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Huntington's disease (HD) is a rare hereditary neurodegenerative disorder characterized by multiple metabolic dysfunctions including defects in mitochondrial homeostasis and functions. Although we have recently reported age-related changes in the respiratory capacities in different brain areas in HD mice, the precise mechanisms of how mitochondria become compromised in HD are still poorly understood. In this study, we investigated mRNA and protein levels of selected subunits of electron transport system (ETS) complexes and ATP-synthase in the cortex and striatum of symptomatic R6/2 mice. Our findings reveal a brain-region-specific differential expression of both nuclear and mitochondrial-encoded ETS components, indicating defects of transcription, translation and/or mitochondrial import of mitochondrial ETS components in R6/2 mouse brains.

Aerobic and anaerobic respiratory systems allow cells to transport the electrons to terminal electron acceptors. The quinone (ubiquinone or menaquinone) pool is central to the electron transport chain. In the majority of Gram-positive bacteria, vitamin K2 (menaquinone) is the sole quinone in the electron transport chain, and thus, the bacterial enzymes catalyzing the synthesis of menaquinone are potential targets for the development of novel antibacterial drugs. This manuscript reviews the role of vitamin K in bacteria and humans, and especially emphasizes on recent aspects of menaquinones in bacterial electron transport chain and on discoveries of inhibitor molecules targeting bacterial electron transport systems for new antibacterial agents. [ABSTRACT FROM AUTHOR]

In plants, flooding-induced oxygen deficiency causes severe stress, leading to growth reduction and yield loss. It is therefore important to understand the molecular mechanisms for adaptation to hypoxia. Aquaporins at the plasma membrane play a crucial role in water uptake. However, their role during hypoxia and membrane redox changes is still not fully understood. The influence of 24 h hypoxia induction on hydroponically grown maize (Zea mays L.) was investigated using an oil-based setup. Analyses of physiological parameters revealed typical flooding symptoms such as increased ethylene and H2O2 levels, an increased alcohol dehydrogenase activity, and an increased redox activity at the plasma membrane along with decreased oxygen of the medium. Transcriptomic analysis and shotgun proteomics of plasma membranes and soluble fractions were performed to determine alterations in maize roots. RNA-sequencing data confirmed the upregulation of genes involved in anaerobic metabolism, biosynthesis of the phytohormone ethylene, and its receptors. Transcripts of several antioxidative systems and other oxidoreductases were regulated. Mass spectrometry analysis of the plasma membrane proteome revealed alterations in redox systems and an increased abundance of aquaporins. Here, we discuss the importance of plasma membrane aquaporins and redox systems in hypoxia stress response, including the regulation of plant growth and redox homeostasis. [ABSTRACT FROM AUTHOR]

Aerobic and anaerobic respiratory systems allow cells to transport the electrons to terminal electron acceptors. The quinone (ubiquinone or menaquinone) pool is central to the electron transport chain. In the majority of gram-positive bacteria, vitamin K2 (menaquinone) is the sole quinone in the electron transport chain, and thus, the bacterial enzymes catalyzing the synthesis of menaquinone are potential targets for the development of novel antibacterial drugs. This manuscript reviews the role of vitamin K in bacteria and humans, and especially emphasizes on recent aspects of menaquinones in bacterial electron transport chain and on discoveries of inhibitor molecules targeting bacterial electron transport systems for new antibacterial agents.

The transformation of prostatic epithelial cells to prostate cancer (PCa) has been characterized as a transition from citrate secretion to citrate oxidation, from which one would anticipate enhanced mitochondrial complex I (CI) respiratory flux. Molecular mechanisms for this transformation are attributed to declining mitochondrial zinc concentrations. The unique metabolic properties of PCa cells have become a hot research area. Several publications have provided indirect evidence based on investigations using pre-clinical models, established cell lines, and fixed or frozen tissue bank samples. However, confirmatory respiratory analysis on fresh human tissue has been hampered by multiple difficulties. Thus, few mitochondrial respiratory assessments of freshly procured human PCa tissue have been published on this question. Our objective is to document relative mitochondrial CI and complex II (CII) convergent electron flow to the Q-junction and to identify electron transport system (ETS) alterations in fresh PCa tissue. The results document a CII succinate: quinone oxidoreductase (SQR) dominant succinate oxidative flux model in the fresh non-malignant prostate tissue, which is enhanced in malignant tissue. CI NADH: ubiquinone oxidoreductase activity is impaired rather than predominant in high-grade malignant fresh prostate tissue. Given these novel findings, succinate and CII are promising targets for treating and preventing PCa. [ABSTRACT FROM AUTHOR]

Simple Summary: Exploring the interactions between organophosphorus flame retardants (OPFRs), microplastics, and freshwater organisms is essential for comprehending the dynamics within freshwater ecosystems to anticipate the potential impacts of organic pollutants and plastic particles. To address this need, the current study examined the exposure effects of 10 mg L−1 of flame-retardant aluminium diethylphosphinate (ALPI), 10 μg mg−1liver of microplastics polyurethane (PU), and their combination on the freshwater planarian Girardia tigrina. Twenty-four-hour exposure of G. tigrina to both ALPI and PU resulted in a sequential effect reflected in a significant reduction in locomotor activity, i.e., exposure may involve a combination of direct neurotoxic effects and the indirect energetic costs associated with the adaptive responses to mitigate the adverse effects. Other biochemical responses, e.g., oxidative stress and metabolic responses, remained unaffected compared to control. Incorporating behavioural indicators into toxicological assays enhances the predictive power of these assessments, enabling a more accurate evaluation of the ecological consequences of pollutant exposure. This integrated approach not only improves our understanding of the complex interactions between organisms and their environment, but also informs more effective strategies for mitigating the detrimental effects of mixtures of pollutants on freshwater ecosystems. Understanding the interplay among organophosphorus flame retardants (OPFRs), microplastics, and freshwater organisms is crucial for unravelling the dynamics within freshwater environments and foreseeing the potential impacts of organic pollutants and plastic contamination. For that purpose, the present research assessed the exposure impact of 10 mg L−1 flame-retardant aluminium diethylphosphinate (ALPI), 10 μg mg−1liver microplastics polyurethane (PU), and the combination of ALPI and PU on the freshwater planarian Girardia tigrina. The exposure to both ALPI and PU revealed a sequential effect, i.e., a decrease in locomotor activity, while oxidative stress biomarkers (total glutathione, catalase, glutathione S-transferase, lipid peroxidation) and metabolic responses (cholinesterase activity, electron transport system, and lactate dehydrogenase) remained unaffected. Despite this fact, it was possible to observe that the range of physiological responses in exposed organisms varied, in particular in the cases of the electron transport system, cholinesterase activity, glutathione S-transferase, catalase, and levels of total glutathione and proteins, showing that the energetic costs for detoxification and antioxidant capacity might be causing a lesser amount of energy allocated for the planarian activity. By examining the physiological, behavioural, and ecological responses of planarians to these pollutants, insights can be gained into broader ecosystem-level effects and inform strategies for mitigating environmental risks associated with OPFRs and microplastic pollution in freshwater environments. [ABSTRACT FROM AUTHOR]

The progress in understanding the pathogenesis and treatment of Alzheimer's disease (AD) is based on the recognition of the primary causes of the disease, which can be deduced from the knowledge of risk factors and biomarkers measurable in the early stages of the disease. Insights into the risk factors and the time course of biomarker abnormalities point to a role for the connection of amyloid beta (Aβ) pathology, tau pathology, mitochondrial dysfunction, and oxidative stress in the onset and development of AD. Coenzyme Q10 (CoQ10) is a lipid antioxidant and electron transporter in the mitochondrial electron transport system. The availability and activity of CoQ10 is crucial for proper mitochondrial function and cellular bioenergetics. Based on the mitochondrial hypothesis of AD and the hypothesis of oxidative stress, the regulation of the efficiency of the oxidative phosphorylation system by means of CoQ10 can be considered promising in restoring the mitochondrial function impaired in AD, or in preventing the onset of mitochondrial dysfunction and the development of amyloid and tau pathology in AD. This review summarizes the knowledge on the pathophysiology of AD, in which CoQ10 may play a significant role, with the aim of evaluating the perspective of the pharmacotherapy of AD with CoQ10 and its analogues. [ABSTRACT FROM AUTHOR]

The use of hypoxic devices among athletes who train in normobaric hypoxia has become increasingly popular; however, the acute effects on heart and brain metabolism are not yet fully understood. This study aimed to investigate the mitochondrial bioenergetics in trained male and female Wistar rats after acute hypoxia training. The experimental plan included exercising for 30 min on a treadmill in a Plexiglas cage connected to a hypoxic generator set at 12.5% O2 or in normoxia. After the exercise, the rats were sacrificed, and their mitochondria were isolated from their brains and hearts. The bioenergetics for each complex of the electron transport chain was tested using a Clark-type electrode. The results showed that following hypoxia training, females experienced impaired oxidative phosphorylation through complex II in heart subsarcolemmal mitochondria, while males had an altered ADP/O in heart interfibrillar mitochondria, without any change in oxidative capacity. No differences from controls were evident in the brain, but an increased electron transport system efficiency was observed with complex I and IV substrates in males. Therefore, the study's findings suggest that hypoxia training affects the heart mitochondria of females more than males. This raises a cautionary flag for female athletes who use hypoxic devices. [ABSTRACT FROM AUTHOR]

Lipoic acid (LA) is a mitochondrial coenzyme that, depending on the concentration and exposure time, can behave as an antioxidant or pro-oxidant agent and has a proven ability to modulate metabolism by promoting lipid and glucose oxidation for energy production. To assess the effects of LA on energy metabolism and redox balance over time, Artemia sp. nauplii was used as an animal model. The administered concentrations of the antioxidant were 0.05, 0.1, 0.5, 1.0, 5.0, and 10.0 µM. Therefore, possible differences in protein, triglyceride, glucose, and lactate concentrations in the artemia samples and total ammoniacal nitrogen (TAN) in the culture water were evaluated. We also measured the effects of LA on in vivo activity of the electron transport system (ETS), antioxidant capacity, and production of reactive oxygen species (ROS) at 6, 12, 18, and 24 h post-hatching. There was a decrease in glucose concentration in the LA-treated animals, and a decrease in ammonia production was observed in the 0.5 µM LA treatment. ETS activity was positively regulated by the addition of LA, with the most significant effects at concentrations of 5.0 and 10.0 µM at 12 and 24 h. For ETS activity, treatments with LA presented the highest values at 24 h, a period when ROS production decreased significantly, for the treatment with 10.0 µM. LA showed positive regulation of energy metabolism together with a decrease in ROS and TAN excretion. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is an important cellular hallmark of aging and neurodegeneration. Platelets are a useful model to study the systemic manifestations of mitochondrial dysfunction. To evaluate the age dependence of mitochondrial parameters, citrate synthase activity, respiratory chain complex activity, and oxygen consumption kinetics were assessed. The effect of cognitive impairment was examined by comparing the age dependence of mitochondrial parameters in healthy individuals and those with neuropsychiatric disease. The study found a significant negative slope of age-dependence for both the activity of individual mitochondrial enzymes (citrate synthase and complex II) and parameters of mitochondrial respiration in intact platelets (routine respiration, maximum capacity of electron transport system, and respiratory rate after complex I inhibition). However, there was no significant difference in the age-related changes of mitochondrial parameters between individuals with and without cognitive impairment. These findings highlight the potential of measuring mitochondrial respiration in intact platelets as a means to assess age-related mitochondrial dysfunction. The results indicate that drugs and interventions targeting mitochondrial respiration may have the potential to slow down or eliminate certain aging and neurodegenerative processes. Mitochondrial respiration in platelets holds promise as a biomarker of aging, irrespective of the degree of cognitive impairment. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a chemotherapeutic agent highly effective at limiting cancer progression. Despite the efficacy of this anticancer drug, the clinical use of DOX is limited due to cardiotoxicity. The cardiac mitochondria are implicated as the primary target of DOX, resulting in inactivation of electron transport system complexes, oxidative stress, and iron overload. However, it is established that the cardiac mitochondrial subpopulations reveal differential responses to DOX exposure, with subsarcolemmal (SS) mitochondria demonstrating redox imbalance and the intermyofibrillar (IMF) mitochondria showing reduced respiration. In this regard, exercise training is an effective intervention to prevent DOX-induced cardiac dysfunction. Although it is clear that exercise confers mitochondrial protection, it is currently unknown if exercise training mitigates DOX cardiac mitochondrial toxicity by promoting beneficial adaptations to both the SS and IMF mitochondria. To test this, SS and IMF mitochondria were isolated from sedentary and exercise-preconditioned female Sprague Dawley rats exposed to acute DOX treatment. Our findings reveal a greater effect of exercise preconditioning on redox balance and iron handling in the SS mitochondria of DOX-treated rats compared to IMF, with rescue of cardiolipin synthase 1 expression in both subpopulations. These results demonstrate that exercise preconditioning improves mitochondrial homeostasis when combined with DOX treatment, and that the SS mitochondria display greater protection compared to the IMF mitochondria. These data provide important insights into the molecular mechanisms that are in part responsible for exercise-induced protection against DOX toxicity. [ABSTRACT FROM AUTHOR]

Mechanical ventilation during cardiothoracic surgery is life-saving but can lead to ventilator-induced diaphragm dysfunction (VIDD) and prolong ventilator weaning and hospital length of stay. Intraoperative phrenic nerve stimulation may preserve diaphragm force production to offset VIDD; we also investigated changes in mitochondrial function after stimulation. During cardiothoracic surgeries (n = 21), supramaximal, unilateral phrenic nerve stimulation was performed every 30 min for 1 min. Diaphragm biopsies were collected after the last stimulation and analyzed for mitochondrial respiration in permeabilized fibers and protein expression and enzymatic activity of biomarkers of oxidative stress and mitophagy. Patients received, on average, 6.2 ± 1.9 stimulation bouts. Stimulated hemidiaphragms showed lower leak respiration, maximum electron transport system (ETS) capacities, oxidative phosphorylation (OXPHOS), and spare capacity compared with unstimulated sides. There were no significant differences between mitochondrial enzyme activities and oxidative stress and mitophagy protein expression levels. Intraoperative phrenic nerve electrical stimulation led to an acute decrease of mitochondrial respiration in the stimulated hemidiaphragm, without differences in biomarkers of mitophagy or oxidative stress. Future studies warrant investigating optimal stimulation doses and testing post-operative chronic stimulation effects on weaning from the ventilator and rehabilitation outcomes. [ABSTRACT FROM AUTHOR]

Adverse maternal environments such as small size, malnutrition, and metabolic conditions are known to influence fetal growth outcomes. Similarly, fetal growth and metabolic alterations may alter the intrauterine environment and affect all fetuses in multiple gestation/litter-bearing species. The placenta is the site of convergence between signals derived from the mother and the developing fetus/es. Its functions are fuelled by energy generated by mitochondrial oxidative phosphorylation (OXPHOS). The aim of this study was to delineate the role of an altered maternal and/or fetal/intrauterine environment in feto-placental growth and placental mitochondrial energetic capacity. To address this, in mice, we used disruptions of the gene encoding phosphoinositol 3-kinase (PI3K) p110α, a growth and metabolic regulator to perturb the maternal and/or fetal/intrauterine environment and study the impact on wildtype conceptuses. We found that feto-placental growth was modified by a perturbed maternal and intrauterine environment, and effects were most evident for wildtype males compared to females. However, placental mitochondrial complex I+II OXPHOS and total electron transport system (ETS) capacity were similarly reduced for both fetal sexes, yet reserve capacity was additionally decreased in males in response to the maternal and intrauterine perturbations. These were also sex-dependent differences in the placental abundance of mitochondrial-related proteins (e.g., citrate synthase and ETS complexes), and activity of growth/metabolic signalling pathways (AKT and MAPK) with maternal and intrauterine alterations. Our findings thus identify that the mother and the intrauterine environment provided by littermates modulate feto-placental growth, placental bioenergetics, and metabolic signalling in a manner dependent on fetal sex. This may have relevance for understanding the pathways leading to reduced fetal growth, particularly in the context of suboptimal maternal environments and multiple gestation/litter-bearing species. [ABSTRACT FROM AUTHOR]

Human vision is mediated by the retina, one of the most critical tissues in the central nervous system. Glaucoma is a complex retinal disease attributed to environmental, genetic, and stochastic factors, all of which contribute to its pathogenesis. Historically, glaucoma had been thought of primarily as a disease of the elderly; however, it is now becoming more problematic as the incidence rate increases among young individuals. In recent years, excessive light exposure has been suggested as contributing to the rise in glaucoma among the younger generation. Blue light induces mitochondrial apoptosis in retinal ganglion cells, causing optic damage; red light increases cytochrome c oxidase activity in the electron transport system, reducing inflammation and increasing antioxidant reactions to promote cell regeneration. In conclusion, the minimization of blue light exposure and the general application of red light treatment strategies are anticipated to show synergistic effects with existing treatments for retinal disease and glaucoma and should be considered a necessary prospect for the future. This review introduces the recent studies that support the relationship between light exposure and the onset of glaucoma and discusses new treatments, such as photobiomodulation therapy. [ABSTRACT FROM AUTHOR]

Methanogenic archaea are important organisms in the global carbon cycle that grow by producing methane gas. Methanosarcina acetivorans is a methanogenic archaeum that can grow using methylated compounds, carbon monoxide, or acetate and produces renewable methane as a byproduct. However, there is limited knowledge of how combinations of substrates may affect metabolic fluxes in methanogens. Previous studies have shown that heterodisulfide reductase, the terminal oxidase in the electron transport system, is an essential enzyme in all methanogens. Deletion of genes encoding the nonessential methylotrophic heterodisulfide reductase enzyme (HdrABC) results in slower growth rate but increased metabolic efficiency. We hypothesized that increased sulfide, supplementation of mercaptoethanesulfonate (coenzyme M, CoM-SH), or acetate would metabolically alleviate the effect of the ΔhdrABC mutation. Increased sulfide improved growth of the mutant as expected; however, supplementation of both CoM-SH and acetate together were necessary to reduce the effect of the ΔhdrABC mutation. Supplementation of CoM-SH or acetate alone did not improve growth. These results support our model for the role of HdrABC in methanogenesis and suggest M.acetivorans is more efficient at conserving energy when supplemented with acetate. Our study suggests decreased Hdr enzyme activity can be overcome by nutritional supplementation with sulfide or coenzyme M and acetate, which are abundant in anaerobic environments. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to assess the relationship between morphology and metabolism during the ontogenetic development of Chelon auratus. The geometric morphometric analysis allowed us to identify morphological variations in the transformation from larvae to juveniles and to establish the growth patterns of each stage. According to our results, the ETS activity is linked to the individual morphology, specifically to the body size and to the posterior area. The fish body shape is a key factor that influences multiple traits such as swimming, foraging, mating, migrations, and predator avoidance. The present study describes the body morphological changes and the growth trajectories during the transformation from 24 to 54 days post-hatching in the golden grey mullet, Chelon auratus, using geometric morphometric analysis (GMA). The results revealed a decrease in morphological variability (i.e., morphological disparity) with the somatic growth. The main changes affected head size, elongation, and widening of the body. Given that this variability could affect the metabolism, some individuals with different morphologies and in different ontogenetic developmental stages were selected to estimate their potential respiration rate using the Electron Transport System (ETS) analysis. Differences were detected depending on the developmental stage, and being significantly smaller after 54 days post-hatching. Finally, a multivariate linear regression indicated that the specific ETS activity was partially related to the fish length and body shape. Thus, our findings emphasized the relevance of larval morphological variability for understanding the physiological processes that occur during the development. [ABSTRACT FROM AUTHOR]

The hatchery culture of bivalve mollusks depends on feeding with fresh microalgae which represent up to 50% of the production costs. We investigated the growth performance of juvenile Ostrea edulis and Ruditapes decussatus under 15% and 30% replacement of microalgae with Saccharomyces cerevisiae. Metabolic indices were measured along with weight-specific growth rate and condition index for 28 days. 15% substitution led to great results, whereas 30% yeast-fed treatments displayed poor growth and a depressed metabolism. [ABSTRACT FROM AUTHOR]

Simple Summary: Coastal systems often serve as sinks for toxic elements, and seasonality has been responsible for many changes in the physical and chemical parameters of waters and sediments, leading to geochemical alterations in aquatic systems and the alteration of element uptake rates in organisms. Diopatra neapolitana worms were collected from five sites of the Ria de Aveiro lagoon in the autumn, winter, spring, and summer of 2018/2019 and were tested to check for differences in the biochemical responses (cell damage, antioxidant enzymes, biotransformation enzymes, and energy-related parameters) among seasons and sites. In general, the results demonstrated that enzyme activities were higher in spring and summer due to high temperatures and element bioaccumulation. Energy-related parameters presented with higher levels in spring and autumn, which was mainly due to element bioaccumulation. Oxidative damage was higher during winter and was related to salinity and decreases in temperature. This study demonstrated that abiotic factors influence the geochemistry of elements and that both significantly affect organism performance in low-contamination systems, such as the Ria de Aveiro lagoon. This knowledge is important to understand how ecological and economically relevant species such as D. neapolitana respond to environmental changes. Polychaetes are known to be good bioindicators of marine pollution, such as inorganic contamination. Major and trace elements are commonly present in sediment and may be accumulated by polychaetes such as the tubiculous Diopatra neapolitana. In this study, D. neapolitana individuals were collected in the autumn, winter, spring, and summer of 2018/2019 from the Ria de Aveiro lagoon (western Portugal) to understand how seasonality influences element accumulation. The impact of the interaction of seasonality and elements on oxidative status, energy metabolism, and oxidative damage was also assessed. The obtained results showed that the activity of the antioxidant enzymes catalase, glutathione S-transferases, and non-protein thiol levels were higher in summer and that superoxide dismutase, lipid peroxidation, and electron transport system activity increased in winter. The lowest glycogen levels were observed during spring, and protein carbonylation was the highest during autumn. These results could mainly be related to high temperatures and the bioaccumulation of Al, As, Mn, and Zn. Energy-related parameters increased during spring and autumn, mainly due to the bioaccumulation of the same elements during spring and summer. Lipid damage was higher during winter, which was mainly due to salinity and temperature decreases. Overall, this study demonstrates that seasonality plays a role in element accumulation by polychaetes and that both impact the oxidative status of D. neapolitana. [ABSTRACT FROM AUTHOR]

Cardiomyocyte dysfunction in patients with end-stage heart failure with reduced ejection fraction (HFrEF) stems from mitochondrial dysfunction, which contributes to an energetic crisis. Mitochondrial dysfunction reportedly relates to increased markers of oxidative stress, but the impact of reversible thiol oxidation on myocardial mitochondrial function in patients with HFrEF has not been investigated. In the present study, we assessed mitochondrial function in ventricular biopsies from patients with end-stage HFrEF in the presence and absence of the thiol-reducing agent dithiothreitol (DTT). Isolated mitochondria exposed to DTT had increased enzyme activity of complexes I (p = 0.009) and III (p = 0.018) of the electron transport system, while complexes II (p = 0.630) and IV (p = 0.926) showed no changes. However, increased enzyme activity did not carry over to measurements of mitochondrial respiration in permeabilized bundles. Oxidative phosphorylation conductance (p = 0.439), maximal respiration (p = 0.312), and ADP sensitivity (p = 0.514) were unchanged by 5 mM DTT treatment. These results indicate that mitochondrial function can be modulated through reversible thiol oxidation, but other components of mitochondrial energy transfer are rate limiting in end-stage HFrEF. Optimal therapies to normalize cardiac mitochondrial respiration in patients with end-stage HFrEF may benefit from interventions to reverse thiol oxidation, which limits complex I and III activities. [ABSTRACT FROM AUTHOR]

This study was undertaken to determine the effect of potassium silicate (K2SiO3) on the physiological and growth characteristics and elemental composition of barley plants. Hydroponically grown barley (Hordeum vulgare L.) var. Wilma was exposed to four different levels of Si in the form of K2SiO3 at concentrations of 0 (Si0), 0.5 (Si0.5), 1 (Si1) or 1.5 (Si1.5) mM Si. Plants were analyzed for root length, number of dry leaves, number of trichomes, electron transport system activity in mitochondria (ETS), leaf pigment content and elemental composition of roots and leaves. Treatment with Si0.5 significantly increased the concentration of total chlorophylls, root length and ETS activity in barley. Plants with no Si added to the nutrient solution had significantly more dry leaves than plants from all Si-treated groups. Necrosis was observed in Si0 plants, while leaf damage was not visible in treated plants. According to the results of the study, we evidenced that plants were stressed due to Si deficiency. The addition of K2SiO3 significantly affected the concentration of Si, K, Ca, Cl, S, Mn, Fe and Zn in roots and leaves of barley. In barley treated with Si0.5, plants showed the best performance in terms of their physiological characteristics and growth. [ABSTRACT FROM AUTHOR]

Beige adipocytes with thermogenic function are activated during cold exposure in white adipose tissue through the process of browning. These cells, similar to brown adipocytes, dissipate stored chemical energy in the form of heat with the help of uncoupling protein 1 (UCP1). Recently, we have shown that tissue transglutaminase (TG2) knock-out mice have decreased cold tolerance in parallel with lower utilization of their epididymal adipose tissue and reduced browning. To learn more about the thermogenic function of this fat depot, we isolated preadipocytes from the epididymal adipose tissue of wild-type and TG2 knock-out mice and differentiated them in the beige direction. Although differentiation of TG2 knock-out preadipocytes is phenotypically similar to the wild-type cells, the mitochondria of the knock-out beige cells have multiple impairments including an altered electron transport system generating lower electrochemical potential difference, reduced oxygen consumption, lower UCP1 protein content, and a higher portion of fragmented mitochondria. Most of these differences are present in preadipocytes as well, and the differentiation process cannot overcome the functional disadvantages completely. TG2 knock-out beige adipocytes produce more iodothyronine deiodinase 3 (DIO3) which may inactivate thyroid hormones required for the establishment of optimal mitochondrial function. The TG2 knock-out preadipocytes and beige cells are both hypometabolic as compared with the wild-type controls which may also be explained by the lower expression of solute carrier proteins SLC25A45, SLC25A47, and SLC25A42 which transport acylcarnitine, Co-A, and amino acids into the mitochondrial matrix. As a consequence, the mitochondria in TG2 knock-out beige adipocytes probably cannot reach the energy-producing threshold required for normal thermogenic functions, which may contribute to the decreased cold tolerance of TG2 knock-out mice. [ABSTRACT FROM AUTHOR]

Epidemiological studies have suggested that coffee consumption is associated with a decrease in the risk of developing obesity and diabetes; however, the detailed mechanisms underlying these effects of coffee consumption remain poorly understood. In this study, we examined the effects of chlorogenic acid on energy metabolism in vitro. Hepatocellular carcinoma G2 (HepG2) cells were cultured in a medium containing chlorogenic acid. Chlorogenic acid increased the activity of mitochondrial enzymes, including citrate synthase, isocitrate dehydrogenase, and malate dehydrogenase (MDH), which are involved in the tricarboxylic acid (TCA) cycle. Proteome analysis using the isobaric tags for the relative and absolute quantitation (iTRAQ) method revealed the upregulation of proteins involved in the glycolytic system, electron transport system, and ATP synthesis in mitochondria. Therefore, we propose a notable mechanism whereby chlorogenic acid enhances energy metabolism, including the TCA cycle, glycolytic system, electron transport, and ATP synthesis. This mechanism provides important insights into understanding the beneficial effects of coffee consumption. [ABSTRACT FROM AUTHOR]

Lateritic duricrusts cover iron ore deposits and form spatially restricted, unique canga ecosystems endangered by mining. Iron cycling, i.e., the dissolution and subsequent precipitation of iron, is able to restitute canga duricrusts, generating new habitats for endangered biota in post-mining landscapes. As iron-reducing bacteria can accelerate this iron cycling, we aim to retrieve microbial enrichment cultures suitable to mediate the large-scale restoration of cangas. For that, we collected water and sediment samples from the Carajás National Forest and cultivated the iron-reducing microorganisms therein using a specific medium. We measured the potential to reduce iron using ferrozine assays, growth rate and metabolic activity. Six out of seven enrichment cultures effectively reduced iron, showing that different environments harbor iron-reducing bacteria. The most promising enrichment cultures were obtained from environments with repeated flooding and drying cycles, i.e., periodically inundated grasslands and a plateau of an iron mining waste pile characterized by frequent soaking. Selected enrichment cultures contained iron-reducing and fermenting bacteria, such as Serratia and Enterobacter. We found higher iron-reducing potential in enrichment cultures with a higher cell density and microorganism diversity. The obtained enrichment cultures should be tested for canga restoration to generate benefits for biodiversity and contribute to more sustainable iron mining in the region. [ABSTRACT FROM AUTHOR]

The application of nanotechnology in agriculture has increased rapidly. However, the fate and effects of various nanoparticles on the soil, plants, and humans are not fully understood. Reports indicate that nanoparticles exhibit positive and negative impacts on biota due to their size, surface property, concentration within the system, and species or cell type under test. In plants, nanoparticles are translocated either by apoplast or symplast pathway or both. Also, it is not clear whether the nanoparticles entering the plant system remain as nanoparticles or are biotransformed into ionic forms or other organic compounds. Controversial results on the toxicity effects of nanomaterials on the plant system are available. In general, the nanomaterial toxicity was exerted by producing reactive oxygen species, leading to damage or denaturation of various biomolecules. The intensity of cyto- and geno-toxicity depends on the physical and chemical properties of nanoparticles. Based on the literature survey, it is observed that the effects of nanoparticles on the growth, photosynthesis, and primary and secondary metabolism of plants are both positive and negative; the response of these processes to the nanoparticle was associated with the type of nanoparticle, the concentration within the tissue, crop species, and stage of growth. Future studies should focus on addressing the key knowledge gaps in understanding the responses of plants to nanoparticles at all levels through global transcriptome, proteome, and metabolome assays and evaluating nanoparticles under field conditions at realistic exposure concentrations to determine the level of entry of nanoparticles into the food chain and assess the impact of nanoparticles on the ecosystem. [ABSTRACT FROM AUTHOR]

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism. The genetic defect in WD affects the ATP7B gene, which encodes the ATP7B transmembrane protein, which is essential for maintaining normal copper homeostasis in the body. It is primarily expressed in the liver and acts by incorporating copper into ceruloplasmin (Cp), the major copper transport protein in the blood. In conditions of excess copper, ATP7B transports it to bile for excretion. Mutations in ATP7B lead to impaired ATP7B function, resulting in copper accumulation in hepatocytes leading to their damage. The toxic "free"—unbound to Cp—copper released from hepatocytes then accumulates in various organs, contributing to their damage and clinical manifestations of WD, including hepatic, neurological, hematological, renal, musculoskeletal, ophthalmological, psychiatric, and other effects. While most clinical manifestations of WD correspond to identifiable organic or cellular damage, the pathophysiology underlying its psychiatric manifestations remains less clearly understood. A search for relevant articles was conducted in PubMed/Medline, Science Direct, Scopus, Willy Online Library, and Google Scholar, combining free text and MeSH terms using a wide range of synonyms and related terms, including "Wilson's disease", "hepatolenticular degeneration", "psychiatric manifestations", "molecular mechanisms", "pathomechanism", and others, as well as their combinations. Psychiatric symptoms of WD include cognitive disorders, personality and behavioral disorders, mood disorders, psychosis, and other mental disorders. They are not strictly related to the location of brain damage, therefore, the question arises whether these symptoms are caused by WD or are simply a coincidence or a reaction to the diagnosis of a genetic disease. Hypotheses regarding the etiology of psychiatric symptoms of WD suggest a variety of molecular mechanisms, including copper-induced CNS toxicity, oxidative stress, mitochondrial dysfunction, mitophagy, cuproptosis, ferroptosis, dysregulation of neurotransmission, deficiencies of neurotrophic factors, or immune dysregulation. New studies on the expression of noncoding RNA in WD are beginning to shed light on potential molecular pathways involved in psychiatric symptomatology. However, current evidence is still insufficient to definitively establish the cause of psychiatric symptoms in WD. It is possible that the etiology of psychiatric symptoms varies among individuals, with multiple biological and psychological mechanisms contributing to them simultaneously. Future studies with larger samples and comprehensive analyses are necessary to elucidate the mechanisms underlying the psychiatric manifestations of WD and to optimize diagnostics and therapeutic approaches. [ABSTRACT FROM AUTHOR]

This investigation studies the properties and composition of extracellular polymeric substances (EPS) of the four tolerant bacterial strains [NH (Cellulosimicrobium cellulans), TH, YH, and HE (Pseudomonas aeruginosa)] under perfluorobutanesulfonic acid (PFBS) stress. The strains were acquired from athickened sludge in a fluorine chemical park. Each strain's EPS were isolated by heating and centrifugation, and their growth, metabolic activity, and EPS alteration research pre- and post-stress were assessed and compared. The strain type was identified by morphological observation and 16S rDNA gene sequence analysis. Under PFBS (100 μg·L−1) stress, the four tolerant strains NH, TH, YH, and HE showed 38.10%, 29.26%, 35.92%, and 30.48% removal of PFBS on day 4, respectively, and the strain's EPS had a substantial impact on main component protein (PR) and polysaccharide (PS) contents. The NH microorganism's ability to metabolize organic matter was markedly stronger; it had a higher quantity, and its impact on main EPS content was greater than the other three tolerant strains. The three-dimensional excitation–emission matrix results showed marked alterations in tryptophan and aromatic protein peaks in the tolerant strain's EPS. Furthermore, the FTIR analysis showed that the intensity of the functional groups in the proteins (-OH, C=O, -NH, and -CN) and the polysaccharides (-OH, C-O-C, and C-O) changed significantly. This investigation indicated that the proteins and polysaccharides of the tolerant strain's EPS could provide more binding sites for PFBS adsorption, where the NH strain had the best biosorption capacity. This research provides a theoretical basis for elucidating efficient biosorbents. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is causing increasing concern among clinicians due to its high mortality and resistance rates. This bacterium is responsible for various infections, especially in hospital settings, affecting some of the most vulnerable patients. Pseudomonas aeruginosa has developed resistance through multiple mechanisms, making treatment challenging. Diagnostic techniques are evolving, with rapid testing systems providing results within 4–6 h. New antimicrobial agents are continuously being developed, offering potential solutions to these complex clinical decisions. This article provides a review of the epidemiology, at-risk populations, resistance mechanisms, and diagnostic and treatment options for Pseudomonas aeruginosa. [ABSTRACT FROM AUTHOR]

In contrast to most other rhabdoviruses, which spread by insect vectors, the rabies virus (RABV) is a very unusual member of the Rhabdoviridae family, since it has evolved to be fully adapted to warm-blooded hosts and spread directly between them. There are differences in the immune responses to laboratory-attenuated RABV and wild-type rabies virus infections. Various investigations showed that whilst laboratory-attenuated RABV elicits an innate immune response, wild-type RABV evades detection. Pathogenic RABV infection bypasses immune response by antagonizing interferon induction, which prevents downstream signal activation and impairs antiviral proteins and inflammatory cytokines production that could eliminate the virus. On the contrary, non-pathogenic RABV infection leads to immune activation and suppresses the disease. Apart from that, through recruiting leukocytes into the central nervous system (CNS) and enhancing the blood–brain barrier (BBB) permeability, which are vital factors for viral clearance and protection, cytokines/chemokines released during RABV infection play a critical role in suppressing the disease. Furthermore, early apoptosis of neural cells limit replication and spread of avirulent RABV infection, but street RABV strains infection cause delayed apoptosis that help them spread further to healthy cells and circumvent early immune exposure. Similarly, a cellular regulation mechanism called autophagy eliminates unused or damaged cytoplasmic materials and destroy microbes by delivering them to the lysosomes as part of a nonspecific immune defense mechanism. Infection with laboratory fixed RABV strains lead to complete autophagy and the viruses are eliminated. But incomplete autophagy during pathogenic RABV infection failed to destroy the viruses and might aid the virus in dodging detection by antigen-presenting cells, which could otherwise elicit adaptive immune activation. Pathogenic RABV P and M proteins, as well as high concentration of nitric oxide, which is produced during rabies virus infection, inhibits activities of mitochondrial proteins, which triggers the generation of reactive oxygen species, resulting in oxidative stress, contributing to mitochondrial malfunction and, finally, neuron process degeneration. [ABSTRACT FROM AUTHOR]

Background/Objectives: Bovine babesiosis is a vector-borne disease transmitted by ticks that causes important losses in livestock worldwide. Recent research performed on the drugs currently used to control bovine babesiosis reported several issues including drug resistance, toxicity impact, and residues in edible tissue, suggesting the need for developing novel effective therapies. The endochin-like quinolones ELQ-316 and buparvaquone (BPQ) act as cytochrome bc1 inhibitors and have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp. and Babesia microti, without showing toxicity in mammals. The objectives of this study are investigating whether ELQ-316, BPQ, and their combination treatment could be effective against Babesia bovis in an in vitro culture model and comparing with imidocarb (ID), the routinely used drug. Methods: In vitro cultured parasites starting at 2% percentage of parasitemia (PPE) were treated with BPQ, ELQ-316, ID, and the combinations of BPQ + ELQ-316 and ID + ELQ-316 at drug concentrations that ranged from 25 to 1200 nM, during four consecutive days. The IC50% and IC99% were reported. Parasitemia levels were evaluated daily using microscopic examination. Data were compared using the non-parametrical Mann–Whitney and Kruskall–Wallis test. Results: All drugs tested, whether used alone or in combination, significantly decreased the survival (p < 0.05) of B. bovis in in vitro cultures. The combination of BPQ + ELQ-316 had the lowest calculated inhibitory concentration 50% (IC50%) values, 31.21 nM (IC95%: 15.06–68.48); followed by BPQ, 77.06 nM (IC95%: 70.16–86.01); ID + ELQ316, 197 nM (IC95%:129.0–311.2); ID, 635.1 nM (IC95%: 280.9–2119); and ELQ316, 654.9 nM (IC95%: 362.3–1411). Conclusions: The results reinforce the higher efficacy of BPQ at affecting B. bovis survival and the potential synergistic effects of its combination with ELQ-316, providing a promising treatment option against B. bovis. [ABSTRACT FROM AUTHOR]

Efforts to increase grape yields have focused on using nitrogen, phosphorus, and potassium fertilizers, often causing unintended magnesium (Mg) deficiencies. To overcome Mg deficiency, different concentrations of MgSO4·7H2O (0, 1, 2, 3, 4 mM) and GABA (2.5 mM), as foliar sprays, were applied during the fruit enlargement and color transition stages. Key physiological parameters such as leaf growth, photosynthesis, and chlorophyll fluorescence were assessed. Interestingly, foliar Mg application increased the key physiological parameters, with the 3 mM treatment (M3) delivering the best improvement. Compared to the control, the M3 treatment increased dry weight and leaf area by 35.9% and 37.2%, respectively. Specifically, the foliar Mg application (M3) improved the photosynthesis (Pn), transpiration (Tr), and stomatal conductance (gs) of leaves when compared to the control. Additionally, the foliar Mg application improved the PSII photosynthetic efficiency, electron yield, and electron transport rates, following the order M2 > M3 > M1 > M0 > M4. This study demonstrated the essential role of foliar-applied Mg, with GABA, in improving grape physiology. Interestingly, the curve-fitting analysis of foliar Mg concentration and grape yield identified 2.14 mM of Mg as the optimal concentration for promoting grape growth. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine lettuce using different concentrations of the biostimulator N-methyl-N-methoxyamide-7-carboxybenzo(1.2.3)thiadiazole (BTHWA), a new benzothiadiazole derivative. Different concentrations of BTHWA during watering and spraying were applied to lettuce. Chlorophyll fluorescence, gas exchange, thermal images, and plant parameter data were used to study physiological process and the growth of lettuce. Chlorophyll fluorescence data showed a strong effect after the first BTHWA application to lettuce. After three applications, the plants were harvested and data were recorded. Similarly, in the second experiment, gas exchange and thermal images were recorded after the first treatment of BTHWA. Our findings showed improved chlorophyll efficiency after the first BTHWA application, and no adverse effects were recorded on the overall photochemistry at any concentration. Regarding growth parameters, spraying BTHWA reduced the fresh weight but decreased the damage index. A lower watering concentration (0.066 mg/L) applied three times did not cause any damage to plants and fresh weight, even after repeated applications. Infrared thermal images showed BTHWA application also significantly affected plant temperature. Gas exchange data revealed that sprayed plants exhibited higher transpiration rates, stomatal conductance, and photosynthetic rates when compared to watered and control plants. This study suggests that application of a low dose of BTHWA is safe to use in agriculture practices in lettuce without compromising its growth and yield. [ABSTRACT FROM AUTHOR]

Water availability and light during the dry and rainy seasons in the Cerrado may influence plants' stomatal movement and the entry of CO2 for organic synthesis, which is the main electron drain. A lower stomatal conductance may contribute to the energy accumulated in the chloroplasts being directed towards the synthesis of compounds, which contributes to the activity of antioxidant enzymes to neutralize reactive oxygen species. Xylopia aromatica is a characteristic Cerrado species, and it is often recommended for recovering degraded areas. This study aimed to investigate the influence of the dry and rainy seasons on the metabolic adjustments of Xylopia aromatica in a portion of the Brazilian savanna in the state of São Paulo. In the rainy season, better photosynthetic performance led to greater investment in essential oil production. In the dry season, the plants may direct part of their reducing sugars to the syntheses of carotenoids and anthocyanins, which may help the antioxidant enzymes to neutralize reactive oxygen species. Carotenoids assist in the dissipation of photosystem energy, which has the potential to cause oxidative stress. During this season, lower stomatal conductance prevented excessive water loss. These results suggest the acclimatization of this species to the conditions of the Brazilian savanna. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD), the most prevalent form of dementia, is a leading neurodegenerative disorder currently affecting approximately 55 million individuals globally, a number projected to escalate to 139 million by 2050. Despite extensive research spanning several decades, the cure for AD remains at a developing stage. The only existing therapeutic options are limited to symptom management, and are often accompanied by adverse side effects. The pathological features of AD, including the accumulation of beta-amyloid plaques and tau protein tangles, result in progressive neuronal death, synaptic loss, and brain atrophy, leading to significant cognitive decline and a marked reduction in quality of life. Objective: In light of the shortcomings of existing pharmacological interventions, this review explores the potential of photobiomodulation (PBM) as a non-invasive therapeutic option for AD. PBM employs infrared light to facilitate cellular repair and regeneration, focusing on addressing the disease's underlying biomechanical mechanisms. Method: This paper presents a comprehensive introduction to the mechanisms of PBM and an analysis of preclinical studies evaluating its impact on cellular health, cognitive function, and disease progression in AD.The review provides a comprehensive overview of the various wavelengths and application methods, evaluating their efficacy in mitigating AD-related symptoms. Conclusions: The findings underscore the significant potential of PBM as a safe and effective alternative treatment for Alzheimer's disease, emphasizing the necessity for further research and clinical trials to establish its therapeutic efficacy conclusively. [ABSTRACT FROM AUTHOR]

Background: The senescence-accelerated mouse 8 (SAMP8) represents a model for Alzheimer's disease (AD) research because it exhibits age-related learning and memory impairments consistent with early onset and rapid progression of senescence. To identify transcriptional changes during AD progression, in this study, we analyzed and compared the gene expression profiles involved in molecular pathways of neurodegeneration and cognitive impairment in senescence-accelerated resistant 1 (SAMR1) and SAMP8 mice. Methods: In total, 48 female SAMR1 and SAMP8 mice were randomly divided into six groups (SAMR1 and SAMP8 at 3, 7, and 9 months of age). Microarray analysis of 22,000 genes was performed, followed by functional analysis using Gene Ontology (NCBI) and examination of altered molecular pathways using the KEGG (Kyoto Encyclopedia of Genes and Genomes). Results: SAMP8 mice had 2516 dysregulated transcripts at 3 months, 2549 transcripts at 7 months, and 2453 genes at 9 months compared to SAMR1 mice of the same age. These accounted for 11.3% of the total number. This showed that with age, the gene expression of downregulated transcripts increases, and that of over-expressed transcripts decreases. Most of these genes were involved in neurodegenerative metabolic pathways associated with Alzheimer's disease: apoptosis, inflammatory response, oxidative stress, and mitochondria. The qPCR results indicated that Ndufs4, TST/Rhodanese, Wnt3, and Sema6a expression was differentially expressed during aging. Conclusions: These results further revealed significant differences in gene expression profiles at different ages between SAMR1 and SAMP8 and showed alteration in genes involved in age-related cognitive decline and mitochondrial processes, demonstrating the relevance of the SAMP8 model as a model for sporadic AD. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) remains the most common cause of mortality in chronic kidney disease (CKD) patients. Several studies suggest that the Mediterranean diet reduces the risk of CVD due to its influence on endothelial function, inflammation, lipid profile, and blood pressure. Integrating metabolomic and proteomic analyses of CKD could provide insights into the pathways involved in uremia-induced CVD and those pathways modifiable by the Mediterranean diet. Methods: We performed metabolomic and proteomic analyses on serum samples from 19 patients with advanced CKD (aCKD) and 27 healthy volunteers. The metabolites were quantified using four different approaches, based on their properties. Proteomic analysis was performed after depletion of seven abundant serum proteins (Albumin, IgG, antitrypsin, IgA, transferrin, haptoglobin, and fibrinogen). Integrative analysis was performed using MetaboAnalyst 4.0 and STRING 11.0 software to identify the dysregulated pathways and biomarkers. Results: A total of 135 metabolites and 75 proteins were differentially expressed in aCKD patients, compared to the controls. Pathway enrichment analysis showed significant alterations in the innate immune system pathways, including complement, coagulation, and neutrophil degranulation, along with disrupted linoleic acid and cholesterol metabolism. Additionally, certain key metabolites and proteins were altered in aCKD patients, such as glutathione peroxidase 3, carnitine, homocitrulline, 3-methylhistidine, and several amino acids and derivatives. Conclusions: Our findings reveal significant dysregulation of the serum metabolome and proteome in aCKD, particularly in those pathways associated with endothelial dysfunction and CVD. These results suggest that CVD prevention in CKD may benefit from a multifaceted approach, including dietary interventions such as the Mediterranean diet. [ABSTRACT FROM AUTHOR]

This review paper focuses on the joint toxicity and interaction of carbon-based nanomaterials (CNMs) with co-existing pollutants in aquatic environments. It explores the potential harmful effects of chemical mixtures with CNMs on aquatic organisms, emphasizing the importance of scientific modeling to predict mixed toxic effects. The study involved a systematic literature review to gather information on the joint toxicity and interaction between CNMs and various co-contaminants in aquatic settings. A total of 53 publications were chosen and analyzed, categorizing the studies based on the tested CNMs, types of co-contaminants, and the used species. Common test models included fish and microalgae, with zebrafish being the most studied species. The review underscores the necessity of conducting mixture toxicity testing to assess whether the combined effects of CNMs and co-existing pollutants are additive, synergistic, or antagonistic. The development of in silico models based on the solid foundation of research data represents the best opportunity for joint toxicity prediction, eliminating the need for a great quantity of experimental studies. [ABSTRACT FROM AUTHOR]

Hydroponic greenhouses and vertical farms provide an alternative crop production strategy in regions that experience low temperatures, suboptimal sunlight, or inadequate soil quality. However, hydroponic systems are soilless and, therefore, have vastly different bacterial microbiota than plants grown in soil. This review highlights some of the most prevalent plant growth-promoting bacteria (PGPB) and destructive phytopathogenic bacteria that dominate hydroponic systems. A complete understanding of which bacteria increase hydroponic crop yields and ways to mitigate crop loss from disease are critical to advancing microbiome research. The section focussing on plant growth-promoting bacteria highlights putative biological pathways for growth promotion and evidence of increased crop productivity in hydroponic systems by these organisms. Seven genera are examined in detail, including Pseudomonas, Bacillus, Azospirillum, Azotobacter, Rhizobium, Paenibacillus, and Paraburkholderia. In contrast, the review of hydroponic phytopathogens explores the mechanisms of disease, studies of disease incidence in greenhouse crops, and disease control strategies. Economically relevant diseases caused by Xanthomonas, Erwinia, Agrobacterium, Ralstonia, Clavibacter, Pectobacterium, and Pseudomonas are discussed. The conditions that make Pseudomonas both a friend and a foe, depending on the species, environment, and gene expression, provide insights into the complexity of plant–bacterial interactions. By amalgamating information on both beneficial and pathogenic bacteria in hydroponics, researchers and greenhouse growers can be better informed on how bacteria impact modern crop production systems. [ABSTRACT FROM AUTHOR]

Purine stretches, sequences of adenine (A) and guanine (G) in DNA, play critical roles in binding regulatory protein factors and influence gene expression by affecting DNA folding. This study investigates the relationship between purine stretches and cancer development, considering the aromaticity of purines, quantified by methods like Hückel's rule and NICS calculations, and the importance of the flanking sequence context. A pronounced avoidance of long purine stretches by typical cancer mutations was observed in public data on the intergenic regions of cancer patients, suggesting a role of intergenic sequences in chromatin reorganization and gene regulation. A statistically significant shortening of purine stretches in cancerous tumors (p value < 0.0001) was found. The insights into the aromatic nature of purines and their stacking energies explain the role of purine stretches in DNA structure, contributing to their role in cancer progression. This research lays the groundwork for understanding the nature of purine stretches, emphasizing their importance in gene regulation and chromatin restructuring, and offers potential avenues for novel cancer therapies and insights into cancer etiology. [ABSTRACT FROM AUTHOR]

β-Tricalcium phosphate (β-TCP) is a well-established biomaterial for bone regeneration, highly regarded for its biocompatibility and osteoconductivity. However, its clinical efficacy is often compromised by susceptibility to bacterial infections. In this study, we address this limitation by integrating femtosecond (fs)-laser processing with the concurrent synthesis of silver nanoparticles (AgNPs) mediated by Azorean green tea leaf extract (GTLE), which is known for its rich antioxidant and anti-inflammatory properties. The fs laser was employed to modify the surface of β-TCP scaffolds by varying scanning velocities, fluences, and patterns. The resulting patterns, formed at lower scanning velocities, display organized nanostructures, along with enhanced roughness and wettability, as characterized by Scanning Electron Microscopy (SEM), optical profilometry, and contact angle measurements. Concurrently, the femtosecond laser facilitated the photoreduction of silver ions in the presence of GTLE, enabling the efficient synthesis of small, spherical AgNPs, as confirmed by UV–vis spectroscopy, Transmission Electron Microscopy (TEM), and Fourier Transform Infrared Spectroscopy (FTIR). The resulting AgNP-embedded β-TCP scaffolds exhibited a significantly improved cell viability and elongation of human bone marrow mesenchymal stem cells (hBM-MSCs), alongside significant antibacterial activity against Staphylococcus aureus (S. aureus). This study underscores the transformative potential of combining femtosecond laser surface modification with GTLE-mediated AgNP synthesis, presenting a novel and effective strategy for enhancing the performance of β-TCP scaffolds in bone-tissue engineering. [ABSTRACT FROM AUTHOR]

Monoamine oxidases (MAOs), mitochondrial enzymes that constantly produce hydrogen peroxide (H2O2) as a byproduct of their activity, have been recently acknowledged as contributors to oxidative stress in cardiometabolic pathologies. The present study aimed to assess whether MAOs are mediators of valvular oxidative stress and interact in vitro with angiotensin 2 (ANG2) to mimic the activation of the renin–angiotensin system. To this aim, valvular tissue samples were harvested from 30 patients diagnosed with severe primary mitral regurgitation and indication for surgical repair. Their reactive oxygen species (ROS) levels were assessed by means of a ferrous oxidation xylenol orange (FOX) assay, while MAO expression was assessed by immune fluorescence (protein) and qRT-PCR (mRNA). The experiments were performed using native valvular tissue acutely incubated or not with angiotensin 2 (ANG2), MAO inhibitors (MAOI) and the angiotensin receptor blocker, irbesartan (Irb). Correlations between oxidative stress and echocardiographic parameters were also analyzed. Ex vivo incubation with ANG2 increased MAO-A and -B expression and ROS generation. The level of valvular oxidative stress was negatively correlated with the left ventricular ejection fraction. MAOI and Irb reduced valvular H2O2. production. In conclusion, both MAO isoforms are expressed in pathological human mitral valves and contribute to local oxidative stress and ventricular functional impairment and can be modulated by the local renin–angiotensin system. [ABSTRACT FROM AUTHOR]

Among the widespread trichothecene mycotoxins, T-2 toxin is considered the most toxic congener. In the present study, we utilized high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR), coupled to the zebrafish (Danio rerio) embryo model, as a toxicometabolomics approach to elucidate the cellular, molecular and biochemical pathways associated with T-2 toxicity. Aligned with previous studies in the zebrafish embryo model, exposure to T-2 toxin was lethal in the high parts-per-billion (ppb) range, with a median lethal concentration (LC50) of 105 ppb. Exposure to the toxins was, furthermore, associated with system-specific alterations in the production of reactive oxygen species (ROS), including decreased ROS production in the liver and increased ROS in the brain region, in the exposed embryos. Moreover, metabolic profiling based on HRMAS NMR revealed the modulation of numerous, interrelated metabolites, specifically including those associated with (1) phase I and II detoxification, and antioxidant pathways; (2) disruption of the phosphocholine lipids of cell membranes; (3) mitochondrial energy metabolism, including apparent disruption of the tricarboxylic acid (TCA) cycle, and the electron transport chain of oxidative phosphorylation, as well as "upstream" effects on carbohydrate, i.e., glucose metabolism; and (4) several compensatory catabolic pathways. Taken together, these observations enabled development of an integrated, system-level model of T-2 toxicity in relation to human and animal health. [ABSTRACT FROM AUTHOR]

Cytochrome b5 (CB5), a small heme-binding protein, plays an important role in plant biotic and abiotic stress. Anthocyanin is a critical determinant for fruit coloration, however, whether CB5 is involved in regulating anthocyanin biosynthesis has not yet been investigated in apple fruit (Malus domestica). In this study, we determined that MdCYB5, an apple CB5 gene, was a positive regulator for anthocyanin biosynthesis in apple fruit. We first found that MdCYB5 showed a high sequence and structural similarity with Arabidopsis cytochrome b5 isoform E (CB5E) at the protein level. Quantitative reverse transcription PCR (qRT-PCR) analysis showed that MdCYB5 responds to light signals. Subcellular localization showed that MdCYB5 is localized to the cytoplasmin inthe epidermal cells of Nicotiana benthamiana leaves. Further investigation revealed that overexpressing MdCYB5 promoted anthocyanin biosynthesis in both apple calli and tissue-cultured apple seedlings. Furthermore, results of transient expression assay showed that overexpressing MdCYB5 promoted anthocyanin accumulation and fruit coloration in apple fruit. Taken together, this study suggests that MdCYB5 has a positive regulatory effect on anthocyanin biosynthesis in apple fruit. [ABSTRACT FROM AUTHOR]

The effects of methylmercury (MeHg) on exposed populations are a public health problem. In contrast to widely studied neurological damage, few cardiovascular changes have been described. Our group evaluated the cardiotoxicity of a cumulative dose of 70 mg.kg−1 fractioned over a 14-day exposure period in mice (MeHg70 group). The effects of MeHg on proteins relevant to cardiac mitochondrial function were also investigated. The results obtained showed a reduction in oxygen consumption in the two settings. In cardiac tissue samples in oxygraphy studies, this reduction was related to a lower efficiency of complexes II and V, which belong to the oxidative phosphorylation system. In vivo, mice in the MeHg70 group presented lower oxygen consumption and running tolerance, as shown by ergometric analyses. Cardiac stress was evident in the MeHg70 group, as indicated by a marked increase in the level of the mRNA encoding atrial natriuretic peptide. Electrocardiogram studies revealed a lower heart rate at rest in the animals from the MeHg70 group, as well as prolonged left ventricular depolarisation and repolarisation. Through echocardiographic analysis, reductions in the left ventricular ejection fraction and left ventricular wall thickness of approximately 10% and 20%, respectively, were detected. These results indicate that the oral intake of MeHg can decrease cardiac function and oxidative metabolism. This finding highlights the importance of monitoring MeHg levels in humans and animals in contaminated areas, as well as periodically carrying out cardiac function tests. [ABSTRACT FROM AUTHOR]

Background and Objective: The alteration of mitochondrial functions, especially the opening of the mitochondrial permeability transition pore (mPTP), has been proposed as a key mechanism in the development of lesions in cerebral ischemia, wherefore it is considered as an important target for drugs against ischemic injury. In this study, we aimed to investigate the effects of mitochondrial complex I inhibitors as possible regulators of mPTP using an in vitro brain ischemia model of the pentobarbital/ketamine (PBK)-anesthetized rats. Results: We found that PBK anesthesia itself delayed Ca2+-induced mPTP opening and partially recovered the respiratory functions of mitochondria, isolated from rat brain cortex and cerebellum. In addition, PBK reduced cell death in rat brain slices of cerebral cortex and cerebellum. PBK inhibited the adenosine diphosphate (ADP)-stimulated respiration of isolated cortical and cerebellar mitochondria respiring with complex I-dependent substrates pyruvate and malate. Moreover, pentobarbital alone directly increased the resistance of isolated cortex mitochondria to Ca2+-induced activation of mPTP and inhibited complex I-dependent respiration and mitochondrial complex I activity. In contrast, ketamine had no direct effect on functions of isolated normal cortex and cerebellum mitochondria. Conclusions: Altogether, this suggests that modulation of mitochondrial complex I activity by pentobarbital during PBK anesthesia may increase the resistance of mitochondria to mPTP opening, which is considered the key event in brain cell necrosis during ischemia. [ABSTRACT FROM AUTHOR]

Salt stress could be a significant factor limiting the growth and development of vegetables. In this study, Fulvic Acid (FA) (0.05%, 0.1%, 0.15%, 0.2%, and 0.25%) was applied under nitrate stress (150 mM), with normal Hoagland nutrient solution as a control to investigate the influence of foliar spray FA on spinach growth, photosynthesis, and oxidative stress under nitrate stress. The results showed that nitrate stress significantly inhibited spinach growth, while ROS (reactive oxygen species) accumulation caused photosystem damage, which reduced photosynthetic capacity. Different concentrations of FA alleviated the damage caused by nitrate stress in spinach to varying degrees in a concentration-dependent manner. The F3 treatment (0.15% FA + 150 mM NO3−) exhibited the most significant mitigating effect. FA application promoted the accumulation of biomass in spinach under nitrate stress and increased chlorophyll content, the net photosynthetic rate, the maximum photochemical quantum yield of PSII (Photosystem II) (Fv/Fm), the quantum efficiency of PSII photochemistry [Y(II)], the electron transport rate, and the overall functional activity index of the electron transport chain between the PSII and PSI systems (PItotal); moreover, FA decreased PSII excitation pressure (1 − qP), quantum yields of regulated energy dissipation of PSII [Y(NPQ)], and the relative variable initial slope of fluorescence. FA application increased superoxide dismutase, peroxidase, and catalase activities and decreased malondialdehyde, H2O2, and O2− levels in spinach under nitrate stress. FA can enhance plant resistance to nitrate by accelerating the utilization of light energy in spinach to mitigate excess light energy and ROS-induced photosystem damage and increase photosynthetic efficiency. [ABSTRACT FROM AUTHOR]

Posterior capsular opacification (PCO) is the most common long-term complication of cataract surgery. Traditionally, the pathogenesis of PCO involves the residual lens epithelial cells (LECs), which undergo transdifferentiation into a myofibroblast phenotype, hyperproliferation, matrix contraction, and matrix deposition. This process is driven by the marked upregulation of inflammatory and growth factors post-surgery. Recently, research on the role of redox environments has gained considerable attention. LECs, which are in direct contact with the aqueous humour after cataract surgery, are subjected to oxidative stress due to decreased levels of reduced glutathione and increased oxygen content compared to contact with the outer fibre layer of the lens before surgery. In this review, we examine the critical role of oxidative stress in PCO formation. We also focus on glutaredoxins (Grxs), which are antioxidative enzymes produced via deglutathionylation, their protective role against PCO formation, and their therapeutic potential. Furthermore, we discuss the latest advancements in PCO therapy, particularly the development of advanced antioxidative pharmacological agents, and emphasise the importance and approaches of anti-inflammatory and antioxidant treatments in PCO management. In conclusion, this review highlights the significant roles of oxidative stress in PCO, the protective effects of Grxs against PCO formation, and the potential of anti-inflammatory and antioxidant therapies in treating PCO. [ABSTRACT FROM AUTHOR]

Photosynthesis fixes CO2 and converts it to sugar, using chemical-energy compounds of both NADPH and ATP, which are produced in the photosynthetic electron transport system. The photosynthetic electron transport system absorbs photon energy to drive electron flow from Photosystem II (PSII) to Photosystem I (PSI). That is, both PSII and PSI are full of electrons. O2 is easily reduced to a superoxide radical (O2−) at the reducing side, i.e., the acceptor side, of PSI, which is the main production site of reactive oxygen species (ROS) in photosynthetic organisms. ROS-dependent inactivation of PSI in vivo has been reported, where the electrons are accumulated at the acceptor side of PSI by artificial treatments: exposure to low temperature and repetitive short-pulse (rSP) illumination treatment, and the accumulated electrons flow to O2, producing ROS. Recently, my group found that the redox state of the reaction center of chlorophyll P700 in PSI regulates the production of ROS: P700 oxidation suppresses the production of O2− and prevents PSI inactivation. This is why P700 in PSI is oxidized upon the exposure of photosynthesis organisms to higher light intensity and/or low CO2 conditions, where photosynthesis efficiency decreases. In this study, I introduce a new molecular mechanism for the oxidation of P700 in PSI and suppression of ROS production from the robust relationship between the light and dark reactions of photosynthesis. The accumulated protons in the lumenal space of the thylakoid membrane and the accumulated electrons in the plastoquinone (PQ) pool drive the rate-determining step of the P700 photo-oxidation reduction cycle in PSI from the photo-excited P700 oxidation to the reduction of the oxidized P700, thereby enhancing P700 oxidation. [ABSTRACT FROM AUTHOR]

This survey reviews modern ideas on the structure and functions of mitochondrial and cytosolic aconitase isoenzymes in eukaryotes. Cumulative experimental evidence about mitochondrial aconitases (Aco2) as one of the main targets of reactive oxygen and nitrogen species is generalized. The important role of Aco2 in maintenance of homeostasis of the intracellular iron pool and maintenance of the mitochondrial DNA is discussed. The role of Aco2 in the pathogenesis of some neurodegenerative diseases is highlighted. Inactivation or dysfunction of Aco2 as well as mutations found in the ACO2 gene appear to be significant factors in the development and promotion of various types of neurodegenerative diseases. A restoration of efficient mitochondrial functioning as a source of energy for the cell by targeting Aco2 seems to be one of the promising therapeutic directions to minimize progressive neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

With increasing numbers of patients worldwide diagnosed with diabetes mellitus, renal disease, and iatrogenic immune deficiencies, an increased understanding of the role of electrolyte interactions in mitigating pathogen virulence is necessary. The levels of divalent cations affect host susceptibility and pathogen survival in persons with relative immune insufficiency. For instance, when host cellular levels of calcium are high compared to magnesium, this relationship contributes to insulin resistance and triples the risk of clinical tuberculosis. The movement of divalent cations within intracellular spaces contributes to the host defense, causing apoptosis or autophagy of the pathogen. The control of divalent cation flow is dependent in part upon the mammalian natural resistance-associated macrophage protein (NRAMP) in the host. Survival of pathogens such as M tuberculosis within the bronchoalveolar macrophage is also dependent upon NRAMP. Pathogens evolve mutations to control the movement of calcium through external and internal channels. The host NRAMP as a metal transporter competes for divalent cations with the pathogen NRAMP in M tuberculosis (whether in latent, dormant, or active phase). This review paper summarizes mechanisms of pathogen offense and patient defense using inflow and efflux through divalent cation channels under the influence of parathyroid hormone vitamin D and calcitonin. [ABSTRACT FROM AUTHOR]