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PeerJ 2024(Thunb.) Makino, a well-known edible and medicinal plant, has anti-aging properties and is used to treataging-associated conditions such as diabetes, metabolic...
BACKGROUND
(Thunb.) Makino, a well-known edible and medicinal plant, has anti-aging properties and is used to treataging-associated conditions such as diabetes, metabolic syndrome, and cardiovascular diseases. Gypenosides (GYPs) are the primary constituents of . Increasing evidence indicates that GYPs are effective at preserving mitochondrial homeostasis and preventing heart failure (HF). This study aimed to uncover the cardioprotective mechanisms of GYPs related to mitochondrial regulation.
METHODS
The bioactive components in GYPs and the potential targets in treating HF were obtained and screened using the network pharmacology approach, followed by drug-disease target prediction and enrichment analyses. The pharmacological effects of GYPs in cardioprotection, mitochondrial function, mitochondrial quality control, and underlying mechanisms were further investigated in Doxorubicin (Dox)-stimulated H9c2 cardiomyocytes.
RESULTS
A total of 88 bioactive compounds of GYPs and their respective 71 drug-disease targets were identified. The hub targets covered MAPK, EGFR, PI3KCA, and Mcl-1. Enrichment analysis revealed that the pathways primarily contained PI3K/Akt, MAPK, and FoxO signalings, as well as calcium regulation, protein phosphorylation, apoptosis, and mitophagy process. In Dox-stimulated H9c2 rat cardiomyocytes, pretreatment with GYPs increased cell viability, enhanced cellular ATP content, restored basal oxygen consumption rate (OCR), and improved mitochondrial membrane potential (MMP). Furthermore, GYPs improved PINK1/parkin-mediated mitophagy without influencing mitochondrial fission/fusion proteins and the autophagic LC3 levels. Mechanistically, the phosphorylation of PI3K, Akt, GSK-3β, and the protein level of Mcl-1 was upregulated by GYP treatment.
CONCLUSION
Our findings reveal that GYPs exert cardioprotective effects by rescuing the defective mitophagy, and PI3K/Akt/GSK-3/Mcl-1 signaling is potentially involved in this process.
Topics: Gynostemma; Mitophagy; Glycogen Synthase Kinase 3 beta; Signal Transduction; Myeloid Cell Leukemia Sequence 1 Protein; Proto-Oncogene Proteins c-akt; Cardiotonic Agents; Plant Extracts; Phosphatidylinositol 3-Kinases; Animals; Rats; Myocytes, Cardiac; Cell Line
PubMed: 38912051
DOI: 10.7717/peerj.17538 -
Scientific Reports Jun 2024Microglia, brain-resident macrophages, can acquire distinct functional phenotypes, which are supported by differential reprogramming of cell metabolism. These...
Microglia, brain-resident macrophages, can acquire distinct functional phenotypes, which are supported by differential reprogramming of cell metabolism. These adaptations include remodeling in glycolytic and mitochondrial metabolic fluxes, potentially altering energy substrate availability at the tissue level. This phenomenon may be highly relevant in the brain, where metabolism must be precisely regulated to maintain appropriate neuronal excitability and synaptic transmission. Direct evidence that microglia can impact on neuronal energy metabolism has been widely lacking, however. Combining molecular profiling, electrophysiology, oxygen microsensor recordings and mathematical modeling, we investigated microglia-mediated disturbances in brain energetics during neuroinflammation. Our results suggest that proinflammatory microglia showing enhanced nitric oxide release and decreased CX3CR1 expression transiently increase the tissue lactate/glucose ratio that depends on transcriptional reprogramming in microglia, not in neurons. In this condition, neuronal network activity such as gamma oscillations (30-70 Hz) can be fueled by increased ATP production in mitochondria, which is reflected by elevated oxygen consumption. During dysregulated inflammation, high energy demand and low glucose availability can be boundary conditions for neuronal metabolic fitness as revealed by kinetic modeling of single neuron energetics. Collectively, these findings indicate that metabolic flexibility protects neuronal network function against alterations in local substrate availability during moderate neuroinflammation.
Topics: Animals; Neurons; Energy Metabolism; Microglia; Mice; Neuroinflammatory Diseases; Glucose; Mitochondria; Nitric Oxide; Lactic Acid; Nerve Net; Brain; Oxygen Consumption; Adenosine Triphosphate; Inflammation; Male; Mice, Inbred C57BL
PubMed: 38909138
DOI: 10.1038/s41598-024-64872-1 -
Free Radical Biology & Medicine Jun 2024The skin is made up of different layers with various gradients, which maintain a complex microenvironment, particularly in terms of oxygen levels. However, all types of... (Review)
Review
The skin is made up of different layers with various gradients, which maintain a complex microenvironment, particularly in terms of oxygen levels. However, all types of skin cells are cultured in conventional incubators that do not reproduce physiological oxygen levels. Instead, they are cultured at atmospheric oxygen levels, a condition that is far removed from physiology and may lead to the generation of free radicals known to induce skin ageing. This review aims to summarize the current literature on the effect of physiological oxygen levels on skin cells, highlight the shortcomings of current in vitro models, and demonstrate the importance of respecting skin oxygen levels. We begin by clarifying the terminology used about oxygen levels and describe the specific distribution of oxygen in the skin. We review and discuss how skin cells adapt their oxygen consumption and metabolism to oxygen levels environment, as well as the changes that are induced, particularly, their redox state, life cycle and functions. We examine the effects of oxygen on both simple culture models and more complex reconstructed skin models. Finally, we present the implications of oxygen modulation for a more therapeutic approach.
PubMed: 38908804
DOI: 10.1016/j.freeradbiomed.2024.06.015 -
The Journal of Nutrition, Health & Aging Jun 2024There is a lack of consensus about the operationalization of vitality, which is one of the intrinsic capacity (IC) domains. In particular, no study has investigated...
BACKGROUND
There is a lack of consensus about the operationalization of vitality, which is one of the intrinsic capacity (IC) domains. In particular, no study has investigated whether cardiorespiratory fitness (CRF) can be considered a vitality indicator.
OBJECTIVE
To examine whether vitality is the upstream domain of IC, and establish the validity of CRF as a vitality indicator, using maximal oxygen consumption (VO max) as a representative.
METHODS
561 older adults from a longitudinal cohort study were included. Variables under consideration were VO max, other IC domains, instrumental activities of daily living (IADL), and handgrip strength, which was considered an already validated indicator of vitality. Using handgrip strength as the reference point, path analyses were performed to examine whether VO max followed a similar hierarchical structure in predicting change in IADL difficulty through other IC domains.
RESULTS
The mean age of the participants was 75.5 years. The path model in which vitality was measured by VO max demonstrated adequate fit, which was similar to the model in which vitality was measured by handgrip strength. Regarding the path coefficients, the model using VO max demonstrated significant total and indirect effects. Notably, the indirect effect was due to the locomotor domain (standardized coefficient = -0.148, p < .001), but not the cognitive or psychological domain.
CONCLUSION
Vitality is the upstream domain of IC. VO max can be considered an indicator to operationalize the vitality concept.
PubMed: 38908298
DOI: 10.1016/j.jnha.2024.100300 -
Nature Communications Jun 2024The introduction of single-atom catalysts (SACs) into Fenton-like oxidation promises ultrafast water pollutant elimination, but the limited access to pollutants and...
The introduction of single-atom catalysts (SACs) into Fenton-like oxidation promises ultrafast water pollutant elimination, but the limited access to pollutants and oxidant by surface catalytic sites and the intensive oxidant consumption still severely restrict the decontamination performance. While nanoconfinement of SACs allows drastically enhanced decontamination reaction kinetics, the detailed regulatory mechanisms remain elusive. Here, we unveil that, apart from local enrichment of reactants, the catalytic pathway shift is also an important cause for the reactivity enhancement of nanoconfined SACs. The surface electronic structure of cobalt site is altered by confining it within the nanopores of mesostructured silica particles, which triggers a fundamental transition from singlet oxygen to electron transfer pathway for 4-chlorophenol oxidation. The changed pathway and accelerated interfacial mass transfer render the nanoconfined system up to 34.7-fold higher pollutant degradation rate and drastically raised peroxymonosulfate utilization efficiency (from 61.8% to 96.6%) relative to the unconfined control. It also demonstrates superior reactivity for the degradation of other electron-rich phenolic compounds, good environment robustness, and high stability for treating real lake water. Our findings deepen the knowledge of nanoconfined catalysis and may inspire innovations in low-carbon water purification technologies and other heterogeneous catalytic applications.
PubMed: 38906879
DOI: 10.1038/s41467-024-49605-2 -
BioRxiv : the Preprint Server For... May 2024Pathogenic variants in were recently linked to a limb-girdle muscular dystrophy (LGMD) phenotype. The protein product HMG CoA reductase (HMGCR) catalyzes a key...
Pathogenic variants in were recently linked to a limb-girdle muscular dystrophy (LGMD) phenotype. The protein product HMG CoA reductase (HMGCR) catalyzes a key component of the cholesterol synthesis pathway. The two other muscle diseases associated with HMGCR, statin-associated myopathy (SAM) and autoimmune anti-HMGCR myopathy, are not inherited in a Mendelian pattern. The mechanism linking pathogenic variants in with skeletal muscle dysfunction is unclear. We knocked down in mouse skeletal myoblasts, knocked down in Drosophila, and expressed three pathogenic variants (c.1327C>T, p.Arg443Trp; c.1522_1524delTCT, p.Ser508del; and c.1621G>A, p.Ala541Thr) in knockdown mouse myoblasts. deficiency was associated with decreased proliferation, increased apoptosis, and impaired myotube fusion. Transcriptome sequencing of knockdown versus control myoblasts revealed differential expression involving mitochondrial function, with corresponding differences in cellular oxygen consumption rates. Both ubiquitous and muscle-specific knockdown of in Drosophila led to lethality. Overexpression of reference cDNA rescued myotube fusion in knockdown cells, whereas overexpression of the pathogenic variants of cDNA did not. These results suggest that the three HMGCR-related muscle diseases share disease mechanisms related to skeletal muscle development.
PubMed: 38903061
DOI: 10.1101/2024.05.06.591934 -
Journal of Thermal Biology Jun 2024The relationship between behavioral thermoregulation and physiological recovery following exhaustive exercise is not well understood. Behavioral thermoregulation could...
The relationship between behavioral thermoregulation and physiological recovery following exhaustive exercise is not well understood. Behavioral thermoregulation could be beneficial for exercise recovery; for example, selection of cooler temperatures could reduce maintenance metabolic cost to preserve aerobic scope for recovery cost, or selection of warmer temperatures could accelerate recovery of exercise metabolites. While post-exercise behavioral thermoregulation has been observed in lizards and frogs, little is known about its importance in fish. We examined the influence of post-exercise recovery temperature on metabolic rate, thermal preference, and metabolite concentrations in juvenile brook char (Salvelinus fontinalis). Fish were acclimated to and exercised at 15 °C, then recovered at either 15 °C or 10 °C while their metabolic rate was measured via respirometry. Metabolite concentrations were measured in fish after exercise at 15 °C and recovery under one of three thermal treatments (to simulate various behavioral thermoregulation scenarios): (i) 6 h recovery at 15 °C, (ii) 6 h recovery at 10 °C, or (iii) 3 h recovery at 10 °C followed by 3 h recovery at 15 °C. Thermal preference was quantified using a static temperature preference system (15 °C vs. 10 °C). Metabolic rates returned to resting faster at 10 °C compared with 15 °C, although at 10 °C there was a tradeoff of delayed metabolite recovery. Specifically, post-exercise plasma osmolality, plasma lactate, and muscle lactate remained elevated for the entire period in fish recovering at 10 °C, whereas these parameters returned to resting levels by 6 h in fish from the other two recovery groups. Regardless, fish did not exhibit clear behavioral thermoregulation (i.e., fish overall did not consistently prefer one temperature) to prioritize either physiological recovery process. The advantage of metabolic rate recovery at cooler temperatures may balance against the advantage of metabolite recovery at warmer temperatures, lessening the usefulness of behavioral thermoregulation as a post-exercise recovery strategy in fish.
PubMed: 38901397
DOI: 10.1016/j.jtherbio.2024.103888 -
Water Research Jun 2024Freshwater ecosystems are critical resources for drinking water. In recent decades, dissolved organic matter (DOM) inputs into aquatic systems have increased...
Freshwater ecosystems are critical resources for drinking water. In recent decades, dissolved organic matter (DOM) inputs into aquatic systems have increased significantly, particularly in central and northern Europe, due to climatic and anthropogenic drivers. The associated increase in dissolved organic carbon (DOC) concentration can change lake ecosystem services and adversely affect drinking water treatment processes. In this study, we examined spatial and temporal patterns of DOM treatability with granular activated carbon (GAC) and biological reactivity based on 14-day bacterial respiration incubations at 11 sites across Mälaren during six-time points between July 2019 and February 2021. Mälaren is the third largest lake in Sweden and provides drinking water for over 2 million people including the capital city Stockholm. In our spatio-temporal analysis, we assessed the influence of phytoplankton abundance, water chemistry, runoff, and climate on DOM composition, GAC removal efficiency, and biological reactivity. Variations in DOM composition were characterized using optical measurements and Orbitrap mass spectrometry. Multivariate statistical analyses indicated that DOM produced during warmer months was easier to remove by GAC. Removal efficiency of GAC varied from 41 to 87 %, and the best predictor of treatability using mass spectrometry was double bond equivalents (DBE), while the best optical predictors were specific UV absorbance (SUVA), and freshness index. The oxygen consumption rate (k) from the bacterial respiration incubations ranged from 0.04 to 0.71 d and higher in warmer months and at deeper basins and was associated with more aliphatic and fresh DOM. The three deepest lake basins with the longest water residence time (WRT) were temporally the most stable in terms of DOM composition and had the highest DOC removal efficiency and k rates. DOM composition in these three lake basins was optically clearer than in basins located closer to terrestrial inputs and had a signature suggesting it was derived from in-lake processes including phytoplankton production and bacterial processing of terrestrial DOM. This means that with increasing WRT, DOM derived from terrestrial sources shifts to more aquatically produced DOM and becomes easier to remove with GAC. These findings indicate WRT can be highly relevant in shaping DOM composition and thereby likely to affect its ease of treatability for drinking water purposes.
PubMed: 38901310
DOI: 10.1016/j.watres.2024.121910 -
Redox Biology Jun 2024We previously demonstrated that the human amniotic fluid (hAF) from II trimester of gestation is a feasible source of stromal progenitors (human amniotic fluid stem...
BACKGROUND
We previously demonstrated that the human amniotic fluid (hAF) from II trimester of gestation is a feasible source of stromal progenitors (human amniotic fluid stem cells, hAFSC), with significant paracrine potential for regenerative medicine. Extracellular vesicles (EVs) separated and concentrated from hAFSC secretome can deliver pro-survival, proliferative, anti-fibrotic and cardioprotective effects in preclinical models of skeletal and cardiac muscle injury. While hAFSC-EVs isolation can be significantly influenced by in vitro cell culture, here we profiled EVs directly concentrated from hAF as an alternative option and investigated their paracrine potential against oxidative stress.
METHODS
II trimester hAF samples were obtained as leftover material from prenatal diagnostic amniocentesis following written informed consent. EVs were separated by size exclusion chromatography and concentrated by ultracentrifugation. hAF-EVs were assessed by nanoparticle tracking analysis, transmission electron microscopy, Western Blot, and flow cytometry; their metabolic activity was evaluated by oximetric and luminometric analyses and their cargo profiled by proteomics and RNA sequencing. hAF-EV paracrine potential was tested in preclinical in vitro models of oxidative stress and dysfunction on murine C2C12 cells and on 3D human cardiac microtissue.
RESULTS
Our protocol resulted in a yield of 6.31 ± 0.98 × 10 EVs particles per hAF milliliter showing round cup-shaped morphology and 209.63 ± 6.10 nm average size, with relevant expression of CD81, CD63 and CD9 tetraspanin markers. hAF-EVs were enriched in CD133/1, CD326, CD24, CD29, and SSEA4 and able to produce ATP by oxygen consumption. While oxidative stress significantly reduced C2C12 survival, hAF-EV priming resulted in significant rescue of cell viability, with notable recovery of ATP synthesis and concomitant reduction of cell damage and lipid peroxidation activity. 3D human cardiac microtissues treated with hAF-EVs and experiencing HO stress and TGFβ stimulation showed improved survival with a remarkable decrease in the onset of fibrosis.
CONCLUSIONS
Our results suggest that leftover samples of II trimester human amniotic fluid can represent a feasible source of EVs to counteract oxidative damage on target cells, thus offering a novel candidate therapeutic option to counteract skeletal and cardiac muscle injury.
PubMed: 38901103
DOI: 10.1016/j.redox.2024.103241 -
Traditional Nostril Yoga Breathing Practices and Oxygen Consumption: A Randomized, Cross-over Study.International Journal of Yoga 2024Traditional yoga texts describe "cross nostril breathing," with inhalation and exhalation through different nostrils. Previous research reported no clear differences in...
BACKGROUND
Traditional yoga texts describe "cross nostril breathing," with inhalation and exhalation through different nostrils. Previous research reported no clear differences in oxygen consumption during uninostril breathing (i.e., inhalation and exhalation through the same nostril), hence not supporting right and left uninostril breathing as activating or relaxing, respectively, with no research on oxygen consumed in "cross nostril breathing."
METHODS
Oxygen consumed during "cross nostril breathing" was measured in healthy participants ( = 47, males, 26.3 ± 6.4 years). Five sessions (viz., right nostril inspiration yoga breathing [RNIYB], left nostril inspiration yoga breathing [LNIYB], alternate nostril yoga breathing [ANYB], breath awareness (BAW), and quiet rest (QR) were conducted on separate days in random order. Sessions were 33 min in duration with pre, during, and post states.
RESULTS
Volume of oxygen consumed (VO) and carbon dioxide eliminated (VCO) increased during RNIYB (9.60% in VO and 23.52% in VCO), LNIYB (9.42% in VO and 21.20% in VCO) and ANYB (10.25% in VO and 22.72% in VCO) with no significant change in BAW and QR. Diastolic blood pressure decreased during BAW and QR and after all five sessions ( < 0.05; in all cases). All comparisons were with the respective preceding state.
CONCLUSION
During the three yoga breathing practices, the volume of oxygen consumed increased irrespective of the nostril breathed through, possibly associated with (i) conscious regulation of the breath; (ii) attention directed to the breath, and (iii) "respiration-locked cortical activation." Restriction of the study to males reduces the generalizability of the findings.
PubMed: 38899139
DOI: 10.4103/ijoy.ijoy_248_23