RESUMO
The growth state of tumor cells is strictly affected by the specific abnormal redox status of the tumor microenvironment (TME). Moreover, redox reactions at the biological level are also central and fundamental to essential energy metabolism reactions in tumors. Accordingly, anti-tumor nanodrugs targeting the disruption of this abnormal redox homeostasis have become one of the hot spots in the field of nanodrugs research due to the effectiveness of TME modulation and anti-tumor efficiency mediated by redox interference. This review discusses the latest research results of nanodrugs in anti-tumor therapy, which regulate the levels of oxidants or reductants in TME through a variety of therapeutic strategies, ultimately breaking the original "stable" redox state of the TME and promoting tumor cell death. With the gradual deepening of study on the redox state of TME and the vigorous development of nanomaterials, it is expected that more anti-tumor nano drugs based on tumor redox microenvironment regulation will be designed and even applied clinically.
Assuntos
Antineoplásicos , Oxirredução , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Animais , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Nanopartículas/químicaRESUMO
BACKGROUND: Supraphysiologic levels of oxygen could have potential adverse effects on the brain that may be dose and time dependent in patients with brain injury. We therefore aimed to assess whether exposure to excess supplemental oxygen, measured as time-weighted mean exposure to hyperoxemia, was associated with intensive care unit (ICU) mortality in patients with intracerebral hemorrhage (ICH). METHODS: In this single-center retrospective cohort study, we included all patients admitted to our ICU with a diagnosis of primary spontaneous ICH. To provide a longitudinal measure of hyperoxemia exposure, we calculated the hyperoxemia dose, defined as the area under the partial pressure of oxygen in arterial blood (PaO2) time curve above the threshold PaO2 value of 100 mm Hg (13.3 kPa) divided by the number of hours of potential exposure. To provide consistent potential exposure windows and limit bias from informative censoring, nested subsets were created with progressively longer exposure periods (0-1 day, 0-2 days, 0-3 days, 0-4 days, 0-5 days, 0-6 days, 0-7 days). We used multivariable Cox regression, with hyperoxemia dose as a time-dependent covariate, to model ICU mortality. Admission ICH and Acute Physiology and Chronic Health Evaluation II scores were included as predictor covariables. A step-function extended Cox model was also fitted. RESULTS: Between September 2019 and July 2022, 275 patients met the inclusion criteria, with 24,588 arterial blood gas results available for analysis. The mean age was 57.19 years (± 13.99), 59.64% were male, 23.64% had an infratentorial origin of hemorrhage, and ICU mortality was 35.64%. Almost all patients (97.45%) were exposed to hyperoxemia during their ICU admission. Cox regression modeling showed an association between hyperoxemia dose and ICU mortality (hazard ratio 1.15, confidence interval 1.05-1.25, p = 0.003). This association was observed in the 0-1 day subset in the step-function extended Cox model (hazard ratio 1.19, confidence interval 1.06-1.35, p = 0.005) but not in any of the subsequent exposure periods. CONCLUSIONS: In patients with ICH admitted to the ICU, we observed an association between hyperoxemia dose and ICU mortality. Further prospective study is required to inform guidance on early systemic oxygen targets in ICH.
RESUMO
Tropical pelagic predators are exploited by fisheries and their movements are influenced by factors including prey availability, temperature, and dissolved oxygen levels. As the biophysical parameters vary greatly within the range of circumtropical species, local studies are needed to define those species' habitat preference and model possible behavioral responses under different climate change scenarios. Here, we tagged yellowfin tuna Thunnus albacares in the Galápagos Marine Reserve and tracked the horizontal and vertical movements of eight individuals for 4-97 days. The tuna traveled a mean of 13.6 km day-1 horizontally and dispersed throughout the archipelago and in offshore waters inside the Galápagos Marine Reserve and in the surrounding Ecuadorian exclusive economic zone. Vertically, they traveled a mean of 2 km day-1 , although high-resolution data from a recovered tag suggested that transmitted data underestimated their vertical movement by a factor of 5.5. The tracked yellowfin tuna spent most of their time near the surface, with an overall mean swimming depth of 24.3 ± 46.6 m, and stayed shallower at night (11.1 ± 16.3 m) than during the day ( 37.7 ± 60.9 m), but on occasion dived to cold, oxygen-poor waters below 200 m. Deep dives were commonly made during the day with a mean recovery period of 51 min between exposures to modeled oxygen-limiting conditions <1.5 mL L-1 , presumably to re-oxygenate. The depth and frequency of dives were likely limited by dissolved oxygen levels, as oxygen-depleted conditions reach shallow depths in this region. The main habitat of tracked yellowfin tunas was in the shallow mixed layer, which may leave them vulnerable to fishing. Vertical expansion of low-oxygen waters under future climate change scenarios may further compress their habitat, increasing their vulnerability to surface fishing gear.
Assuntos
Oxigênio , Atum , Humanos , Animais , Atum/fisiologia , Temperatura , Mudança Climática , EcossistemaRESUMO
This article explores the role that oxygen levels in US spacecraft from 1961 to 1998 have on the development of cataracts induced by space radiation in astronauts and whether oxygen levels are well accounted for in experimental studies examining cataractogenesis. The first epidemiological report in 2001 linked an increased risk of the primary types of cataracts, and nuclear cataract alone, for astronauts with higher lens doses. However, later studies of US astronauts in 2009 and 2012 reported a higher risk of cortical cataract and posterior subcapsular cataract, but not for nuclear cataract. Firstly, it is postulated that the high oxygen level atmospheres of spacecraft employed before 1976 were a factor in promoting nuclear cataract. The high oxygen levels of hyperbaric oxygen therapy are reportedly associated with nuclear cataract, and the low intraocular oxygen levels of diabetic patients are possibly linked to their higher risk of posterior subcapsular cataract and cortical cataract. Secondly, it is hypothesized that the normal hypoxic environment of the lens and lens epithelial cells (LECs), and all stem/progenitor cells in general, have an optimal Goldilocks range of oxygen levels. Too high a lenticular oxygen level increases oxidative stress and radiosensitivity due to the oxygen effect. Whereas too low an oxygen tension also increases oxidative stress and disrupts LEC differentiation. Even so, a focused literature search of the PubMed database of in vitro experiments with LECs shows that studies rarely account for the hypoxic state of the normal lens, whether ionizing radiation is a factor or not. It is therefore recommended that ocular physioxic levels should therefore be considered when designing in vitro studies to better understand the progression of cataractogenesis on long-duration missions to the Moon and Mars.
Assuntos
Catarata , Cristalino , Astronautas , Catarata/etiologia , Humanos , Cristalino/efeitos da radiação , OxigênioRESUMO
Marine sponges are an ideal source for isolating as yet undiscovered microorganisms with some sponges having about 50% of their biomass composed of microbial symbionts. This study used a variety of approaches to investigate the culturable diversity of the sponge-associated bacterial community from samples collected from the South Australian marine environment. Twelve sponge samples were selected from two sites and their bacterial population cultivated using seven different agar media at two temperatures and three oxygen levels over 3 months. These isolates were identified using microscopic, macroscopic, and 16S rRNA gene analysis. A total of 1234 bacterial colonies were isolated which consisted of four phyla: Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes, containing 21 genera. The diversity of the bacterial population was demonstrated to be influenced by the type of isolation medium, length of the incubation period and temperature, sponge type, and oxygen level. The findings of this study showed that marine sponges of South Australia can yield considerable bacterial culturable diversity if a comprehensive isolation strategy is implemented. Two sponges, with the highest and the lowest diversity of culturable isolates, were examined using next-generation sequencing to better profile the bacterial population. A marked difference in terms of phyla and genera was observed using culture-based and culture-independent approaches. This observed variation displays the importance of utilizing both methods to reflect a more complete picture of the microbial population of marine sponges. KEY POINTS: Improved bacterial diversity due to long incubations, 2 temperatures, and 3 oxygen levels. Isolates identified by morphology, restriction digests, and 16S rRNA gene sequencing. At least 70% of culturable genera were not revealed by NGS methods.
Assuntos
Biodiversidade , Poríferos , Animais , Austrália , Bactérias , Filogenia , Poríferos/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Oxygen is a key regulator of both development and homeostasis and a promising candidate to bridge the influence of the environment and the evolution of new traits. To clarify the various ways in which oxygen may modulate embryogenesis, its effects are reviewed at distinct organizational levels. First, the role of pathways that sense dioxygen levels and reactive oxygen species are reviewed. Then, the effects of microenvironmental oxygen on metabolism, stemness, and differentiation throughout embryogenesis are discussed. Last, the interplay between ecology and development are reexamined with a focus on the evolution of tetrapods, including during the emergence of a novel mechanism that shapes amniote limbs-interdigital cell death. Both genetic and environmental components work together during the formation of organisms, highlighting the importance of a multidisciplinary approach for understanding the evolution of new traits.
Assuntos
Ecologia , Oxigênio , Evolução Biológica , Extremidades , Fenótipo , Espécies Reativas de OxigênioRESUMO
Atovaquone (AV) acts on the malaria parasite by competing with ubiquinol (UQH2) for its union to the mitochondrial bc1 complex, preventing the ubiquinone-8 and ubiquinone-9 (UQ-8 and UQ-9) redox recycling, which is a necessary step in pyrimidine biosynthesis. This study focused on UQ biosynthesis in Plasmodium falciparum and adopted proof-of-concept research to better elucidate the mechanism of action of AV and improve its efficacy. Initially, UQ biosynthesis was evaluated using several radioactive precursors and chromatographic techniques. This methodology was suitable for studying the biosynthesis of both UQ homologs and its redox state. Additionally, the composition of UQ was investigated in parasites cultivated at different oxygen saturations or in the presence of AV. AV affected the redox states of both UQ-8 and UQ-9 homologs by increasing the levels of the respective reduced forms. Conversely, low-oxygen environments specifically inhibited UQ-9 biosynthesis and increased the antimalarial efficacy of AV. These findings encouraged us to investigate the biological importance and the potential of UQ biosynthesis as a drug target based on its inhibition by 4-nitrobenzoate (4-NB), a 4-hydroxybenzoate (4-HB) analog. 4-NB effectively inhibits UQ biosynthesis and enhances the effects of AV on parasitic growth and respiration rate. Although 4-NB itself exhibits poor antimalarial activity, its 50% inhibitory concentration (IC50) value increased significantly in the presence of a soluble UQ analog, p-aminobenzoic acid (pABA), or 4-HB. These results indicate the potential of AV combined with 4-NB as a novel therapy for malaria and other diseases caused by AV-sensitive pathogens.
Assuntos
Malária , Ubiquinona , Atovaquona/farmacologia , Humanos , Mitocôndrias/metabolismo , Oxirredução , Ubiquinona/metabolismoRESUMO
Vacuum packaging (VP) is used to reduce exposure of retail meat samples to ambient oxygen (O2) and preserve their quality. A simple sensor system produced from commercial components is described, which allows for non-destructive monitoring of the O2 concentration in VP raw meat samples. Disposable O2 sensor inserts were produced by spotting small aliquots of the cocktail of the Pt-benzoporphyrin dye and polystyrene in ethyl acetate onto pieces of a PVDF membrane and allowing them to air-dry. These sensor dots were placed on top of the beef cuts and vacuum-packed. A handheld reader, FirestinGO2, was used to read nondestructively the sensor phase shift signals (dphi°) and relate them to the O2 levels in packs (kPa or %). The system was validated under industrial settings at a meat processing plant to monitor O2 in VP meat over nine weeks of shelf life storage. The dphi° readings from individual batch-calibrated sensors were converted into the O2 concentration by applying the following calibration equation: O2 (%) = 0.034 * dphi°2 - 3.413 * dphi° + 85.02. In the VP meat samples, the O2 levels were seen to range between 0.12% and 0.27%, with the sensor dphi signals ranging from 44.03° to 56.02°. The DIY sensor system demonstrated ease of use on-site, fast measurement time, high sample throughput, low cost and flexibility.
Assuntos
Embalagem de Alimentos , Carne , Animais , Bovinos , Microbiologia de Alimentos , Carne/análise , Oxigênio/análise , VácuoRESUMO
The bacterial communities are challenged with oxidative stress during their exposure to bactericidal antibiotics, metals, and different levels of dissolved oxygen (DO) encountered in diverse environmental habitats. The frequency of antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) co-selection is increased by selective pressure posed by oxidative stress. Hence, study of resistance acquisition is important from an evolutionary perspective. To understand the dependence of oxidative stress on the dissemination of ARGs and MRGs through a pathogenic bacterial population, 12 metagenomes belonging to gut, water and soil habitats were evaluated. The metagenome-wide analysis showed the chicken gut to pose the most diverse pool of ARGs (30.4 ppm) and pathogenic bacteria (Simpson diversity = 0.98). The most common types of resistances found in all the environmental samples were efflux pumps (13.22 ppm) and genes conferring resistance to vancomycin (12.4 ppm), tetracycline (12.1 ppm), or beta-lactam (9.4 ppm) antibiotics. Additionally, limiting DO level in soil was observed to increase the abundance of excision nucleases (uvrA and uvrB), DNA polymerase (polA), catalases (katG), and other oxidative stress response genes (OSGs). This was further evident from major variations occurred in antibiotic efflux genes due to the effect of DO concentration on two human pathogens, namely Salmonella enterica and Shigella sonnei found in all the selected habitats. In conclusion, the microbial community, when challenged with oxidative stress caused by environmental variations in oxygen level, tends to accumulate higher amounts of ARGs with increased dissemination potential through triggering non-lethal mutagenesis. Furthermore, the genetic linkage or co-occurrence of ARGs and MRGs provides evidence for selecting ARGs under high concentrations of heavy metals.
Assuntos
Metais Pesados , Microbiota , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Humanos , Metais Pesados/toxicidade , Estresse OxidativoRESUMO
The disordered network of blood vessels that arises from tumour angiogenesis results in variations in the delivery of oxygen into the tumour tissue. This brings about regions of chronic hypoxia (i.e. sustained low oxygen levels) and regions with alternating periods of low and relatively higher oxygen levels, and makes it necessary for cancer cells to adapt to fluctuating environmental conditions. We use a phenotype-structured model to dissect the evolutionary dynamics of cell populations exposed to fluctuating oxygen levels. In this model, the phenotypic state of every cell is described by a continuous variable that provides a simple representation of its metabolic phenotype, ranging from fully oxidative to fully glycolytic, and cells are grouped into two competing populations that undergo heritable, spontaneous phenotypic variations at different rates. Model simulations indicate that, depending on the rate at which oxygen is consumed by the cells, dynamic nonlinear interactions between cells and oxygen can stimulate chronic hypoxia and cycling hypoxia. Moreover, the model supports the idea that under chronic-hypoxic conditions lower rates of phenotypic variation lead to a competitive advantage, whereas higher rates of phenotypic variation can confer a competitive advantage under cycling-hypoxic conditions. In the latter case, the numerical results obtained show that bet-hedging evolutionary strategies, whereby cells switch between oxidative and glycolytic phenotypes, can spontaneously emerge. We explain how these results can shed light on the evolutionary process that may underpin the emergence of phenotypic heterogeneity in vascularised tumours.
Assuntos
Adaptação Fisiológica , Modelos Biológicos , Neoplasias/metabolismo , Oxigênio/metabolismo , Biologia Computacional , Simulação por Computador , Glicólise , Humanos , Conceitos Matemáticos , Neoplasias/irrigação sanguínea , Neoplasias/patologia , Neovascularização Patológica , Dinâmica não Linear , Oxirredução , Consumo de Oxigênio , Fenótipo , Processos Estocásticos , Hipóxia Tumoral/fisiologiaRESUMO
STUDY QUESTION: Does the oxygen concentration in the culture medium [either physiologic (5%) or atmospheric (20%)] affect mitochondrial ultrastructure and function in preimplantation mouse embryos generated by IVF? SUMMARY ANSWER: Embryos cultured in 20% oxygen show increased mitochondrial abnormalities compared to embryos cultured in 5% oxygen. WHAT IS KNOWN ALREADY: ART are widely used and have resulted in the birth of more than 8 million children. A variety of media and oxygen concentrations are used to culture embryos. Embryos cultured under physiological O2 tension (5%) reach the blastocyst stage faster and have fewer alterations in gene expression when compared with embryos cultured under atmospheric oxygen conditions (20%). The mechanisms by which oxygen tension affects preimplantation development remain unclear, but mitochondria are believed to play an important role. The aim of this study was to evaluate how mitochondrial ultrastructure and function in IVF embryos were affected by culture under physiologic (5%) or atmospheric (20%) oxygen concentrations. STUDY DESIGN, SIZE, DURATION: Zygotes, 2-cell, 4-cell, morula and blastocyst were flushed out of the uterus after natural fertilization and used as controls. IVF was performed in CF1 x B6D2F1 mice and embryos were cultured in Potassium simplex optimized medium (KSOM) with amino acids (KAA) under 5% and 20% O2 until the blastocyst stage. Embryo development with the addition of antioxidants was also tested. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mitochondrial function was assessed by measuring mitochondrial membrane potential, reactive oxygen species (ROS) production, ATP levels, and the expression of selected genes involved in mitochondrial function. Mitochondria ultrastructure was evaluated by transmission electron microscopy (TEM). MAIN RESULTS AND THE ROLE OF CHANCE: Embryos cultured under 20% O2 had fewer mitochondria and more vacuoles and hooded (abnormal) mitochondria compared to the other groups (P < 0.05). At the blastocyst stage the mitochondria of IVF embryos cultured in 20% O2 had lower mtDNA copy number, a denser matrix and more lamellar cristae than controls. Overall IVF-generated blastocysts had lower mitochondrial membrane potential, higher ROS levels, together with changes in the expression of selected mitochondrial genes (P < 0.05). ATP levels were significantly lower than controls only under 5% O2, with the 20% O2 IVF group having intermediate levels. Unexpectedly, adding antioxidant to the culture medium did not improve development. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Findings in mice embryos might be different from human embryos. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that changes in the mitochondria may be part of the mechanism by which lower oxygen concentration leads to better embryo development and further emphasize the importance of mitochondria as a locus of reprogramming. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by R01 HD 082039 to PFR, the Department of Life, Health and Environmental Sciences, University of L'Aquila, Italy (RIA 2016-2018) and the Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, La Sapienza University of Rome, Italy (University grants 2016-2017). The authors declare no competing interests.
Assuntos
Blastocisto/metabolismo , Técnicas de Cultura Embrionária/métodos , Fertilização in vitro/métodos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Oxigênio/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Meios de Cultura/química , DNA Mitocondrial/genética , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Masculino , Potencial da Membrana Mitocondrial , Camundongos , Microscopia Eletrônica de Transmissão , Mitocôndrias/genética , Espécies Reativas de Oxigênio/metabolismo , Transcriptoma , Vacúolos/metabolismoRESUMO
Respiratory parameters of grass carp were studied during dissolved oxygen (DO) changes from normal DO to hypoxia, then return to normal DO at 15, 25, and 30 °C acclimation, respectively. The results showed that with increases of acclimation temperature at normoxia the respiratory frequency (fR), oxygen consumption rate (VO2), respiratory stroke volume (VS.R), gill ventilation (VG), and VG/VO2 of grass carp increased significantly, but the oxygen extraction efficiency (EO2) of fish decreased significantly (P < 0.05). With declines of DO levels, the fR, VS.R, VG, and VG/VO2 of fish increased significantly at different acclimation temperatures (P < 0.05). A slight increase was found in VO2, and the EO2 of fish remained almost constant above DO levels of 3.09, 2.91, and 2.54 mg l-1 at 15, 25, and 30 °C, while the VO2 and EO2 began to decrease significantly with further reductions in DO levels (P < 0.05). After 0.5 h of recovery to normoxia from hypoxia at three acclimation, the fR, VS.R, VG, and VG/VO2 of the fish decreased sharply; meanwhile, the VO2 and EO2 increased sharply (P < 0.05). The respiratory parameters of fish gradually approached initial values with prolonged recovery time to normoxia, and reached their initial values in 2.5 h at 25 and 30 °C acclimation. The critical oxygen concentrations (Cc) of fish for VO2 were 2.42 mg l-1 at 15 °C, 2.02 mg l-1 at 25 °C, and 1.84 mg l-1 at 30 °C, respectively. The results suggest that grass carp are highly adapted to varied DO and short-term hypoxia environments.
Assuntos
Aclimatação , Carpas/fisiologia , Consumo de Oxigênio/fisiologia , Oxigênio/química , Temperatura , Animais , Brânquias/fisiologia , Oxigênio/metabolismo , Água/químicaRESUMO
Brain is the major consumer of glucose in the human body, whose pattern of consumption changes through lifetime, decreasing during adolescence up to adulthood. This evidence leads to the hypothesis that, in cerebral developmental stages, glycolysis might be the driving force for the high-energy requirement. Furthermore, several studies claim that neurogenesis process is accompanied by a shift into mitochondrial oxidative metabolism. Herein, we discuss recent work about cell metabolism during neuronal differentiation process, in particular the mitochondrial role in cellular bioenergy dynamics.
Assuntos
Encéfalo/citologia , Encéfalo/metabolismo , Mitocôndrias/metabolismo , Neurogênese/fisiologia , Neurônios/metabolismo , Animais , Sobrevivência Celular/fisiologia , Glicólise/fisiologia , Humanos , Oxirredução , Estresse Oxidativo/fisiologiaRESUMO
Cardiac stem cells reside in niches where the oxygen levels are close to 3%. For cytotherapy, cells are conventionally expanded in ambient oxygen (21% O2) which represents hyperoxia compared to the oxygen tension of niches. Cardiosphere-derived cells (CDCs) are then transplanted to host tissue with lower-O2 levels. The high-O2 gradient can reduce the efficacy of cultured cells. Based on the assumption that minimizing injury due to O2 gradients will enhance the yield of functionally efficient cells, CDCs were cultured in 3% O2 and compared with cells maintained in ambient O2. CDCs were isolated from human right atrial explants and expanded in parallel in 21 and 3% oxygen and compared with regard to survival, proliferation, and retention of stemness. Increased cell viability even in the tenth passage and enhanced cardiosphere formation was observed in cells expanded in 3% O2. The cell yield from seven passages was fourfold higher for cells cultured in 3% O2. Preservation of stemness in hypoxic environment was evident from the proportion of c-kit-positive cells and reduced myogenic differentiation. Hypoxia promoted angiogenesis and reduced the tendency to differentiate to noncardiac lineages (adipocytes and osteocytes). Mimicking the microenvironment at transplantation, when shifted to 5% O2, viability and proliferation rate were significantly higher for CDCs expanded in 3% O2. Expansion of CDCs, from atria in sub-physiological oxygen, helps in obtaining a higher yield of healthy cells with better preservation of stem cell characteristics. The cells so cultured are expected to improve engraftment and facilitate myocardial regeneration.
Assuntos
Proliferação de Células , Miocárdio/metabolismo , Oxigênio/metabolismo , Células-Tronco/metabolismo , Hipóxia Celular , Sobrevivência Celular , Átrios do Coração/citologia , Átrios do Coração/metabolismo , Humanos , Miocárdio/citologia , Células-Tronco/citologiaRESUMO
Within this special issue, many eminent investigators report on measurements of oxygen (O2) levels in tissues. Given the complexities of spatial and temporal heterogeneities of O2 in tissues and its many sources, this commentary draws attention to what such measurements do and do not actually assess regarding O2 levels in tissues. Given this limitation, it also discusses how these results can be used most effectively. To provide a convenient mechanism to discuss these issues more fully, this analysis focuses on measurements using EPR oximetry, but these considerations apply to all other techniques. The nature of the delivery of O2 to tissues and the mechanisms by which O2 is consumed necessarily result in very different levels of O2 within the volume of each voxel of a measurement. Better spatial resolution cannot fully resolve the problem because the variations include O2 gradients within each cell. Improved resolution of the time-dependent variation in O2 is also very challenging because O2 levels within tissues can have fluctuations of O2 levels in the range of milliseconds, while most methods require longer times to acquire the data from each voxel. Based on these issues, we argue that the values obtained inevitably are complex aggregates of averages of O2 levels across space and time in the tissue. These complexities arise from the complex physiology of tissues and are compounded by the limitations of the technique and its ability to acquire data. However, one often can obtain very meaningful and useful results if these complexities and limitations are taken into account. We illustrate this, using results obtained with in vivo EPR oximetry, especially utilizing its capacity to make repeated measurements to follow changes in O2 levels that occur with interventions and/or over time.
Assuntos
Oximetria , Oxigênio , Oxigênio/metabolismo , Humanos , Oximetria/métodos , Animais , Espectroscopia de Ressonância de Spin Eletrônica/métodosRESUMO
Global change mediated shifts in ocean temperature and circulation patterns, compounded by human activities, are leading to the expansion of marine oxygen minimum zones (OMZs) with concomitant alterations in nutrient and climate-active trace gas cycling. While many studies have reported distinct bacterial communities within OMZs, much of this research compares across depths rather with oxygen status and does not include eukayrotic microbes. Here, we investigated the Bay of Bengal (BoB) OMZ, where low oxygen conditions are persistent, but trace levels of oxygen remain (< 20 µM from 200 to 500 m). As other environmental variables are similar between OMZ and non-OMZ (NOZ) stations, we compared the abundance, diversity, and community composition of several microbial groups (bacterioplankton, Labyrinthulomycetes, and fungi) across oxygen levels. While prokaryote abundance decreased with depth, no significant differences existed across oxygen groups. In contrast, Labyrinthulomycetes abundance was significantly higher in non-OMZ stations but did not change significantly with depth, while fungal abundance was patchy without clear depth or oxygen-related trends. Bacterial and fungal diversity was lower in OMZ stations at 500 m, while Labyrinthulomycetes diversity only showed a depth-related profile, decreasing below the euphotic zone. Surprisingly, previously reported OMZ-associated bacterial taxa were not significantly more abundant at OMZ stations. Furthermore, compared to the bacterioplankton, fewer Labyrinthulomycetes and fungi taxa showed responses to oxygen status. Thus, this research identifies stronger oxygen-level linkages within the bacterioplankton than in the examined microeukaryotes.
Assuntos
Bactérias , Microbiota , Oxigênio , Água do Mar , Oxigênio/análise , Água do Mar/microbiologia , Água do Mar/química , Bactérias/classificação , Biodiversidade , Fungos , Microbiologia da ÁguaRESUMO
This study examined the effect of dissolved oxygen (DO) level on critical thermal maximum (CTMax) in diploid and triploid brook charr (Salvelinus fontinalis) exposed to a temperature increase of 3°C/h. Because gas solubility is inversely proportional to temperature, DO declines during standard CTMax tests. With this treatment as a baseline, oxygen or nitrogen injection was used to provide three other DO conditions during CTMax tests: two hyperoxic (maintenance at initial 10mg/L and increase from 10mg/L at 2mg/L/h) and one hypoxic (decrease from 10mg/L at 2mg/L/h). Hyperoxia had no effect on temperature at CTMax or time taken to reach CTMax. Hypoxia, on the other hand, resulted in a significantly lower CTMax and shorter time to CTMax than under standard or hyperoxic conditions, with both indices affected by triploidy but not in a consistent fashion: in one experiment triploids had a lower CTMax and shorter time to CTMax than diploids and in a second experiment they had a higher CTMax and longer time to CTMax than diploids. Indices of the secondary stress response (plasma glucose and ions) during CTMax tests under hypoxia responded as would be predicted for an acute stress, with no difference between triploids and diploids.
Assuntos
Resposta ao Choque Térmico , Oxigênio/metabolismo , Truta/metabolismo , Animais , Glicemia , Feminino , Masculino , Potássio/sangue , Sódio/sangue , Triploidia , Truta/genéticaRESUMO
BACKGROUND: Robotic-Assisted Hysterectomies (RAH) require Trendelenburg positioning and pneumoperitoneum, which further accentuate alteration in respiratory mechanics induced by general anesthesia. The role of Recruitment Maneuver (RM) as a lung-protective strategy during intraoperative surgical settings has not been much studied. We planned this study to evaluate the effect of RM on perioperative oxygenation and postoperative spirometry using PaO2/FiO2 and FEV1/FVC, respectively in patients undergoing RAH. METHODS: Sixty-six ASA IâII female patients scheduled for elective RAH were randomized into group R (recruitment maneuver, n = 33) or group C (control, n = 33). Portable spirometry was done one day before surgery. Patients were induced with general anesthesia, and mechanical ventilation started with volume control mode, with Tidal Volume (TV) of 6-8 mL.kg-1, Respiratory Rate (RR) of 12 min, inspiratory-expiratory ratio (I: E ratio) of 1:2, FiO2 of 0.4, and Positive End-Expiratory Pressure (PEEP) of 5 cmH2O. Patients in group R received recruitment maneuvers of 30 cmH2O every 30 minutes following tracheal intubation. The primary objectives were comparison of oxygenation and ventilation between two groups intraoperatively and portable spirometry postoperatively. Postoperative pulmonary complications, like desaturation, pulmonary edema, pneumonia, were monitored. RESULTS: Patients who received RM had significantly higher PaO2 (mmHg) (203.2+-24.3 vs. 167.8+-27.3, p < 0.001) at T2 (30 min after the pneumoperitoneum). However, there was no significant difference in portable spirometry between the groups in the postoperative period (FVC, 1.40 ± 0.5 L vs. 1.32 ± 0.46 L, p = 0.55). CONCLUSION: This study concluded that intraoperative recruitment did not prevent deterioration of postoperative spirometry values; however, it led to improved oxygenation intraoperatively.
Assuntos
Pneumoperitônio , Procedimentos Cirúrgicos Robóticos , Humanos , Feminino , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Pneumoperitônio/complicações , Método Simples-Cego , Pulmão , Volume de Ventilação Pulmonar , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Histerectomia/efeitos adversos , Período Pós-OperatórioRESUMO
Theragnostics is a promising approach that integrates diagnostics and therapeutics into a single personalized strategy. To conduct effective theragnostic studies, it is essential to create an in vitro environment that accurately reflects the in vivo conditions. In this review, we discuss the importance of redox homeostasis and mitochondrial function in the context of personalized theragnostic approaches. Cells have several ways to respond to metabolic stress, including changes in protein localization, density, and degradation, which can promote cell survival. However, disruption of redox homeostasis can lead to oxidative stress and cellular damage, which are implicated in various diseases. Models of oxidative stress and mitochondrial dysfunction should be developed in metabolically conditioned cells to explore the underlying mechanisms of diseases and develop new therapies. By choosing an appropriate cellular model, adjusting cell culture conditions and validating the cellular model, it is possible to identify the most promising therapeutic options and tailor treatments to individual patients. Overall, we highlight the importance of precise and individualized approaches in theragnostics and the need to develop accurate in vitro models that reflect the in vivo conditions.
RESUMO
Construction and mining activities in acid-producing alum shale regions often produce large volumes of crushed rock. Disposal under groundwater level (e.g., a bog) may minimize oxygen access. In this study, the effect of varying oxygen access on the leaching potential of alum shale was investigated by submerging tunnel construction rock debris in synthetic rainwater under atmospheric (AOC) and low oxygen conditions (LOC) for 52 weeks. The sulphate increase and nitrate decrease in the leachates suggested that pyrite (FeS2) in the alum shale was oxidized, but carbonates originating from calcite dissolution provided sufficient buffering capacity (leachate pH ~7.7 over 52 weeks), resulting in neutral rock drainage. Less available oxygen led to significantly lower production of sulphate and acid from pyrite oxidation, reducing the release of harmful elements. Under LOC, the leaching of Mo, Co, Ni, Zn and Cd was 2-4 times lower than under AOC and the lower buffering requirement diminished the release of Ca as well as divalent cations (Mg, Sr, Mn) likely present as impurities in calcite. Contrastingly, limited pyrite oxidation led to less oversaturation with respect to BaSO4 and lower release of Fe in the LOC leachates. Thus, co-precipitation of 226Ra was inhibited and scavenging of leached V, As and Sb by newly formed Fe(OH)3 was not as dominant as in the AOC systems. Leaching of U was ~20 % higher under LOC likely due to enhanced complexation by dissolved carbonate. In general, element leaching rates were slower under low O2 levels. Characterization of water collected at the disposal site after ~1.2 years of discarding tunnel materials showed that the weathering of debris submerged in the open, water-filled pond occurred similarly to leaching under low oxygen conditions. Overall, these results highlight the importance of minimal oxygen access or anaerobic conditions when acid-producing rock waste is stored under water.