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1.
Nat Commun ; 12(1): 5243, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475406

RESUMO

Peroxisome, a special cytoplasmic organelle, possesses one or more kinds of oxidases for hydrogen peroxide (H2O2) production and catalase for H2O2 degradation, which serves as an intracellular H2O2 regulator to degrade toxic peroxides to water. Inspired by this biochemical pathway, we demonstrate the reactive oxygen species (ROS) induced tumor therapy by integrating lactate oxidase (LOx) and catalase (CAT) into Fe3O4 nanoparticle/indocyanine green (ICG) co-loaded hybrid nanogels (designated as FIGs-LC). Based on the O2 redistribution and H2O2 activation by cascading LOx and CAT catalytic metabolic regulation, hydroxyl radical (·OH) and singlet oxygen (1O2) production can be modulated for glutathione (GSH)-activated chemodynamic therapy (CDT) and NIR-triggered photodynamic therapy (PDT), by manipulating the ratio of LOx and CAT to catalyze endogenous lactate to produce H2O2 and further cascade decomposing H2O2 into O2. The regulation reactions of FIGs-LC significantly elevate the intracellular ROS level and cause fatal damage to cancer cells inducing the effective inhibition of tumor growth. Such enzyme complex loaded hybrid nanogel present potential for biomedical ROS regulation, especially for the tumors with different redox state, size, and subcutaneous depth.


Assuntos
Antineoplásicos/farmacologia , Nanogéis/química , Peroxissomos/enzimologia , Fotoquimioterapia/métodos , Animais , Antineoplásicos/química , Catalase/química , Catalase/metabolismo , Catálise , Linhagem Celular Tumoral , Óxido Ferroso-Férrico/química , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Verde de Indocianina/química , Camundongos , Oxigenases de Função Mista/química , Oxigenases de Função Mista/metabolismo , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral/efeitos dos fármacos
2.
BMC Plant Biol ; 21(1): 376, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399701

RESUMO

BACKGROUND: Glycolytic pathway is common in all plant organs, especially in oxygen-deficient tissues. Phosphofructokinase (PFK) is a rate-limiting enzyme in the glycolytic pathway and catalyses the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate. Cassava (M. esculenta) root is a huge storage organ with low amount of oxygen. However, less is known about the functions of PFK from M. esculenta (MePFK). We conducted a systematic analysis of MePFK genes to explore the function of the MePFK gene family under hypoxic stress. RESULTS: We identified 13 MePFK genes and characterised their sequence structure. The phylogenetic tree divided the 13 genes into two groups: nine were MePFKs and four were pyrophosphate-fructose-6-phosphate phosphotransferase (MePFPs). We confirmed by green fluorescent protein fusion protein expression that MePFK03 and MePFPA1 were localised in the chloroplast and cytoplasm, respectively. The expression profiles of the 13 MePFKs detected by quantitative reverse transcription polymerase chain reaction revealed that MePFK02, MePFK03, MePFPA1, MePFPB1 displayed higher expression in leaves, root and flower. The expression of MePFK03, MePFPA1 and MePFPB1 in tuber root increased gradually with plant growth. We confirmed that hypoxia occurred in the cassava root, and the concentration of oxygen was sharply decreasing from the outside to the inside root. The expression of MePFK03, MePFPA1 and MePFPB1 decreased with the decrease in the oxygen concentration in cassava root. Waterlogging stress treatment showed that the transcript level of PPi-dependent MePFP and MeSuSy were up-regulated remarkably and PPi-dependent glycolysis bypass was promoted. CONCLUSION: A systematic survey of phylogenetic relation, molecular characterisation, chromosomal and subcellular localisation and cis-element prediction of MePFKs were performed in cassava. The expression profiles of MePFKs in different development stages, organs and under waterlogging stress showed that MePFPA1 plays an important role during the growth and development of cassava. Combined with the transcriptional level of MeSuSy, we found that pyrophosphate (PPi)-dependent glycolysis bypass was promoted when cassava was under waterlogging stress. The results would provide insights for further studying the function of MePFKs under hypoxic stress.


Assuntos
Genoma de Planta , Manihot/enzimologia , Manihot/genética , Fosfofrutoquinases/genética , Fosfofrutoquinases/metabolismo , Cloroplastos/enzimologia , Mapeamento Cromossômico , Cromossomos de Plantas , Sequência Conservada , Citoplasma/enzimologia , Éxons , Flores/enzimologia , Íntrons , Família Multigênica , Oxigênio/metabolismo , Filogenia , Folhas de Planta/enzimologia , Raízes de Plantas/enzimologia , Regiões Promotoras Genéticas , Estresse Fisiológico/genética , Transcriptoma
5.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445551

RESUMO

Cancer-specific isoenzyme of phosphofructokinase II (PFKFB4), as our previous research has shown, may be one of the most important enzymes contributing to the intensification of glycolysis in hypoxic malignant melanoma cells. Although the PFKFB4 gene seems to play a crucial role in the progression of melanoma, so far there are no complete data on the expression of PFKFB4 at the isoform level and the influence of hypoxia on alternative splicing. Using RT-qPCR and semi-quantitative RT-PCR, we presented the PFKFB4 gene expression profile at the level of six isoforms described in the OMIM NCBI database in normoxic and hypoxic melanoma cells. Additionally, using VMD software, we analyzed the structure of isoforms at the protein level, concluding about the catalytic activity of individual isoforms. Our research has shown that five isoforms of PFKFB4 are expressed in melanoma cells, of which the D and F isoforms are highly constitutive, while the canonical B isoform seems to be the main isoform induced in hypoxia. Our results also indicate that the expression profile at the level of the PFKFB4 gene does not reflect the expression at the level of individual isoforms. Our work clearly indicates that the PFKFB4 gene expression profile should be definitely analyzed at the level of individual isoforms. Moreover, the analysis at the protein level allowed the selection of those isoforms whose functional validation should be performed to fully understand the importance of PFKFB4 expression in the metabolic adaptation of malignant melanoma cells.


Assuntos
Processamento Alternativo , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Hipóxia/fisiopatologia , Melanoma/patologia , Oxigênio/metabolismo , Fosfofrutoquinase-2/genética , Biomarcadores Tumorais/genética , Glicólise , Humanos , Melanoma/genética , Melanoma/metabolismo , Células Tumorais Cultivadas
6.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360967

RESUMO

Microbial biodegradation is one of the acceptable technologies to remediate and control the pollution by polycyclic aromatic hydrocarbon (PAH). Several bacteria, fungi, and cyanobacteria strains have been isolated and used for bioremediation purpose. This review paper is intended to provide key information on the various steps and actors involved in the bacterial and fungal aerobic and anaerobic degradation of pyrene, a high molecular weight PAH, including catabolic genes and enzymes, in order to expand our understanding on pyrene degradation. The aerobic degradation pathway by Mycobacterium vanbaalenii PRY-1 and Mycobactetrium sp. KMS and the anaerobic one, by the facultative bacteria anaerobe Pseudomonas sp. JP1 and Klebsiella sp. LZ6 are reviewed and presented, to describe the complete and integrated degradation mechanism pathway of pyrene. The different microbial strains with the ability to degrade pyrene are listed, and the degradation of pyrene by consortium is also discussed. The future studies on the anaerobic degradation of pyrene would be a great initiative to understand and address the degradation mechanism pathway, since, although some strains are identified to degrade pyrene in reduced or total absence of oxygen, the degradation pathway of more than 90% remains unclear and incomplete. Additionally, the present review recommends the use of the combination of various strains of anaerobic fungi and a fungi consortium and anaerobic bacteria to achieve maximum efficiency of the pyrene biodegradation mechanism.


Assuntos
Klebsiella/metabolismo , Mycobacterium/metabolismo , Pseudomonas/metabolismo , Pirenos/metabolismo , Klebsiella/genética , Consórcios Microbianos , Mycobacterium/genética , Oxigênio/metabolismo , Pseudomonas/genética
7.
ACS Appl Mater Interfaces ; 13(33): 39055-39065, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433248

RESUMO

Polymer photosensitizers (PPSs) with the distinctive properties of good light-harvesting capability, high photostability, and excellent tumor retention effects have aroused great research interest in photodynamic therapy (PDT). However, their potential translation into clinic was often constrained by the hypoxic nature of tumor microenvironment, the aggregation-caused reduced production of reactive oxygen species (ROS), and the tedious procedure of manufacture. As a powerful and versatile strategy, vacancy engineering possesses the unique capability to effectively improve the photogenerated electron efficiency of nanomaterials for high-performance O2 and ROS production. Herein, by introducing vacancy engineering into the design of PPSs for PDT for the first time, we synthesized a novel PPS of Au-decorated polythionine (PTh) nanoconstructs (PTh@Au NCs) with the unique integrated features of distinguished O2 self-evolving function and highly efficient ROS generation for achieving the greatly enhanced PDT efficacy toward hypoxic tumor both in vitro and in vivo. The incorporation of Au into PTh leads to the special PTh-Au heterostructure-induced sulfur vacancies in PTh@Au NCs, which results in an efficient electron-hole separation performance and also plays a key role in a long lifetime of free electrons and holes. Accordingly, an ∼2- to 3-fold ROS generation and an ∼1.5-fold increase of O2 self-supply than the pure PTh nanoparticles (NPs) were obtained even under hypoxic conditions upon exposure to 650 nm light. By combining such superior ROS generation and O2 self-supply performances with the outstanding cellular internalization and tumor accumulation capacities, an advanced antitumor effect with the achievement of almost complete hypoxic tumor elimination in vivo or 88% cell destruction in vitro was acquired by the PTh@Au NCs. In addition, the distinctive facile one-step redox strategy for PTh@Au NCs synthesis compared to the reported PPSs for PDT also makes it beneficial for potential practical application. The first introduction of vacancy engineering concept into PPSs in the field of PDT proposed in this work offers a new strategy for the development and design highly efficient PPSs for PDT applications.


Assuntos
Antineoplásicos/química , Ouro/química , Nanopartículas Metálicas/química , Fenotiazinas/química , Fármacos Fotossensibilizantes/química , Polímeros/química , Animais , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Feminino , Humanos , Hipóxia/metabolismo , Camundongos , Neoplasias Experimentais , Oxigênio/metabolismo , Fenotiazinas/farmacocinética , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacocinética , Polímeros/farmacocinética , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica , Microambiente Tumoral
8.
Theranostics ; 11(16): 7813-7828, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335966

RESUMO

Non-invasive monitoring of hemodynamic tumor responses to chemotherapy could provide unique insights into the development of therapeutic resistance and inform therapeutic decision-making in the clinic. Methods: Here, we examined the longitudinal and dynamic effects of the common chemotherapeutic drug Taxotere on breast tumor (KPL-4) blood volume and oxygen saturation using eigenspectra multispectral optoacoustic tomography (eMSOT) imaging over a period of 41 days. Tumor vascular function was assessed by dynamic oxygen-enhanced eMSOT (OE-eMSOT). The obtained in vivo optoacoustic data were thoroughly validated by ex vivo cryoimaging and immunohistochemical staining against markers of vascularity and hypoxia. Results: We provide the first preclinical evidence that prolonged treatment with Taxotere causes a significant drop in mean whole tumor oxygenation. Furthermore, application of OE-eMSOT showed a diminished vascular response in Taxotere-treated tumors and revealed the presence of static blood pools, indicating increased vascular permeability. Conclusion: Our work has important translational implications and supports the feasibility of eMSOT imaging for non-invasive assessment of tumor microenvironmental responses to chemotherapy.


Assuntos
Neoplasias da Mama/metabolismo , Hemodinâmica/fisiologia , Tomografia Óptica/métodos , Animais , Neoplasias da Mama/diagnóstico por imagem , Linhagem Celular Tumoral , Docetaxel/farmacologia , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hipóxia/metabolismo , Camundongos , Camundongos SCID , Oxigênio/metabolismo , Técnicas Fotoacústicas/métodos , Tomografia/métodos , Tomografia Computadorizada por Raios X/métodos , Microambiente Tumoral/fisiologia
9.
Glob Heart ; 16(1): 47, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381669

RESUMO

Background: The implications of city lockdown on vital signs during the COVID-19 outbreak are unknown. Objective: We longitudinally tracked vital signs using data from wearable sensors and determined associations with anxiety and depression. Methods: We selected all participants in the HUAWEI Heart Study from Wuhan and four nearby large provincial capital cities (Guangzhou, Chongqing, Hangzhou, Zhengzhou) and extracted all data from 26 December 2019 (one month before city lockdown) to 21 February 2020. Sleep duration and quality, daily steps, oxygen saturation and heart rate were collected on a daily basis. We compared the vital signs before and after the lockdown using segmented regression analysis of the interrupted time series. The depression and anxiety cases were defined as scores ≥8 on the Hospital Anxiety and Depression Scale depression and anxiety subscales [HADS-D and HADS-A] in 727 participants who finished the survey. Results: We included 19,960 participants (mean age 36 yrs, 90% men). Compared with pre-lockdown, resting heart rate dropped immediately by 1.1 bpm after city lockdown (95% confidence interval [CI]: -1.8, -0.4). Sleep duration increased by 0.5 hour (95% CI: 0.3, 0.8) but deep sleep ratio decreased by 0.9% (95% CI: -1.2, -0.6). Daily steps decreased by 3352 steps (95% CI: -4333, -2370). Anxiety and depression existed in 26% and 17% among 727 available participants, respectively, and associated with longer sleep duration (0.2 and 0.1 hour, both p < 0.001). Conclusions: Lockdown of Wuhan in China was associated with an adverse vital signs profile (reduced physical activity, heart rate, and sleep quality, but increased sleep duration). Wearable devices in combination with mobile-based apps may be useful to monitor both physical and mental health. Clinical trial registration: The trial is registered at Chinese Clinical Trial Registry (ChiCTR) website (ChiCTR-OOC-17014138).


Assuntos
COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Exercício Físico , Frequência Cardíaca , Oxigênio/metabolismo , Política Pública , Sono , Adulto , Ansiedade/psicologia , China/epidemiologia , Cidades/epidemiologia , Depressão/psicologia , Feminino , Humanos , Análise de Séries Temporais Interrompida , Masculino , Pessoa de Meia-Idade , Oximetria , Estudos Retrospectivos , SARS-CoV-2 , Sinais Vitais , Dispositivos Eletrônicos Vestíveis , Adulto Jovem
10.
Zool Res ; 42(5): 592-605, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34387415

RESUMO

The large yellow croaker (Larimichthys crocea), which is an economically important mariculture fish in China, is often exposed to environmental hypoxia. Reactive oxygen species (ROS) homeostasis is essential for the maintenance of normal physiological conditions in an organism. Direct evidence that environmental hypoxia leads to ROS overproduction is scarce in marine fish. Furthermore, the sources of ROS overproduction in marine fish under hypoxic stress are poorly known. In this study, we investigated the effects of hypoxia on redox homeostasis in L. crocea and the impact of impaired redox homeostasis on fish. We first confirmed that hypoxia drove ROS production mainly via the mitochondrial electron transport chain and NADPH oxidase complex pathways in L. crocea and its cell line (large yellow croaker fry (LYCF) cells). We subsequently detected a marked increase in the antioxidant systems of the fish. However, imbalance between the pro-oxidation and antioxidation systems ultimately led to excessive ROS and oxidative stress. Cell viability showed a remarkable decrease while oxidative indicators, such as malondialdehyde, protein carbonylation, and 8-hydroxy-2 deoxyguanosine, showed a significant increase after hypoxia, accompanied by tissue damage. N-acetylcysteine (NAC) reduced ROS levels, alleviated oxidative damage, and improved cell viability in vitro. Appropriate uptake of ROS scavengers (e.g., NAC and elamipretide Szeto-Schiller-31) and inhibitors (e.g., apocynin, diphenylene iodonium, and 5-hydroxydecanoate) may be effective at overcoming hypoxic toxicity. Our findings highlight previously unstudied strategies of hypoxic toxicity resistance in marine fish.


Assuntos
Antioxidantes/metabolismo , Peixes/metabolismo , Estresse Oxidativo/fisiologia , Oxigênio/química , Oxigênio/metabolismo , Espécies Reativas de Oxigênio , Animais , Linhagem Celular , Sobrevivência Celular , Meio Ambiente , Homeostase , NADP
11.
Science ; 373(6553)2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34437092

RESUMO

Systematic and extensive investigation of enzymes is needed to understand their extraordinary efficiency and meet current challenges in medicine and engineering. We present HT-MEK (High-Throughput Microfluidic Enzyme Kinetics), a microfluidic platform for high-throughput expression, purification, and characterization of more than 1500 enzyme variants per experiment. For 1036 mutants of the alkaline phosphatase PafA (phosphate-irrepressible alkaline phosphatase of Flavobacterium), we performed more than 670,000 reactions and determined more than 5000 kinetic and physical constants for multiple substrates and inhibitors. We uncovered extensive kinetic partitioning to a misfolded state and isolated catalytic effects, revealing spatially contiguous regions of residues linked to particular aspects of function. Regions included active-site proximal residues but extended to the enzyme surface, providing a map of underlying architecture not possible to derive from existing approaches. HT-MEK has applications that range from understanding molecular mechanisms to medicine, engineering, and design.


Assuntos
Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Fosfatase Alcalina/antagonistas & inibidores , Fosfatase Alcalina/química , Biocatálise , Domínio Catalítico , Flavobacterium/enzimologia , Hidrólise , Cinética , Microfluídica , Modelos Moleculares , Mutação , Oxigênio/metabolismo , Fosfatos/metabolismo , Conformação Proteica , Dobramento de Proteína , Termodinâmica
12.
Nat Commun ; 12(1): 4621, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330928

RESUMO

Cytochromes bd are ubiquitous amongst prokaryotes including many human-pathogenic bacteria. Such complexes are targets for the development of antimicrobial drugs. However, an understanding of the relationship between the structure and functional mechanisms of these oxidases is incomplete. Here, we have determined the 2.8 Å structure of Mycobacterium smegmatis cytochrome bd by single-particle cryo-electron microscopy. This bd oxidase consists of two subunits CydA and CydB, that adopt a pseudo two-fold symmetrical arrangement. The structural topology of its Q-loop domain, whose function is to bind the substrate, quinol, is significantly different compared to the C-terminal region reported for cytochromes bd from Geobacillus thermodenitrificans (G. th) and Escherichia coli (E. coli). In addition, we have identified two potential oxygen access channels in the structure and shown that similar tunnels also exist in G. th and E. coli cytochromes bd. This study provides insights to develop a framework for the rational design of antituberculosis compounds that block the oxygen access channels of this oxidase.


Assuntos
Proteínas de Bactérias/ultraestrutura , Microscopia Crioeletrônica/métodos , Grupo dos Citocromos b/ultraestrutura , Complexo de Proteínas da Cadeia de Transporte de Elétrons/ultraestrutura , Mycobacterium smegmatis/enzimologia , Oxirredutases/ultraestrutura , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Grupo dos Citocromos b/química , Grupo dos Citocromos b/metabolismo , Transporte de Elétrons , Complexo de Proteínas da Cadeia de Transporte de Elétrons/química , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Heme/química , Heme/metabolismo , Modelos Moleculares , Mycobacterium smegmatis/genética , Oxirredutases/química , Oxirredutases/metabolismo , Oxigênio/metabolismo , Conformação Proteica , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/ultraestrutura , Especificidade por Substrato
13.
J Plant Physiol ; 264: 153471, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34315029

RESUMO

During germination, the availability of sugars, oxygen, or cellular energy fluctuates under dynamic environmental conditions, likely affecting the global RNA profile of rice genes. Most genes that exhibit sugar-regulation in rice embryos under aerobic conditions are responsive to low energy and anaerobic conditions, indicating that sugar regulation is strongly associated with energy and anaerobic signaling. The interference pattern of sugar regulation by either anaerobic or low energy conditions indicates that induction is likely the more prevalent regulatory mechanism than repression for altering the expression of sugar-regulated genes. Among the aerobically sugar-regulated genes, limited genes exhibit sugar regulation under anaerobic conditions, indicating that anaerobic conditions strongly influence sugar regulated gene expression. Anaerobically responsive genes substantially overlap with low energy responsive genes. In particular, the expression levels of anaerobically downregulated genes are consistent with those provoked by low energy conditions, suggesting that anaerobic downregulation results from the prevention of aerobic respiration due to the absence of the final electron acceptor, i.e., molecular oxygen. It has been noted that abscisic acid (ABA) responsive genes are over representative of genes upregulated under low energy conditions, in contrast to downregulated genes. This suggests that either ABA itself or upstream signaling components of the ABA signaling pathway are likely to be involved in the signaling pathways activated by low energy conditions.


Assuntos
Germinação , Oryza/embriologia , Sementes/metabolismo , Metabolismo Energético , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Análise de Sequência com Séries de Oligonucleotídeos , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Sementes/crescimento & desenvolvimento , Açúcares/metabolismo
14.
DNA Cell Biol ; 40(7): 979-987, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34227845

RESUMO

Long noncoding RNA X-inactive specific transcript (XIST) has been identified as a crucial regulator in neurodegenerative disorders. However, the role and mechanism of XIST in ischemic stroke remain elusive. In our study, we found that XIST expression was upregulated in both mice subjected to middle cerebral artery occlusion and oxygen-glucose deprivation (OGD)-treated neurons. Functional assays disclosed that the interference of XIST accelerated viability, and suppressed apoptosis and caspase-3 activity in OGD-treated neurons. Moreover, XIST interacted with miR-98, and miR-98 targeted BTB-to-CNC homology 1 (BACH1). miR-98 silencing or BACH1 overexpression counteracted XIST knockdown-mediated effects on cell viability and apoptosis in OGD-treated neurons. In conclusion, our data demonstrated that XIST facilitated the progression of ischemic stroke through regulating the miR-98/BACH1 axis. These findings might provide a novel therapeutic strategy for ischemic stroke treatment.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , AVC Isquêmico/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Apoptose/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Isquemia Encefálica/genética , Sobrevivência Celular/genética , China , Glucose/metabolismo , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/metabolismo , AVC Isquêmico/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Neurônios/metabolismo , Oxigênio/metabolismo , RNA Longo não Codificante/metabolismo , Acidente Vascular Cerebral/genética
15.
Int J Mol Sci ; 22(14)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34299177

RESUMO

Adaptation of bacteria to a changing environment is often accompanied by remodeling of the transcriptome. In the facultative phototroph Rhodobacter sphaeroides the alternative sigma factors RpoE, RpoHI and RpoHII play an important role in a variety of stress responses, including heat, oxidative stress and nutrient limitation. Photooxidative stress caused by the simultaneous presence of chlorophylls, light and oxygen is a special challenge for phototrophic organisms. Like alternative sigma factors, several non-coding sRNAs have important roles in the defense against photooxidative stress. RNAseq-based transcriptome data pointed to an influence of the stationary phase-induced StsR sRNA on levels of mRNAs and sRNAs with a role in the photooxidative stress response. Furthermore, StsR also affects expression of photosynthesis genes and of genes for regulators of photosynthesis genes. In vivo and in vitro interaction studies revealed that StsR, that is under control of the RpoHI and RpoHII sigma factors, targets rpoE mRNA and affects its abundance by altering its stability. RpoE regulates expression of the rpoHII gene and, consequently, expression of stsR. These data provide new insights into a complex regulatory network of protein regulators and sRNAs involved in defense against photooxidative stress and the regulation of photosynthesis genes.


Assuntos
Proteínas de Bactérias/metabolismo , Estresse Oxidativo , Oxigênio/metabolismo , RNA Bacteriano/genética , Rhodobacter sphaeroides/crescimento & desenvolvimento , Fator sigma/metabolismo , Transcriptoma , Proteínas de Bactérias/genética , Rhodobacter sphaeroides/genética , Rhodobacter sphaeroides/metabolismo , Fator sigma/genética
16.
Methods Mol Biol ; 2314: 247-260, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34235656

RESUMO

Non-replicating persistence (NRP) is a functional adaptation that mycobacteria undergo in response to the stresses of the granuloma, facilitating antibiotic tolerance and long-term infection. These stresses, or NRP-inducing factors, include hypoxia, nutrient deprivation, and nitric oxide assault, which mycobacteria are well evolved to tolerate through a series of metabolic and physiological adaptations producing the NRP state. Most attempts to replicate these conditions in vitro have focused on only one of these factors at a time for ease and simplicity, but as a result, do not necessarily produce physiologically relevant phenotypes. Here, we provide the methods for two different in vitro NRP strategies that are useful for drug susceptibility testing and high-throughput screening.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Hipóxia/fisiopatologia , Mycobacterium tuberculosis/crescimento & desenvolvimento , Nutrientes/metabolismo , Oxigênio/metabolismo , Preparações Farmacêuticas/administração & dosagem , Estresse Fisiológico , Humanos , Técnicas In Vitro , Mycobacterium tuberculosis/efeitos dos fármacos
17.
Photochem Photobiol Sci ; 20(7): 843-857, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34216374

RESUMO

Photosensitizers of singlet oxygen exhibit three main types of reverse intersystem-crossing (RISC): thermally activated, triplet-triplet annihilation, and singlet oxygen feedback. RISC can be followed by delayed fluorescence (DF) emission, which can provide important information about the excited state dynamics in the studied system. An excellent model example is a widely used clinical photosensitizer Protoporphyrin IX, which manifests all three mentioned types of RISC and DF. Here, we estimated rate constants of individual RISC and DF processes in Protoporphyrin IX in dimethylformamide, and we showed how these affect triplet decays and DF signals under diverse experimental conditions, such as a varying oxygen concentration or excitation intensity. This provided a basis for a general discussion on guidelines for a more precise analysis of long-lived signals. Furthermore, it has been found that PpIX photoproducts and potential transient excited complexes introduce a new overlapping delayed luminescence spectral band with a distinct lifetime. These findings are important for design of more accurate biological oxygen sensors and assays based on DF and triplet lifetime.


Assuntos
Fluorescência , Hipóxia , Fármacos Fotossensibilizantes/metabolismo , Protoporfirinas/metabolismo , Humanos , Oxigênio/química , Oxigênio/metabolismo , Fármacos Fotossensibilizantes/química , Protoporfirinas/química
18.
Nat Commun ; 12(1): 4522, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312399

RESUMO

Loss of oxygen in the global ocean is accelerating due to climate change and eutrophication, but how acute deoxygenation events affect tropical marine ecosystems remains poorly understood. Here we integrate analyses of coral reef benthic communities with microbial community sequencing to show how a deoxygenation event rapidly altered benthic community composition and microbial assemblages in a shallow tropical reef ecosystem. Conditions associated with the event precipitated coral bleaching and mass mortality, causing a 50% loss of live coral and a shift in the benthic community that persisted a year later. Conversely, the unique taxonomic and functional profile of hypoxia-associated microbes rapidly reverted to a normoxic assemblage one month after the event. The decoupling of ecological trajectories among these major functional groups following an acute event emphasizes the need to incorporate deoxygenation as an emerging stressor into coral reef research and management plans to combat escalating threats to reef persistence.


Assuntos
Antozoários/fisiologia , Recifes de Corais , Ecossistema , Oxigênio/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Região do Caribe , Mudança Climática , Peixes/fisiologia , Geografia , Metagenômica/métodos , Modelos Biológicos , Panamá , Filogenia , Água do Mar/microbiologia
19.
FASEB J ; 35(8): e21773, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34324735

RESUMO

Acute hypoxia has previously been suggested to potentiate resistance training-induced hypertrophy by activating satellite cell-dependent myogenesis rather than an improvement in protein balance in human. Here, we tested this hypothesis after a 4-week hypoxic vs normoxic resistance training protocol. For that purpose, 19 physically active male subjects were recruited to perform 6 sets of 10 repetitions of a one-leg knee extension exercise at 80% 1-RM 3 times/week for 4 weeks in normoxia (FiO2 : 0.21; n = 9) or in hypoxia (FiO2 : 0.135, n = 10). Blood and skeletal muscle samples were taken before and after the training period. Muscle fractional protein synthetic rate was measured over the whole period by deuterium incorporation into the protein pool and muscle thickness by ultrasound. At the end of the training protocol, the strength gain was higher in the hypoxic vs the normoxic group despite no changes in muscle thickness and in the fractional protein synthetic rate. Only early myogenesis, as assessed by higher MyoD and Myf5 mRNA levels, appeared to be enhanced by hypoxia compared to normoxia. No effects were found on myosin heavy chain expression, markers of oxidative metabolism and lactate transport in the skeletal muscle. Though the present study failed to unravel clearly the mechanisms by which hypoxic resistance training is particularly potent to increase muscle strength, it is important message to keep in mind that this training strategy could be effective for all athletes looking at developing and optimizing their maximal muscle strength.


Assuntos
Proteínas Musculares/metabolismo , Força Muscular/fisiologia , Músculo Esquelético/anatomia & histologia , Oxigênio/metabolismo , Treinamento de Força/métodos , Regulação da Expressão Gênica , Humanos , Masculino , Músculo Esquelético/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Satélites de Músculo Esquelético/fisiologia , Adulto Jovem
20.
Nature ; 595(7865): 58-65, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34194019

RESUMO

The natural world provides many examples of multiphase transport and reaction processes that have been optimized by evolution. These phenomena take place at multiple length and time scales and typically include gas-liquid-solid interfaces and capillary phenomena in porous media1,2. Many biological and living systems have evolved to optimize fluidic transport. However, living things are exceptionally complex and very difficult to replicate3-5, and human-made microfluidic devices (which are typically planar and enclosed) are highly limited for multiphase process engineering6-8. Here we introduce the concept of cellular fluidics: a platform of unit-cell-based, three-dimensional structures-enabled by emerging 3D printing methods9,10-for the deterministic control of multiphase flow, transport and reaction processes. We show that flow in these structures can be 'programmed' through architected design of cell type, size and relative density. We demonstrate gas-liquid transport processes such as transpiration and absorption, using evaporative cooling and CO2 capture as examples. We design and demonstrate preferential liquid and gas transport pathways in three-dimensional cellular fluidic devices with capillary-driven and actively pumped liquid flow, and present examples of selective metallization of pre-programmed patterns. Our results show that the design and fabrication of architected cellular materials, coupled with analytical and numerical predictions of steady-state and dynamic behaviour of multiphase interfaces, provide deterministic control of fluidic transport in three dimensions. Cellular fluidics may transform the design space for spatial and temporal control of multiphase transport and reaction processes.


Assuntos
Células/metabolismo , Microfluídica/instrumentação , Microfluídica/métodos , Absorção Fisico-Química , Dióxido de Carbono/metabolismo , Gases/metabolismo , Nutrientes/metabolismo , Oxigênio/metabolismo , Transpiração Vegetal , Gravação de Videodisco , Água/metabolismo
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