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1.
Commun Biol ; 7(1): 551, 2024 May 08.
Article En | MEDLINE | ID: mdl-38720110

Fusobacterium nucleatum, a gram-negative oral bacterium, has been consistently validated as a strong contributor to the progression of several types of cancer, including colorectal (CRC) and pancreatic cancer. While previous in vitro studies have shown that intracellular F. nucleatum enhances malignant phenotypes such as cell migration, the dependence of this regulation on features of the tumor microenvironment (TME) such as oxygen levels are wholly uncharacterized. Here we examine the influence of hypoxia in facilitating F. nucleatum invasion and its effects on host responses focusing on changes in the global epigenome and transcriptome. Using a multiomic approach, we analyze epigenomic alterations of H3K27ac and global transcriptomic alterations sustained within a hypoxia and normoxia conditioned CRC cell line HCT116 at 24 h following initial infection with F. nucleatum. Our findings reveal that intracellular F. nucleatum activates signaling pathways and biological processes in host cells similar to those induced upon hypoxia conditioning in the absence of infection. Furthermore, we show that a hypoxic TME favors F. nucleatum invasion and persistence and therefore infection under hypoxia may amplify malignant transformation by exacerbating the effects induced by hypoxia alone. These results motivate future studies to investigate host-microbe interactions in tumor tissue relevant conditions that more accurately define parameters for targeted cancer therapies.


Colorectal Neoplasms , Epigenome , Fusobacterium Infections , Fusobacterium nucleatum , Oxygen , Transcriptome , Humans , Fusobacterium nucleatum/genetics , Fusobacterium nucleatum/physiology , Fusobacterium nucleatum/pathogenicity , Colorectal Neoplasms/genetics , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , HCT116 Cells , Fusobacterium Infections/genetics , Fusobacterium Infections/microbiology , Fusobacterium Infections/metabolism , Oxygen/metabolism , Tumor Microenvironment/genetics , Gene Expression Regulation, Neoplastic
2.
Artif Cells Nanomed Biotechnol ; 52(1): 291-299, 2024 Dec.
Article En | MEDLINE | ID: mdl-38733371

Haemorrhagic shock is a leading cause of death worldwide. Blood transfusions can be used to treat patients suffering severe blood loss but donated red blood cells (RBCs) have several limitations that limit their availability and use. To solve the problems associated with donated RBCs, several acellular haemoglobin-based oxygen carriers (HBOCs) have been developed to restore the most important function of blood: oxygen transport. One promising HBOC is the naturally extracellular haemoglobin (i.e. erythrocruorin) of Lumbricus terrestris (LtEc). The goal of this study was to maximise the portability of LtEc by lyophilising it and then testing its stability at elevated temperatures. To prevent oxidation, several cryoprotectants were screened to determine the optimum formulation for lyophilisation that could minimise oxidation of the haem iron and maximise recovery. Furthermore, samples were also deoxygenated prior to storage to decrease auto-oxidation, while resuspension in a solution containing ascorbic acid was shown to partially reduce LtEc that had oxidised during storage (e.g. from 42% Fe3+ to 11% Fe3+). Analysis of the oxygen equilibria and size of the resuspended LtEc showed that the lyophilisation, storage, and resuspension processes did not affect the oxygen transport properties or the structure of the LtEc, even after 6 months of storage at 40 °C. Altogether, these efforts have yielded a shelf-stable LtEc powder that can be stored for long periods at high temperatures, but future animal studies will be necessary to prove that the resuspended product is a safe and effective oxygen transporter in vivo.


Freeze Drying , Hemoglobins , Oligochaeta , Animals , Oligochaeta/metabolism , Hemoglobins/chemistry , Hemoglobins/metabolism , Oxygen/metabolism , Oxygen/chemistry , Oxidation-Reduction , Blood Substitutes/chemistry
3.
Braz J Med Biol Res ; 57: e13299, 2024.
Article En | MEDLINE | ID: mdl-38716981

25-hydroxycholesterol (25-HC) plays a role in the regulation of cell survival and immunity. However, the effect of 25-HC on myocardial ischemia/reperfusion (MI/R) injury remains unknown. Our present study aimed to investigate whether 25-HC aggravated MI/R injury through NLRP3 inflammasome-mediated pyroptosis. The overlapping differentially expressed genes (DEGs) in MI/R were identified from the GSE775, GSE45818, GSE58486, and GSE46395 datasets in Gene Expression Omnibus (GEO) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the database of Annotation, Visualization and Integration Discovery (DAVID). The protein-protein interaction (PPI) network of the overlapping DEGs was established using the Search Tool for the Retrieval of Interacting Genes (STRING) database. These bioinformatics analyses indicated that cholesterol 25-hydroxylase (CH25H) was one of the crucial genes in MI/R injury. The oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was established to simulate MI/R injury. Western blot and RT-qPCR analysis demonstrated that CH25H was significantly upregulated in OGD/R-stimulated H9C2 cardiomyocytes. Moreover, knockdown of CH25H inhibited the OGD/R-induced pyroptosis and nod-like receptor protein 3 (NLRP3) inflammasome activation, as demonstrated by cell counting kit-8 (CCK8), lactate dehydrogenase (LDH), RT-qPCR, and western blotting assays. Conversely, 25-HC, which is synthesized by CH25H, promoted activation of NLRP3 inflammasome in OGD/R-stimulated H9C2 cardiomyocytes. In addition, the NLRP3 inhibitor BAY11-7082 attenuated 25-HC-induced H9C2 cell injury and pyroptosis under OGD/R condition. In conclusion, 25-HC could aggravate OGD/R-induced pyroptosis through promoting activation of NLRP3 inflammasome in H9C2 cells.


Glucose , Hydroxycholesterols , Inflammasomes , Myocardial Reperfusion Injury , Myocytes, Cardiac , NLR Family, Pyrin Domain-Containing 3 Protein , Pyroptosis , Animals , Rats , Blotting, Western , Glucose/metabolism , Hydroxycholesterols/metabolism , Hydroxycholesterols/pharmacology , Inflammasomes/metabolism , Myocardial Reperfusion Injury/metabolism , Myocytes, Cardiac/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Oxygen/metabolism , Pyroptosis/physiology
4.
Int J Mol Sci ; 25(9)2024 Apr 23.
Article En | MEDLINE | ID: mdl-38731800

Understanding the molecular underpinnings of neurodegeneration processes is a pressing challenge for medicine and neurobiology. Alzheimer's disease (AD) and Parkinson's disease (PD) represent the most prevalent forms of neurodegeneration. To date, a substantial body of experimental evidence has strongly implicated hypoxia in the pathogenesis of numerous neurological disorders, including AD, PD, and other age-related neurodegenerative conditions. Hypoxia-inducible factor (HIF) is a transcription factor that triggers a cell survival program in conditions of oxygen deprivation. The involvement of HIF-1α in neurodegenerative processes presents a complex and sometimes contradictory picture. This review aims to elucidate the current understanding of the interplay between hypoxia and the development of AD and PD, assess the involvement of HIF-1 in their pathogenesis, and summarize promising therapeutic approaches centered on modulating the activity of the HIF-1 complex.


Homeostasis , Hypoxia-Inducible Factor 1, alpha Subunit , Neurodegenerative Diseases , Oxygen , Parkinson Disease , Humans , Oxygen/metabolism , Animals , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Parkinson Disease/metabolism , Parkinson Disease/pathology , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/etiology , Hypoxia-Inducible Factor 1/metabolism , Hypoxia/metabolism
5.
J Biomed Opt ; 29(Suppl 3): S33302, 2024 Jun.
Article En | MEDLINE | ID: mdl-38707651

Significance: Cerebral oximeters have the potential to detect abnormal cerebral blood oxygenation to allow for early intervention. However, current commercial systems have two major limitations: (1) spatial coverage of only the frontal region, assuming that surgery-related hemodynamic effects are global and (2) susceptibility to extracerebral signal contamination inherent to continuous-wave near-infrared spectroscopy (NIRS). Aim: This work aimed to assess the feasibility of a high-density, time-resolved (tr) NIRS device (Kernel Flow) to monitor regional oxygenation changes across the cerebral cortex during surgery. Approach: The Flow system was assessed using two protocols. First, digital carotid compression was applied to healthy volunteers to cause a rapid oxygenation decrease across the ipsilateral hemisphere without affecting the contralateral side. Next, the system was used on patients undergoing shoulder surgery to provide continuous monitoring of cerebral oxygenation. In both protocols, the improved depth sensitivity of trNIRS was investigated by applying moment analysis. A dynamic wavelet filtering approach was also developed to remove observed temperature-induced signal drifts. Results: In the first protocol (28±5 years; five females, five males), hair significantly impacted regional sensitivity; however, the enhanced depth sensitivity of trNIRS was able to separate brain and scalp responses in the frontal region. Regional sensitivity was improved in the clinical study given the age-related reduction in hair density of the patients (65±15 years; 14 females, 13 males). In five patients who received phenylephrine to treat hypotension, different scalp and brain oxygenation responses were apparent, although no regional differences were observed. Conclusions: The Kernel Flow has promise as an intraoperative neuromonitoring device. Although regional sensitivity was affected by hair color and density, enhanced depth sensitivity of trNIRS was able to resolve differences in scalp and brain oxygenation responses in both protocols.


Cerebrovascular Circulation , Spectroscopy, Near-Infrared , Humans , Spectroscopy, Near-Infrared/methods , Spectroscopy, Near-Infrared/instrumentation , Female , Male , Adult , Cerebrovascular Circulation/physiology , Hemodynamics/physiology , Oximetry/methods , Oximetry/instrumentation , Oxygen/blood , Oxygen/metabolism , Brain/diagnostic imaging , Brain/blood supply , Equipment Design
6.
Opt Lett ; 49(10): 2669-2672, 2024 May 15.
Article En | MEDLINE | ID: mdl-38748132

Central venous oxygen saturation (ScvO2) is an important parameter for assessing global oxygen usage and guiding clinical interventions. However, measuring ScvO2 requires invasive catheterization. As an alternative, we aim to noninvasively and continuously measure changes in oxygen saturation of the internal jugular vein (SijvO2) by a multi-channel near-infrared spectroscopy system. The relation between the measured reflectance and changes in SijvO2 is modeled by Monte Carlo simulations and used to build a prediction model using deep neural networks (DNNs). The prediction model is tested with simulated data to show robustness to individual variations in tissue optical properties. The proposed technique is promising to provide a noninvasive tool for monitoring the stability of brain oxygenation in broad patient populations.


Jugular Veins , Monte Carlo Method , Oxygen Saturation , Jugular Veins/physiology , Humans , Oxygen Saturation/physiology , Neural Networks, Computer , Oxygen/metabolism , Spectroscopy, Near-Infrared/methods , Male
7.
Med Sci Monit ; 30: e943089, 2024 May 10.
Article En | MEDLINE | ID: mdl-38725228

BACKGROUND One-lung ventilation is the separation of the lungs by mechanical methods to allow ventilation of only one lung, particularly when there is pathology in the other lung. This retrospective study from a single center aimed to compare 49 patients undergoing thoracoscopic cardiac surgery using one-lung ventilation with 48 patients undergoing thoracoscopic cardiac surgery with median thoracotomy. MATERIAL AND METHODS This single-center retrospective study analyzed patients who underwent thoracoscopic cardiac surgery based on one-lung ventilation (experimental group, n=49). Other patients undergoing a median thoracotomy cardiac operation were defined as the comparison group (n=48). The oxygenation index and the mechanical ventilation time were also recorded. RESULTS There was no significant difference in the immediate oxygenation index between the experimental group and comparison group (P>0.05). There was no significant difference for the oxygenation index between men and women in both groups (P>0.05). The cardiopulmonary bypass time significantly affected the oxygenation index (F=7.200, P=0.009). Operation methods (one-lung ventilation thoracoscopy or median thoracotomy) affected postoperative ventilator use time (F=8.337, P=0.005). Cardiopulmonary bypass time (F=16.002, P<0.001) and age (F=4.384, P=0.039) had significant effects on ventilator use time. There was no significant effect of sex (F=0.75, P=0.389) on ventilator use time. CONCLUSIONS Our results indicated that one-lung ventilation thoracoscopic cardiac surgery did not affect the immediate postoperative oxygenation index; however, cardiopulmonary bypass time did significantly affect the immediate postoperative oxygenation index. Also, one-lung ventilation thoracoscopic cardiac surgery had a shorter postoperative mechanical ventilation use time than did traditional median thoracotomy cardiac surgery.


Cardiac Surgical Procedures , One-Lung Ventilation , Thoracoscopy , Thoracotomy , Humans , Male , Female , Thoracotomy/methods , One-Lung Ventilation/methods , Middle Aged , Thoracoscopy/methods , Retrospective Studies , Cardiac Surgical Procedures/methods , Aged , Oxygen/metabolism , Respiration, Artificial/methods , Adult , Cardiopulmonary Bypass/methods , Lung/surgery , Lung/metabolism
8.
Crit Care Explor ; 6(5): e1094, 2024 May 01.
Article En | MEDLINE | ID: mdl-38727717

OBJECTIVES: Near-infrared spectroscopy (NIRS) is a potentially valuable modality to monitor the adequacy of oxygen delivery to the brain and other tissues in critically ill patients, but little is known about the physiologic determinants of NIRS-derived tissue oxygen saturations. The purpose of this study was to assess the contribution of routinely measured physiologic parameters to tissue oxygen saturation measured by NIRS. DESIGN: An observational sub-study of patients enrolled in the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) randomized feasibility trial. SETTING: Two ICUs in the United Kingdom. PATIENTS: Patients were recruited for the RADAR-2 study, which compared a conservative approach to fluid therapy and deresuscitation with usual care. Those included in this sub-study underwent continuous NIRS monitoring of cerebral oxygen saturations (SctO2) and quadriceps muscle tissue saturations (SmtO2). INTERVENTION: Synchronized and continuous mean arterial pressure (MAP), heart rate (HR), and pulse oximetry (oxygen saturation, Spo2) measurements were recorded alongside NIRS data. Arterial Paco2, Pao2, and hemoglobin concentration were recorded 12 hourly. Linear mixed effect models were used to investigate the association between these physiologic variables and cerebral and muscle tissue oxygen saturations. MEASUREMENTS AND MAIN RESULTS: Sixty-six patients were included in the analysis. Linear mixed models demonstrated that Paco2, Spo2, MAP, and HR were weakly associated with SctO2 but only explained 7.1% of the total variation. Spo2 and MAP were associated with SmtO2, but together only explained 0.8% of its total variation. The remaining variability was predominantly accounted for by between-subject differences. CONCLUSIONS: Our findings demonstrated that only a small proportion of variability in NIRS-derived cerebral and tissue oximetry measurements could be explained by routinely measured physiologic variables. We conclude that for NIRS to be a useful monitoring modality in critical care, considerable further research is required to understand physiologic determinants and prognostic significance.


Critical Illness , Oximetry , Oxygen Saturation , Spectroscopy, Near-Infrared , Humans , Spectroscopy, Near-Infrared/methods , Male , Female , Oxygen Saturation/physiology , Middle Aged , Aged , Oximetry/methods , Monitoring, Physiologic/methods , Brain/metabolism , Brain/blood supply , United Kingdom , Oxygen/metabolism , Oxygen/blood , Oxygen/analysis , Intensive Care Units , Quadriceps Muscle/metabolism , Quadriceps Muscle/blood supply
9.
PLoS One ; 19(5): e0301605, 2024.
Article En | MEDLINE | ID: mdl-38739592

Oxygen minimum zones (OMZ) represent ~8% of the ocean, with the Pacific as the largest and top expanding area. These regions influence marine ecosystems, promoting anaerobic microbial communities. Nevertheless, only a fraction of microbial diversity has been studied, with fungi being the less explored component. So, herein we analyzed fungal diversity patterns in surface and subsurface sediments along a bathymetric transect using metabarcoding of the ITS1 region in the OMZ of the Mexican Pacific off Mazatlán. We identified 353 amplicon sequence variants (ASV), within the Ascomycota, Basidiomycota, and Rozellomycota. Spatial patterns evidenced higher alpha diversity in nearshore and subsurface subsamples, probably due to temporal fluctuations in organic matter inputs. Small-scale heterogeneity characterized the community with the majority of ASV (269 ASV) occurring in a single subsample, hinting at the influence of local biogeochemical conditions. This baseline data evidenced a remarkable fungal diversity presenting high variation along a bathymetric and vertical transects.


Biodiversity , DNA Barcoding, Taxonomic , Fungi , Geologic Sediments , Oxygen , Geologic Sediments/microbiology , Oxygen/metabolism , Oxygen/analysis , Fungi/genetics , Fungi/classification , Fungi/isolation & purification , Pacific Ocean , Phylogeny
10.
PeerJ ; 12: e17259, 2024.
Article En | MEDLINE | ID: mdl-38699194

Iron (Fe) plays a fundamental role in coral symbiosis, supporting photosynthesis, respiration, and many important enzymatic reactions. However, the extent to which corals are limited by Fe and their metabolic responses to inorganic Fe enrichment remains to be understood. We used respirometry, variable chlorophyll fluorescence, and O2 microsensors to investigate the impact of increasing Fe(III) concentrations (20, 50, and 100 nM) on the photosynthetic capacity of two Mediterranean coral species, Cladocora caespitosa and Oculina patagonica. While the bioavailability of inorganic Fe can rapidly decrease, we nevertheless observed significant physiological effects at all Fe concentrations. In C. caespitosa, exposure to 50 nM Fe(III) increased rates of respiration and photosynthesis, while the relative electron transport rate (rETR(II)) decreased at higher Fe(III) exposure (100 nM). In contrast, O. patagonica reduced respiration, photosynthesis rates, and maximum PSII quantum yield (Fv/Fm) across all iron enrichments. Both corals exhibited increased hypoxia (<50 µmol O2 L-1) within their gastric cavity at night when exposed to 50 and 100 nM Fe(III), leading to increased polyp contraction time and reduced O2 exchange with the surrounding water. Our results indicate that C. caespitosa, but not O. patagonica, might be limited in Fe for achieving maximal photosynthetic efficiency. Understanding the multifaceted role of iron in corals' health and their response to environmental change is crucial for effective coral conservation.


Anthozoa , Iron , Oxygen , Photosynthesis , Anthozoa/drug effects , Anthozoa/metabolism , Animals , Photosynthesis/drug effects , Iron/metabolism , Oxygen/metabolism , Mediterranean Sea , Symbiosis
11.
Phys Med Biol ; 69(10)2024 May 03.
Article En | MEDLINE | ID: mdl-38700988

Liew and Mairani commented on our paper 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation' (Shiraishiet al2024aPhys. Med. Biol.69015017), which proposed a biophysical model to predict the dose-response curve of surviving cell fractions after ultra-high dose rate irradiation following conventional dose rate irradiation by considering DNA damage yields. They suggested the need to consider oxygen concentration in our prediction model and possible issues related to the data selection process used for the benchmarking test in our paper. In this reply, we discuss the limitations of both the present model and the available experimental data for determining the model's parameters. We also demonstrate that our proposed model can reproduce the experimental survival data even when using only the experimental DNA damage data measured reliably under normoxic conditions.


Cell Survival , DNA Damage , Dose-Response Relationship, Radiation , Models, Biological , Cell Survival/radiation effects , Radiation Dosage , Humans , Oxygen/metabolism
12.
Nat Commun ; 15(1): 3712, 2024 May 02.
Article En | MEDLINE | ID: mdl-38697963

The discovery of nitrogen fixation in unicellular cyanobacteria provided the first clues for the existence of a circadian clock in prokaryotes. However, recalcitrance to genetic manipulation barred their use as model systems for deciphering the clock function. Here, we explore the circadian clock in the now genetically amenable Cyanothece 51142, a unicellular, nitrogen-fixing cyanobacterium. Unlike non-diazotrophic clock models, Cyanothece 51142 exhibits conspicuous self-sustained rhythms in various discernable phenotypes, offering a platform to directly study the effects of the clock on the physiology of an organism. Deletion of kaiA, an essential clock component in the cyanobacterial system, impacted the regulation of oxygen cycling and hindered nitrogenase activity. Our findings imply a role for the KaiA component of the clock in regulating the intracellular oxygen dynamics in unicellular diazotrophic cyanobacteria and suggest that its addition to the KaiBC clock was likely an adaptive strategy that ensured optimal nitrogen fixation as microbes evolved from an anaerobic to an aerobic atmosphere under nitrogen constraints.


Bacterial Proteins , Circadian Clocks , Cyanothece , Nitrogen Fixation , Oxygen , Oxygen/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Circadian Clocks/genetics , Circadian Clocks/physiology , Cyanothece/metabolism , Cyanothece/genetics , Nitrogenase/metabolism , Nitrogenase/genetics , Circadian Rhythm Signaling Peptides and Proteins/metabolism , Circadian Rhythm Signaling Peptides and Proteins/genetics , Gene Expression Regulation, Bacterial , Cyanobacteria/metabolism , Cyanobacteria/genetics
13.
Microb Cell Fact ; 23(1): 125, 2024 May 02.
Article En | MEDLINE | ID: mdl-38698392

BACKGROUND: The facultatively anaerobic thermophile Parageobacillus thermoglucosidasius is able to produce hydrogen gas (H2) through the water-gas shift (WGS) reaction. To date this process has been evaluated under controlled conditions, with gas feedstocks comprising carbon monoxide and variable proportions of air, nitrogen and hydrogen. Ultimately, an economically viable hydrogenogenic system would make use of industrial waste/synthesis gases that contain high levels of carbon monoxide, but which may also contain contaminants such as H2, oxygen (O2) and other impurities, which may be toxic to P. thermoglucosidasius. RESULTS: We evaluated the effects of synthesis gas (syngas) mimetic feedstocks on WGS reaction-driven H2 gas production by P. thermoglucosidasius DSM 6285 in small-scale fermentations. Improved H2 gas production yields and faster onset towards hydrogen production were observed when anaerobic synthetic syngas feedstocks were used, at the expense of biomass accumulation. Furthermore, as the WGS reaction is an anoxygenic process, we evaluated the influence of O2 perturbation on P. thermoglucosidasius hydrogenogenesis. O2 supplementation improved biomass accumulation, but reduced hydrogen yields in accordance with the level of oxygen supplied. However, H2 gas production was observed at low O2 levels. Supplementation also induced rapid acetate consumption, likely to sustain growth. CONCLUSION: The utilisation of anaerobic syngas mimetic gas feedstocks to produce H2 and the relative flexibility of the P. thermoglucosidasius WGS reaction system following O2 perturbation further supports its applicability towards more robust and continuous hydrogenogenic operation.


Fermentation , Hydrogen , Oxygen , Hydrogen/metabolism , Oxygen/metabolism , Carbon Monoxide/metabolism , Anaerobiosis , Biomass , Gases/metabolism
14.
Nihon Yakurigaku Zasshi ; 159(3): 165-168, 2024.
Article Ja | MEDLINE | ID: mdl-38692881

Molecular oxygen suffices the ATP production required for the survival of us aerobic organisms. But it is also true that oxygen acts as a source of reactive oxygen species that elicit a spectrum of damages in living organisms. To cope with such intrinsic ambiguity of biological activity oxygen exerts, aerobic mechanisms are equipped with an exquisite adaptive system, which sensitively detects partial pressure of oxygen within the body and controls appropriate oxygen supply to the tissues. Physiological responses to hypoxia are comprised of the acute and chronic phases, in the former of which the oxygen-sensing remains controversial particularly from mechanistic points of view. Recently, we have revealed that the prominently redox-sensitive cation channel TRPA1 plays key roles in oxygen-sensing mechanisms identified in the peripheral tissues and the central nervous system. In this review, we summarize recent development of researches on oxygen-sensing mechanisms including that in the carotid body, which has been recognized as the oxygen receptor organ central to acute oxygen-sensing. We also discuss how ubiquitously the TRPA1 contributes to the mechanisms underlying the acute phase of adaptation to hypoxia.


Oxygen , TRPA1 Cation Channel , Transient Receptor Potential Channels , TRPA1 Cation Channel/metabolism , Humans , Oxygen/metabolism , Animals , Transient Receptor Potential Channels/metabolism , Hypoxia/metabolism , Calcium Channels/metabolism , Nerve Tissue Proteins/metabolism , Reactive Oxygen Species/metabolism , Carotid Body/metabolism
15.
Stomatologiia (Mosk) ; 103(2): 18-23, 2024.
Article Ru | MEDLINE | ID: mdl-38741530

OBJECTIVE: Increasing the effectiveness of treatment of chronic generalized periodontitis using PDT based on clinical and functional substantiation of the effects of a photosensitizer. MATERIALS AND METHODS: A clinical and functional study and treatment of moderate chronic generalized periodontitis was carried out in 62 people (26 men and 36 women) aged from 35 to 55 years without a somatic model with an orthognathic occlusion diagnosed according to ICD-10 - K05.3. Of these, 2 groups were divided depending on the type of treatment: Group 1 (main) - patients with moderate chronic generalized periodontitis - 32 people. (17 men and 15 women, average age of the group - 43.2±2.2 years); Group 2 (control) - patients with moderate chronic generalized periodontitis - 30 people. (14 men and 16 women, average age of the group - 44.0±3.3 years). Complex treatment consisted of sanitation of the mouth, removal of dental plaque and curettage of periodontal pockets in group 1, followed by PDT with Revixan gel using a special wired aligner REVIXAN DENTAL LED (16 r). The clinical condition of the periodontium was assessed using the Greene Vermillion Hygienic Index (OHI-S), the Mühlleman Bleeding Index (SBI) modified by Cowell, and the periodontal index PI. To study the state of microcirculation in the gum tissue, the laser Doppler flowmetry (LDF) method was used using the LAKK-M device (NPP «Lazma¼, Russia). The state of microcirculation was assessed by the microcirculation index (M), which characterizes the level of tissue blood flow; parameter - «σ¼, which determines the fluctuation of the erythrocyte flow. According to Wavelet analysis of LDF-grams, the shunt index (SH) of blood flow was determined. In the «LDF + spectrometry¼ mode, oxygenation in periodontal tissues was studied using optical tissue oximetry (OTO), based on the results of which the perfusion saturation index (Sm) and the specific oxygen consumption index (U, %) were determined. RESULTS: According to LDF data, after PDT (group 1), normalization of clinical indices and the level of microcirculation in periodontal tissues was established, which was accompanied by an increase in the level of blood flow (M) and its activity (σ), which persisted after 3 and 6 months. after PDT. The perfusion saturation index (Sm) and specific oxygen consumption (U) increased more significantly after PDT, which persisted after 3 and 6 months. In the control group, the dynamics of indicators was less pronounced. CONCLUSION: The use of PDT with Revixan gel normalizes the clinical condition of the periodontium, indicators of microhemodynamics and oxygen metabolism.


Chronic Periodontitis , Microcirculation , Photochemotherapy , Humans , Female , Male , Adult , Microcirculation/drug effects , Middle Aged , Chronic Periodontitis/drug therapy , Chronic Periodontitis/therapy , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Periodontium/blood supply , Periodontium/drug effects , Periodontium/metabolism , Oxygen/metabolism
16.
Autoimmunity ; 57(1): 2345919, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38721693

Dual-specificity phosphatase 12 (DUSP12) is abnormally expressed under various pathological conditions and plays a crucial role in the pathological progression of disorders. However, the role of DUSP12 in cerebral ischaemia/reperfusion injury has not yet been investigated. This study explored the possible link between DUSP12 and cerebral ischaemia/reperfusion injury using an oxygen-glucose deprivation/reoxygenation (OGD/R) model. Marked decreases in DUSP12 levels have been observed in cultured neurons exposed to OGD/R. DUSP12-overexpressed neurons were resistant to OGD/R-induced apoptosis and inflammation, whereas DUSP12-deficient neurons were vulnerable to OGD/R-evoked injuries. Further investigation revealed that DUSP12 overexpression or deficiency affects the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) in neurons under OGD/R conditions. Moreover, blockade of ASK1 diminished the regulatory effect of DUSP12 deficiency on JNK and p38 MAPK activation. In addition, DUSP12-deficiency-elicited effects exacerbating neuronal OGD/R injury were reversed by ASK1 blockade. In summary, DUSP12 protects against neuronal OGD/R injury by reducing apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway. These findings imply a neuroprotective function for DUSP12 in cerebral ischaemia/reperfusion injury.


Apoptosis , Dual-Specificity Phosphatases , Glucose , Inflammation , MAP Kinase Kinase Kinase 5 , Neurons , Oxygen , Reperfusion Injury , p38 Mitogen-Activated Protein Kinases , Animals , Mice , Cells, Cultured , Dual-Specificity Phosphatases/metabolism , Dual-Specificity Phosphatases/genetics , Glucose/metabolism , Inflammation/metabolism , Inflammation/pathology , MAP Kinase Kinase Kinase 5/metabolism , MAP Kinase Signaling System , Neurons/metabolism , Neurons/pathology , Oxygen/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Signal Transduction , Mitogen-Activated Protein Kinase 14
17.
Proc Natl Acad Sci U S A ; 121(19): e2319937121, 2024 May 07.
Article En | MEDLINE | ID: mdl-38696469

Subtropical oceans contribute significantly to global primary production, but the fate of the picophytoplankton that dominate in these low-nutrient regions is poorly understood. Working in the subtropical Mediterranean, we demonstrate that subduction of water at ocean fronts generates 3D intrusions with uncharacteristically high carbon, chlorophyll, and oxygen that extend below the sunlit photic zone into the dark ocean. These contain fresh picophytoplankton assemblages that resemble the photic-zone regions where the water originated. Intrusions propagate depth-dependent seasonal variations in microbial assemblages into the ocean interior. Strikingly, the intrusions included dominant biomass contributions from nonphotosynthetic bacteria and enrichment of enigmatic heterotrophic bacterial lineages. Thus, the intrusions not only deliver material that differs in composition and nutritional character from sinking detrital particles, but also drive shifts in bacterial community composition, organic matter processing, and interactions between surface and deep communities. Modeling efforts paired with global observations demonstrate that subduction can flux similar magnitudes of particulate organic carbon as sinking export, but is not accounted for in current export estimates and carbon cycle models. Intrusions formed by subduction are a particularly important mechanism for enhancing connectivity between surface and upper mesopelagic ecosystems in stratified subtropical ocean environments that are expanding due to the warming climate.


Bacteria , Oceans and Seas , Seawater , Seawater/microbiology , Seawater/chemistry , Bacteria/metabolism , Carbon/metabolism , Carbon Cycle , Chlorophyll/metabolism , Ecosystem , Phytoplankton/metabolism , Seasons , Biomass , Microbiota/physiology , Oxygen/metabolism
18.
Bioresour Technol ; 401: 130704, 2024 Jun.
Article En | MEDLINE | ID: mdl-38636879

In this study, a SNAD-SBBR process was implemented to achieve ammonia removal and carbon reduction of mature landfill leachate under extremely low dissolved oxygen conditions (0.051 mg/L) for a continuous operation of 266 days. The process demonstrated excellent removal performance, with ammonia nitrogen removal efficiency reaching 100 %, total nitrogen removal efficiency reaching 87.56 %, and an average removal rate of 0.180 kg/(m3·d). The recalcitrant organic compound removal efficiency reached 34.96 %. Nitrogen mass balance analysis revealed that the Anammox process contributed to approximately 98.1 % of the nitrogen removal. Candidatus Kuenenia achieved a relative abundance of 1.49 % in the inner layer of the carrier. In the SNAD-SBBR system, the extremely low DO environment created by the highly efficient partial nitrification stage enabled the coexistence of AnAOB, denitrifying bacteria, and Nitrosomonas, synergistically achieving ammonia removal and carbon reduction. Overall, the SNAD-SBBR process exhibits low-cost and high-efficiency characteristics, holding tremendous potential for landfill leachate treatment.


Carbon , Denitrification , Nitrification , Nitrogen , Oxygen , Water Pollutants, Chemical , Oxygen/metabolism , Water Pollutants, Chemical/metabolism , Ammonia/metabolism , Bioreactors , Oxidation-Reduction , Biodegradation, Environmental , Water Purification/methods , Bacteria/metabolism , Anaerobiosis
19.
J Colloid Interface Sci ; 668: 88-97, 2024 Aug 15.
Article En | MEDLINE | ID: mdl-38669999

Nanotheranostic platforms, which can respond to tumor microenvironments (TME, such as low pH and hypoxia), are immensely appealing for photodynamic therapy (PDT). However, hypoxia in solid tumors harms the treatment outcome of PDT which depends on oxygen molecules to generate cytotoxic singlet oxygen (1O2). Herein, we report the design of TME-responsive smart nanotheranostic platform (DOX/ZnO2@Zr-Ce6/Pt/PEG) which can generate endogenously hydrogen peroxide (H2O2) and oxygen (O2) to alleviate hypoxia for improving photodynamic-chemo combination therapy of tumors. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite was prepared by the synthesis of ZnO2 nanoparticles, in-situ assembly of Zr-Ce6 as typical metal-organic framework (MOF) on ZnO2 surface, in-situ reduction of Pt nanozymes, amphiphilic lipids surface coating and then doxorubicin (DOX) loading. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite exhibits average sizes of ∼78 nm and possesses a good loading capacity (48.8 %) for DOX. When DOX/ZnO2@Zr-Ce6/Pt/PEG dispersions are intratumorally injected into mice, the weak acidic TEM induces the decomposition of ZnO2 core to generate endogenously H2O2, then Pt nanozymes catalyze H2O2 to produce O2 for alleviating tumor hypoxia. Upon laser (630 nm) irradiation, the Zr-Ce6 component in DOX/ZnO2@Zr-Ce6/Pt/PEG can produce cytotoxic 1O2, and 1O2 generation rate can be enhanced by 2.94 times due to the cascaded generation of endogenous H2O2/O2. Furthermore, the generated O2 can suppress the expression of hypoxia-inducible factor α, and further enable tumor cells to become more sensitive to chemotherapy, thereby leading to an increased effectiveness of chemotherapy treatment. The photodynamic-chemo combination therapy from DOX/ZnO2@Zr-Ce6/Pt/PEG nanoplatform exhibits remarkable tumor growth inhibition compared to chemotherapy or PDT. Thus, the present study is a good demonstration of a TME-responsive nanoplatform in a multimodal approach for cancer therapy.


Doxorubicin , Hydrogen Peroxide , Oxygen , Photochemotherapy , Theranostic Nanomedicine , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/metabolism , Animals , Mice , Doxorubicin/pharmacology , Doxorubicin/chemistry , Doxorubicin/administration & dosage , Oxygen/chemistry , Oxygen/metabolism , Humans , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Particle Size , Surface Properties , Drug Screening Assays, Antitumor , Cell Survival/drug effects , Cell Proliferation/drug effects , Cell Line, Tumor , Peroxides/chemistry , Peroxides/pharmacology , Nanoparticles/chemistry , Mice, Inbred BALB C , Zinc/chemistry , Zinc/pharmacology , Tumor Microenvironment/drug effects , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/administration & dosage
20.
Bioresour Technol ; 401: 130752, 2024 Jun.
Article En | MEDLINE | ID: mdl-38685514

Oxygenic photogranules (OPGs) are currently obtained in permanent famine or cyclic feast-famine regimes. Whether photogranulation occurs under a permanent feast regime and how these regimes impact OPGs are unknown. Herein, the three regimes, each applied in two replicate hydrodynamic reactors, were established by different feeding frequencies. Results showed that OPGs were successfully cultivated in all regimes after 24-36 days of photogranulation phases with similar microbial community functions, including filamentous gliding, extracellular polymeric substances production, and carbon/nitrogen metabolism. The OPGs were then operated under the same sequencing batch mode and all achieved efficient removal of chemical oxygen demand (>91 %), ammonium (>96 %), and total nitrogen (>76 %) after different adaptation periods (19-41 days). Notably, the permanent feast regime obtained OPGs with the best physicochemical properties, the shortest adaptation period, and the lowest effluent turbidity, thus representing a novel means of hydrodynamic cultivating OPGs with better performances for sustainable wastewater treatment.


Hydrodynamics , Nitrogen , Oxygen , Oxygen/metabolism , Bioreactors , Biological Oxygen Demand Analysis , Wastewater/chemistry , Carbon/chemistry , Water Purification/methods
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