Changes In Oxygen Metabolism Research Articles

Study on the Effects of Acupuncture with the "Yizhi Tiaoshen" Acupoint Formula on Blood Oxygen Metabolism and Neural Function in Key Brain Regions of AD Rats.

Exploring the effects of acupuncture at the "Yizhi Tiaoshen" acupoint on blood oxygen metabolism and neurological function changes in the brain regions of AD model rats. The AD model was replicated by intraperitoneal injection of D-galactose combined with bilateral hippocampal CA1 injection of Okadaic acid (OA). Thirty rats with successfully replicated model were selected through Morris water maze experiment and randomly divided into model group, donepezil hydrochloride group, and acupuncture group, with 10 rats in each group. After treatment, fNIRs were used to detect changes in Oxy Hb, Deoxy Hb, and Total Hb in the cerebral cortex of rats in each group, in order to evaluate the neurological function changes in key brain areas. The escape latency of the donepezil hydrochloride group and the acupuncture group was shortened, the number of crossings through the original platform increased, and the duration of stay in the quadrant where the original platform was located was prolonged. Based on fNIRs detection, the main differential channels of blood oxygen metabolism in AD rats were identified as 2-2 and 8-7, corresponding to the prefrontal and parietal lobes, respectively. The concentrations of Oxy Hb and Total Hb were significantly increased in both treatment groups, while the concentration of Deoxy Hb was significantly decreased. Acupuncture with the "Yizhi Tiaoshen" acupoint formula and donepezil hydrochloride can improve the learning and memory function of AD rats, and its mechanism may be related to improving blood oxygen metabolism in the prefrontal and parietal regions and protecting neuronal function.

Non-invasive determination of critical dissolved oxygen thresholds for stress physiology in fish using triple-oxygen stable isotopes and aquatic respirometry

ABSTRACT Understanding the critical thresholds of dissolved oxygen (O2) that trigger adaptive physiological responses in aquatic organisms is long hampered by a lack of robust, non-lethal or non-invasive methodologies. The isotope fractionation of triple O2 isotopes (18O/17O/16O) during respiration is linked to the amount of oxygen utilised, offering a potential avenue for new insights. Our experimental research involved measuring the oxygen isotope fractionation of dissolved O2 in closed-system aquatic respirometry experiments with wild sticklebacks (Gasterosteus aculeatus). These fish were either naturally adapted or experimentally acclimated to hypoxic and normoxic conditions. The aim was to observe their oxygen usage and isotope fractionation in response to increasingly severe hypoxia. Initial observations revealed a progressive 18O enrichment from the preferential uptake of 16O to a dissolved oxygen threshold of 3–5 mg O2 L–1, followed by an apparent reversal in oxygen isotope fractionation, which is mixing of 16O and 17O with the remaining O2 pool across all populations and indicative of a systematic change in oxygen metabolism among the fish. Unexpectedly, sticklebacks adapted to hypoxia but acclimated to normoxia exhibited stronger oxygen isotope fractionation compared to those adapted to normoxia and acclimated to hypoxia, contradicting the hypothesis that hypoxia adaptation would lead to reduced isotope discrimination due to more efficient oxygen uptake. These preliminary experimental results highlight the novel potential of using dissolved O2 isotopes as a non-invasive, non-lethal method to quantitatively assess metabolic thresholds in aquatic organisms. This approach could significantly improve our understanding of the critical oxygen responses and adaptation mechanisms in fish and other aquatic organisms across different oxygen environments, marking a significant step forward in aquatic ecological and physiological research.

Oxygen metabolism after cardiac arrest: Patterns and associations with survival

AimWhether changes in oxygen metabolism, as measured by oxygen consumption (VO2), carbon dioxide production (VCO2) and the respiratory exchange ratio (RER), are associated with survival after cardiac arrest is poorly understood. In this prospective observational study, we investigated the association between VO2, VCO2, and RER in the initial 12 and 24 h after return of spontaneous circulation (ROSC) and survival to hospital discharge. MethodsAdults with ROSC after cardiac arrest, admitted to the intensive care unit, requiring mechanical ventilation and treated with targeted temperature management were included. VO2 and VCO2 were measured continuously for 24 h after ROSC, using a noninvasive anesthesia monitor. Area under the curve for VO2, VCO2 & RER was calculated using all available values over 12 and 24 h after ROSC. Using logistic regression, we evaluated the relationship between these metabolic variables and survival to hospital discharge. Analyses were adjusted for temperature, vasopressors, and neuromuscular blockade. ResultsSixty four patients were included. Mean age was 64 ± 16 years, and 59% were women. There was no significant association between the area under the curve of VO2 or VCO2 and survival. A higher RER in the initial 12 h was associated with better survival (aOR = 3.97, 95% CI [1.01,15.6], p = 0.048). Survival was lower in those with median RER < 0.7 in the initial 12 h compared with those with a median RER ≥ 0.7 (25% vs 67%, p = 0.011). ConclusionHigher RER in the initial 12 h was associated with survival after cardiac arrest. The etiology of unusually low RERs in this patient population remains unclear.

Assessment of brain oxygen extraction fraction between normal cognition and mild cognitive impairment in an elderly cohort using quantitative BOLD

AbstractBackgroundThis study is to quantify oxygen extraction fraction (OEF), an important physiological biomarker for brain hemodynamic impairment, in the elderly cohort using non‐invasive quantitative BOLD (qBOLD) modeling, which is an MRI method for assessment of hemodynamic and metabolic properties.Methods56 participants (75.4±7.0yo, 37F), including 46 cognitively normal (CN) individuals (75.2±7.3yo, 29F) and 10 mild‐cognitive‐impairment (MCI) patients (76.0±6.1yo, 7F), were recruited from UC Davis Alzheimer’s Disease Research Center cohort. MRI scans were acquired on a 3T scanner (Siemens Tim Trio) with a 32‐channel head coil, including an Asymmetric Spin Echo (ASE) scan (TR/TE, 2800/66ms; 2.3×2.3.x1.3mm3 resolution; FOV, 224mm; 13 values of the spin echo displacement time, from 0 to 52ms) and a T1‐weighted MPRAGE. T1‐weighted images were segmented into regions of interest (ROI), including gray matter (GM), white matter (WM), and cortical lobes (frontal, parietal, occipital, temporal) using FSL FAST. ASE signal curves were preprocessed and fit to two‐compartment qBOLD model with Variational Bayesian framework to estimate deoxygenated blood volume (DBV) and transverse relaxation rate (R2 ’), which are used to quantify OEF with known physiological constants (Cherukara et al., NeuroImage 2019). Average OEF values were calculated and compared for each ROI between CN and MCI groups using pairwise t‐tests with Bonferroni correction. The correlation between OEF and age were assessed using a linear mixed effects model that accounted for subject clustering.ResultsCompared to CN, reduced DBV and increased OEF were observed throughout most of the brain on the group average level in MCI (Figure 1). In regional analysis, we observed a trend of increased OEF in MCI compared to CN in several ROIs, which was significant in the occipital lobe (p = 0.007) (Figure 2). In Figure 3, OEF was inversely correlated with age in the parietal lobe for CN (p = 0.026). In contrast, there was a positive trend of association between OEF and age for MCI across all regions.ConclusionThis study showed that age has an association with brain oxygen extraction that are differently affected by normal aging and MCI. Higher brain OEF in MCI individuals may reflect changes in oxygen metabolism because of underlying pathology, including vascular injury and compensation for hypoperfusion.

Assessment of brain oxygen extraction fraction between normal cognition and mild cognitive impairment in an elderly cohort using quantitative BOLD

AbstractBackgroundThis study is to quantify oxygen extraction fraction (OEF), an important physiological biomarker for brain hemodynamic impairment, in the elderly cohort using non‐invasive quantitative BOLD (qBOLD) modeling, which is an MRI method for assessment of hemodynamic and metabolic properties.Method56 participants (75.4±7.0yo, 37F), including 46 cognitively normal (CN) individuals (75.2±7.3yo, 29F) and 10 mild‐cognitive‐impairment (MCI) patients (76.0±6.1yo, 7F), were recruited from UC Davis Alzheimer’s Disease Research Center cohort. MRI scans were acquired on a 3T scanner (Siemens Tim Trio) with a 32‐channel head coil, including an Asymmetric Spin Echo (ASE) scan (TR/TE, 2800/66ms; 2.3×2.3.x1.3mm3 resolution; FOV, 224mm; 13 values of the spin echo displacement time, from 0 to 52ms) and a T1‐weighted MPRAGE. T1‐weighted images were segmented into regions of interest (ROI), including gray matter (GM), white matter (WM), and cortical lobes (frontal, parietal, occipital, temporal) using FSL FAST. ASE signal curves were preprocessed and fit to two‐compartment qBOLD model with Variational Bayesian framework to estimate deoxygenated blood volume (DBV) and transverse relaxation rate (R2’), which are used to quantify OEF with known physiological constants (Cherukara et al., NeuroImage 2019). Average OEF values were calculated and compared for each ROI between CN and MCI groups using pairwise t‐tests with Bonferroni correction. The correlation between OEF and age were assessed using a linear mixed effects model that accounted for subject clustering.ResultCompared to CN, reduced DBV and increased OEF were observed throughout most of the brain on the group average level in MCI (Figure 1). In regional analysis, we observed a trend of increased OEF in MCI compared to CN in several ROIs, which was significant in the occipital lobe (p = 0.007) (Figure 2). In Figure 3, OEF was inversely correlated with age in the parietal lobe for CN (p = 0.026). In contrast, there was a positive trend of association between OEF and age for MCI across all regions.ConclusionThis study showed that age has an association with brain oxygen extraction that are differently affected by normal aging and MCI. Higher brain OEF in MCI individuals may reflect changes in oxygen metabolism because of underlying pathology, including vascular injury and compensation for hypoperfusion.

Diminished ovarian reserve causes adverse ART outcomes attributed to effects on oxygen metabolism function in cumulus cells

BackgroundDeclining oocyte quality in women with advanced age has been a major impediment to assisted reproductive treatments’ (ART) success rate. However, aging is often accompanied by a diminished ovarian reserve (DOR). Cumulus cells (CCs) are known to play an important role in the development and maturation of oocytes, and the quality of CCs actually reflects the quality of the oocyte. In this study, CCs were used to investigate the real reasons for the decline in oocyte quality in older women.MethodsNinety-nine CC samples were subdivided into 4 different groups according to the different age and ovarian reserve status. Other than clinical ART results, transcriptional expression profiles were performed in CCs to detect the differences.ResultsThe results were that DOR, no matter in young or advanced age group, was found to be significantly associated with adverse ART outcomes. Of note, there were no statistically significant changes in ART outcomes in the group at advanced age with normal ovarian reserve (NOR), compared to the young with NOR. DOR induced a series of transcriptional variations in CCs commonly enriched in oxygen metabolism.ConclusionOur results revealed that the ART outcomes in advanced patients were attributable to the DOR. The oxygen metabolic changes may interfere with CCs’ function of supporting oocytes. This study can provide guidance for ART practice that not age but ovarian reserve status is the main predictor for ART outcomes, and ovarian reserve status should be timely assessed when the clinical manifestations are still mild in elderly women.

Investigating the link between regional oxygen metabolism and cognitive speed in multiple sclerosis: Implications for fatigue

BackgroundMost multiple sclerosis (MS) patients experience fatigue and cognitive decline but the underlying mechanisms remain unknown. Previous work has shown whole brain resting cerebral metabolic rate of oxygen (CMRO2) is associated with the extent of these symptoms. However, it is not known if the association between global CMRO2 and MS-related cognitive speed and fatigue can be localized to specific brain regions. Based upon previous research suggesting prefrontal involvement in MS-related changes in cognitive speed and fatigue, we hypothesized that oxygen metabolic changes within prefrontal cortex (PFC) might form the pathophysiologic basis of cognitive performance and fatigue in MS patients. ObjectiveInvestigate whether PFC ΔCMRO2 is associated with cognitive speed and fatigue in MS. MethodsMS and healthy control (HC) participants were scanned using a dual-­echo fMRI sequence and underwent a hypercapnia calibration experiment that permitted estimation of ΔCMRO2 while performing a scanner version of symbol-digit modalities task, a measure of information processing speed and utilized in the clinic as a reliable sentinel biomarker for global cognitive impairment in MS. Participants then completed the Modified Fatigue Impact Scale (MFIS) to measure fatigue. ResultsMS patients exhibited significant reductions in cognitive performance relative to HCs (p < 0.04). Prefrontal ΔCMRO2 explained significant variability (ΔR2 = 0.11) in cognitive speed, over and above disease and demographic variables, for the MS group only. Prefrontal ΔCMRO2 was not associated with fatigue across groups. ΔCMRO2 in visual and motor areas were not associated with cognitive performance or fatigue for either group. ConclusionPrefrontal oxygen metabolism may be a sensitive measure of MS-related cognitive decline.

Physiological modeling of the BOLD signal and implications for effective connectivity: A primer

In this primer, I provide an overview of the physiological processes that contribute to the observed BOLD signal (i.e., the generative biophysical model), including their time course properties within the framework of the physiologically-informed dynamic causal modeling (P-DCM). The BOLD signal is primarily determined by the change in paramagnetic deoxygenated hemoglobin, which results from combination of changes in oxygen metabolism, and cerebral blood flow and volume. Specifically, the physiological origin of the so-called BOLD signal “transients” will be discussed, including the initial overshoot, steady-state activation and the post-stimulus undershoot. I argue that incorrect physiological assumptions in the generative model of the BOLD signal can lead to incorrect inferences pertaining to both local neuronal activity and effective connectivity between brain regions. In addition, I introduce the recent laminar BOLD signal model, which extends P-DCM to cortical depths-resolved BOLD signals, allowing for laminar neuronal activity to be determined using high-resolution fMRI data.

Hyperbaric Oxygen Therapy versus placebo for post-concussion syndrome (HOT-POCS): A randomized, double-blinded controlled pilot study

Post-Concussion Syndrome (PCS) refers to the persistence of physical, cognitive, and emotional symptoms following mild traumatic brain injury (mTBI)/concussion, occurring in roughly 15–30% of individuals. Hyperbaric oxygen therapy (HBOT) has been suggested as a potential treatment for PCS; however, the evidence to date is mixed due to inconsistencies in the treatment protocol and focus on veterans with combat-related injuries, which may not be generalizable to the general population. The goal of Hyperbaric Oxygen Therapy for Post-Concussion Syndrome (HOT-POCS) is to assess the efficacy and safety of HBOT for the treatment of PCS in the civilian population. This randomized, controlled pilot study will be using a standardized HBOT protocol (20 sessions of 100% O2 at 2.0 atm absolute [ATA]) compared with a true placebo gas system that mimics the oxygen composition at room air (20 sessions of 10.5% O2 and 89.5% nitrogen at 2.0 ATA) in a cohort of 100 adults with persistent post-concussive symptoms 3–12 months following injury. Change in symptoms on the Rivermead Post-concussion Questionnaire (RPQ) will be the primary outcome of interest. Secondary outcomes include the rate of adverse events, change in the quality of life, and change in cognitive function. Exploratory outcome measures will include changes in physical function and changes in cerebral brain perfusion and oxygen metabolism on MRI brain imaging. Overall, the HOT-POCS study will compare the efficacy of a standardized HBOT treatment protocol against a true placebo gas for the treatment of PCS within 12 months after injury.

Novel prognostication biomarker adipophilin reveals a metabolic shift in uveal melanoma and new therapeutic opportunities.

Metastatic uveal melanoma remains incurable at present. We previously demonstrated that loss of BAP1 gene expression in tumour cells triggers molecular mechanisms of immunosuppression in the tumour microenvironment (TME) of metastatic uveal melanoma. Adipophilin is a structural protein of lipid droplets involved in fat storage within mammalian cells, and its expression has been identified in uveal melanoma. We comprehensively evaluated adipophilin expression at the RNA (PLIN2) and protein levels of 80 patients of the GDC-TCGA-UM study and in a local cohort of 43 primary uveal melanoma samples respectively. PLIN2 expression is a survival prognosticator biomarker in uveal melanoma. Loss of adipophilin expression is significantly associated with monosomy 3 status and nuclear BAP1 losses in uveal melanoma tumours. Integrative transcriptomic and secretome studies show a relationship between transient loss of adipophilin expression and increased levels of tumour-associated macrophages and hypoxia genes, suggesting PLIN2-dependent changes in oxygen and lipid metabolism in the TME of low and high-metastatic risk uveal melanoma. We designed four adipophilin-based multigene signatures for uveal melanoma prognostication using a transcriptomic and secretome survival-functional network approach. Adipophilin-based multigene signatures were validated in BAP1-positive and BAP1-negative uveal melanoma cell lines using a next-generation RNA sequencing approach. We identified existing small molecules, mostly adrenergic, retinoid, and glucocorticoid receptor agonists, MEK, and RAF inhibitors, with the potential to reverse this multigene signature expression in uveal melanoma. Some of these molecules were able to impact tumour cell viability, and carvedilol, an adrenergic receptor antagonist, restored PLIN2 levels, mimicking the expression of normoxia/lipid storage signatures and reversing the expression of hypoxia/lipolysis signatures in co-cultures of uveal melanoma cells with human macrophages. These findings open up a new research line for understanding the lipid metabolic regulation of immune responses, with implications for therapeutic innovation in uveal melanoma. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Photoacoustic Microscopic Imaging of Cerebral Vessels for Intensive Monitoring of Metabolic Acidosis.

Metabolic acidosis as one of the most common perioperative complications has been associated with increased risks for poor prognosis. Routine monitoring methods include blood gas analysis and electrocardiogram, which are limited by time delay effects. And the existing intravital imaging modalities are difficult to achieve in one step. Here, we present a dual-wavelength photoacoustic imaging approach to overcome this dilemma. The aim of this study was to develop a rapid approach for intensive monitoring of acid-base imbalance and cerebral oxygen metabolism. We characterized the cerebrovascular structure by label-free dual-wavelength (532 and 559nm) photoacoustic microscopy in healthy and diabetic mouse models with metabolic acidosis. Concurrently, we developed a single-vessel analysis method to accurately delineate the differential responses of small vessels and quantify the cerebral oxygenation following experimental alteration of pH. We demonstrated that there was an increasing trend in changes of vascular measurements (density, diameter, and relative hemoglobin concentration) and cerebral microvascular oxygen metabolism with the aggravation of acidosis. Furthermore, we established a clinical nomogram for the diagnosis of disease severity and yielded good discrimination ability with area under the curve of 0.920-0.967 and accuracy of 81.9-93.0%. The nomogram was also validated well in the diabetic mouse model with metabolic acidosis. Our photoacoustic imaging approach has great potential for rapid detection of metabolic acidosis and brain oxygen metabolism, which could potentially be applied as a bedside monitoring method for brain protection and timely treatment of acid-base abnormalities.

Assessing Cerebral Oxygen Metabolism Changes in Patients With Preeclampsia Using Voxel-Based Morphometry of Oxygen Extraction Fraction Maps in Magnetic Resonance Imaging.

The objective of this study was to analyze the different brain oxygen metabolism statuses in preeclampsia using magnetic resonance imaging and investigate the factors that affect cerebral oxygen metabolism in preeclampsia. Forty-nine women with preeclampsia (mean age 32.4 years; range, 18-44 years), 22 pregnant healthy controls (PHCs) (mean age 30.7 years; range, 23-40 years), and 40 non-pregnant healthy controls (NPHCs) (mean age 32.5 years; range, 20-42 years) were included in this study. Brain oxygen extraction fraction (OEF) values were computed using quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude-based OEF mapping (QSM + quantitative blood oxygen level-dependent imaging or QQ) obtained with a 1.5-T scanner. Voxel-based morphometry (VBM) was used to investigate the differences in OEF values in the brain regions among the groups. Among the three groups, the average OEF values were significantly different in multiple brain areas, including the parahippocampus, multiple gyri of the frontal lobe, calcarine, cuneus, and precuneus (all P-values were less than 0.05, after correcting for multiple comparisons). The average OEF values of the preeclampsia group were higher than those of the PHC and NPHC groups. The bilateral superior frontal gyrus/bilateral medial superior frontal gyrus had the largest size of the aforementioned brain regions, and the OEF values in this area were 24.2 ± 4.6, 21.3 ± 2.4, and 20.6 ± 2.8 in the preeclampsia, PHC, and NPHC groups, respectively. In addition, the OEF values showed no significant differences between NPHC and PHC. Correlation analysis revealed that the OEF values of some brain regions (mainly involving the frontal, occipital, and temporal gyrus) were positively correlated with age, gestational week, body mass index, and mean blood pressure in the preeclampsia group (r = 0.361-0.812). Using whole-brain VBM analysis, we found that patients with preeclampsia had higher OEF values than controls.

Retracted: Changes of Entropy Index and Cerebral Oxygen Metabolism in the Maintenance of Remifentanil Anesthesia and Their Predictive Value for Postoperative Hyperalgesia.

[This retracts the article DOI: 10.1155/2022/1080858.].

SCARA5 induced ferroptosis to effect ESCC proliferation and metastasis by combining with Ferritin light chain

BackgroundEsophageal squamous cell carcinoma (ESCC) remains one of the most lethal cancers worldwide accompany with an extremely poor prognosis. Therefore, this study aims to screen for new molecules affecting ESCC and explore their mechanisms of action to provide ideas for targeted therapies for ESCC.MethodsFirstly, we screened out the membrane protein SCARA5 by high-throughput sequencing of the ESCC patient tissues, and RT-qPCR and WB were used to verify the differential expression of SCARA5 in esophageal cell lines, and IHC analyzed the expression localization of SCARA5 in ESCC tissue. Then, flow cytometry, wound healing assay, Transwell assay and CCK-8 assay were used to explore the effects of SCARA5 on cell cycle, migration and invasion as well as cell proliferation activity of esophageal squamous carcinoma cells. Meanwhile, transmission electron microscopy was used to detect changes in cellular mitochondrial morphology, and flow cytometry were used to detect changes in intracellular reactive oxygen metabolism, and immunofluorescence and flow cytometry were used to detect changes in intracellular Fe2+. Mechanistically, co-immunoprecipitation was used to detect whether SCARA5 binds to ferritin light chain, and ferroptosis-related protein expression was detected by WB. Finally, the tumor xenograft model was applied to validation the role of SCARA5 tumor growth inhibition in vivo.ResultsWe found that SCARA5 was aberrantly decreased in ESCC tissues and cell lines. Furthermore, we confirmed that SCARA5 suppressed the cell cycle, metastasis and invasion of ESCC cells. Meanwhile, we also found that overexpression of SCARA5 caused changes in mitochondrial morphology, accumulation of intracellular reactive oxygen species and increased intracellular Fe2+ in ESCC cells, which induced ferroptosis in ESCC cells. Mechanically, we validated that SCARA5 combined with ferritin light chain and increased intracellular Fe2+. As well as, overexpression SCARA5 induced ferroptosis by increasing ferritin light chain in nude mice subcutaneous tumors and inhibited the growth of nude mice subcutaneous tumors.ConclusionCollectively, our findings demonstrated that SCARA5 suppressed the proliferation and metastasis of ESCC by triggering ferroptosis through combining with ferritin light chain.

Retinal blood flow and oxygen metabolism in diabetes

AbstractDiabetic retinopathy is the leading cause for blindness in the Western countries and its prevalence is constantly increasing. In the last years, evidence has accumulated that alterations in the retinal microcirculation and changes in retinal oxygen metabolism play a key role in the disease process. In particular, tissue hypoxia seems to be a major trigger of neovascularization and macular edema in the retina of patients with diabetes.Recently, new methods to assess the retinal vasculature, such as Doppler Optical Coherence Tomography (OCT) or OCT angiography have become available, providing valuable findings in patients with diabetes. Combining these methods with techniques such as the assessment of retinal oxygen saturation, more information about retinal oxygen metabolism can be obtained.The present talk will summarize the current knowledge on retinal blood flow and oxygen metabolism in patients with diabetes.Acknowledgements: Part of the work presented was funded by the Austrian Science Fund (FWF), Projects No. KLI 721 and P26157.

Electrochemical sensing of oxygen metabolism for a three-dimensional cultured model with biomimetic vascular flow

Microphysiological systems (MPSs) with three-dimensional (3D) cultured models have attracted considerable interest because of their potential to mimic human health and disease conditions. Recent MPSs have shown significant advancements in engineering perfusable vascular networks integrated with 3D culture models, realizing a more physiological environment in vitro; however, a sensing system that can monitor their activity under biomimetic vascular flow is lacking. We designed an open-top microfluidic device with sensor capabilities and demonstrated its application in analyzing oxygen metabolism in vascularized 3D tissue models. We first validated the platform by using human lung fibroblast (hLF) spheroids. Then, we applied the platform to a patient-derived cancer organoid and evaluated the changes in oxygen metabolism during drug administration through the vascular network. We found that the platform could integrate a perfusable vascular network with 3D cultured cells, and the electrochemical sensor could detect the change in oxygen metabolism in a quantitative, non-invasive, and real-time manner. This platform would become a monitoring system for 3D cultured cells integrated with a perfusable vascular network.

Biomarker Changes in Oxygen Metabolism, Acid-Base Status, and Performance after the Off-Season in Well-Trained Cyclists.

During the off-season, cyclists reduce their volume and intensity of training in order to recover the body from the high workload during the competitive season. Some studies have examined the effects of the off-season on cardiovascular, metabolic, and performance levels but have not evaluated oxygen metabolism, acid-base status, and electrolytes in cyclists. Therefore, our main objective was to analyze these markers in the off-season period (8 weeks) via finger capillary blood gasometry in well-trained cyclists. We found an increase in oxygen saturation (sO2) and oxyhemoglobin (O2Hb) (p ≤ 0.05) and a decrease in fat oxidation at maximum fat oxidation (FatMax) (p ≤ 0.05). In addition, we observed a decreasing trend of VO2 in the ventilatory threshold 2 (VT2) and maximum oxygen consumption (VO2MAX) (p ≤ 0.06) after the off-season in well-trained cyclists. Negative correlations were found between the pre–post off-season differences in the VO2 at ΔFatMax and ΔHCO3− (bicarbonate ion) and between power generated at the ΔeFTP (functional power threshold) and the ΔVO2MAX with the pH (r ≥ −0.446; p ≤ 0.05). After the off-season period, well-trained cyclists had increased markers of oxygen metabolism, decreased fat oxidation at low exercise intensities, and decreased VO2 at the VT2 and VO2MAX. Relationships were found between changes in the ΔeFTP and VO2MAX with changes in the pH and between the pH and HCO3− with changes in La−.

Using quantitative MRI to study the association of isocitrate dehydrogenase (IDH) status with oxygen metabolism and cellular structure changes in glioma

ObjectiveTo investigate the characteristics of oxygen metabolism and the cellular structure of glioma using quantitative MRI to predict the isocitrate dehydrogenase 1 (IDH1) status and to further understand the biological characteristics of gliomas. MethodsIn this retrospective study, 94 patients with gliomas eventually received quantitative MRI measures to study oxygen metabolism. The oxygen metabolism biomarker maps (oxygen extraction fraction [OEF] and cerebral metabolic rate of oxygen [CMRO2]) and the tissue-cellular-specific (R2t*) MRI relaxation parameter were evaluated in different regions of glioma. ResultsMRI results showed differences in oxygen metabolism measures in all patients with gliomas of different IDH1 statuses. Compared to patients with IDH1 mutant gliomas, patients with IDH1 wild type gliomas showed increased (P < 0.01) CMRO2, OEF, cerebral blood volume [CBF], and R2t* measures in tumor regions, while only OEF, CBF and R2t* were found to be increased (P < 0.05) in the peritumoral area. OEF achieved the best performance for distinguishing IDH1 wild type and mutant gliomas in the tumor area (AUC = 0.732, P < 0.001). R2t* values correlated with Ki-67(R = 0.35, P < 0.001) in the tumor area, while no significant correlations between Ki-67 and R2t* were found in the peritumoral area (R = 0.19, P = 0.072). ConclusionQuantitative MRI has potential applications in studying the tumor and peritumoral areas of glioma, and it has the ability to predict and reveal the characteristics of oxygen metabolism and cellular structure in different regions of gliomas.

Retinal Vascular Physiology Biomarkers in a 5XFAD Mouse Model of Alzheimer's Disease.

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder that affects the brain and retina and lacks reliable biomarkers for early diagnosis. As amyloid beta (Aβ) manifestations emerge prior to clinical symptoms and plaques of amyloid may cause vascular damage, identification of retinal vascular biomarkers may improve knowledge of AD pathophysiology and potentially serve as therapeutic targets. The purpose of the current study was to test the hypothesis that retinal hemodynamic and oxygen metrics are altered in 5XFAD mice. Methods: Thirty-two male mice were evaluated at 3 months of age: sixteen 5XFAD transgenic and sixteen wild-type mice. Spectral-domain optical coherence tomography, vascular oxygen tension, and blood flow imaging were performed in one eye of each mouse. After imaging, the imaged and fellow retinal tissues were submitted for histological sectioning and amyloid protein analysis, respectively. Protein analysis was also performed on the brain tissues. Results: Retinal physiological changes in venous diameter and blood velocity, arterial and venous oxygen contents, coupled with anatomical alterations in the thickness of retinal cell layers were detected in 5XFAD mice. Moreover, an increase in Aβ42 levels in both the retina and brain tissues was observed in 5XFAD mice. Significant changes in retinal oxygen delivery, metabolism, or extraction fraction were not detected. Based on compiled data from both groups, arterial oxygen content was inversely related to venous blood velocity and nerve fiber/ganglion cell layer thickness. Conclusions: Concurrent alterations in retinal hemodynamic and oxygen metrics, thickness, and tissue Aβ42 protein levels in 5XFAD mice at 3 months of age corresponded to previously reported findings in human AD. Overall, these results suggest that this mouse model can be utilized for studying pathophysiology of AD and evaluating potential therapies.

Body composition, mitochondrial oxygen metabolism and metabolome of patients with obesity before and after bariatric surgery (COMMITMENT): protocol for a monocentric prospective cohort study

IntroductionObesity, defined as a body mass index ≥30 kg/m2, is one of the most prevalent health conditions worldwide. It is part of the metabolic syndrome, which encompasses arterial hypertension, dyslipoproteinaemia and diabetes. Obesity is viewed as a systemic disease with pathophysiological mechanisms on the molecular level. Dysfunction of the mitochondrion and systemic low-grade inflammation are among the proposed causes for the metabolic changes. In severe cases of obesity, laparoscopic sleeve gastrectomy, a bariatric operation, can achieve the desired weight loss and has been associated with clinical outcome improvement. Hitherto, the influence of patients’ body composition on mitochondrial function and concomitant metabolic changes has not been fully understood. This study aims to quantify the patient’s body composition before and after laparoscopic sleeve gastrectomy and to correlate these findings with changes in mitochondrial oxygen metabolism, metabolome and immune status.Methods and analysisIn this prospective monocentric cohort study, patients undergoing laparoscopic sleeve gastrectomy (n=30) at Jena University Hospital (Germany) will be assessed before surgery and at four time points during a 1-year follow-up. Body composition will be measured by bioimpedance analysis. Non-invasive assessment of mitochondrial oxygen metabolism using protoporphyrin IX-triplet state lifetime technique (PPIX-TSLT) and blood sampling for, among other, metabolomic and immunological analysis, will be performed. The primary outcome is the difference in relative fat mass between the preoperative time point and 6 months postoperatively. Further outcomes comprise longitudinal changes of PPIX-TSLT and metabolic and immunological variables. Outcomes will be assessed using paired t-tests, Wilcoxon signed-rank tests and regression analyses.Ethics and disseminationThe study was approved by the Ethics Committee of Friedrich Schiller University Jena (2018-1192-BO). Written informed consent will be obtained from all patients prior to enrolment in the study. The results will be published in peer-reviewed journals and presented at appropriate conferences.Trial registration numberDRKS00015891.