNs. The antiviral transcriptional response in circulating immune cells is strongly associated with a specific subset of IFNs, most prominently IFNA2 and IFNG. In contrast, proteomics signatures indicative of endothelial damage and platelet activation associate with high levels of IFNB1 and IFNA6. Seroconversion and time since hospitalization associate with a significant decrease in a specific subset of IFNs. Additionally, differential IFN subtype production is linked to distinct constellations of circulating myeloid and lymphoid immune cell types. Each IFN has a unique metabolic signature, with IFNG being the most associated with activation of the kynurenine pathway. IFNs also show differential relationships with clinical markers of poor prognosis and disease severity. For example, whereas IFNG has the strongest association with C-reactive protein and other immune markers of poor prognosis, IFNB1 associates with increased neutrophil to lymphocyte ratio, a marker of late severe disease. Altogether, these results reveal specialized IFN action in COVID-19, with potential diagnostic and therapeutic implications.


Assuntos
Sangue/metabolismo , COVID-19/imunologia , Interferons/sangue , Proteoma , Transcriptoma , COVID-19/sangue , Estudos de Casos e Controles , Conjuntos de Dados como Assunto , Humanos , Pacientes Internados
2.
Biochem Biophys Res Commun ; 599: 134-141, 2022 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-35182939

RESUMO

Metabolic abnormalities are tightly connected to the perturbation of normal brain functions, thereby causing multiple neurodegenerative diseases. The hypothalamus is the master unit that controls the whole-body energy homeostasis. Thus, altered metabolic activity in the hypothalamus could be a crucial clue to better understand the development of metabolic disorders during aging. The current study aimed to investigate the changes in hypothalamic metabolites according to the aging process using gas chromatography-mass spectrometry. We identified that multiple metabolites and neurotransmitters were effectively reduced in the hypothalamus of aged mice. In addition, we observed increased levels of genes linked to the production and utilization of monocarboxylates in the aged hypothalamus, indicating the initiation of metabolic activity to produce alternative nutrient sources. Lastly, we found a reduced number of astrocytes in the hypothalamus of aged mice, suggesting that reduced nutrient availability in the hypothalamus might be associated with the decreased activity of astrocytes during aging. Collectively, the present study suggests that the deterioration of metabolic activities in the hypothalamus might be a primary cause and/or outcome of metabolic diseases associated with the aging process.


Assuntos
Envelhecimento/metabolismo , Hipotálamo/metabolismo , Metaboloma/fisiologia , Animais , Astrócitos/metabolismo , Sangue/metabolismo , Regulação da Expressão Gênica , Proteína Glial Fibrilar Ácida/imunologia , Hipotálamo/citologia , Hipotálamo/fisiologia , Imuno-Histoquímica/métodos , Masculino , Camundongos Endogâmicos C57BL
3.
Nat Genet ; 54(1): 52-61, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34980918

RESUMO

The gut microbiome has been implicated in a variety of physiological states, but controversy over causality remains unresolved. Here, we performed bidirectional Mendelian randomization analyses on 3,432 Chinese individuals with whole-genome, whole-metagenome, anthropometric and blood metabolic trait data. We identified 58 causal relationships between the gut microbiome and blood metabolites, and replicated 43 of them. Increased relative abundances of fecal Oscillibacter and Alistipes were causally linked to decreased triglyceride concentration. Conversely, blood metabolites such as glutamic acid appeared to decrease fecal Oxalobacter, and members of Proteobacteria were influenced by metabolites such as 5-methyltetrahydrofolic acid, alanine, glutamate and selenium. Two-sample Mendelian randomization with data from Biobank Japan partly corroborated results with triglyceride and with uric acid, and also provided causal support for published fecal bacterial markers for cancer and cardiovascular diseases. This study illustrates the value of human genetic information to help prioritize gut microbial features for mechanistic and clinical studies.


Assuntos
Sangue/metabolismo , Microbioma Gastrointestinal/genética , Estudos de Coortes , Fezes/microbiologia , Variação Genética , Estudo de Associação Genômica Ampla , Ácido Glutâmico/sangue , Humanos , Análise da Randomização Mendeliana , Metagenoma , Triglicerídeos/sangue
4.
J Mol Med (Berl) ; 100(2): 285-301, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34741638

RESUMO

The risk of severe COVID-19 increases with age as older patients are at highest risk. Thus, there is an urgent need to identify how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with blood components during aging. We investigated the whole blood transcriptome from the Genotype-Tissue Expression (GTEx) database to explore differentially expressed genes (DEGs) translated into proteins interacting with viral proteins during aging. From 22 DEGs in aged blood, FASLG, CTSW, CTSE, VCAM1, and BAG3 were associated with immune response, inflammation, cell component and adhesion, and platelet activation/aggregation. Males and females older than 50 years old overexpress FASLG, possibly inducing a hyperinflammatory cascade. The expression of cathepsins (CTSW and CTSE) and the anti-apoptotic co-chaperone molecule BAG3 also increased throughout aging in both genders. By exploring single-cell RNA-sequencing data from peripheral blood of SARS-CoV-2-infected patients, we found FASLG and CTSW expressed in natural killer cells and CD8 + T lymphocytes, whereas BAG3 was expressed mainly in CD4 + T cells, naive T cells, and CD14 + monocytes. In addition, T cell exhaustion was associated with increased expression of CCL4L2 and DUSP4 over blood aging. LAG3, PDCD1, TIGIT, VCAM1, HLA-DRA, and TOX also increased in individuals aged 60-69 years old; conversely, the RGS2 gene decreased with aging. We further identified a distinct gene expression profile associated with type I interferon signaling following blood aging. These results revealed changes in blood molecules potentially related to SARS-CoV-2 infection throughout aging, emphasizing them as therapeutic candidates for aggressive clinical manifestation of COVID-19. KEY MESSAGES: • Prediction of host-viral interactions in the whole blood transcriptome during aging. • Expression levels of FASLG, CTSW, CTSE, VCAM1, and BAG3 increase in aged blood. • Blood interactome reveals targets involved with immune response, inflammation, and blood clots. • SARS-CoV-2-infected patients with high viral load showed FASLG overexpression. • Gene expression profile associated with T cell exhaustion and type I interferon signaling were affected with blood aging.


Assuntos
Envelhecimento/sangue , Proteínas Sanguíneas/análise , COVID-19/genética , SARS-CoV-2/patogenicidade , Transcriptoma , Adulto , Idoso , Envelhecimento/genética , Sangue/metabolismo , Análise Química do Sangue , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/virologia , COVID-19/sangue , COVID-19/imunologia , COVID-19/fisiopatologia , Fenômenos Fisiológicos Cardiovasculares/genética , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/virologia , Estudos de Coortes , Feminino , Estudos de Associação Genética , Humanos , Imunidade Inata/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Parasit Vectors ; 14(1): 457, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493324

RESUMO

BACKGROUND: Behavioural shifts in the canonical location and timing of biting have been reported in natural populations of anopheline malaria vectors following the implementation of insecticide-based indoor vector control interventions. These modifications increase the likelihood of human-vector contact and allow mosquitoes to avoid insecticides, both conditions being favourable to residual transmission of the malarial parasites. The biting behaviour of mosquitoes follows rhythms that are under the control of biological clocks and environmental conditions, modulated by physiological states. In this work we explore modifications of spontaneous locomotor activity expressed by mosquitoes in different physiological states to highlight phenotypic variability associated to circadian control that may contribute to explain residual transmission in the field. METHODS: The F10 generation progeny of field-collected Anopheles coluzzii from southwestern Burkina Faso was tested using an automated recording apparatus (Locomotor Activity Monitor, TriKinetics Inc.) under LD 12:12 or DD light regimens in laboratory-controlled conditions. Activity recordings of each test were carried out for a week with 6-day-old females belonging to four experimental treatments, representing factorial combinations of two physiological variables: insemination status (virgin vs inseminated) and gonotrophic status (glucose fed vs blood fed). Chronobiological features of rhythmicity in locomotor activity were explored using periodograms, diversity indices, and generalized linear mixed modelling. RESULTS: The average strength of activity, onset of activity, and acrophase were modulated by both nutritional and insemination status as well as by the light regimen. Inseminated females showed a significant excess of arrhythmic activity under DD. When rhythmicity was observed in DD, females displayed sustained activity also during the subjective day. CONCLUSIONS: Insemination and gonotrophic status influence the underlying light and circadian control of chronobiological features of locomotor activity. Overrepresentation of arrhythmic chronotypes as well as the sustained activity of inseminated females during the subjective day under DD conditions suggests potential activity of natural populations of A. coluzzii during daytime under dim conditions, with implications for residual transmission of malarial parasites.


Assuntos
Anopheles/fisiologia , Sangue/metabolismo , Comportamento Alimentar , Inseminação , Locomoção , Mosquitos Vetores/fisiologia , Animais , Anopheles/classificação , Burkina Faso , Relógios Circadianos , Feminino , Malária/parasitologia , Malária/transmissão , Controle de Mosquitos/métodos , Mosquitos Vetores/parasitologia
6.
ACS Appl Mater Interfaces ; 13(33): 38947-38958, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433245

RESUMO

Although dressing blood-contacting devices with robust and synergistic antibacterial and antithrombus properties has been explored for several decades, it still remains a great challenge. In order to endow materials with remarkable antibacterial and antithrombus abilities, a stable and antifouling hydrogel coating was developed via surface-initiated polymerization of sulfobetaine methacrylate and acrylic acid on a polymeric substrate followed by embedding of antimicrobial peptides (AMPs), including WR (sequence: WRWRWR-NH2) or Bac2A (sequence: RLARIVVIRVAR-NH2) AMPs. The chemical composition of the AMP-embedded hydrogel coating was determined through XPS, zeta potential, and SEM-EDS measurements. The AMP-embedded antifouling hydrogel coating showed not only good hemocompatibility but also excellent bactericidal and antiadhesion properties against Gram-positive and Gram-negative bacteria. Moreover, the hydrogel coating could protect the AMPs with long-term bioactivity and cover the positive charge of the dotted distributed AMPs, which in turn well retained the hemocompatibility and antifouling capacity of the bulk hydrogels. Furthermore, the microbiological results of animal experiments also verified the anti-infection performance in vivo. Histological and immunological data further indicated that the hydrogel coating had an excellent anti-inflammatory function. Therefore, the present study might provide a promising approach to prevent bacterial infections and thrombosis in clinical applications of blood-contacting devices and related implants.


Assuntos
Antibacterianos/química , Materiais Revestidos Biocompatíveis/química , Fibrinolíticos/química , Hidrogéis/química , Proteínas Citotóxicas Formadoras de Poros/química , Resinas Acrílicas/química , Antibacterianos/farmacologia , Bandagens , Sangue/metabolismo , Sobrevivência Celular , Materiais Revestidos Biocompatíveis/metabolismo , Eritrócitos , Fibrinolíticos/farmacologia , Hemólise , Humanos , Hidrogéis/metabolismo , Metacrilatos/química , Adesividade Plaquetária/efeitos dos fármacos , Polimerização , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Propriedades de Superfície
7.
J Inorg Biochem ; 224: 111566, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34418714

RESUMO

Casiopeinas® are among the few CuII compounds patented for their antitumor activity, but their mode of action has not been fully elucidated yet. One of them, Cas II-gly, is formed by 4,7-dimethyl-1,10-phenanthroline (Me2phen) and glycinato (Gly). In blood and cells, Cas II-gly can keep its identity or form mixed species with serum or cytosol bioligands (bL or cL) with composition CuII-Me2phen-bL/cL, CuII-Gly-bL/cL, or CuII-bL/cL. In this study, the binding of Cas II-gly with low molecular mass bioligands of blood serum (citric, L-lactic acid, and L-histidine) and cytosol (reduced glutathione (GSH), reduced nicotinamide adenine dinucleotide (NADH), adenosine triphosphate (ATP), and l-ascorbic acid) was examined through the application of instrumental (ElectroSpray Ionization-Mass Spectrometry and Electron Paramagnetic Resonance) and computational (Density Functional Theory) methods. The results indicated that mixed species CuII-Me2phen-bL/cL are formed, with the bioligands replacing glycinato. The formation of these adducts may participate in the copper transport toward the target organs and facilitate the cellular uptake or, in constrast, preclude it. In the systems with GSH, NADH and L-ascorbate, a redox reaction occurs with the partial oxidation of cL to the corresponding oxidized form (GSSG, NAD+ and dehydroascorbate) which interact with CuII. Formed CuI ion does not give complexation reactions with reduced or oxidized form of bioligands for its 'soft' character and low affinity for oxygen and nitrogen donors compared to CuII. However, CuI could promote Fenton-like reactions with production of reactive oxygen species (ROS) related to the antitumor activity of Casiopeinas®.


Assuntos
Antineoplásicos/metabolismo , Sangue/metabolismo , Cobre/metabolismo , Citosol/metabolismo , Compostos Organometálicos/metabolismo , Ácido Ascórbico/metabolismo , Cobre/química , Teoria da Densidade Funcional , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Glutationa/metabolismo , Histidina/metabolismo , Humanos , Ligantes , NAD/metabolismo , Compostos Organometálicos/química , Oxirredução , Fenantrolinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Massas por Ionização por Electrospray/métodos
8.
Nat Commun ; 12(1): 4967, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34426576

RESUMO

Today's smallest energy storage devices for in-vivo applications are larger than 3 mm3 and lack the ability to continuously drive the complex functions of smart dust electronic and microrobotic systems. Here, we create a tubular biosupercapacitor occupying a mere volume of 1/1000 mm3 (=1 nanoliter), yet delivering up to 1.6 V in blood. The tubular geometry of this nano-biosupercapacitor provides efficient self-protection against external forces from pulsating blood or muscle contraction. Redox enzymes and living cells, naturally present in blood boost the performance of the device by 40% and help to solve the self-discharging problem persistently encountered by miniaturized supercapacitors. At full capacity, the nano-biosupercapacitors drive a complex integrated sensor system to measure the pH-value in blood. This demonstration opens up opportunities for next generation intravascular implants and microrobotic systems operating in hard-to-reach small spaces deep inside the human body.


Assuntos
Técnicas Biossensoriais , Sangue/metabolismo , Capacitância Elétrica , Nanopartículas/química , Animais , Cães , Eletroquímica , Eletrodos , Humanos , Concentração de Íons de Hidrogênio , Transporte de Íons , Células Madin Darby de Rim Canino , Temperatura
9.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360924

RESUMO

Extracellular vesicles (EVs) are important players for intercellular communication. EVs are secreted by almost all cell types; they can transfer information between nearby or distant cells, and they are highly abundant in body fluids. In this review, we describe the general characteristics of EVs, as well as isolation and characterization approaches. Then, we focus on one of the most relevant sources of EVs: the blood. Indeed, apart from EVs secreted by blood cells, EVs of diverse origins travel in the bloodstream. We present the numerous types of EVs that have been found in circulation. Besides, the implications of blood-derived EVs in both physiological and pathological processes are summarized, highlighting their potential as biomarkers for the diagnosis, treatment monitoring, and prognosis of several diseases, and also as indicators of physiological modifications. Finally, the applications of EVs introduced in the circulatory system are discussed. We describe the use of EVs from distinct origins, naturally produced or engineered, autologous, allogeneic, or even from different species and the effects they have when introduced in circulation. Therefore, the present work provides a comprehensive overview of the components, effects, and applications of EVs in blood.


Assuntos
Sangue/metabolismo , Vesículas Extracelulares/fisiologia , Animais , Biomarcadores/metabolismo , Humanos
10.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361026

RESUMO

In the presented study, a capillary electrophoresis-mass spectrometry method combining high separation efficiency and sensitive detection has been developed and validated, for the first time, to quantify branched chain amino acids (valine, isoleucine, leucine) in commercial food and sport supplement samples and human plasma samples. The separations were performed in a bare fused silica capillary. The background electrolyte was composed of 500 mM formic acid with pH 2.0. The plasma sample pretreatment was realized by simple protein precipitation with acetonitrile. Injection of a short zone of highly basic electrolyte before the sample injection and application of the negative pressure on the separation were accompanied by enhanced resolution of the isobaric amino acids-isoleucine and leucine. The developed method was characterized by favorable validation parameters, such as linearity (r2 > 0.99), accuracy and precision, the limit of detection, lower limit of quantification, or robustness. These parameters were more than sufficient for the quantification of branched chain amino acids in various samples. The determined concentrations of branched chain amino acids in food and sports supplements were in very good agreement with the content declared by the manufacturer. The investigated concentrations of branched chain amino acids were in the range 294.68-359.24 µM for valine, 91.76-95.67 µM for isoleucine, and 196.78-251.24 µM for leucine. These concentrations fall within the physiological limits. The developed CE-MS/MS method represents a suitable alternative to traditional approaches used in branched chain amino acid quality control and bioanalysis.


Assuntos
Aminoácidos de Cadeia Ramificada/análise , Sangue/metabolismo , Suplementos Nutricionais , Eletroforese Capilar/métodos , Espectrometria de Massas/métodos , Adulto , Aminoácidos de Cadeia Ramificada/sangue , Análise Química do Sangue/métodos , Humanos , Masculino
11.
J Mater Sci Mater Med ; 32(8): 86, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313865

RESUMO

Over the years, several devices have been created (and the development of many others is currently in progress) to be in permanent contact with blood: mechanical circulatory supports represent an example thereof. The hemocompatibility of these devices largely depends on the chemical composition of blood-contacting components. In the present work, an innovative material (hybrid membrane) is proposed to fabricate the inner surfaces of a pulsatile ventricular chamber: it has been obtained by coupling a synthetic polymer (e.g., commercial polycarbonate urethane) with decellularized porcine pericardium. The hemocompatibility of the innovative material has been preliminarily assessed by measuring its capacity to promote thrombin generation and induce platelet activation. Our results demonstrated the blood compatibility of the proposed hybrid membrane.


Assuntos
Plaquetas/efeitos dos fármacos , Sangue/efeitos dos fármacos , Materiais Revestidos Biocompatíveis , Membranas Artificiais , Ativação Plaquetária , Adulto , Animais , Sangue/metabolismo , Feminino , Humanos , Teste de Materiais/métodos , Pericárdio/química , Pericárdio/efeitos dos fármacos , Cimento de Policarboxilato/química , Polímeros/química , Estresse Mecânico , Propriedades de Superfície , Suínos , Trombina/química , Uretana/química
12.
Methods Mol Biol ; 2341: 127-131, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34264468

RESUMO

Staphylococcus aureus is an important human pathogen that causes a plethora of diverse infections within the human host that range in severity from the relatively minor to the severe. Of note, bloodstream infections caused by this organism result in high mortality rates, often following failed rounds of surgical and antibiotic intervention. The capacity for S. aureus to exist in blood is driven by myriad virulence factors that engage in a manipulation of various host responses to evade destruction and ensure survival. These include both secreted elements, such as coagulase and von Willebrand factor protein, as well as surface displayed factors, including clumping factor A and fibronectin binding protein A. In addition to this, there are a number of other loci within the S. aureus genome whose products have been shown to contribute to blood survival by more indirect means. Accordingly, ex vivo whole human blood survival assays are often used as a preliminary study to investigate host-bacterial interactions in an effort to delineate the pathogenicity of S. aureus strains. Herein we provide a detailed assessment of the protocol required to perform such studies.


Assuntos
Sangue/microbiologia , Staphylococcus aureus/crescimento & desenvolvimento , Fatores de Virulência/metabolismo , Proteínas de Bactérias/metabolismo , Sangue/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Viabilidade Microbiana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidade
13.
Nat Methods ; 18(7): 779-787, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34239103

RESUMO

Chimeric MS/MS spectra contain fragments from multiple precursor ions and therefore hinder compound identification in metabolomics. Historically, deconvolution of these chimeric spectra has been challenging and relied on specific experimental methods that introduce variation in the ratios of precursor ions between multiple tandem mass spectrometry (MS/MS) scans. DecoID provides a complementary, method-independent approach where database spectra are computationally mixed to match an experimentally acquired spectrum by using LASSO regression. We validated that DecoID increases the number of identified metabolites in MS/MS datasets from both data-independent and data-dependent acquisition without increasing the false discovery rate. We applied DecoID to publicly available data from the MetaboLights repository and to data from human plasma, where DecoID increased the number of identified metabolites from data-dependent acquisition data by over 30% compared to direct spectral matching. DecoID is compatible with any user-defined MS/MS database and provides automated searching for some of the largest MS/MS databases currently available.


Assuntos
Algoritmos , Metabolômica/métodos , Espectrometria de Massas em Tandem/métodos , Sangue/metabolismo , Bases de Dados Factuais , Escherichia coli/metabolismo , Humanos , Reprodutibilidade dos Testes , Saccharomycetales/metabolismo , Processamento de Sinais Assistido por Computador
14.
Drug Deliv ; 28(1): 1501-1509, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34259095

RESUMO

Extracellular vesicles (EVs) are nanovesicles released by various cell types. EVs are known for cell-to-cell communications and have potent biological activities. Despite great progress in recent years for studies exploring the potentials of EVs for early disease detection, therapeutic application and drug delivery, determination of the favorable storage conditions of EVs has been challenging. The understanding of the impact of storage conditions on EVs before and after isolation is still limited. Storage may change the size, number, contents, functions, and behaviors of EVs. Here, we summarized current studies about the stability of EVs in different conditions, focusing on temperatures, durations, and freezing and thawing cycles. -80 °C seems to remain the most favorable condition for storage of biofluids and isolated EVs, while isolated EVs may be stored at 4 °C shortly. Lyophilization is promising for storage of EV products. Challenges remain in the understanding of storage-mediated change in EVs and in the development of advanced preservation techniques of EVs.


Assuntos
Estabilidade de Medicamentos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Biomarcadores , Sangue/metabolismo , Técnicas de Cultura de Células , Sistemas de Liberação de Medicamentos , Liofilização , Leite Humano/metabolismo , Sêmen/metabolismo , Temperatura , Urina/citologia
15.
ACS Appl Mater Interfaces ; 13(30): 35494-35505, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34288640

RESUMO

Polymer nanocapsules, with a hollow structure, are increasingly finding widespread use as drug delivery carriers; however, quantitatively evaluating the bio-nano interactions of nanocapsules remains challenging. Herein, poly(ethylene glycol) (PEG)-based metal-phenolic network (MPN) nanocapsules of three sizes (50, 100, and 150 nm) are engineered via supramolecular template-assisted assembly and the effect of the nanocapsule size on bio-nano interactions is investigated using in vitro cell experiments, ex vivo whole blood assays, and in vivo rat models. To track the nanocapsules by mass cytometry, a preformed gold nanoparticle (14 nm) is encapsulated into each PEG-MPN nanocapsule. The results reveal that decreasing the size of the PEG-MPN nanocapsules from 150 to 50 nm leads to reduced association (up to 70%) with phagocytic blood cells in human blood and prolongs in vivo systemic exposure in rat models. The findings provide insights into MPN-based nanocapsules and represent a platform for studying bio-nano interactions.


Assuntos
Sangue/metabolismo , Estruturas Metalorgânicas/química , Nanocápsulas/química , Polietilenoglicóis/química , Pirogalol/análogos & derivados , Animais , Citometria de Fluxo/métodos , Ouro/química , Ouro/metabolismo , Ouro/farmacocinética , Ouro/toxicidade , Humanos , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Estruturas Metalorgânicas/metabolismo , Estruturas Metalorgânicas/farmacocinética , Estruturas Metalorgânicas/toxicidade , Camundongos , Nanocápsulas/toxicidade , Tamanho da Partícula , Polietilenoglicóis/metabolismo , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/toxicidade , Pirogalol/metabolismo , Pirogalol/farmacocinética , Pirogalol/toxicidade , Células RAW 264.7 , Ratos Sprague-Dawley
16.
Molecules ; 26(14)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34299389

RESUMO

Currently, most clinical studies in metabolomics only consider a single type of sample such as urine, plasma, or feces and use a single analytical platform, either NMR or MS. Although some studies have already investigated metabolomics data from multiple fluids, the information is limited to a unique analytical platform. On the other hand, clinical studies investigating the human metabolome that combine multi-analytical platforms have focused on a single biofluid. Combining data from multiple sample types for one patient using a multimodal analytical approach (NMR and MS) should extend the metabolome coverage. Pre-analytical and analytical phases are time consuming. These steps need to be improved in order to move into clinical studies that deal with a large number of patient samples. Our study describes a standard operating procedure for biological specimens (urine, blood, saliva, and feces) using multiple platforms (1H-NMR, RP-UHPLC-MS, and HILIC-UHPLC-MS). Each sample type follows a unique sample preparation procedure for analysis on a multi-platform basis. Our method was evaluated for its robustness and was able to generate a representative metabolic map.


Assuntos
Sangue/metabolismo , Fezes/química , Metaboloma , Saliva/química , Manejo de Espécimes/normas , Urina/química , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Espectroscopia de Ressonância Magnética/métodos
17.
Transfus Apher Sci ; 60(3): 103162, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34083162

RESUMO

Aging is associated with the impairment of stem cell activation, leading to the functional decline of tissues and increasing the risk for age-associated diseases. The old, damaged or unrepaired tissues disturb distant tissue homeostasis by secreting factors into the circulation, which may not only serve as biomarkers for specific age-associated pathologies but also induce a variety of degenerative phenotypes. In this review, we summarize and discuss systemic determinants that perpetuate age-related tissue dysfunction. We further elaborate on the effects of attenuating these circulating factors by highlighting recent advances which utilize plasmapheresis in a pre-clinical or clinical setting. Overall, we postulate that repositioning therapeutic plasma exchange (TPE) to dilute the systemic factors, which become deleterious at their age-elevated levels, could be a rapidly effective rejuvenation therapy that recalibrates crucial signaling pathways to a youthful state.


Assuntos
Sangue/metabolismo , Plasmaferese/métodos , Fatores Etários , Animais , Humanos , Camundongos
18.
Cell Stress Chaperones ; 26(4): 705-720, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34080136

RESUMO

Heat stress has detrimental effects on livestock via diverse immune and physiological changes; heat-stressed animals are rendered susceptible to diverse diseases. However, there is relatively little information available regarding the altered immune responses of domestic animals in heat stress environments, particularly in cattle steers. This study aimed to determine the changes in the immune responses of Holstein and Jersey steers under heat stress. We assessed blood immune cells and their functions in the steers of two breeds under normal and heat stress conditions and found that immune cell proportions and functions were altered in response to different environmental conditions. Heat stress notably reduced the proportions of CD21+MHCII+ B cell populations in both breeds. We also observed breed-specific differences. Under heat stress, in Holstein steers, the expression of myeloperoxidase was reduced in the polymorphonuclear cells, whereas heat stress reduced the WC1+ γδ T cell populations in Jersey steers. Breed-specific changes were also detected based on gene expression. In response to heat stress, the expression of IL-10 and IL-17A increased in Holstein steers alone, whereas that of IL-6 increased in Jersey steers. Moreover, the mRNA expression pattern of heat shock protein genes such as Hsp70 and Hsp90 was significantly increased in only Holstein steers. Collectively, these results indicate that altered blood immunological profiles may provide a potential explanation for the enhanced susceptibility of heat-stressed steers to disease. The findings of this study provide important information that will contribute to developing new strategies to alleviate the detrimental effects of heat stress on steers.


Assuntos
Células Sanguíneas/citologia , Sangue/metabolismo , Resposta ao Choque Térmico/imunologia , Temperatura Alta , Neutrófilos/citologia , Animais , Sangue/imunologia , Células Sanguíneas/imunologia , Bovinos , Transtornos de Estresse por Calor/imunologia , Lactação/imunologia , Lactação/fisiologia , Neutrófilos/imunologia
19.
Mol Nutr Food Res ; 65(17): e2001154, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34184401

RESUMO

SCOPE: To examine the relationship between changes in circulating metabolites during diet-induced weight loss and changes of adiposity. This study also investigates changes in these metabolites in relation to body weight and adiposity regain during a weight loss maintenance period. METHODS AND RESULTS: This cohort study is nested within the Satiety Innovation (SATIN) study. Participants (n = 162) achieving ≥8% weight loss during an initial 8-week low-calorie formula diet (LCD) are included in a 12-week weight loss maintenance period. A targeted metabolite profiling (123 metabolites) approach is applied using three different platforms (proton nuclear magnetic resonance, liquid chromatography mass spectrometry, gas chromatography mass spectrometry). Changes in several lipid species and citric acid are significantly associated with greater reduction of body weight, total fat, and abdominal adiposity distribution during the LCD. Decreases in the concentrations of lysophosphatidylcholines (LPCs) 14:0, LPC 20:3, phosphatidylcholine (PC) 32:2, PC 38:3, sphingomyelin (SM) 32:2, and increases in citric acid concentrations during the LCD are associated with adiposity regain and loss, respectively, during the weight loss maintenance period. CONCLUSIONS: The results show that weight loss is associated with changes in lipid species and citric acid. These changes are related to subsequent weight and adiposity regain identifying the adipose lipid metabolism as an important factor for the maintenance of lost weight and adiposity.


Assuntos
Adiposidade , Sangue/metabolismo , Restrição Calórica , Programas de Redução de Peso/métodos , Adulto , Composição Corporal , Peso Corporal , Ácido Cítrico/sangue , Feminino , Humanos , Lipídeos/sangue , Lisofosfatidilcolinas/sangue , Masculino , Pessoa de Meia-Idade , Perda de Peso
20.
Parasit Vectors ; 14(1): 317, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112224

RESUMO

BACKGROUND: The human flea, Pulex irritans, is widespread globally and has a long association with humans, one of its principal hosts. Its role in plague transmission is still under discussion, although its high prevalence in plague-endemic regions and the presence of infected fleas of this species during plague outbreaks has led to proposals that it has been a significant vector in human-to-human transmission in some historical and present-day epidemiologic situations. However, based on a limited number of studies, P. irritans is considered to be a poor vector and receives very little attention from public health policymakers. In this study we examined the vector competence of P. irritans collected from foxes and owls in the western United States, using a standard protocol and artificial infection system. METHODS: Wild-caught fleas were maintained in the laboratory and infected by allowing them to feed on human or rat blood containing 2 × 108 to 1 × 109 Y. pestis/ml. The fleas were then monitored periodically for infection rate and bacterial load, mortality, feeding rate, bacterial biofilm formation in the foregut (proventricular blockage), and ability to transmit Y. pestis after their single infectious blood meal. RESULTS: P. irritans were susceptible to infection, with more than 30% maintaining high bacterial loads for up to 20 days. Transmission during this time was infrequent and inefficient, however. Consistent with previous studies, a low level of early-phase transmission (3 days after the infectious blood meal) was detected in some trials. Transmission at later time points was also sporadic, and the incidence of proventricular blockage, required for this mode of transmission, was low in fleas infected using rat blood and never occurred in fleas infected using human blood. The highest level of blockage and transmission was seen in fleas infected using rat blood and allowed to feed intermittently rather than daily, indicating that host blood and feeding frequency influence vector competence. CONCLUSIONS: Our results affirm the reputation of P. irritans as a feeble vector compared to rodent flea species examined similarly, and its vector competence may be lower when infected by feeding on bacteremic human blood.


Assuntos
Insetos Vetores/microbiologia , Peste/transmissão , Sifonápteros/microbiologia , Yersinia pestis/fisiologia , Animais , Sangue/metabolismo , Surtos de Doenças , Feminino , Infestações por Pulgas/transmissão , Raposas/parasitologia , Humanos , Peste/microbiologia , Estrigiformes/parasitologia , Estados Unidos
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