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1.
Medicine (Baltimore) ; 100(9): e24575, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655923

RESUMO

BACKGROUND: Sonography enhances diagnostic accuracy by the detection of the epineural or intraneuronal blood flow.[1-4] Power Doppler ultrasonography (PDUS) in carpal tunnel syndrome (CTS) has been previously studied and shown to be valid and reliable for grading the intraneural flow.[3,4] However, superb microvascular imaging (SMI) represents a new era in diagnostic sonography, and this new technology enables accurate visualization of vascular structures with intensive clutter suppression to provide flow signals for large to small vessels, and it presents these data at high frame rates.[5-7] Studies suggested that SMI is more sensitive in demonstrating blood flow in the diagnosis of CTS compared with PDUS.[7] In order to gain clarity, a meta-analysis to systematically review and synthesize relevant data on the evaluating intraneural blood flow of the median nerve (MN) using SMI and PDUS was undertaken. METHODS: We will search PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases from their inceptions to the December 31, 2020, without language restrictions. Two authors will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. Review Manager 5.2 and Stata 14.0 software will be used for data analysis. RESULTS: This systematic review will investigate whether superb microvascular imaging is more sensitive to display the blood flow in the MN with CTS than PDUS. CONCLUSION: Its findings will provide strong evidence for the feasibility of superb microvascular imaging on the detection of the neovascularization of the MN with CTS. SYSTEMATIC REVIEW REGISTRATION: INPLASY202110018.


Assuntos
Síndrome do Túnel Carpal/diagnóstico por imagem , Nervo Mediano/irrigação sanguínea , Neovascularização Patológica/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Ultrassonografia/métodos , Humanos , Metanálise como Assunto , Microvasos/diagnóstico por imagem , Fluxo Sanguíneo Regional , Reprodutibilidade dos Testes , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
2.
Nat Biomed Eng ; 5(3): 252-263, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33686281

RESUMO

Contrast agents for magnetic resonance imaging (MRI) improve anatomical visualizations. However, owing to poor image resolution in whole-body MRI, resolving fine structures is challenging. Here, we report that a nanoparticle with a polysaccharide supramolecular core and a shell of amorphous-like hydrous ferric oxide generating strong T1 MRI contrast (with a relaxivity coefficient ratio of ~1.2) facilitates the imaging, at resolutions of the order of a few hundred micrometres, of cerebral, coronary and peripheral microvessels in rodents and of lower-extremity vessels in rabbits. The nanoparticle can be synthesized at room temperature in aqueous solution and in the absence of surfactants, has blood circulation and renal clearance profiles that prevent opsonization, and leads to better imaging performance than Dotarem (gadoterate meglumine), a clinically approved gadolinium-based MRI contrast agent. The nanoparticle's biocompatibility and imaging performance may prove advantageous in a broad range of preclinical and clinical applications of MRI.


Assuntos
Dextranos/química , Compostos Férricos/química , Imagem por Ressonância Magnética/métodos , Nanopartículas/química , Animais , Materiais Biocompatíveis/química , Meios de Contraste/química , Gadolínio/química , Meglumina/química , Camundongos , Camundongos Endogâmicos BALB C , Microvasos/patologia , Compostos Organometálicos/química , Tamanho da Partícula , Polissacarídeos/química , Coelhos , Ratos , Ratos Sprague-Dawley
3.
Cardiol Rev ; 29(3): 143-149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33758123

RESUMO

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 has affected the health of people across the globe. Cardiovascular diseases (CVDs) have a significant relationship with COVID-19, both as a risk factor and prognostic indicator, and as a complication of the disease itself. In addition to predisposing to CVD complications, the ongoing pandemic has severely affected the delivery of timely and appropriate care for cardiovascular conditions resulting in increased mortality. The etiology behind the cardiac injury associated with severe acute respiratory syndrome coronavirus-2 is likely varied, including coronary artery disease, microvascular thrombosis, myocarditis, and stress cardiomyopathy. Further large-scale investigations are needed to better determine the underlying mechanism of myocardial infarction and other cardiac injury in COVID-19 patients and to determine the incidence of each type of cardiac injury in this patient population. Telemedicine and remote monitoring technologies can play an important role in optimizing outcomes in patients with established CVD. In this article, we summarize the various impacts that COVID-19 has on the cardiovascular system, including myocardial infarction, myocarditis, stress cardiomyopathy, thrombosis, and stroke.


Assuntos
/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , /complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Trombose Coronária/etiologia , Trombose Coronária/fisiopatologia , Humanos , /etiologia , Microvasos , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/fisiopatologia , Miocardite/etiologia , Miocardite/fisiopatologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Cardiomiopatia de Takotsubo/etiologia , Cardiomiopatia de Takotsubo/fisiopatologia , Trombose/etiologia , Trombose/fisiopatologia
4.
Medicine (Baltimore) ; 100(10): e24670, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725826

RESUMO

ABSTRACT: To report the rationale, design, and baseline demographic characteristics of TuYou-County Pediatric Eye study, which mainly aimed to determine the retinal microvascular changes with optical coherence tomography angiography (OCTA) and its association with eye abnormalities in school aged children and adolescents at suburban location in Northern China.TuYou-County Pediatric Eye study was a school-based survey conducted in TuYou-County. Multi-ethnic (Mongol, Han, and Hui) participants will be followed up for 5 years. Standardized ophthalmological examinations include visual acuity, ocular biometry, retinal photography, and OCTA. A questionnaire survey was conducted to collect variables regarding to eye disease such as parental history of eye diseases, near work, outdoor activities, living and eating habits, etc.After sampling, 687 participants were eligible for investigation, and 20 students did not attend the investigation, living 667 (response rate, 97.1%) students completed questionnaires and all ocular examinations. The average age of all participants was 14.9 ±â€Š5.11.TYPE study is the first large-scale school-based multi-ethnic survey in suburban site of Northern China. Continuous identification of retinal microvascular changes with eye diseases will provide new insights into the control related diseases in school-age children and adolescents.


Assuntos
Microvasos/diagnóstico por imagem , Projetos de Pesquisa , Retina/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Transtornos da Visão/diagnóstico , Adolescente , Angiografia , Criança , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Prevalência , Instituições Acadêmicas/estatística & dados numéricos , População Suburbana/estatística & dados numéricos , Tomografia de Coerência Óptica , Transtornos da Visão/epidemiologia , Acuidade Visual
5.
Physiol Rep ; 9(5): e14796, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33687143

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to be a world-wide pandemic with overwhelming socioeconomic impact. Since inflammation is one of the major causes of COVID-19 complications, the associated molecular mechanisms have been the focus of many studies to better understand this disease and develop improved treatments for patients contracting SARS-CoV-2. Among these, strong emphasis has been placed on pro-inflammatory cytokines, associating severity of COVID-19 with so-called "cytokine storm." More recently, peptide bradykinin, its dysregulated signaling or "bradykinin storm," has emerged as a primary mechanism to explain COVID-19-related complications. Unfortunately, this important development may not fully capture the main molecular players that underlie the disease severity. To this end, in this focused review, several lines of evidence are provided to suggest that in addition to bradykinin, two closely related vasoactive peptides, substance P and neurotensin, are also likely to drive microvascular permeability and inflammation, and be responsible for development of COVID-19 pathology. Furthermore, based on published experimental observations, it is postulated that in addition to ACE and neprilysin, peptidase neurolysin (Nln) is also likely to contribute to accumulation of bradykinin, substance P and neurotensin, and progression of the disease. In conclusion, it is proposed that "vasoactive peptide storm" may underlie severity of COVID-19 and that simultaneous inhibition of all three peptidergic systems could be therapeutically more advantageous rather than modulation of any single mechanism alone.


Assuntos
Bradicinina/metabolismo , Neprilisina/metabolismo , Neurotensina/metabolismo , Substância P/metabolismo , Animais , /patologia , Citocinas/metabolismo , Humanos , Microvasos/metabolismo , Microvasos/patologia
6.
Physiol Rep ; 9(3): e14726, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33523608

RESUMO

Corona virus disease 2019 (COVID-19) causes symptoms from multiple organs after infection by severe acute respiratory syndrome corona virus 2 (SARS CoV-2). They range from early, low blood oxygen levels (hypoxemia) without breathlessness ("silent hypoxia"), delirium, rashes, and loss of smell (anosmia), to persisting chest pain, muscle weakness and -pain, fatigue, confusion, memory problems and difficulty to concentrate ("brain fog"), mood changes, and unexpected onset of hypertension or diabetes. SARS CoV-2 affects the microcirculation, causing endothelial cell swelling and damage (endotheliitis), microscopic blood clots (microthrombosis), capillary congestion, and damage to pericytes that are integral to capillary integrity and barrier function, tissue repair (angiogenesis), and scar formation. Similar to other instances of critical illness, COVID-19 is also associated with elevated cytokine levels in the systemic circulation. This review examines how capillary damage and inflammation may contribute to these acute and persisting COVID-19 symptoms by interfering with blood and tissue oxygenation and with brain function. Undetectable by current diagnostic methods, capillary flow disturbances limit oxygen diffusion exchange in lungs and tissue and may therefore cause hypoxemia and tissue hypoxia. The review analyzes the combined effects of COVID-19-related capillary damage, pre-existing microvascular changes, and upstream vascular tone on tissue oxygenation in key organs. It identifies a vicious cycle, as infection- and hypoxia-related inflammation cause capillary function to deteriorate, which in turn accelerates hypoxia-related inflammation and tissue damage. Finally, the review addresses the effects of low oxygen and high cytokine levels in brain tissue on neurotransmitter synthesis and mood. Methods to assess capillary functions in human organs and therapeutic means to protect capillary functions and stimulate capillary bed repair may prove important for the individualized management of COVID-19 patients and targeted rehabilitation strategies.


Assuntos
/complicações , Microvasos/patologia , Consumo de Oxigênio , Oxigênio/metabolismo , Animais , /patologia , Humanos , Inflamação , Microvasos/metabolismo , Microvasos/virologia , Oxigênio/sangue , /patogenicidade
7.
Methods Mol Biol ; 2235: 27-35, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33576968

RESUMO

Pericytes are mural cells closely associated with endothelial cells in capillaries and microvessels. They are precursors of mesenchymal stem/stromal cells that have historically been retrospectively characterized in culture. We established a protocol, described in this chapter, to characterize and isolate pericytes from multiple human organs by flow cytometry and fluorescence-activated cell sorting. This prospective purification of pericytes brings us a step forward in the development of strategies for their use in the clinic.


Assuntos
Citometria de Fluxo/métodos , Pericitos/citologia , Pericitos/transplante , Capilares/citologia , Técnicas de Cultura de Células/métodos , Separação Celular/métodos , Células Cultivadas , Células Endoteliais/citologia , Humanos , Células-Tronco Mesenquimais/citologia , Microvasos/citologia , Pericitos/metabolismo , Fenótipo
8.
Methods Mol Biol ; 2235: 37-45, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33576969

RESUMO

Pericytes are found in all vascularized organs and are defined anatomically as perivascular cells that closely surround endothelial cells in capillaries and microvessels and are embedded within the same basement membrane. They have been shown to have diverse physiological and pathological functions including regulation of blood pressure, and tissue regeneration and scarring. Fundamental to understanding the role these cells play in these diverse processes is the ability to accurately identify and localize them in vivo. To do this, we have developed multicolor immunohistochemistry protocols described in this chapter.


Assuntos
Imuno-Histoquímica/métodos , Pericitos/citologia , Pericitos/transplante , Capilares/citologia , Diferenciação Celular/fisiologia , Células Cultivadas , Técnicas de Cocultura , Células Endoteliais/citologia , Humanos , Microvasos/citologia , Pericitos/metabolismo , Fenótipo
9.
Methods Mol Biol ; 2235: 47-59, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33576970

RESUMO

We report the use of self-assembled peptide (F2/S) hydrogels and cellular metabolomics to identify a number of innate molecules that are integral to the metabolic processes which drive cellular differentiation of multipotent pericyte stem cells. The culture system relies solely on substrate mechanics to induce differentiation in the absence of traditional differentiation media and therefore is a non-invasive approach to assessing cellular behavior at the molecular level and identifying key metabolites in this process. This novel approach demonstrates that simple metabolites can provide an alternative means to direct stem cell differentiation and that biomaterials can be used to identify them simply and quickly.


Assuntos
Metabolômica/métodos , Pericitos/citologia , Pericitos/transplante , Animais , Materiais Biocompatíveis/metabolismo , Capilares/citologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Células Cultivadas , Células Endoteliais/citologia , Humanos , Hidrogéis/química , Microvasos/citologia , Células-Tronco Multipotentes/efeitos dos fármacos , Peptídeos/química , Pericitos/metabolismo , Fenótipo
10.
Medicine (Baltimore) ; 100(4): e23635, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530166

RESUMO

BACKGROUND: As a novel ultrasound technique, superb microvascular imaging (SMI) can quickly, simply, and noninvasively study the microvascular distribution in the tumor and evaluate the microvascular perfusion. Studies suggested that SMI is helpful for the differentiation between benign and malignant parotid tumors. However, the results of these studies have been contradictory. Therefore, the present meta-analysis aimed at determining the accuracy of SMI in the differential diagnosis between benign and malignant parotid tumors. METHODS: We will search PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases from their inceptions to September 30, 2020, without language restrictions. Two authors will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. Review Manager 5.2 and Stata14.0 software will be used for data analysis. RESULTS: This systematic review will determine the accuracy of SMI in the differential diagnosis between benign and malignant parotid tumors. CONCLUSION: Its findings will provide helpful evidence for the accuracy of SMI in the differential diagnosis between benign and malignant parotid tumors. SYSTEMATIC REVIEW REGISTRATION: INPLASY2020100093.


Assuntos
Angiografia/estatística & dados numéricos , Microvasos/diagnóstico por imagem , Neoplasias Parotídeas/diagnóstico por imagem , Ultrassonografia/estatística & dados numéricos , Angiografia/métodos , Diagnóstico Diferencial , Humanos , Metanálise como Assunto , Reprodutibilidade dos Testes , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Ultrassonografia/métodos
11.
Life Sci ; 272: 119234, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33607158

RESUMO

Stroke still ranks as a most lethal disease worldwide. Angiogenesis during the chronic phase of ischemic stroke can alleviate ischemic injury and attenuate neurological deficit. XQ-1H is a new compound derived from the structure modification of ginkgolide B, which exerts anti-inflammation and neuroprotection against cerebral ischemic injury during the acute or subacute phase. However, whether XQ-1H facilitates angiogenesis and neural functional recovery during the chronic phase remains unclear. This research was designed to explore whether XQ-1H promotes angiogenesis after ischemic stroke and to preliminarily elucidate the mechanism. In vitro, XQ-1H was found to facilitate proliferation, migration and tube formation in bEnd.3 cells. In vivo, XQ-1H raised the CD31 positive microvessel number and increased focal cerebral blood flow in mice exposed to cerebral ischemic injury, and improved the neurological function. Mechanism studies revealed that XQ-1H exerted angiogenesis promoting effect via the PI3K/Akt/GSK3ß/ß-catenin/VEGF signal pathway, which was reversed by LY294002 (the specific inhibitor of PI3K/Akt). In conclusion, XQ-1H exerts angiogenetic effect both in vivo and in vitro, which is a potential agent against ischemic stroke during chronic phase.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Ginkgolídeos/metabolismo , Ginkgolídeos/farmacologia , Lactonas/metabolismo , Lactonas/farmacologia , Animais , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , China , Glicogênio Sintase Quinase 3 beta/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microvasos/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Acidente Vascular Cerebral/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , beta Catenina/metabolismo
12.
Medicine (Baltimore) ; 100(5): e24417, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592889

RESUMO

BACKGROUND: Contrast-enhanced ultrasound (CEUS) refers to a technique that uses contrast medium to strengthen the echo of backscatter, which can significantly improve the resolution, sensitivity and specificity of ultrasound diagnosis. As a quantitative imaging examination of blood flow signals, CEUS has allowed detection of synovial microvascularization in the joints of patients with rheumatoid arthritis (RA). However, the results of these studies have been contradictory. Therefore, the purpose of this study is to evaluate the value of CEUS in the activity of RA disease. METHODS: We will search PubMed, Embase, Cochrane Library, and CNKI from their inception to the December 20, 2020, without restrictions of language and publication status. Two investigators will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. This study will only include high quality clinical cohort or case control studies. Statistical analysis was performed by using the Review Manager version 5.3 and the STATA version 14.0 (Stata Corp, College Station, TX, USA) softwares. RESULTS: This systematic review will determine the value of CEUS in RA activity scores. CONCLUSION: The results of this study will provide a useful basis for high-quality CEUS to evaluate RA activity score. SYSTEMATIC REVIEW REGISTRATION: INPLASY2020120125.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Meios de Contraste , Microvasos/diagnóstico por imagem , Membrana Sinovial/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Metanálise como Assunto , Projetos de Pesquisa , Membrana Sinovial/irrigação sanguínea , Revisões Sistemáticas como Assunto
13.
Medicine (Baltimore) ; 100(3): e23985, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545987

RESUMO

PURPOSE: To assess expression levels of Ephrin type-A receptor 2 (EphA2), vascular endothelial growth factor (VEGF), and von Willebrand factor (vWF), and assess their potentials as prognostic biomarkers to predict the risk of poor survival in patients with primary lower grade glioma. METHOD: The study included75 patients with histopathologically confirmed primary glioma (World Health Organization Grade IV). All patients underwent combined surgery and postoperative radiotherapy for the management of primary glioma. Immuno-histochemical analysis was performed to evaluate expression levels ofEphA2 and VEGF. Evaluation of tumor microvessel density was also performed at angiogenesis hot spots due to tumor growth. Main outcomes of the study were the prognostic efficiencies of EphA2, VEGF, and vWF in primary low-grade glioma, as well as whether their expression levels were associated with cancer progression. RESULTS: Of the patients with glioma, 67% had very strong expression of EphA2. Overall survival was inversely correlated with the expression of EphA2. Regarding VEGF expression, 38 patients (51%) had strong expression, 29 patients (39%) had weak expression, and 8 patients (11%) had no expression. Strong VEGF expression was associated with poor prognosis and poor survival. CONCLUSION: EphA2, VEGF, and vWF could be considered prognostic markers for assessment of primary glioma.


Assuntos
Neoplasias do Sistema Nervoso Central/mortalidade , Efrina-A2/metabolismo , Glioma/mortalidade , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de von Willebrand/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Sistema Nervoso Central/irrigação sanguínea , Neoplasias do Sistema Nervoso Central/genética , Feminino , Glioma/genética , Humanos , Imuno-Histoquímica , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Neovascularização Patológica , Prognóstico
14.
PLoS One ; 16(2): e0246636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33556081

RESUMO

BACKGROUND: Data on microcirculatory pattern of COVID-19 critically ill patients are scarce. The objective was to compare sublingual microcirculation parameters of critically ill patients according to the severity of the disease. METHODS: The study is a single-center prospective study with critically ill COVID-19 patients admitted in ICU. Sublingual microcirculation was assessed by IDF microscopy within 48 hours of ICU admission. Microcirculatory flow index (MFI), proportion of perfused vessel (PPV), total vessel density (TVD), De Backer score (DBS), perfused vessel density (PVD) and heterogeneity index (HI) were assessed. Patients were divided in 2 groups (severe and critical) according to the World health organization definition. FINDINGS: From 19th of March to 7th of April 2020, 43 patients were included. Fourteen patients (33%) were in the severe group and twenty-nine patients (67%) in the critical group. Patients in the critical group were all mechanically ventilated. The critical group had significantly higher values of MFI, DBS and PVD in comparison to severe group (respectively, PaCO2: 49 [44-45] vs 36 [33-37] mmHg; p<0,0001, MFI: 2.8 ± 0.2 vs 2.5 ± 0.3; p = 0.001, DBS: 12.7 ± 2.6 vs 10.8 ± 2.0 vessels mm-2; p = 0.033, PVD: 12.5 ± 3.0 vs 10.1 ± 2.4 mm.mm-2; p = 0.020). PPV, HI and TVD were similar between groups Correlation was found between microcirculatory parameters and PaCO2 levels. CONCLUSION: Critical COVID-19 patients under mechanical ventilation seem to have higher red blood cell velocity than severe non-ventilated patients.


Assuntos
/fisiopatologia , Estado Terminal , Microcirculação/fisiologia , Microvasos/fisiopatologia , Idoso , Dióxido de Carbono/metabolismo , Feminino , Hemodinâmica , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismo , Pressão Parcial , Estudos Prospectivos , /fisiologia
15.
Nat Metab ; 3(2): 196-210, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33619377

RESUMO

Ketone bodies are generated in the liver and allow for the maintenance of systemic caloric and energy homeostasis during fasting and caloric restriction. It has previously been demonstrated that neonatal ketogenesis is activated independently of starvation. However, the role of ketogenesis during the perinatal period remains unclear. Here, we show that neonatal ketogenesis plays a protective role in mitochondrial function. We generated a mouse model of insufficient ketogenesis by disrupting the rate-limiting hydroxymethylglutaryl-CoA synthase 2 enzyme gene (Hmgcs2). Hmgcs2 knockout (KO) neonates develop microvesicular steatosis within a few days of birth. Electron microscopic analysis and metabolite profiling indicate a restricted energy production capacity and accumulation of acetyl-CoA in Hmgcs2 KO mice. Furthermore, acetylome analysis of Hmgcs2 KO cells revealed enhanced acetylation of mitochondrial proteins. These findings suggest that neonatal ketogenesis protects the energy-producing capacity of mitochondria by preventing the hyperacetylation of mitochondrial proteins.


Assuntos
Metabolismo Energético/fisiologia , Corpos Cetônicos/biossíntese , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Ácido 3-Hidroxibutírico/metabolismo , Acetilação , Animais , Animais Recém-Nascidos , Hidroximetilglutaril-CoA Sintase/genética , Hidroximetilglutaril-CoA Sintase/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Microvasos/fisiologia , Consumo de Oxigênio
16.
Cells ; 10(2)2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578631

RESUMO

Clinical manifestations of coronavirus disease 2019 (COVID-19) in pregnant women are diverse, and little is known of the impact of the disease on placental physiology. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been detected in the human placenta, and its binding receptor ACE2 is present in a variety of placental cells, including endothelium. Here, we analyze the impact of COVID-19 in placental endothelium, studying by immunofluorescence the expression of von Willebrand factor (vWf), claudin-5, and vascular endothelial (VE) cadherin in the decidua and chorionic villi of placentas from women with mild and severe COVID-19 in comparison to healthy controls. Our results indicate that: (1) vWf expression increases in the endothelium of decidua and chorionic villi of placentas derived from women with COVID-19, being higher in severe cases; (2) Claudin-5 and VE-cadherin expression decrease in the decidua and chorionic villus of placentas from women with severe COVID-19 but not in those with mild disease. Placental histological analysis reveals thrombosis, infarcts, and vascular wall remodeling, confirming the deleterious effect of COVID-19 on placental vessels. Together, these results suggest that placentas from women with COVID-19 have a condition of leaky endothelium and thrombosis, which is sensitive to disease severity.


Assuntos
/complicações , Placenta/irrigação sanguínea , Placenta/patologia , Complicações Cardiovasculares na Gravidez/etiologia , Complicações Infecciosas na Gravidez/etiologia , Trombose/etiologia , Adulto , Antígenos CD/análise , /virologia , Caderinas/análise , Claudina-5/análise , Endotélio/irrigação sanguínea , Endotélio/patologia , Endotélio/virologia , Feminino , Humanos , Recém-Nascido , Microvasos/patologia , Microvasos/virologia , Gravidez , Complicações Cardiovasculares na Gravidez/patologia , Complicações Cardiovasculares na Gravidez/virologia , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/virologia , Trombose/patologia , Trombose/virologia , Adulto Jovem , Fator de von Willebrand/análise
17.
Methods Mol Biol ; 2240: 43-55, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33423225

RESUMO

Intravital microscopy (IVM) is an essential experimental approach for evaluating, in real time, cell interactions in the blood and rheological parameters in the microcirculation of the living animals. Different tissues are surgically exposed to the visualization of the microvascular network in optical microscopies connected to video cameras and image software. By evaluating in situ microcirculatory network, IVM allows the visualization and quantification of physiological and pathological processes in the blood or in the adjacent tissues considering the whole system. Therefore, IVM has been used to evaluate the effects and mechanisms of actions in the microvascular network caused by pharmacological or toxic chemical agents. In this chapter, different experimental approaches are described to study the toxic effects and mechanisms of xenobiotics in the microcirculatory network.


Assuntos
Microscopia Intravital/métodos , Microvasos/efeitos dos fármacos , Nanoconjugados/toxicidade , Testes de Toxicidade/métodos , Xenobióticos/toxicidade , Animais , Microscopia Intravital/instrumentação , Microvasos/diagnóstico por imagem , Reologia/métodos , Xenobióticos/farmacocinética
18.
Phys Rev Lett ; 126(2): 028102, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33512186

RESUMO

The ability to reroute and control flow is vital to the function of venation networks across a wide range of organisms. By modifying individual edges in these networks, either by adjusting edge conductances or creating and destroying edges, organisms robustly control the propagation of inputs to perform specific tasks. However, a fundamental disconnect exists between the structure and function: networks with different local architectures can perform the same functions. Here, we answer the question of how changes at the level of individual edges collectively create functionality at the scale of an entire network. Using persistent homology, we analyze networks tuned to perform complex tasks. We find that the responses of such networks encode a hidden topological structure composed of sectors of nearly uniform pressure. Although these sectors are not apparent in the underlying network structure, they correlate strongly with the tuned function. The connectivity of these sectors, rather than that of individual nodes, provides a quantitative relationship between structure and function in flow networks.


Assuntos
Microvasos , Modelos Biológicos , Animais , Relação Estrutura-Atividade
19.
J Neurol Sci ; 421: 117308, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33497950

RESUMO

We evaluated the incidence, distribution, and histopathologic correlates of microvascular brain lesions in patients with severe COVID-19. Sixteen consecutive patients admitted to the intensive care unit with severe COVID-19 undergoing brain MRI for evaluation of coma or neurologic deficits were retrospectively identified. Eleven patients had punctate susceptibility-weighted imaging (SWI) lesions in the subcortical and deep white matter, eight patients had >10 SWI lesions, and four patients had lesions involving the corpus callosum. The distribution of SWI lesions was similar to that seen in patients with hypoxic respiratory failure, sepsis, and disseminated intravascular coagulation. Brain autopsy in one patient revealed that SWI lesions corresponded to widespread microvascular injury, characterized by perivascular and parenchymal petechial hemorrhages and microscopic ischemic lesions. Collectively, these radiologic and histopathologic findings add to growing evidence that patients with severe COVID-19 are at risk for multifocal microvascular hemorrhagic and ischemic lesions in the subcortical and deep white matter.


Assuntos
Lesões Encefálicas/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Microvasos/diagnóstico por imagem , Índice de Gravidade de Doença , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Lesões Encefálicas/etiologia , Humanos , Unidades de Terapia Intensiva/tendências , Masculino , Microvasos/lesões , Pessoa de Meia-Idade , Estudos Retrospectivos
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