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The identification of the power output that separates the heavy intensity exercise domain, wherein steady states in blood [lactate] and pulmonary V̇O2 are achievable, from the severe intensity domain, wherein they are not, has conceptual and practical value in exercise physiology. Purpose: This study aimed to develop a new method that more closely represents the heavy to severe exercise domain boundary by evaluating the rates of blood lactate accumulation during the constant power output exercise bouts that are used in the assessment of the maximal lactate steady state (MLSS). Methods: Eight well-trained male cyclists completed five exercise tests of up to 30 min for the determination of the traditional MLSS (MLSSTRAD) and a further four maximal tests for the determination of critical power (CP). The rates of change of blood [lactate] between 10 min and the end of exercise in the MLSS tests were plotted against the corresponding power outputs, and a two-segment linear regression model was used to identify individualized break points in lactate accumulation versus power output (modified MLSS [MLSSMOD]). Results: MLSSMOD was significantly higher than MLSSTRAD (297 ± 41 vs 278 ± 41 W, P < 0.001) but was not significantly different from CP (297 ± 41 W, P > 0.05); MLSSMOD and CP were closely aligned (r = 0.97, bias = −0.52 W, SEE = 10 W, limits of agreement = −20 to 19 W). The rates of change of both blood [lactate] and V̇O2 were significantly greater, and exercise intolerance occurred before 30 min, at a power output slightly above MLSSMOD. Conclusions: A novel method for evaluating blood lactate kinetics during MLSSTRAD protocol produces MLSSMOD that is not different from CP and better represents the heavy to severe exercise domain boundary. [ABSTRACT FROM AUTHOR]

Simple Summary: The nitroblue tetrazolium (NBT) reduction test measures metabolic activity in cells. This study aimed to compare reactive oxygen species (ROS) production in neutrophils from healthy dogs, dogs with superficial pyoderma, and dogs with sterile neutrophilic pustular dermatitis. Twenty-eight dogs were divided into three groups, and their blood was tested using the NBT reduction method. The results showed that dogs with sterile neutrophilic dermatitis had higher NBT rates, especially if they tested positive for Leishmania spp. The NBT test may help identify systemic neutrophil activation in immune-mediated diseases, but it was less effective in distinguishing between healthy dogs and those with superficial pyoderma. This study aimed to evaluate differences in the production of reactive oxygen species (ROS) by peripheral blood neutrophils in healthy dogs, dogs with superficial pyoderma, and dogs with sterile neutrophilic dermatitis using the nitroblue tetrazolium (NBT) reduction test. Additionally, the study assessed the potential of the NBT reduction test as a diagnostic tool to differentiate between these clinical conditions. A total of 28 dogs were divided into three groups: healthy (n = 10), superficial pyoderma (n = 10), and sterile neutrophilic dermatitis (n = 8). The results showed significantly higher neutrophil activation in dogs with sterile neutrophilic dermatitis (19 ± 10%) compared with healthy dogs (7.3 ± 5%) (p < 0.01) and dogs with superficial pyoderma (10 ± 2.8%) (p < 0.05). Dogs with sterile neutrophilic dermatitis and a high positive result for Leishmania spp. antibodies (n = 3) exhibited even higher NBT reduction rates (30 ± 4.6%) compared with seronegative dogs with sterile neutrophilic dermatitis (n = 5) (13 ± 5.3%) (p < 0.05). These findings suggest that the NBT reduction test could be useful for detecting systemic neutrophil activation in sterile neutrophilic dermatitis, especially when associated with Leishmania infection. However, no significant differences were observed between healthy dogs and those with superficial pyoderma, indicating that the test may not be effective in detecting systemic neutrophil activation in superficial bacterial infections. [ABSTRACT FROM AUTHOR]

Background/Objectives: Previous studies have shown that neuromuscular electrical stimulation (NMES), while expensive, can provide some of the health benefits of exercise to people who cannot exercise their legs normally. The aim of this study was to quantify the increases in muscle metabolism in four muscles of the legs of able-bodied individuals with NMES. Methods: Healthy college-aged students were tested. NMES of four muscle groups was performed with inexpensive stimulators and reusable tin foil electrodes. The biceps femoris, vastus lateralis, medial gastrocnemius, and tibialis anterior muscles on one leg were stimulated for ten minutes with twitch stimulations at the highest comfortable stimulation current. Muscle metabolism was measured using the slope of oxygen consumption measured with near-infrared spectroscopy (NIRS) during 5 s of cuff ischemia. Results: Initial studies found fold increases in muscle metabolism above rest of 8.9 ± 8.6 for the vastus lateralis, 7.9 ± 11.9 for the biceps femoris, 6.6 ± 7.8 for the medial gastrocnemius, and 4.9 ± 3.9 for the tibialis anterior. Some participants were able to obtain large increases in muscle metabolism, while other participants had lower increases. Conclusions: The ability to produce large increases in metabolism has the potential to allow NMES to replace or augment exercise to improve health in people who cannot otherwise exercise. The devices used were inexpensive and could be adapted for easy use by a wide range of individuals. [ABSTRACT FROM AUTHOR]

Background: Microglia play a crucial role in brain development and repair by facilitating processes such as synaptic pruning and debris clearance. They can be activated in response to various stimuli, leading to either pro-inflammatory or anti-inflammatory responses associated with specific metabolic alterations. The imbalances between microglia activation states contribute to chronic neuroinflammation, a hallmark of neurodegenerative diseases. N-acetylaspartate (NAA) is a brain metabolite predominantly produced by neurons and is crucial for central nervous system health. Alterations in NAA metabolism are observed in disorders such as Multiple Sclerosis and Canavan disease. While NAA's role in oligodendrocytes and astrocytes has been investigated, its impact on microglial function remains less understood. Methods: The murine BV2 microglial cell line and primary microglia were used as experimental models. Cells were treated with exogenous NAA and stimulated with LPS/IFN-γ to reproduce the pro-inflammatory phenomenon. HPLC and immunofluorescence analysis were used to study lipid metabolism following NAA treatment. Automated fluorescence microscopy was used to analyze phagocytic activity. The effects on the pro-inflammatory response were evaluated by analysis of protein/mRNA expression and ChIP assay of typical inflammatory markers. Results: NAA treatment promotes an increase in both lipid synthesis and degradation, and enhances the phagocytic activity of BV2 cells, thus fostering surveillant microglia characteristics. Importantly, NAA decreases the pro-inflammatory state induced by LPS/IFN-γ via the activation of histone deacetylases (HDACs). These findings were validated in primary microglial cells, highlighting the impact on cellular metabolism and inflammatory responses. Conclusions: The study highlighted the role of NAA in reinforcing the oxidative metabolism of surveillant microglial cells and, most importantly, in buffering the inflammatory processes characterizing reactive microglia. These results suggest that the decreased levels of NAA observed in neurodegenerative disorders can contribute to chronic neuroinflammation. [ABSTRACT FROM AUTHOR]

Oxidative metabolism declines with aging in humans leading to multiple metabolic ailments and subsequent inflammation. In mice, there is evidence of age-related suppression of fatty acid oxidation and oxidative phosphorylation in the liver, heart, and muscles. Many interventions that extend healthy lifespan of mice have been developed, including genetic, pharmacological, and dietary interventions. In this article, we review the literature on oxidative metabolism changes in response to those interventions. We also discuss the molecular pathways that mediate those changes, and their potential as targets for future longevity interventions. [Display omitted] • Oxidative metabolism is downregulated in multiple tissues with aging and age-related diseases. • Lifespan extending interventions upregulated OXPHOS and fatty acid oxidation enzymes at the transcriptional level. • Molecular pathways that mediate those effects include activation of PGC-1α and PPARs, and inhibition of NCOR1 and mTORC1. [ABSTRACT FROM AUTHOR]

This study evaluated tilapia fed diets supplemented with levels of betaine and l-carnitine, simultaneously. Diets supplemented with levels of l-carnitine (500 and 1000 mg kg−1 of feed) and betaine (500 and 1000 mg kg−1 of feed) were used, in addition to the control diet. Weight gain, daily weight gain, and specific growth rate in fish fed diets containing 1000–500 and 1000–1000 mg kg−1 betaine and l-carnitine performed worse than the other inclusion levels, including the control diet. The lipid content of fish fillets was higher in those fed with levels of 1000–1000 mg kg−1 of betaine and l-carnitine in the diet. There was a reduction in total plasma protein levels in fish fed with 1000–500 mg kg−1 of betaine and l-carnitine in the diets, and glucose was higher when fish were fed with levels of 1000–1000 mg kg−1 of betaine and l-carnitine in feed. Catalase activity was higher at levels of 1000–500 mg kg−1 of betaine and l-carnitine in the diet. The height and width of the villi had greater development in fish fed with 1000–500 mg kg−1 of betaine and l-carnitine in the diet. Assessment of muscle histology indicated the interaction of betaine and l-carnitine at levels of 1000–500 mg kg−1 of inclusion in the diet, triggering greater muscle growth. The inclusion of 500–500 mg kg−1 of betaine and l-carnitine in diets improves the development of fish, providing a reduction in carcass lipids and greater muscle development, and reducing oxidative stress in the liver. [ABSTRACT FROM AUTHOR]

Background and Purpose: There is a growing interest in use vibration foam rolling as a warm up and recovery tool. However, whether vibration foam rolling offers additional benefits to traditional foam rolling is unclear. The current study aims to compare the effects of acute foam rolling, with and without vibration, on skeletal muscle metabolism and microvascular reactivity. Methods: Fifteen physically active young males were tested on two different days, with gastrocnemius muscle microvascular function assessed using near-infrared spectroscopy coupled with the post-occlusive reactive hyperemia technique, before and after foam rolling, performed with or without vibration. The slope of tissue saturation index (TSI) decrease during occlusion between 120 s to 150 s (TSI occlusion slope) was assessed for muscle metabolic rate. Three commonly used microvascular function indexes, including the first10s TSI slope after occlusion (TSI10), time for TSI to reach half of peak magnitude (TSI1/2), and TSI peak reactive hyperemia, were also assessed. Results: None of the measured indexes showed significance for interaction or method (all p > 0.05). However, there was a main effect for time for TSI occlusion slope, TSI1/2, and TSI peak reactive hyperemia (p = 0.005, 0.034 and 0.046, respectively). No main effect for time for TSI10 was detected (p = 0.963). Conclusions: The application of foam rolling can decrease muscle metabolism, and may improve some aspects of muscle microvascular function. However, vibration foam rolling does not seem to offer any additional benefits compared to traditional foam rolling alone. [ABSTRACT FROM AUTHOR]

Chinese hamster ovary (CHO) cells are widely used to manufacture biopharmaceuticals, most of all monoclonal antibodies (mAbs). Some CHO cell lines exhibit production instability, where the productivity of the cells decreases as a function of time in culture. To counter this, we designed a passaging strategy that, rather than maximizing the time spent in log‐growth phase, mimics the first 7 days of a fed‐batch production process. Cultures passaged using this method had lower net growth rates and were more oxidative throughout 6 weeks of passaging. Fed‐batch cultures inoculated by cells passaged using this method had increased net growth rates, oxidative metabolism, and volumetric productivity compared to cells passaged using a conventional strategy. Cells from unstable cell lines passaged by this new method produced 80%–160% more mAbs per unit volume than cells passaged by a conventional method. This new method, named Super7, provides the ability to mitigate the impact of production instability in CHO‐K1 cell lines without a need for further cell line creation, genetic engineering, or medium development. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is a muscle disorder causing a progressive reduction of muscle mass and strength, but the mechanism of its manifestation is still partially unknown. The three main parameters to assess are: muscle strength, muscle volume or quality and low physical performance. There is not a definitive approach to assess the musculoskeletal condition of frail population and often the available tests to be performed in those clinical bedridden patients is reduced because of physical impairments. In this paper, we propose a novel instrumental multi-domain and non-invasive approach during a well-defined protocol of measurements for overcoming these limitations. A group of 28 bedridden elder people, subjected to surgery after hip fracture, was asked to perform voluntary isometric contractions at the 80% of their maximum voluntary contraction with the non-injured leg. The sensor employed before and/or during the exercise were: ultrasound to determine the muscle architecture (vastus lateralis); force acquisition with a load cell placed on the chair, giving an indication of the muscle strength; surface electromyography (EMG) for monitoring muscular electrical activity; time-domain (TD) near-infrared spectroscopy (NIRS) for evaluating muscle oxidative metabolism. Results: A personalized "report card" for each subject was created. It includes: the force diagram (both instantaneous and cumulative, expected and measured); the EMG–force diagram for a comparison between EMG derived median frequency and measured force; two graphs related to the hemodynamic parameters for muscle oxidative metabolism evaluation, i.e., oxy-, deoxy-, total-hemoglobin and tissue oxygen saturation for the whole exercise period. A table with the absolute values of the previous hemodynamic parameters during the rest and the ultrasound related parameters are also included. Conclusions: In this work, we present the union of protocols, multi-domain sensors and parameters for the evaluation of the musculoskeletal condition. The novelties are the use of sensors of different nature, i.e., force, electrical and optical, together with a new way to visualize and combine the results, by means of a concise, exhaustive and personalized medical report card for each patient. This assessment, totally non-invasive, is focused on a bedridden population, but can be extended to the monitoring of rehabilitation progresses or of the training of athletes. [ABSTRACT FROM AUTHOR]

Aims: Poly (ADP‐ribose) polymerase (PARP) has been extensively investigated in human cancers. Recent studies verified that current available PARP inhibitors (Olaparib or Veliparib) provided clinical palliation of clinical patients suffering from paclitaxel‐induced neuropathic pain (PINP). However, the underlying mechanism of PARP overactivation in the development of PINP remains to be investigated. Methods and Results: We reported induction of DNA oxidative damage, PARP‐1 overactivation, and subsequent nicotinamide adenine dinucleotide (NAD+) depletion as crucial events in the pathogenesis of PINP. Therefore, we developed an Olaparib PROTAC to achieve the efficient degradation of PARP. Continuous intrathecal injection of Olaparib PROTAC protected against PINP by inhibiting the activity of PARP‐1 in rats. PARP‐1, but not PARP‐2, was shown to be a crucial enzyme in the development of PINP. Specific inhibition of PARP‐1 enhanced mitochondrial redox metabolism partly by upregulating the expression and deacetylase activity of sirtuin‐3 (SIRT3) in the dorsal root ganglions and spinal cord in the PINP rats. Moreover, an increase in the NAD+ level was found to be a crucial mechanism by which PARP‐1 inhibition enhanced SIRT3 activity. Conclusion: The findings provide a novel insight into the mechanism of DNA oxidative damage in the development of PINP and implicate PARP‐1 as a possible therapeutic target for clinical PINP treatment. [ABSTRACT FROM AUTHOR]

The mechanistic relationships between the progression of growth chondrocyte differentiation, matrix mineralization, oxidative metabolism, and mitochondria content and structure were examined in the ATDC5 murine chondroprogenitor cell line. The progression of chondrocyte differentiation was associated with a statistically significant (p ≤ 0.05) ~2‐fold increase in oxidative phosphorylation. However, as matrix mineralization progressed, oxidative metabolism decreased. In the absence of mineralization, cartilage extracellular matrix mRNA expression for Col2a1, Aggrecan, and Col10a1 were statistically (p ≤ 0.05) ~2–3‐fold greater than observed in mineralizing cultures. In contrast, BSP and Phex that are associated with promoting matrix mineralization showed statistically (p ≤ 0.05) higher ~2–4 expression, while FGF23 phosphate regulatory factor was significantly lower (~50%) in mineralizing cultures. Cultures induced to differentiate under both nonmineralizing and mineralizing media conditions showed statistically greater basal oxidative metabolism and ATP production. Maximal respiration and spare oxidative capacity were significantly elevated (p ≤ 0.05) in differentiated nonmineralizing cultures compared to those that mineralized. Increased oxidative metabolism was associated with both an increase in mitochondria volume per cell and mitochondria fusion, while mineralization diminished mitochondrial volume and appeared to be associated with fission. Undifferentiated and mineralized cells showed increased mitochondrial co‐localization with the actin cytoskeletal. Examination of proteins associated with mitochondria fission and apoptosis and mitophagy, respectively, showed levels of immunological expression consistent with the increasing fission and apoptosis in mineralizing cultures. These results suggest that chondrocyte differentiation is associated with intracellular structural reorganization, promoting increased mitochondria content and fusion that enables increased oxidative metabolism. Mineralization, however, does not need energy derived from oxidative metabolism; rather, during mineralization, mitochondria appear to undergo fission and mitophagy. In summary, these studies show that as chondrocytes underwent hypertrophic differentiation, they increased oxidative metabolism, but as mineralization proceeds, metabolism decreased. Mitochondria structure also underwent a structural reorganization that was further supportive of their oxidative capacity as the chondrocytes progressed through their differentiation. Thus, the mitochondria first underwent fusion to support increased oxidative metabolism, then underwent fission during mineralization, facilitating their programed death. [ABSTRACT FROM AUTHOR]

Exogenous application of sodium nitroprusside (SNP) has previously been reported to trigger plant tolerance against a variety of environmental stresses. The present study was planned to investigate the possible role/s of exogenously applied SNP (50 or 100 μM) in alleviating cadmium (Cd)-induced effects on physio-biochemical processes, yield attributes, and grain quality traits of three fragrant rice cultivars, viz., Meixiangzhan-2 (MXZ), Guixiangzhan (GXZ), and Xiangyaxiangzhan (XYXZ) under 50 mg Cd kg−1 of soil. The results revealed that foliar spray of SNP (50 or 100 μM) on Cd-stressed rice plants reduced oxidative stress (lower hydrogen peroxide (H2O2), malondialdehyde (MDA), and electrolyte leakage (EL)) and improved the photosynthetic apparatus through higher chlorophyll contents, gas exchange attributes, and intact chloroplast configurations, and reduced Cd concentration in the leaves and grains of aromatic rice cultivars. The reduced levels of cellular ROS, MDA, and EL were related to the endogenous NO-mediated improvement in the activity of anti-oxidative enzymes and those involved during the ascorbate–glutathione cycle. However, among the different SNP levels, the foliar spraying of 50 μM of SNP was recorded to be the best treatment for fragrant rice growth, which increased grain yield by 42.06%, 46.03%, and 31.21%, and the quality trait of 2-acetyl-1-pyrroline (2-AP) content by 43.12%, 55.84%, and 35.72% in MXZ, GXZ, and XYXZ respectively, suggesting that GXZ is more responsive to SNP than MXZ and XYXZ fragrant rice cultivars. Collectively, our results deduced that cultivating the GXZ fragrant rice cultivar along with foliar application of 50 μM of SNP could sustain the grain yield and quality features of aromatic rice cultivation in heavy metal (especially Cd)-polluted soils. [ABSTRACT FROM AUTHOR]

In several mammalian species, the measurement of mitochondrial oxygen consumption (MITOX) under different metabolic conditions has demonstrated a positive correlation with sperm motility and may be a sensitive indicator of mitochondrial health. In general, the maintenance of sperm motility and many key sperm functions and fertilizing events are heavily energy‐dependent processes, and some species‐specific substrate preferences exist. Although canine sperm have been known to undergo capacitation and maintain motility with supplementation of a wide range of energy substrates, the relationship between mitochondrial function, and the maintenance of oxidative metabolism and sperm motility remain unclear. The objective of this study was to explore the metabolic flexibility of canine sperm, and to investigate the relationship between mitochondrial function, and maintenance of motility under differing nutrient conditions. We explored substrate preferences and the bioenergetics underlying maintenance of canine sperm motility by monitoring mitochondrial oxidative function and sperm kinematics in the presence of mitochondrial effector drug treatments: FCCP, antimycin (ANTI), and oligomycin (OLIGO). We hypothesized that canine sperm possess the ability to use compensatory pathways and utilize diverse nutrient sources in the maintenance of motility. Oxygen consumption (change in pO2, oxygen partial pressure) and sperm kinematics (CASA) were measured concurrently (t0–t30) to assess the relationship between oxidative metabolism and maintenance of sperm motility in dogs. Four media were tested: containing glucose, lactate, and pyruvate (GLP), containing glucose (G), fructose (F), or lactate and pyruvate (LP). In the absence of pharmacological inhibition of the electron transport chain, energetic substrate had no effect on sperm kinematics in fertile dogs. Following mitochondrial disruption by ANTI and OLIGO, mitochondrial oxygen consumption was negatively correlated with several sperm motility parameters in GLP, G, F, and LP media. In every media, FCCP treatment quickly induced significantly higher oxygen consumption than in untreated sperm, and spare respiratory capacity, the maximal inducible oxidative metabolism, was high. With respiratory control ratios RCR >1 there was no indication of bioenergetic dysfunction in any media type, indicating that sperm mitochondria of fertile dogs have a high capacity for substrate oxidation and ATP turnover regardless of substrate. Our results suggest MITOX assessment is a valuable tool for assessing mitochondrial functionality, and that canine sperm employ flexible energy management systems which may be exploited to improve sperm handling and storage. [ABSTRACT FROM AUTHOR]

Understanding the complex biological processes of cells in culture, particularly those related to metabolism, can be biased by culture conditions, since the choice of energy substrate impacts all of the main metabolic pathways. When glucose is replaced by galactose, cells decrease their glycolytic flux, working as an in vitro model of limited nutrient availability. However, the effect of these changes on related physiological processes such as redox control is not well documented, particularly in endothelial cells, where mitochondrial oxidation is considered to be low. We evaluated the differences in mitochondrial dynamics and function in endothelial cells exposed to galactose or glucose culture medium. We observed that cells maintained in galactose-containing medium show a higher mitochondrial oxidative capacity, a more fused mitochondrial network, and higher intercellular coupling. These factors are documented to impact the cellular response to oxidative stress. Therefore, we analyzed the levels of two main redox regulators and found that bovine aortic endothelial cells (BAEC) in galactose media had higher levels of FOXO3 and lower levels of Nrf2 than those in glucose-containing media. Thus, cultures of endothelial cells in a galactose-containing medium may provide a more suitable target for the study of in vitro mitochondrial-related processes than those in glucose-containing media; the medium deeply influences redox signaling in these cells. [ABSTRACT FROM AUTHOR]

Understanding post-stroke changes in skeletal muscle oxidative metabolism and microvascular reactivity could help create therapeutic targets that optimize rehabilitative interventions. Due to disuse atrophy, we hypothesized that basal muscle oxygen consumption rate and microvascular endothelial function would be impaired in the tibialis anterior (TA) muscle of the affected leg of chronic stroke survivors compared with the nonaffected leg and versus matched controls. Fifteen chronic stroke survivors (10 females) and 15 matched controls (9 females) completed this study. A near-infrared spectroscopy oximeter measured tissue oxygen saturation (StO2) of the TA in both legs of stroke survivors and the dominant leg of controls. A cuff was placed around the thigh and inflated to 225 mmHg for 5 min while StO2 was continuously measured. The rate of change in StO2 was calculated during cuff occlusion and immediately post-cuff release. The rate of oxygen desaturation was similar between the legs of the stroke survivors (paretic –0.12 ± 0.04%·s−1 vs. nonparetic –0.16 ± 011%·s−1; P = 0.49), but the paretic leg had a reduced desaturation rate versus controls (–0.25 ± 0.18%·s−1; P = 0.007 vs. paretic leg). After cuff release, there was a greater oxygen resaturation rate in the nonparetic leg compared with the paretic leg (3.13 ± 2.08%·s−1 vs. 1.60 ± 1.11%·s−1, respectively; P = 0.01). The control leg had a similar resaturation rate versus the nonparetic leg (control = 3.41 ± 1.79%·s−1; P = 0.69) but was greater than the paretic leg (P = 0.003). The TA in the paretic leg had an impaired muscle oxygen consumption rate and reduced microvascular endothelial function compared with controls. NEW & NOTEWORTHY: Secondary consequences of stroke are not well described. In this study, we show that basal muscle oxidative consumption and microvascular endothelial function are reduced in the paretic tibialis anterior muscle of chronic stroke survivors compared with matched controls using near-infrared spectroscopy and the vascular occlusion technique. There was a moderately strong correlation between microvascular endothelial function and paretic leg strength. [ABSTRACT FROM AUTHOR]

Introduction: The world is experiencing exponential growth in communication, especially wireless communication. Wireless connectivity has recently become a part of everyone's daily life. Recent developments in low-cost, low-power, and miniature devices contribute to a significant rise in radiofrequency-electromagnetic field (RF-EM) radiation exposure in our environment, raising concern over its effect on biological systems. The inconsistent and conflicting research results make it difficult to draw definite conclusions about how RF-EM radiation affects living things. Objectives: This study identified two micro-environments based on their level of exposure to cellular RF-EM radiation, one with significantly less exposure and another with very high exposure to RF-EM radiation. Emphasis is given to studying the metabolites in the urine samples of humans naturally exposed to these two different microenvironments to understand short-term metabolic dysregulations. Methods: Untargeted 1H NMR spectroscopy was employed for metabolomics analyses to identify dysregulated metabolites. A total of 60 subjects were recruited with 5 ml urine samples each. These subjects were divided into two groups: one highly exposed to RF-EM (n = 30) and the other consisting of low-exposure populations (n = 30). Results: The study found that the twenty-nine metabolites were dysregulated. Among them, 19 were downregulated, and 10 were upregulated. In particular, Glyoxylate and dicarboxylate and the TCA cycle metabolism pathway have been perturbed. The dysregulated metabolites were validated using the ROC curve analysis. Conclusion: Untargeted urine metabolomics was conducted to identify dysregulated metabolites linked to RF-EM radiation exposure. Preliminary findings suggest a connection between oxidative stress and gut microbiota imbalance. However, further research is needed to validate these biomarkers and understand the effects of RF-EM radiation on human health. Further research is needed with a diverse population. [ABSTRACT FROM AUTHOR]

In vitro studies using rat, mouse, and human microsomes and hepatocytes on the bacterial β-glucuronidase inhibitor 1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl)-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea) (Inh 1) revealed extensive metabolism in all species. The intrinsic clearances of Inh 1 in human, mouse, and rat hepatic microsomes were 30.9, 67.8, and 201 µL/min/mg, respectively. For intact hepatocytes intrinsic clearances of 21.6, 96.0, and 129 µL/min/106 cells were seen for human, mouse and rat, respectively. The metabolism of Inh 1 involved an uncommon desulphurisation reaction in addition to oxidation, deethylation, and conjugation reactions at multiple sites. Six metabolites were detected in microsomal incubations in human and rat, and seven for the mouse. With hepatocytes, 18 metabolites were characterised, 9 for human, and 11 for mouse and rat. Following IV administration to mice (3 mg/kg), plasma concentrations of Inh 1 exhibited a monophasic decline with a terminal elimination half-life of 0.91 h and low systemic clearance (11.8% of liver blood flow). After PO dosing to mice (3 mg/kg), peak observed Inh 1 concentrations of 495 ng/mL were measured 0.5 h post dose, declining to under 10 ng/mL at 8 h post dose. The absolute oral bioavailability of Inh 1 in the mouse was ca. 26%. [ABSTRACT FROM AUTHOR]

Autophagy is essential for proteostasis, energetic balance, and cell defense and is a key pathway in aging. Identifying associations between autophagy gene expression patterns in skeletal muscle and physical performance outcomes would further our knowledge of mechanisms related with proteostasis and healthy aging. Muscle biopsies were obtained from participants in the Study of Muscle, Mobility, and Aging (SOMMA). For 575 participants, RNA was sequenced and expression of 281 genes related to autophagy regulation, mitophagy, and mTOR/upstream pathways was determined. Associations between gene expression and outcomes including mitochondrial respiration in muscle fiber bundles (MAX OXPHOS), physical performance (VO2 peak, 400 m walking speed, and leg power), and thigh muscle volume, were determined using negative binomial regression models. For autophagy, key transcriptional regulators including TFE3 and NFKB‐related genes (RELA, RELB, and NFKB1) were negatively associated with outcomes. On the contrary, regulators of oxidative metabolism that also promote overall autophagy, mitophagy, and pexophagy (PPARGC1A, PPARA, and EPAS1) were positively associated with multiple outcomes. In line with this, several mitophagy, fusion, and fission‐related genes (NIPSNAP2, DNM1L, and OPA1) were also positively associated with outcomes. For mTOR pathway and related genes, expression of WDR59 and WDR24, both subunits of GATOR2 complex (an indirect inhibitor of mTORC1), and PRKAG3, which is a regulatory subunit of AMPK, were negatively correlated with multiple outcomes. Our study identifies autophagy and selective autophagy such as mitophagy gene expression patterns in human skeletal muscle related to physical performance, muscle volume, and mitochondrial function in older persons which may lead to target identification to preserve mobility and independence. [ABSTRACT FROM AUTHOR]

In this study, the toxicogenomic effects of five cytostatics (tamoxifen, methotrexate, capecitabine, cyclophosphamide, and ifosfamide) on fathead minnow (Pimephales promelas) larvae were evaluated. Post-fertilization eggs were exposed to increasing concentrations of the drugs for six days. The expression levels of two genetic biomarkers for toxicity and four thyroid hormone-related gene pathways were measured. Interestingly, the results showed that all concentrations of the five cytostatics affect the transcription levels of both toxicity biomarker genes. Additionally, the thyroid hormone-related genes had different expression levels than the control, with the most significant changes observed in those larvae exposed to cyclophosphamide and ifosfamide. While a previous study found no effects on fish morphology, this study suggests that the five cytostatics modify subtle molecular responses of P. promelas, highlighting the importance of assessing multibiological level endpoints throughout the lifecycle of animals to understand the full portrait of potential effects of cytostatics and other contaminants. [ABSTRACT FROM AUTHOR]

Background and Purpose There is a growing interest in use vibration foam rolling as a warm up and recovery tool. However, whether vibration foam rolling offers additional benefits to traditional foam rolling is unclear. The current study aims to compare the effects of acute foam rolling, with and without vibration, on skeletal muscle metabolism and microvascular reactivity. Methods Fifteen physically active young males were tested on two different days, with gastrocnemius muscle microvascular function assessed using near-infrared spectroscopy coupled with the post-occlusive reactive hyperemia technique, before and after foam rolling, performed with or without vibration. The slope of tissue saturation index (TSI) decrease during occlusion between 120 s to 150 s (TSI occlusion slope) was assessed for muscle metabolic rate. Three commonly used microvascular function indexes, including the first10s TSI slope after occlusion (TSI10), time for TSI to reach half of peak magnitude (TSI1/2), and TSI peak reactive hyperemia, were also assessed. Results None of the measured indexes showed significance for interaction or method (all p > 0.05). However, there was a main effect for time for TSI occlusion slope, TSI1/2, and TSI peak reactive hyperemia (p = 0.005, 0.034 and 0.046, respectively). No main effect for time for TSI10 was detected (p = 0.963). Conclusions The application of foam rolling can decrease muscle metabolism, and may improve some aspects of muscle microvascular function. However, vibration foam rolling does not seem to offer any additional benefits compared to traditional foam rolling alone.

This study aimed to evaluate differences in the production of reactive oxygen species (ROS) by peripheral blood neutrophils in healthy dogs, dogs with superficial pyoderma, and dogs with sterile neutrophilic dermatitis using the nitroblue tetrazolium (NBT) reduction test. Additionally, the study assessed the potential of the NBT reduction test as a diagnostic tool to differentiate between these clinical conditions. A total of 28 dogs were divided into three groups: healthy (n = 10), superficial pyoderma (n = 10), and sterile neutrophilic dermatitis (n = 8). The results showed significantly higher neutrophil activation in dogs with sterile neutrophilic dermatitis (19 ± 10%) compared with healthy dogs (7.3 ± 5%) (p < 0.01) and dogs with superficial pyoderma (10 ± 2.8%) (p < 0.05). Dogs with sterile neutrophilic dermatitis and a high positive result for Leishmania spp. antibodies (n = 3) exhibited even higher NBT reduction rates (30 ± 4.6%) compared with seronegative dogs with sterile neutrophilic dermatitis (n = 5) (13 ± 5.3%) (p < 0.05). These findings suggest that the NBT reduction test could be useful for detecting systemic neutrophil activation in sterile neutrophilic dermatitis, especially when associated with Leishmania infection. However, no significant differences were observed between healthy dogs and those with superficial pyoderma, indicating that the test may not be effective in detecting systemic neutrophil activation in superficial bacterial infections.

Background/Objectives: Previous studies have shown that neuromuscular electrical stimulation (NMES), while expensive, can provide some of the health benefits of exercise to people who cannot exercise their legs normally. The aim of this study was to quantify the increases in muscle metabolism in four muscles of the legs of able-bodied individuals with NMES. Methods: Healthy college-aged students were tested. NMES of four muscle groups was performed with inexpensive stimulators and reusable tin foil electrodes. The biceps femoris, vastus lateralis, medial gastrocnemius, and tibialis anterior muscles on one leg were stimulated for ten minutes with twitch stimulations at the highest comfortable stimulation current. Muscle metabolism was measured using the slope of oxygen consumption measured with near-infrared spectroscopy (NIRS) during 5 s of cuff ischemia. Results: Initial studies found fold increases in muscle metabolism above rest of 8.9 ± 8.6 for the vastus lateralis, 7.9 ± 11.9 for the biceps femoris, 6.6 ± 7.8 for the medial gastrocnemius, and 4.9 ± 3.9 for the tibialis anterior. Some participants were able to obtain large increases in muscle metabolism, while other participants had lower increases. Conclusions: The ability to produce large increases in metabolism has the potential to allow NMES to replace or augment exercise to improve health in people who cannot otherwise exercise. The devices used were inexpensive and could be adapted for easy use by a wide range of individuals.

In this study, an online electrochemistry coupling high-performance liquid chromatography-mass spectrometry (EC-HPLC-MS) technology has been developed for simulating metabolic reactions and rapid analysis of metabolites of flavone, quercetin, and rutin, which are not only widely present compounds with pharmacological activity in nature, but also have structural similarity and variability. The simulated metabolic processes of the substrates (phase I and phase II metabolism) were implemented on the surface of glassy carbon electrode (GCE) by using different electrochemical methods. After online chromatographic separation, the products were transmitted to a mass spectrometer for detection, in order to speculate relevant reaction pathways and structural information of the reaction product. The main metabolites, including methylation, hydroxylation, hydrolysis, and conjugation reaction products, had been successfully identified through the designed in situ hyphenated technique. Furthermore, compared with metabolites produced by in vitro incubation of rat liver microsomes, it was found that the products of electrochemical simulated metabolism were more abundant with diverse metabolic pathways. The results indicated that the proposed method exhibited advantages in the sample pretreatment process and detection cycle without compromising the reliability and accuracy of the results. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSC) are the leading cause of the failure of anti-tumor treatments. These aggressive cancer cells are preserved and sustained by adjacent cells forming a specialized microenvironment, termed niche, among which tumor-associated macrophages (TAMs) are critical players. The cycle of tricarboxylic acids, fatty acid oxidation path, and electron transport chain have been proven to play central roles in the development and maintenance of CSCs and TAMs. By improving their oxidative metabolism, cancer cells are able to extract more energy from nutrients, which allows them to survive in nutritionally defective environments. Because mitochondria are crucial bioenergetic hubs and sites of these metabolic pathways, major hopes are posed for drugs targeting mitochondria. A wide range of medications targeting mitochondria, electron transport chain complexes, or oxidative enzymes are currently investigated in phase 1 and phase 2 clinical trials against hard-to-treat tumors. This review article aims to highlight recent literature on the metabolic adaptations of CSCs and their supporting macrophages. A focus is provided on the resistance and dormancy behaviors that give CSCs a selection advantage and quiescence capacity in particularly hostile microenvironments and the role of TAMs in supporting these attitudes. The article also describes medicaments that have demonstrated a robust ability to disrupt core oxidative metabolism in preclinical cancer studies and are currently being tested in clinical trials. [ABSTRACT FROM AUTHOR]

Near-infrared spectroscopy (NIRS) during repeated limb occlusions is a noninvasive tool for assessing muscle oxidative capacity. However, the method's reliability and validity remain under investigation. This study aimed to determine the reliability of the NIRS-derived mitochondrial power of the musculus vastus lateralis and its correlation with whole-body (cycling) aerobic power ( V ̇ O2 peak). Eleven healthy active men (28 ± 10 y) twice (2 days apart) underwent repeated arterial occlusions to induce changes in muscle oxygen delivery after 15 s of electrical muscle stimulation. The muscle oxygen consumption (m V ̇ O2) recovery time and rate (k) constants were calculated from the NIRS O2Hb signal. We assessed the reliability (coefficient of variation and intraclass coefficient of correlation [ICC]) and equivalency (t-test) between visits. The results showed high reproducibility for the m V ̇ O2 recovery time constant (ICC = 0.859) and moderate reproducibility for the k value (ICC = 0.674), with no significant differences between visits (p > 0.05). NIRS-derived k did not correlate with the V ̇ O2 peak relative to body mass (r = 0.441, p = 0.17) or the absolute V ̇ O2 peak (r = 0.366, p = 0.26). In conclusion, NIRS provides a reproducible estimate of muscle mitochondrial power, which, however, was not correlated with whole-body aerobic capacity in the current study, suggesting that even if somewhat overlapping, not the same set of factors underpin these distinct indices of aerobic capacity at the different (peripheral and whole-body systemic) levels. [ABSTRACT FROM AUTHOR]

Our previous studies have shown that 'Palmer' mangoes immersed in solutions containing 2.5% sorbitol and stored under a controlled atmosphere (CA) at 8 °C for 30 days had fewer symptoms of a chilling injury. However, there is no information regarding the effectiveness of sorbitol treatment in other atmospheres and/or in combination with lower temperatures. Thus, the objective of this study was to assess the impact of dipping 'Palmer' mangoes in 0.1% and 2.5% (w/v) sorbitol solutions and storing the fruit under a CA without atmosphere modification (21 kPa O2 + 0.03 kPa CO2) at 8 °C/95% relative humidity (RH) or with 5 kPa O2 + 5 kPa CO2 at 4 °C/95% RH for 28 days. The fruits were evaluated periodically for chilling injuries, quality, and oxidative metabolism. A chilling injury (CI) was correlated with increased fresh weight loss (FWL) and changes in the color of the epicarp (Lpeel, h°peel, and Cpeel) and mesocarp (L*pulp). Lipid peroxidation (LPpulp and LPpeel) and the hydrogen peroxide content (H2O2peel and H2O2pulp) were associated with the development of a CI, particularly after being transferred to ambient. The treatment with 2.5% sorbitol was more effective in minimizing the chilling injury symptoms and did not compromise the fruit quality, especially when it was stored at 4 °C in association with a CA containing 5 kPa O2 + 5 kPa CO2. This treatment reduced lipid peroxidation and increased the activities of the superoxide dismutase (SOD) and ascorbate peroxidase (APX) enzymes in the epicarp and mesocarp, providing greater cold tolerance. The use of 2.5% sorbitol has been identified as the most efficacious approach for mitigating the adverse impacts of chilling injuries, preserving the fruit quality, and enhancing oxidative metabolism, even at lower temperatures. Thus, this treatment represents a viable alternative for managing chilling injuries in mangoes. [ABSTRACT FROM AUTHOR]

This study evaluated the intestinal effects of alkalinized filtered water in lean and obese adult Zucker rats. For 3 months, 12-week-old rats consumed either tap water or filtered alkalinized tap water from Madrid city. Weight gain was monitored, changes in metabolism were evaluated by indirect calorimetry, and total antioxidant capacity and levels of inflammatory mediators were measured in plasma. Feces were collected, their microbial composition was analyzed and histological analysis of the small and large intestine was performed, assessing the general state of the mucosa (MUC2), the inflammatory state (F4/80) and the presence of oxidative modifications in protein 4-Hydroxynonenal (4-HNE) by immunofluorescence (IF) and immunohistochemistry (IHC). The results obtained showed that the consumption of alkalinized filtered water improved the composition of the intestinal microbiome and the state of the intestinal mucosa, reducing both local and systemic inflammation and the level of oxidative stress. These changes were accompanied by a better maintenance of the oxidative status in rats. No differences were observed in antioxidant capacity nor in weight gain. The incorporation of probiotics in the diet had a significant impact on the microbiome. These effects were indicative of an improvement in general metabolic, oxidative and inflammatory status. [ABSTRACT FROM AUTHOR]

Chinese black truffle (Tuber indicum) is a hypogenous fungus of great value due to its distinctive aroma. In this study, both transcriptome and physicochemical analyses were performed to investigate the changes of nutrients and gene expression in truffle fruiting bodies during cold storage. The results of physicochemical analysis revealed the active metabolism of fruiting bodies in cold storage, showing the decreased contents of protein and soluble sugar, the variations in both polyphenol oxidase activity and total phenol content, and the detrimental effect of reactive oxygen species production caused by heavy metals (cadmium and lead) in truffles. Transcriptome analysis identified a total of 139,489 unigenes. Down-regulated expression of genes encoding the catalase-like domain-containing protein (katE), glutaredoxin protein (GRX), a copper/zinc superoxide dismutase (Sod_Cu), and aspartate aminotransferase (AAT) affected the degradation metabolism of intracellular oxides. Ribulose-5-phosphate-3-epimerase (RPE) was a key enzyme in response to oxidative stress in truffle cells through the pentose phosphate pathway (PPP). A total of 51,612 simple sequence repeats were identified, providing valuable resources for further genetic diversity analysis, molecular breeding, and genetic map-ping in T. indicum. Transcription factors GAL4 and SUF4-like protein were involved in glucose metabolism and histone methylation processes, respectively. Our study provided a fundamental characterization of the physicochemical and molecular variations in T. indicum during the cold storage at 4°C, providing strong experimental evidence to support the improvement of storage quality of T. indicum.

ABSTRACT Malondialdehyde (MDA) is a biomarker of oxidative metabolism, released under situations such as the stretching of atrial myocytes, a fact related to the development of chronic mitral valve disease (MVD) in dogs. This study aimed to evaluate the serum concentration of MDA in dogs at different stages of MVD and correlate it with echocardiographic and radiographic parameters referring to cardiomegaly signs. Thirty-seven dogs were divided into four stages of the disease: GA (n=10), GB1 (n=10), GB2 (n=9), and GC (n=8), following the criteria of the American College of Veterinary Internal Medicine (ACVIM). Blood was collected by jugular puncture and then the serum was frozen for later measurement of MDA concentration by the spectrophotometry technique. No difference was found in MDA concentration between groups despite the presence of cardiac remodeling in dogs at advanced stages of MVD. Moreover, no significant relationship was observed between MDA values and the studied cardiovascular parameters. Serum MDA showed no variation throughout MVD development even with evidence of its release, with no possibility of demonstrating the relationship between its concentration and the cardiovascular alterations caused by the disease in dogs.

The Lactate Shuttle hypothesis is supported by a variety of techniques including mass spectrometry analytics following infusion of carbon-labeled isotopic tracers. However, there has been controversy over whether lactate tracers measure lactate (L) or pyruvate (P) turnover. Here, we review the analytical errors, use of inappropriate tissue and animal models, failure to consider L and P pool sizes in modeling results, inappropriate tracer and blood sampling sites, and failure to anticipate roles of heart and lung parenchyma on L⇔P interactions. With support from magnetic resonance spectroscopy (MRS) and immunocytochemistry, we conclude that carbon-labeled lactate tracers can be used to quantitate lactate fluxes.

The development of anti-pain technologies in the complex treatment of pain syndromes is one of the most urgent tasks of modern medicine. We undertook a placebo-controlled experimental study of the therapeutic potential of low-intensity laser radiation when applied to acupuncture points that are directly related to the autonomic nervous system. The adaptation effect of puncture photobiomodulation on the induction of stress-mediated autonomic reactions, oxidative metabolism and microcirculation in animals during the acute phase of pain stress was revealed. The data obtained are of interest for use in the complex rehabilitation of patients with pain syndromes.

Cancer stem cells (CSC) are the leading cause of the failure of anti-tumor treatments. These aggressive cancer cells are preserved and sustained by adjacent cells forming a specialized microenvironment, termed niche, among which tumor-associated macrophages (TAMs) are critical players. The cycle of tricarboxylic acids, fatty acid oxidation path, and electron transport chain have been proven to play central roles in the development and maintenance of CSCs and TAMs. By improving their oxidative metabolism, cancer cells are able to extract more energy from nutrients, which allows them to survive in nutritionally defective environments. Because mitochondria are crucial bioenergetic hubs and sites of these metabolic pathways, major hopes are posed for drugs targeting mitochondria. A wide range of medications targeting mitochondria, electron transport chain complexes, or oxidative enzymes are currently investigated in phase 1 and phase 2 clinical trials against hard-to-treat tumors. This review article aims to highlight recent literature on the metabolic adaptations of CSCs and their supporting macrophages. A focus is provided on the resistance and dormancy behaviors that give CSCs a selection advantage and quiescence capacity in particularly hostile microenvironments and the role of TAMs in supporting these attitudes. The article also describes medicaments that have demonstrated a robust ability to disrupt core oxidative metabolism in preclinical cancer studies and are currently being tested in clinical trials.

The central dogma of molecular biology dictates the general flow of molecular information from DNA that leads to a functional cellular outcome. In skeletal muscle fibers, the extent to which global myonuclear transcriptional alterations, accounting for epigenetic and post-transcriptional influences, contribute to an adaptive stress response is not clearly defined. In this investigation, we leveraged an integrated analysis of the myonucleus-specific DNA methylome and transcriptome, as well as myonuclear small RNA profiling to molecularly define the early phase of skeletal muscle fiber hypertrophy. The analysis of myonucleus-specific mature microRNA and other small RNA species provides new directions for exploring muscle adaptation and complemented the methylation and transcriptional information. Our integrated multi-omics interrogation revealed a coordinated myonuclear molecular landscape during muscle loading that coincides with an acute and rapid reduction of oxidative metabolism. This response may favor a biosynthesis-oriented metabolic program that supports rapid hypertrophic growth. Graphical Abstract [ABSTRACT FROM AUTHOR]

A hallmark of inherited retinal degenerative diseases such as retinitis pigmentosa (RP) is progressive structural and functional remodeling of the remaining retinal cells as photoreceptors degenerate. Extensive remodeling of the retina stands as a barrier for the successful implementation of strategies to restore vision. To understand the molecular basis of remodeling, we performed analyses of single-cell transcriptome data from adult zebrafish retina of wild type AB strain (WT) and a P23H mutant rhodopsin transgenic model of RP with continuous degeneration and regeneration. Retinas from both female and male fish were pooled to generate each library, combining data from both sexes. We provide a benchmark atlas of retinal cell type transcriptomes in zebrafish and insight into how each retinal cell type is affected in the P23H model. Oxidative stress is found throughout the retina, with increases in reliance on oxidative metabolism and glycolysis in the affected rods as well as cones, bipolar cells, and retinal ganglion cells. There is also transcriptional evidence for widespread synaptic remodeling and enhancement of glutamatergic transmission in the inner retina. Notably, changes in circadian rhythm regulation are detected in cones, bipolar cells, and retinal pigmented epithelium. We also identify the transcriptomic signatures of retinal progenitor cells and newly formed rods essential for the regenerative process. This comprehensive transcriptomic analysis provides a molecular road map to understand how the retina remodels in the context of chronic retinal degeneration with ongoing regeneration. [ABSTRACT FROM AUTHOR]

Sepsis is a major health problem in the United States (US), constituting a leading contributor to mortality among critically ill patients. Despite advances in treatment the underlying pathophysiology of sepsis remains elusive. Reactive oxygen species (ROS) have a significant role in antimicrobial host defense and inflammation and its dysregulation leads to maladaptive responses because of excessive inflammation. There is growing evidence for crosstalk between the central nervous system and the immune system in response to infection. The hypothalamic-pituitary and adrenal axis and the sympathetic nervous system are the two major pathways that mediate this interaction. Epinephrine (Epi) and norepinephrine (NE), respectively are the effectors of these interactions. Upon stimulation, NE is released from sympathetic nerve terminals locally within lymphoid organs and activate adrenoreceptors expressed on immune cells. Similarly, epinephrine secreted from the adrenal gland which is released systemically also exerts influence on immune cells. However, understanding the specific impact of neuroimmunity is still in its infancy. In this review, we focus on the sympathetic nervous system, specifically the role the neurotransmitter norepinephrine has on immune cells. Norepinephrine has been shown to modulate immune cell responses leading to increased anti-inflammatory and blunting of pro-inflammatory effects. Furthermore, there is evidence to suggest that norepinephrine is involved in regulating oxidative metabolism in immune cells. This review attempts to summarize the known effects of norepinephrine on immune cell response and oxidative metabolism in response to infection. [ABSTRACT FROM AUTHOR]

Manganese (Mn) is one of the essential mineral micronutrients most demanded by cacao. Cadmium (Cd) is highly toxic to plants and other living beings. There are indications that Mn can interact with Cd and mitigate its toxicity. The objective of this study was to evaluate the action of Mn on the toxic effect of Cd in young plants of the CCN 51 cacao genotype, subjected to different doses of Mn, Cd, and Mn+Cd in soil, through physiological, biochemical, molecular, and micromorphological and ultrastructural changes. High soil Mn doses favored the maintenance and performance of adequate photosynthetic processes in cacao. However, high doses of Cd and Mn+Cd in soil promoted damage to photosynthesis, alterations in oxidative metabolism, and the uptake, transport, and accumulation of Cd in roots and leaves. In addition, high Cd concentrations in roots and leaf tissues caused irreversible damage to the cell ultrastructure, compromising cell function and leading to programmed cell death. However, there was a mitigation of Cd toxicity when cacao was grown in soils with low Cd doses and in the presence of Mn. Thus, damage to the root and leaf tissues of cacao caused by Cd uptake from contaminated soils can be attenuated or mitigated by the presence of high Mn doses in soil. [ABSTRACT FROM AUTHOR]

One of the challenges facing science/biology today is uncovering the molecular bases that support and determine animal and human longevity. Nature, in offering a diversity of animal species that differ in longevity by more than 5 orders of magnitude, is the best 'experimental laboratory' to achieve this aim. Mammals, in particular, can differ by more than 200-fold in longevity. For this reason, most of the available evidence on this topic derives from comparative physiology studies. But why can human beings, for instance, reach 120 years whereas rats only last at best 4 years? How does nature change the longevity of species? Longevity is a species-specific feature resulting from an evolutionary process. Long-lived animal species, including humans, show adaptations at all levels of biological organization, from metabolites to genome, supported by signaling and regulatory networks. The structural and functional features that define a long-lived species may suggest that longevity is a programmed biological property. Compendium of phenotypic features present in long-lived animal species. [Display omitted] • Animal longevity is a species-specific biological trait. • Oxidative metabolism is an endogenous process present throughout life at a characteristic rate in each animal species. • Oxidative metabolism is the basic biologic mechanism whose adaptations define animal longevity. • The molecular features of long-lived animal species may suggest that longevity is a programmed species-specific trait. [ABSTRACT FROM AUTHOR]

Calorie restriction (CR) is a widely recognized dietary approac h with beneficial impacts on the entire body, including enhancements in oxidative metabolism and life span extension, while maintaining nutritional balance and calorie intake. However, CR leads to reductions in skeletal muscle and fat mass due to decreased food intake. Consequently, CR significantly modifies the metabolic profile of the entire body and its tissues. The observed benefits in skeletal muscle during CR may be attributed to CR-induced signaling mediators or significant changes in blood profiles asso ciated with CR that regulate homeostasis maintenance. This study aimed to examine the mammalian target of rapamycin signaling and mitochondrial function of skeletal muscle from mice that undergone 8 weeks of CR and cells cultured in their serum to determine whether changes in blood secreted factors during CR affect skeletal musc le cells. C57BL6/J male mice were used. For 8 weeks, these were subjected to ad libitum (AL) or 40% CR. C2C12 myotubes were subsequently treated with media containing 10% mo use serum from AL or CR for 24 h. The results indicated that 8 weeks of CR dec reased muscle mass and protein synthesis response compared with the AL group. Inte restingly, myotubes conditioned with CR serum exhibited an elevation in the protein synthesis response compared with those treated with AL serum. Furthermore, mitocho ndrial function was enhanced in both CR mice and cells treated with CR serum. These findings suggest that while CR decreases the protein synthesis response, secretory factors present in the blood during CR can activate protein synthesis and promote mitochondrial function. [ABSTRACT FROM AUTHOR]

The objective of this work is to evaluate the influence of pomegranate peel extract (PPE) in the behavior of breast cell lines (epithelial and tumor type) and related oxidative metabolism. Fruit-based functional foods have been the target of increasing scientific research for their physiological and pathophysiological properties. Pomegranate (Punica granatum) is a suitable example with both prophylactic and medicinal effects. MCF-7 cell line from tumor breast carcinoma, and MCF-10A cell line from normal epithelial mammary gland were used and subjected to different concentrations of PPE, ranging from 1 to 5 mM of gallic acid equivalents (GAE). Viability, proliferation, mobility, and cytotoxicity assays were performed along with the quantification of antioxidant enzymes, namely, catalase, superoxide dismutase (SOD) and reduced (GSH) and oxidized (GSSG) glutathione. We observed a decrease in viability and proliferation of MCF-7 cells, at higher concentrations of PPE, with no influence in epithelial cells. Interestingly, in a concentration-dependent manner, PPE triggered a significant decrease in migration on both cell lines, with a more pronounced effect in breast cancer cell line. Regarding antioxidant enzyme activity, on tumor cells higher concentrations of PPE decreased catalase activity and significantly increased SOD activity. Regarding GSH and GSSG, we observed different expression levels between MCF-7 and MCF-10A, with MCF-7 presenting lower levels compared to MCF-10A. GSH/GSSG ratio was notably higher in MCF-7 at 5 mM GAE. PPE exhibits anti-tumor effects without significantly affecting normal epithelial cells. Our work strengthens the potential antitumoral effect of PPE by reducing MCF-7 cell viability and proliferation through the imbalance of antioxidant enzymes. [ABSTRACT FROM AUTHOR]

Normal contractile function of the heart depends on a constant and reliable production of ATP by cardiomyocytes. Dysregulation of cardiac energy metabolism can result in immature heart development and disrupt the ability of the adult myocardium to adapt to stress, potentially leading to heart failure. Further, restoration of abnormal mitochondrial function can have beneficial effects on cardiac dysfunction. Previously, we identified a novel protein termed Perm1 (PGC-1 and estrogen-related receptor (ERR)-induced regulator, muscle 1) that is enriched in skeletal and cardiac-muscle mitochondria and transcriptionally regulated by PGC-1 (peroxisome proliferator-activated receptor gamma coactivator 1) and ERR. The role of Perm1 in the heart is poorly understood and is studied here. We utilized cell culture, mouse models, and human tissue, to study its expression and transcriptional control, as well as its role in transcription of other factors. Critically, we tested Perm1's role in cardiomyocyte mitochondrial function and its ability to protect myocytes from stress-induced damage. Our studies show that Perm1 expression increases throughout mouse cardiogenesis, demonstrate that Perm1 interacts with PGC-1α and enhances activation of PGC-1 and ERR, increases mitochondrial DNA copy number, and augments oxidative capacity in cultured neonatal mouse cardiomyocytes. Moreover, we found that Perm1 reduced cellular damage produced as a result of hypoxia and reoxygenation-induced stress and mitigated cell death of cardiomyocytes. Taken together, our results show that Perm1 promotes mitochondrial biogenesis in mouse cardiomyocytes. Future studies can assess the potential of Perm1 to be used as a novel therapeutic to restore cardiac dysfunction induced by ischemic injury.

Understanding the complex biological processes of cells in culture, particularly those related to metabolism, can be biased by culture conditions, since the choice of energy substrate impacts all of the main metabolic pathways. When glucose is replaced by galactose, cells decrease their glycolytic flux, working as an in vitro model of limited nutrient availability. However, the effect of these changes on related physiological processes such as redox control is not well documented, particularly in endothelial cells, where mitochondrial oxidation is considered to be low. We evaluated the differences in mitochondrial dynamics and function in endothelial cells exposed to galactose or glucose culture medium. We observed that cells maintained in galactose-containing medium show a higher mitochondrial oxidative capacity, a more fused mitochondrial network, and higher intercellular coupling. These factors are documented to impact the cellular response to oxidative stress. Therefore, we analyzed the levels of two main redox regulators and found that bovine aortic endothelial cells (BAEC) in galactose media had higher levels of FOXO3 and lower levels of Nrf2 than those in glucose-containing media. Thus, cultures of endothelial cells in a galactose-containing medium may provide a more suitable target for the study of in vitro mitochondrial-related processes than those in glucose-containing media; the medium deeply influences redox signaling in these cells.

Sepsis is a major health problem in the United States (US), constituting a leading contributor to mortality among critically ill patients. Despite advances in treatment the underlying pathophysiology of sepsis remains elusive. Reactive oxygen species (ROS) have a significant role in antimicrobial host defense and inflammation and its dysregulation leads to maladaptive responses because of excessive inflammation. There is growing evidence for crosstalk between the central nervous system and the immune system in response to infection. The hypothalamic-pituitary and adrenal axis and the sympathetic nervous system are the two major pathways that mediate this interaction. Epinephrine (Epi) and norepinephrine (NE), respectively are the effectors of these interactions. Upon stimulation, NE is released from sympathetic nerve terminals locally within lymphoid organs and activate adrenoreceptors expressed on immune cells. Similarly, epinephrine secreted from the adrenal gland which is released systemically also exerts influence on immune cells. However, understanding the specific impact of neuroimmunity is still in its infancy. In this review, we focus on the sympathetic nervous system, specifically the role the neurotransmitter norepinephrine has on immune cells. Norepinephrine has been shown to modulate immune cell responses leading to increased anti-inflammatory and blunting of pro-inflammatory effects. Furthermore, there is evidence to suggest that norepinephrine is involved in regulating oxidative metabolism in immune cells. This review attempts to summarize the known effects of norepinephrine on immune cell response and oxidative metabolism in response to infection.