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Revista Clinica Espanola Jun 2024To describe the predictors of mortality in hospitalized patients with severe acute respiratory syndrome (SARS) due to COVID-19 presenting with silent hypoxemia.
OBJECTIVE
To describe the predictors of mortality in hospitalized patients with severe acute respiratory syndrome (SARS) due to COVID-19 presenting with silent hypoxemia.
MATERIAL AND METHODS
Retrospective cohort study of hospitalized patients with SARS due to COVID-19 and silent hypoxemia at admission, in Brazil, from January to June 2021. The primary outcome of interest was in-hospital death. Multivariable logistic regression analysis was performed.
RESULTS
Of 46,102 patients, the mean age was 59 ± 16 years, and 41.6% were female. During hospitalization, 13,149 patients died. Compared to survivors, non-survivors were older (mean age, 66 vs. 56 years; P < 0.001), less frequently female (43.6% vs. 40.9%; P < 0.001), and more likely to have comorbidities (74.3% vs. 56.8%; P < 0.001). Non-survivors had higher needs for invasive mechanical ventilation (42.4% vs 6.6%; P < 0.001) and intensive care unit admission (56.9% vs 20%; P < 0.001) compared to survivors. In the multivariable regression analysis, advanced age (OR 1.04; 95%CI 1.037-1.04), presence of comorbidities (OR 1.54; 95%CI 1.47-1.62), cough (OR 0.74; 95%CI 0.71-0.79), respiratory distress (OR 1.32; 95%CI 1.26-1.38), and need for non-invasive respiratory support (OR 0.37; 95%CI 0.35-0.40) remained independently associated with death.
CONCLUSIONS
Advanced age, presence of comorbidities, and respiratory distress were independent risk factors for mortality, while cough and requirement for non-invasive respiratory support were independent protective factors against mortality in hospitalized patients due to SARS due to COVID-19 with silent hypoxemia at presentation.
PubMed: 38945525
DOI: 10.1016/j.rceng.2024.06.010 -
Comparative Biochemistry and... Jun 2024Animals living at high-altitude are faced with unremitting low oxygen availability. This can make it difficult to perform daily tasks that require increases in aerobic...
Animals living at high-altitude are faced with unremitting low oxygen availability. This can make it difficult to perform daily tasks that require increases in aerobic metabolism. An activity important for survival is aerobic locomotion, and the rapid recovery of muscle metabolism post exercise. Past work shows that hypoxia acclimated high-altitude mice (Peromyscus maniculatus) have a greater reliance on carbohydrates to power exercise than low altitude mice. However, it is unclear how quickly after aerobic exercise these mice can recovery and replenish muscle glycogen stores. The gastrocnemius muscle of high-altitude deer mice has a more aerobic phenotype and a greater capacity to oxidize lipids than low altitude deer mice. This suggests that high altitude mice may recover more rapidly from exercise than their lowland counterparts due to a greater capacity to support glycogen replenishment using intramuscular triglycerides (IMTG). To explore this possibility, we used low- and high-altitude native deer mice born and raised in common lab conditions and acclimated to chronic hypoxia. We determined changes in oxygen consumption following 15 min of aerobic exercise in 12% O and sampled skeletal muscles and liver at various time points during recovery to examine changes in key metabolites, including glycogen and IMTG. We found depletion in glycogen stores during exercise only in lowlanders, which returned to resting levels following 90 min of recovery. In contrast, IMTG's did not change significantly with exercise or during recovery in either population. These data suggest that exercise recovery is influenced by altitude ancestry in deer mice.
PubMed: 38945522
DOI: 10.1016/j.cbpb.2024.111004 -
The Science of the Total Environment Jun 2024East-Central Europe's largest shallow lake, Balaton, experienced strong eutrophication in the 1970-80s, followed by water quality improvement and oligotrophication by...
East-Central Europe's largest shallow lake, Balaton, experienced strong eutrophication in the 1970-80s, followed by water quality improvement and oligotrophication by 2010 CE. Recently however, repeated cyanobacterial blooms occurred and warned that internal P-recycling can act similarly to external P load, therefore we need a better understanding of past water level (WL) and trophic changes in the lake. In this study we discuss the last 500-yr trophic, WL and habitat changes of the lake using paleoecological (chironomids, pollen) and geochemical (sediment chlorophyll, TOC, TS, TN, C/H ratio, major and trace element) methods. We demonstrate that the most intensive and irreversible change in the macroinvertebrate fauna occurred during the period of economic boom between the First and Second World War (~1925-1940 CE), when large-scale built-in and leisure use of the lake has intensified. At that time, the Procladius-Microchironomus-Stempellina dominated community transformed to Procladius-Chironomus plumosus-type-Microchironomus community that coincided with land use changes, intensified erosion and water-level regulation in the lake with the maintenance of year-round high WL. This was followed by the impoverishment and population size decrease of the chironomid fauna and Procladius dominance since 1940 CE, without any recovery after 1994 CE despite the ongoing oligotrophication. Accelerated rate of change and turnover of the fauna was connected to an increase in the benthivorous fish biomass and eutrophication. The basin lost almost completely its once characteristic Stempellina species between 1927 and 1940 CE due to trophic level increase and seasonal anoxia in the Szemes Basin. Reference conditions for ecosystem improvement were assigned to 1740-1900 CE. We conclude that in spite of the ongoing oligotrophication, the re-establishment of the Procladius-Microchironomus-Stempellina assemblage is hampered, and requires fish population regulation.
PubMed: 38945249
DOI: 10.1016/j.scitotenv.2024.174191 -
Journal of Microencapsulation Jun 2024This study aimed to encapsulate natural killer (NK) cells in a hydrogel to sustain their function within the hypoxic tumour microenvironments.
AIMS
This study aimed to encapsulate natural killer (NK) cells in a hydrogel to sustain their function within the hypoxic tumour microenvironments.
METHODS
An alginate-gelatine hydrogel was generated via electrospray technology. Hydrogel biocompatibility was assessed through cell counting kit-8 and Live/Dead assays to ascertain cell. Moreover, we analysed lactate dehydrogenase assays to evaluate the cytotoxicity against tumours and utilised RT-qPCR to analyse cytokine gene level.
RESULTS
Alginate and gelatine formed hydrogels with diameters ranging from 489.2 ± 23.0 μm, and the encapsulation efficiency was 34.07 ± 1.76%. Encapsulated NK cells exhibited robust proliferation and tumour-killing capabilities under normoxia and hypoxia. Furthermore, encapsulation provided a protective shield against cell viability under hypoxia. Importantly, tumour-killing cytotoxicity through cytokines upregulation such as granzyme B and interferon-gamma was preserved under hypoxia.
CONCLUSION
The encapsulation of NK cells not only safeguards their viability but also reinforces anticancer capacity, countering the inhibition of activation induced by hypoxia.
PubMed: 38945166
DOI: 10.1080/02652048.2024.2362170 -
Biochemical and Biophysical Research... Jun 2024The tumor microenvironment (TME) comprises cancer and non-cancerous stromal cells, including fibroblasts. Free fatty acids (FFAs) regulate various biological responses...
The tumor microenvironment (TME) comprises cancer and non-cancerous stromal cells, including fibroblasts. Free fatty acids (FFAs) regulate various biological responses by binding to G protein-coupled FFA receptors (FFARs). In this study, we examined the impact of FFAR1 and FFAR4 on the cell migration of pancreatic cancer PANC-1 cells co-cultured with 3T3 fibroblast cells under hypoxic conditions. PANC-1 cells cultured at 1 % O exhibited elevated FFAR1 expression and decreased FFAR4 expression compared to those at 21 % O. Cell migration of PANC-1 cells was reduced under 1 % O conditions. FFAR1 knockdown enhanced PANC-1 cell migration, whereas FFAR4 knockdown inhibited it. Co-culture of PANC-1 cells with 3T3 cells at 1 % O significantly increased FFAR4 expression, while FFAR1 expression remained unchanged. To evaluate the effects of FFAR1 and FFAR4 on PANC-1 cell migration in co-culture with 3T3 cells, we conducted a wound healing assay using the Culture-Insert 2 Well. PANC-1 and 3T3 cells were individually seeded into the two wells and incubated at both 21 % and 1 % O for 13 h. The cell migration of PANC-1 cells co-cultured with 3T3 cells at 1 % O was notably higher compared to 21 % O. TUG-770 reduced and TUG-891 enhanced the cell migration of PANC-1 cells co-cultured with 3T3 cells under both 21 % and 1 % O conditions. These findings suggest that FFAR1 and FFAR4 play important roles in regulating the cell migration of PANC-1 cells co-cultured with 3T3 cells under hypoxic conditions.
PubMed: 38945064
DOI: 10.1016/j.bbrc.2024.150322 -
Journal of Environmental Management Jun 2024Turnover in lakes and reservoirs causes circulation in the water column from the bottom to the surface when the water column stability becomes low. Previous studies...
Turnover in lakes and reservoirs causes circulation in the water column from the bottom to the surface when the water column stability becomes low. Previous studies commonly mentioned that turnover occurs when stratification indices become small, but the threshold is rarely discussed. While turnover phenomena have been extensively studied by evaluating changes in bottom dissolved oxygen (DO), the relationship between the disappearance of hypoxia and water temperature indices has not been determined. This study focused on the factors influencing the minimum thermal gradient (TG) and Schmidt Stability Index (SSI), and the timing of turnover events using DO as an indicator of mixing in the Ogouchi reservoir from 1992 to 2001. The results showed that the occurrence of minimum TG and SSI is mainly driven by inflow retention time and average maximum wind speed. Moreover, minimum air temperature and outflow retention time have few contributions to minimum SSI. It was found that 7 out of 10 years exhibited full winter turnover, while the remaining years showed incomplete mixing with persistent hypoxia at the reservoir bottom. This study identifies four cases based on onset thresholds of 0.0035 °C m for TG and 30 J m for SSI to explain turnover event: Case 1: an ideal state with stratification indices below the threshold, resulting in the disappearance of hypoxia; Case 2: indices above the threshold sustain hypoxia; Case 3: an irregular state where the indices exceed the threshold, yet hypoxia disappears; and Case 4: an unexpected persistence of hypoxia despite being below the threshold. The majority of the years (70 percent) were explained by thresholds. The multiple regression analysis indicated the importance of wind speed on the turnover event. Therefore, the effect of wind shear was analyzed for 30 percent of the years that cannot be explained by thresholds (cases 3 and 4). Case 3 shows turnover occurrence due to strong accumulated wind shear, despite exceeding thresholds. Conversely, Case 4 reveals weak wind shear preventing bottom water upwelling, even below thresholds. In conclusion, the precise TG and SSI thresholds for the onset of turnover event were determined using DO data. The thresholds explained the occurrence and non-occurrence of turnover event in most of the years and wind speed clarified unexplained cases by thresholds. The presented method successfully evaluated the timing of turnover and can be applicable elsewhere.
PubMed: 38944954
DOI: 10.1016/j.jenvman.2024.121537 -
International Immunopharmacology Jun 2024Obstructive sleep apnea, typically characterized by chronic intermittent hypoxia (CIH), is linked to cognitive dysfunction in children. Ferroptosis, a novel form of cell...
Obstructive sleep apnea, typically characterized by chronic intermittent hypoxia (CIH), is linked to cognitive dysfunction in children. Ferroptosis, a novel form of cell death characterized by lethal iron accumulation and lipid peroxidation, is implicated in neurodegenerative diseases and ischemia-reperfusion injuries. Nevertheless, its contribution to CIH-induced cognitive dysfunction and its interaction with endoplasmic reticulum stress (ERS) remain uncertain. In this study, utilizing a CIH model in 4-week-old male mice, we investigated ferroptosis and its potential involvement in ERS regulation during cognitive dysfunction. Our findings indicate ferroptosis activation in prefrontal cortex neurons, leading to neuron loss, mitochondrial damage, decreased levels of GPX4, SLC7A11, FTL, and FTH, increased levels of reactive oxygen species (ROS), malondialdehyde (MDA), Fe, ACSL4, TFRC, along with the activation of ERS-related PERK-ATF4-CHOP pathway. Treatment with the ferroptosis inhibitor liproxstatin-1 (Lip-1) and the iron chelator deferoxamine (DFO) effectively mitigated the neuron injury and cognitive dysfunction induced by CIH, significantly reducing Fe and partly restoring expression levels of ferroptosis-related proteins. Furhermore, the use of Lip-1 and DFO downregulated p-PERK, ATF4 and CHOP, and upregulated Nrf2 expression, suggesting that inhibiting ferroptosis reduce ERS and that the transcription factor Nrf2 is involved in the process. In summary, our findings indicate that cognitive impairment in CIH mice correlates with the induction of neuronal ferroptosis, facilitated by the System x - GPX4 functional axis, lipid peroxidation, and the iron metabolism pathway, along with ferroptosis-mediated ERS in the prefrontal cortex. Nrf2 has been identified as a potential regulator of ferroptosis and ERS involved in the context of CIH.
PubMed: 38944951
DOI: 10.1016/j.intimp.2024.112579 -
Microcirculation (New York, N.Y. : 1994) Jun 2024This study focuses on evaluating the disruptions in key physiological parameters during microstroke events to assess their severity.
OBJECTIVE
This study focuses on evaluating the disruptions in key physiological parameters during microstroke events to assess their severity.
METHODS
A mathematical model was developed to simulate the changes in cerebral tissue pO, glucose concentration, and temperature due to blood flow interruptions. The model considers variations in baseline cerebral blood flow (CBF), capillary density, and blood oxygen/glucose levels, as well as ambient temperature changes.
RESULTS
Simulations indicate that complete blood flow obstruction still allows for limited glucose availability, supporting nonoxidative metabolism and potentially exacerbating lactate buildup and acidosis. Partial obstructions decrease tissue pO, with minimal impact on glucose level, which can remain almost unchanged or even slightly increase. Reduced CBF, capillary density, or blood oxygen due to aging or disease enhances hypoxia risk at lower obstruction levels, with capillary density having a significant effect on stroke severity by influencing both pO and glucose levels. Conditions could lead to co-occurrence of hypoxia/hypoglycemia or hypoxia/hyperglycemia, each worsening outcomes. Temperature effects were minimal in deep brain regions but varied near the skull by 0.2-0.8°C depending on ambient temperature.
CONCLUSIONS
The model provides insights into the conditions driving severe stroke outcomes based on estimated levels of hypoxia, hypoglycemia, hyperglycemia, and temperature changes.
PubMed: 38944839
DOI: 10.1111/micc.12872 -
Cancer Genomics & Proteomics 2024Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We,...
BACKGROUND/AIM
Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We, herein, aimed to implement oxygen-enhanced MRI (OE-MRI) in xenografts derived from muscle-invasive bladder cancer (MIBC) for future hypoxia biomarker discovery work; and generate gene expression data for future biomarker discovery.
MATERIALS AND METHODS
The flanks of female CD-1 nude mice inoculated with HT1376 MIBC cells. Mice with small (300 mm) or large (700 mm) tumours were imaged, breathing air then 100% O, 1 h post injection with pimonidazole in an Agilant 7T 16cm bore magnet interfaced to a Bruker Avance III console with a T2-TurboRARE sequence using a dynamic MPRAGE acquisition. Dynamic Spoiled Gradient Recalled Echo images were acquired for 5 min, with 0.1mmol/kg Gd-DOTA (Dotarem, Guerbet, UK) injected after 60 s (1 ml/min). Voxel size and field of view of dynamic contrast enhanced (DCE)-MRI and OE-MRI scans were matched. The voxels considered as perfused with significant post-contrast enhancement (p<0.05) in DCE-MRI scans and tissue were further split into pOxyE (normoxic) and pOxyR (hypoxic) regions. Tumours harvested in liquid N, sectioned, RNA was extracted and transcriptomes analysed using Clariom S microarrays.
RESULTS
Imaged hypoxic regions were greater in the larger versus smaller tumour. Expression of known hypoxia-inducible genes and a 24 gene bladder cancer hypoxia score were higher in pimonidazole-high versus -low regions: CA9 (p=0.012) and SLC2A1 (p=0.012) demonstrating expected transcriptomic behaviour.
CONCLUSION
OE-MRI was successfully implemented in MIBC-derived xenografts. Transcriptomic data derived from hypoxic and non-hypoxic xenograft regions will be useful for future studies.
Topics: Urinary Bladder Neoplasms; Animals; Humans; Mice; Magnetic Resonance Imaging; Female; Oxygen; Pilot Projects; Mice, Nude; Genomics; Hypoxia; Tumor Hypoxia; Cell Line, Tumor; Heterografts; Xenograft Model Antitumor Assays
PubMed: 38944425
DOI: 10.21873/cgp.20455 -
Journal of Ethnopharmacology Jun 2024Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang,...
ETHNOPHARMACOLOGICAL RELEVANCE
Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang, benefiting essence and blood and moistening the intestinal tract. Cistache deserticola phenylethanoid glycoside (PGS), an active component found in Cistanche deserticola Ma, have potential kidney tonifying, intellectual enhancing, and neuroprotective effects. Cistanche total glycoside capsule has been marketed to treat vascular dementia disease.
AIM OF THE STUDY
To identify the potential renal, intellectual enhancing and neuroprotective effects of PGS and explore the exact targets and mechanisms of PGS.
MATERIALS AND METHODS
This study systematically investigated the four types of pathways leading to ferroptosis through transcriptome, metabolome, ultrastructure and molecular biology techniques and explored the molecular mechanism by which multiple PGS targets and pathways synergistically exert neuroprotective effects on hypoxia.
RESULTS
PGS alleviated learning and memory dysfunction and pathological injury in mice exposed to hypobaric hypoxia by attenuating hypobaric hypoxia-induced hippocampal histopathological damage, impairing blood‒brain barrier integrity, increasing oxidative stress levels, and increasing the expression of cognitive proteins. PGS reduced the formation of lipid peroxides and improved ferroptosis by upregulating the GPX-4/SCL7A311 axis and downregulating the ACSL4/LPCAT3/LOX axis. PGS also reduced ferroptosis by facilitating cellular Fe efflux and regulating mitochondrial Fe transport and effectively antagonized cell ferroptosis induced by erastin (a ferroptosis inducer).
CONCLUSIONS
This study demonstrated the mechanism by which PGS prevents hypobaric hypoxic nerve injury through four types of ferroptosis pathways, achieved neuroprotective effects and alleviated learning and memory dysfunction in hypobaric hypoxia mice. This study provides a theoretical basis for the development and application of PGS.
PubMed: 38944360
DOI: 10.1016/j.jep.2024.118465