Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Histone lysine modifications were well-established epigenetic markers, with many types identified and extensively studied. The discovery of histone lysine lactylation had revealed a new form of epigenetic modification. The intensification of this modification was associated with glycolysis and elevated intracellular lactate levels, both of which were closely linked to cellular metabolism. Histone lactylation plays a crucial role in multiple cellular homeostasis, including immune regulation and cancer progression, thereby significantly influencing cell fate. Lactylation can modify both histone and non-histone proteins. This paper provided a comprehensive review of the typical epigenetic effects and lactylation on classical transcription-related lysine sites and summarized the known enzymes involved in histone lactylation and delactylation. Additionally, some discoveries of histone lactylation in tumor biology were also discussed, and some prospects for this field were put forward.

Abstract Hyperlactatemia is common during tumor craniotomy, but the underlying pathophysiology is unclear. This study measured simultaneous arterial and jugular‐bulb lactate concentrations in patients undergoing brain tumor craniotomy to investigate the hypothesis that hyperlactatemia was associated with a net cerebrovascular lactate input. In 20 patients, arterial and jugular‐bulb blood was collected hourly from the start of surgery to 6 h postoperatively for measurement of lactate, glucose, and oxygen concentration. For each marker, data were analyzed using a linear mixed‐effects model with jugular‐bulb concentration as dependent variable, arterial concentration as fixed effect, and patient as random effect. Furthermore, we generated regression lines between arterial and jugular‐bulb concentrations. The slope of the regression line between arterial and jugular‐bulb lactate was 0.95 (95% CI 0.93–0.97, R2 = 0.98), indicating that increasing arterial lactate levels were associated with an increasingly positive net cerebrovascular balance (net input). The line crossed the identity line at 2.86 (95% CI 0.57–5.16) mmol/L, indicating that lower levels of lactate were associated with a negative net cerebrovascular balance (net output). This suggests a switch from net lactate output during normolactatemia towards net input during hyperlactatemia. Hyperlactatemia in tumor‐craniotomy patients probably does not originate from the brain.

IntroductionStrength training (ST) is a strategy to enhance quality of life through increased strength, muscle hypertrophy, and functional capacity. Training systems are associated with manipulation of volume and intensity, generating different stimuli, such as Rest-Pause (RP) and Sarcoplasmic Stimulating Training (SST). These systems induce greater mechanical and physiological stress, leading to increased strength and muscle hypertrophy. However, the metabolic and psycho-affective effects of advanced systems in experienced practitioners remain inconclusive. The purpose of the study is to analyze the acute effects of RP, SST, and Traditional (TMS) systems on metabolic and psycho-affective responses in adult men.MethodsThis experimental crossover study assessed 15 subjects (30.38 ± 2.06 years; 88.40 ± 6.50 kg; 1.74 ± 0.07 cm) experienced in ST, evaluated under TMS, RP, and SST during flat bench press and leg press 45° exercises. Body composition, muscular strength via 1-RM testing, lactate concentration (LAC), and psycho-affective measures (Rating of Perceived Exertion-RPE; Visual Analog Scale-VAS; Feeling Scale-FS) were determined. Statistical analysis was performed using the Minitab software, with p ≤ 0.05, IC-95%).ResultsThe finals results showed SST exhibited a 38.10% lower LAC concentration post-training session compared to TMS, while RP showed 37.20% lower LAC concentration than TMS post-session. Average RPE values for RP and SST were higher (8.50 ± 1.10 and 8.60 ± 0.90, respectively) than TMS (6.00 ± 1.10). VAS displayed higher average values for RP and SST (8.00 ± 2.00 and 8.00 ± 1.00, respectively) compared to TMS (5.00 ± 1.00), with affective ratings indicating positive values for TMS and values between 0 and −5 for RP (40%) and SST (60%) post-training sessions, suggesting that RP and SST induced less affective response than TMS.DiscussionThe results lead to the conclusion that manipulation of training volume and intensity led to higher RPE and pain (VAS). The data suggest that inappropriate prescription of these systems could lead to greater displeasure, leading us to hypothesize that a higher likelihood of discontinuation from strength training programs would occur, suggesting that greater repetition volumes (RP and SST) should be targeted at individuals with a higher training level.

Fructose and lactate are present in high concentrations in uterine luminal fluid, fetal fluids and fetal blood of ungulates and cetaceans, but their roles have been ignored and they have been considered waste products of pregnancy. This review provides evidence for key roles of both fructose and lactate in support of key metabolic pathways required for growth and development of fetal-placental tissues, implantation and placentation. The uterus and placenta of ungulates convert glucose to fructose via the polyol pathway. Fructose is sequestered within the uterus and cannot be transported back into the maternal circulation. Fructose is phosphorylated by ketohexokinase to fructose-1-PO4 (F1P) by that is metabolized via the fructolysis pathway to yield dihydoxyacetone phosphate and glyceraldehyde-3-PO4 that are downstream of phosphofructokinase. Thus, there is no inhibition of the fructolysis pathway by low pH, citrate or ATP which allows F1P to continuously generate substrates for the pentose cycle, hexosamine biosynthesis pathway, one-carbon metabolism and tricarboxylic acid cycle, as well as lactate. Lactate sustains the activity of hypoxia-inducible factor alpha and its downstream targets such as vascular endothelial growth factor to increase utero-placental blood flow critical to growth and development of the fetal-placental tissues and a successful outcome of pregnancy. Pregnancy has been referred to as a controlled cancer and this review addresses similarities regarding metabolic aspects of tumors and the placenta.

Lactylation, a novel discovered posttranslational modification, is a vital component of lactate function and is prevalent in a wide range of cells, interacting with both histone and non-histone proteins. Recent studies have confirmed that lactylation as a new contributor to epigenetic landscape is involved in multiple pathological processes. Accumulating evidence reveals that lactylation exists in different pathophysiological states and leads to inflammation and cancer; however, few mechanisms of lactylation have been elaborated. This review summarizes the biological processes and pathophysiological roles of lactylation in cancer, as well as discusses the relevant mechanisms and potential therapeutic targets, aiming to provide new insights for targeted cancer therapy.

Abstract Cognitive dysfunction is not only a common symptom of major depressive disorder, but also a more common residual symptom after antidepressant treatment and a risk factor for chronic and recurrent disease. The disruption of hypocretin regulation is known to be associated with depression, however, their exact correlation is remains to be elucidated. Hypocretin‐1 levels are increased in the plasma and hypothalamus from chronic unpredictable mild stress (CUMS) model mice. Excessive hypocretin‐1 conducted with hypocretin receptor 1 (HCRTR1) reduced lactate production and brain‐derived neurotrophic factor (BDNF) expression by hypoxia‐inducible factor‐1α (HIF‐1α), thus impairing adult hippocampal neuroplasticity, and cognitive impairment in CUMS model. Subsequently, it is found that HCRTR1 antagonists can reverse these changes. The direct effect of hypocretin‐1 on hippocampal lactate production and cognitive behavior is further confirmed by intraventricular injection of hypocretin‐1 and microPET‐CT in rats. In addition, these mechanisms are further validated in astrocytes and neurons in vitro. Moreover, these phenotypes and changes in molecules of lactate transport pathway can be duplicated by specifically knockdown of HCRTR1 in hippocampal astrocytes. In summary, the results provide molecular and functional insights for involvement of hypocretin‐1‐HCRTR1 in altered cognitive function in depression.

PurposeMethylene blue (MB) has been used to increase blood pressure in patients with septic shock by acting on guanylate cyclase and nitric oxide synthase.ObjectiveTo determine whether the administration of MB to patients in the initial phase of septic shock leads to a reduction in the use of vasopressors compared to the Control group.MethodsThis was a 1:1 randomized clinical trial of two groups (MB and Control). Forty-two patients were included in the present study; 23 patients were allocated to the Control group, and 19 were randomized to the MB group. Both groups had access to standard treatment, consisting of fluid replacement, vasopressors, and antibiotic therapy. Patients received a loading dose of MB (3 mg/kg) and maintenance (0.5 mg/kg/h) for 48 h. Vasopressor doses, laboratory test results, inflammatory and anti-inflammatory cytokine levels, and hemodynamic monitoring were recorded before the infusion of MB (T1) and after 20 min (T2), 2 h (T3), 24 h (T4), 48 h after the infusion started (T5) and 24 h after weaning (T6).ResultsMB therapy was started together with the indication of vasopressin (VAS) as a second vasopressor. The MB group showed an immediate reduction in NOR dosage, an earlier reduction in VAS dosage, and higher IL-10 levels compared to the Control group.ConclusionEarly administration of MB in combination with standard treatment for septic shock might be reduce vasopressors dose. Continuous infusion of MB for 48 h was considered safe and there was no adverse events. These results highlight the potential of MB as a safe adjuvant therapeutic option in the treatment of septic shock.Clinical trial registrationhttps://clinicaltrials.gov/, identifier RBR-96584w4.

Tumor cells undergo metabolic reprogramming through shared pathways, resulting in a hypoxic, acidic, and highly permeable internal tumor microenvironment (TME). Lactate, once only regarded as a waste product of glycolysis, has an inseparable dual role with tumor immunity. It can not only provide a carbon source for immune cells to enhance immunity but also help the immune escape through a variety of ways. Lymphoma also depends on the proliferation signal of TME. This review focuses on the dynamic process of lactate metabolism and immune function changes in lymphoma and aims to comprehensively summarize and explore which genes, transcription factors, and pathways affect the biological changes and functions of immune cells. To deeply understand the complex and multifaceted role of lactate metabolism and immunity in lymphoma, the combination of lactate targeted therapy and classical immunotherapy will be a promising development direction in the future.

In recent years, ferroptosis has gradually attracted increasing attention because of its important role in tumors. Ferroptosis resistance is an important cause of tumor metastasis, recurrence and drug resistance. Exploring the initiating factors and specific mechanisms of ferroptosis has become a key strategy to block tumor progression and improve drug sensitivity. As the external space in direct contact with tumor cells, the tumor microenvironment has a great impact on the biological function of tumor cells. The relationships between abnormal environmental characteristics (hypoxia, lactic acid accumulation, etc.) in the microenvironment and ferroptosis of tumor cells has not been fully characterized. This review focuses on the characteristics of the tumor microenvironment and summarizes the mechanisms of ferroptosis under different environmental factors, aiming to provide new insights for subsequent targeted therapy. Moreover, considering the presence of anticancer drugs in the microenvironment, we further summarize the mechanisms of ferroptosis to provide new strategies for the sensitization of tumor cells to drugs.

IntroductionLactate is a pivotal molecule with diverse functions in the metabolic reprogramming of cancer cells. Beyond its role in metabolism, lactate exerts a modulatory effect within the tumor microenvironment; it is utilized by stromal cells and has been implicated in the suppression of the immune response against the tumor.MethodsUsing in vitro assays (including flow cytometry, live-cell imaging and metabolic analyses), the impact of lactate dehydrogenase inhibitors (LDHIs) on melanoma cells were assessed. The therapeutic potential of LDHIs with immune checkpoint inhibitors (ICIs) were tested in vivo in murine models of melanoma tumors.ResultsA potent anti-proliferative effect (via both cell cycle alterations and enhanced apoptosis) of LDHIs, Oxamate (Oxa) and methyl 1-hydroxy-6-phenyl-4-(trifluoromethyl)-1H-indole-2-carboxylate (NHI-2), was found upon treatment of melanoma cell lines. Using a combination of Oxa and NHI-2, a synergistic effect to inhibit proliferation, glycolysis, and ATP production was observed. Metabolic analysis revealed significant alteration in glycolysis and oxidative phosphorylation, while metabolite profiling emphasized consequential effects on lactate metabolism and induced energy depletion by LDHIs. Detection of increased RANTES and MCP-1, with Oxa and NHI-2 treatment, prompted the consideration of combining LDHIs with ICIs. In vivo studies using a murine B78 melanoma tumor model revealed a significant improvement in treatment efficacy when LDHIs were combined with ICIs.ConclusionsThese findings propose the potential of targeting lactate metabolism to enhance the efficacy of ICI treatments in patients with melanoma.

Abstract Regulatory cell death is an important way to eliminate the DNA damage that accompanies the rapid proliferation of neural stem cells during cortical development, including pyroptosis, apoptosis, and so on. Here, the study reports that the absence of GSDMD‐mediated pyroptosis results in defective DNA damage sensor pathways accompanied by aberrant neurogenesis and autism‐like behaviors in adult mice. Furthermore, GSDMD is involved in organizing the mitochondrial electron transport chain by regulating the AMPK/PGC‐1α pathway to target Aifm3. This process promotes a switch from oxidative phosphorylation to glycolysis. The perturbation of metabolic homeostasis in neural progenitor cells increases lactate production which acts as a signaling molecule to regulate the p38MAPK pathway. And activates NF‐𝜿B transcription to disrupt cortex development. This abnormal proliferation of neural progenitor cells can be rescued by inhibiting glycolysis and lactate production. Taken together, the study proposes a metabolic axis regulated by GSDMD that links pyroptosis with metabolic reprogramming. It provides a flexible perspective for the treatment of neurological disorders caused by genotoxic stress and neurodevelopmental disorders such as autism.

Background: Lactate is a crucial intermediary, facilitating communication between myocardial energy metabolism and microenvironmental regulation. The present study aimed to investigate the relationship between lactate-related genes (LRGs) and myocardial infarction (MI). Methods: A total of 23 LRGs exhibited differential expression between individuals with MI and healthy controls. Lasso regression analysis and validation with the GSE61144 dataset identified three hub genes: COX20, AGK, and PDHX. Single-gene GSEA of these genes revealed strong enrichment in pathways related to amino acid metabolism, cell cycle, and immune functions. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was utilized to validate the expression levels of the hub genes. Results: Immune infiltration analysis revealed differences in CD4+ T and CD8+ T cells between the MI and control groups. Additionally, 67 candidate drugs targeting the three hub LRGs were identified, and a ceRNA network was constructed to explore the intricate interactions among these genes. Conclusions: These findings enhance the understanding of MI and have potential therapeutic implications.

In 2019, a novel post-translational modification termed lactylation was identified, which established a connection among lactate, transcriptional regulation and epigenetics. Lactate, which is traditionally viewed as a metabolic byproduct, is now recognized for its significant functional role, including modulating the tumor microenvironment, engaging in signaling and interfering in immune regulation. While research on lactylation (KLA) is advancing, the focus has primarily been on histone lactylation. This paper aims to explore the less-studied area of nonhistone lactylation, highlighting its involvement in certain diseases and physiological processes. Additionally, the clinical relevance and potential implications of nonhistone lactylation will be discussed.

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that thrives in environments associated with human activity, including soil and water altered by agriculture or pollution. Because L-lactate is a significant product of plant and animal metabolism, it can serve as a carbon source for P. aeruginosa in the diverse settings that it inhabits. In this study, we evaluate the production and use of two redundant P. aeruginosa L-lactate dehydrogenases, termed LldD and LldA. We confirm that the protein LldR represses lldD and identify a new transcription factor, called LldS, that activates lldA; these distinct regulators and the genomic contexts of lldD and lldA contribute to their differential expression. We demonstrate that the lldD and lldA genes are conditionally controlled in response to lactate isomers as well as to glycolate and ɑ-hydroxybutyrate, which, like lactate, are ɑ-hydroxycarboxylates. We also show that lldA is induced when iron availability is low. Our examination of lldD and lldA expression across depth in biofilms indicates a complex pattern that is consistent with the effects of glycolate production, iron availability, and cross-regulation on enzyme preference. Finally, macrophage infection assays reveal that both lldD and lldA contribute to persistence within host cells, underscoring the potential role of L-lactate as a carbon source during P. aeruginosa–eukaryote interactions. Together, these findings help us understand the metabolism of a key resource that may promote P. aeruginosa’s success as a resident of contaminated environments and animal hosts.IMPORTANCEPseudomonas aeruginosa is a major cause of lung infections in people with cystic fibrosis, of hospital-acquired infections, and of wound infections. It consumes L-lactate, which is found at substantial levels in human blood and tissues. In this study, we investigated the spatial regulation of two redundant enzymes, called LldD and LldA, which enable L-lactate metabolism in P. aeruginosa biofilms. We uncovered mechanisms and identified compounds that control the preference of P. aeruginosa for LldD versus LldA. We also showed that both enzymes contribute to its ability to survive within macrophages, a behavior that is thought to augment the chronicity and recalcitrance of infections. Our findings shed light on a key metabolic strategy used by P. aeruginosa and have the potential to inform the development of therapies targeting bacterial metabolism during infection.

Prolonged inhalation of environmental crystalline silica (CS) can cause silicosis, characterized by persistent pulmonary inflammation and irreversible fibrosis, but the mechanism has not been elucidated. To uncover the role and underlying mechanism of glycolytic reprogramming in CS-induced pulmonary inflammation, the mouse silicosis models and glycolysis inhibition models were established in vivo. And the CS-induced macrophage activation models were utilized to further explore the underlying mechanism in vitro. The results showed that CS induced lung inflammation accompanied by glycolytic reprogramming and pyroptosis. The application of glycolysis inhibitor (2-DG) suppressed CS-induced pyroptosis and alleviated lung inflammation. In vitro, 2-DG effectively impeded CS-induced macrophage pyroptosis and inflammatory response. Mechanistically, 2-DG suppressed pyroptosis by inhibiting NLRP3 inflammasome activation both in vivo and in vitro. Furtherly, metabolite lactate facilitated NLRP3-dependent pyroptosis synergistically with CS particles, while blocking the source of lactate largely alleviated NLRP3 inflammasome activation and subsequent pyroptosis triggered by CS. More profoundly, the increment of lactate induced by CS might drive NLRP3-dependent pyroptosis by increasing histone lactylation levels. In conclusion, our findings demonstrated inhibiting glycolytic reprogramming could alleviate CS-induced inflammatory response through suppressing NLRP3 -dependent pyroptosis. Increased glycolytic metabolite lactate and protein lactylation modifications might represent significant mechanisms during CS-induced NLRP3 activation and macrophage pyroptosis.

High levels of urinary lactate are an increased risk of progression in patients with diabetic kidney disease (DKD). However, it is still unveiled how lactate drive DKD. Epithelial-mesenchymal transition (EMT), which is characterized by the loss of epithelial cells polarity and cell-cell adhesion, and the acquisition of mesenchymal-like phenotypes, is widely recognized a critical contributor to DKD. Here, we found a switch from oxidative phosphorylation (OXPHOS) toward glycolysis in AGEs-induced renal tubular epithelial cells, thus leading to elevated levels of renal lactic acid. We demonstrated that reducing the lactate levels markedly delayed EMT progression and improved renal tubular fibrosis in DKD. Mechanically, we observed lactate increased the levels of histone H3 lysine 14 lactylation (H3K14la) in DKD. ChIP-seq & RNA-seq results showed histone lactylation contributed to EMT process by facilitating KLF5 expression. Moreover, KLF5 recognized the promotor of cdh1 and inhibited its transcription, which accelerated EMT of DKD. Additionally, nephro-specific knockdown and pharmacological inhibition of KLF5 diminished EMT development and attenuated DKD fibrosis. Thus, our study provides better understanding of epigenetic regulation of DKD pathogenesis, and new therapeutic strategy for DKD by disruption of the lactate-drived H3K14la/KLF5 pathway.

Purpose: Investigate whether a cloth facemask could affect physiological and perceptual responses to exercise at distinct exercise intensities in untrained individuals. Methods: Healthy participants (n = 35; 17 men, age 30 [4] y, and 18 women, age 28 [5] y) underwent a progressive square wave test at 4 intensities: (1) 80% of ventilatory anaerobic threshold; (2) ventilatory anaerobic threshold; (3) respiratory compensation point; and (4) exercise peak (Peak) to exhaustion, 5-minute stages, with or without a triple-layered cloth facemask (Mask or No-Mask). Several physiological and perceptual measures were analyzed. Results: Mask reduced inspiratory capacity at all exercise intensities (P <.0001). Mask reduced respiratory frequency (P =.001) at Peak (−8.3 breaths·min−1; 95% confidence interval [CI], −5.8 to −10.8), respiratory compensation point (−6.9 breaths·min−1; 95% CI, −4.6 to −9.2), and ventilatory anaerobic threshold (−6.5 breaths·min−1; 95% CI, −4.1 to −8.8), but not at Baseline or 80% of ventilatory anaerobic threshold. Mask reduced tidal volume (P <.0001) only at respiratory compensation point (−0.5 L; 95% CI, −0.3 to −0.6) and Peak (−0.8 L; 95% CI, −0.6 to −0.9). Shallow breathing index was increased with Mask only at Peak (11.3; 95% CI, 7.5 to 15.1). Mask did not change HR, lactate, ratings of perceived exertion, blood pressure, or oxygen saturation. Conclusions: A cloth facemask reduced time to exhaustion but had no major impact on cardiorespiratory parameters and had a slight but clinically meaningless impact on respiratory variables at higher intensities. Moderate to heavy activity is safe and tolerable for healthy individuals while wearing a cloth facemask. ClinicalTrials.gov: NCT04887714. [ABSTRACT FROM AUTHOR]

This pilot study aimed to evaluate the efficacy of the 4-h mean lactate clearance (LACclr) level as a predictive factor for in-hospital outcomes, 30-day mortality, and treatment success in patients with acute cardiogenic pulmonary edema (ACPE), a significant clinical form of acute heart failure (AHF).

A prominent cause of cancer-related fatalities with a poor prognosis is lung adenocarcinoma (LUAD). KIF5A, a crucial member of the kinesin superfamily, is linked to drug resistance in malignancies. This work aims to investigate the mechanism of KIF5A in docetaxel (DTX) resistance in LUAD cells. The results of bioinformatics analysis, qRT-PCR and western blot analysis show that KIF5A, which is involved in the glycolysis pathway, is highly expressed in LUAD and is positively correlated with glycolysis-related genes. We further verify that silencing of KIF5A inhibits DTX resistance, glycolysis, and lactate production in LUAD cells via cell counting kit-8 (CCK-8), flow cytometry, Seahorse XFe 96, lactate, and glucose assays. Mechanistically, KIF5A promotes DTX resistance in LUAD, and this effect is attenuated upon the addition of an LDHA inhibitor. Chromatin immunoprecipitation and dual-luciferase reporter assays reveal that FOXP3 transcriptionally activates KIF5A. Knockdown of FOXP3 reduces lactate production and enhances DTX sensitivity in LUAD, which is restored upon simultaneous overexpression of KIF5A. Our findings reveal that FOXP3 increases DTX resistance in LUAD cells by enhancing lactate production through the upregulation of KIF5A level. In conclusion, our study provides a novel treatment target for improving chemosensitivity in LUAD.

Abstract Background The causes of perioperative hyperlactatemia vary, but they are generally associated with hypoperfusion. Here, we report the case of a pediatric patient who developed unexplained hyperlactatemia during anesthesia with propofol and sevoflurane, which recurred during a second surgery under anesthesia with remimazolam. Case presentation. An 8-year-old boy with Perthes disease and no remarkable past or family history was scheduled for an osteotomy. Anesthesia was induced with propofol and rocuronium and then maintained with sevoflurane and remifentanil. The patient developed lactic acidosis without hemodynamic instability during anesthesia, with a normal lactate/pyruvate ratio after surgery, suggesting a lack of hypoperfusion. We used remimazolam instead of propofol during the second surgery 6 months later, considering the possibility of drug-induced lactic acidosis, including malignant hyperthermia and propofol infusion syndrome, where the unexplained hyperlactatemia recurred. Conclusions Distinguishing the causes of hyperlactatemia, particularly in the absence of other symptoms, is challenging. The lactate/pyruvate ratio during episodes of hyperlactatemia can provide insights into the underlying pathology.

Abstract Background Serum lactate is associated with mortality in diverse kinds of patients. This study aimed to investigate whether serum lactate level may independently predict mortality in acute kidney injury (AKI) patients. Methods A total of 4461 AKI patients were collected from the Medical Information Mart for Intensive Care (MIMIC III) database and followed up for 365 days. According to serum lactate tertiles, participants were divided into three groups (Q1–Q3) by: Q1 ≤ 1.60 mg/dl, Q2 = 1.61–2.70 mg/dl, and Q3 ≥ 2.71 mg/dl. We calculated the hazard ratio (HR) and 95% confidence intervals (Cls) for mortality across each tertile of lactate by using the Q1 as reference and constructed four models to adjust for the HR of mortality. Results Nonsurvivors had significantly higher lactate compared with patients in the survival group. Mortality rate gradually elevated with the increase in serum lactate level (Q1: 29.30%, Q2: 33.40%, Q3: 37.40%). When compared with Q1 after adjustment of all confounders, the HRs of Q3 still was 1.20 (95% Cl 1.05–1.37). Conclusions This study demonstrated that high serum lactate levels were an independent predictor of mortality in AKI patients.

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung diseases, which mainly existed in middle-aged and elderly people. The accumulation of reactive oxygen species (ROS) is a common characteristic of IPF. Previous research also shown that lactate levels can be abnormally elevated in IPF patients. Emerging evidence suggested a relationship between lactate and ROS in IPF which needs further elucidation. In this article, we utilized a mouse model of BLM-induced pulmonary fibrosis to detect alterations in ROS levels and other indicators associated with fibrosis. Lactate could induce mitochondrial fragmentation by modulating expression and activity of DRP1 and ERK. Moreover, Increased ROS promoted P65 translocation into nucleus, leading to expression of lung fibrotic markers. Finally, Ulixertinib, Mdivi-1 and Mito-TEMPO, which were inhibitor activity of ERK, DRP1 and mtROS, respectively, could effectively prevented mitochondrial damage and production of ROS and eventually alleviate pulmonary fibrosis. Taken together, these findings suggested that lactate could promote lung fibrosis by increasing mitochondrial fission-derived ROS via ERK/DRP1 signaling, which may provide novel therapeutic solutions for IPF.

Abstract Background Zymomonas mobilis is well known for its outstanding ability to produce ethanol with both high specific productivity and with high yield close to the theoretical maximum. The key enzyme in the ethanol production pathway is the pyruvate decarboxylase (PDC) which is converting pyruvate to acetaldehyde. Since it is widely considered that its gene pdc is essential, metabolic engineering strategies aiming to produce other compounds derived from pyruvate need to find ways to reduce PDC activity. Results Here, we present a new platform strain (sGB027) of Z. mobilis in which the native promoter of pdc was replaced with the IPTG-inducible PT7A1, allowing for a controllable expression of pdc. Expression of lactate dehydrogenase from E. coli in sGB027 allowed the production of D-lactate with, to the best of our knowledge, the highest reported specific productivity of any microbial lactate producer as well as with the highest reported lactate yield for Z. mobilis so far. Additionally, by expressing the L-alanine dehydrogenase of Geobacillus stearothermophilus in sGB027 we produced L-alanine, further demonstrating the potential of sGB027 as a base for the production of compounds other than ethanol. Conclusion We demonstrated that our new platform strain can be an excellent starting point for the efficient production of various compounds derived from pyruvate with Z. mobilis and can thus enhance the establishment of this organism as a workhorse for biotechnological production processes.

Abstract Background Sepsis is an infection-related systemic inflammatory response that often leads to elevated lactate levels. Monitoring lactate levels during severe sepsis is vital for influencing clinical outcomes. The aim of this study was to assess the association between plasma lactate levels and mortality in children with severe sepsis or septic shock. Methods The current prospective study was conducted in the PICU of University Children’s Hospital. The International Paediatric Sepsis Consensus Conference criteria for Definitions of Sepsis and Organ Failure in 2005 were used to diagnose patients with sepsis. We measured plasma lactate levels upon admission (Lac H0) and 6 h later (Lac H6). The static indices included the absolute lactate values (Lac H0 and Lac H6), while the dynamic indices included the delta-lactate level (ΔLac) and the 6-hour lactate clearance. The 6-hour lactate clearance was calculated using the following formula: [(Lac H0–Lac H6)100/Lac H0]. ΔLac was calculated as the difference between the Lac H0 and Lac H6 levels. Patient survival or death after a PICU stay was the primary outcome. Results A total of 46 patients were included in this study: 25 had septic shock, and 21 had severe sepsis. The mortality rate was 54.3%. The Lac H0 did not significantly differ between survivors and nonsurvivors. In contrast, the survivors had significantly lower Lac H6 levels, higher ΔLac levels, and higher 6-hour lactate clearance rates than nonsurvivors. Lactate clearance rates below 10%, 20%, and 30% were significantly associated with mortality. The best cut-off values for the lactate clearance rate and Lac H6 for the prediction of mortality in the PICU were

Physical activity and glycemic control are important factors in preventing chronic disease such as Type II diabetes. Glycemic control may be enhanced during recovery from acute exercise. OBJECTIVES To test the effects of resistance exercise (RT) vs. aerobic interval exercise (AER) on post-exercise blood glucose (BG) control during an oral glucose tolerance test (OGTT). METHODS Ten volunteers completed three separate trials (counter-balanced order): a resting control trial (CON) consisting of a 75-min OGTT following consumption of a 25% glucose solution dosed at 1 g/kg body mass; a RT trial in which subjects completed a 30-min circuit protocol (6-7 sets) of 6 reps/set using 10-RM load for squat, bench press, knee extension and biceps curl; and the AER trial where subjects alternated between treadmill exercise (3 min) and arm crank ergometry (2-min) over a 30-min period (intensity target of 15 on the Borg 6-20 point Rating of Perceived Exertion scale). Both exercise trials were followed by the same 75-min OGTT. BG was assessed via fingertip sampling prior to exercise, mid-exercise, post-exercise, and every 15-min during the OGTT. Blood lactate was collected at rest, mid-exercise, post-exercise and at 15 min of the OGTT. RESULTS Both exercise trials elicited significantly increased lactate but were not different from one another. BG was significantly elevated during the OGTT for all conditions but was not different by condition. BG area under the curve (AUC) was 5.6% smaller (p>0.05) following RT and AER vs. CON (CON: 10687±381; RT: 10087±343; AER: 10093±299 arbitrary units). CONCLUSIONS Acute resistance and aerobic interval exercise were not found to elicit significantly enhanced post-exercise glycemic control. Post-exercise glycemic control may be related to the total energy deficit achieved in young, healthy adults.

OBJECTIVES This study analyzed the possibility of brain function activation after exercise training of high-intensity interval exercise and moderate-intensity continuous exercise in elderly people. METHODS The subjects of the study were elderly female people aged 65 years or older and were divided into three groups : control group, moderate-intensity continuous training (MICT), and high-intensity interval training (HIIT). Changes of body composition, physical fitness, cognitive function, and cognitive function-related blood variables were compared between before and after 12 weeks of exercise training. RESULTS Body weight, BMI (body mass index), and WHR (waist hip ratio) of body composition in HIIT group decreased significantly (p

In the study, the acute effects of two different concurrent training models including high intensity interval training (HIIT) and high intensity interval functional training (HIFT) plus strength training (S) on physiological indicators (lactate and heart rate) and performance (balance and explosive power) parameters were examined in soccer players. A total of 13 moderately active young soccer players (19.92; ±1.44 years) participated in the study. In the study, body composition measurements, heart rate, lactate, explosive strength measurement and balance testing were measured. Training models (S+HIIT-S+HIFT) were applied sequentially with a crossover design. The training sessions were conducted with a three-day interval. Parameters were analyzed with SPSS24 (SPSS Inc., Chicago, IL, USA). Repeated Measure Analysis of Variance (ANOVA) was used for repeated measures and Bonferroni Correction was used for pairwise comparisons. Significance level was accepted as p

Background: Despite advances in surgical approaches and various treatment regimens, postoperative mortality after pancreatic surgery remains high (3.8%). Lactate levels and base excess show metabolic changes in the body and are useful prognostic markers of in-hospital mortality.Objective: To evaluate the prognostic significance of lactate levels and arterial base excess in patients after pancreatic surgery. Materials and methods: We retrospectively analyzed a database of patients who underwent pancreatic surgery (n=134) between 2019 and 2023. The patients were grouped: group 1 (n=11) for the patients who died in the hospital in the postoperative period and group 2 (n=123) for the patients discharged from the hospital.Results: In group 1, the lactate level at the time of admission was significantly higher than in group 2: 5.61 (2.51-11.13) mmol/L and 1.84 (1.33-2.98) mmol/L, respectively, P

Abstract Background The role of lactate level in selecting the timing of definitive surgery for isolated extremity fracture remains unclear. Therefore, we aimed to elucidate the use of preoperative lactate level for predicting early postoperative complications. Methods This was a single-center retrospective observational study of patients with isolated extremity fracture who underwent orthopedic surgery. Patients who underwent lactate level assessment within 24 h prior to surgery were included. The incidence of early postoperative complications was compared between patients with a preoperative lactate level of ≥ 2 and

Abstract Background Comparatively little is known regarding the initial cardiorespiratory response of young racehorses to training. The objectives were to compare physiological parameters before and after introductory training and determine whether young Thoroughbreds show endoscopic signs of exercise-induced pulmonary hemorrhage (EIPH). Ten Thoroughbreds (20–23 months) underwent 12-weeks of introductory training, including weekly speed sessions. Two 600 m high-speed exercise tests (HSET) were performed following weeks 4 and 12 while wearing a validated ergospirometry facemask. Peak oxygen consumption (V̇O2pk) and ventilatory parameters (tidal volume, VT; peak inspiratory and expiratory flow, PkV̇I, PkV̇E; respiratory frequency, Rf; minute ventilation, V̇E) were measured. The ventilatory equivalent of oxygen (V̇E/V̇O2) and the aerobic and anaerobic contributions to energy production were calculated. Maximal heart rate (HRmax) and HR at maximal speed (HRVmax) were determined. Post-exercise hematocrit, plasma ammonia and blood lactate were measured. Evidence of EIPH was investigated via tracheobronchoscopy post-exercise. Results were compared (paired t-test, P

Abstract Background Liver cancer ranks sixth in incidence and third in mortality globally and hepatocellular carcinoma (HCC) accounts for 90% of it. Hypoxia, glycolysis, and lactate metabolism have been found to regulate the progression of HCC separately. However, there is a lack of studies linking the above three to predict the prognosis of HCC. The present study aimed to identify a hypoxia–glycolysis–lactate-related gene signature for assessing the prognosis of HCC. Methods This study collected 510 hypoxia-glycolysis-lactate genes from Molecular Signatures Database (MSigDB) and then classified HCC patients from TCGA-LIHC by analyzing their hypoxia-glycolysis-lactate genes expression. Differentially expressed genes (DEGs) were screened out to construct a gene signature by LASSO-Cox analysis. Univariate and multivariate regression analyses were used to evaluate the independent prognostic value of the gene signature. Analyses of immune infiltration, somatic cell mutations, and correlation heatmap were conducted by “GSVA” R package. Single-cell analysis conducted by “SingleR”, “celldex”, “Seurat”, and “CellCha” R packages revealed how signature genes participated in hypoxia/glycolysis/lactate metabolism and PPI network identified hub genes. Results We classified HCC patients from TCGA-LIHC into two clusters and screened out DEGs. An 18-genes prognostic signature including CDCA8, CBX2, PDE6A, MED8, DYNC1LI1, PSMD1, EIF5B, GNL2, SEPHS1, CCNJL, SOCS2, LDHA, G6PD, YBX1, RTN3, ADAMTS5, CLEC3B, and UCK2 was built to stratify the risk of HCC. The risk score of the hypoxia-glycolysis-lactate gene signature was further identified as a valuable independent factor for estimating the prognosis of HCC. Then we found that the features of clinical characteristics, immune infiltration, somatic cell mutations, and correlation analysis differed between the high-risk and low-risk groups. Furthermore, single-cell analysis indicated that the signature genes could interact with the ligand-receptors of hepatocytes/fibroblasts/plasma cells to participate in hypoxia/glycolysis/lactate metabolism and PPI network identified potential hub genes in this process: CDCA8, LDHA, YBX1. Conclusion The hypoxia–glycolysis–lactate-related gene signature we built could provide prognostic value for HCC and suggest several hub genes for future HCC studies.

Abstract Background Sepsis-3 emphasizes the recognition of sepsis-induced cellular metabolic abnormalities, and utilizes serum lactate level as a biomarker of cellular metabolic abnormalities. Magnesium plays an important role as a cofactor in glucose metabolism, although it is not well known that magnesium deficiency causes elevated serum lactate levels. Additionally, it remains unclear how magnesium status affects the role of serum lactate levels as a marker of metabolic abnormalities in sepsis. Thus, this study aimed to investigate the association between serum magnesium and lactate levels in patients with sepsis and explore this relationship from the perspectives of time course and circulatory abnormalities. Methods This retrospective observational study of adult patients with sepsis was performed at the 16-bed intensive care unit of Jichi Medical University Hospital between June 2011 and December 2017. The relationship between serum magnesium and lactate levels for 5 days from intensive care unit admission was investigated along the time course. Multivariate logistic regression analysis was performed to evaluate the association between serum magnesium and lactate levels during intensive care unit admission. Results Among 759 patients included, 105 had hypomagnesemia (magnesium level 2.4 mg/dL) at intensive care unit admission. From intensive care unit admission to day 5, the hypomagnesemia group had higher serum lactate levels and a higher frequency of lactic acidosis than the normal magnesium level and hypermagnesemia groups (70% vs. 51.6% vs. 50%; P 2 mmol/L (odds ratio, 2.76; 95% confidence interval, 1.60–4.76; P

Abstract Background Lactate has emerged as a critical regulator within the tumor microenvironment, including glioma. However, the precise mechanisms underlying how lactate influences the communication between tumor cells and tumor-associated macrophages (TAMs), the most abundant immune cells in glioma, remain poorly understood. This study aims to elucidate the impact of tumor-derived lactate on TAMs and investigate the regulatory pathways governing TAM-mediated tumor-promotion in glioma. Methods Bioinformatic analysis was conducted using datasets from TCGA and CGGA. Single-cell RNA-seq datasets were analyzed by using UCSC Cell Browser and Single Cell Portal. Cell proliferation and mobility were evaluated through CCK8, colony formation, wound healing, and transwell assays. Western blot and immunofluorescence staining were applied to assess protein expression and cell distribution. RT-PCR and ELISA were employed to identify the potential secretory factors. Mechanistic pathways were explored by western blotting, ELISA, shRNA knockdown, and specific inhibitors and activators. The effects of pathway blockades were further assessed using subcutaneous and intracranial xenograft tumor models in vivo. Results Elevated expressions of LDHA and MCT1 were observed in glioma and exhibited a positive correlation with M2-type TAM infiltration. Lactate derived from glioma cells induced TAMs towards M2-subtype polarization, subsequently promoting glioma cells proliferation, migration, invasion, and mesenchymal transition. GPR65, highly expressed on TAMs, sensed lactate-stimulation in the TME, fueling glioma cells malignant progression through the secretion of HMGB1. GPR65 on TAMs triggered HMGB1 release in response to lactate stimulation via the cAMP/PKA/CREB signaling pathway. Disrupting this feedback loop by GPR65-knockdown or HMGB1 inhibition mitigated glioma progression in vivo. Conclusion These findings unveil the intricate interplay between TAMs and tumor cells mediated by lactate and HMGB1, driving tumor progression in glioma. GPR65, selectively highly expressed on TAMs in glioma, sensed lactate stimulation and fostered HMGB1 secretion via the cAMP/PKA/CREB signaling pathway. Blocking this feedback loop presents a promising therapeutic strategy for GBM.

The goal of this work is to create highly sensitive and selective electrochemical sensors that can detect lactate, an essential substance in the body's anaerobic breakdown of carbohydrates, by utilizing lactate oxidase (LOx) and glutaraldehyde (GA)-modified indium-doped zinc oxide (ZnO) nanorods. Several structural investigations validated the effective immobilization of LOx and GA on the modified glassy carbon electrode (GCE) with indium-doped ZnO nanorods. Lactate was detected with the LOx-GA/In-doped ZnO biosensor, which showed linear range of 0.1–36 mM, sensitivity value of 0.73301 µA/mM, and quantification and detection limits of 2.7 μM and 0.8 μM, respectively. The biosensor also displayed stability, repeatability, and selectivity. The sensor demonstrated remarkable lactate recovery rates when applied to real serum and urine specimens from athletes. The serum samples ranged from 96.00% to 99.28% with a relative standard deviation (RSD%) of 3.77–4.25, and the urine samples from 94.00 to 98.58 with an RSD% of 3.55–4.62. These results point to the LOx-GA/In-doped ZnO/GCE sensor platform's potential for a range of biomedical uses.

Cancer is regarded as one of the most cunning and perilous diseases globally. Numerous studies have emphasized the significance of exercise both prior to cancer diagnosis and after hospital discharge, in conjunction with various treatment approaches. However, the role of exercise during cancer itself remains an unresolved query. Oncology research reveals that three crucial factors for metastasis and tumor progression during cancer are lactate, platelets, and angiogenesis. Interestingly, exercise can also have a noteworthy impact on stimulating these three factors. In this brief review, our aim is to shed light on the potential appropriateness of exercise during cancer.

Background: Upper gastrointestinal bleeding is a common presenting complaint in the emergency department (ED) and carries a small but significant mortality rate. In spite of the availability of various scoring systems, risk stratification for in hospital morbidity and mortality remains difficult. There is no single test that can reliably predict active bleeding from the upper gastrointestinal tract for use at primary health level. Aims and Objectives: To study the role of lactate clearance as a predictor of active bleeding and also to determine whether an ED arterial lactate can predict adverse outcomes like increased hospital length of stay, in hospital, 30-day and 60-day mortality. Methods and Material: Prospective single centre observational study at a tertiary hospital in north Kerala that included all stable adult patients who presented with the complaints of hematemesis, melena or both to the ED Arterial lactate was drawn at the bedside, a priori initial arterial lactate cut-off value of 2.2 mmol/L was selected and in patients with lactate value above the cut-off, a second lactate was measured to calculate lactate clearance. Results: Lactate clearance ≤13.39% was found to be associated with a high risk for active bleeding (odds ratio: 23.33; 95% CI = 4.337 to 125.512, P < 0.001). Optimal cut-off points for lactate as well as lactate clearance were derived using receiver operating characteristics curve. Conclusions: Lactate clearance can reliably rule in as well as rule out active bleeding in patients who might seem hemodynamically stable at the initial presentation to the ED.

Background: In the pediatric intensive care unit (PICU), sepsis, sepsis syndromes, septic shock, and multiorgan system failure are frequently encountered and are considered important conditions; Methods: This is a retrospective, observational study over a period of 3 years, that is aimed to investigate the predictive role of lactate levels at admission in order to evaluate disease progression of pediatric patients with septic shock syndrome with the role to identify whether lactate levels at admission could serve as a significant predictor of adverse outcomes. The sample consisted of 21 patients between 1 and 36 months, diagnosed and treated for hemodynamic shock in a tertiary center; Results: The study found that lactate level at admission greater than or equal to 4.95 was associated with 32.5 times increased odds of serious evolution. The study also identified other potential predictors, such as lactate level 12 hours after admission, hemodynamic parameters, and demographic factors; Conclusions: These findings suggest that monitoring lactate levels at admission can provide important information to predict mortality and guiding treatment decisions in pediatric patients with shock syndrome.