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1.
Medicine (Baltimore) ; 102(1): e32295, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607871

RESUMO

Adjunctive therapy for hypertension is in high demand for clinical research. Therefore, several meta-analyses have provided sufficient evidence for meditation as an adjunct therapy, without being anchored on reliable physiological grounds. Meditation modulates the autonomic nervous system. Herein, we propose a hierarchical-dependent effect for the carotid body (CB) in attenuating blood pressure (BP) and ventilatory variability (VV) fine-tuning due to known nerve connections between the CB, prefrontal brain, hypothalamus, and solitary tract nucleus. The aim of this exploratory study was to investigate the role of CB in the possible decrease in BP and changes in VV that could occur in response to meditation. This was a prospective, single-center, parallel-group, randomized, controlled clinical trial with concealed allocation. Eligible adult subjects of both sexes with stage 1 hypertension will be randomized into 1 of 2 groups: transcendental meditation or a control group. Subjects will be invited to 3 visits after randomization and 2 additional visits after completing 8 weeks of meditation or waiting-list control. Thus, subjects will undergo BP measurements in normoxia and hyperoxia, VV measurements using the Poincaré method at rest and during exercise, and CB activity measurement in the laboratory. The primary outcome of this study was the detection of changes in BP and CB activity after 8 weeks. Our secondary outcome was the detection of changes in the VV at rest and during exercise. We predict that interactions between hyperoxic deactivation of CB and meditation; Will reduce BP beyond stand-alone intervention or alternatively; Meditation will significantly attenuate the effects of hyperoxia as a stand-alone intervention. In addition, VV can be changed, partially mediated by a reduction in CB activity. Trial registration number: ReBEC registry (RBR-55n74zm). Stage: pre-results.


Assuntos
Corpo Carotídeo , Hiperóxia , Hipertensão , Meditação , Adulto , Masculino , Feminino , Humanos , Meditação/métodos , Estudos Prospectivos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Sci Rep ; 13(1): 143, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599874

RESUMO

Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are among the most common morbidities affecting extremely premature infants who receive oxygen therapy. Many clinical studies indicate that BPD is associated with advanced ROP. However, the mechanistic link between hyperoxia, BPD, and ROP remains to be explored. Gasdermin D (GSDMD) is a key executor of inflammasome-induced pyroptosis and inflammation. Inhibition of GSDMD has been shown to attenuate hyperoxia-induced BPD and brain injury in neonatal mice. The objective of this study was to further define the mechanistic roles of GSDMD in the pathogenesis of hyperoxia-induced BPD and ROP in mouse models. Here we show that global GSDMD knockout (GSDMD-KO) protects against hyperoxia-induced BPD by reducing macrophage infiltration, improving alveolarization and vascular development, and decreasing cell death. In addition, GSDMD deficiency prevented hyperoxia-induced ROP by reducing vasoobliteration and neovascularization, improving thinning of multiple retinal tissue layers, and decreasing microglial activation. RNA sequencing analyses of lungs and retinas showed that similar genes, including those from inflammatory, cell death, tissue remodeling, and tissue and vascular developmental signaling pathways, were induced by hyperoxia and impacted by GSDMD-KO in both models. These data highlight the importance of GSDMD in the pathogenesis of BPD and ROP and suggest that targeting GSDMD may be beneficial in preventing and treating BPD and ROP in premature infants.


Assuntos
Displasia Broncopulmonar , Retinopatia da Prematuridade , Animais , Camundongos , Animais Recém-Nascidos , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/metabolismo , Modelos Animais de Doenças , Hiperóxia/complicações , Hiperóxia/metabolismo , Hipertensão Pulmonar/patologia , Pulmão/patologia , Proteínas de Ligação a Fosfato/genética , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Retinopatia da Prematuridade/genética , Retinopatia da Prematuridade/complicações , /metabolismo
3.
Shock ; 59(1): 20-27, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36703274

RESUMO

ABSTRACT: Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) can easily lead to supranormal oxygenation. The impact of hyperoxygenation beyond the early VA-ECMO support phase is unexplored. We sought to investigate its association with short- and long-term mortality. Methods: A total of 10,615 arterial blood gases of 179 patients undergoing VA-ECMO between 2013 and 2018 in our cardiosurgical tertiary center were analyzed for partial pressure of oxygen (PaO2) and its association with in-hospital, 90-day, and 1-year mortality. Patients were stratified into terciles (T) based on PaO2. Results: The median systemic PaO2 during VA-ECMO was 122 mm Hg (Q1-Q3, 111-158 mm Hg) and was significantly higher in 90-day nonsurvivors versus survivors (134 mm Hg [Q1-Q3, 114-175 mm Hg] vs. 114 mm Hg [Q1-Q3, 109-136 mm Hg]; P < 0.001). The incidence of mortality increased at all time points tested after VA-ECMO implantation along with the increasing terciles of PaO2. The lowest mortality rates were noted for patients with median PaO2 values of <115 mm Hg (T1), whereas patients with median PaO2 values of >144 mm Hg (T3) had the highest mortality rates. Bonferroni multiple testing analysis found the T3 of PaO2 to be a predictor of decreased 90-day survival in comparison with T1 (P < 0.001) and T2 (P = 0.002). Multivariable Cox regression analyses for in-hospital, 90-day, and 1-year mortality showed a significant association of the T3 compared with the T2 and the T1 of PaO2 to mortality across all endpoints. Conclusion: Hyperoxygenation during VA-ECMO might be associated with increased all-cause mortality. The results of our study further document the known toxicity of hyperoxygenation in general critical care patients and mark the need to focus specifically on VA-ECMO patients.


Assuntos
Oxigenação por Membrana Extracorpórea , Hiperóxia , Humanos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Oxigênio , Mortalidade Hospitalar , Incidência , Estudos Retrospectivos , Choque Cardiogênico
4.
PeerJ ; 11: e14530, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36620750

RESUMO

The well-being of fish used in aquaculture is of great interest. Oxygen and temperature are the main factors affecting the welfare of the crucian carp (carassius); however, there are few studies on the combined effects of these on the species. Therefore, this study investigated the impact of different temperatures (18 °C, 24 °C, 30 °C) and oxygen concentrations (2.1 mgL-1, 5.4 mgL-1, 9.3 mgL-1) on serum antibacterial activity, antioxidant activity, hematological parameters and growth performance of the crucian carp. The results showed that there were greater antibacterial properties under conditions of hypoxia at 18 °C (L18) and hyperoxia at 24 °C (H24). The activities of catalase, glutathione peroxidase and total superoxide dismutase were the highest at 24 °C under hypoxia and hyperoxia. In addition, the contents of glucose and total protein first increased and then decreased with the change of temperature; triglycerides were the lowest at 30 °C. The blood parameters of the carp were within a normal range at 24 °C; however, the growth rate was at its lowest under hypoxia treatment at 30 °C (L30). This study showed that high temperature impairs the antibacterial ability, antioxidant capacity and growth performance of the crucian carp, and high oxygen levels can alleviate these adverse reactions. This research provides a theoretical basis for subsequent aquaculture studies.


Assuntos
Carpas , Hiperóxia , Animais , Oxigênio/metabolismo , Temperatura , Carpas/metabolismo , Antioxidantes , Hipóxia/metabolismo
5.
Respir Res ; 24(1): 16, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647045

RESUMO

BACKGROUND: The level of linked N-acetylglucosamine (O-GlcNAc) has been proved to be a sensor of cell state, but its relationship with hyperoxia-induced alveolar type 2 epithelial cells injure and bronchopulmonary dysplasia (BPD) has not been clarified. In this study, we evaluated if these effects ultimately led to functional damage in hyperoxia-induced alveolar cells. METHODS: We treated RLE-6TN cells at 85% hyperoxia for 0, 24 and 48 h with Thiamet G (TG), an OGA inhibitor; OSMI-1 (OS), an OGT inhibitor; or with UDP-GlcNAc, which is involved in synthesis of O-GlcNAc as a donor. The metabolic rerouting, cell viability and apoptosis resulting from the changes in O-GlcNAc glycosyltransferase levels were evaluated in RLE-6TN cells after hyperoxia exposure. We constructed rat Park2 overexpression and knockdown plasmmids for in vitro verification and Co-immunoprecipitation corroborated the binding of Parkin and O-GlcNAc. Finally, we assessed morphological detection in neonatal BPD rats with TG and OS treatment. RESULTS: We found a decrease in O-GlcNAc content and levels of its metabolic enzymes in RLE-6TN cells under hyperoxia. However, the inhibition of OGT function with OSMI-1 ameliorated hyperoxia-induced lung epithelial cell injury, enhanced cell metabolism and viability, reduced apoptosis, and accelerated the cell proliferation. Mitochondrial homeostasis was affected by O-GlcNAc and regulated Parkin. CONCLUSION: The results revealed that the decreased O-GlcNAc levels and increased O-GlcNAcylation of Parkin might cause hyperoxia-induced alveolar type II cells injurys.


Assuntos
Hiperóxia , Ubiquitina-Proteína Ligases , Animais , Ratos , Acetilglucosamina/metabolismo , Células Epiteliais Alveolares/metabolismo , Homeostase , Hiperóxia/genética , Hiperóxia/metabolismo , Mitofagia , Ubiquitina-Proteína Ligases/genética
6.
Nat Commun ; 14(1): 273, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650158

RESUMO

Senescence causes age-related diseases and stress-related injury. Paradoxically, it is also essential for organismal development. Whether senescence contributes to lung development or injury in early life remains unclear. Here, we show that lung senescence occurred at birth and decreased throughout the saccular stage in mice. Reducing senescent cells at this stage disrupted lung development. In mice (<12 h old) exposed to hyperoxia during the saccular stage followed by air recovery until adulthood, lung senescence increased particularly in type II cells and secondary crest myofibroblasts. This peaked during the alveolar stage and was mediated by the p53/p21 pathway. Decreasing senescent cells during the alveolar stage attenuated hyperoxia-induced alveolar and vascular simplification. Conclusively, early programmed senescence orchestrates postnatal lung development whereas later hyperoxia-induced senescence causes lung injury through different mechanisms. This defines the ontogeny of lung senescence and provides an optimal therapeutic window for mitigating neonatal hyperoxic lung injury by inhibiting senescence.


Assuntos
Hiperóxia , Lesão Pulmonar , Animais , Camundongos , Hiperóxia/metabolismo , Alvéolos Pulmonares/metabolismo , Animais Recém-Nascidos , Lesão Pulmonar/metabolismo , Pulmão/metabolismo
7.
Respir Physiol Neurobiol ; 307: 103973, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36180019

RESUMO

Newborn mammals exhibit biphasic hypoxic ventilatory responses (HVR) characterized by an initial increase in ventilation and a secondary ventilatory depression. The magnitude of the hypoxic ventilatory decline (HVD) in the late phase of the HVR normally decreases with age, but this occurs sooner in rats reared in 60% O2. We investigated whether a lower level of hyperoxia (30% O2) or a short period of recovery (1 or 3 d in 21% O2) would affect the expression of this plasticity. Similar to 60% O2, rat pups reared in 30% O2 until 3-4 days of age exhibited a less biphasic HVR to 12% O2. When pups reared in 60% O2 were returned to normoxia, the magnitude of HVD increased such that pups expressed a biphasic HVR appropriate for their chronological age. Blocking synaptic input from the carotid bodies revealed that CNS hypoxia depressed ventilation less in hyperoxia-reared rats immediately following hyperoxia and after 1 d in normoxia despite recovery of the biphasic HVR. This suggests that recovery of the biphasic HVR occurs in pathways regulating HVD that depend on carotid body activity. The early, carotid body-mediated phase of the HVR was also blunted immediately and 1 d after the hyperoxia exposure, but not after 3 d of recovery. These data confirm that short exposures to mild-to-moderate hyperoxia elicit developmental plasticity in the HVR. However, reemergence of the biphasic HVR after return to normoxia argues against a heterokairic process for the premature transition from biphasic HVR to sustained HVR in hyperoxia-reared rat pups.


Assuntos
Hiperóxia , Ratos , Animais , Animais Recém-Nascidos , Ventilação Pulmonar/fisiologia , Ratos Sprague-Dawley , Hipóxia , Mamíferos
8.
J Cell Mol Med ; 27(2): 304-308, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36573439

RESUMO

Evidence points to the indispensable function of alveolar macrophages (AMs) in normal lung development and tissue homeostasis. However, the importance of AMs in bronchopulmonary dysplasia (BPD) has not been elucidated. Here, we identified a significant role of abnormal AM proliferation and polarization in alveolar dysplasia during BPD, which is closely related to the activation of the IL-33-ST2 pathway. Compared with the control BPD group, AMs depletion partially abolished the epithelialmesenchymal transition process of AECII and alleviated pulmonary differentiation arrest. In addition, IL-33 or ST2 knockdown has protective effects against lung injury after hyperoxia, which is associated with reduced AM polarization and proliferation. The protective effect disappeared following reconstitution of AMs in injured IL-33 knockdown mice, and the differentiation of lung epithelium was blocked again. In conclusion, the IL-33-ST2 pathway regulates AECII transdifferentiation by targeting AMs proliferation and polarization in BPD, which shows a novel strategy for manipulating the IL-33-ST2-AMs axis for the diagnosis and intervention of BPD.


Assuntos
Displasia Broncopulmonar , Hiperóxia , Humanos , Recém-Nascido , Animais , Camundongos , Displasia Broncopulmonar/complicações , Macrófagos Alveolares/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Transdiferenciação Celular , Interleucina-33/genética , Interleucina-33/metabolismo , Pulmão/metabolismo , Modelos Animais de Doenças , Animais Recém-Nascidos
9.
Biomaterials ; 293: 121943, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36527790

RESUMO

Recent trends in the design of regenerative materials include the development of bioactive matrices to harness the innate healing ability of the body using various biophysicochemical stimuli (defined as in situ tissue regeneration). Among these, hyperoxia (>21% pO2) is a well-known therapeutic factor for promoting tissue regeneration, such as immune cell recruitment, cell proliferation, angiogenesis, and fibroblast differentiation into myofibroblast. Although various strategies to induce hyperoxia are reported, developing advanced hyperoxia-inducing biomaterials for tissue regeneration is still challenging. In this study, a catalase-immobilized syringe (defined as an Oxyringe) via calcium peroxide-mediated surface modification is developed as a new type of oxygen-supplying system. Hyperoxia-inducible hydrogels are fabricated utilizing Oxyringe. This hydrogel plays a role as a physical barrier for hemostasis. In addition, hyperoxic matrices induce transient hyperoxia in vivo (up to 46.0% pO2). Interestingly, the hydrogel-induced hyperoxia boost the initial macrophage recruitment and rapid inflammation resolution. Furthermore, hyperoxic oxygen release of hydrogels facilitates neovascularization and cell proliferation involved in the proliferation phase, expediting tissue maturation related to the remodeling phase in wound healing. In summary, Oxyringe has excellent potential as an advanced oxygen-supplying platform to create hyperoxia-inducing hydrogels for in situ tissue regeneration.


Assuntos
Hiperóxia , Humanos , Hiperóxia/tratamento farmacológico , Hidrogéis/farmacologia , Seringas , Oxigênio , Cicatrização
11.
Pharmacol Res ; 187: 106624, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36563868

RESUMO

Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory. We hypothesized that the combination with oxygen therapy might improve the treatment efficacy of selenium in hypoxic tumors through the changes of redox environment. In this work, two selenium compounds, Na2SeO3 and CysSeSeCys, were selected to interrogate their therapeutic effects on hepatocellular carcinoma (HCC) under different oxygen levels. In tumor-bearing mice, both selenium compounds significantly inhibited the tumor growth, and combined with oxygen therapy further reduced the tumor volume about 50 %. In vitro HepG2 cell experiments, selenium induced autophagy and delayed apoptosis under hypoxia (1 % O2), while inhibited autophagy and accelerated apoptosis under hyperoxia (60 % O2). We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H2Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H2O2, leading to inhibit the expression level of Nrf2 and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis. Once the Nrf2 gene was knocked down, selenium compounds combined with hyperoxia treatment would further activate the MAPK signaling pathway and further increase apoptosis. These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways, thus providing novel therapeutic strategy for the hypoxic tumors and pave the way for the application of selenium in clinical treatment.


Assuntos
Carcinoma Hepatocelular , Hiperóxia , Neoplasias Hepáticas , Compostos de Selênio , Selênio , Animais , Camundongos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Selênio/farmacologia , Selênio/uso terapêutico , Compostos de Selênio/metabolismo , Compostos de Selênio/farmacologia , Compostos de Selênio/uso terapêutico , Peróxido de Hidrogênio/farmacologia , Transdução de Sinais , Apoptose , Hipóxia , Oxigênio , Microambiente Tumoral
12.
Int Immunopharmacol ; 113(Pt A): 109386, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36461593

RESUMO

IL-17D is a new member of the IL-17 family. Currently, it is believed that IL-17D can directly act on immune cells or may indirectly modulate immune responses by regulating cytokine expression. Herein, we hypothesized that IL-17D regulates the expression of chemokines in intestinal epithelial cells, in turn modulating the immune response within intestinal mucosa under hyperoxia. To explore this notion, newborn rats were divided into a hyperoxia group (85 % O2) and control group (21 % O2). Small intestinal tissues were obtained from neonatal rats at 3, 7, 10, and 14 days. Similarly, intestinal epithelial cells were treated by hyperoxia (85 % O2) as the hyperoxia group or were incubated under normal oxygen (21 % O2) as the control group. Finally, intestinal epithelial cells subjected to hyperoxia were treated with recombinant IL-17D and IL-17D antibodies for 24, 48, and 72 h. Immunohistochemistry, western blot, and reverse transcription-quantitative polymerase chain reaction were used to detect the expression levels of chemokines and chemokine receptors in intestinal tissues of newborn rats and intestinal epithelial cells. We found that hyperoxia affected chemokine expression both in vivo and in vitro. Under hyperoxia, IL-17D promoted the expression of CCL2, CCL25, CCL28, and CCR9 in intestinal epithelial cells while downregulating CCR2, CCR5, CCL5, and CCL20. Our findings provide a basis for further study on the effects of hyperoxia-induced intestinal inflammation and intestinal injury.


Assuntos
Hiperóxia , Interleucina-27 , Ratos , Animais , Receptores de Quimiocinas , Células Epiteliais , Intestinos , Fatores Imunológicos , Oxigênio
14.
BMJ Open ; 12(12): e062299, 2022 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-36523244

RESUMO

INTRODUCTION: Oxygen is the most common drug used in critical care patients to correct episodes of hypoxaemia. The adoption of new technologies in clinical practice, such as closed-loop systems for an automatic oxygen titration, may improve outcomes and reduce the healthcare professionals' workload at the bedside; however, certainty of the evidence regarding the safety and benefits still remains low. We aim to evaluate the effectiveness, efficacy and safety of the closed-loop oxygen control for patients with hypoxaemia during the hospitalisation period by conducting a systematic review and meta-analysis. METHODS AND ANALYSIS: MEDLINE, CENTRAL, EMBASE, LILACS, CINAHL and LOVE evidence databases will be searched. Randomised controlled trials and cross-over studies investigating the PICO (Population, Intervention, Comparator and Outcome) framework will be included. The primary outcomes will be the time in the peripheral oxygen saturation target. Secondary outcomes will include time for oxygen weaning time; length of stay; costs; adverse events; mortality; healthcare professionals' workload, and percentage of time with hypoxia and hyperoxia. Two reviewers will independently screen and extract data and perform quality assessment of included studies. The Cochrane risk of bias tool will be used to assess risk of bias. The RevMan V.5.4 software will be used for statistical analysis. Heterogeneity will be analysed using I2 statistics. Mean difference or standardised mean difference with 95% CI and p value will be used to calculate treatment effect for outcome variables. ETHICS AND DISSEMINATION: Ethical approval is not required because this systematic review and meta-analysis is based on previously published data. Final results will be published in peer-reviewed journals and presented at relevant conferences and events. PROSPERO REGISTRATION NUMBER: CRD42022306033.


Assuntos
Hiperóxia , Oxigênio , Humanos , Oxigênio/uso terapêutico , Hipóxia/terapia , Cuidados Críticos , Hospitalização , Metanálise como Assunto , Revisões Sistemáticas como Assunto
15.
Diving Hyperb Med ; 52(4)2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36525683

RESUMO

INTRODUCTION: Previous studies have highlighted hyperoxia-induced microcirculation modifications, but few have focused on hyperbaric oxygen (HBO) effects. Our primary objective was to explore hyperbaric hyperoxia effects on the microcirculation of healthy volunteers and investigate whether these modifications are adaptative or not. METHODS: This single centre, open-label study included 15 healthy volunteers. Measurements were performed under five conditions: T0) baseline value (normobaric normoxia); T1) hyperbaric normoxia; T2) hyperbaric hyperoxia; T3) normobaric hyperoxia; T4) return to normobaric normoxia. Microcirculatory data were gathered via laser Doppler, near-infrared spectroscopy and transcutaneous oximetry (PtcO2). Vascular-occlusion tests were performed at each step. We used transthoracic echocardiography and standard monitoring for haemodynamic investigation. RESULTS: Maximal alterations were observed under hyperbaric hyperoxia which led, in comparison with baseline, to arterial hypertension (mean arterial pressure 105 (SD 12) mmHg vs 95 (11), P < 0.001) and bradycardia (55 (7) beats·min⁻¹ vs 66 (8), P < 0.001) while cardiac output remained unchanged. Hyperbaric hyperoxia also led to microcirculatory vasoconstriction (rest flow 63 (74) vs 143 (73) perfusion units, P < 0.05) in response to increased PtcO2 (104.0 (45.9) kPa vs 6.3 (2.4), P < 0.0001); and a decrease in laser Doppler parameters indicating vascular reserve (peak flow 125 (89) vs 233 (79) perfusion units, P < 0.05). Microvascular reactivity was preserved in every condition. CONCLUSIONS: Hyperoxia significantly modifies healthy volunteer microcirculation especially during HBO exposure. The rise in PtcO2 promotes an adaptative vasoconstrictive response to protect cellular integrity. Microvascular reactivity remains unaltered and vascular reserve is mobilised in proportion to the extent of the ischaemic stimulus.


Assuntos
Oxigenoterapia Hiperbárica , Hiperóxia , Humanos , Microcirculação/fisiologia , Voluntários Saudáveis , Oxigênio , Hemodinâmica/fisiologia , Oxigenoterapia Hiperbárica/métodos
16.
Adv Exp Med Biol ; 1395: 69-73, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36527616

RESUMO

Supplementation of oxygen at concentrations significantly above environmental level for prolonged periods may lead to hyperoxia and tissue toxicity. The mammalian brain undergoes structural and functional changes during adaptation to hypoxia and hyperoxia. In this study we investigated the effect of prolonged hyperoxic exposure on cognitive and motor performance in mice. Two-month-old male mice were placed in either hyperoxic (50% O2) or normoxic conditions for 3 weeks. Cognitive function was measured using the Y-maze test. High alteration rate between the three arms of the maze is indicative of sustained memory and cognitive function. Motor function was measured using the grip strength and rotarod tests. In the rotarod test high speed and long latency are indicative of coordination and resistance. After 3 weeks of exposure, hematocrit levels were significantly decreased in the hyperoxia group compared to normoxic control littermates (%, mean ± SD, 37.8 ± 1.3, n = 15 vs. 49.9 ± 5.1, n = 15, p < 0.05). In the Y-maze test, chronic hyperoxic exposure resulted in a statistically significant decrease in alteration rate compared to normoxic control (%, mean ± SD, 53.4 ± 9.9, n = 30 vs. 61.2 ± 9.5, n = 15, p < 0.05). The rotarod and grip strength tests did not show statistically significant changes between the two groups. Our data suggest that chronic hyperoxia may lead to decreased cognitive performance in adult mice, which may be secondary to structural and functional changes in the brain.


Assuntos
Hiperóxia , Animais , Camundongos , Masculino , Hipóxia , Oxigênio , Adaptação Fisiológica , Cognição , Mamíferos
17.
Cells ; 11(23)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36496995

RESUMO

The global epidemic of obesity is tightly associated with numerous comorbidities, such as type II diabetes, cardiovascular diseases and the metabolic syndrome. Among the key features of obesity, some studies have suggested the abnormal expansion of adipose-tissue-induced local endogenous hypoxic, while other studies indicated endogenous hyperoxia as the opposite trend. Endogenous hypoxic aggravates dysfunction in adipose tissue and stimulates secretion of inflammatory molecules, which contribute to obesity. In contrast, hypoxic exposure combined with training effectively generate exogenous hypoxic to reduce body weight and downregulate metabolic risks. The (patho)physiological effects in adipose tissue are distinct from those of endogenous hypoxic. We critically assess the latest advances on the molecular mediators of endogenous hypoxic that regulate the dysfunction in adipose tissue. Subsequently we propose potential therapeutic targets in adipose tissues and the small molecules that may reverse the detrimental effect of local endogenous hypoxic. More importantly, we discuss alterations of metabolic pathways in adipose tissue and the metabolic benefits brought by hypoxic exercise. In terms of therapeutic intervention, numerous approaches have been developed to treat obesity, nevertheless durability and safety remain the major concern. Thus, a combination of the therapies that suppress endogenous hypoxic with exercise plans that augment exogenous hypoxic may accelerate the development of more effective and durable medications to treat obesity and comorbidities.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperóxia , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/metabolismo , Hipóxia/metabolismo , Tecido Adiposo/metabolismo , Hiperóxia/complicações
18.
Nutrients ; 14(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36558387

RESUMO

A high fiber diet (HFD) and dietary supplementation with acetate have been reported to have beneficial effects in a variety of diseases. We investigated the effects of a HFD and acetate supplementation on the gut microbiota and hyperoxia-induced acute lung injury (HALI) in mice. Mice were fed a control diet, HFD, or acetate supplementation for three weeks, and their gut microbiome composition, lung tissues, and bronchoalveolar lavage fluid (BALF) were examined after exposure to ambient air or hyperoxia. Both the HFD and acetate supplementation modified the gut microbiota community and increased the proportion of acetate-producing bacteria in mice exposed to hyperoxia. The HFD and acetate supplementation also increased the abundance of Bacteroides acidifaciens and reduced gut dysbiosis according to the ratio of Firmicutes to Bacteroidetes. Compared with hyperoxia-exposed mice fed a control diet, both the HFD and acetate supplementation significantly increased the survival time while reducing the severity of pulmonary edema and the concentrations of protein and inflammatory mediators in BALF. Moreover, the HFD and acetate supplementation reduced the production of free radicals, attenuated NF-κB signaling activation, and decreased apoptosis in the lung tissues. Overall, this study indicates that a HFD or acetate supplementation reduces the severity of HALI through alterations in the gut microbiota to exert anti-inflammatory effects.


Assuntos
Lesão Pulmonar Aguda , Hiperóxia , Camundongos , Animais , Dieta Hiperlipídica , Acetatos , Suplementos Nutricionais , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Camundongos Endogâmicos C57BL
19.
Respir Res ; 23(1): 340, 2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36496404

RESUMO

BACKGROUND: Premature infants, subjected to supplemental oxygen and mechanical ventilation, may develop bronchopulmonary dysplasia, a chronic lung disease characterized by alveolar dysplasia and impaired vascularization. We and others have shown that hyperoxia causes senescence in cultured lung epithelial cells and fibroblasts. Although miR-34a modulates senescence, it is unclear whether it contributes to hyperoxia-induced senescence. We hypothesized that hyperoxia increases miR-34a levels, leading to cellular senescence. METHODS: We exposed mouse lung epithelial (MLE-12) cells and primary human small airway epithelial cells to hyperoxia (95% O2/5% CO2) or air (21% O2/5% CO2) for 24 h. Newborn mice (< 12 h old) were exposed to hyperoxia (> 95% O2) for 3 days and allowed to recover in room air until postnatal day 7. Lung samples from premature human infants requiring mechanical ventilation and control subjects who were not mechanically ventilated were employed. RESULTS: Hyperoxia caused senescence as indicated by loss of nuclear lamin B1, increased p21 gene expression, and senescence-associated secretory phenotype factors. Expression of miR-34a-5p was increased in epithelial cells and newborn mice exposed to hyperoxia, and in premature infants requiring mechanical ventilation. Transfection with a miR-34a-5p inhibitor reduced hyperoxia-induced senescence in MLE-12 cells. Additionally, hyperoxia increased protein levels of the oncogene and tumor-suppressor Krüppel-like factor 4 (KLF4), which were inhibited by a miR-34a-5p inhibitor. Furthermore, KLF4 knockdown by siRNA transfection reduced hyperoxia-induced senescence. CONCLUSION: Hyperoxia increases miR-34a-5p, leading to senescence in lung epithelial cells. This is dictated in part by upregulation of KLF4 signaling. Therefore, inhibiting hyperoxia-induced senescence via miR-34a-5p or KLF4 suppression may provide a novel therapeutic strategy to mitigate the detrimental consequences of hyperoxia in the neonatal lung.


Assuntos
Displasia Broncopulmonar , Hiperóxia , Fator 4 Semelhante a Kruppel , MicroRNAs , Animais , Humanos , Camundongos , Animais Recém-Nascidos , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/tratamento farmacológico , Dióxido de Carbono , Senescência Celular , Células Epiteliais/metabolismo , Hiperóxia/genética , Hiperóxia/metabolismo , Fator 4 Semelhante a Kruppel/genética , Fator 4 Semelhante a Kruppel/metabolismo , Pulmão/metabolismo , MicroRNAs/metabolismo
20.
Undersea Hyperb Med ; 49(4): 395-413, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36446287

RESUMO

Depending on pO2 and exposure time hyperoxic breathing gas may cause injury in many organs including the lungs. Pulmonary oxygen toxicity (POT) may be asymptomatic, but will initially present as a tracheobronchitis in symptomatic subjects. A number of objective measurements of POT have been investigated, but the decrement in vital capacity (VC) has remained the most accepted outcome measure. The unit pulmonary toxic dose (UPTD) has been established as the most common exposure index for POT in diving. UPTD is calculated based on the pO2 and exposure time. A literature search identified five models predicting POT, but no model would accurately predict VC change for the full range of pO2 variation and exposure time relevant for surface-oriented diving. Nevertheless, compared to UPTD, the K-index (K = t2*pO24.57, where t = time (hours) and pO2 = inspired pO2 (atm)) suggested by Arieli performed better for pO2 > 150 kPa and allowed estimation of recovery. We recommend that the Arieli K-index should replace UPTD as the POT exposure index for all surface-oriented diving. Based on the limited data available we suggest a daily threshold of K = 120 for a maximum of two diving days followed by two days of recovery. For five consecutive days of diving, we recommend that the threshold should not exceed K=70 and two recovery days should be allowed. For multiday diving without days of recovery, the daily exposure should probably be limited to K = 40-50.


Assuntos
Mergulho , Hiperóxia , Humanos , Mergulho/efeitos adversos , Hiperóxia/complicações , Capacidade Vital , Oxigênio , Pulmão
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