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Lactate accumulation and macrophage infiltration are pivotal features of both chronic inflammation and cancer. Lactate, once regarded merely as an aftereffect of glucose metabolism, is now gaining recognition for its burgeoning spectrum of biological roles and immunomodulatory significance. Recent studies have evidenced that macrophages display divergent immunophenotypes in different diseases, which play a pivotal role in disease management by modulating macrophage polarization within the disease microenvironment. The specific polarization patterns of macrophages in a high-lactate environment and their contribution to the progression of chronic inflammation and cancer remain contentious. This review presents current evidence on the crosstalk of lactate and macrophage in chronic inflammation and cancer. Additionally, we provide an in-depth exploration of the pivotal yet enigmatic mechanisms through which lactate orchestrates disease pathogenesis, thereby offering novel perspectives to the development of targeted therapeutic interventions for chronic inflammation and cancer.

Barrett’s esophagus (BE) is a common precancerous lesion that can progress to esophageal adenocarcinoma (EAC). There are significant alterations in the esophageal microbiome in the progression from healthy esophagus to BE to EAC, including an increased abundance of a variety of lactate-producing bacteria and an increase of lactate in the tumor microenvironment, as predicted by metabolic modeling. The role of bacterial lactate in EAC is unknown. Here, we utilize patient-derived organoid (PDO) models of EAC and demonstrate that lactate inhibits the growth and proliferation of EAC PDOs through alterations in the tumor NADH/NAD+ redox state. Further RNA sequencing of EAC PDOs identifies ID1 and RSAD2 as potential regulatory molecules crucial in mediating lactate’s ability to suppress glycolysis and proliferation. Gene ontology analysis also identifies the activation of inflammatory and immunological pathways in addition to alterations in the metabolic pathways in EAC PDOs exposed to lactate, suggesting a multi-faceted role for lactate in the pathogenesis of EAC.

Cancer cells can release EGF-like peptides, acquiring the capacity of autocrine stimulation via EGFR-mediated signaling. One of these peptides (HBEGF) was found to be released from a membrane-bound precursor protein and is critically implicated in the proliferative potential of cancer cells. We observed that the increased lactate levels characterizing neoplastic tissues can induce the release of uPA, a protease promoting HBEGF shedding. This effect led to EGFR activation and increased ERK1/2 phosphorylation. Since EGFR-mediated signaling potentiates glycolytic metabolism, this phenomenon can induce a self-sustaining deleterious loop, favoring tumor growth. A well characterized HBEGF inhibitor is CRM197, a single-site variant of diphtheria toxin. We observed that, when administered individually, CRM197 did not trigger evident antineoplastic effects. However, its association with a uPA inhibitor caused dampening of EGFR-mediated signaling and apoptosis induction. Overall, our study highlights that the increased glycolytic metabolism and lactate production can foster the activated state of EGFR receptor and suggests that the inhibition of EGFR-mediated signaling can be attempted by means of CRM197 administered with an appropriate protease inhibitor. This attempt could help in overcoming the problem of the acquired resistance to the conventionally used EGFR inhibitors.

Background/Objectives: Hyperlactatemia is a common predictive factor for poor post-cardiovascular surgery outcomes. However, it is not well understood whether the rapid postoperative lactate level elevation in a short period of time is associated with patient outcomes. Herein, we investigated the relationship between the degree of change in serum lactate levels and postoperative serious adverse events (PSAEs), including mortality, within 24 h of cardiovascular surgery. Methods: In this retrospective study, we evaluated the relationship between a rapid serum lactate level increase and PSAEs after open-heart and major vascular surgery. We divided the patients into those with and without PSAEs. Univariate and multivariate analyses were performed to evaluate the association between PSAEs and rapid lactate level increases. Results: We enrolled 445 patients; 16% (n = 71) had PSAEs. The peak lactate levels during the first 24 h of intensive care unit (ICU) stay were higher in patients with PSAEs than in those without. The maximum change in lactate levels between two consecutive lactate measurements during the first 24 h after ICU admission was higher in patients with PSAEs than in those without. A multivariate logistic regression analysis revealed that changes in lactate levels of 2 mmol/L or more between two consecutive lactate measurements were associated with PSAEs. ICU peak lactate levels of 3 mmol/L or more were not associated with PSAEs. Conclusions: Rapid serum lactate level increases of 2 mmol/L or more during the first 24 h of ICU admission post-cardiovascular surgery are associated with PSAEs.

Background: The prognostic value of baseline inflammatory markers in sepsis remains controversial, with conflicting evidence regarding their association with mortality. The dynamic changes in these markers over time might offer additional insights into disease progression and patient outcomes. Methods: This retrospective observational study included 138 patients with severe infections. The inflammatory biomarkers procalcitonin (PCT), C-reactive protein (CRP), and lactate (LAC) were measured at three time points: upon hospital admission (baseline), approximately 24–48 h after admission (second measurement; M2), and 48–72 h after admission (third measurement; M3). The primary outcome was 30-day mortality. A Mann–Whitney U test was used to compare the biomarker levels between the survivors and non-survivors. A Spearman’s correlation was used to assess the relationships between the baseline parameters. A logistic regression and a receiver operating characteristic (ROC) curve analysis were employed to evaluate the prognostic value of the baseline markers and their dynamic changes. Results: The baseline LAC and SOFA score were significantly associated with 30-day mortality. The percentage decrease in PCT, CRP, and LAC from the baseline to M3 emerged as strong predictors of survival, with the ROC curve analysis demonstrating superior discriminatory ability compared to the baseline values. CRP_Delta exhibited the highest AUC (0.903), followed by PCT_Delta (0.843) and LAC_Delta (0.703). Conclusions: The dynamic changes in these inflammatory biomarkers, particularly PCT, CRP, and LAC, offer valuable prognostic information beyond their baseline levels in predicting 30-day mortality in severe infections. These findings highlight the importance of monitoring biomarker trends for early risk stratification and potential treatment guidance.

The lactate to albumin ratio (LAR) has been associated with the severity and outcome of critical illness and sepsis. However, there are no studies on the kinetics of the LAR during the early phase of sepsis. Therefore, we aimed to investigate the LAR and its kinetics in critically ill patients with new onset sepsis regarding the severity and outcome of sepsis. We prospectively enrolled 102 patients with sepsis or septic shock within 48 h from diagnosis. LARs were recorded at inclusion in the study and one week later. Patients were followed for 28 days. LAR was significantly lower one week after enrollment compared to baseline in all patients (p < 0.001). LARs were significantly higher in patients with septic shock and in nonsurvivors compared to patients with sepsis and survivors, respectively, both at inclusion (p < 0.001, p < 0.001) and at one week later (p < 0.001, p < 0.001). LARs at baseline were positively associated with the severity of sepsis (APACHE II: r = 0.29, p = 0.003; SOFA: r = 0.33, p < 0.001) and inflammatory biomarkers, such as C-reactive protein (r = 0.29, p < 0.1), procalcitonin (r = 0.47, p < 0.001), interleukin 6 (r = 0.28, p = 0.005) interleukin 10 (r = 0.3, p = 0.002) and suPAR (r = 0.28, p = 0.004). In addition, a higher LAR, but not its kinetics, was an independent predictor of 28-day mortality (at inclusion: HR 2.27, 95% C.I. 1.01–5.09, p = 0.04; one week later: HR: 4.29, 95% C.I. 1.71–10.78, p = 0.002). In conclusion, the LAR may be a valuable prognostic indicator in critically ill patients with sepsis at admission and one week later.

6′-Sialyllactose (6′-SL), found in human breast milk, exhibits anti-inflammatory, immune function-enhancing, brain development-promoting, and gut health-improving effects. However, its effects on muscle fatigue remain unknown. Here, we aimed to investigate the effects of 6′-SL on blood lactate level, muscle fiber type, and oxidative phosphorylation protein complexes (OXPHOS) in muscle after exercise using C57BL/6J male mice. C57BL/6J mice were randomly assigned to control or 100 mg/kg 6′-SL. After 12 weeks of 6′-SL administration, the mice were made to perform treadmill exercise; their blood lactate and glucose levels were measured at the basal level (rest) and 0, 5, and 10 min after treadmill exercise. Results showed that 6′-SL treatment in C57BL/6J mice significantly reduced blood lactate level and improved blood glucose level. Moreover, 6′-SL increased the expression of slow-myosin heavy chain (MHC) and OXPHOS in gastrocnemius muscle. In addition, 6′-SL treatment for 12 weeks did not affect food intake, serum biomarkers of tissue injury, and lipid profiles compared with those of the controls. These findings indicate that non-toxic 6′-SL suppressed muscle fatigue during exercise by promoting protein expression of muscle fibers, especially slow-twitch muscle fibers characterized by abundant OXPHOS complexes and decreased blood lactate level. This study suggests that 6′-SL holds promise as a nutritional supplement in exercise and clinical settings, subject to further validation.

Trail runners (TRs) must carry an extra load of equipment, food (bars and gels) and liquids, to delay the anticipation of fatigue and dehydration during their competitions. Therefore, we aimed to evaluate how an extra load can influence the metabolic level. Thirteen well-trained trail runners performed a randomized crossover study (total n = 39), completing three treadmill running sessions with a weighted vest of 0%, 5% and 10% of their body mass during a combined test (rectangular test + ramp test). In addition, biomarkers of oxygen metabolism, acid–base and electrolyte status pre-, during and post-test, as well as the rectangular from capillary blood of the finger and time to exhaustion, were analyzed. Repeated-measures ANOVA showed no significant difference between conditions for any of the analyzed biomarkers of blood gas. However, one-way ANOVA showed a significant difference in trial duration between conditions (p ≤ 0.001). Tukey’s post hoc analysis observed a significant decrease in time to exhaustion in the weighted vest of 10% compared to 0% (p ≤ 0.001) and 5% (p ≤ 0.01) and 5% compared to 0% (p = 0.030). In addition, repeated-measures ANOVA detected a significant difference in pH in the group x time interaction (p = 0.035). Our results show that increasing the weighted vest (5% and 10%) anticipates fatigue in runners trained in TR. In addition, increasing the load decreased pH by a smaller magnitude at 10% compared to 0% and 5% at the end of the exercise protocol.

Rowing races require extreme physical and psychological effort from every athlete. This study aimed to determine the dynamics of the salivary cortisol and alpha-amylase, as well as blood lactate throughout the specific load represented by a 6 km rowing race, conducted on a rowing ergometer. The sample consisted of 11 junior and senior rowers from HVK Gusar in Split (n = 11) who actively competed at club and international levels. Variables consisted of three repeated oral samples of the hormone cortisol and the enzyme alpha-amylase determined in saliva and three repeated blood lactate samples. Potential differences in the levels of the studied variables at different time points were determined using a repeated-measures ANOVA test. The results showed different dynamics of hormonal (cortisol) and metabolic (alpha-amylase and lactates) variables. All variables experienced a significant post-race increase, while other changes were not significant. The results highlighted that high-intensity rowing causes an increase in the body’s cortisol, alpha-amylase, and lactate levels. This should be implemented in rowing training to find the right balance between high and low-intensity rowing, enabling athletes’ progression while reducing the risk of overtraining.

During some trail running races, athletes have to carry hydration support, food, and technical and safety equipment, which generates an additional load that must be mobilized during the race. The aim of the present study was to determine the physiological responses to overload running and the effect they may have on metabolic zones. Seventeen well-trained male trail runners (n = 17) completed three maximal treadmill tests with weighted vests at 0%, 5%, and 10% of their body mass (L0, L5, and L10). Their gas exchange was monitored to assess their ventilatory thresholds 1 (VT1) and 2 (VT2), maximal fat oxidation zone (FatMax), and peak oxygen consumption (VO2peak). Their heart rate (HR), power, and velocity (V) were tracked to compare their behavior. One-way ANOVA showed significant differences in the V (p < 0.001; ηp2 = 0.4620) as a limitation for reaching the peak velocity (Vpeak), with a significant decrease in the Vpeak with the L10 compared to the L0 (p = 0.002) and L5 (p = 0.004). In addition, one-way ANOVA showed significant differences in the peak absolute power (p < 0.001; ηp2 = 0.468) among the groups, detecting higher power production between the L10 and L0 (p < 0.001) and between the L10 and L5 (p = 0.015). Loads higher than L5 could generated important physiological and mechanical modifications, while a load of L5 managed to maintain the working conditions without overloading. These insights shed light on nuanced strategies for optimizing performance and endurance, offering valuable considerations for athletes seeking to enhance their training regimens during overload conditions.

Believed for a long time to be merely a waste product of cell metabolism, lactate is now considered a molecule with several roles, having metabolic and signalling functions together with a new, recently discovered role as an epigenetic modulator. Lactate produced by the skeletal muscle during physical exercise is conducted to the liver, which uses the metabolite as a gluconeogenic precursor, thus generating the well-known “Cori cycle”. Moreover, the presence of lactate in the mitochondria associated with the lactate oxidation complex has become increasingly clear over the years. The signalling role of lactate occurs through binding with the GPR81 receptor, which triggers the typical signalling cascade of the G-protein-coupled receptors. Recently, it has been demonstrated that lactate regulates chromatin state and gene transcription by binding to histones. This review aims to describe the different roles of lactate in skeletal muscle, in both healthy and pathological conditions, and to highlight how lactate can influence muscle regeneration by acting directly on satellite cells.

A complex evaluation of colorectal cancer (CRC) in relation to screening, diagnosis, stage determination, prognosis, and treatment requires valuable biomarkers. The aim of this study was to measure selected biomarkers—uric acid (UA), lactate, Na+, Cl−, and osmolality—in CRC patients and to assess their diagnostic value to distinguish between CRC and healthy controls. Plasma lactate (2.21 ± 0.11 vs. 2.88 ± 0.19, p < 0.01), Na+ (130.79 ± 0.42 vs. 133.23 ± 0.25, p < 0.001), Cl− (102.59 ± 0.45 vs. 103.94 ± 0.23, p < 0.01), and osmolality (266.44 ± 0.86 vs. 271.72 ± 0.62, p < 0.001) were found to be significantly lower in CRC patients as compared to the healthy controls group. Among them, with satisfactory diagnostic potential, were plasma Na+ concentrations and osmolality (AUCNa+ = 0.752, p < 0.0001; AUCosmolality = 0.757, p < 0.05), respectively. UA concentrations were detected at higher concentrations in CRC patients (333.67 ± 13.05 vs. 295.88 ± 13.78, p < 0.05). The results of this study contribute to the elucidation of molecular mechanisms of CRC pathogenesis and the role of studied metabolic parameters in this process. Plasma uric acid, lactate, and osmolality parameters can be used for screening and monitoring colorectal cancer. Further studies are required to elucidate the molecular mechanisms of their action in cancer development. The action of circulating plasma lactate may be different from those locally produced in the tumor microenvironment.

The tumor cells reprogram their metabolism to cover their high bioenergetic demands for maintaining uncontrolled growth. This response can be mediated by cytokines such as IL-2, which binds to its receptor and activates the JAK/STAT pathway. Some reports show a correlation between the JAK/STAT pathway and cellular metabolism, since the constitutive activation of STAT proteins promotes glycolysis through the transcriptional activation of genes related to energetic metabolism. However, the role of STAT proteins in the metabolic switch induced by cytokines in cervical cancer remains poorly understood. In this study, we analyzed the effect of IL-2 on the metabolic switch and the role of STAT5 in this response. Our results show that IL-2 induces cervical cancer cell proliferation and the tyrosine phosphorylation of STAT5. Also, it induces an increase in lactate secretion and the ratio of NAD+/NADH, which suggest a metabolic reprogramming of their metabolism. When STAT5 was silenced, the lactate secretion and the NAD+/NADH ratio decreased. Also, the expression of HIF1α and GLUT1 decreased. These results indicate that STAT5 regulates IL-2-induced cell proliferation and the metabolic shift to aerobic glycolysis by regulating genes related to energy metabolism. Our results suggest that STAT proteins modulate the metabolic switch in cervical cancer cells to attend to their high demand of energy required for cell growth and proliferation.

Here, a comprehensive investigation was conducted under various operational strategies aimed at enhancing biohydrogen production via dark fermentation, with a specific focus on the lactate metabolic pathway, using powdered cheese whey as a substrate. Initially, a batch configuration was tested to determine both the maximum hydrogen yield (100.2 ± 4.2 NmL H2/g CODfed) and the substrate (total carbohydrates) consumption efficiency (94.4 ± 0.8%). Subsequently, a transition to continuous operation was made by testing five different operational phases: control (I), incorporation of an inert support medium for biomass fixation (II), addition of carbon-coated, zero-valent iron nanoparticles (CC-nZVI NPs) at 100 mg/L (III), and supplementation of Fe2O3 nanoparticles at concentrations of 100 mg/L (IV) and 300 mg/L (V). The results emphasized the critical role of the support medium in stabilizing the continuous system. On the other hand, a remarkable increase of 10% in hydrogen productivity was observed with the addition of Fe2O3 NPs (300 mg/L). The analysis of the organic acids’ composition unveiled a positive correlation between high butyrate concentrations and improved volumetric hydrogen production rates (25 L H2/L-d). Moreover, the presence of iron-based NPs effectively regulated the lactate concentration, maintaining it at low levels. Further exploration of the bacterial community dynamics revealed a mutually beneficial interaction between lactic acid bacteria (LAB) and hydrogen-producing bacteria (HPB) throughout the experimental process, with Prevotella, Clostridium, and Lactobacillus emerging as the predominant genera. In conclusion, this study highlighted the promising potential of nanoparticle addition as a tool for boosting biohydrogen productivity via lactate-driven dark fermentation.

Tissue hypoxia is associated with the development of organ dysfunction and death in critically ill patients commonly captured using blood lactate. The kinetic parameters of serial lactate evaluations are superior at predicting mortality compared with single values. S-adenosylhomocysteine (SAH), which is also associated with hypoxia, was recently established as a useful predictor of septic organ dysfunction and death. We evaluated the performance of kinetic SAH parameters for mortality prediction compared with lactate parameters in a cohort of critically ill patients. For lactate and SAH, maxima and means as well as the normalized area scores were calculated for two periods: the first 24 h and the total study period of up to five days following ICU admission. Their performance in predicting in-hospital mortality were compared in 99 patients. All evaluated parameters of lactate and SAH were significantly higher in non-survivors compared with survivors. In univariate analysis, the predictive power for mortality of SAH was higher compared with lactate in all forms of application. Multivariable models containing SAH parameters demonstrated higher predictive values for mortality than models based on lactate parameters. The optimal models for mortality prediction incorporated both lactate and SAH parameters. Compared with lactate, SAH displayed stronger predictive power for mortality in static and dynamic application in critically ill patients.

Red spinach extract is high in inorganic nitrate/nitrite (NO3/NO2) which has been shown to enhance vascular function, cognition, and physical performance. To date, there have been no investigations as to whether red spinach extract serves as an effective strategy to improve repeated exercise performance, which is applicable to many sports and activities. The purpose of this study was to investigate the effect of acute red spinach extract ingestion on repeated sprint ability in female athletes. Eleven Division I NCAA female athletes (ages 18–24) were recruited. In a double-blinded, randomized, counterbalanced design, participants completed two separate visits each with a different treatment: placebo (placebo; tomato juice) or red spinach extract (~400 mg nitrate). For each trial, participants consumed their respective treatment two hours before exercise. Following a warm-up, participants completed 3 × 15 s Wingate Anaerobic Tests (WAnTs) separated by 2 min of recovery. A capillary blood sample was obtained pre-exercise to measure NO2 concentrations. Performance outcomes, heart rate (heart rate), and rate of perceived exertion were measured following each WAnT. Blood lactate (La-) was obtained prior to exercise (PRE) and after the completion of the repeated sprints (POST). Each visit was separated by a minimal recovery period of 72 h. Mean power (p = 0.204), peak power (p = 0.067), heart rate (p = 0.151), and rate of perceived exertion (p = 0.379) were not significantly different between treatments. POST La- concentration was significantly higher with red spinach extract when compared to the placebo (p = 0.030). Furthermore, the fatigue index (p = 0.018) was significantly lower with red spinach extract. The results do not support the use of red spinach extract for the enhancement of power output during repeated anaerobic exercise. However, it may result in improved La-/H+ removal from the muscle, thereby combating physical fatigue.

Human evolution is characterized by rapid brain enlargement and the emergence of unique cognitive abilities. Besides its distinctive cytoarchitectural organization and extensive inter-neuronal connectivity, the human brain is also defined by high rates of synaptic, mainly glutamatergic, transmission, and energy utilization. While these adaptations’ origins remain elusive, evolutionary changes occurred in synaptic glutamate metabolism in the common ancestor of humans and apes via the emergence of GLUD2, a gene encoding the human glutamate dehydrogenase 2 (hGDH2) isoenzyme. Driven by positive selection, hGDH2 became adapted to function upon intense excitatory firing, a process central to the long-term strengthening of synaptic connections. It also gained expression in brain astrocytes and cortical pyramidal neurons, including the CA1-CA3 hippocampal cells, neurons crucial to cognition. In mice transgenic for GLUD2, theta-burst-evoked long-term potentiation (LTP) is markedly enhanced in hippocampal CA3-CA1 synapses, with patch-clamp recordings from CA1 pyramidal neurons revealing increased sNMDA receptor currents. D-lactate blocked LTP enhancement, implying that glutamate metabolism via hGDH2 potentiates L-lactate-dependent glia–neuron interaction, a process essential to memory consolidation. The transgenic (Tg) mice exhibited increased dendritic spine density/synaptogenesis in the hippocampus and improved complex cognitive functions. Hence, enhancement of neuron–glia communication, via GLUD2 evolution, likely contributed to human cognitive advancement by potentiating synaptic plasticity and inter-neuronal connectivity.

Streptococcus pyogenes, group A streptococci (GAS) bacteriaemia, is a life-threatening infection with high mortality, requiring fast diagnosis together with the use of appropriate antibiotic therapy as soon as possible. Our study analysed data from 93 patients with GAS bacteraemia at the General University Hospital in Prague between January 2006 and March 2024. In the years 2016–2019 there was an increase in GAS bacteraemia. Mortality in the period 2006–2019 was 21.9%; in the period 2020–2024, the mortality increased to 41.4%, p = 0.08. At the same time, in the post-2020 period, the time from hospital admission to death was reduced from 9.5 days to 3 days. A significant predictor of worse outcome in this period was high levels of procalcitonin, >35.1 µg/L (100% sensitivity and 82.35% specificity), and lactate, >5 mmol/L (90.91% sensitivity and 91.67% specificity). Myoglobin was a significant predictor in both compared periods, the AUC was 0.771, p = 0.044, and the AUC was an even 0.889, p ≤ 0.001, respectively. All isolates of S. pyogenes were susceptible to penicillin, and resistance to clindamycin was 20.3% from 2006–2019 and 10.3% in 2020–2024. Appropriate therapy was initiated in 89.1%. and 96.6%, respectively. We hypothesise that the increase in mortality after 2020 might be due to a decrease in the immune status of the population.

Disuse muscle atrophy (DMA) is a significant healthcare challenge characterized by progressive loss of muscle mass and function resulting from prolonged inactivity. The development of effective strategies for muscle recovery is essential. In this study, we established a DMA mouse model through hindlimb suspension to evaluate the therapeutic potential of lactate in alleviating the detrimental effects on the gastrocnemius muscle. Using NMR-based metabolomic analysis, we investigated the metabolic changes in DMA-injured gastrocnemius muscles compared to controls and evaluated the beneficial effects of lactate treatment. Our results show that lactate significantly reduced muscle mass loss and improved muscle function by downregulating Murf1 expression, decreasing protein ubiquitination and hydrolysis, and increasing myosin heavy chain levels. Crucially, lactate corrected perturbations in four key metabolic pathways in the DMA gastrocnemius: the biosynthesis of phenylalanine, tyrosine, and tryptophan; phenylalanine metabolism; histidine metabolism; and arginine and proline metabolism. In addition to phenylalanine-related pathways, lactate also plays a role in regulating branched-chain amino acid metabolism and energy metabolism. Notably, lactate treatment normalized the levels of eight essential metabolites in DMA mice, underscoring its potential as a therapeutic agent against the consequences of prolonged inactivity and muscle wasting. This study not only advances our understanding of the therapeutic benefits of lactate but also provides a foundation for novel treatment approaches aimed at metabolic restoration and muscle recovery in conditions of muscle wasting.

Coastal environments present dynamic challenges necessitating rapid and efficient responses during aquatic emergencies. Lifeguards, as pivotal links in the intervention chain, rely on various tools, with rescue time being paramount. The choice of fins, specifically long versus short ones, plays a critical role in optimizing lifeguard performance during rescues. This randomized cross-over study explores the impact of flipper size on ocean rescues, employing a sample of 14 lifeguards. Long fins (LFs) and short fins (SFs) were compared in terms of rescue time (RT) and physiological load (PL). Tests included ocean rescues without fins (R), with LF (R-LF), and with SF (R-SF). Variables recorded encompassed swim approach time, tow-in time, overall rescue time, perceived exertion rates (RPEs), and post-rescue lactate concentration. Long fins demonstrated superior performance in swim approach and tow-in times compared to both short fins and no fins (p < 0.001). Overall rescue time favored long fins significantly (p < 0.001), indicating their efficiency in practical ocean rescue scenarios. Physiologically, long fins induced lower perceived exertion in arms (p = 0.033) compared to short fins. Lactate concentrations post-rescue revealed no significant differences (p > 0.05). This study demonstrates that long fins significantly improve lifeguard performance during ocean rescues, reducing rescue times and alleviating arm fatigue.

Campylobacter jejuni is the leading cause of foodborne human gastroenteritis in the developed world. Infections are largely acquired from poultry produced for human consumption and poor food handling is thus a major risk factor. Chicken exudate (CE) is a liquid produced from defrosted commercial chicken products that facilitates C. jejuni growth. We examined the response of C. jejuni to growth in CE using a multi-omics approach. Changes in the C. jejuni proteome were assessed by label-based liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We quantified 1328 and 1304 proteins, respectively, in experiments comparing 5% CE in Mueller–Hinton (MH) medium and 100% CE with MH-only controls. These proteins represent 81.8% and 80.3% of the predicted C. jejuni NCTC11168 proteome. Growth in CE induced profound remodelling of the proteome. These changes were typically conserved between 5% and 100% CE, with a greater magnitude of change observed in 100% CE. We confirmed that CE induced C. jejuni biofilm formation, as well as increasing motility and resistance against oxidative stress, consistent with changes to proteins representing those functions. Assessment of the C. jejuni metabolome showed CE also led to increased intracellular abundances of serine, proline, and lactate that were correlated with the elevated abundances of their respective transporters. Analysis of carbon source uptake showed prolonged culture supernatant retention of proline and succinate in CE-supplemented medium. Metabolomics data provided preliminary evidence for the uptake of chicken-meat-associated dipeptides. C. jejuni exposed to CE showed increased resistance to several antibiotics, including polymyxin B, consistent with changes to tripartite efflux system proteins and those involved in the synthesis of lipid A. The C. jejuni CE proteome was also characterised by very large increases in proteins associated with iron acquisition, while a decrease in proteins containing iron–sulphur clusters was also observed. Our data suggest CE is both oxygen- and iron-limiting and provide evidence of factors required for phenotypic remodelling to enable C. jejuni survival on poultry products.

Numerous post-translational modifications are involved in oocyte maturation and embryo development. Recently, lactylation has emerged as a novel epigenetic modification implicated in the regulation of diverse cellular processes. However, it remains unclear whether lactylation occurs during oocyte maturation and embryo development processes. Herein, the lysine lactylation (Kla) modifications were determined during mouse oocyte maturation and early embryo development by immunofluorescence staining. Exogenous lactate was supplemented to explore the consequences of modulating histone lactylation levels on oocyte maturation and embryo development processes by transcriptomics. Results demonstrated that lactylated proteins are widely present in mice with tissue- and cell-specific distribution. During mouse oocyte maturation, immunofluorescence for H3K9la, H3K14la, H4K8la, and H4K12la was most intense at the germinal vesicle (GV) stage and subsequently weakened or disappeared. Further, supplementing the culture medium with 10 mM sodium lactate elevated both the oocyte maturation rate and the histone Kla levels in GV oocytes, and there were substantial increases in Kla levels in metaphase II (MII) oocytes. It altered the transcription of molecules involved in oxidative phosphorylation. Moreover, histone lactylation levels changed dynamically during mouse early embryogenesis. Sodium lactate at 10 mM enhanced early embryo development and significantly increased lactylation, while impacting glycolytic gene transcription. This study reveals the roles of lactylation during oocyte maturation and embryo development, providing new insights to improving oocyte maturation and embryo quality.

L-Lactate is an important bioanalyte in the food industry, biotechnology, and human healthcare. In this work, we report the development of a new L-lactate electrochemical biosensor based on the use of multiwalled carbon nanotubes non-covalently functionalized with avidin (MWCNT-Av) deposited at glassy carbon electrodes (GCEs) as anchoring sites for the bioaffinity-based immobilization of a new recombinant biotinylated lactate oxidase (bLOx) produced in Escherichia coli through in vivo biotinylation. The specific binding of MWCNT-Av to bLOx was characterized by amperometry, surface plasmon resonance (SPR), and electrochemical impedance spectroscopy (EIS). The amperometric detection of L-lactate was performed at −0.100 V, with a linear range between 100 and 700 µM, a detection limit of 33 µM, and a quantification limit of 100 µM. The proposed biosensor (GCE/MWCNT-Av/bLOx) showed a reproducibility of 6.0% and it was successfully used for determining L-lactate in food and enriched serum samples.

Lactate has emerged as a key player in regulating neural functions and cognitive processes. Beyond its function as an energy substrate and signal molecule, recent research has revealed lactate to serve as an epigenetic regulator in the brain. However, the molecular mechanisms by which lactate regulates spatial memory and its role in the prevention of cognitive disorders remain unclear. Herein, we injected L-lactate (10 μmol/kg/d for 6 d) into the mouse’s hippocampus, followed by the Morris water maze (MWM) test and molecular analyses. Improved spatial memory performances were observed in mice injected with lactate. Besides, lactate upregulated the expression of synaptic proteins post-synaptic density 95 (PSD95), synaptophysin (SYP), and growth associated protein 43 (GAP43) in hippocampal tissues and HT22 cells, suggesting a potential role in synaptic transmission and memory formation. The facilitative role of monocarboxylate transporter 2 (MCT2), a neuron-specific lactate transporter, in this process was confirmed, as MCT2 antagonists attenuated the lactate-induced upregulation of synaptic proteins. Moreover, lactate induced protein lactylation, a post-translational modification, which could be suppressed by MCT2 inhibition. RNA sequencing of lactated-injected hippocampal tissues revealed a comprehensive gene expression profile influenced by lactate, with significant changes in genes associated with transcriptional progress. These data demonstrate that hippocampal lactate injection enhances spatial memory in mice, potentially through the upregulation of synaptic proteins and induction of protein lactylation, with MCT2 playing a crucial role in these processes. Our findings shed light on the multi-faceted role of lactate in neural function and memory regulation, opening new avenues for therapeutic interventions targeting cognitive disorders.

The neuroblastoma cell lines SH-SY5Y and Neuro2A are commonly utilized models in neurobiological research. DMEM supplemented with different nutrients and 5–10% Fetal Calf Serum (FCS) is typically used for culturing these cell lines. During special treatments, a reduced FCS content is often deployed to reduce cellular proliferation or the content of bioactive compounds. The impact of the reduction of FCS in culture media on the metabolic profile of SH-SY5Y and Neuro2A cells is currently unknown. Using an Amplex Red Assay, this study showed that the consumption of L-glutamine decreased after FCS reduction. Glucose and pyruvate consumption increased in both cell lines after the reduction of FCS. Thus, lactate production also increased with reduced FCS concentration. The reduction of FCS in the cell culture medium resulted in a reduced aerobic ATP production for SH-SY5Y cells and a complete shut down of aerobic ATP production for Neuro2A cells, measured using the Seahorse XF Real-Time ATP Rate Assay. Utilizing the Seahorse XF Glutamine Oxidation Stress Test, Neuro2A cells showed an increased utilization of L-glutamine oxidation after reduction of FCS. These results indicate that changes in FCS concentration in culture media have an impact on the different energy production strategies of SH-SY5Y and Neuro2A cells which must be considered when planning special treatments.

Background: Knowledge on the effect of heat on recovery is still incomplete. The present study aimed to evaluate the effect of a passive acute hyperthermic stimulus before and after a lactic anaerobic test on the production and oxidation of lactate blood concentrations. In addition, the purpose was to evaluate the effect that the application of this previous hyperthermic stimulus may have on the athletic performance in the test. Methods: For this purpose, a cross-over design through an anaerobic treadmill test in three different situations (normothermia, pre-test hyperthermia, and post-test hyperthermia) was performed. Twelve male subjects participated (age: 21.25 ± 1.64 years; height: 1.76 m ± 0.08; weight: 72.59 ± 9.44 kg). An anthropometric assessment was carried out with weight, height, skinfolds, body perimeters and diameters, and external and internal body temperatures in each of the tests. A nutritional survey was also carried out 48 h prior to each test. Results: The results of the study showed a decrease in blood lactate concentrations when the hyperthermic effect was applied as passive recovery just after the end of the test (p < 0.05). A decrease in lactate concentrations was also achieved when applying the hyperthermic effect just before the start of the test (p < 0.05). However, no significant improvements were obtained from this application of heat on test performance. Conclusions: The results suggest that the application of passive acute hyperthermia has a favourable effect in terms of decreasing blood lactate concentrations in a 5 min recovery period after lactic anaerobic activity.

Introduction: Numerous studies suggest that alterations in blood parameters, such as changes in platelet, lymphocyte, hemoglobin, eosinophil, and basophil counts; increased neutrophil counts; and elevated neutrophil/lymphocyte and platelet/lymphocyte ratios, signal COVID-19 infection and predict worse outcomes. Leveraging these insights, our study seeks to create a predictive mortality model by assessing age and crucial laboratory markers. Materials and Methods: Patients were categorized into two groups based on their hospital outcomes: 130 survivors who recovered from their Intensive Care Unit (ICU) stay (Group 1) and 74 who died (Group 2). We then developed a predictive mortality model using patients’ age, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), procalcitonin levels, and ferritin lactate (FL) index results. Results: A total of 204 patients were included. Patients in Group 2 had a notably higher mean age compared to those in Group 1 (76 ± 11 vs. 66 ± 15 years) (p < 0.001). Using specific cut-off values, our analysis revealed varying effectiveness in predicting COVID-19 mortality: Those aged over 73 years showed 74% sensitivity and 60% specificity, with an area under the curve (AUC) of 0.701. Procalcitonin levels above 0.35 ng/mL balanced true-positive and -negative identifications well, achieving an AUC of 0.752. The FL index, with a threshold of 1228 mg/dL, had 68% sensitivity and 65% specificity with an AUC of 0.707. A PLR higher than 212 resulted in 48% sensitivity and 69% specificity, with an AUC of 0.582. An NLR higher than 5.8 resulted in 55% sensitivity and 63% specificity, with an AUC of 0.640, showcasing diverse predictive accuracies across parameters. The statistical analysis evaluated the effects of age (>73), procalcitonin levels (>0.35), FL > 1228, PLR > 212, and NLR > 5.8 on mortality variables using logistic regression. Ages over 73 significantly increased event odds by 2.1 times (p = 0.05), procalcitonin levels above 0.35 nearly quintupled the odds (OR = 5.6, p < 0.001), high FL index levels more than tripled the odds (OR = 3.5, p = 0.003), a PLR > 212 significantly increased event odds by 3.5 (p = 0.030), and an NLR > 5.8 significantly increased event odds by 1.6 (p = 0.043). Conclusions: Our study highlights significant predictors of mortality in COVID-19 ICU patients, including advanced age, elevated procalcitonin, FL index levels, the PLR, and the NLR.

Lactate, once merely regarded as an indicator of tissue hypoxia and muscular fatigue, has now gained prominence as a pivotal biomarker across various medical disciplines. Recent research has unveiled its critical role as a high-value prognostic marker in critical care medicine. The current practice of lactate detection involves periodic blood sampling. This approach is invasive and confined to measurements at six-hour intervals, leading to resource expenditure, time consumption, and patient discomfort. This review addresses non-invasive sensors that enable continuous monitoring of lactate in critical care patients. After the introduction, it discusses the iontophoresis system, followed by a description of the structural materials that are universally employed to create an interface between the integumentary system and the sensor. Subsequently, each method is detailed according to its physical principle, outlining its advantages, limitations, and pertinent aspects. The study concludes with a discussion and conclusions, aiming at the design of an intelligent sensor (Internet of Medical Things or IoMT) to facilitate continuous lactate monitoring and enhance the clinical decision-making support system in critical care medicine.

In cyanobacteria, the interplay of ATP and lactate dynamics underpins cellular energetics; their pronounced shifts in response to zero-valent iron (nZVI) nanoparticles and ampicillin highlight the nuanced metabolic adaptations to environmental challenges. In this study, we investigated the impact of nZVIs and ampicillin on Fremyella diplosiphon cellular energetics as determined by adenosine triphosphate (ATP) content, intracellular and extracellular lactate levels, and their impact on cell morphology as visualized by transmission electron microscopy. While a significant increase in ATP concentration was observed in 0.8 mg/L ampicillin-treated cells compared to the untreated control, a significant decline was noted in cells treated with 3.2 mg/L nZVIs. ATP levels in the combination regimen of 0.8 mg/L ampicillin and 3.2 mg/L nZVIs were significantly elevated (p < 0.05) compared to the 3.2 mg/L nZVI treatment. Intracellular and extracellular lactate levels were significantly higher in 0.8 mg/L ampicillin, 3.2 mg/L nZVIs, and the combination regimen compared to the untreated control; however, extracellular lactate levels were the highest in cells treated with 3.2 mg/L nZVIs. Visualization of morphological changes indicated increased thylakoid membrane stacks and inter-thylakoidal distances in 3.2 mg/L nZVI-treated cells. Our findings demonstrate a complex interplay of nanoparticle and antibiotic-induced responses, highlighting the differential impact of these stressors on F. diplosiphon metabolism and cellular integrity.

Objective: To explore the lactate-related genes (LRGs) in lung adenocarcinoma (LUAD) by various methods, construct a prognostic model, and explore the relationship between lactate subtypes and the immune tumor microenvironment (TME). Methods: 24 LRGs were collected. The mutation landscape and the prognosis value of LRGs were explored by using The Cancer Genome Atlas (TCGA) data. Consensus clustering analysis was used for different lactate subtype identification. Based on the lactate subtypes, we explore the landscape of TME cell infiltration. A risk-score was calculated by using the LASSO-Cox analysis. A quantitative real-time PCR assay was utilized to validate the expression of characteristic genes in clinical cancer tissues and paracarinoma tissues from LUAD patients. Results: Comparing the normal samples, 18 LRGs were differentially expressed in tumor samples, which revealed that the differential expression of LRGs may be related to Copy Number Variation (CNV) alterations. The two distinct lactate subtypes were defined. Compared to patients in the LRGcluster A group, LUAD patients in the LRGcluster B group achieved better survival. The prognostic model was constructed based on differentially expressed genes (DEGs) via the LASSO-Cox analysis, which showed the accuracy of predicting the prognosis of LUAD patients using the ROC curve. A high-risk score was related to a high immune score, stromal score, and tumor mutation burden (TMB). Patients had better OS with low risk compared with those with high risk. The sensitivities of different risk groups to chemotherapeutic drugs were explored. Finally, the expression of characteristic genes in clinical cancer tissues and paracarinoma tissues from LUAD patients was verified via qRT-PCR. Conclusions: The lactate subtypes were independent prognostic biomarkers in LUAD. Additionally, the difference in the lactate subtypes was an indispensable feature for the individual TME. The comprehensive evaluation of the lactate subtypes in the single tumor would help us to understand the infiltration characteristics of TME and guide immunotherapy strategies.

Background: This study aimed to compare acute hemodynamic, metabolic (glucose and blood lactate concentrations), hormonal (growth hormone and normetanephrine), heart rate variability (HRV), and rating of perceived exertion (RPE) responses before and after bouts of a boxing exergame with and without blood flow restriction (BFR) in non-athlete young individuals. Methods: Fourteen participants (age: 30 ± 10 y; BMI: 21 ± 3 kg.m−2) participated in two sessions of a 20 min boxing exergame. During week one, the participants were randomly divided into two groups and played against one another under normal (n = 7) and BFR (n = 7) conditions. Over the next exercise session, participants were then reallocated to the opposite condition (normal vs. BFR) for data collection. Hemodynamic, metabolic, HRV, and hormonal parameters were measured before and immediately after the exercise protocols. Results: Playing exergame led to a significant increase in hemodynamic variables (except for diastolic blood pressure) regardless of BFR condition with no between-group differences. Regarding HRV, significant reductions in total power (TP) and low-frequency (LF) waves were identified in the non-BFR group (p < 0.0001) compared with the BFR group. Conversely, a significant increase in very LF (VLF) waves was noted for the BFR group (p = 0.050), compared with the non-BFR group. Significant increases were observed in serum concentrations of growth hormone, normetanephrine, and blood lactate concentration from pre- to post-exercise under both conditions (p ≤ 0.05), with no significant differences between the groups. Moreover, no statistically significant changes were observed in glucose levels. RPE responses were significantly greater (p ≤ 0.05) in the BFR group compared with the non-BFR group throughout the exercise session. Conclusions: We observed similar hemodynamic, hormonal, and metabolic responses after an acute boxing exergame session in young individuals, whether conducted with or without BFR. However, notable differences were observed in certain HRV markers and RPE. Specifically, the inclusion of BFR resulted in an elevation of VLF and a heightened perceived exertion. These findings suggest that BFR may alter cardiac autonomic and perceptual responses during exergaming. Further research is warranted to understand the long-term implications and potential benefits of incorporating BFR into exergaming routines.

The dysregulation of the intestinal epithelial barrier significantly contributes to the inflammatory progression of ulcerative colitis. Recent studies have indicated that lactate, produced by gut bacteria or derived from fermented foods, plays a key role in modulating inflammation via G-protein-coupled receptor 81 (GPR81). In this study, we aimed to investigate the potential role of GPR81 in the progression of colitis and to assess the impact of lactate/GPR81 signaling on intestinal epithelial barrier function. Our findings demonstrated a downregulation of GPR81 protein expression in patients with colitis. Functional verification experiments showed that Gpr81-deficient mice exhibited more severe damage to the intestinal epithelial barrier and increased susceptibility to DSS-induced colitis, characterized by exacerbated oxidative stress, elevated inflammatory cytokine secretion, and impaired expression of tight-junction proteins. Mechanistically, we found that lactate could suppress TNF-α-induced MMP-9 expression and prevent the disruption of tight-junction proteins by inhibiting NF-κB activation through GPR81 in vitro. Furthermore, our study showed that dietary lactate could preserve intestinal epithelial barrier function against DSS-induced damage in a GPR81-dependent manner in vivo. Collectively, these results underscore the crucial involvement of the lactate/GPR81 signaling pathway in maintaining intestinal epithelial barrier function, providing a potential therapeutic strategy for ulcerative colitis.

Chlorella supplementation is reported to improve V˙O2max following extended supplementation periods (~3 weeks). However, there is little research on its impact over submaximal exercise intensities and following shorter supplementation regimens. This study aimed to investigate the efficacy of 6 g/day 2-day chlorella supplementation on exercise performance in healthy young adults. Twenty young healthy adults (Males = 16, Females = 4) (Age 22 ± 6 years, V˙O2max 42.7 ± 9.6 mL/(kg·min)) were recruited for this double-blinded, randomised cross-over study. Participants ingested 6 g/day of chlorella or a placebo for 2 days, with a one-week washout period between trials. Exercise testing consisted of a 20 min submaximal cycle at 40% of their work rate max (WRmax) (watts), followed by an incremental V˙O2max test. Lactate (mmol/L), heart rate (b/min), oxygen consumption (mL/(kg·min)), O2 pulse (mL/beat), respiratory exchange ratio (RER), and WRmax were compared across conditions. Following chlorella supplementation, blood lactate levels were significantly lower (p < 0.05) during submaximal exercise (3.05 ± 0.92 mmol/L vs. 2.67 ± 0.79 mmol/L) and following V˙O2max tests (12.79 ± 2.61 mmol/L vs. 11.56 ± 3.43 mmol/L). The O2 pulse was significantly higher (p < 0.05) following chlorella supplementation during submaximal (12.6 ± 3.5 mL/beat vs. 13.1 ± 3.5 mL/beat) and maximal exercise intensity (16.7 ± 4.6 mL/beat vs. 17.2 ± 4.5 mL/beat). No differences existed between conditions for oxygen consumption, RER, V˙O2max, or WRmax. A total of 2 days of 6 g/day chlorella supplementation appears to lower the blood lactate response and increase O2 pulse during both submaximal and maximal intensity exercise but did not lead to any improvements in V˙O2max.

Lactate serves as a crucial biomarker that indicates sepsis assessment in critically ill patients. A rapid, accurate, and portable analytical device for lactate detection is required. This work developed a stepwise polyurethane–polyaniline–m-phenylenediamine via a layer-by-layer based electrochemical biosensor, using a screen-printed gold electrode for lactate determination in blood samples. The developed lactate biosensor was electrochemically fabricated with layers of m-phenylenediamine, polyaniline, a crosslinking of a small amount of lactate oxidase via glutaraldehyde, and polyurethane as an outer membrane. The lactate determination using amperometry revealed the biosensor’s performance with a wide linear range of 0.20–5.0 mmol L−1, a sensitivity of 12.17 ± 0.02 µA·mmol−1·L·cm−2, and a detection limit of 7.9 µmol L−1. The developed biosensor exhibited a fast response time of 5 s, high selectivity, excellent long-term storage stability over 10 weeks, and good reproducibility with 3.74% RSD. Additionally, the determination of lactate in human blood plasma using the developed lactate biosensor was examined. The results were in agreement with the enzymatic colorimetric gold standard method (p > 0.05). Our developed biosensor provides efficiency, reliability, and is a great potential tool for advancing lactate point-of-care testing applications in the early diagnosis of sepsis.

Background: Blood lactate is a potentially useful biomarker to predict the mortality and severity of sepsis. The purpose of this study is to systematically review the ability of lactate to predict hierarchical sepsis clinical outcomes and distinguish sepsis, severe sepsis and septic shock. Methods: We conducted an exhaustive search of the PubMed, Embase and Cochrane Library databases for studies published before 1 October 2022. Inclusion criteria mandated the presence of case–control, cohort studies and randomized controlled trials that established the association between before-treatment blood lactate levels and the mortality of individuals with sepsis, severe sepsis or septic shock. Data was analyzed using STATA Version 16.0. Results: A total of 127 studies, encompassing 107,445 patients, were ultimately incorporated into our analysis. Meta-analysis of blood lactate levels at varying thresholds revealed a statistically significant elevation in blood lactate levels predicting mortality (OR = 1.57, 95% CI 1.48–1.65, I2 = 92.8%, p < 0.00001). Blood lactate levels were significantly higher in non-survivors compared to survivors in sepsis patients (SMD = 0.77, 95% CI 0.74–0.79, I2 = 83.7%, p = 0.000). The prognostic utility of blood lactate in sepsis mortality was validated through hierarchical summary receiver operating characteristic curve (HSROC) analysis, yielding an area under the curve (AUC) of 0.72 (95% CI 0.68–0.76), accompanied by a summary sensitivity of 0.65 (95% CI 0.59–0.7) and a summary specificity of 0.7 (95% CI 0.64–0.75). Unfortunately, the network meta-analysis could not identify any significant differences in average blood lactate values’ assessments among sepsis, severe sepsis and septic shock patients. Conclusions: This meta-analysis demonstrated that high-level blood lactate was associated with a higher risk of sepsis mortality. Lactate has a relatively accurate predictive ability for the mortality risk of sepsis. However, the network analysis found that the levels of blood lactate were not effective in distinguishing between patients with sepsis, severe sepsis and septic shock.

Multiple lines of evidence have shown that lactate-mediated pH alterations in the brains of patients with neuropsychiatric diseases such as schizophrenia (SCZ), Alzheimer’s disease (AD) and autism may be attributed to mitochondrial dysfunction and changes in energy metabolism. While neuronal activity is associated with reduction in brain pH, astrocytes are responsible for rebalancing the pH to maintain the equilibrium. As lactate level is the main determinant of brain pH, neuronal activities are impacted by pH changes due to the binding of protons (H+) to various types of proteins, altering their structure and function in the neuronal and non-neuronal cells of the brain. Lactate and pH could affect diverse types of epigenetic modifications, including histone lactylation, which is linked to histone acetylation and DNA methylation. In this review, we discuss the importance of pH homeostasis in normal brain function, the role of lactate as an essential epigenetic regulatory molecule and its contributions to brain pH abnormalities in neuropsychiatric diseases, and shed light on lactate-based and pH-modulating therapies in neuropsychiatric diseases by targeting epigenetic modifications. In conclusion, we attempt to highlight the potentials and challenges of translating lactate-pH-modulating therapies to clinics for the treatment of neuropsychiatric diseases.

Given its polygenic nature, there is a need for a personalized approach to schizophrenia. The aim of the study was to select laboratory biomarkers from blood, brain imaging, and clinical assessment, with an emphasis on patients’ self-report questionnaires. Metabolomics studies of serum samples from 51 patients and 45 healthy volunteers, based on the liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS), led to the identification of 3 biochemical indicators (cortisol, glutamate, lactate) of schizophrenia. These metabolites were sequentially correlated with laboratory tests results, imaging results, and clinical assessment outcomes, including patient self-report outcomes. The hierarchical cluster analysis on the principal components (HCPC) was performed to identify the most homogeneous clinical groups. Significant correlations were noted between blood lactates and 11 clinical and 10 neuroimaging parameters. The increase in lactate and cortisol were significantly associated with a decrease in immunological parameters, especially with the level of reactive lymphocytes. The strongest correlations with the level of blood lactate and cortisol were demonstrated by brain glutamate, N-acetylaspartate and the concentrations of glutamate and glutamine, creatine and phosphocreatine in the prefrontal cortex. Metabolomics studies and the search for associations with brain parameters and self-reported outcomes may provide new diagnostic evidence to specific schizophrenia phenotypes.

Physical exercise (EX) is well established for its positive impact on brain health. However, conventional EX may not be feasible for certain individuals. In this regard, this study explores electromyostimulation (EMS) as a potential alternative for enhancing cognitive function. Conducted on both human participants and rats, the study involved two sessions of EMS applied to the quadriceps with a duration of 30 min at one-week intervals. The human subjects experienced assessments of cognition and mood, while the rats underwent histological and biochemical analyses on the prefrontal cortex, hippocampus, and quadriceps. Our findings indicated that EMS enhanced executive functions and reduced anxiety in humans. In parallel, our results from the animal studies revealed an elevation in brain-derived neurotrophic factor (BDNF), specifically in the hippocampus. Intriguingly, this increase was not associated with heightened neuronal activity or cerebral hemodynamics; instead, our data point towards a humoral interaction from muscle to brain. While no evidence of increased muscle and circulating BDNF or FNDC5/irisin pathways could be found, our data highlight lactate as a bridging signaling molecule of the muscle–brain crosstalk following EMS. In conclusion, our results suggest that EMS could be an effective alternative to conventional EX for enhancing both brain health and cognitive function.

Hyperglycemia, lipotoxicity, and insulin resistance are known to increase the secretion of extracellular matrix from cardiac fibroblasts as well as the activation of paracrine signaling from cardiomyocytes, immune cells, and vascular cells, which release fibroblast-activating mediators. However, their influences on vascular smooth muscle cells (vSMCs) have not been well examined. This study aimed to investigate whether contractile vascular vSMCs could develop a more synthetic phenotype in response to hyperglycemia. The results showed that contractile and synthetic vSMCs consumed high glucose in different ways. Lactate/GPR81 promotes the synthetic phenotype in vSMCs in response to high glucose levels. The stimulation of high glucose was associated with a significant increase in fibroblast-like features: synthetic vSMC marker expression, collagen 1 production, proliferation, and migration. GPR81 expression is higher in blood vessels in diabetic patients and in the high-glucose, high-lipid diet mouse. The results demonstrate that vSMCs assume a more synthetic phenotype when cultured in the presence of high glucose and, consequently, that the high glucose could trigger a vSMC-dependent cardiovascular disease mechanism in diabetes via lactate/GPR81.

The division of glycolysis into two separate pathways, aerobic and anaerobic, depending on the presence or absence of oxygen, respectively, was formulated over eight decades ago. The former ends with pyruvate, while the latter ends with lactate. Today, this division is confusing and misleading as research over the past 35 years clearly has demonstrated that glycolysis ends with lactate not only in cancerous cells but also in healthy tissues and cells. The present essay offers a review of the history of said division and the more recent knowledge that has been gained about glycolysis and its end-product, lactate. Then, it presents arguments in an attempt to explain why separating glycolysis into aerobic and anaerobic pathways persists among scientists, clinicians and teachers alike, despite convincing evidence that such division is not only wrong scientifically but also hinders progress in the field of energy metabolism.

Trichophyton rubrum is the leading causative agent of dermatophytosis worldwide. Keratinocytes are the first line of defense that drives an immune response against fungal invasion. Host-specific pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs) to trigger immunological pathways. Fungal cell wall components are the primary sources of fungal PAMPs, and some pathogens increase cell wall rearrangement to evade the immune system. Glycolysis and enhanced lactate levels are critical for improving host immune responses to fungal infections. Using reverse transcription–quantitative polymerase chain reaction (RT-qPCR), we evaluated the transcriptional responses of human genes involved in fungal recognition and glycolytic metabolism and fungal cell-wall-related genes in a co-culture model of human keratinocytes with T. rubrum. We observed the upregulation of several Toll-like receptors (TLRs), NOD-like receptors (NLRs), and glycolytic genes. Complementarily, we measured intra- and extracellular glucose levels and the increase in lactate production in the co-culture supernatant. We noted a distinct transcriptional regulation pattern of fungal cell-wall-related genes from fungal growth on keratin as the primary carbon source compared to co-culture with human keratinocytes. Our results showed new insights into the transcriptional adaptation of keratinocytes, particularly in regulating genes involved in sensing and metabolic processes, during the interaction with T. rubrum.

Mitochondrial biogenesis and fusion are essential for maintaining healthy mitochondria and ATP production. High-intensity interval training (HIIT) can enhance mitochondrial function in mouse hippocampi, but its underlying mechanism is not completely understood. Lactate generated during HIIT may mediate the beneficial effects of HIIT on neuroplasticity by activating the lactate receptor GPR81. Furthermore, growing evidence shows that lactate contributes to mitochondrial function. Given that mitochondrial function is crucial for cerebral physiological processes, the current study aimed to determine the mechanism of HIIT in hippocampal mitochondrial function. In vivo, GPR81 was knocked down in the hippocampi of mice via the injection of adeno-associated virus (AAV) vectors. The GPR81-knockdown mice were subjected to HIIT. The results demonstrated that HIIT increased mitochondria numbers, ATP production, and oxidative phosphorylation (OXPHOS) in the hippocampi of mice. In addition, HIIT induced mitochondrial biogenesis, fusion, synaptic plasticity, and ERK1/2 phosphorylation but not in GPR81-knockdown mice. In vitro, Neuro-2A cells were treated with L-lactate, a GPR81 agonist, and an ERK1/2 inhibitor. The results showed that both L-lactate and the GPR81 agonist increased mitochondrial biogenesis, fusion, ATP levels, OXPHOS, mitochondrial membrane potential, and synaptic plasticity. However, the inhibition of ERK1/2 phosphorylation blunted L-lactate or the GPR81 agonist-induced promotion of mitochondrial function and synaptic plasticity. In conclusion, our findings suggest that lactate mediates HIIT-induced promotion of mitochondrial function through the GPR81-ERK1/2 pathway.

Almost a quarter of a millennium after the discovery of an acidic substance in sour milk by Swedish chemist Carl Wilhelm Scheele and more than 100 years after the demonstration of a tight connection between this lactic acid and tissue hypoxia in shock, we are still surrounded by false beliefs and misunderstandings regarding this fascinating molecule. Common perceptions of lactate, the conjugate base of lactic acid, as a plain waste product of anaerobic metabolism and a marker of cellular distress could not be further from the truth. Lactate is formed and utilized continuously by our cells, even under fully aerobic conditions, in large quantities, and although marked hyperlactatemia is always a red flag in our patients, not all these conditions are life-threatening and vice versa—not all critically ill patients have hyperlactatemia. Lactate also does not promote acidosis by itself; it is not toxic, nor is it a metabolic renegade. On the contrary, it has many beneficial properties, and an interpretation of hyperlactatemia might be trickier than we tend to think. The aim of this article is to debunk some of the deeply rooted myths regarding this fascinating molecule.

The capacity of laboratory tests to predict competition performance has been broadly researched across several endurance sports. The aim of the present study was to analyse how pool swimming performance can predict the result of the swimming segment in triathlon competitions and compare predictability differences based on competition level and distance. Eighteen male triathletes participated in the study. Three were ranked world-class, ten elite/international level, and five highly trained/national level. A total of sixty-one graded multi-stage swimming tests were conducted. Blood lactate was measured to calculate the following hypothetical predictor variables: speed at lactate threshold 1 (LT1), speed at lactate threshold 2 (LT2), and speed in the last repetition of the test (SL200). The following data were collected for a total of 75 races: time in the swimming leg (TSL); position after the swimming leg (PSL); time difference with the first triathlete after the swimming leg (DFT); and final race position. The race levels were divided according to participant levels as follows: world series (WS) (n = 22); World Cup (WC) (n = 22); Continental Cup (CC) (n = 19); national championship (N) (n = 5); and local race (L) (n = 5). Based on distance, they were divided into Olympic distance (OD) (n = 37) and sprint distance (SD) (n = 38). A moderate to strong positive association was found between LT1, LT2, SL200 and PSL and TSl at all race levels except for the SD CC, SD WC, and OD CC races, where no or weak-to-moderate correlations were found. The present study demonstrated that performance measured in a graded multi-stage pool lactate test can predict performance in a triathlon swimming segment. This finding is highly useful for coaches as it can help them to obtain a reliable measure of the triathlete’s specific capabilities in the swimming leg.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease characterized by excessive deposition of fibrotic connective tissue in the lungs. Emerging evidence suggests that metabolic alterations, particularly glycolysis reprogramming, play a crucial role in the pathogenesis of IPF. Lactate, once considered a metabolic waste product, is now recognized as a signaling molecule involved in various cellular processes. In the context of IPF, lactate has been shown to promote fibroblast activation, myofibroblast differentiation, and extracellular matrix remodeling. Furthermore, lactate can modulate immune responses and contribute to the pro-inflammatory microenvironment observed in IPF. In addition, lactate has been implicated in the crosstalk between different cell types involved in IPF; it can influence cell–cell communication, cytokine production, and the activation of profibrotic signaling pathways. This review aims to summarize the current research progress on the role of glycolytic reprogramming and lactate in IPF and its potential implications to clarify the role of lactate in IPF and to provide a reference and direction for future research. In conclusion, elucidating the intricate interplay between lactate metabolism and fibrotic processes may lead to the development of innovative therapeutic strategies for IPF.

S100B is a calcium-binding protein produced and secreted by astrocytes in response to various extracellular stimuli. C6 glioma cells are a lineage commonly employed for astroglial studies due to the expression of astrocyte specific markers and behavior. However, in high-glucose medium, C6 S100B secretion increases, in contrast to the trend in primary astrocyte cultures. Additionally, S100B secretion decreases due to fluorocitrate (FC), a Krebs cycle inhibitor, highlighting a connection between S100B and metabolism. Herein, we investigate the impact of FC on S100B secretion in primary astrocyte cultures, acute hippocampal slices and C6 glioma cells, as well as lactate mediation. Our results demonstrated that C6 responded similarly to astrocytes in various parameters, despite the decrease in S100B secretion, which was inversely observed in astrocytes and slices. Furthermore, FC inversely altered extracellular lactate in both models, suggesting a role for lactate in S100B secretion. This was reinforced by a decrease in S100B secretion in hippocampal slices treated with lactate and its agonist, but not in C6 cells, despite HCAR1 expression. Our findings indicate that extracellular lactate mediates the decrease in S100B secretion in astrocytes exposed to FC. They also emphasize the differences in C6 glioma cells regarding energetic metabolism. The proposed mechanism via HCAR1 provides further compelling evidence of the relationship between S100B and glucose metabolism.

Based on in silico, in vitro, in situ, and in vivo evaluations, this study aims to establish and optimize the chemical exchange saturation transfer (CEST) imaging of lactate (Lactate-CEST—LATEST). To this end, we optimized LATEST sequences using Bloch–McConnell simulations for optimal detection of lactate with a clinical 3 T MRI scanner. The optimized sequences were used to image variable lactate concentrations in vitro (using phantom measurements), in situ (using nine human cadaveric lower leg specimens), and in vivo (using four healthy volunteers after exertional exercise) that were then statistically analyzed using the non-parametric Friedman test and Kendall Tau-b rank correlation. Within the simulated Bloch–McConnell equations framework, the magnetization transfer ratio asymmetry (MTRasym) value was quantified as 0.4% in the lactate-specific range of 0.5–1 ppm, both in vitro and in situ, and served as the imaging surrogate of the lactate level. In situ, significant differences (p < 0.001) and strong correlations (τ = 0.67) were observed between the MTRasym values and standardized intra-muscular lactate concentrations. In vivo, a temporary increase in the MTRasym values was detected after exertional exercise. In this bench-to-bedside comprehensive feasibility study, different lactate concentrations were detected using an optimized LATEST imaging protocol in vitro, in situ, and in vivo at 3 T, which prospectively paves the way towards non-invasive quantification and monitoring of lactate levels across a broad spectrum of diseases.

The Warburg Effect is characterized by high rates of glucose uptake and lactate production. Monocarboxylate transporters (MCTs) are crucial to avoid cellular acidosis by internal lactate accumulation, being largely overexpressed by cancer cells and associated with cancer aggressiveness. The MCT1-specific inhibitor AZD3965 has shown encouraging results in different cancer models. However, it has not been tested in urothelial bladder cancer (UBC), a neoplasm where rates of recurrence, progression and platinum-based resistance are generally elevated. We used two muscle-invasive UBC cell lines to study AZD3965 activity regarding lactate production, UBC cells’ viability and proliferation, cell cycle profile, and migration and invasion properties. An “in vivo” assay with the chick chorioallantoic membrane model was additionally performed, as well as the combination of the compound with cisplatin. AZD3965 demonstrated anticancer activity upon low levels of MCT4, while a general lack of sensitivity was observed under MCT4 high expression. Cell viability, proliferation and migration were reduced, cell cycle was arrested, and tumor growth “in vivo” was inhibited. The compound sensitized these MCT4-low-expressing cells to cisplatin. Thus, AZD3965 seems to display anticancer properties in UBC under a low MCT4-expression setting, but additional studies are necessary to confirm AZD3965 activity in this cancer model.

Blood testing has traditionally been the gold standard for the physiological analysis and monitoring of professional athletes. In recent years, blood testing has moved out of the laboratory thanks to portable handheld devices, such as lactate meters. However, despite its usefulness and widespread use, blood testing has several drawbacks and limitations, such as the need for the athlete to stop exercising for blood extraction and the inability to have data continuously collected. In this scenario, sweat has become an alternative to blood testing because of its rich content of electrolytes and metabolites, as well as small quantities of sugars, proteins, and ions. Nevertheless, there are few devices capable of analyzing this biofluid and providing useful information to users. In this paper, an electronic system designed for the autonomous analysis of sweat electrolytes and metabolites along with heart rate dynamics is presented. This system is part of a novel wearable device tailored for athletes that offers to the user a real-time assessment of their physiological status and performance.

Objective: Lactate is a marker of hypoperfusion in critically ill patients. Whether lactate is useful for identifying and stratifying neonates with a higher risk of adverse outcomes remains unknown. This study aimed to investigate the association between lactate and morbidity and mortality in neonates. Methods: A meta-analysis was performed to determine the association between blood lactate levels and outcomes in neonates. Ovid MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched from inception to 1 May 2021. A total of 49 observational studies and 14 data accuracy test studies were included. The risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the QUADAS-2 tool for data accuracy test studies. The primary outcome was mortality, while the secondary outcomes included acute kidney injury, necessity for renal replacement therapy, neurological outcomes, respiratory morbidities, hemodynamic instability, and retinopathy of prematurity. Results: Of the 3184 articles screened, 63 studies fulfilled all eligibility criteria, comprising 46,069 neonates. Higher lactate levels are associated with mortality (standard mean difference, −1.09 [95% CI, −1.46 to −0.73]). Using the estimated sensitivity (0.769) and specificity (0.791) and assuming a prevalence of 15% for adverse outcomes (median of prevalence among studies) in a hypothetical cohort of 10,000 neonates, assessing the lactate level alone would miss 346 (3.46%) cases (false negative) and wrongly diagnose 1776 (17.76%) cases (false positive). Conclusions: Higher lactate levels are associated with a greater risk of mortality and morbidities in neonates. However, our results do not support the use of lactate as a screening test to identify adverse outcomes in newborns. Research efforts should focus on analyzing serial lactate measurements, rather than a single measurement.