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Background: Evidence from animal and human studies suggests glutamatergic dysfunction in posttraumatic stress disorder (PTSD). The purpose of this study was to investigate glutamate abnormalities in the dorsolateral prefrontal cortex (DLFPC) of individuals with PTSD using 7T MRS, which has better spectral resolution and signal-to-noise ratio than lower field strengths, thus allowing for better spectral quality and higher sensitivity. We hypothesized that individuals with PTSD would have lower glutamate levels compared to trauma-exposed individuals without PTSD and individuals without trauma exposure. Additionally, we explored potential alterations in other neurometabolites and the relationship between glutamate and psychiatric symptoms. Methods: Individuals with PTSD (n = 27), trauma-exposed individuals without PTSD (n = 27), and individuals without trauma exposure (n = 26) underwent 7T MRS to measure glutamate and other neurometabolites in the left DLPFC. The severities of PTSD, depression, anxiety, and dissociation symptoms were assessed. Results: We found that glutamate was lower in the PTSD and trauma-exposed groups compared to the group without trauma exposure. Furthermore, N -acetylaspartate (NAA) was lower and lactate was higher in the PTSD group compared to the group without trauma exposure. Glutamate was negatively correlated with depression symptom severity in the PTSD group. Glutamate was not correlated with PTSD symptom severity. Conclusion: In this first 7T MRS study of PTSD, we observed altered concentrations of glutamate, NAA, and lactate. Our findings provide evidence for multiple possible pathological processes in individuals with PTSD. High-field MRS offers insight into the neurometabolic alterations associated with PTSD and is a powerful tool to probe trauma- and stress-related neurotransmission and metabolism in vivo. [ABSTRACT FROM AUTHOR]

Under hydrothermal condition, lactate derivative (R)‐4‐(1‐ carboxyethoxy)‐2‐methylbenzoic acid ((R)‐H2cma) as chiral synthon assembled with 4,4′‐di(1H‐imidazol‐1‐yl)‐1,1′‐biphenyl (4,4'‐dib) and Ni(II) ions to obtain complex {[Ni2((R)‐cma)2(4,4'‐dib)2(H2O)] ⋅ 2H2O}n (HU20‐R). In complex HU20‐R, carboxyl group from lactate unit of (R)‐cma2− anion and coordinating H2O molecule adopt a μ2‐coordination mode to obtain dinuclear [Ni2(CO2)2(H2O)]2+ cluster. (R)‐cma2− anions and Ni(II) ions build single left‐handed (R)‐cma‐Ni‐chain, while 4,4'‐dib ligands are bridged by different Ni(II) centers to form double left‐handed 4,4'‐dib‐Ni‐chain. These helical secondary structures are further connected together to result in an 8‐connected 3D framework. PXRD tests indicated that complex HU20‐R has well hydro‐stability. UV‐vis absorption experiment confirmed that HU20‐R is a semi‐conducting material with strong absorption capacity for ultraviolet‐visible (UV‐vis) light. Additionally, electrochemical experiment revealed that HU20‐R has low impedance and high charge transport capacity. Further test results confirm that HU20‐R has noticeable photo‐catalytic effect in photodegradation of Rhodamine B (RhB) and antiferromagnetic property. [ABSTRACT FROM AUTHOR]

Background: Fluid administration is the first line treatment in intensive care unit (ICU) patients with sepsis and septic shock. While fluid boluses administration can be titrated by predicting preload dependency, the amount of other forms of fluids may be more complex to be evaluated. We conducted a retrospective analysis in a tertiary hospital, to assess the ratio between fluids given as boluses and total administered fluid intake during early phases of ICU stay, and to evaluate the impact of fluid strategy on ICU mortality. Data related to fluid administration during the first four days of ICU stay were exported from an electronic health records system (ICCA®, Philips Healthcare). Demographic data, severity score, norepinephrine dose at ICU admission, overall fluid balance and the percentage of different fluid components of the overall volume administered were included in a multivariable logistic regression model, evaluating the association with ICU survival. Results: We analyzed 220 patients admitted with septic shock and sepsis-induced hypotension from 1st July 2021 to 31st December 2023. Fluid boluses and maintenance represented 49.3% ± 22.8 of the overall fluid intake, being balanced solution the most represented (40.4% ± 22.0). The fluid volume for drug infusion represented 34.0% ± 2.9 of the total fluid intake, while oral or via nasogastric tube fluid intake represented 18.0% ± 15.7 of the total fluid intake. Fluid volume given as boluses represented 8.6% of the total fluid intake over the four days, with a reduction from 25.1% ± 24.0 on Day 1 to 4.8% ± 8.7 on Day 4. A positive fluid balance [OR 1.167 (1.029–1.341); p = 0.021] was the most important factor associated with ICU mortality. Non-survivors (n = 66; 30%) received a higher amount of overall inputs than survivors only on Day 1 [2493 mL vs. 1855 mL; p = 0.022]. Conclusions: This retrospective analysis of fluids given over the early phases of septic shock and sepsis-induced hypotension showed that the overall volume given by boluses ranges from about 25% on Day 1 to about 5% on Day 4 from ICU admission. Our data confirms that a positive fluid balance over the first 4 days of ICU is associated with mortality. [ABSTRACT FROM AUTHOR]

Modulation of testing conditions such as resting lactate (Larest) levels or carbohydrate intake may affect the calculation of the maximal glycolytic rate (νLa.max). To evaluate the impact of elevated Larest as well as reduced and increased carbohydrate availability on νLa.max in running sprints (RST), twenty‐one participants completed five 15‐s RST tests on a running track under five different conditions: (I). baseline: Larest ≤1.5 mmol·L−1; (II). Lactate+: Larest ≥2.5 mmol·L−1; (III). CHO−: carbohydrate intake: ≤ 1 g·kg−1 BW d−1 for 3 days; (IV). CHO+: carbohydrate intake: ≥ 9 g·kg−1 BW d−1 for one day; and (V). acuteCHO: 500 mL glucose containing beverage consumed before RST. νLa.max was significantly reduced in lactate+ and CHO− conditions compared to the baseline RST, due to a reduction in the arithmetic mean delta (∆) between Lapeak and Larest lactate concentration (Lapeak, mmol · L−1). AcuteCHO led to an increase in Larest compared to baseline, CHO− and CHO+ with a high interindividual variability but did not significantly reduce νLa.max. Therefore, avoiding low carbohydrate nutrition before νLa.max testing, along with carefully adjusting Larest to below ≤1.5 mmol·L‐1, is crucial to prevent the unintentional underestimation of νLa.max. [ABSTRACT FROM AUTHOR]

Simple Summary: The Aerococcus viridans bacterial lactate oxidase (LOX) is an enzyme absent in mammalian cells. LOX catalyzes lactate to pyruvate and hydrogen peroxide (H2O2), a function that was recently used for tumor microenvironment (TME) lactate removal and H2O2 production to induce cancer cell death. However, the functions of TME lactate other than being a metabolic intermediate or an energy source and the mechanism of LOX disruption of lactate-mediated cancer cell survival remain unknown. Our study aims at addressing these important cancer-related biological questions. We identified a novel onco-signaling nexus initiated by TME lactate activation of its cellular receptor hydroxycarboxylic acid receptor 1 (HCAR1) and amplified by HCAR-associated proteins that mediate the RAS and the PI3K pathways. This signaling model could explain many key survival strategies exerted by RAS, PI3K, and their effectors for cancer cell adaptation to TME changes, especially in the cells' use of lactate beyond an energy source. LOX was recently shown to inhibit cancer cell proliferation and tumor growth. The mechanism of this inhibition, however, has been exclusively attributed to LOX depletion of TME lactate, a cancer cell energy source, and production of H2O2, an oxidative stressor. We report that TME lactate triggers the assembly of the lactate receptor hydroxycarboxylic acid receptor 1 (HCAR1)-associated protein complex, which includes GRB2, SOS1, KRAS, GAB1, and PI3K, for the activation of both the RAS and the PI3K oncogenic signaling pathways in breast cancer (BCa) cells. LOX treatment decreased the levels of the proteins in the protein complex via induction of their proteasomal degradation. In addition, LOX inhibited lactate-stimulated expression of the lactate transporters MCT1 and MCT4. Our data suggest that HCAR1 activation by lactate is crucial for the assembly and function of the RAS and PI3K signaling nexus. Shutting down lactate signaling by disrupting this nexus could be detrimental to cancer cells. HCAR1 is therefore a promising target for the control of the RAS and the PI3K signaling required for BCa progression. Thus, our study provides insights into lactate signaling regulation of cancer progression and extends our understanding of LOX's functional mechanisms that are fundamental for exploring its therapeutic potential. [ABSTRACT FROM AUTHOR]

Under the long‐term pressure overload stimulation, the heart experiences embryonic gene activation, leading to myocardial hypertrophy and ventricular remodelling, which can ultimately result in the development of heart failure. Identifying effective therapeutic targets is crucial for the prevention and treatment of myocardial hypertrophy. Histone lysine lactylation (HKla) is a novel post‐translational modification that connects cellular metabolism with epigenetic regulation. However, the specific role of HKla in pathological cardiac hypertrophy remains unclear. Our study aims to investigate whether HKla modification plays a pathogenic role in the development of cardiac hypertrophy. The results demonstrate significant expression of HKla in cardiomyocytes derived from an animal model of cardiac hypertrophy induced by transverse aortic constriction surgery, and in neonatal mouse cardiomyocytes stimulated by Ang II. Furthermore, research indicates that HKla is influenced by glucose metabolism and lactate generation, exhibiting significant phenotypic variability in response to various environmental stimuli. In vitro experiments reveal that exogenous lactate and glucose can upregulate the expression of HKla and promote cardiac hypertrophy. Conversely, inhibition of lactate production using glycolysis inhibitor (2‐DG), LDH inhibitor (oxamate) and LDHA inhibitor (GNE‐140) reduces HKla levels and inhibits the development of cardiac hypertrophy. Collectively, these findings establish a pivotal role for H3K18la in pathological cardiac hypertrophy, offering a novel target for the treatment of this condition. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming is a key hallmark of tumors, developed in response to hypoxia and nutrient deficiency during tumor progression. In both cancer and immune cells, there is a metabolic shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, also known as the Warburg effect, which then leads to lactate acidification, increased lipid synthesis, and glutaminolysis. This reprogramming facilitates tumor immune evasion and, within the tumor microenvironment (TME), cancer and immune cells collaborate to create a suppressive tumor immune microenvironment (TIME). The growing interest in the metabolic reprogramming of the TME, particularly its significance in colorectal cancer (CRC)--one of the most prevalent cancers--has prompted us to explore this topic. CRC exhibits abnormal glycolysis, glutaminolysis, and increased lipid synthesis. Acidosis in CRC cells hampers the activity of anti-tumor immune cells and inhibits the phagocytosis of tumor-associated macrophages (TAMs), while nutrient deficiency promotes the development of regulatory T cells (Tregs) and M2-like macrophages. In CRC cells, activation of G-protein coupled receptor 81 (GPR81) signaling leads to overexpression of programmed death-ligand 1 (PD-L1) and reduces the antigen presentation capability of dendritic cells. Moreover, the genetic and epigenetic cell phenotype, along with the microbiota, significantly influence CRC metabolic reprogramming. Activating RAS mutations and overexpression of epidermal growth factor receptor (EGFR) occur in approximately 50% and 80% of patients, respectively, stimulating glycolysis and increasing levels of hypoxia-inducible factor 1 alpha (HIF-1a) and MYC proteins. Certain bacteria produce short-chain fatty acids (SCFAs), which activate CD8+ cells and genes involved in antigen processing and presentation, while other mechanisms support pro-tumor activities. The use of immune checkpoint inhibitors (ICIs) in selected CRC patients has shown promise, and the combination of these with drugs that inhibit aerobic glycolysis is currently being intensively researched to enhance the efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • Lactate is a protective molecule against stress in the early stages of brain disorders. • Lactate inhibits microglia-mediated neuroinflammation. • Lactate also provides energy, acts as a signaling molecule, and promotes neurogenesis. Lactate in the brain is produced endogenously and exogenously. The primary functional cells that produce lactate in the brain are astrocytes. Astrocytes release lactate to act on neurons, thereby affecting neuronal function, through a process known as the astrocyte-neuron shuttle. Lactate affects microglial function as well and inhibits microglia-mediated neuroinflammation. Lactate also provides energy, acts as a signaling molecule, and promotes neurogenesis. This article summarizes the role of lactate in cells, animals, and humans. Lactate is a protective molecule against stress in healthy organisms and in the early stages of brain disorders. Thus, lactate may be a potential therapeutic target for brain disorders. Further research on the role of lactate in microglia may have great prospects. This article provides a new perspective and research direction for the study of lacate in brain disorders. [ABSTRACT FROM AUTHOR]

Background: Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP. Methods: BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions. Results: Results in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06–2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk. Conclusions: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP. Trial registration: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212. [ABSTRACT FROM AUTHOR]

Background: The selection of adequate indicators of tissue hypoxia for guiding the resuscitation process of septic patients is a highly relevant issue. Current guidelines advocate for the use of lactate as sole metabolic marker, which may be markedly limited, and the integration of different variables seems more adequate. In this study, we explored the metabolic profile and its implications in the response to the administration of a fluid challenge in early septic shock patients. Methods: Observational study including septic shock patients within 24 h of ICU admission, monitored with a cardiac output estimation system, with ongoing resuscitation. Hemodynamic and metabolic variables were measured before and after a fluid challenge (FC). A two-step cluster analysis was used to define the baseline metabolic profile, including lactate, central venous oxygen saturation (ScvO2), central venous-to-arterial carbon dioxide difference (PcvaCO2), and PcvaCO2 corrected by the difference in arterial-to-venous oxygen content (PcvaCO2/CavO2). Results: Seventy-seven fluid challenges were analyzed. Cluster analysis revealed two distinct metabolic profiles at baseline. Cluster A exhibited lower ScvO2, higher PcvaCO2, and lower PcvaCO2/CavO2. Increases in cardiac output (CO) were associated with increases in VO2 exclusively in cluster A. Baseline isolated metabolic variables did not correlate with VO2 response, and changes in ScvO2 and PcvaCO2 were associated to VO2 increase only in cluster A. Conclusions: In a population of early septic shock patients, two distinct metabolic profiles were identified, suggesting tissue hypoxia or dysoxia. Integrating metabolic variables enhances the ability to detect those patients whose VO2 might increase as results of fluid administration. [ABSTRACT FROM AUTHOR]

AIM To assess the association of Lactate, Lactate Albumin Ratio, Procalcitonin and Immature Platelet Fraction in comparison to SOFA Score on admission as marker of severity in sepsis patients OBJECTIVES • To assess Lactate / Albumin Ratio (LAR) in patients with sepsis. • To assess Lactate value in patients with sepsis . • To assess Procalcitonin (PCT) value in patients with sepsis. • To assess Immature Platelet Function (IPF) value in patients with sepsis. • To compare Lactate, LAR, PCT and IPF with SOFA score on admission in patients with sepsis for prognostication MATERIAL AND METHODS • Hospital based Observational Cross-Sectional Study was conducted at Mahatma Gandhi Hospital, Jaipur between September 2022 to December 2023. Data of 180 patients was collected according to inclusion criteria. Sepsis biomarkers that is Lactate, LAR, IPF, PCT were calculated and were compared to SOFA score at the time of admission for the purpose of prognostication. RESULT These intra-group analyses underscore the nuanced interactions between biomarkers and organ dysfunction severity as assessed by SOFA scores in sepsis. While Procalcitonin demonstrated significant associations, highlighting their clinical relevance in stratifying disease severity, Lactate, Lacto-albumin ratio and IPF showed more variable associations. CONCLUSION In this study all four markers positively correlated with SOFA score, that is the level of markers increased along with severity of sepsis. But our study particularly identifies significant associations: SOFA scores correlate significantly with procalcitonin. The biomarkers of sepsis used in our study that is Lactate, Lactate Albumin Ratio (LAR), Immature Platelet Fraction (IPF), Procalcitonin (PCT) can be used to enhance early risk stratification and guide more tailored therapeutic interventions for septic patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess metabolic changes to monitor the progression from normal liver to hepatitis B virus (HBV)-related hepatitis and liver fibrosis using hyperpolarized 13C magnetic resonance imaging (MRI). Procedures: Hepatitis was induced in mice (n = 16) via hydrodynamic injection of HBV 1.2 plasmid (25 μg). Among them, liver fibrosis was induced in the mice (n = 8) through weight-adapted administration of thioacetamide with ethanol. Normal control mice (n = 8) were injected with a phosphate buffer solution. Subsequently, a hyperpolarized 13C MRI was performed on the mouse liver in vivo. The level of hepatitis B surface antigen (HBsAg) in blood serum was measured. Statistical analysis involved comparing the differential metabolite ratios, blood biochemistry values, and body weight among the three groups using the Kruskal–Wallis one-way analysis of variance. Results: HBsAg was absent in the normal and fibrosis groups, while it was detected in the hepatitis group. The ratios of [1-13C] lactate/pyruvate, [1-13C] alanine/pyruvate, [1-13C] lactate/total carbon, and [1-13C] alanine/total carbon were significantly lower in the normal control group than in the hepatitis and fibrosis groups (p < 0.05). Moreover, these ratios were significantly higher in the fibrosis group than in the hepatitis group (p < 0.05). However, no significant differences were observed in either [1-13C] pyruvate-hydrate/pyruvate or [1-13C] pyruvate-hydrate/total carbon among the three groups. Conclusions: The levels of [1-13C] lactate and [1-13C] alanine in vivo may serve as valuable indicators for differentiating between HBV-related hepatitis, liver fibrosis, and normal liver. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the effects of a 7-d high-intensity interval training shock microcycle (HIIT-SM) with or without additional low-intensity training (LIT) on aerobic fitness and endurance performance compared with a control group (CG). Methods: Thirty-three endurance-trained athletes (7 women, 26 men, mean ± SD: age, 30.2 ± 6.9 yr;maximal oxygen uptake (VO2max), 59.8 ± 4.9 mL·min-1·kg-1) performed exercise testing at T1 and were randomly assigned to one of three groups: i) HSM, 10 running-based HIIT sessions (5 × 4 min at 90%-95% maximal heart rate) over 7 d; ii)HSM+ LIT, equal toHSMwith additional 30 min of LIT after each HIIT; iii) CG, regular training. Exercise testing was repeated 3 d (T2), 7 d (T3), and 14 d (T4) after the intervention. A 5-km time trial (TT5km) was performed 3-4 d before T1 and 10-11 d after the intervention. Data were analyzed by two-way repeated-measures ANOVA. Results: No interaction effect was found for VO2max (P = 0.170, pη² = 0.09), peak power output (P = 0.734, pη² = 0.04), and work economy (P = 0.804, pη² = 0.03). There was an interaction for velocity at lactate threshold (P = 0.006, pη² = 0.18) with increased velocity in HSM at T2 (3.2%, P = 0.030), T3 (4%, P = 0.006), T4 (4%, P = 0.003), as well as in HSM + LIT for T2 (3.2%, P = 0.011), whereas CG showed no change. There was an interaction for TT5km (P = 0.044, pη² = 0.19), with HSM improving 2.7% (P = 0.003) and HSM + LIT 2.3% (P = 0.010), whereas CG was, on average, -0.3% (P = 0.821) slower. Conclusions: HIIT-SM with or without additional LIT has negligible effects on VO2max but improves other key endurance variables in endurance-trained athletes. No superiority of either intervention group was demonstrated. Therefore, additional LIT during HIIT-SM is not beneficial. [ABSTRACT FROM AUTHOR]

Classical training theory postulates that performance fatigability following a training session should be proportional to the total work done (TWD); however, this notion has been questioned. This study investigated indices of performance and perceived fatigability after primary sessions of high-intensity interval training (HIIT) and constant work rate (CWR) cycling, each followed by a cycling time-to-task failure (TTF) bout. On separate days, 16 participants completed an incremental cycling test, and, in a randomized order, (i) a TTF trial at 80% of peak power output (PPO), (ii) an HIIT session, and (iii) a CWR session, both of which were immediately followed by a TTF trial at 80% PPO. Central and peripheral aspects of performance fatigability were measured using interpolated twitch technique, and perceptual measures were assessed prior to and following the HIIT and CWR trials, and again following the TTF trial. Despite TWD being less following HIIT (P = 0.029), subsequent TTF trial was an average of 125 s shorter following HIIT versus CWR (P < 0.001), and this was accompanied by greater impairments in voluntary and electrically evoked forces (P < 0.001), as well as exacerbated perceptual measures (P < 0.001); however, there were no differences in any fatigue measure following the TTF trial (P ≥ 0.149). There were strong correlations between the decline in TTF and indices of peripheral (r = 0.70) and perceived fatigability (r ≥ 0.80) measured at the end of HIIT and CWR. These results underscore the dissociation between TWD and performance fatigability and highlight the importance of peripheral components of fatigability in limiting endurance performance during high-intensity cycling exercise. [ABSTRACT FROM AUTHOR]

Podocytes are crucial for regulating glomerular permeability. They have foot processes that are integral to the renal filtration barrier. Understanding their energy metabolism could shed light on the pathogenesis of filtration barrier injury. Lactate has been increasingly recognized as more than a waste product and has emerged as a significant metabolic fuel and reserve. The recent identification of lactate transporters in podocytes, the expression of which is modulated by glucose levels and lactate, highlights lactate's relevance. The present study investigated the impact of lactate on podocyte respiratory efficiency and mitochondrial dynamics. We confirmed lactate oxidation in podocytes, suggesting its role in cellular energy production. Under conditions of glucose deprivation or lactate supplementation, a significant shift was seen toward oxidative phosphorylation, reflected by an increase in the oxygen consumption rate/extracellular acidification rate ratio. Notably, lactate dehydrogenase A (LDHA) and lactate dehydrogenase B (LDHB) isoforms, which are involved in lactate conversion to pyruvate, were detected in podocytes for the first time. The presence of lactate led to higher intracellular pyruvate levels, greater LDH activity, and higher LDHB expression. Furthermore, lactate exposure increased mitochondrial DNA-to-nuclear DNA ratios and resulted in upregulation of the mitochondrial biogenesis markers peroxisome proliferator-activated receptor coactivator-1α and transcription factor A mitochondrial, regardless of glucose availability. Changes in mitochondrial size and shape were observed in lactate-exposed podocytes. These findings suggest that lactate is a pivotal energy source for podocytes, especially during energy fluctuations. Understanding lactate's role in podocyte metabolism could offer insights into renal function and pathologies that involve podocyte injury. [Display omitted] • Lactate serves as an important precursor for cellular energy production in podocytes. • Lactate stimulation alters mitochondrial dynamics and respiratory efficiency. • Lactate augments mitochondrial biogenesis in podocytes. • Lactate regulates LDH isoforms expression and activity in podocytes. [ABSTRACT FROM AUTHOR]

Our purpose was to determine how age affects metabolic flexibility and underlying glucose kinetics in healthy young and older adults. Therefore, glucose and lactate tracers along with pulmonary gas exchange data were used to determine glucose kinetics and respiratory exchange ratios [RER = carbon dioxide production (V̇ co 2)/oxygen consumption (V̇ o 2)] during a 2-h 75-g oral glucose tolerance test (OGTT). After an 12-h overnight fast, 28 participants, 15 young (21–35 yr; 7 men and 8 women) and 13 older (60–80 yr; 7 men and 6 women), received venous primed-continuous infusions of [6,6-2H]glucose and [3-13C]lactate with a H 13 C O 3 − bolus. After a 90-min metabolic stabilization and tracer equilibration period, volunteers underwent an OGTT. Arterialized glucose concentrations ([glucose]) started to rise 15 min post glucose consumption, peaked at 60 min, and remained elevated. As assessed by rates of appearance (Ra) and disposal (Rd) and metabolic clearance rate (MCR), glucose kinetics were suppressed in older compared to young individuals. As well, unlike in young individuals, fractional gluconeogenesis (fGNG) remained elevated in the older population after the oral glucose challenge. Finally, there were no differences in 12-h fasting baseline or peak RER values following an oral glucose challenge in older compared to young men and women, making RER an incomplete measure of metabolic flexibility in the volunteers we evaluated. Our study revealed that glucose kinetics are significantly altered in a healthy aged population after a glucose challenge. Furthermore, those physiological deficits are not detected from changes in RER during an OGTT. NEW & NOTEWORTHY: To determine metabolic flexibility in response to an OGTT, we studied healthy young and older men and women to determine glucose kinetics and changes in RER. Compared to young subjects, glucose kinetics were suppressed in older healthy individuals during an OGTT. Surprisingly, the age-related changes in glucose flux were not reflected in RER measurements; thus, RER measurements do not give a complete view of metabolic flexibility in healthy individuals. [ABSTRACT FROM AUTHOR]

Aim: In this study, we investigated glucose and lactate kinetics during a 75 g oral glucose tolerance test (OGTT) in 23 overweight and obese adolescents and assessed putative differences among participants with and without metabolic dysfunction‐associated steatotic liver disease (MASLD). Methods: We enrolled 23 young people (six girls) with obesity [body mass index 33 (29‐37)]. Glucose‐lactate kinetics parameters (disposal glucose insulin sensitivity, SID; fraction of glucose converted into lactate, fr; fractional lactate clearance rate, kL) and lactate production rate (LPR) were estimated using the oral glucose‐lactate minimal model. MASLD presence was assessed using the proton density fat fraction. We analysed glucose, lactate and LPR time to peak, peak values and area under the curve and evaluated differences using the Wilcoxon test. MASLD and no‐MASLD participants were compared using the Mann‐Whitney test. Correlations between parameters were assessed using the Spearman correlation coefficient (ρ). We also tested the performance of two (4 or 3 h OGTT) protocols in estimating oral glucose‐lactate minimal model and LPR parameters. Results: Glucose peaks 30 min earlier than lactate (p =.0019). This pattern was present in the no‐MASLD group (p <.001). LPR peaks 30 min later in the MASLD group (p =.02). LPR and kL were higher in MASLD, suggesting higher glycolysis and lactate utilization. SID and fr correlate significantly (ρ = −0.55, p =.008). SID and fr were also correlated with the body mass index, (ρ = −0.45, p =.04; and ρ = 0.45; p =.03). The protocol duration did not influence the estimates of the parameters. Discussion: Youth with MASLD showed a delayed glucose metabolism, possibly because of greater utilization of the underlying substrates. A 3‐h OGTT may be used to assess lactate metabolism effectively. [ABSTRACT FROM AUTHOR]

Cancer cachexia is a complex systemic wasting syndrome. Nutritional mechanisms that span energy intake, nutrient metabolism, body composition, and energy balance may be impacted by, and may contribute to, the development of cachexia. To date, clinical management of cachexia remains elusive. Leaning on discoveries and novel methodologies from other fields of research may bolster new breakthroughs that improve nutritional management and clinical outcomes. Characteristics that compare and contrast cachexia and obesity may reveal opportunities for cachexia research to adopt methodology from the well-established field of obesity research. This review outlines the known nutritional mechanisms and gaps in the knowledge surrounding cancer cachexia. In parallel, we present how obesity may be a different side of the same coin and how obesity research has tackled similar research questions. We present insights into how cachexia research may utilize nutritional methodology to expand our understanding of cachexia to improve definitions and clinical care in future directions for the field. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to ascertain the optimal test duration to elicit the highest maximal lactate formation rate ( V ˙ Lamax), whilst exploring the underpinning energetics, and identifying the optimal blood lactate sampling period. Methods: Fifteen trained to well-trained males (age 27 ± 6 years; peak power: 1134 ± 174 W) participated in a randomised cross-over design completing three all-out sprint cycling tests of differing test durations (10, 15, and 30 s). Peak and mean power output (W and W.kg−1), oxygen uptake, and blood lactate concentrations were measured. V ˙ Lamax and energetic contributions (phosphagen, glycolytic, and oxidative) were determined using these parameters. Results: The shortest test duration of 10 s elicited a significantly (p = 0.003; p < 0.001) higher V ˙ Lamax (0.86 ± 0.17 mmol.L−1.s−1; 95% CI 0.802–0.974) compared with both 15 s (0.68 ± 0.18 mmol.L−1.s−1; 95% CI 0.596–0.794) and 30 s (0.45 ± 0.07 mmol.L−1.s−1; 95% CI 0.410–0.487). Differences in V ˙ Lamax were associated with large effect sizes (d = 1.07, d = 3.15). We observed 81% of the PCr and 53% of the glycolytic work completed over the 30 s sprint duration was attained after 10 s. BLamaxpost were achieved at 5 ± 2 min (ttest 10 s), 6 ± 2 min (ttest 15 s), and 7 ± 2 min (ttest 30 s), respectively. Conclusion: Our findings demonstrated a 10 s test duration elicited the highest V ˙ Lamax. Furthermore, the 10 s test duration mitigated the influence of the oxidative metabolism during all-out cycling. The optimal sample time to determine peak blood lactate concentration following 10 s was 5 ± 2 min. [ABSTRACT FROM AUTHOR]

We examine the impact of the acute manipulation of oxygen availability during discrete phases (active and passive) of a repeated‐sprint cycling protocol on performance, physiological, and perceptual responses. On separate days, twelve trained males completed four sets of five 5‐s 'all out' cycle sprints (25‐s inter‐sprint recovery and 5‐min interset rest) in four randomized conditions: normobaric hypoxia (inspired oxygen fraction of 12.9%) applied continuously (C‐HYP), intermittently during only the sets of sprints (I‐HYPSPRINT) or between‐sets recovery periods (I‐HYPRECOVERY), or not at all (C‐NOR). Peak and mean power output, peripheral oxygen saturation, heart rate, blood lactate concentration, exercise‐related sensations, and vastus lateralis muscle oxygenation using near‐infrared spectroscopy were assessed. Peak and mean power output was ∼4%–5% lower for C‐HYP compared to C‐NOR (P ≤ 0.050) and I‐HYPRECOVERY (P ≤ 0.027). Peripheral oxygen saturation was lower during C‐HYP and I‐HYPSPRINT compared with C‐NOR and I‐HYPRECOVERY during sets of sprints (∼83–85 vs. ∼95%–97%; P < 0.001), while lower values were obtained for C‐HYP and I‐HYPRECOVERY than C‐NOR and I‐HYPSPRINT during between‐sets rest period (∼84–85 vs. ∼96%; P < 0.001). Difficulty in breathing was ∼21% higher for C‐HYP than C‐NOR (P = 0.050). Ratings of perceived exertion (P = 0.435), limb discomfort (P = 0.416), heart rate (P = 0.605), blood lactate concentration (P = 0.976), and muscle oxygenation‐derived variables (P = 0.056 to 0.605) did not differ between conditions. In conclusion, the method of hypoxic exposure application (continuous vs. intermittent) affects mechanical performance, while internal demands remained essentially comparable during repeated cycle sprints. Highlights: Continuous hypoxic exposure resulted in reduced repeated sprint performance compared to both normoxia and intermittent hypoxia during recoveries.Cardiovascular solicitation and glycolytic contribution showed no significant differences between ambient air and hypoxic conditions regardless of the timing of hypoxic gas administration (entire session, sprints only, or recovery only).The method of applying hypoxic exposure significantly affected mechanical performance, while internal physiological demands remained essentially comparable between conditions during repeated cycle sprints. [ABSTRACT FROM AUTHOR]

Inflammation and aberrant cellular metabolism are widely recognized as hallmarks of cancer. In pancreatic ductal adenocarcinoma (PDAC), inflammatory signaling and metabolic reprogramming are tightly interwoven, playing pivotal roles in the pathogenesis and progression of the disease. However, the regulatory functions of inflammatory mediators in metabolic reprogramming in pancreatic cancer have not been fully explored. Earlier, we demonstrated that pro-inflammatory mediator macrophage migration inhibitory factor (MIF) enhances disease progression by inhibiting its downstream transcriptional factor nuclear receptor subfamily 3 group C member 2 (NR3C2). Here, we provide evidence that MIF and NR3C2 interactively regulate metabolic reprogramming, resulting in MIF-induced cancer growth and progression in PDAC. MIF positively correlates with the HK1 (hexokinase 1), HK2 (hexokinase 2) and LDHA (lactate dehydrogenase) expression and increased pyruvate and lactate production in PDAC patients. Additionally, MIF augments glucose uptake and lactate efflux by upregulating HK1, HK2 and LDHA expression in pancreatic cancer cells in vitro and in mouse models of PDAC. Conversely, a reduction in HK1, HK2 and LDHA expression is observed in tumors with high NR3C2 expression in PDAC patients. NR3C2 suppresses HK1, HK2 and LDHA expression, thereby inhibiting glucose uptake and lactate efflux in pancreatic cancer. Mechanistically, MIF-mediated regulation of glycolytic metabolism involves the activation of the mitogen-activated protein kinase–ERK signaling pathway, whereas NR3C2 interacts with the activator protein 1 to regulate glycolysis. Our findings reveal an interactive role of the MIF/NR3C2 axis in regulating glucose metabolism supporting tumor growth and progression and may be a potential target for designing novel approaches for improving disease outcome. [ABSTRACT FROM AUTHOR]

To compare the acute responses to different set configurations (cluster [CLU] vs. traditional [TRA]) under distinct blood flow conditions (free vs. restricted) in full-squat (SQ). Twenty resistance-trained males performed 4 protocols that differed in the set configuration (TRA: continuous repetitions; vs. CLU: 30 seconds of rest every 2 repetitions) and in the blood flow condition (FF: free-flow; vs. blood flow restriction [BFR]: 50% of arterial occlusion pressure). The relative intensity (60% 1RM), volume (3 sets of 8 repetitions), and resting time (2 minutes) were equated. Mean propulsive force (MPF), velocity (MPV) and power (MPP), and electromyography (EMG) parameters were recorded during each repetition. Ten-siomyography (TMG), blood lactate, countermovement jump (CMJ) height, maximal voluntary isometric contraction, in SQ, and movement velocity against the load that elicited a 1 m⋅s-1 velocity at baseline (V1-load) in SQ were assessed at pre- and post-exercise. The CLU protocols allowed a better maintenance of MPF, MPV, MPP, and EMG median frequency during the exercise compared to TRA (clu-time interaction, p < 0.05). The TRA protocols experienced greater impairments post-exercise in TMG- and EMG-derived variables (clu-time interaction, p < 0.05) and SQ and CMJ performance (clu-time interaction, p = 0.08 andp < 0.05, respectively), as well as higher blood lactate concentrations (clu-time interaction, p < 0.001) than CLU. Moreover, BFR displayed decreases in TMG variables (bfr-time interaction, p < 0.01), but BFR-CLU resulted in the greatest reduction in twitch contraction time (p < 0.001). Cluster sets reduced fatigue during and after the training session and BFR exacerbated impairments in muscle mechanical properties; however, the combination of both could improve contraction speed after exercise. [ABSTRACT FROM AUTHOR]

Different approaches exist for characterizing athletes, e.g., physiological and locomotor profiling. The aims of this study were to generate and compare physiological and locomotor profiles of male and female runners and to evaluate relationships between the different approaches. Thirty-four highly trained adolescent and young adult female and male athletes (n = 11 sprinters; n = 11,400-m runners; n = 12 middle-distance runners) performed two 100-m sprints on a running track to determine maximal sprinting speed (MSS) and maximal lactate accumulation rate (ċLamax). A cardiopulmonary exercise test was performed on a treadmill to determine maximal aerobic speed (MAS) and maximal oxygen uptake (...o2max). Anaerobic speed reserve (ASR) was calculated as the difference between MSS and MAS. Group comparisons were conducted with a 2-way ANOVA (discipline x sex; p < 0.05) and Bonferroni post hoc tests and Cohen's d as effect size. Parameters were correlated by Pearson's correlation coefficients. Maximal aerobic speed and ...o2max were higher in 400-m and middle-distance runners compared with sprinters (p ≤ 0.02; -2.24 ≤ d ≤ -1.29). Maximal sprinting speed and ċLamax were higher in sprinters and 400-m runners compared with middle-distance runners (0.03 ≤ p ≤ 0.28; 0.73 ≤ d ≤ 1.23). Anaerobic speed reserve was highest in sprinters and lowest in middle-distance runners (p ≤ 0.03; 1.24 ≤ d ≤ 2.79). High correlations were found between ASR and MAS, MSS, and ċLamax (p < 0.01; -0.55 ≤ r ≤ 0.91) and between ċLamax and MSS (p < 0.01; r = 0.74). Our results indicate that athletes of different sprinting and running disciplines show differing physiological and locomotor profiles, and that the parameters of these approaches are related to each other. This can be of interest for assessing strengths and weaknesses (e.g., for talent identification) or training prescription in these disciplines. [ABSTRACT FROM AUTHOR]

Simple Summary: NSCLC is one of the most life-threatening forms of oncological diseases. Although targeted and immunotherapy treatments have improved NSCLC prognosis, the chance of surviving is still limited for many patients. Therefore, further efforts are required to improve NSCLC care. AdipoRon is emerging as an antineoplastic molecule in the treatment of different cancers, but its potential in NSCLC is yet to be explored. Herein, we demonstrated that AdipoRon strongly impairs viability, growth and stemness in NSCLC cells. We also recorded higher glucose consumption and lactate accumulation as a result of AdipoRon treatment. Remarkably, the employment of glycolytic-interfering agents enhanced its antiproliferative features. A signaling pathways analysis revealed a marked AMPK phosphorylation, while, in contrast, its abrogation by Compound-C significantly counteracted AdipoRon effectiveness. Altogether, these findings emphasize AdipoRon's anticancer feature even in NSCLC, supporting its endorsement as a future candidate in cancer and NSCLC therapy. Despite the countless therapeutic advances achieved over the years, non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. To this primacy contribute both non-oncogene addicted and advanced NSCLCs, in which conventional therapies are only partially effective. The adiponectin receptor agonist AdipoRon has revealed antiproliferative action in different cancers, including osteosarcoma and pancreatic cancer. Herein, we investigated its potential anticancer role in NSCLC for the first time. We proved that AdipoRon strongly inhibits viability, growth and colony formation in H1299 and A549 NSCLC cells, mainly through a slowdown in cell cycle progression. Along with the biological behaviors, a metabolic switching was observed after AdipoRon administration in NSCLC cells, consisting of higher glucose consumption and lactate accumulation. Remarkably, both 2-Deoxy Glucose and Oxamate glycolytic-interfering agents greatly enhanced AdipoRon's antiproliferative features. As a master regulator of cell metabolism, AMP-activated protein kinase (AMPK) was activated by AdipoRon. Notably, the ablation of AdipoRon-induced AMPK phosphorylation by Compound-C significantly counteracted its effectiveness. However, the engagement of other pathways should be investigated afterwards. With a focus on NSCLC, our findings further support the ability of AdipoRon in acting as an anticancer molecule, driving its endorsement as a future candidate in NSCLC therapy. [ABSTRACT FROM AUTHOR]

Transformation of methyl lactate to acrylic acid was investigated over Ca3(PO4)2, Ca2(P2O7) and their mixture in the temperature range of 250-425 °C. The initial concentration of methyl lactate in water was varied from 2 wt% to neat methyl lactate. The results showed that these phosphate catalysts did not contain any measurable amounts of either acid sites or basic sites. The best catalyst was Ca3(PO4)2 giving 62% selectivity to acrylic acid at 75% conversion at 400 °C using GHSV of 95280 h−1 and 2 wt% methyl lactate in the initial feed. This catalyst exhibited larger surface area in comparison to Ca2(P2O7). Elemental analysis revealed that some Ca leaching occurred during reaction, while in case of Ca2(P2O7) the calcium leaching was 3.4 fold higher than observed for Ca3(PO4)2. Long-term results over Ca3(PO4)2 showed that extensive catalyst deactivation occurred during the first 11 h time-on-stream, after which the activity dropped only slightly. In addition to kinetic studies with different parameters, also, kinetic modeling was performed and the activation energies for formation of different products were determined over different catalysts. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is considered one of the major pathogenic mechanisms of sepsis-induced cardiomyopathy (SIC). Pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of mitochondrial metabolism, is essential for maintaining mitochondrial function. However, its specific role in SIC remains unclear. To investigate this, we established an in vitro model of septic cardiomyopathy using lipopolysaccharide (LPS)-induced H9C2 cardiomyocytes. Our study revealed a significant increase in PDK4 expression in LPS-treated H9C2 cardiomyocytes. Inhibiting PDK4 with dichloroacetic acid (DCA) improved cell survival, reduced intracellular lipid accumulation and calcium overload, and restored mitochondrial structure and respiratory capacity while decreasing lactate accumulation. Similarly, Oxamate, a lactate dehydrogenase inhibitor, exhibited similar effects to DCA in LPS-treated H9C2 cardiomyocytes. To further validate whether PDK4 causes cardiomyocyte and mitochondrial damage in SIC by promoting lactate production, we upregulated PDK4 expression using PDK4-overexpressing lentivirus in H9C2 cardiomyocytes. This resulted in elevated lactate levels, impaired mitochondrial structure, and reduced mitochondrial respiratory capacity. However, inhibiting lactate production reversed the mitochondrial dysfunction caused by PDK4 upregulation. In conclusion, our study highlights the pathogenic role of PDK4 in LPS-induced cardiomyocyte and mitochondrial damage by promoting lactate production. Therefore, targeting PDK4 and its downstream product lactate may serve as promising therapeutic approaches for treating SIC. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Quantify the relationship between perioperative anaerobic lactate production, microcirculatory blood flow, and mitochondrial respiration in patients after cardiovascular surgery with cardiopulmonary bypass. DESIGN: Serial measurements of lactate-pyruvate ratio (LPR), microcirculatory blood flow, plasma tricarboxylic acid cycle cycle intermediates, and mitochondrial respiration were compared between patients with a normal peak lactate (≤ 2 mmol/L) and a high peak lactate (≥ 4 mmol/L) in the first 6 hours after surgery. Regression analysis was performed to quantify the relationship between clinically relevant hemodynamic variables, lactate, LPR, and microcirculatory blood flow. SETTING: This was a single-center, prospective observational study conducted in an academic cardiovascular ICU. PATIENTS: One hundred thirty-two patients undergoing elective cardiovascular surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with a high postoperative lactate were found to have a higher LPR compared with patients with a normal postoperative lactate (14.4 ± 2.5 vs. 11.7 ± 3.4; p = 0.005). Linear regression analysis found a significant, negative relationship between LPR and microcirculatory flow index (r = --0.225; β = --0.037; p = 0.001 and proportion of perfused vessels: r = --0.17; β = --0.468; p = 0.009). There was not a significant relationship between absolute plasma lactate and microcirculation variables. Last, mitochondrial complex I and complex II oxidative phosphorylation were reduced in patients with high postoperative lactate levels compared with patients with normal lactate (22.6 ± 6.2 vs. 14.5 ± 7.4 pmol O2/s/106 cells; p = 0.002). CONCLUSIONS: Increased anaerobic lactate production, estimated by LPR, has a negative relationship with microcirculatory blood flow after cardiovascular surgery. This relationship does not persist when measuring lactate alone. In addition, decreased mitochondrial respiration is associated with increased lactate after cardiovascular surgery. These findings suggest that high lactate levels after cardiovascular surgery, even in the setting of normal hemodynamics, are not simply a type B phenomenon as previously suggested. [ABSTRACT FROM AUTHOR]

Lactate is an oncometabolite that play important role in tumor aggressiveness. Lactate from the tumor microenvironment (TME) is taken up by cancer cells as an energy resource via mitochondrial oxidative phosphorylation (or OXPHOS). In the present study, by using an online meta‐analysis tool we demonstrated that in oral squamous cancer cells (OSCCs) glycolytic and OXPHOS governing genes are overexpressed, like in breast cancer. For experimental demonstration, we treated the OSCC cell line (SCC4) and breast cancer cells (MDA‐MB‐231) with sodium L‐lactate and analyzed its effects on changes in EMT and migration. For the therapeutic intervention of lactate metabolism, we used AZD3965 (an MCT1 inhibitor), and 7ACC2 (an MPC inhibitor). Like breast cancer, oral cancer tissues showed increased transcripts of 12 genes that were previously shown to be associated with glycolysis and OXPHOS. We experimentally demonstrated that L‐lactate treatment induced mesenchymal markers and migration of cancer cells, which was significantly neutralized by MPC inhibitor that is, 7ACC2. Such an effect on EMT status was not observed with AZD3965. Furthermore, we showed that lactate treatment increases the MPC1 expression in both cancer cells, and this might be the reason why cancer cells in the high lactate environment are more sensitive to 7ACC2. Overall, our present findings demonstrate that extracellular lactate positively regulates the MPC1 protein expression in cancer cells, thereby putting forward the notion of using 7ACC2 as a potential therapeutic alternative to inhibit malignant oxidative cancers. Future preclinical studies are warranted to validate the present findings. [ABSTRACT FROM AUTHOR]

A novel optical lactate biosensor is presented that utilizes a colorimetric interaction between H2O2 liberated by a binary enzymatic reaction and bis(neocuproine)copper(II) complex ([Cu(Nc)2]2+) known as CUPRAC (cupric reducing antioxidant capacity) reagent. In the first step, lactate oxidase (LOx) and pyruvate oxidase (POx) were separately immobilized on silanized magnetite nanoparticles (SiO2@Fe3O4 NPs), and thus, 2 mol of H2O2 was released per 1 mol of the substrate due to a sequential enzymatic reaction of the mixture of LOx-SiO2@Fe3O4 and POx-SiO2@Fe3O4 NPs with lactate and pyruvate, respectively. In the second step, the absorbance at 450 nm of the yellow-orange [Cu(Nc)2]+ complex formed through the color reaction of enzymatically produced H2O2 with [Cu(Nc)2]2+ was recorded. The results indicate that the developed colorimetric binary enzymatic biosensor exhibits a broad linear range of response between 0.5 and 50.0 µM for lactate under optimal conditions with a detection limit of 0.17 µM. The fabricated biosensor did not respond to other saccharides, while the positive interferences of certain reducing compounds such as dopamine, ascorbic acid, and uric acid were minimized through their oxidative removal with a pre-oxidant (NaBiO3) before enzymatic and colorimetric reactions. The fabricated optical biosensor was applied to various samples such as artificial blood, artificial/real sweat, and cow milk. The high recovery values (close to 100%) achieved for lactate-spiked samples indicate an acceptable accuracy of this colorimetric biosensor in the determination of lactate in real samples. Due to the increase in H2O2 production with the bienzymatic lactate sensor, the proposed method displays double-fold sensitivity relative to monoenzymatic biosensors and involves a neat color reaction with cupric-neocuproine having a clear stoichiometry as opposed to the rather indefinite stoichiometry of analogous redox dye methods. [ABSTRACT FROM AUTHOR]

We compared the immediate response and recovery of femoral cartilage morphology following aerobic or resistance exercise to a control condition. Fifteen healthy young males (23.9 years; 170.1 cm; 69.7 kg) visited the laboratory three separate days and randomly performed one of the 30-min exercise aerobic exercises (treadmill running), resistance exercises (leg presses, back squats, and knee extensions), or seated rest as the control, each followed by the 50-min recovery. Ultrasonographic images of the femoral cartilage cross-sectional area (CSA) were obtained before and after exercise and every 5 min thereafter. To test exercise effects over time, a mixed model analysis of variance and Tukey–Kramer post-hoc tests were performed (p <0.05). The femoral cartilage CSA was different (condition×time: F34,742 =4.30, p <0.0001) and the femoral cartilage CSA was decreased after the aerobic (−5.8%, p <0.0001) and the resistance (−3.4%, p =0.04) exercises compared to the p re-exercise levels. Deformed femoral cartilage CSA took 35 and 10 min to return to the pre-exercise levels after aerobic and resistance exercises (p +>+0.09), respectively. Thirty minutes of moderate exertion performing aerobic or resistance exercises immediately reduced the femoral cartilage CSA. A rest period ranging from 10 to 35 min was required for cartilage recovery after weight-bearing exercises. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the effects of subtetanic neuromuscular electrical stimulation combined with voluntary exercise between repeated Wingate tests on sprint exercise performance and blood lactate accumulation during sprint interval training. Fifteen healthy young males volunteered. After 1-min baseline, participants underwent the Wingate test twice. They performed a 4-min intervention between tests: neuromuscular electrical stimulation with free-weight cycling or voluntary cycling alone [43.6 (8.0) watts], which matched oxygen consumption with neuromuscular electrical stimulation with free-weight cycling. The blood lactate concentration was assessed at the end of the baseline, at 3-min intervention, and on recovery at 1, 3, 5, and 10 min after the second Wingate test. Peak and mean blood lactate concentration during recovery were significantly greater with neuromuscular electrical stimulation with free-weight cycling than voluntary cycling alone (P>0.036 and P=0.011, respectively). Peak power, mean power, and rate of decline (fatigue index) were not significantly different between conditions in both Wingate tests (condition/interaction all P>0.300, partial η2 <0.1). Subtetanic neuromuscular electrical stimulation combined with voluntary exercise indicated similar exercise performance and fatigue levels during Wingate tests, but enhanced blood lactate accumulation compared to oxygen consumption-matched voluntary cycling during sprint interval training. [ABSTRACT FROM AUTHOR]

Once considered a metabolic waste product, today it is considered an important signaling molecule continuously forming under aerobic conditions. Lactate, a molecule primarily known as a byproduct of glycolysis, has gained importance in recent years due to its multifaceted role in various biological processes. Misconceptions surrounding lactate have persisted for centuries, especially the belief that elevated lactate levels were solely a result of low oxygen levels shaped early understanding. However, current research challenges this view and expands our comprehension of lactate's various roles. Unfortunately, despite all of the mentioned above lactate is rooted in modern society as a deterrent word and many people do not know its value in the human body, let alone clinical implementations or physical performance. The main goal of this review is to refresh current knowledge regarding lactate research and spread the overall information among a professional society. [ABSTRACT FROM AUTHOR]

Herein, novel amperometric based biosensor using a MXene-Pt nanocomposite was fabricated and utilized for lactate analysis. MXene-Pt provided a desirable matrix for the anchoring of lactate oxidase (LOD). Excellent electron transfer occurred at the interface between the receptor and glassy carbon electrode (GCE) due to the synergetic effect between MXene layers and Pt nanoparticles (NPs). The uniform distribution of small sized Pt NPs gives rise to superior electron transfer kinetics, thereby maximizing the lactate detection abilities of the LOD-MXene-Pt modified GCE. The novel sensing platform displays this linear response in buffer medium (pH = 7.4) within the range of concentrations of 0.02–0.75 mM, and the detection limit of 10 µM based on 3σ was obtained for lactate detection. The accurate analysis of lactate in physiological samples indicated that the presence method is a very specific tool. It was used for successful measurement of lactate concentration in saliva samples during sport practice. The proposed strategy is convenient and less expensive, quick analysis time and offers an efficient procedure of lactate monitoring in the common clinical tests. [Display omitted] • New biosensor for lactate detection was manufactured using MXene-Pt substrate. • The lactate biosensor illustrated a good linear range with low detection limit. • The biosensor was employed for lactate analysis in saliva samples during sport practice. [ABSTRACT FROM AUTHOR]

Objectives: Reflecting the need for an effective support for the daily oral hygiene routine of patients experiencing (symptoms of) gum inflammation, a new mouthwash has been developed containing an amine + zinc lactate + fluoride system. The in vitro efficacy of this product was assessed using traditional laboratory methods, as well as novel experimentation. Materials and Methods: This mouthwash has been evaluated in a series of laboratory tests including two short interval kill tests (SIKTs), a 12‐h (longer term) biofilm regrowth assay, a plaque glycolysis assay, and an aerobic, repeated exposure biofilm model, as well as tests for soft tissue uptake and LPS neutralization. Results: Several laboratory studies demonstrate that a mouthwash containing an amine + zinc lactate + fluoride system provides short‐term and long‐term antibacterial activity. While the immediate efficacy of this formula has been shown to be driven by the presence of the amine, zinc lactate provides a long‐term antibacterial effect, as well as is able to inhibit bacterial metabolism. Conclusions: This research provides the basis for understanding the mode of action of this new mouthwash formulation and explains the previously observed clinical efficacy of this formula against plaque and gingivitis. [ABSTRACT FROM AUTHOR]

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Copyright of Ciencia y Educación (2707-3378) is the property of Duanys Miguel Pena Lopez and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Scabies is a parasitic infestation of the skin with high prevalence in crowded spaces. In some instances, scabies becomes the underlying factor for complicated skin-borne opportunistic pathogens infections in both children and adults. Geographic area and socio-economic factors are determinants of the endemic pattern of this disease. Currently, the treatment of scabies has been under special attention. A combination of oral therapy with Ivermectin and sulfur-based ointments are the gold standard. However, caution is required in patients with kidney impairment. The renal involvement in children with scabies is mainly caused by acute glomerulonephritis. The severity of the nephritic syndrome can lead to other complications. Also, Ivermectin possesses a nephrotoxic effect. Severe hypertension can lead to neurological complications. The aim of our case report is to present two unusual complications in brothers with scabies. We report the cases of two brothers with scabies who presented with severe skin infection that developed acute post infectious glomerulonephritis (APIGN). In addition, one of the brothers presented with posterior reversible encephalopathy syndrome (PRES). The other one developed acute tubule-interstitial acute kidney injury following Ivermectin administration. The evolution of skin lesions was favorable, and kidney function returned to normal in both brothers. [ABSTRACT FROM AUTHOR]

Sun exposure induces major skin alterations, but its effects on skin metabolites and lipids remain largely unknown. Using an original reconstructed human epidermis (RHE) model colonized with human microbiota and supplemented with human sebum, we previously showed that a single dose of simulated solar radiation (SSR) significantly impacted the skin metabolome and microbiota. In this article, we further analyzed SSR‐induced changes on skin metabolites and lipids in the same RHE model. Among the significantly altered metabolites (log2‐fold changes with p ≤ 0.05), we found several natural moisturizing factors (NMFs): amino acids, lactate, glycerol, urocanic acid, pyrrolidone carboxylic acid and derivatives. Analyses of the stratum corneum lipids also showed that SSR induced lower levels of free fatty acids and higher levels of ceramides, cholesterols and its derivatives. An imbalance in NMFs and ceramides combined to an increase of proinflammatory lipids may participate in skin permeability barrier impairment, dehydration and inflammatory reaction to the sun. Our skin model also allowed the evaluation of an innovative ultraviolet/blue light (UV/BL) broad‐spectrum sunscreen with a high sun protection factor (SPF50+). We found that using this sunscreen prior to SSR exposure could in part prevent SSR‐induced alterations in NMFs and lipids in the skin ecosystem RHE model. [ABSTRACT FROM AUTHOR]

Background: Acetogens, a diverse group of anaerobic autotrophic bacteria, are promising whole-cell biocatalysts that fix CO2 during their growth. However, because of energetic constraints, acetogens exhibit slow growth and the product spectrum is often limited to acetate. Enabling acetogens to form more valuable products such as volatile fatty acids during autotrophic growth is imperative for cementing their place in the future carbon neutral industry. Co-cultivation of strains with different capabilities has the potential to ease the limiting energetic constraints. The lactate-mediated co-culture of an Acetobacterium woodii mutant strain, capable of lactate production, with the Clostridium drakei SL1 type strain can produce butyrate and hexanoate. In this study, the preceding co-culture is characterized by comparison of monocultures and different co-culture approaches. Results: C. drakei grew with H2 + CO2 as main carbon and energy source and thrived when further supplemented with D-lactate. Gas phase components and lactate were consumed in a mixotrophic manner with acetate and butyrate as main products and slight accumulation of hexanoate. Formate was periodically produced and eventually consumed by C. drakei. A lactate-mediated co-culture of the A. woodii [PbgaL_ldhD_NFP] strain, engineered for autotrophic lactate production, and C. drakei produced up to 4 ± 1.7 mM hexanoate and 18.5 ± 5.8 mM butyrate, quadrupling and doubling the respective titers compared to a non-lactate-mediated co-culture. Further co-cultivation experiments revealed the possible advantage of sequential co-culture over concurrent approaches, where both strains are inoculated simultaneously. Scanning electron microscopy of the strains revealed cell-to-cell contact between the co-culture partners. Finally, a combined pathway of A. woodii [PbgaL_ldhD_NFP] and C. drakei for chain-elongation with positive ATP yield is proposed. Conclusion: Lactate was proven to be a well-suited intermediate to combine the high gas uptake capabilities of A. woodii with the chain-elongation potential of C. drakei. The cell-to-cell contact observed here remains to be further characterized in its nature but hints towards diffusive processes being involved in the co-culture. Furthermore, the metabolic pathways involved are still speculatory for C. drakei and do not fully explain the consumption of formate while H2 + CO2 is available. This study exemplifies the potential of combining metabolically engineered and native bacterial strains in a synthetic co-culture. [ABSTRACT FROM AUTHOR]

Lactate and glucose are widely used biochemical parameters in current predictive risk scores for cardiogenic shock. Data regarding the relationship between lactate and glucose levels in cardiogenic shock are limited. Thus, we aimed to analyze glucose and lactate as early markers for in-hospital mortality in cardiogenic shock. In this retrospective cohort study, 312 patients presenting with cardiogenic shock to a tertiary-care hospital between 2016 and 2018 were included. Apparent cardiogenic shock was defined as hypoperfusion with hemodynamic compromise and biochemical marker increase due to diminished tissue perfusion, corresponding to SCAI shock stages. In-hospital mortality was assessed as the primary endpoint. The median age of the study population was 71 (60–79) years and the etiology of cardiogenic shock was acute myocardial infarction in 45.8%. Overall in-hospital mortality was 67.6%. In the receiver operating curve analysis, the area under the receiver-operating curve (AUC) for prediction of in-hospital mortality was higher for lactate (AUC: 0.757) than for glucose (AUC: 0.652). Both values were significantly associated with outcome (groups created with best cutoff values obtained from the Youden index). Correlation analysis showed a significant non-linear association of both values. In a multivariable stepwise Cox regression analysis, lactate remained an independent predictor for in-hospital mortality, whilst glucose, despite being implicated in energy metabolism, was not independently predictive for mortality. Together, these data suggest that lactate at admission is superior for mortality prediction in patients with apparent cardiogenic shock. Glucose was not independently predictive for mortality. [ABSTRACT FROM AUTHOR]

Sepsis is characterized by a metabolic disorder of amino acid occurs in the early stage; however, the profile of serum amino acids and their alterations associated with the onset of sepsis remain unclear. Thus, our objective is to identify the specific kinds of amino acids as diagnostic biomarkers in pediatric patients with sepsis. Serum samples were collected from patients with sepsis admitted to the pediatric intensive care unit (PICU) between January 2019 and December 2019 on the 1st, 3rd and 7th day following admission. Demographic and laboratory variables were also retrieved from the medical records specified times. Serum amino acid concentrations were detected by UPLC-MS/MS system. PLS-DA (VIP > 1.0) and Kruskal-Wallis test (p < 0.05) were employed to identify potential biomarkers. Spearman's rank correlation analysis was conducted to find the potential association between amino acid levels and clinical features. The diagnostic utility for pediatric sepsis was assessed using receiver operating characteristic (ROC) curve analysis. Most of amino acid contents in serum were significantly decreased in patients with sepsis, but approached normal levels by the seventh day post-diagnosis. Threonine (THR), lysine (LYS), valine (VAL) and alanine (ALA) emerged as potential biomarkers related for sepsis occurrence, though they were not associated with PELOD/PELOD-2 scores. Moreover, alterations in serum THR, LYS and ALA were linked to complications of brain injury, and serum ALA levels were also related to sepsis-associated acute kidney injury. Further analysis revealed that ALA was significantly correlated with the Glasgow score, serum lactate and glucose levels, C-reactive protein (CRP), and other indicators for liver or kidney dysfunction. Notably, the area under the ROC curve (AUC) for ALA in distinguishing sepsis from healthy controls was 0.977 (95% CI: 0.925-1.000). The serum amino acid profile of children with sepsis is significantly altered compared to that of healthy controls. Notably, ALA shows promise as a potential biomarker for the early diagnosis in septic children. [ABSTRACT FROM AUTHOR]

The high level of lactate in tumor microenvironment not only promotes tumor development and metastasis, but also induces immune escape, which often leads to failures of various tumor therapy strategies. We here report a sono‐triggered cascade lactate depletion strategy by using semiconducting polymer nanoreactors (SPNLCu) for cancer cuproptosis‐immunotherapy. The SPNLCu mainly contain a semiconducting polymer as sonosensitizer, lactate oxidase (LOx) conjugated via a reactive oxygen species (ROS)‐cleavable linker and chelated Cu2+. Upon ultrasound (US) irradiation, the semiconducting polymer generates singlet oxygen (1O2) to cut ROS‐cleavable linker to allow the release of LOx that catalyzes lactate depletion to produce hydrogen peroxide (H2O2). The Cu2+ will be reduced to Cu+ in tumor microenvironment, which reacts with the produced H2O2 to obtain hydroxyl radical (⋅OH) that further improves LOx release via destroying ROS‐cleavable linkers. As such, sono‐triggered cascade release of LOx achieves effective lactate depletion, thus relieving immunosuppressive roles of lactate. Moreover, the toxic Cu+ induces cuproptosis to cause immunogenic cell death (ICD) for activating antitumor immunological effect. SPNLCu are used to treat both subcutaneous and deep‐tissue orthotopic pancreatic cancer with observably enhanced efficacy in restricting the tumor growths. This study thus provides a precise and effective lactate depletion tactic for cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is the most aggressive among the tumors of the central nervous system (CNS), and has a dismal prognosis. Altered metabolism, especially the increased rate of aerobic glycolysis promotes rapid proliferation of GBM cells. Here, we investigated the role of aldehyde dehydrogenase 5 family member A1 (ALDH5A1), a mitochondrial enzyme in the aspect of GBM metabolism. We also studied the regulatory mechanisms of altered ALDH5A1 expression in GBM. Approach and results: We show that ALDH5A1 is significantly downregulated in GBM patients in a grade dependent manner as compared to control brain and its low expression is associated with poor prognosis. It is significantly downregulated under hypoxia and is a direct target of the hypoxia induced microRNA: miR-210. Ectopic overexpression of ALDH5A1 in GBM cell lines U-87 MG and T98G markedly reduced their proliferation, 3D spheroid forming ability, and formation of reactive oxygen species (ROS). ALDH5A1 upregulation increased the oxygen consumption rate (OCR), and reduced the extracellular acidification rate (ECAR) of GBM cells while miR-210 overexpression showed the opposite. A significant downregulation in the transcript levels of LDHA, PDK1, and SLC2A1; coupled with lower glucose uptake and lactate production upon ALDH5A1 overexpression reveals that ALDH5A1 significantly reduces the glycolytic capacity of GBM cells. Total ATP generated in 24 h was more when miR-210 was overexpressed, while a slight decrease in ATP formation was observed upon ALDH5A1 upregulation. Interestingly, we also observed that ALDH5A1 expression is elevated and miR-210 levels are downregulated in IDH-mutant glioma as compared to its wild-type form. Conclusion: Overall, our findings suggest that miR-210 mediated downregulation of ALDH5A1 plays a critical role in tumor metabolism and helps maintaining a high glycolytic phenotype in GBM. [ABSTRACT FROM AUTHOR]

Hepatitis B Virus (HBV) is a hepatotropic virus that can establish a persistent and chronic infection in humans. Chronic hepatitis B (CHB) infection is associated with an increased risk of hepatic decompensation, cirrhosis, and hepatocellular carcinoma (HCC). Lactate level, as the end product of glycolysis, plays a substantial role in metabolism beyond energy production. Emerging studies indicate that lactate is linked to patient mortality rates, and HBV increases overall glucose consumption and lactate production in hepatocytes. Excessive lactate plays a role in regulating the tumor microenvironment (TME), immune cell function, autophagy, and epigenetic reprogramming. The purpose of this review is to gather and summarize the existing knowledge of the lactate's functions in the dysregulation of the immune system, which can play a crucial role in the development of HBV-related HCC. Therefore, it is reasonable to hypothesize that lactate with intriguing functions can be considered an immunomodulatory metabolite in immunotherapy. [ABSTRACT FROM AUTHOR]

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

Anaerobic performance diagnostics in athletes relies on accurate measurements of blood lactate concentration and the calculation of blood lactate accumulation resulting from glycolytic processes. In this study, we investigated the impact of pedaling frequency on blood lactate accumulation during 10-second maximal isokinetic cycling sprints. Thirteen trained males completed five 10-second maximal isokinetic cycling sprints on a bicycle ergometer at different pedaling frequencies (90 rpm, 110 rpm, 130 rpm, 150 rpm, 170 rpm) with continuous power and frequency measurement. Capillary blood samples were taken pre-exercise and up to 30 minutes post-exercise to determine the maximum blood lactate concentration. Blood lactate accumulation was calculated as the difference between maximal post-exercise and pre-start blood lactate concentration. Repeated measurement ANOVA with Bonferroni-adjusted post hoc t-tests revealed significant progressive increases in maximal blood lactate concentration and accumulation with higher pedaling frequencies (p<0.001; η2 +>+0.782). The findings demonstrate a significant influence of pedaling frequency on lactate accumulation, emphasizing its relevance in anaerobic diagnostics. Optimal assessment of maximal lactate formation rate is suggested to require a pedaling frequency of at least 130 rpm or higher, while determining metabolic thresholds using the maximal lactate formation rate may benefit from a slightly lower pedaling frequency. [ABSTRACT FROM AUTHOR]

This study aimed (i) to analyze the 1500 m open water swimming performance, (ii) to examine the associations between physiological and biomechanical variables with swimming performance, and (iii) to determine which variables can predict swimming performance in triathletes. Fourteen elite triathletes (23.4±3.8 y) performed a 1500 m test in open water swimming conditions. Swimming performance was assessed using World Aquatics Points Scoring, and data were obtained from the 1500 m open water swimming test. Heart rate, end-exercise oxygen uptake (EE˙VO2) and blood lactate concentrations were measured. The initial 250 m of the 1500 m swimming test presented the highest values of biomechanical variables in males (i. e. swimming speed, stroke rate (SR), length (SL), index (SI)). A decrease in SL was observed in the last 250 m in both sexes. Positive association were found between EE˙VO2 (r=0.513; p =0.030), swimming speed (r=0.873; p <0.001) and SI (r=0.704; p =0.002) with swimming performance. In contrast, time constant of the oxygen uptake (r=−0.500; p =0.034) and buoy-turn times (r=−0.525; p =0.027) were negatively associated with performance. SI was the main predictor (R2 =0.495) of open water swimming performance in triathletes. In conclusion, triathletes and coaches must conduct open water training sessions to maximize SI (i. e. swimming efficiency). [ABSTRACT FROM AUTHOR]

Objective: To investigate the mechanism by cryptotanshinone regulates the signaling pathway of stromal cell derived factor 1 (SDF-1)/C-X-C chemokine receptor 4 (CXCR4) and inhibits hydrogen peroxide induced cell apoptosis of human bone marrow mesenchymal stem cells (BMSCs). Methods: Cultivated human bone marrow mesenchymal stem cells (HBMSCs) in vitro and established an oxidative stress model by H2O2. Divided HBMSC cells into control group (without oxidative stress induction) and model group (500 μmol/L H2O2 induction for 24 hours), low-dose group of cryptotanshinone(10 μmol/L), medium dose group of cryptotanshinone (20 μmol/L), high-dose group of cryptotanshinone(40 μmol/L). Cell activity was detected by Cell Count Kit (CCK-8). Cell apoptosis was detected by flow cytometry detection. Cellular glucose uptake and lactate levels was detected by enzyme linked immunosorbent assay(Elisa) testing. The content of glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in cells were detected by micro method. Cysteine aspartate protease 3(caspase-3), B-lymphoblastoma-2 associated X protein (Bax), B-lymphoblastoma-2 (Bcl-2), expression of SDF-1 and CXCR4 proteins was detected by western blot detection (Western blot). Results: Compared with the control group, the glucose uptake and lactate levels, GSH, SOD activity, Bcl-2 protein expression, and SDF-1/CXCR4 signaling pathway protein expression of HBMSC cells in the model group decreased, while the cell apoptosis rate, expression of apoptotic protein caspase-3, Bax, and MDA content increased(P<0.05). Compared with the model group, the low, medium, and high dose groups of cryptotanshinone showed an increase in glucose uptake and lactate levels, GSH, SOD activity, Bcl-2 protein expression, and SDF-1/CXCR4 signaling pathway protein expression in HBMSC cells, while the cell apoptosis rate, expression of apoptotic proteins caspase-3, Bax, and MDA content decreased (P<0.05). The differences in various indicators among the low, medium, and high dose groups of cryptotanshinone were statistically significant(P<0.05). Conclusion: Cryptotanshinone may inhibit oxidative stress damage and apoptosis of BMSC induced by hydrogen peroxide by promoting SDF-1/CXCR4 signaling pathway transduction, with high-dose cryptotanshinone having the best effect. [ABSTRACT FROM AUTHOR]

Objective: To analyze and explore the expression of TRIM29 in osteosarcoma and its potential molecular mechanism. E3 ubiquitination ligase TRIM29 is closely related to the malignant growth of tumors. Methods: The expression of TRIM29 gene in osteosarcoma was analyzed by Western blot, IHC and qRT-PCR, CCK8 and EDU were used to detect the value-added level of osteosarcoma cells after downregulation of TRIM29. Further, glucose uptake, lactate production and G6P were used to detect the changes of glycolysis level and analyze the underlying mechanism. A subcutaneous tumor model of BACB/C nude mice was established to observe the effect of downregulation of TRIM29 on the growth of transplanted tumors. Results: qRT-PCR results confirmed that the mRNA expression level of TRIM29 in osteosarcoma tissues was significantly higher than that in normal tissues. Similarly, Western blot and IHC results also confirmed that the protein level of TRIM29 in osteosarcoma tissues was significantly higher. After downregulating the expression of TRIM29 in osteosarcoma cells, CCK-8 and EDU experiments both showed that its value-added ability was weakened, on the contrary, its apoptosis rate was increased. In the G1 phase of cells, its lactate production, glucose consumption, G6P were also correspondingly weakened, and the glycolytic joint rate limiting enzymes HKII, PFKFB3, PKM, LDHAA, GLUT1 and other proteins were also correspondingly reduced. Similarly, in vivo experiments also showed that after downregulating the expression of TRIM29, the weight and growth rate were reduced accordingly. Conclusion: TRIM29 is highly expressed in osteosarcoma cells. After inhibiting the expression of TRIM29 in osteosarcoma cells, its cell proliferation ability and glycolysis level are decreased. TRIM29 inhibits the growth of osteosarcoma cells by restraining the glycolysis level of cells [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to explore the effect of treadmill slope on ground reaction forces and local muscle oxygenation as putative limiting factors of peak oxygen uptake in graded maximal incremental running tests. Thirteen trained male runners completed five maximal incremental running tests on treadmill at − 15%, − 7.5%, 0%, 7.5% and 15% slopes while cardiorespiratory and local muscle oxygenation responses as well as ground reaction forces were continuously recorded. Blood lactate concentration and isometric knee extensor torque were measured before and after each test. Results: Peak oxygen uptake was lower at − 15% slope compared to all other conditions (from − 10 to − 17% lower, p < 0.001), with no difference between − 7.5 and + 15% slope. Maximal heart rate and ventilation values were reached in all conditions. The negative external mechanical work increased from steep uphill to steep downhill slopes (from 6 to 92% of total external work) but was not correlated with the peak oxygen uptake reduction. Local muscle oxygenation remained higher in − 15% slope compared to level running (p = 0.003). Conclusions: Similar peak oxygen uptake can be reached in downhill running up to − 7.5% slope. At more severe downhill slopes (i.e., − 15%), greater negative muscle work and limited local muscle deoxygenation occurred, even in subjects familiarized to downhill running, presumably preventing the achievement of similar to other condition's peak oxygen uptake. Key Points: Trained male runners can reach like level running V̇O2peak at moderate but not at severe negative slope. Negative external mechanical work increases with increasing negative slope. At maximal intensity Vastus Lateralis muscle oxygenation is higher in steep negative slope. Knee extensor isometric muscle torque is preserved after maximal level and uphill running, but reduced after downhill running, despite lower blood lactate. Progressive reduction of V̇O2 at maximal effort with increasing negative slope might be related to the metabolic consequences of increased lower limb negative external work (i.e., eccentric muscle actions). [ABSTRACT FROM AUTHOR]