Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42.638
Filtrar
1.
Nat Commun ; 11(1): 5075, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033245

RESUMO

Nickel-iron composites are efficient in catalyzing oxygen evolution. Here, we develop a microorganism corrosion approach to construct nickel-iron hydroxides. The anaerobic sulfate-reducing bacteria, using sulfate as the electron acceptor, play a significant role in the formation of iron sulfide decorated nickel-iron hydroxides, which exhibit excellent electrocatalytic performance for oxygen evolution. Experimental and theoretical investigations suggest that the synergistic effect between oxyhydroxides and sulfide species accounts for the high activity. This microorganism corrosion strategy not only provides efficient candidate electrocatalysts but also bridges traditional corrosion engineering and emerging electrochemical energy technologies.


Assuntos
Desulfotomaculum/metabolismo , Hidróxidos/metabolismo , Níquel/metabolismo , Oxigênio/metabolismo , Corrosão , Teoria da Densidade Funcional , Eletroquímica , Eletrodos , Análise Espectral Raman , Espectroscopia por Absorção de Raios X
2.
Nat Commun ; 11(1): 4928, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004791

RESUMO

High-altitude adaptation of Tibetans represents a remarkable case of natural selection during recent human evolution. Previous genome-wide scans found many non-coding variants under selection, suggesting a pressing need to understand the functional role of non-coding regulatory elements (REs). Here, we generate time courses of paired ATAC-seq and RNA-seq data on cultured HUVECs under hypoxic and normoxic conditions. We further develop a variant interpretation methodology (vPECA) to identify active selected REs (ASREs) and associated regulatory network. We discover three causal SNPs of EPAS1, the key adaptive gene for Tibetans. These SNPs decrease the accessibility of ASREs with weakened binding strength of relevant TFs, and cooperatively down-regulate EPAS1 expression. We further construct the downstream network of EPAS1, elucidating its roles in hypoxic response and angiogenesis. Collectively, we provide a systematic approach to interpret phenotype-associated noncoding variants in proper cell types and relevant dynamic conditions, to model their impact on gene regulation.


Assuntos
Aclimatação/genética , Cromatina/metabolismo , Grupos Étnicos/genética , Redes Reguladoras de Genes , Modelos Genéticos , Altitude , Doença da Altitude/etnologia , Doença da Altitude/genética , Doença da Altitude/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Hipóxia Celular/genética , Células Cultivadas , Cromatina/genética , Sequenciamento de Cromatina por Imunoprecipitação , Resistência à Doença/genética , Feminino , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Oxigênio/metabolismo , Polimorfismo de Nucleotídeo Único , Gravidez , Cultura Primária de Células , RNA-Seq , Elementos Reguladores de Transcrição/genética , Seleção Genética , Tibet/etnologia , Fatores de Transcrição/metabolismo , Sequenciamento Completo do Genoma
3.
BMC Pulm Med ; 20(1): 269, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066765

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has spread to almost 100 countries, infected over 31 M patients and resulted in 961 K deaths worldwide as of 21st September 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute respiratory distress syndrome (ARDS) with multi-functional failure as a result of a cytokine storm with increased serum levels of cytokines. The pathogenesis of the respiratory failure in COVID-19 is yet unknown, but diffuse alveolar damage with interstitial thickening leading to compromised gas exchange is a plausible mechanism. Hypoxia is seen in the COVID-19 patients, however, patients present with a distinct phenotype. Intracellular levels of nitric oxide (NO) play an important role in the vasodilation of small vessels. To elucidate the intracellular levels of NO inside of RBCs in COVID-19 patients compared with that of healthy control subjects. METHODS: We recruited 14 COVID-19 infected cases who had pulmonary involvement of their disease, 4 non-COVID-19 healthy controls (without pulmonary involvement and were not hypoxic) and 2 hypoxic non-COVID-19 patients subjects who presented at the Masih Daneshvari Hospital of Tehran, Iran between March-May 2020. Whole blood samples were harvested from patients and intracellular NO levels in 1 × 106 red blood cells (RBC) was measured by DAF staining using flow cytometry (FACS Calibour, BD, CA, USA). RESULTS: The Mean florescent of intensity for NO was significantly enhanced in COVID-19 patients compared with healthy control subjects (P ≤ 0.05). As a further control for whether hypoxia induced this higher intracellular NO, we evaluated the levels of NO inside RBC of hypoxic patients. No significant differences in NO levels were seen between the hypoxic and non-hypoxic control group. CONCLUSIONS: This pilot study demonstrates increased levels of intracellular NO in RBCs from COVID-19 patients. Future multi-centre studies should examine whether this is seen in a larger number of COVID-19 patients and whether NO therapy may be of use in these severe COVID-19 patients.


Assuntos
Dióxido de Carbono/metabolismo , Infecções por Coronavirus/metabolismo , Eritrócitos/metabolismo , Hipóxia/metabolismo , Óxido Nítrico/metabolismo , Oxigênio/metabolismo , Pneumonia Viral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Betacoronavirus , Gasometria , Estudos de Casos e Controles , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Feminino , Citometria de Fluxo , Humanos , Hipóxia/sangue , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pressão Parcial , Projetos Piloto , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/metabolismo , Vasodilatação , Adulto Jovem
4.
J Affect Disord ; 277: 772-778, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33065816

RESUMO

BACKGROUND: The wearing of respiratory protective devices (RPDs) correctly and continually in situations where people are at risk of respiratory infections is crucial for infection prevention. Certain people are poorly compliant with RPDs due to RPD-related annoyance, including respiratory discomfort. We hypothesized that individuals vulnerable to panic attacks are included in this group. No published studies on this topic are available. The evidence for our hypothesis was reviewed in this study as a starting point for future research. METHODS: We selected a set of experimental studies that measured the respiratory physiological burden in RPD wearers through objective and validated methods. We conducted a bibliographic search of publications in the PubMed database (January 2000-May 2020) to identify representative studies that may be of interest for panic respiratory pathophysiology. RESULTS: Five studies were included. Wearing RPDs exerted significant respiratory effects, including increased breathing resistance, CO2 rebreathing due to CO2 accumulation in the RPD cavity, and decreased inhaled O2 concentration. We discussed the implications of these effects on the respiratory pathophysiology of panic. LIMITATIONS: Most studies had a small sample size, with a preponderance of young participants. Different methodologies were used across the studies. Furthermore, differences in physical responses between wearing RPDs in experimental settings or daily life cannot be excluded. CONCLUSIONS: This research supports the idea that panic-prone individuals may be at higher risk of respiratory discomfort when wearing RPDs, thereby reducing their tolerance for these devices. Strategies to decrease discomfort should be identified to overcome the risk of poor compliance.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Transtorno de Pânico/fisiopatologia , Pneumonia Viral/prevenção & controle , Transtornos Respiratórios/fisiopatologia , Respiração , Dispositivos de Proteção Respiratória/efeitos adversos , Resistência das Vias Respiratórias , Betacoronavirus , Dióxido de Carbono/metabolismo , Humanos , Oxigênio/metabolismo , Transtorno de Pânico/metabolismo , Transtorno de Pânico/psicologia , Transtornos Respiratórios/etiologia , Transtornos Respiratórios/metabolismo , Transtornos Respiratórios/psicologia , Rinomanometria , Espirometria
5.
Nat Commun ; 11(1): 4706, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943618

RESUMO

Yeast physiology is temporally regulated, this becomes apparent under nutrient-limited conditions and results in respiratory oscillations (YROs). YROs share features with circadian rhythms and interact with, but are independent of, the cell division cycle. Here, we show that YROs minimise energy expenditure by restricting protein synthesis until sufficient resources are stored, while maintaining osmotic homeostasis and protein quality control. Although nutrient supply is constant, cells sequester and store metabolic resources via increased transport, autophagy and biomolecular condensation. Replete stores trigger increased H+ export which stimulates TORC1 and liberates proteasomes, ribosomes, chaperones and metabolic enzymes from non-membrane bound compartments. This facilitates translational bursting, liquidation of storage carbohydrates, increased ATP turnover, and the export of osmolytes. We propose that dynamic regulation of ion transport and metabolic plasticity are required to maintain osmotic and protein homeostasis during remodelling of eukaryotic proteomes, and that bioenergetic constraints selected for temporal organisation that promotes oscillatory behaviour.


Assuntos
Metabolismo Energético/fisiologia , Células Eucarióticas/fisiologia , Proteostase/fisiologia , Autofagia/fisiologia , Reatores Biológicos , Ritmo Circadiano , Glicogênio/metabolismo , Resposta ao Choque Térmico , Ionomicina , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Metabolômica , Chaperonas Moleculares , Concentração Osmolar , Pressão Osmótica , Oxigênio/metabolismo , Biossíntese de Proteínas , Processamento de Proteína Pós-Traducional , Proteoma , Proteômica , Ribossomos , Leveduras/fisiologia
6.
Nat Commun ; 11(1): 4755, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958772

RESUMO

We hereby provide the initial portrait of lincNORS, a spliced lincRNA generated by the MIR193BHG locus, entirely distinct from the previously described miR-193b-365a tandem. While inducible by low O2 in a variety of cells and associated with hypoxia in vivo, our studies show that lincNORS is subject to multiple regulatory inputs, including estrogen signals. Biochemically, this lincRNA fine-tunes cellular sterol/steroid biosynthesis by repressing the expression of multiple pathway components. Mechanistically, the function of lincNORS requires the presence of RALY, an RNA-binding protein recently found to be implicated in cholesterol homeostasis. We also noticed the proximity between this locus and naturally occurring genetic variations highly significant for sterol/steroid-related phenotypes, in particular the age of sexual maturation. An integrative analysis of these variants provided a more formal link between these phenotypes and lincNORS, further strengthening the case for its biological relevance.


Assuntos
Homeostase , Oxigênio/metabolismo , RNA Longo não Codificante/fisiologia , Esteróis/biossíntese , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Colesterol/metabolismo , Estrogênios/metabolismo , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/metabolismo , Humanos , Células MCF-7 , Fenótipo , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
7.
Cells ; 9(9)2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32911794

RESUMO

All-trans-retinoic acid (atRA) is the essential derivative of vitamin A and is of interest due to its various biological key functions. As shown in the recent literature, atRA also plays a role in the failing heart during myocardial infarction, the leading cause of death globally. To date insufficient mechanistic information has been available on related hypoxia-induced cell damage and reperfusion injuries. However, it has been demonstrated that a reduction in cellular atRA uptake abrogates hypoxia-mediated cell and tissue damage, which may offer a new route for intervention. Consequently, in this study, the effect of the novel cardio-protective compound 5-methoxyleoligin (5ML) on cellular atRA uptake was tested in human umbilical-vein endothelial cells (HUVECs). For this purpose, a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to assess intra-cellular levels of the active substance and corresponding levels of vitamin A and its derivatives, including potential cis/trans isomers. This work also focused on light-induced isomerization and the stability of biological sample material to ensure sample integrity and avoid biased conclusions. This study provides evidence of the inhibitory effect of 5ML on cellular atRA uptake, a promising step toward a novel therapy for myocardial infarction.


Assuntos
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Oxigênio/metabolismo , Tretinoína/metabolismo , Hipóxia Celular , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lignanas/farmacologia
8.
J Med Internet Res ; 22(9): e23565, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32930099

RESUMO

BACKGROUND: Northwell Health, an integrated health system in New York, has treated more than 15,000 inpatients with COVID-19 at the US epicenter of the SARS-CoV-2 pandemic. OBJECTIVE: We describe the demographic characteristics of patients who died of COVID-19, observation of frequent rapid response team/cardiac arrest (RRT/CA) calls for non-intensive care unit (ICU) patients, and factors that contributed to RRT/CA calls. METHODS: A team of registered nurses reviewed the medical records of inpatients who tested positive for SARS-CoV-2 via polymerase chain reaction before or on admission and who died between March 13 (first Northwell Health inpatient expiration) and April 30, 2020, at 15 Northwell Health hospitals. The findings for these patients were abstracted into a database and statistically analyzed. RESULTS: Of 2634 patients who died of COVID-19, 1478 (56.1%) had oxygen saturation levels ≥90% on presentation and required no respiratory support. At least one RRT/CA was called on 1112/2634 patients (42.2%) at a non-ICU level of care. Before the RRT/CA call, the most recent oxygen saturation levels for 852/1112 (76.6%) of these non-ICU patients were at least 90%. At the time the RRT/CA was called, 479/1112 patients (43.1%) had an oxygen saturation of <80%. CONCLUSIONS: This study represents one of the largest reviewed cohorts of mortality that also captures data in nonstructured fields. Approximately 50% of deaths occurred at a non-ICU level of care despite admission to the appropriate care setting with normal staffing. The data imply a sudden, unexpected deterioration in respiratory status requiring RRT/CA in a large number of non-ICU patients. Patients admitted at a non-ICU level of care suffered rapid clinical deterioration, often with a sudden decrease in oxygen saturation. These patients could benefit from additional monitoring (eg, continuous central oxygenation saturation), although this approach warrants further study.


Assuntos
Infecções por Coronavirus/mortalidade , Demografia , Pneumonia Viral/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Estudos de Coortes , Feminino , Parada Cardíaca/epidemiologia , Parada Cardíaca/mortalidade , Mortalidade Hospitalar , Equipe de Respostas Rápidas de Hospitais , Hospitalização/estatística & dados numéricos , Humanos , Pacientes Internados/estatística & dados numéricos , Unidades de Terapia Intensiva , Masculino , Registros Médicos , Pessoa de Meia-Idade , New York/epidemiologia , Oxigênio/metabolismo , Pandemias , Adulto Jovem
9.
Proc Natl Acad Sci U S A ; 117(37): 23140-23147, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32868422

RESUMO

In higher plants, molecular responses to exogenous hypoxia are driven by group VII ethylene response factors (ERF-VIIs). These transcriptional regulators accumulate in the nucleus under hypoxia to activate anaerobic genes but are destabilized in normoxic conditions through the action of oxygen-sensing plant cysteine oxidases (PCOs). The PCOs catalyze the reaction of oxygen with the conserved N-terminal cysteine of ERF-VIIs to form cysteine sulfinic acid, triggering degradation via the Cys/Arg branch of the N-degron pathway. The PCOs are therefore a vital component of the plant oxygen signaling system, connecting environmental stimulus with cellular and physiological response. Rational manipulation of PCO activity could regulate ERF-VII levels and improve flood tolerance, but requires detailed structural information. We report crystal structures of the constitutively expressed PCO4 and PCO5 from Arabidopsis thaliana to 1.24 and 1.91 Å resolution, respectively. The structures reveal that the PCOs comprise a cupin-like scaffold, which supports a central metal cofactor coordinated by three histidines. While this overall structure is consistent with other thiol dioxygenases, closer inspection of the active site indicates that other catalytic features are not conserved, suggesting that the PCOs may use divergent mechanisms to oxidize their substrates. Conservative substitution of two active site residues had dramatic effects on PCO4 function both in vitro and in vivo, through yeast and plant complementation assays. Collectively, our data identify key structural elements that are required for PCO activity and provide a platform for engineering crops with improved hypoxia tolerance.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Oxigênio/metabolismo , Cisteína Dioxigenase/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Oxirredução , Transdução de Sinais/fisiologia , Fatores de Transcrição
10.
Curr Opin Anaesthesiol ; 33(5): 646-650, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32769747

RESUMO

PURPOSE OF REVIEW: Intraoperative hypotension (IOH) may render patients at a risk of cerebral hypoperfusion with decreasing cerebral blood flow (CBF), and lead to postoperative neurological injury. On the basis of the literature in recent years, this review attempts to refine the definition of IOH and evaluate its impact on neurological outcomes. RECENT FINDINGS: Although both absolute and relative blood pressure (BP) thresholds, with or without a cumulative period, have been used in collective clinical studies, no definitive threshold of IOH has been established for neurological complications, including perioperative stroke, postoperative cognitive disorder and delirium. The CBF is jointly modulated by multiple pressure processes (i.e. cerebral pressure autoregulation) and nonpressure processes, including patient, surgical and anaesthesia-related confounding factors. The confounding factors and variability in cerebral pressure autoregulation might impede evaluating the effect of IOH on the neurological outcomes. Furthermore, the majority of the evidence presented in this review are cohort studies, which are weak in demonstrating a cause--effect relationship between IOH and neurological complications. The maintenance of target BP based on the monitoring of regional cerebral oxygen saturation (rScO2) or cerebral pressure autoregulation seems to be associated with the decreased incidence of postoperative neurological complications. SUMMARY: Despite the lack of a known threshold value, IOH is a modifiable risk factor targeted to improve neurological outcomes. Ideal BP management is recommended in order to maintain target BP based on the monitoring of rScO2 or cerebral pressure autoregulation.


Assuntos
Circulação Cerebrovascular/fisiologia , Hipotensão/etiologia , Complicações Intraoperatórias , Complicações Pós-Operatórias , Pressão Sanguínea/fisiologia , Estudos de Coortes , Humanos , Oximetria/métodos , Oxigênio/metabolismo , Procedimentos Cirúrgicos Operatórios
11.
Medicine (Baltimore) ; 99(34): e21821, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846824

RESUMO

BACKGROUND: Traditional Chinese medicine Tongxinluo (TXL) has been widely used to treat coronary artery disease in China, since it could reduce myocardial infarct size and ischemia/reperfusion injury in both non-diabetic and diabetic conditions. It has been shown that TXL could regulate peroxisome proliferator activated receptor-α (PPAR-α), a positive modulator of angiopoietin-like 4 (Angptl4), in diabetic rats. Endothelial junction substructure components, such as VE-cadherin, are involved in the protection of reperfusion injury. Thus, we hypothesized cell-intrinsic and endothelial-specific Angptl4 mediated the protection of TXL on endothelial barrier under high glucose condition against ischemia/reperfusion-injury via PPAR-α pathway. METHODS: Incubated with high glucose medium, the human cardiac microvascular endothelial cells (HCMECs) were then exposed to oxygen-glucose-serum deprivation (2 hours) and restoration (2 hours) stimulation, with or without TXL, insulin, or rhAngptl4 pretreatment. RESULTS: TXL, insulin, and rhAngptl4 had similar protective effects on the endothelial barrier. TXL treatment reversed the endothelial barrier breakdown in HCMECs significantly as identified by decreasing endothelial permeability, upregulating the expression of JAM-A, VE-cadherin, and integrin-α5 and increasing the membrane location of VE-cadherin and integrin-α5, and these effects of TXL were as effective as insulin and rhAngptl4. However, Angptl4 knock-down with small interfering RNA (siRNA) interference and PPAR-α inhibitor MK886 partially abrogated these beneficial effects of TXL. Western blotting also revealed that similar with insulin, TXL upregulated the expression of Angptl4 in HCMECs, which could be inhibited by Angptl4 siRNA or MK886 exposure. TXL treatment increased PPAR-α activity, which could be diminished by MK886 but not by Angptl4 siRNA. CONCLUSION: These data suggest cell-intrinsic and endothelial-specific Angptl4 mediates the protection of TXL against endothelial barrier breakdown during oxygen-glucose-serum deprivation and restoration under high glucose condition partly via the PPAR-α/Angptl4 pathway.


Assuntos
Proteína 4 Semelhante a Angiopoietina/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/efeitos dos fármacos , Endotélio/efeitos dos fármacos , Endotélio/fisiopatologia , PPAR alfa/metabolismo , Proteína 4 Semelhante a Angiopoietina/genética , Proteína 4 Semelhante a Angiopoietina/farmacologia , Caderinas/metabolismo , Permeabilidade Capilar , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Vasos Coronários/citologia , Técnicas de Silenciamento de Genes , Glucose/metabolismo , Glucose/farmacologia , Humanos , Indóis/farmacologia , Insulina/farmacologia , Integrina alfa5/metabolismo , Inibidores de Lipoxigenase/farmacologia , Microvasos/citologia , Oxigênio/metabolismo , Oxigênio/farmacologia , Receptores de Superfície Celular/metabolismo , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais
12.
J Med Life ; 13(2): 206-210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742515

RESUMO

Nausea is a mental sensation of unease and discomfort before vomiting. Vomiting refers to the return of the contents of the upper gastrointestinal tract to the mouth caused by contractions of chest and abdomen muscles. Postoperative nausea and vomiting is an unpleasant experience with high treatment costs. Therefore, this study aimed to compare the effects of haloperidol, metoclopramide, dexmedetomidine, and ginger on postoperative nausea and vomiting after laparoscopy. This double-blind clinical trial was performed on all laparoscopy candidates at Valiasr hospital, Arak, Iran. The patients were randomly divided into four groups (haloperidol, metoclopramide, dexmedetomidine and ginger), and all patients underwent general anesthesia using fentanyl, midazolam, atracurium, and propofol. After intubation, tube fixation, and stable hemodynamic conditions, the patients received four ginger capsules with a hint of lemon. A group of patients received 25 µg of dexmedetomidine. In the Plasil group, 10 mg of metoclopramide was given 30 minutes before the completion of surgery. In addition, 0.5 cc of haloperidol (5 mg) was administered to a group of patients. Heart rate, blood pressure, and oxygen saturation were recorded from the beginning of surgery, every 15 minutes until the end of the surgery. Furthermore, the occurrence of nausea and vomiting was recorded during recovery, 2 and 4 hours after surgery. Data were then analyzed using the SPSS software v.23. Eighty-eight patients were enrolled in the study. The youngest and the oldest were 30 years and 70 years old, respectively, and the mean age was 48.02 ± 9.31 years. Moreover, the number of women in the four groups was higher than that of men. Blood pressure in the dexmedetomidine group was lower than the other four groups (P <0.05). The lowest heart rate was observed in the haloperidol group, while the highest heart rate was seen in the plasil group (P <0.05). The occurrence of vomiting and nausea was not significantly different between the four groups (P <0.05). Our results showed no significant difference in postoperative nausea and vomiting between the four drugs. Due to the hemodynamic changes induced by each drug, it is best to use these drugs based on the patient's condition. Ginger is also a herbal remedy that has fewer side effects, and this drug can be a good option for patients when there is no contraindication.


Assuntos
Colecistectomia Laparoscópica/efeitos adversos , Dexmedetomidina/uso terapêutico , Gengibre/química , Haloperidol/uso terapêutico , Metoclopramida/uso terapêutico , Extratos Vegetais/uso terapêutico , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Náusea e Vômito Pós-Operatórios/etiologia , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Dexmedetomidina/farmacologia , Método Duplo-Cego , Feminino , Haloperidol/farmacologia , Humanos , Irã (Geográfico) , Masculino , Metoclopramida/farmacologia , Pessoa de Meia-Idade , Oxigênio/metabolismo
13.
Int J Nanomedicine ; 15: 5687-5700, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821097

RESUMO

Background and Purpose: Sonodynamic therapy (SDT) has been widely used for the noninvasive treatment of solid tumors, but the hypoxic tumor microenvironment limits its therapeutic effect. The current methods of reoxygenation to enhance SDT have limitations, prompting reconsideration of the design of therapeutic approaches. Here, we developed a tumor microenvironment-responsive nanoplatform by reducing oxygen consumption to overcome hypoxia-induced resistance to cancer therapy. Methods: A pH-responsive drug-loaded liposome (MI-PEOz-lip) was prepared and used to reduce oxygen consumption, attenuating hypoxia-induced resistance to SDT and thereby improving therapeutic efficiency. Photoacoustic imaging (PAI) and fluorescence imaging (FI) of MI-PEOz-lip were evaluated in vitro and in breast xenograft tumor models. The pH-sensitive functionality of MI-PEOz-lip was applied for pH-triggered cargo release, and its capacity was evaluated. The MI-PEOz-lip-mediated SDT effect was compared with other treatments in vivo. Results: MI-PEOz-lip was demonstrated to specifically accumulate in tumors. Metformin molecules in liposomes selectively accumulate in tumors by pH-responsive drug release to inhibit the mitochondrial respiratory chain while releasing IR780 to the tumor area. These pH-responsive liposomes demonstrated PAI and FI imaging capabilities in vitro and in vivo, providing potential for treatment guidance and monitoring. In particular, the prepared MI-PEOz-lip combined with ultrasound irradiation effectively inhibited breast tumors by producing toxic reactive singlet oxygen species (ROS), while the introduction of metformin inhibited mitochondrial respiration and reduced tumor oxygen consumption, resulting in excellent sonodynamic therapy performance compared with other treatments. Conclusion: In this study, we present a novel strategy to achieve high therapeutic efficacy of SDT by the rational design of multifunctional nanoplatforms. This work provides a new strategy that can solve the current problems of inefficient oxygen delivery strategies and weaken resistance to various oxygen-dependent therapies.


Assuntos
Mitocôndrias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Hipóxia Tumoral , Terapia por Ultrassom , Animais , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Respiração Celular/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Lipossomos , Metformina/farmacologia , Camundongos , Oxigênio/metabolismo , Técnicas Fotoacústicas , Distribuição Tecidual/efeitos dos fármacos , Microambiente Tumoral
14.
PLoS Comput Biol ; 16(8): e1008157, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32817659

RESUMO

Oxygen (O2) delivery facilitated by hemoglobin (Hb)-based O2 carriers (HBOCs) is a promising strategy to increase the effectiveness of chemotherapeutics for treatment of solid tumors. However, the heterogeneous vascular structures present within tumors complicates evaluating the oxygenation potential of HBOCs within the tumor microenvironment. To account for spatial variations in the vasculature and tumor tissue that occur during tumor growth, we used a computational model to develop artificial tumor constructs. With these simulated tumors, we performed a polymerized human hemoglobin (hHb) (PolyhHb) enhanced oxygenation simulation accounting for differences in the physiologic characteristics of human and mouse blood. The results from this model were used to determine the potential effectiveness of different treatment options including a top load (low volume) and exchange (large volume) infusion of a tense quaternary state (T-State) PolyhHb, relaxed quaternary state (R-State) PolyhHb, and a non O2 carrying control. Principal component analysis (PCA) revealed correlations between the different regimes of effectiveness within the different simulated dosage options. In general, we found that infusion of T-State PolyhHb is more likely to decrease tissue hypoxia and modulate the metabolic rate of O2 consumption. Though the developed models are not a definitive descriptor of O2 carrier interaction in tumor capillary networks, we accounted for factors such as non-uniform vascular density and permeability that limit the applicability of O2 carriers during infusion. Finally, we have used these validated computational models to establish potential benchmarks to guide tumor treatment during translation of PolyhHb mediated therapies into clinical applications.


Assuntos
Hemoglobinas/metabolismo , Neoplasias/irrigação sanguínea , Oxigênio/administração & dosagem , Animais , Humanos , Camundongos , Neoplasias/patologia , Oxigênio/metabolismo
15.
PLoS One ; 15(8): e0236720, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32776946

RESUMO

Hemoglobin (Hb) is associated with cerebral oxygenation status owing to its important role of carrying oxygen to systemic tissues. However, data concerning the associations between Hb levels and cerebral regional oxygen saturation (rSO2) of hemodialysis (HD) patients is limited. We aimed to identify these associations to consider a target Hb level for renal anemia management. This study included 375 HD patients. Cerebral rSO2 before HD was monitored using the INVOS 5100c oxygen saturation monitor. Multivariable linear regression analysis showed that cerebral rSO2 was independently associated with natural logarithm (Ln)-HD duration (standardized coefficient: -0.36), mean blood pressure (standardized coefficient: 0.13), pH (standardized coefficient: -0.10), serum albumin (standardized coefficient: 0.14), presence of diabetes mellitus (standardized coefficient: -0.20), and Hb level (standardized coefficient: 0.29). Furthermore, a generalized linear model with restricted cubic spline function was used to investigate the non-linear association between cerebral rSO2 and Hb levels. In the multivariable analysis for the adjustment with Ln-HD duration, mean blood pressure, pH, serum albumin, and presence of diabetes mellitus, a linear relationship was demonstrated between the two variables (p for linearity = 0.79). Hb levels revealed the positive and significant association with cerebral rSO2 in this study. Moreover, the relationship between cerebral rSO2 and Hb level was proven to be linear. Therefore, the target Hb level in renal anemia management would be considered to be the upper limits for the appropriate management of renal anemia by previous guidelines and position statement from the viewpoint of maintaining cerebral oxygenation in HD patients.


Assuntos
Encéfalo/metabolismo , Hemoglobinas/metabolismo , Oxigênio/metabolismo , Diálise Renal , Espectroscopia de Luz Próxima ao Infravermelho , Idoso , Feminino , Humanos , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Masculino
16.
Gene ; 761: 145039, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32777527

RESUMO

The wood frog (Rana sylvatica) can tolerate full body freezing in winter. As a protective response, wood frogs dehydrate their cells and accumulate large quantities of glucose as an intracellular cryoprotectant. Freezing causes ischemia since blood delivery to organs is interrupted. Fascinatingly, wood frogs can tolerate dehydration, extreme hyperglycemia, and anoxia independently of freezing. In response to low oxygen levels, wood frogs strategically reduce their metabolic rates and allocate the finite amount of intracellular fuel available to pro-survival processes while reducing or interrupting all others. In this study, the involvement of advanced glycation end products (AGEs) and the high mobility group box 1 (HMGB1) protein in activating RAGE (AGE receptor) were investigated. The results show that freezing, anoxia and dehydration induced the expression of total HMGB1 and its acetylation in the heart. RAGE levels were induced in response to all stress conditions, which resulted in differential regulation of the ETS1 transcription factor. While the nuclear localization of total ETS1 was not affected, the DNA binding activity of total and its active form increased in response to freezing and dehydration but not in response to anoxia. Current results indicate that ETS1 acts as a transcriptional activator for peroxiredoxin 1 in response to freezing but acts as a transcriptional repressor of several nuclear-encoded mitochondrial genes in response to all stresses. Altogether, current results show that the HMGB1/RAGE axis may activate ETS1 and that this activation could result in both transcriptional activation and/or repression in a stress-dependent manner.


Assuntos
Mitocôndrias/metabolismo , Miocárdio/metabolismo , Ranidae/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Desidratação/metabolismo , Congelamento , Glucose/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Produtos Finais de Glicação Avançada/fisiologia , Proteína HMGB1/metabolismo , Proteína HMGB1/fisiologia , Coração/fisiologia , Hipóxia/metabolismo , Oxigênio/metabolismo , Ranidae/genética , Receptor para Produtos Finais de Glicação Avançada/fisiologia , Estresse Fisiológico/fisiologia
17.
PLoS One ; 15(8): e0237388, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760167

RESUMO

INTRODUCTION: The heart rate (HR) method is a promising approach for evaluating oxygen uptake ([Formula: see text]), energy demands and exercise intensities in different forms of physical activities. It would be valuable if the HR method, established on ergometer cycling, is interchangeable with other regular activities, such as level walking. This study therefore aimed to examine the interchangeability of the HR method when estimating [Formula: see text] for ergometer cycling and level treadmill walking in submaximal conditions. METHODS: Two models of [Formula: see text] regression equations for cycle ergometer exercise (CEE) and treadmill exercise (TE) were established with 34 active commuters. Model 1 consisted of three submaximal intensities of ergometer cycling or level walking, model 2 included also one additional workload of maximal ergometer cycling or running. The regression equations were used for estimating [Formula: see text] with seven individual HR values based on 25-85% of HR reserve (HRR). The [Formula: see text] estimations were compared between CEE and TE, within and between each model. RESULTS: Only minor, and in most cases non-significant, average differences were observed when comparing the estimated [Formula: see text] levels between CEE and TE. Model 1 ranged from -0.4 to 4.8% (n.s.) between 25-85%HRR. In model 2, the differences between 25-65%HRR ranged from 1.3 to -2.7% (n.s.). At the two highest intensities, 75 and 85%HRR, [Formula: see text] was slightly lower (3.7%, 4.4%; P < 0.05), for CEE than TE. The inclusion of maximal exercise in the [Formula: see text] relationships reduced the individual [Formula: see text] variations between the two exercise modalities. CONCLUSION: The HR methods, based on submaximal ergometer cycling and level walking, are interchangeable for estimating mean [Formula: see text] levels between 25-85% of HRR. Essentially, the same applies when adding maximal exercise in the [Formula: see text] relationships. The inter-individual [Formula: see text] variation between ergometer cycling and treadmill exercise is reduced when using the HR method based on both submaximal and maximal workloads.


Assuntos
Ergometria/instrumentação , Teste de Esforço/instrumentação , Frequência Cardíaca , Caminhada/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismo
18.
Science ; 369(6506)2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32820091

RESUMO

Oxygenic photosynthesis is the main process that drives life on earth. It starts with the harvesting of solar photons that, after transformation into electronic excitations, lead to charge separation in the reaction centers of photosystems I and II (PSI and PSII). These photosystems are large, modular pigment-protein complexes that work in series to fuel the formation of carbohydrates, concomitantly producing molecular oxygen. Recent advances in cryo-electron microscopy have enabled the determination of PSI and PSII structures in complex with light-harvesting components called "supercomplexes" from different organisms at near-atomic resolution. Here, we review the structural and spectroscopic aspects of PSI and PSII from plants and algae that directly relate to their light-harvesting properties, with special attention paid to the pathways and efficiency of excitation energy transfer and the regulatory aspects.


Assuntos
Proteínas de Algas/química , Clorófitas/enzimologia , Oxigênio/farmacologia , Fotossíntese , Complexo de Proteína do Fotossistema I/química , Complexo de Proteína do Fotossistema II/química , Microscopia Crioeletrônica , Transferência de Energia , Oxigênio/metabolismo , Fótons
19.
PLoS One ; 15(8): e0237596, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785283

RESUMO

Blood was collected from wild captured green and Kemp's ridley turtles off the west coast of Florida, USA. Blood gases and biochemical values were analyzed using a point of care (POC) device in the field. Analytes include pH, partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), total carbon dioxide (TCO2), bicarbonate (HCO3), base excess (BE), oxygen saturation (sO2), lactate, sodium (Na), potassium (K), chloride (Cl), total carbon dioxide (TCO2), anion gap, ionized calcium, glucose, blood urea nitrogen (BUN), creatinine (Crea), hematocrit (Hct), and hemoglobin (Hb). These are novel data for wild healthy Kemp's ridley turtles, and results for green turtles were generally consistent with past studies of green turtles with exceptions primarily in blood gas values. Ninety percent of the green turtles had fibropapillomatosis (FP), but none of the blood analytes were correlated with disease severity. Only BUN was correlated with weight of green turtles, and there was no correlation between blood parameters and weight of Kemp's ridley turtles. This study provides data that are useful in understanding the physiologic status of sea turtles specific to this region, allowing for comparisons to other populations, life stages, and disease states.


Assuntos
Gasometria/veterinária , Nitrogênio da Ureia Sanguínea , Oxigênio/metabolismo , Tartarugas/metabolismo , Veias/metabolismo , Animais , Bicarbonatos/análise , Dióxido de Carbono/análise , Potássio/análise , Sódio/análise , Tartarugas/classificação
20.
Eur Rev Med Pharmacol Sci ; 24(15): 8219-8225, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32767353

RESUMO

OBJECTIVE: At the end of 2019, the Novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), spread rapidly from China to the whole world. Circadian rhythms can play crucial role in the complex interplay between viruses and organisms, and temporized schedules (chronotherapy) have been positively tested in several medical diseases. We aimed to compare the possible effects of a morning vs. evening antiviral administration in COVID patients. PATIENTS AND METHODS: We retrospectively evaluated all patients admitted to COVID internal medicine units with confirmed SARS-CoV-2 infection, and treated with darunavir-ritonavir (single daily dose, for seven days). Age, sex, length of stay (LOS), pharmacological treatment, and timing of antiviral administration (morning or evening), were recorded. Outcome indicators were death or LOS, and laboratory parameters, e.g., variations in C-reactive protein (CRP) levels, ratio of arterial oxygen partial pressure (PaO2, mmHg) to fractional inspired oxygen (FiO2) (PaO2/FiO2), and leucocyte count. RESULTS: The total sample consisted of 151 patients, 33 (21.8%) of whom were selected for antiviral treatment. The mean age was 61.8±18.3 years, 17 (51.5%) were male, and the mean LOS was 13.4±8.6 days. Nine patients (27.3%) had their antiviral administration in the morning, and 24 (72.7%) had antiviral administration in the evening. No fatalities occurred. Despite the extremely limited sample size, morning group subjects showed a significant difference in CRP variation, compared to that in evening group subjects (-65.82±33.26 vs. 83.32±304.89, respectively, p<0.032). No significant differences were found for other parameters. CONCLUSIONS: This report is the first study evaluating temporized morning vs. evening antiviral administration in SARS-CoV-2 patients. The morning regimen was associated with a significant reduction in CRP values. Further confirmations with larger and multicenter samples of patients could reveal novel potentially useful insights.


Assuntos
Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Darunavir/administração & dosagem , Cronoterapia Farmacológica , Mortalidade Hospitalar , Tempo de Internação/estatística & dados numéricos , Pneumonia Viral/tratamento farmacológico , Ritonavir/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Gasometria , Proteína C-Reativa , Infecções por Coronavirus/metabolismo , Quimioterapia Combinada , Humanos , Itália , Contagem de Leucócitos , Pessoa de Meia-Idade , Oxigênio/metabolismo , Pandemias , Pressão Parcial , Pneumonia Viral/metabolismo , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA