Search Results (3,995)

Little is known about the effects of statins, which are cholesterol-lowering drugs, on the bioenergetic functions of mitochondria in the brain. This study aimed to elucidate the direct effects of atorvastatin and simvastatin on the bioenergetics of isolated rat brain mitochondria by measuring the statin-induced changes in respiratory chain activity, ATP synthesis efficiency, and the production of reactive oxygen species (ROS). Our results in isolated brain mitochondria are the first to demonstrate that atorvastatin and simvastatin dose-dependently significantly inhibit the activity of the mitochondrial respiratory chain, resulting in a decreased respiratory rate, a decreased membrane potential, and increased ROS formation. Moreover, the tested statins reduced mitochondrial coupling parameters, the ADP/O ratio, the respiratory control ratio, and thus, the oxidative phosphorylation efficiency in brain mitochondria. Among the oxidative phosphorylation complexes, statin-induced mitochondrial impairment concerned complex I, complex III, and ATP synthase activity. The calcium-containing atorvastatin had a significantly more substantial effect on isolated brain mitochondria than simvastatin. The higher inhibitory effect of atorvastatin was dependent on calcium ions, which may lead to the disruption of calcium homeostasis in mitochondria. These findings suggest that while statins are effective in their primary role as cholesterol-lowering agents, their use may impair mitochondrial function, which may have consequences for brain health, particularly when mitochondrial energy efficiency is critical. Full article

Arsenic (As) contamination poses significant environmental and health concerns globally, particularly in regions with high exposure levels due to anthropogenic activities. As phytoremediation, particularly through the hyperaccumulator fern Pteris vittata, offers a promising approach to mitigate arsenic pollution. Bacteria and mycorrhizal fungi colonizing P. vittata roots are involved in As metabolism and resistance and plant growth promotion under stressful conditions. A total of 45 bacterial strains were isolated from bulk soil and the rhizosphere of mycorrhizal P. vittata growing in an industrial As-polluted site. Bacteria were characterized by their plant-beneficial traits, tolerance to sodium arsenate and arsenite, and the occurrence of As-resistant genes. This study highlights differences between the culturable fraction of the microbiota associated with the rhizosphere of mycorrhizal P. vittata plants and the bulk soil. Moreover, several strains showing arsenate tolerance up to 600 mM were isolated. All the bacterial strains possessed arsC genes, and about 70% of them showed arrA genes involved in the anaerobic arsenate respiration pathway. The possible exploitation of such bacterial strains in strategies devoted to the assisted phytoremediation of arsenic highlights the importance of such a study in order to develop effective in situ phytoremediation strategies. Full article

Metabolomics, the study of small-molecule metabolites within biological systems, has become a potent instrument for understanding cellular processes. Despite its profound insights into health, disease, and drug development, identifying the protein partners for metabolites, especially dietary phytochemicals, remains challenging. In the present study, we introduced an innovative in silico, structure-based target prediction approach to efficiently predict protein targets for metabolites. We analyzed 27 blood serum metabolites from nutrition intervention studies’ blueberry-rich diets, known for their health benefits, yet with elusive mechanisms of action. Our findings reveal that blueberry-derived metabolites predominantly interact with Carbonic Anhydrase (CA) family proteins, which are crucial in acid-base regulation, respiration, fluid balance, bone metabolism, neurotransmission, and specific aspects of cellular metabolism. Molecular docking showed that these metabolites bind to a common pocket on CA proteins, with binding energies ranging from −5.0 kcal/mol to −9.0 kcal/mol. Further molecular dynamics (MD) simulations confirmed the stable binding of metabolites near the Zn binding site, consistent with known compound interactions. These results highlight the potential health benefits of blueberry metabolites through interaction with CA proteins. Full article

The concept of the “central governor” in exercise physiology suggests the brain plays a key role in regulating exercise performance by continuously monitoring physiological and psychological factors. In this case report, we monitored, for the first time, a marathon runner using a metabolic portable system and an EEG wireless device during an entire marathon to understand the influence of brain activity on performance, particularly the phenomenon known as “hitting the wall”. The results showed significant early modification in brain activity between the 10th and 15th kilometers, while the RPE remained low and cardiorespiratory responses were in a steady state. Thereafter, EEG responses decreased after kilometer 15, increased briefly between kilometers 20 and 25, then continued at a slower pace. After kilometer 30, both speed and respiration values dropped, along with the respiratory exchange ratio, indicating a shift from carbohydrate to fat metabolism, reflecting glycogen depletion. The runner concluded the race with a lower speed, higher RPE (above 15/20 on the Borg RPE scale), and reduced brain activity, suggesting mental exhaustion. The findings suggest that training strategies focused on recognizing and responding to brain signals could allow runners to optimize performance and pacing strategies, preventing premature exhaustion and improving overall race outcomes. Full article

Seed quality declines during storage depending on relative humidity, temperature, and oxygen concentration. Low-oxygen atmospheres significantly enhanced the germination and vigor of seeds during storage in laboratory-scale experiments. Low-oxygen atmospheres include self-modified atmospheres, where gas composition changes due to microbial respiration and oxidative processes, as well as modified atmospheres, where gas composition is initially altered from an external source without further adjustments. However, the potential of low-oxygen atmospheres to preserve the quality of maize (Zea mays) seeds in bags of 25–50 kg capacity, like those employed by seed companies and small-scale farmers, remains underexplored, hindering a broader adoption of this storage technology. Our study assessed the feasibility of applying low-oxygen atmospheres for seed storage on the pilot scale, i.e., hermetic containers of 25 kg capacity made of polyethylene and polyamide, under controlled conditions. We first evaluated the ability of the hermetic containers to maintain low oxygen levels over time. Then, we compared the germination and vigor of seeds stored in the hermetic containers under modified and self-modified atmospheres with those stored in traditional poly-paper bags under normal atmospheric conditions. The seeds had 14% moisture content (wet basis) and were stored at 25 °C and 10 °C. Maintaining low oxygen levels in polyethylene–polyamide bags was feasible. Moreover, at 25 °C, modified and self-modified atmospheres maintained higher germination values (95.8% and 94.4%, respectively) compared to traditional storage (68.3%), and both were as effective as refrigeration (97.6%). However, refrigeration was better for preserving seed vigor, with radicle emergence values of 85.2% in self-modified atmospheres and 78.9% in modified atmospheres, compared to 65.0% and 61.2%, respectively, at 25 °C. In conclusion, the advantages of modified atmospheres observed in laboratory-scale studies are achievable on a larger scale with a proper container design, advancing the prospects for the practical application of this technology for the seed industry and small farmers. Full article

As the largest carbon reservoir within terrestrial ecosystems, forest ecosystems play a major role as carbon sinks in the global carbon cycle. There are still some uncertainties regarding the responses of different carbon fluxes to environmental changes in cold temperate climate forest ecosystems. Here, 14 cold temperate forest flux sites for at least ten years were investigated, including carbon fluxes and environmental variables such as temperature, precipitation, shortwave radiation, and vapor pressure deficit. By calculating the Spearman correlation coefficient, there was a congruence between photosynthetic productivity (i.e., gross primary productivity, GPP) and carbon sequestration (i.e., net ecosystem productivity, NEP) at thirteen forest sites, and at one forest site, GPP and NEP were decoupled. Annual GPP and NEP displayed a consistent trend when temperature and precipitation had significantly opposite trends and when temperature had a significantly positive correlation with VPD. But when VPD was significantly negatively correlated with both temperature and SW in spring and when temperature was negatively correlated with both SW and VPD in summer, a decoupling of GPP and NEP occurred. The impacts of various environmental factors on the annual carbon fluxes were calculated for each year and season using the path analysis method. At forest sites with consistent trends in GPP and NEP, annual, spring, and summer temperatures had significant positive correlations with GPP and ecosystem respiration (RE). While at the decoupled forest site, environmental factors had a stronger effect on RE, which then contributed to the observed decoupling of GPP and NEP. Finally, the Partial Least Squares method was used to analyze the relative contribution of each environmental factor to annual carbon fluxes. The results revealed that temperature and summer precipitation were the key environmental factors affecting forest ecosystems. This study provides important insights into the different responses of carbon fluxes in forest ecosystems undergoing environmental changes. Full article

Many fatal inhalational accidents occurring during construction typically involving confined spaces and structures that confine the atmosphere continue to defy identification. Very little information is available, principally from accident summaries and government reports. Increasingly, these identify CO₂ (carbon dioxide) as a probable cause. This article discusses situations identified in accident summaries and worldwide databases. CO₂ lacks an odor and other means of identification without the use of monitoring instruments. Emissions typically involve exhaust gases; aerobic and anaerobic respiration in microbiological systems in wastewater and landfills; geological deposits capable of chemical reaction to produce CO₂; and unintended discharge from pressurized systems. Emissions can occur continuously or abruptly subject to the type of system and conditions involved. Anaerobic systems that behave as shear-thinning, pseudoplastic, non-Newtonian fluids emit abruptly on the application of a shear force. A lethal concentration can develop almost instantaneously. Upon cessation of the stress, the ambient condition restores rapidly. Chemical and physical processes provide reservoirs for the storage of gas. Very limited methods are available for the prevention of these accidents because of the infrequency and unpredictability of the emission. Preventive measures include mandatory atmospheric monitoring and ventilation at all times, where hazardous conditions can develop, and sometimes the use of high-level respiratory protection. Full article

Photorespiration, caused by oxygenation of the enzyme Rubisco, is considered a wasteful process, because it reduces photosynthetic carbon gain, but it also supplies amino acids and is involved in amelioration of stress. Here, we show that a sudden increase in photorespiratory activity not only reduced carbon acquisition and production of sugars and starch, but also affected diurnal dynamics of amino acids not obviously involved in the process. Flux calculations based on diurnal metabolite profiles suggest that export of proline from leaves increases, while aspartate family members accumulate. An immense increase is observed for turnover in the cyclic reaction of glutamine synthetase/glutamine-oxoglutarate aminotransferase (GS/GOGAT), probably because of increased production of ammonium in photorespiration. The hpr1-1 mutant, defective in peroxisomal hydroxypyruvate reductase, shows substantial alterations in flux, leading to a shift from the oxoglutarate to the aspartate family of amino acids. This is coupled to a massive export of asparagine, which may serve in exchange for serine between shoot and root. Full article

The purple carrot cultivar ‘Purple Sun’ (Daucus carota L.) is characterized by a relevant content of phenolic compounds and anthocyanins, which may play an important role in reducing the risk of chronic diseases and in the treatment of metabolic syndrome. In the present study, the genetic diversity, phytochemical composition, and bioactivities of this outstanding variety were studied for the first time. Genetic analysis by molecular markers estimated the level of genetic purity of this carrot cultivar, whose purple-pigmented roots were used for obtaining the purple carrot ethanol extract (PCE). With the aim to identify specialized metabolites potentially responsible for the bioactivities, the analysis of the metabolite profile of PCE by LC-ESI/LTQ Orbitrap/MS/MS was carried out. LC-ESI/HRMS analysis allowed the assignment of twenty-eight compounds, putatively identified as isocitric acid (1), phenolic acid derivatives (2 and 6), hydroxycinnamic acid derivatives (9, 10, 12–14, 16, 17, 19, 22, and 23), anthocyanins (3–5, 7, 8, 11, and 18), flavanonols (15 and 21), flavonols (20 and 24), oxylipins (25, 26, and 28), and the sesquiterpene 11-acetyloxytorilolone (27); compound 26, corresponding to the primary metabolite trihydroxyoctanoic acid (TriHOME), was the most abundant compound in the LC-ESI/HRMS analysis of the PCE, and hydroxycinnamic acid derivatives followed by anthocyanins were the two most represented groups. The antioxidant activity of PCE, expressed in terms of reactive oxygen species (ROS) level and antioxidant enzymes activity, and its pro-metabolic effect were evaluated. Moreover, the antibacterial activity on Gram (−) and (+) bacterial strains was investigated. An increase in the activity of antioxidant enzymes (SOD, CAT, and GPx), reaching a maximum at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL), was observed. PCE induced an initial decrease in ROS levels at 0.1 and 0.25 mg/mL concentrations, reaching the ROS levels of control at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL). Moreover, significant antioxidant and pro-metabolic effects of PCE on myoblasts were shown by a reduction in ROS content and an increase in ATP production linked to the promotion of mitochondrial respiration. Finally, the bacteriostatic activity of PCE was shown on the different bacterial strains tested, while the bactericidal action of PCE was exclusively observed against the Gram (+) Staphylococcus aureus. The bioactivities of PCE were also investigated from cellular and molecular points of view in colon and hematological cancer cells. The results showed that PCE induces proliferative arrest and modulates the expression of important cell-cycle regulators. For all these health-promoting effects, also supported by initial computational predictions, ‘Purple Sun’ is a promising functional food and an optimal candidate for pharmaceutical and/or nutraceutical preparations. Full article

Microplastics (MPs) are present in ambient air in a respirable size fraction; however, their potential impact on human health via inhalation routes is not well documented. In the present study, methods for a lab-scale generation of MPs from regularly used and littered plastic articles were optimized. The toxicity of 11 different types of MPs, both commercially purchased and in-lab prepared MPs, was investigated in lung epithelial cells using cell viability, immune and inflammatory response, and genotoxicity endpoints. The underlying mechanisms were identified by microarray analysis. Although laborious, the laboratory-scale methods generated a sufficient quantity of well characterized MPs for toxicity testing. Of the 11 MPs tested, the small sized polyethylene terephthalate (PETE) MPs prepared from disposable water bottles induced the maximum toxicity. Specifically, the smaller size PETE MPs induced a robust activation of the interferon signaling pathway, implying that PETE MPs are perceived by cells by similar mechanisms as those employed to recognize pathogens. The PETE MPs of heterogenous size and shapes induced cell injury, triggering cell death, inflammatory cascade, and DNA damage, hallmark in vitro events indicative of potential in vivo tissue injury. The study establishes toxicity of specific types of plastic materials in micron and nano size. Full article

Agaricus bisporus is one of the most popular mushroom species in the world; however, mushrooms are highly susceptible to browning due to the absence of a protective cuticle layer and high respiration rate. The molecular mechanism underlying the process of mushroom browning needs to be explored. Here, we analyzed the transcriptomic and metabolomic data from A. bisporus at ambient temperature. Specifically, a total of 263 significantly changed metabolites and 4492 differentially expressed genes were identified. Lipid metabolites associated with cell membrane degradation were predominantly up-regulated during ambient storage. Transcriptomic data further revealed the alterations of the expression of membrane lipid metabolism-related enzymes. Additionally, energy metabolic processes and products such as glycolysis and linoleic acid changed significantly during ambient storage, indicating their potential roles in the quality deterioration of A. bisporus. These findings provide new insights into the underlying lipid metabolic mechanisms of A. bisporus during postharvest ambient storage and will provide values for mushroom preservation techniques. Full article

α-glucosidase, a pharmacological target for type 2 diabetes mellitus (T2DM), is present in the intestinal brush border membrane and catalyzes the hydrolysis of sugar linkages during carbohydrate digestion. Since α-glucosidase inhibitors (AGIs) modulate intestinal metabolism, they may influence oxidative stress and glycolysis inhibition, potentially addressing intestinal dysfunction associated with T2DM. Herein, we report on a study of an ortho-carbonyl substituted hydroquinone series, whose members differ only in the number and position of methyl groups on a common scaffold, on radical-scavenging activities (ORAC assay) and correlate them with some parameters obtained by density functional theory (DFT) analysis. These compounds’ effect on enzymatic activity, their molecular modeling on α-glucosidase, and their impact on the mitochondrial respiration and glycolysis of the intestinal Caco-2 cell line were evaluated. Three groups of compounds, according their effects on the Caco-2 cells metabolism, were characterized: group A (compounds 2, 3, 5, 8, 9, and 10) reduces the glycolysis, group B (compounds 1 and 6) reduces the basal mitochondrial oxygen consumption rate (OCR) and increases the extracellular acidification rate (ECAR), suggesting that it induces a metabolic remodeling toward glycolysis, and group C (compounds 4 and 7) increases the glycolysis lacking effect on OCR. Compounds 5 and 10 were more potent as α-glucosidase inhibitors (AGIs) than acarbose, a well-known AGI with clinical use. Moreover, compound 5 was an OCR/ECAR inhibitor, and compound 10 was a dual agent, increasing the proton leak-driven OCR and inhibiting the maximal electron transport flux. Additionally, menadione-induced ROS production was prevented by compound 5 in Caco-2 cells. These results reveal that slight structural variations in a hydroquinone scaffold led to diverse antioxidant capability, α-glucosidase inhibition, and the regulation of mitochondrial bioenergetics in Caco-2 cells, which may be useful in the design of new drugs for T2DM and metabolic syndrome. Full article

Blossom end enlargement (BEE) is a postharvest deformation that may be related to the influx of photosynthetic assimilates before harvest. To elucidate the mechanism by which BEE occurs, expression marker genes that indicate the physiological condition of BEE-symptomatic fruit are necessary. First, we discovered that preharvest treatment with a synthetic cytokinin, N-(2-Chloro-4-pyridyl)-N’-phenylurea (CPPU), promoted fruit growth and suppressed BEE occurrence. This suggests that excessive assimilate influx is not a main cause of BEE occurrence. Subsequently, the expression levels of seven sugar-starvation marker genes, CsSEF1, AS, CsFDI1, CsPID, CsFUL1, CsETR1, and CsERF1B, were compared among symptomatic and asymptomatic fruits, combined with and without CPPU treatment. Only CsSEF1 showed a higher expression level in asymptomatic fruits than in symptomatic fruits, regardless of CPPU treatment. This was then tested using fruits stored via the modified-atmosphere packaging technique, which resulted in a lower occurrence of BEE, and the asymptomatic fruits showed a higher CsSEF1 expression level than symptomatic fruits, regardless of the packaging method. CsSEF1 codes a CCCH-type zinc finger protein, and an increase in the expression of CsSEF1 was correlated with a decrease in the fruit respiration rate. Thus, CsSEF1 may be usable as a BEE expression marker gene. Full article

Overdose of acetaminophen (APAP) produces fulminant hepatic necrosis. The underlying mechanism of APAP hepatotoxicity involves mitochondrial dysfunction, including mitochondrial oxidant stress and the onset of mitochondrial permeability transition (MPT). Reactive oxygen species (ROS) play an important role in APAP-induced hepatotoxicity, and iron is a critical catalyst for ROS formation. This review summarizes the role of mitochondrial ROS formation in APAP hepatotoxicity and further focuses on the role of iron. Normally, hepatocytes take up Fe³⁺-transferrin bound to transferrin receptors via endocytosis. Concentrated into lysosomes, the controlled release of iron is required for the mitochondrial biosynthesis of heme and non-heme iron-sulfur clusters. After APAP overdose, the toxic metabolite, NAPQI, damages lysosomes, causing excess iron release and the mitochondrial uptake of Fe²⁺ by the mitochondrial calcium uniporter (MCU). NAPQI also inhibits mitochondrial respiration to promote ROS formation, including H₂O₂, with which Fe²⁺ reacts to form highly reactive •OH through the Fenton reaction. •OH, in turn, causes lipid peroxidation, the formation of toxic aldehydes, induction of the MPT, and ultimately, cell death. Fe²⁺ also facilitates protein nitration. Targeting pathways of mitochondrial iron movement and consequent iron-dependent mitochondrial ROS formation is a promising strategy to intervene against APAP hepatotoxicity in a clinical setting. Full article

In a biological signal analysis system, signals of the same type may exhibit significant variations in their feature waveforms. Biological signals are typically weak, which increases the complexity of their analysis. Furthermore, clinical biomedical signals are susceptible to various interferences from the human body itself, including muscle movements, respiration, and heartbeat. These interference factors further escalate the complexity and difficulty of signal analysis. Therefore, precise and targeted preprocessing is often required before analyzing these clinical biomedical signals to enhance the accuracy and reliability of subsequent feature extraction and classification. Here, we have established an effective and practical algorithm model that integrates preprocessing with the initial localization of target feature waveforms, achieving the following four objectives: 1. Determining the periodic positions of target feature waveforms. 2. Preserving the original amplitude and shape of target feature waveforms while eliminating negative interference. 3. Reducing or eliminating interference from other feature waveforms in the input signal. 4. Decreasing noise in the input signal, such as baseline drift, powerline interference, and muscle artifacts commonly found in biological signals. We have validated the algorithm on clinical electrocardiogram (ECG) data and the authoritative MIT-BIH open-source ECG database demonstrating its effectiveness and reliability. Full article