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Guarana (GUA) seed extract, containing caffeine (CAF) and additional bioactive compounds, may positively affect mental performance, but evidence regarding exercise is limited. This investigation assessed acute GUA ingestion compared with CAF on endurance performance. Eleven endurance-trained noncyclists and cyclists (V ˙ O 2 peak = 49.7 ± 5.9, 60.4 ± 4.6 ml·kg·min−1) completed a double-blind, crossover experiment after ingesting (a) 100 mg CAF, (b) 500 mg GUA (containing 130 mg CAF), or (c) placebo (P) prior to 60-min fixed cycling workload (FIX) + 15-min time trial. Oxygen uptake, heart rate, respiratory exchange ratio, blood glucose, and lactate were not different (p ≥.052) during FIX. A significant interaction (p =.042) for perceived exertion was observed at 50-min FIX with lower rating (p =.023) for GUA versus CAF but not compared with P. Work accumulated over 15-min time trial was greater (p =.038) for GUA versus P due to higher early (1–11 min) work outputs. Work performance favored (effect size = 0.18; 95% confidence interval [0.003, 0.355], p =.046) GUA (241.4 ± 39.9 kJ) versus P (232.1 ± 46.6 kJ), but CAF (232.3 ± 43.9) was not different from GUA (effect size = 0.19; 95% confidence interval [−0.022, 0.410], p =.079) or P. Postexercise strength loss was not attenuated with GUA (−5.6 ± 8.5%) or CAF (−8.3 ± 9.4%) versus P (−10.3 ± 5.1%). Acute GUA ingestion improved work performance relative to P, but effects were trivial to small and unrelated to altered substrate oxidation or muscular strength. Ergogenicity may involve central mechanisms reducing perceived effort with GUA (containing 130 mg caffeine). Due to issues related to identical matching of dosage, whether GUA confers additional benefits beyond its CAF content cannot be determined at present. [ABSTRACT FROM AUTHOR]

Purpose: Out-of-hospital cardiac arrest (OHCA) carries a relatively poor prognosis and requires multimodal prognostication to guide clinical decisions. Identification of previously unrecognized metabolic routes associated with patient outcome may contribute to future biomarker discovery. In OHCA, inhaled xenon elicits neuro- and cardioprotection. However, the metabolic effects remain unknown. Materials and methods: In this post-hoc study of the randomised, 2-group, single-blind, phase 2 Xe-Hypotheca trial, 110 OHCA survivors were randomised 1:1 to receive targeted temperature management (TTM) at 33°C with or without inhaled xenon during 24 h. Blood samples for nuclear magnetic resonance spectroscopy metabolic profiling were drawn upon admission, at 24 and 72 h. Results: At 24 h, increased lactate, adjusted hazard-ratio 2.25, 95% CI [1.53; 3.30], p<0.001, and decreased branched-chain amino acids (BCAA) leucine 0.64 [0.5; 0.82], p = 0.007, and valine 0.37 [0.22; 0.63], p = 0.003, associated with 6-month mortality. At 72 h, increased lactate 2.77 [1.76; 4.36], p<0.001, and alanine 2.43 [1.56; 3.78], p = 0.001, and decreased small HDL cholesterol ester content (S-HDL-CE) 0.36 [0.19; 0.68], p = 0.021, associated with mortality. No difference was observed between xenon and control groups. Conclusions: In OHCA patients receiving TTM with or without xenon, high lactate and alanine and decreased BCAAs and S-HDL-CE associated with increased mortality. It remains to be established whether current observations on BCAAs, and possibly alanine and lactate, could reflect neural damage via their roles in the metabolism of the neurotransmitter glutamate. Xenon did not significantly alter the measured metabolic profile, a potentially beneficial attribute in the context of compromised ICU patients. Trial registration: Trial Registry number: ClinicalTrials.gov Identifier: NCT00879892. [ABSTRACT FROM AUTHOR]

Background: Serum lactate, as a single and an easily available biomarker, has been applied in various diseases. Aims: In this study, we aimed to explore the predictive value of serum lactate for short-term and long-term prognosis in acute pancreatitis (AP) admitted in intensive care unit (ICU) based on a large-scale database. Methods: AP patients admitted in ICU in the MIMIC-IV database were included. We constructed three different models to investigate the relationships between serum lactate and clinical outcomes, including 30-day, 180-day and 1-year mortality in AP. Smooth fitting curves were performed for intuitively demonstrating the relationship between serum lactate and different outcomes in AP by the generalized additive model. Results: A total of 895 AP patients admitted in ICU were included. The mortalities of 30 days, 180 days, and 1 year were 12.63% (n = 113), 16.87% (n = 151), and 17.54% (n = 157). In model B, with 1-mmol/L increment in serum lactate, the values of OR in 30-day, 180-day and 1-year mortality were 1.20 (95%CI 1.04–1.37, P = 0.0094), 1.21 (95%CI 1.06–1.37, P = 0.0039), and 1.21 (95%CI 1.07–1.38, P = 0.0035). The AUCs of serum lactate for predicting 30-day, 180-day, and 1-year mortality in AP were 0.688 (95%CI 0.633–0.743), 0.655 (95%CI 0.605–0.705), and 0.653 (95%CI 0.603–0.701), respectively. The cut-off value of serum lactate predicting 30-day, 180-day and 1-year mortality in AP was 2.4 mmol/L. Conclusion: Serum lactate could be an indicator for short-term and long-term mortality in patients with AP admitted in ICU. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the potential of glucose, glycine, and a combination of glucose and glycine supplemented into Ringer's lactate extender on the quality of pre- and postcryopreservation of semen of local chickens. Semen samples were collected from KUB roosters. The research procedures involved formulation of the extender, semen collection, assessment of fresh semen, dilution, packaging, cryopreservation, storage, and subsequent assessment of cryopreserved semen. Parameters assessed in fresh, pre-cryopreservation, and post-thawed semen using computerassisted semen analysis (CASA), included motility (total motility, progressive, static, and slow motilities), kinematics, spermatozoa morphology, malondialdehyde (MDA) concentration, and scanning electron microscopy (SEM). There were four treatments: T1= control, T2= 50 mM glucose, T3= 60 mM glycine, and T4= a combination of 50 mM glucose and 60 mM glycine. Each treatment was repeated 10 times. The results showed that the addition of 60 mM glycine and the combination of 50 mM glucose and 60 mM glycine effectively preserved total motility, maintained progressive motility, and reduced damage to the bent tail during the equilibration process (prior to cryopreservation). In addition, total motility, progressive motility, DAP, DSL, DCL, VAP, VSL, VCL, STR, and LIN were significantly increased after thawing. This approach also minimized the formation of MDA. Furthermore, observations using SEM showed comparatively more intact acrosomes compared to the other treatments. In conclusion, the addition of 60 mM glycine and a combination of 60 mM glycine and 50 mM glucose to Ringer's lactate-egg yolk extender proved to be effective in preserving the quality of domestic chicken spermatozoa during semen cryopreservation. [ABSTRACT FROM AUTHOR]

Increased lactate levels and metastasis in tumours are strongly associated with dismal outcomes. But prognostic value of lactate metabolism and transport-related lncRNAs in gastric adenocarcinoma (GA) patients remains unaddressed. Gene expression data of GA were provided by The Cancer Genome Atlas. Lactate metabolism and transport-related gene data were accessed from GSEA. LncRNAs related to lactate metabolism and transport were identified by correlation analysis. A prognostic model was built by regression analysis. Validity of prognostic model was confirmed through survival analysis and receiver operating characteristic (ROC) curve. Immunity of each risk group was evaluated by immune correlation analysis.LncRNA-mRNA network was built by correlation analysis using Cytoscape software. A 12-gene prognostic model based on lactate metabolism and transport-related lncRNAs was built in GA. Median riskscore was utilized to classify GA samples into high- and low-risk groups. Survival analysis and ROC curves demonstrated validity of prognostic model. Most immune checkpoint molecules and TIDE scores were lower in the low-risk group. LINC01303 and LINC01545 may be the key prognostic factors in patients with GA. This study successfully built a prognostic model of lactate metabolism and transport-related lncRNAs in GA. The findings guide prognostic management of GA patients. [ABSTRACT FROM AUTHOR]

Caffeic acid (CA), a polyphenolic compound, has demonstrated antibacterial and antioxidant properties, suggesting potential benefits in preventing atherosclerosis and other cardiovascular disorders. However, its potential carcinogenicity to humans assigns it to category 2B. Hence, vigilant monitoring of the decreasing accuracy in CA determination becomes imperative. In this work, we proposed the synthesis of an ethyl imidazolium lactate ionic-liquid-assisted M-type barium ferrite grafted reduced graphene oxide nanocomposite (BF@rGO) and evaluate its electrocatalytic action towards CA sensor. The prepared samples are examined for their physicochemical nature using variety of spectro- and microscopic studies. The examined morphology outcomes exposed the well distribution of BF nanoparticles on the rGO nanosheets. The electrochemical detection of CA with the BF@rGO-modified electrode unveiled a higher current with minimal sensing working potential than that of other electrodes inspected in this study. The three-order magnitude analysis revealed adsorption-controlled kinetics and the quasi-reversible process of the BF@rGO-modified electrode toward CA detection. The detection limit of CA is assessed to be 0.77 nM, with a broad linear range of 0.01–892.51 μM, respectively. A supernatant coffee sample was used for real-time analysis, and a well-thought-of recovery percentage of 99.41% was attained. Therefore, the proposed BF@rGO-modified electrode demonstrates practical reliability in the detection of CA in food samples. [ABSTRACT FROM AUTHOR]

Context The metabolic response to stress can deplete the remaining thiamine stores, leading to thiamine deficiency. Objective This study is the first meta-analysis of the effectiveness of thiamine supplementation on clinical and biochemical outcomes in adult patients admitted to the intensive care unit (ICU). Data Sources Scopus, PubMed, and Cochrane databases were searched to select studies up to 20 November 2022. Study Selection Studies investigating the effect of thiamine supplementation on serum lactate and creatinine levels, the need for renal replacement therapy, length of ICU stay, and mortality rate in ICU patients were selected. Data Extraction After excluding studies based on title and abstract screening, 2 independent investigators reviewed the full texts of the remaining articles. In the next step, a third investigator resolved any discrepancy in the article selection process. Results Of 1628 retrieved articles, 8 were selected for final analysis. This study showed that thiamine supplementation reduced the serum creatinine level (P =.03) compared with placebo. In addition, according to subgroup analysis, serum creatinine concentration was significantly lower in patients >60 years old (P < .00001). However, there was no statistically significant difference in the lactate level between the thiamine supplementation and placebo groups (P =.26). Thiamine supplementation did not decrease the risk of all-cause mortality (P =.71) or the need for renal replacement therapy (P =.14). The pooled results of eligible randomized controlled trials also showed that thiamine supplementation did not reduce the length of ICU stay in comparison to the placebo group (P =.39). Conclusion This meta-analysis provides evidence that thiamine supplementation has a protective effect against blood creatinine increase in ICU patients. However, further high-quality trials are needed to discover the effect of thiamine supplementation on clinical and biochemical outcomes in ICU patients. Systematic Review Registration PROSPERO no. CRD42023399710 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=399710). [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a serious threat to women's health with high morbidity and mortality. The development of more effective therapies for the treatment of breast cancer is strongly warranted. Growing evidence suggests that targeting glucose metabolism may be a promising cancer treatment strategy. We previously identified a new glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor, DC-5163, which shows great potential in inhibiting tumor growth. Here, we evaluated the anticancer potential of DC-5163 in breast cancer cells. Methods: The effects of DC-5163 on breast cancer cells were investigated in vitro and in vivo. Seahorse, glucose uptake, lactate production, and cellular ATP content assays were performed to examine the impact of DC-5163 on cellular glycolysis. Cell viability, colony-forming ability, cell cycle, and apoptosis were assessed by CCK8 assay, colony formation assay, flow cytometry, and immunoblotting respectively. The anticancer activity of DC-5163 in vivo was evaluated in a mouse breast cancer xenograft model. Results: DC-5163 suppressed aerobic glycolysis and reduced energy supply of breast cancer cells, thereby inhibiting breast cancer cell growth, inducing cell cycle arrest in the G0/G1 phase, and increasing apoptosis. The therapeutic efficacy was assessed using a breast cancer xenograft mouse model. DC-5163 treatment markedly suppressed tumor growth in vivo without inducing evident systemic toxicity. Micro-PET/CT scans revealed a notable reduction in tumor 18F-FDG and 18F-FLT uptake in the DC-5163 treatment group compared to the DMSO control group. Conclusions: Our results suggest that DC-5163 is a promising GAPDH inhibitor for suppressing breast cancer growth without obvious side effects. 18F-FDG and 18F-FLT PET/CT can noninvasively assess the levels of glycolysis and proliferation in tumors following treatment with DC-5163. [ABSTRACT FROM AUTHOR]

Background: Recent studies have provided evidence supporting the functional role and mechanism of lactate in suppressing anticancer immunity. However, there is no systematic analysis of lactate metabolism-related genes (LMRGs) and ovarian cancer (OV) prognosis. Results: Six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) were selected as prognostic genes and a prognostic model was utilized. Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) analyses were further performed and indicated that the prognostic model was effective. Subsequently, the neoplasm_cancer_status and RiskScore were determined as independent prognostic factors, and a nomogram was established with relatively accurate forecasting ability. Additionally, 2 types of immune cells (Central memory CD8 T cell and Immature B cell), 4 types of immune functions (APC co inhibition, DCs, Tfh and Th1 cells), 9 immune checkpoints (BTLA, CTLA4, IDO1, LAG3, VTCN1, CXCL10, CXCL9, IFNG, CD27) and tumor immune dysfunction and exclusion (TIDE) scores were significantly different between risk groups. The expression of 6 genes were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the expression of 6 genes were higher in the high-grade serous carcinoma (HGSC) samples. Conclusion: A prognostic model related to lactate metabolism was established for OV based on six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) that could provide new insights into therapy. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Background: The initiation of fibroblast growth factor 1 (FGF1) expression coincident with the decrease of FGF2 expression is a well-documented event in prostate cancer (PCa) progression. Lactate dehydrogenase A (LDHA) and LDHB are essential metabolic products that promote tumor growth. However, the relationship between FGF1/FGF2 and LDHA/B-mediated glycolysis in PCa progression is not reported. Thus, we aimed to explore whether FGF1/2 could regulate LDHA and LDHB to promote glycolysis and explored the involved signaling pathway in PCa progression. Methods: In vitro studies used RT‒qPCR, Western blot, CCK-8 assays, and flow cytometry to analyze gene and protein expression, cell viability, apoptosis, and cell cycle in PCa cell lines. Glycolysis was assessed by measuring glucose consumption, lactate production, and extracellular acidification rate (ECAR). For in vivo studies, a xenograft mouse model of PCa was established and treated with an FGF pathway inhibitor, and tumor growth was monitored. Results: FGF1, FGF2, and LDHA were expressed at high levels in PCa cells, while LDHB expression was low. FGF1/2 positively modulated LDHA and negatively modulated LDHB in PCa cells. The depletion of FGF1, FGF2, or LDHA reduced cell proliferation, induced cell cycle arrest, and inhibited glycolysis. LDHB overexpression showed similar inhibitory effect on PCa cells. Mechanistically, we found that FGF1/2 positively regulated STAT1 and STAT1 transcriptionally activated LDHA expression while suppressed LDHB expression. Furthermore, the treatment of an FGF pathway inhibitor suppressed PCa tumor growth in mice. Conclusion: The FGF pathway facilitates glycolysis by activating LDHA and suppressing LDHB in a STAT1-dependent manner in PCa. [ABSTRACT FROM AUTHOR]

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most common neurological problems occurring in the perinatal period. However, there still is not a promising approach to reduce long-term neurodevelopmental outcomes of HIE. Recently, itaconate has been found to exhibit anti-oxidative and anti-inflammatory effects. However, the therapeutic efficacy of itaconate in HIE remains inconclusive. Therefore, this study attempts to explore the pathophysiological mechanisms of oxidative stress and inflammatory responses in HIE as well as the potential therapeutic role of a derivative of itaconate, 4-octyl itaconate (4OI). Methods: We used 7-day-old mice to induce hypoxic-ischemic (HI) model by right common carotid artery ligation followed by 1 h of hypoxia. Behavioral experiments including the Y-maze and novel object recognition test were performed on HI mice at P60 to evaluate long-term neurodevelopmental outcomes. We employed an approach combining non-targeted metabolomics with transcriptomics to screen alterations in metabolic profiles and gene expression in the hippocampal tissue of the mice at 8 h after hypoxia. Immunofluorescence staining and RT-PCR were used to evaluate the pathological changes in brain tissue cells and the expression of mRNA and proteins. 4OI was intraperitoneally injected into HI model mice to assess its anti-inflammatory and antioxidant effects. BV2 and C8D1A cells were cultured in vitro to study the effect of 4OI on the expression and nuclear translocation of Nrf2. We also used Nrf2-siRNA to further validate 4OI-induced Nrf2 pathway in astrocytes. Results: We found that in the acute phase of HI, there was an accumulation of pyruvate and lactate in the hippocampal tissue, accompanied by oxidative stress and pro-inflammatory, as well as increased expression of antioxidative stress and anti-inflammatory genes. Treatment of 4OI could inhibit activation and proliferation of microglial cells and astrocytes, reduce neuronal death and relieve cognitive dysfunction in HI mice. Furthermore, 4OI enhanced nuclear factor erythroid-2-related factor (Nfe2l2; Nrf2) expression and nuclear translocation in astrocytes, reduced pro-inflammatory cytokine production, and increased antioxidant enzyme expression. Conclusion: Our study demonstrates that 4OI has a potential therapeutic effect on neuronal damage and cognitive deficits in HIE, potentially through the modulation of inflammation and oxidative stress pathways by Nrf2 in astrocytes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this paper, we consider a singular nonlinear differential system that characterizes the intricate dynamics of brain lactate kinetics between cells and capillaries, as described by System (1.1) below. We begin by establishing the existence and uniqueness of nonnegative solutions for our system through the application of Schauder's fixed-point theorem. Subsequently, we explore the behavior of these solutions as the viscosity term approaches zero, shedding light on the system's dynamic evolution in such scenarios. To provide empirical validation for our theoretical findings, we offer a series of numerical simulations. These simulations not only confirm the results we have obtained but also reinforce prior research, underscoring the model's efficiency in capturing the complexities of the brain's lactate kinetics. Our work contributes not only to the theoretical underpinning of this field but also to its practical implications, making it a valuable resource for both researchers and practitioners seeking to comprehend and manipulate these vital biological processes. [ABSTRACT FROM AUTHOR]

Polylactic acid (PLA), a biomass material, has garnered increasing interest as a biodegradable alternative for the production of eco-friendly plastics. Accordingly, the sustainable synthesis of lactic acid (LA) and its derivatives from biomass sources is emerging as a viable approach. In this work, an In-TS-1 zeolite with exceptional catalytic activity and stability was successfully synthesized using a hydrothermal method and applied for the efficient one-pot conversion of fructose into methyl lactate (MLA). Characterization of the resulting catalysts, including pyridine-adsorbed Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, ultraviolet-visible diffuse reflectance spectroscopy, and energy dispersive X-ray spectroscopy for elemental mapping, confirmed that the uniform dispersion of indium (In) species contributed to its favorable acidity and significantly boosted the reaction efficiency. Under optimized reaction conditions, a remarkable MLA yield of 71.9% was achieved upon the complete conversion of fructose. The selectivity of MLA remained consistent over 14 cycles, underscoring its extraordinary stability under hydrothermal conditions attributed to the confinement of In species within the zeolite framework. This research technique establishes a potential strategy for the large-scale manufacture of LA and its esters, offering a sustainable and efficient path for the development of biodegradable plastics. [ABSTRACT FROM AUTHOR]

Background: Metabolic reprogramming and epigenetic alterations contribute to the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). Lactate-dependent histone modification is a new type of histone mark, which links glycolysis metabolite to the epigenetic process of lactylation. However, the role of histone lactylation in PDAC remains unclear. Methods: The level of histone lactylation in PDAC was identified by western blot and immunohistochemistry, and its relationship with the overall survival was evaluated using a Kaplan-Meier survival plot. The participation of histone lactylation in the growth and progression of PDAC was confirmed through inhibition of histone lactylation by glycolysis inhibitors or lactate dehydrogenase A (LDHA) knockdown both in vitro and in vivo. The potential writers and erasers of histone lactylation in PDAC were identified by western blot and functional experiments. The potential target genes of H3K18 lactylation (H3K18la) were screened by CUT&Tag and RNA-seq analyses. The candidate target genes TTK protein kinase (TTK) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) were validated through ChIP-qPCR, RT-qPCR and western blot analyses. Next, the effects of these two genes in PDAC were confirmed by knockdown or overexpression. The interaction between TTK and LDHA was identified by Co-IP assay. Results: Histone lactylation, especially H3K18la level was elevated in PDAC, and the high level of H3K18la was associated with poor prognosis. The suppression of glycolytic activity by different kinds of inhibitors or LDHA knockdown contributed to the anti-tumor effects of PDAC in vitro and in vivo. E1A binding protein p300 (P300) and histone deacetylase 2 were the potential writer and eraser of histone lactylation in PDAC cells, respectively. H3K18la was enriched at the promoters and activated the transcription of mitotic checkpoint regulators TTK and BUB1B. Interestingly, TTK and BUB1B could elevate the expression of P300 which in turn increased glycolysis. Moreover, TTK phosphorylated LDHA at tyrosine 239 (Y239) and activated LDHA, and subsequently upregulated lactate and H3K18la levels. Conclusions: The glycolysis-H3K18la-TTK/BUB1B positive feedback loop exacerbates dysfunction in PDAC. These findings delivered a new exploration and significant inter-relationship between lactate metabolic reprogramming and epigenetic regulation, which might pave the way toward novel lactylation treatment strategies in PDAC therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and performance of an implantable near-infrared (NIR) spectroscopy sensor for multi-metabolite monitoring of glucose, ketones, lactate, and ethanol. Research design and methods: This is an early feasibility study (GLOW, NCT04782934) including 7 participants (4 with type 1 diabetes (T1D), 3 healthy volunteers) in whom the YANG NIR spectroscopy sensor (Indigo) was implanted for 28 days. Metabolic challenges were used to vary glucose levels (40–400 mg/dL, 2.2–22.2 mmol/L) and/or induce increases in ketones (ketone drink, up to 3.5 mM), lactate (exercise bike, up to 13 mM) and ethanol (4–8 alcoholic beverages, 40-80g). NIR spectra for glucose, ketones, lactate, and ethanol levels analyzed with partial least squares regression were compared with blood values for glucose (Biosen EKF), ketones and lactate (GlucoMen LX Plus), and breath ethanol levels (ACE II Breathalyzer). The effect of potential confounders on glucose measurements (paracetamol, aspartame, acetylsalicylic acid, ibuprofen, sorbitol, caffeine, fructose, vitamin C) was investigated in T1D participants. Results: The implanted YANG sensor was safe and well tolerated and did not cause any infectious or wound healing complications. Six out 7 sensors remained fully operational over the entire study period. Glucose measurements were sufficiently accurate (overall mean absolute (relative) difference MARD of 7.4%, MAD 8.8 mg/dl) without significant impact of confounders. MAD values were 0.12 mM for ketones, 0.16 mM for lactate, and 0.18 mM for ethanol. Conclusions: The first implantable multi-biomarker sensor was shown to be well tolerated and produce accurate measurements of glucose, ketones, lactate, and ethanol. Trial registration: Clinical trial identifier: NCT04782934. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine whether bone morphogenetic protein-4 (BMP-4), which increases in response to intimal hyperplasia, promotes phenotype transition in vascular smooth muscle cells (VSMCs). Methods: Balloon injury was used to induce intimal hyperplasia in rats. Hematoxylin-eosin staining was used to detect the alteration of vascular structure. Serum levels of BMP-4 and lactate were detected by ELISA. Human aortic smooth muscle cells (HA-SMCs) were cultured. Protein and mRNA expression levels were detected through Western blot and real-time PCR. Cell migration was measured by transwell assay. Results: Our data showed that serum concentration of BMP-4 was upregulated after balloon injury. Treatment with BMP-4 inhibitor DMH1 (4-(6-(4-isopropoxyphenyl)pyrazolo(1,5-a)pyrimidin-3-yl)quinoline) suppressed the abnormal expression of BMP-4 and inhibited the intimal hyperplasia induced by balloon injury. Compared to BMP-4-negative medium, BMP-4-positive medium was associated with higher synthetic VSMC marker expression levels and lower in contractile gene markers in cultured HA-SMCs. Transfection of monocarboxylic acid transporters-4 (MCT-4) siRNA inhibited the excretion of lactate induced by BMP-4. Conclusion: Our analyses provided evidence that BMP-4 and its regulator Smad-4 are key regulators in MCT-4-mediated lactate excretion. This indicates that BMP-4 stimulates the phenotypic transition of VSMCs via SMAD-4/MCT-4 signaling pathway. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore the association between lactate/albumin ratio and the prognosis of sepsis patients. Methods: A computerized search was performed in Pubmed, EMbase, Ovid, Medline, and Google Scholar to collate relevant studies. The results were compared using standardized mean differences (SMD)/odds ratio (OR) and 95% confidence intervals (CI). Prospective and retrospective cohort studies were both included in this study. Results: A total of nine studies involving 3039 participants were included. Pooled analysis revealed that survivors had substantially lower lactate/albumin ratio than non-survivors (SMD=-2.02, 95% CI: -2.76 to -1.28, I2=97.4%). Further, our results also indicated that elevated lactate/albumin ratio is an independent risk factor for mortality (OR=2.16, 95% CI: 1.58 to 2.95, I2=76.2%) and multiple organ dysfunction syndrome (MODS) (OR=3.41, 95% CI: 1.78 to 6.50, I2=0.0%) in septic patients. Moreover, according to the area under curve (AUC) results, the lactate/albumin ratio also presented good discriminatory power to predict mortality (AUC=0.75, 95% CI: 0.68 to 0.84, I2=92.9%) and MODS (AUC=0.78, 95% CI: 0.68 to 0.91, I2= 65.1%) in septic patients. Begg's and Egger's tests suggested no publication bias in the included studies. Conclusion: Our results highlighted that the lactate/albu- min ratio is an important prognostic factor for MODS and mortality in sepsis patients, having good capabilities in identifying MODS and mortality. Elevated lactate/albumin ratio is an independent risk factor for mortality and multiple organ dysfunction syndrome (MODS) in septic patients. The lactate/albumin ratio also presented good discriminatory power to predict mortality and MODS in septic patients. [ABSTRACT FROM AUTHOR]

Background: Major surgeries can develop metabolic acidosis during the perioperative period. Any clinical condition leading to decreased tissue oxygenation causes lactate levels to rise proportionally. Aims and Objectives: This study was aimed at evaluating perioperative serum lactate as a predictor of length of hospital stay and in-hospital mortality in patients undergoing emergency major abdominal surgeries. Materials and Methods: Adult patients posted for emergency abdominal surgical procedures were enrolled for 2 years. Patients were observed intraoperatively and lactate levels were measured. In post-operative period lactate levels were recorded for 24 h. Relationship of lactate with hospital length of stay and in-hospital mortality was analyzed. Results: Total of 93 patients were enrolled for 2 years. Mean age was 50.4 years. Mean baseline lactate was 2.95 mmol/L. Total in-hospital mortality was 16.1%. Thirteen patients had perioperative serum lactate level of = 2 mmol/l, with a mean hospital length of stay of 8.6 days and no mortality. Fifty-one patients having perioperative serum lactate between 2 and 4 mmol/L, with a mean hospital length of stay of 11.2 days and mortality of 13.3%. Twenty-nine patients had serum lactate of >4 mmol/L, with a mean hospital length of stay of 17.3 days and mortality of 86.7%. Elevated serum lactate was associated with a longer length of hospital stay, with lactate at 12 h having the highest predictive value (area under curve 0.987). Similarly, lactate at 12 h had the highest accuracy at predicting mortality as per receiver operating characteristic (AUC 0.895). Conclusion: Serum lactate was associated with increased in-hospital mortality and longer length of hospital stay in emergency abdominal surgeries. [ABSTRACT FROM AUTHOR]

OBJECTIVES The multifactorial dynamic perfusion index was recently introduced as a predictor of cardiac surgery-associated acute kidney injury. The multifactorial dynamic perfusion index was developed based on retrospective data retrieved from the patient files. The present study aims to prospectively validate this index in an external series of patients, through an on-line measure of its various components. METHODS Inclusion criteria were adult patients undergoing cardiac surgery with cardiopulmonary bypass. Data collection included preoperative factors and cardiopulmonary bypass-related factors. These were collected on-line using a dedicated monitor. Factors composing the multifactorial dynamic perfusion index are the nadir haematocrit, the nadir oxygen delivery, the time of exposure to a low oxygen delivery, the nadir mean arterial pressure, cardiopulmonary bypass duration, the use of red blood cell transfusions and the peak arterial lactates. RESULTS Two hundred adult patients were investigated. The multifactorial dynamic perfusion index had a good (c-statistics 0.81) discrimination for cardiac surgery-associated acute kidney injury (any stage) and an excellent (c-statistics 0.93) discrimination for severe patterns (stage 2–3). Calibration was modest for cardiac surgery-associated acute kidney injury (any stage) and good for stage 2–3. The use of vasoconstrictors was an additional factor associated with cardiac surgery-associated acute kidney injury. CONCLUSIONS The multifactorial dynamic perfusion index is validated for discrimination of cardiac surgery-associated acute kidney injury risk. It incorporates modifiable risk factors, and may help in reducing the occurrence of cardiac surgery-associated acute kidney injury. [ABSTRACT FROM AUTHOR]

Herein, a self-powered lactate biosensor (SPLBs) was assembled to detect lactate in sweat based on flexible textile matrix enzymatic electrodes. A porous three-dimensional electrode with high flexibility and electrical conductivity was obtained by decorating composites of reduced graphene oxide and carboxylate multiwalled carbon nanotubes onto a cellulose fabric substrate. The excellent enzyme embedding method using a gel electrolyte showed a Michaelis–Menten constant of 1.46 mM, indicating the high enzymatic activity of lactate dehydrogenase. Moreover, the assembled (SPLBs) displayed a sensitivity of 3.16 µW mM−1 cm−2 with a linear range of 0–10 mM and a detection limit of 9.49 µM. Additionally, the biosensor has good tensile flexural stability, selectivity, and long-term stability. When integrated into clothing, the (SPLBs) recovered 91.5–102.3% of lactate from real sweat, with a relative standard deviation of less than 4.16%. This biosensor is promising for sensing lactate in human sweat. [ABSTRACT FROM AUTHOR]

Introduction Alcohol ingestion influences metabolism during a subsequent exercise session, as evidenced by increased blood lactate concentration during fixed-intensity exercise. Therefore, augmented blood concentrations of alcohol may interfere with the anaerobic metabolism during high-intensity, short-duration exercise bout, thereby leading to impaired athletic performance. Objective This study investigated whether the acute ingestion of alcohol as ethanol modulates performance parameters derived from the power–duration relationship in a 3-min all-out cycling test that allows for identifying the power output related to heavy and severe exercise intensities. Methods Twenty-four recreationally active cyclists (16 men and 8 women) ingested a beverage containing either 0.4 g ethanol.kg−1 body mass (EtOH) or a placebo (PLA) solution. Thirty minutes following ingestion, they completed a 3-min all-out test to measure power output and determine the end-test power (EP) and the work done above EP (WEP). Results Alcohol ingestion decreased WEP by 16% (EtOH: 5.6 ± 2.5 kJ vs. PLA: 6.7 ± 2.4 kJ; P  = .003) but did not change EP (EtOH: 211 ± 44 W vs. PLA: 212 ± 44 W; P  = .671). The alcohol-mediated effect in WEP was not influenced when controlling for participants' sex or accuracy in identifying the beverage ingested. Conclusion Our data indicate that alcohol ingestion impaired the anaerobic work capacity, as evidenced by the reduction in WEP during the 3-min all-out test. Moreover, the ability to exercise at an intensity above the heavy domain may be decreased after ingestion of a moderate alcohol dose. [ABSTRACT FROM AUTHOR]

• Glycolysis-related proteins and lactate production was related with increased expression of PRMT6 in the ipsilateral spinal cord dorsal horn of CCI mice. • PRMT6 deficiency or prophylactic and therapeutic intrathecal administration of PRMT6 inhibitor (EPZ020411) ameliorated CCI-induced NP, inflammation and glycolysis. • PRMT6 could interact with and methylate HIF-1α, which increased HIF-1α protein stability. • Inhibiting PRMT6 might be a new treatment strategy for NP. Microglia induced chronic inflammation is the critical pathology of Neuropathic pain (NP). Metabolic reprogramming of macrophage has been intensively reported in various chronic inflammation diseases. However, the metabolic reprogramming of microglia in chronic pain remains to be elusive. Here, we reported that immuno-metabolic markers (HIF-1α, PKM2, GLUT1 and lactate) were related with increased expression of PRMT6 in the ipsilateral spinal cord dorsal horn of the chronic construction injury (CCI) mice. PRMT6 deficiency or prophylactic and therapeutic intrathecal administration of PRMT6 inhibitor (EPZ020411) ameliorated CCI-induced NP, inflammation and glycolysis in the ipsilateral spinal cord dorsal horn. PRMT6 knockout or knockdown inhibited LPS-induced inflammation, proliferation and glycolysis in microglia cells. While PRMT6 overexpression exacerbated LPS-induced inflammation, proliferation and glycolysis in BV2 cells. Recent research revealed that PRMT6 could interact with and methylate HIF-1α, which increased HIF-1α protein stability. In sum, increased expression of PRMT6 exacerbates NP progress by increasing glycolysis and neuroinflammation through interacting with and stabilizing HIF-1α in a methyltransferase manner, which outlines novel pathological mechanism and drug target for NP. [ABSTRACT FROM AUTHOR]

Introduction: Acute type A aortic dissection (ATAAD) is one of the most critical emergencies in cardiovascular surgery. Additional complications such as organ malperfusion can significantly decrease the chances of survival. Despite promptly performed surgical treatment, impaired organ perfusion may persist, thus close postoperative monitoring is recommended. But, is there a surgical consequence due to the existence of a preoperatively known malperfusion and is there a correlation between pre-, peri- and postoperative levels of serum lactate and proven malperfusion? Methods: Between 2011 and 2018, 200 patients (66% male; median age: 62.5 years; interquartile range: +/−12.4 years) that received surgical treatment at our institution for an acute dissection DeBakey type I were enrolled in this study. The cohort was divided into two groups according to the preoperative existence of malperfusion and non-malperfusion. At least one kind of malperfusion occurred in 74 patients (Group A: 37%), while 126 patients (Group B: 63%) showed no evidence of malperfusion. Furthermore, lactate levels of both cohorts were differentiated into four periods: preoperative, intraoperative, 24 hours after surgery, and 2–4 days after surgery. Results: The patients' status differed significantly prior to surgery. Group A (malperfusion) showed an elevated requirement for mechanical resuscitation (A: 10.8%; B: 5.6%; p : 0.173), were significantly more often admitted in an intubated state (A: 14.9%; B: 2.4%; p : 0.001) and showed higher incidences of stroke (A: 18.9% (n = 149); B: 3.2% (n = 4); p : 0.001). Levels of serum lactate from the preoperative period until days 2–4 were significantly increased in the malperfusion cohort at all times. Conclusions: Preexisting malperfusion due to ATAAD may significantly increase the chance of early mortality in patients with ATAAD. Serum lactate levels were a reliable marker for inadequate perfusion from admission until day 4 after surgery. Despite this, early intervention survival in this cohort remains limited. [ABSTRACT FROM AUTHOR]

At work rate corresponds to heavy or severe exercise, a slowly developing component of the V ˙ O 2 response, named V ˙ O 2 slow component appear. A clear picture of the mechanism underlying the slow-component rise in V ˙ O 2 remains to be described. We argue in this article that the V ˙ O 2 slow component could be explained by a progressive lactate and pyruvate availability for mitochondria observed only when oxidative capacity of muscle is challenged (above lactate threshold). In this kind of exercise, the work rate requires the use of a large number of mitochondria that could only be involved when the pyruvate/lactate concentration in the cells is increased. This mechanism would then operate according to the law of mass action. The resynthesize of ATP should become progressively more aerobic than anaerobic. The hypothesis of a pyruvate/lactate concentration mechanism of V ˙ O 2 slow component needs further experimental validation. [ABSTRACT FROM AUTHOR]

The production of short chain fatty acids (SCFAs) by the colonic microbiome has numerous benefits for human health, including maintenance of epithelial barrier function, suppression of colitis, and protection against carcinogenesis. Despite the therapeutic potential, there is currently no optimal approach for elevating the colonic microbiome's synthesis of SCFAs. In this study, poly(D, l -lactide- co -glycolide) (PLGA) was investigated for this application, as it was hypothesised that the colonic microbiota would metabolise PLGA to its lactate monomers, which would promote the resident microbiota's synthesis of SCFAs. Two grades of spray dried PLGA, alongside a lactate bolus control, were screened in an advanced model of the human colon, known as the M-SHIME® system. Whilst the high molecular weight (Mw) grade of PLGA was stable in the presence of the microbiota sourced from three healthy humans, the low Mw PLGA (PLGA 2) was found to be metabolised. This microbial degradation led to sustained release of lactate over 48 h and increased concentrations of the SCFAs propionate and butyrate. Further, microbial synthesis of harmful ammonium was significantly reduced compared to untreated controls. Interestingly, both types of PLGA were found to influence the composition of the luminal and mucosal microbiota in a donor-specific manner. An in vitro model of an inflamed colonic epithelium also showed the polymer to affect the expression of pro- and anti-inflammatory markers, such as interleukins 8 and 10. The findings of this study reveal PLGA's sensitivity to enzymatic metabolism in the gut, which could be harnessed for therapeutic elevation of colonic SCFAs. [Display omitted] • PLGA is susceptible to metabolism by the human gut microbiome. • Digestion of PLGA with Mw 2000–2500 g/mol led to sustained lactate release. • Lactate from PLGA was converted to propionate and butyrate in a colonic model. • PLGA affected the abundance and composition of luminal and mucosal microbiota. • PLGA exerted donor-specific effects on intestinal epithelial cells. [ABSTRACT FROM AUTHOR]

Heart Rate (HR) is widely used for erobic exercise intensity prescriptions and/or studies of exercise training. It is often assumed that exercising at a given HR results in similar physiological response, regardless of exercise modality. This study aimed to gauge cellular immune mobilization to submaximal exercise at a given target HR on a cycle ergometer (CE) and treadmill (TM). Thirteen healthy male adults (23.2 ± 3.5 y.o) completed 4 laboratory visits. Participants performed two graded exercise tests to exhaustion on CE and TM and two 30‐min constant exercise challenges at 70% HR reserve on CE or TM in random order. Rating of Perceived Exertion (RPE) was recorded every 5 min, and blood was drawn before and after exercise to measure leukocytes subpopulation levels, lactate, and IL‐6. HR was successfully "clamped" during the exercise in CE and TM (CE 156.7 ± 1.1; TM 159.3 ± 1.6 bpm). Cycling was perceived as more strenuous than running and was accompanied by a greater increase in lactate post‐exercise (p < 0.0001; 6.2 ± 0.3 vs. 2.9 ± 0.3 mmol/L). IL‐6 and leukocytes subpopulations were significantly elevated post‐exercise (p < 0.003) with no difference between exercise modalities (monocytes; CE 57.6% TM 61.2%, granulocytes; CE 41.37%, TM 50.1%, lymphocytes; CE 91.03%, TM 78.8%). The findings revealed that HR is not sufficient in and of itself to fully assess the metabolic stress associated with a given exercise modality. However, despite different metabolic and subjective stress, the IL‐6 and leukocyte counts relative changes were similar in the two modalities. Highlights: These findings provide valuable insights into the leukocytes and lactate responses to cycling and running at the same target heart rate. The study further elaborates on the shared patterns and distinctions in physiological and metabolic responses and their implications for designing targeted training programs.At the same target heart rate, running resulted in significantly lower lactate levels and subjective rate of perceived exertion (RPE) while yielding higher VO2 levels compared to cycling.Leukocytes and IL‐6 increases post‐exercise were not different between running and cycling, indicating that they did not reflect the distinct metabolic and subjective perceived loads associated with cycling and running.Since heart rate in and of itself is not sufficient to fully characterize the metabolic stress induced by a specific exercise modality, it is important to consider the modality of exercise when prescribing training programs for improving cardiovascular fitness or achieving target energy expenditure through heart rate monitoring. [ABSTRACT FROM AUTHOR]

Bimetallic AuCu/SiO2 nanosized catalysts were prepared using the wet chemical reduction technique. From among Au0.1–1.5Cu10/SiO2 catalysts, the Au0.5Cu10/SiO2 catalyst gave the highest yield of calcium lactate of 87% at a glycerol conversion of 96% when the reaction of glycerol with calcium hydroxide at a mole ratio of calcium hydroxide to glycerol of 0.8:1 was conducted under an anaerobic atmosphere at 200 °C for 2 h. The interactions between metallic Au0 and Cu0 nanoparticles facilitate calcium lactate formation. The simulation of glycerol consumption rate with an empirical power-function reaction kinetics equation yielded a reaction activation energy of 44.3 kJ∙mol−1, revealing that the catalytic reaction of glycerol with calcium hydroxide to calcium lactate can be conducted by overcoming a mild energy barrier. The synthesis of calcium lactate through the catalytic reaction of glycerol with calcium hydroxide on a bimetallic AuCu/SiO2 nanosized catalyst under a safe anaerobic atmosphere is an alternative to the conventional calcium lactate production technique through the reaction of expensive lactic acid with calcium hydroxide. [ABSTRACT FROM AUTHOR]

BACKGROUND: Clinical assessment and laboratory markers provide valuable information on tissue perfusion and enhance the optimalisation of management in the treatment of patients on extracorporeal membrane oxygenation (ECMO). The PCO2 gap is a reliable marker of cardiac output (CO) and perfusion. The aim of this study was to evaluate the PCO2 gap as a marker of tissue hypoperfusion and to compare it to lactate and SvO². METHODS: A single-center retrospective study on 131 adult cardiac patients who underwent ECMO implantation in the period between 2010 and 2021. Baseline characteristics, laboratory markers and mortality were analyzed. RESULTS: There was a statistically significant difference in the plasmatic levels of lactate, SvO2 and PCO2 gap between patients that survived and those who died post ECMO implantation (3.6±3.29 vs 7.15±7.38 mmol/l, p<0.001; 69.13±9 vs 67.38±10%, p<0.001; 7.65±2.93 vs 8.34±3.71, p<0.001 respectively). There was a statistically significant difference in PCO2 gap in the first 5 arterial blood gas (ABG) samples post ECMO implantation between patients that survived and those who died (9.08±4.79 vs 10.37±5.35, p<0.003). For SvO2, this difference was not statistically significant (69.82±11.91 vs 68.51±11.72, p<0.104). There was a statistically significant but low negative correlation between SvO2 and PCO2 gap post ECMO implantation (r = -0.354, p<0.001). CONCLUSION: The PCO2 gap is a valuable biomarker for monitoring tissue perfusion in patients on ECMO. It is associated with increased mortality and should be an integral part of clinical evaluation. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is one of the most common gynecological cancers. Accumulated evidence shows that long non‐coding RNAs (lncRNAs) play essential roles in cervical cancer occurrence and progression, but their specific functions and mechanisms remain to be further explored. Methods: The RT‐qPCR assay was used to detect the expression of NEAT1 in cervical cancer tissues and cell lines. CCK‐8, colony formation, flow cytometry, western blotting, and Transwell assays were used to evaluate the impact of NEAT1 on the malignant behavior of cervical cancer cells. Glucose consumption, lactate production, ATP levels, ROS levels, MMP levels, and the mRNA expressions of glycolysis‐related genes and tricarboxylic acid cycle‐related genes were detected to analyze the effect of NEAT1 on metabolism reprograming in cervical cancer cells. The expressions of PDK1, β‐catenin and downstream molecules of the WNT/β‐catenin signaling pathway in cervical cancer cells and tissues were detected by western blotting, RT‐qPCR, immunofluorescence and immunohistochemistry assays. Results: This study investigated the role and possible molecular mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in cervical cancer. Our results showed that NEAT1 was highly expressed in cervical cancer tissues and cell lines. Downregulation of NEAT1 inhibited the proliferation, migration, invasion and glycolysis of cervical cancer cells, while overexpression of NEAT1 led to the opposite effects. Mechanistically, NEAT1 upregulated pyruvate dehydrogenase kinase (PDK1) through the WNT/β‐catenin signaling pathway, which enhanced glycolysis and then facilitated cervical cancer metastasis. Furthermore, NEAT1 maintained the protein stability of β‐catenin but did not affect its mRNA level. We also excluded the direct binding of NEAT1 to the β‐catenin protein via RNA pull‐down assay. The suppressive impact of NEAT1 knockdown on cell proliferation, invasion, and migration was rescued by β‐catenin overexpression. The WNT inhibitor iCRT3 attenuated the carcinogenic effect induced by NEAT1 overexpression. Conclusion: In summary, these findings indicated that NEAT1 may contribute to the progression of cervical cancer by activating the WNT/β‐catenin/PDK1 signaling axis. [ABSTRACT FROM AUTHOR]

Within the initial minutes of square-wave exercise transitions above the moderate-intensity domain, the reliance on the anaerobic energy sources may induce some levels of metabolic instability; however, no study has attempted to limit metabolic instability at exercise onset by manipulating the exercise transition phase to a target work rate (WR). Purpose: This study aimed to investigate whether a ramp-to-constant WR (rCWR) transition compared with a square-wave-to-constant WR (CWR) transition within the heavy-intensity domain can reduce metabolic instability and decrease the oxygen cost of exercise. Methods: Fourteen individuals performed (i) a ramp-incremental test to task failure, (ii) a 21-min CWR within the heavy-intensity domain, and (iii) an rCWR to the same WR. Oxygen uptake (...O2), lactate concentration ([La-]), and muscle oxygen saturation (SmO2) were measured. ...O2 and ...O2 gain (...O2-G) during the first 10-min steady-state ...O2 were analyzed. [La-] before, at, and after steady-state ...O2 and SmO2 during the entire 21-min steady-state exercise were also examined. Results: ...O2 and ...O2-G during rCWR (2.49 ± 0.58 L⋅min-1 and 10.7 ± 0.2 mL⋅min-1⋅W-1, respectively) were lower (P < 0.001) than CWR (2.57 ± 0.60 L⋅min-1 and 11.3 ± 0.2 mL⋅min-1⋅W-1, respectively). [La-] before and at steady-state ...O2 during the rCWR condition (1.94 ± 0.60 and 3.52 ± 1.19 mM, respectively) was lower than the CWR condition (3.05 ± 0.82 and 4.15 ± 1.25 mM, respectively) (P <0.001). [La-] dynamics after steady-state ...O2 were unstable for the rCWR (P = 0.011). SmO2 was unstable within the CWR condition from minutes 4 to 13 (P <0.05). Conclusions: The metabolic disruption caused by the initial minutes of square-wave exercise transitions is a primary contributor to metabolic instability, leading to an increased ...O2-G compared with the rCWR condition approach. The reduced early reliance on anaerobic energy sources during the rCWR condition may be responsible for the lower ...O2-G. [ABSTRACT FROM AUTHOR]

The human gut hosts numerous ecological niches for microbe–microbe and host–microbe interactions. Gut lactate homeostasis in humans is crucial and relies on various bacteria. Veillonella spp., gut lactate‐utilizing bacteria, and lactate‐producing bacteria were frequently co‐isolated. A recent clinical trial has revealed that lactate‐producing bacteria in humans cross‐feed lactate to Veillonella spp.; however, their interspecies interaction mechanisms remain unclear. Veillonella dispar, an obligate anaerobe commonly found in the human gut and oral cavity, ferments lactate into acetate and propionate. In our study, we investigated the interaction between V. dispar ATCC 17748T and three representative phylogenetically distant strains of lactic acid bacteria, Lactobacillus acidophilus ATCC 4356T, Lacticaseibacillus paracasei subsp. paracasei ATCC 27216T, and Lactiplantibacillus plantarum ATCC 10241. Bacterial growth, viability, metabolism and gene level adaptations during bacterial interaction were examined. V. dispar exhibited the highest degree of mutualism with L. acidophilus. During co‐culture of V. dispar with L. acidophilus, both bacteria exhibited enhanced growth and increased viability. V. dispar demonstrated an upregulation of amino acid biosynthesis pathways and the aspartate catabolic pathway. L. acidophilus also showed a considerable number of upregulated genes related to growth and lactate fermentation. Our results support that V. dispar is able to enhance the fermentative capability of L. acidophilus by presumably consuming the produced lactate, and that L. acidophilus cross‐feed not only lactate, but also glutamate, to V. dispar during co‐culture. The cross‐fed glutamate enters the central carbon metabolism in V. dispar. These findings highlight an intricate metabolic relationship characterized by cross‐feeding of lactate and glutamate in parallel with considerable gene regulation within both L. acidophilus (lactate‐producing) and V. dispar (lactate‐utilizing). The mechanisms of mutualistic interactions between a traditional probiotic bacterium and a potential next‐generation probiotic bacterium were elucidated in the production of short‐chain fatty acids. [ABSTRACT FROM AUTHOR]

Ethyl lactate is the most abundant ester in semi-solid rice baijiu fermentation, affecting the flavor of baijiu to a great extent. The present study aimed to investigate the spatial distribution and formation contributor of ethyl lactate by removing the microorganisms and extracellular enzymes from the upper, middle, and lower fermentation broth during the later fermentation stage. The removal of suspended substances by centrifugation did not affect the ethyl lactate content in the top and middle fermentation broth containing free cells, enzymes, and starch particles. After day 5 of fermentation, only the lower fermentation broth containing granular cells attached to the starch could continue to accumulate lactic acid, thereby increasing the ethyl lactate content. The results showed that the chemical reactions were the main contributor to the increased ethyl lactate content at the anaphase of fermentation rather than enzymatic catalysis or microbial metabolism. Sequencing of granular cells revealed the main lactic acid producers at different fermentation stages. Lactobacillus helveticus showed the highest abundance of 94.45–95.40% on day 5, which decreased to 29.58–30.20% on day 15, while Lactobacillus acetotolerans showed the highest abundance of 47.93–49.72% at day 15. Additionally, the granular cells were recovered and used for supplementary inoculation in the next batch, which significantly increased the ethyl lactate content. This study provided a novel strategy for improving the ethyl lactate content in semi-solid baijiu fermentation. [Display omitted] • Esterification of cells and enzymes was studied in baijiu fermentation anaphase. • Ethyl lactate was mainly formed by chemical rather than biological reaction. • Lactic acid was mainly produced by granular cells attached to starch on the bottom. • Lactobacillus helveticus and L. acetotolerans were the major lactic acid producers. • Adding recovered granular cells in anaphase could much increase ethyl lactate. [ABSTRACT FROM AUTHOR]

Limited substrate availability because of the blood–brain barrier (BBB) has made the brain develop specific molecular mechanisms to survive, using lactate synthesized by astrocytes as a source of energy in neurons. To understand if lactate improves cellular viability and susceptibility to glutamate toxicity, primary cortical cells were incubated in glucose- or lactate-containing media and toxic concentrations of glutamate for 24 h. Cell death was determined by immunostaining and lactate dehydrogenase (LDH) release. Mitochondrial membrane potential and nitric oxide (NO) levels were measured using Tetramethylrhodamine, methyl ester (TMRM) and 4-Amino-5-Methylamino-2′,7′-Difluorofluorescein Diacetate (DAF-FM) live staining, respectively. LDH activity was quantified in single cells in the presence of lactate (LDH substrate) and oxamate (LDH inhibitor). Nuclei of cells were stained with DAPI and neurons with MAP2. Based on the distance between neurons and glial cells, they were classified as linked (<10 µm) and non-linked (>10 µm) neurons. Lactate increased cell death rate and the mean value of endogenous NO levels compared to glucose incubations. Mitochondrial membrane potential was lower in the cells cultured with lactate, but this effect was reversed when glutamate was added to the lactate medium. LDH activity was higher in linked neurons compared to non-linked neurons, supporting the hypothesis of the existence of the lactate shuttle between astrocytes and at least a portion of neurons. In conclusion, glucose or lactate can equally preserve primary cortical neurons, but those neurons having a low level of LDH activity and incubated with lactate cannot cover high energetic demand solely with lactate and become more susceptible to glutamate toxicity. [ABSTRACT FROM AUTHOR]

During prolonged running at moderate‐to‐high intensity, running economy (RE) deteriorates and attainable maximal oxygen consumption (VO2max) decreases. Whether these changes appear similarly in trained and untrained runners exercising at the same relative intensity is not clear. We recruited 10 trained runners (TR) and 10 active adults (AA), and compared RE and attainable VO2max before and after 1 h of running at 70% of VO2max. Submaximal VO2 increased more (p = 0.019) in AA (0.20 ± 0.13 L min−1) than in TR (0.07 ± 0.05 L min−1). Attainable VO2max decreased in AA (−0.21 ± 0.15 L min−1, p = 0.002), but remained unchanged in TR (−0.05 ± 0.10 L min−1, p = 0.18). Relative intensity (i.e., VO2/attainable VO2max), increased more (p = 0.001) in AA (8.3 ± 4.4%) than in TR (2.6 ± 1.9%). These results demonstrate that the ability to resist changes in RE and VO2max following prolonged running is superior in trained versus untrained runners, when exercising at the same relative intensity. [ABSTRACT FROM AUTHOR]

Background: Delayed time from collection to centrifugation may cause erroneously high lactate levels in vitro (from continued blood cell metabolism under anaerobic conditions in the collection tube) if not collected in appropriate collection devices, consequently increasing the risk for inappropriate patient care or harm. We undertook a study to determine the turnaround time for lactate testing in a tertiary care setting and also performed short- and long-term lactate stability studies in blood collected in sodium fluoride/potassium oxalate (NaF/KOx) collection tubes. Methods: The hospital lab information system was mined for 6 months to determine patient samples that may have exceeded the time from collection-to-receival in lab of 15-min. Lactate stability was evaluated in unspun NaF/KOx collection tubes at 15 min intervals for to 2 h; and separately at 2, 6, 12, 24, and 48-h post-collection. Results: A total of 8,929 plasma samples were collected in 6 months, and 1/3 were not received in the lab within 15 min from collection. In NaF/KOx additive, lactate levels had minor increases over 2 h, and incremental increases at an average rate of 0.0035 mmol/L/h over 48 h with maximum increase of 9.8% at 48 h. However, the average change across all time points were within local allowable performance goals (at ≤4 mmol/L ± 0.5 mmol/L; at >4 mmol/L ± 12%). Conclusion: A small proportion of lactate specimens may experience delay in processing. Although lactate levels may incrementally increase over 48-h at room temperature in unspun NaF/KOx collection tubes, the changes may not be clinically impactful. [ABSTRACT FROM AUTHOR]

Spirulina supplementation has been reported to increase hemoglobin concentration as well as a variety of cardiorespiratory and lactate-based performance parameters during maximal and submaximal states of exercise. This study investigates the efficacy of supplementing a 6 g/day dosage of spirulina for 14-days in recreationally active individuals, analyzing cardiorespiratory parameters during maximal and submaximal cycling as well as the potential mechanistic role of hemoglobin augmentation. 17 recreationally active individuals (Male = 14, Female = 3, Age 23 ± 5 years, V̇O2max 43.3 ± 8.6 ml/min·kg) ingested 6 g/day of spirulina or placebo for 14-days in a double-blinded randomized crossover study, with a 14-day washout period between trials. Participants completed a 20-min submaximal cycle at 40% maximal power output (WRmax), followed by a V̇O2max test. Hemoglobin (g/L), WRmax (watts), time to fatigue (seconds), heart rate (bpm), oxygen uptake (ml/min·kg), RER and blood lactate response (mmol/L) were measured and compared between conditions. Cardiorespiratory variables were recorded at 5-min intervals and lactate was measured at 10-min intervals during the submaximal exercise. There was a significant 3.4% increase in hemoglobin concentration after spirulina supplementation in comparison to placebo (150.4 ± 9.5 g/L Vs 145.6 ± 9.4 g/L, p = 0.047). No significant differences existed between either condition in both testing protocols for V̇O2max, WRmax, time to fatigue, heart rate, oxygen uptake, RER and blood lactate response (p > 0.05). 14-days of spirulina supplementation significantly improved hemoglobin concentration but did not lead to any considerable ergogenic improvements during maximal or submaximal exercise at a 6 g/day dosage in recreationally active individuals whilst cycling. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has emerged as a potent clinical approach for cancer treatment, but only subsets of cancer patients can benefit from it. Targeting lactate metabolism (LM) in tumor cells as a method to potentiate anti-tumor immune responses represents a promising therapeutic strategy. Methods: Public single-cell RNA-Seq (scRNA-seq) cohorts collected from patients who received immunotherapy were systematically gathered and scrutinized to delineate the association between LM and the immunotherapy response. A novel LM-related signature (LM.SIG) was formulated through an extensive examination of 40 pan-cancer scRNA-seq cohorts. Then, multiple machine learning (ML) algorithms were employed to validate the capacity of LM.SIG for immunotherapy response prediction and survival prognostication based on 8 immunotherapy transcriptomic cohorts and 30 The Cancer Genome Atlas (TCGA) pan-cancer datasets. Moreover, potential targets for immunotherapy were identified based on 17 CRISPR datasets and validated via in vivo and in vitro experiments. Results: The assessment of LM was confirmed to possess a substantial relationship with immunotherapy resistance in 2 immunotherapy scRNA-seq cohorts. Based on large-scale pan-cancer data, there exists a notably adverse correlation between LM.SIG and anti-tumor immunity as well as imbalance infiltration of immune cells, whereas a positive association was observed between LM.SIG and pro-tumorigenic signaling. Utilizing this signature, the ML model predicted immunotherapy response and prognosis with an AUC of 0.73/0.80 in validation sets and 0.70/0.87 in testing sets respectively. Notably, LM.SIG exhibited superior predictive performance across various cancers compared to published signatures. Subsequently, CRISPR screening identified LDHA as a pan-cancer biomarker for estimating immunotherapy response and survival probability which was further validated using immunohistochemistry (IHC) and spatial transcriptomics (ST) datasets. Furthermore, experiments demonstrated that LDHA deficiency in pancreatic cancer elevated the CD8+ T cell antitumor immunity and improved macrophage antitumoral polarization, which in turn enhanced the efficacy of immunotherapy. Conclusions: We unveiled the tight correlation between LM and resistance to immunotherapy and further established the pan-cancer LM.SIG, holds the potential to emerge as a competitive instrument for the selection of patients suitable for immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Ginsenoside Rh2 (G-Rh2), a steroidal compound extracted from roots of ginseng, has been extensively studied in tumor therapy. However, its specific regulatory mechanism in non-small cell lung cancer (NSCLC) is not well understood. Pyruvate dehydrogenase kinase 4 (PDK4), a central regulator of cellular energy metabolism, is highly expressed in various malignant tumors. We investigated the impact of G-Rh2 on the malignant progression of NSCLC and how it regulated PDK4 to influence tumor aerobic glycolysis and mitochondrial function. Method: We examined the inhibitory effect of G-Rh2 on NSCLC through I proliferation assay, migration assay and flow cytometry in vitro. Subsequently, we verified the ability of G-Rh2 to inhibit tumor growth and metastasis by constructing subcutaneous tumor and metastasis models in nude mice. Proteomics analysis was conducted to analyze the action pathways of G-Rh2. Additionally, we assessed glycolysis and mitochondrial function using seahorse, PET-CT, Western blot, and RT-qPCR. Result: Treatment with G-Rh2 significantly inhibited tumor proliferation and migration ability both in vitro and in vivo. Furthermore, G-Rh2 inhibited the tumor's aerobic glycolytic capacity, including glucose uptake and lactate production, through the HIF1-α/PDK4 pathway. Overexpression of PDK4 demonstrated that G-Rh2 targeted the inhibition of PDK4 expression, thereby restoring mitochondrial function, promoting reactive oxygen species (ROS) accumulation, and inducing apoptosis. When combined with sodium dichloroacetate, a PDK inhibitor, it complemented the inhibitory capacity of PDKs, acting synergistically as a detoxifier. Conclusion: G-Rh2 could target and down-regulate the expression of HIF-1α, resulting in decreased expression of glycolytic enzymes and inhibition of aerobic glycolysis in tumors. Additionally, by directly targeting mitochondrial PDK, it elevated mitochondrial oxidative phosphorylation and enhanced ROS accumulation, thereby promoting tumor cells to undergo normal apoptotic processes. [ABSTRACT FROM AUTHOR]

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 < 2 mmol/L. Moreover, subgroup analyses were performed based on the time from hospital arrival to surgery and fracture type. Results: In total, 187 patients were included in the study. The incidence of postoperative complications was significantly higher in patients with a preoperative lactate level of ≥ 2 mmol/L than those with a preoperative lactate level of < 2 mmol/L. This result did not change after adjusting for age and severity. Further, a high preoperative lactate level was associated with a greater incidence of postoperative complications in patients who underwent definitive surgery within 6 h after arrival. Conclusion: A preoperative lactate level of ≥ 2 mmol/L was associated with a greater incidence of early postoperative complications in isolated extremity fractures. Nevertheless, this correlation was only observed among patients who underwent definitive fixation within 6 h after hospital arrival. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a persistent autoimmune condition characterized by synovitis and joint damage. Recent findings suggest a potential link to abnormal lactate metabolism. This study aims to identify lactate metabolism-related genes (LMRGs) in RA and investigate their correlation with the molecular mechanisms of RA immunity. Data on the gene expression profiles of RA synovial tissue samples were acquired from the gene expression omnibus (GEO) database. The RA database was acquired by obtaining the common LMRDEGs, and selecting the gene collection through an SVM model. Conducting the functional enrichment analysis, followed by immuno-infiltration analysis and protein–protein interaction networks. The results revealed that as possible markers associated with lactate metabolism in RA, KCNN4 and SLC25A4 may be involved in regulating macrophage function in the immune response to RA, whereas GATA2 is involved in the immune mechanism of DC cells. In conclusion, this study utilized bioinformatics analysis and machine learning to identify biomarkers associated with lactate metabolism in RA and examined their relationship with immune cell infiltration. These findings offer novel perspectives on potential diagnostic and therapeutic targets for RA. [ABSTRACT FROM AUTHOR]

Chronic wound monitoring can provide personalized pathophysiological information for wound management and treatment. Continuously monitoring the wound milieu via the holographic pH sensor can reflect the wound healing processes. However, the integration with wearable devices is hindered by its inherently restricted interrogation angle dependency within 5°. Herein, a ball bearing‐based double photopolymerization method is developed to fabricate holographic pH sensors with a broader interrogation angle range of 15°–60° in wound exudates. The fabricated holographic pH sensor is then integrated with the flexible ultrathin polyurethane substrate, which replays a total Bragg peak shift of approximately 150 nm with physiological pH changes from 7.00 to 8.75. The conformable holographic pH sensing bandages demonstrate the ability to quantify the pH value under various bending manipulations, simulating the mounting on the body surface. The reversibility in artificial wound exudate demonstrates the durability and capability of real‐time pH monitoring in the wound milieu with minimal effect on the replay wavelength. The addition of electrolytes, albumin, urea, uric acid, lactate, and glucose does not interfere with the readout over the physiological pH range of wound exudates. The obtained conformable holographic sensing bandage benefits the wound healing process monitoring through colorimetric interrogation at point‐of‐care (POC) settings. [ABSTRACT FROM AUTHOR]

This study aimed to test the reproducibility of the 3-min all-out effort applied using shuttle running and compare its values to aerobic parameters. On the first day, 14 futsal players underwent an exhaustive test to determine the maximal incremental speed (MIS) and anaerobic threshold (AnT). On the second day, the participants performed the 3-min all-out effort (n=14), which was repeated after 48 h (third day) to test its reproducibility (n=11). Peak oxygen consumption (V̇ O2PEAK) and peak blood lactate concentrations ([La-]) were determined from 3-min all-out efforts performed through a 20-m shuttle run on the official court. The distance covered, mean speed, and critical speed (CS) during the 3-min all-out presented direct relationships with aerobic parameters determined through the incremental test (r>0.62). The distance covered above CS (D') presented a direct relationship with peak lactate concentrations induced by a 3-min all-out effort (r=0.81). Despite the acceptable levels of reproducibility observed for most of the 3-min all-out variables, the minimal detectable change for D' was high (72%). Our results demonstrated the potential use of mean speed to evaluate aerobic fitness. However, the applicability of the 3-min all-out shuttle run test to monitor training adaptations should be avoided, at least in nonexperienced athletes. [ABSTRACT FROM AUTHOR]

CrossFit is characterized by being a standardized training program that improves physical performance through the provision of several stimuli regardless of the participant's strength level. This study aimed to compare the acute response in total repetitions as a measurement of performance, jump ability, physiological demand (heart rate and blood lactate), and perceived effort considering the participants' strength level with individualized intensity in CrossFit. Thirty-five participants were assessed and asked to participate on two separate days in a standardized and relative 'As Many Repetitions As Possible' (AMRAP) CrossFit circuit. Both AMRAPs comprised strength, gymnastic and aerobic exercises, although only strength was individualized according to the participant's level. Before the statistical analysis, participants were allocated to higher- or lower-strength groups following the one-repetition maximum-bodyweight ratio in the push press exercise. Results support the existence of a strong relationship between strength level and total repetitions in both AMRAPs. In addition, differences in total repetitions and rate of perceived exertion between strength groups are discarded when AMRAP intensity is individualized while physiological demand and jump ability are maintained. Thus, the higher-strength participants may benefit from similar responses with a lower number of repetitions. Therefore, CrossFit trainers should be encouraged to prescribe strength tasks based on the percentage of 1RM for every training. [ABSTRACT FROM AUTHOR]

pH-sensitive amphiphilic diblock polyphosphoesters containing lactic acid units were synthesized by multistep one-pot polycondensation reactions. They comprise acid-labile P(O)-O-C and C(O)-O-C bonds, the cleavage of which depends on the pH of the medium. The structure of these copolymers was characterized by 1H, 13C {H}, 31P NMR, and size exclusion chromatography (SEC). The newly synthesized polymers self-assembled into the micellar structure in an aqueous solution. The effects of the molecular weight of the copolymer and the length of the hydrophobic chain on micelle formation and stabilityand micelle size were studied via dynamic light scattering (DLS). Drug loading and encapsulation efficiency tests using doxorubicin revealed that hydrophobic drugs can be delivered by copolymers. It was established that the molecular weight of the copolymer, length of the hydrophobic chain and content of lactate units affects the size of the micelles, drug loading, and efficiency of encapsulation. A copolymer with 10.7% lactate content has drug loading (3.2 ± 0.3) and efficiency of encapsulation (57.4 ± 3.2), compared to the same copolymer with 41.8% lactate content (1.63%) and (45.8%), respectively. It was demonstrated that the poly[alkylpoly(ethylene glycol) phosphate-b-alkylpoly(ethylene glycol)lactate phosphate] DOX system has a pH-sensitive response capability in the result in which DOX was selectively accumulated into the tumor, where pH is acidic. The results obtained indicate that amphiphilic diblock polyphosphoesters have potential as drug carriers. [ABSTRACT FROM AUTHOR]

Lactate is now considered an additional fuel or signaling molecule in the brain. In this study, using an oxygen–glucose deprivation (OGD) model, we found that treatment with lactate inhibited the global increase in intracellular calcium ion concentration ([Ca2+]) in neurons and astrocytes, decreased the percentage of dying cells, and caused a metabolic shift in astrocytes and neurons toward aerobic oxidation of substrates. OGD resulted in proinflammatory changes and increased expression of cytokines and chemokines, whereas incubation with lactate reduced these changes. Pure astrocyte cultures were less sensitive than neuroglia cultures during OGD. Astrocytes exposed to lipopolysaccharide (LPS) also showed pro‐inflammatory changes that were reduced by incubation with lactate. Our study suggests that lactate may have neuroprotective effects under ischemic and inflammatory conditions. [ABSTRACT FROM AUTHOR]

Background: Metastasis is the leading cause of cancer-related death in non-small cell lung cancer (NSCLC) patients. We previously showed that low HERC5 expression predicts early tumor dissemination and a dismal prognosis in NSCLC patients. Here, we performed functional studies to unravel the mechanism underlying the "metastasis-suppressor" effect of HERC5, with a focus on mitochondrial metabolism pathways. Methods: We assessed cell proliferation, colony formation potential, anchorage-independent growth, migration, and wound healing in NSCLC cell line models with HERC5 overexpression (OE) or knockout (KO). To study early tumor cell dissemination, we used these cell line models in zebrafish experiments and performed intracardial injections in nude mice. Mass spectrometry (MS) was used to analyze protein changes in whole-cell extracts. Furthermore, electron microscopy (EM) imaging, cellular respiration, glycolytic activity, and lactate production were used to investigate the relationships with mitochondrial energy metabolism pathways. Results: Using different in vitro NSCLC cell line models, we showed that NSCLC cells with low HERC5 expression had increased malignant and invasive properties. Furthermore, two different in vivo models in zebrafish and a xenograft mouse model showed increased dissemination and metastasis formation (in particular in the brain). Functional enrichment clustering of MS data revealed an increase in mitochondrial proteins in vitro when HERC5 levels were high. Loss of HERC5 leads to an increased Warburg effect, leading to improved adaptation and survival under prolonged inhibition of oxidative phosphorylation. Conclusions: Taken together, these results indicate that low HERC5 expression increases the metastatic potential of NSCLC in vitro and in vivo. Furthermore, HERC5-induced proteomic changes influence mitochondrial pathways, ultimately leading to alterations in energy metabolism and demonstrating its role as a new potential metastasis suppressor gene. [ABSTRACT FROM AUTHOR]

Background: The metabolism of cancer cells generally differs from that of normal cells. Indeed, most cancer cells have a high rate of glycolysis, even at normal oxygen concentrations. These metabolic properties can potentially be exploited for therapeutic intervention. In this context, we have developed troglitazone derivatives to treat hormone-sensitive and triple-negative breast cancers, which currently lack therapeutic targets, have an aggressive phenotype, and often have a worse prognosis than other subtypes. Here, we studied the metabolic impact of the EP13 compound, a desulfured derivative of Δ2-troglitazone that we synthetized and is more potent than its parent compounds. Methods: EP13 was tested on two triple-negative breast cancer cell lines, MDA-MB-231 and Hs578T, and on the luminal cell line MCF-7. The oxygen consumption rate (OCR) of the treated cell lines, Hs578T mammospheres and isolated mitochondria was measured using the XFe24 Seahorse analyser. ROS production was quantified using the MitoSOX fluorescent probe. Glycolytic activity was evaluated through measurement of the extracellular acidification rate (ECAR), glucose consumption and lactate production in extracellular medium. The synergistic effect of EP13 with glycolysis inhibitors (oxamate and 2-deoxyglucose) on cell cytotoxicity was established using the Chou-Talalay method. Results: After exposure to EP13, we observed a decrease in the mitochondrial oxygen consumption rate in MCF7, MDA-MB-231 and Hs578T cells. EP13 also modified the maximal OCR of Hs578T spheroids. EP13 reduced the OCR through inhibition of respiratory chain complex I. After 24 h, ATP levels in EP13-treated cells were not altered compared with those in untreated cells, suggesting compensation by glycolysis activity, as shown by the increase in ECAR, the glucose consumption and lactate production. Finally, we performed co-treatments with EP13 and glycolysis inhibitors (oxamate and 2-DG) and observed that EP13 potentiated their cytotoxic effects. Conclusion: This study demonstrates that EP13 inhibits OXPHOS in breast cancer cells and potentiates the effect of glycolysis inhibitors. [ABSTRACT FROM AUTHOR]

The advent of digital technologies has spurred the development of wearable sensing devices marking a significant shift in obtaining real-time physiological information. The principal objective is to transition from blood-centric monitoring to minimally invasive modalities, which will enable movement from specialised settings to more accessible environments such as the practices of general practitioners or even home settings. While subcutaneously implanted continuous monitoring devices have demonstrated this transition, detection of analytes from sample matrices like skin interstitial fluid (ISF), is a frontier that offers attractive minimally invasive routes for detection of biomarkers. This manuscript presents a comprehensive overview of our work in subdermal wearable biosensing patches for the simultaneous monitoring of glucose and lactate from ISF in ambulatory conditions. The performance of the subdermal wearable glucose monitoring patch was evaluated over a duration of three days, which is the longest reported duration reported till date. The subdermal wearable lactate sensing patch was worn for the duration of the exercise. Our findings highlight a critical observation that biofouling effects become apparent after a 24 h period. The data presented in this manuscript extends on the knowledge in the areas of continuous metabolite monitoring by introducing multifunctional polyphenol polymer films that can be used for both glucose and lactate monitoring with appropriate modifications. This study underscores the potential of subdermal wearable patches as versatile tools for real-time metabolite monitoring, positioning them as valuable assets in the evolution of personalised healthcare in diverse settings. [ABSTRACT FROM AUTHOR]