Deciphering recovery paradigms: Foam rolling's impact on DOMS and lactate dynamics in elite volleyball athletes.

This study examines the effects of Self-Myofascial Release (SMR) techniques on post-exercise recovery in elite volleyball athletes. Through a controlled investigation involving eighteen Chinese Men's National Volleyball Team athletes, the research assessed the impact of foam rolling (FR) versus passive recovery (PAS) on blood lactate clearance and Delayed Onset Muscle Soreness (DOMS), as measured by Visual Analogue Scale (VAS) scores. Findings indicated that FR significantly reduces VAS scores and facilitates lactate clearance when compared to PAS, suggesting foam rolling may enhance post-exercise recovery. While confirming foam rolling's benefits, this research calls for further exploration into recovery mechanisms, emphasizing a cautious interpretation of foam rolling as part of a comprehensive recovery strategy.

The effects of coenzyme Q10 supplementation on biomarkers of exercise-induced muscle damage, physical performance, and oxidative stress: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials.

PURPOSE: This study aims to elucidate the dose-dependent effect of coenzyme Q10 supplementation (CoQ10) on exercise-induced muscle damage (EIMD), physical performance, and oxidative stress in adults. METHODS: A systematic search was conducted through PubMed, Scopus, and ISI Web of Science databases up to August 2023, focusing on randomized control trials (RCTs) that investigated the effects of CoQ10 supplementation on EIMD recovery, physical performance and oxidative stress mitigation in adults. The weighted mean difference (WMD) and 95 % confidence interval (95 %CI) were estimated using the random-effects model. RESULTS: The meta-analysis incorporated 28 RCTs, encompassing 830 subjects. CoQ10 supplementation significantly decreased creatine kinase (CK) (WMD: -50.64 IU/L; 95 %CI: -74.75, -26.53, P < 0.001), lactate dehydrogenase (LDH) (WMD: -52.10 IU/L; 95 %CI: -74.01, -30.19, P < 0.001), myoglobin (Mb) (WMD: -21.77 ng/ml; 95 %CI: -32.59, -10.94, P < 0.001), and Malondialdehyde (MDA) (WMD: -0.73 µmol/l; 95 %CI: -1.26, -0.20, P = 0.007) levels. No significant alteration in total antioxidant capacity was observed post-CoQ10 treatment. Each 100 mg/day increase in CoQ10 supplementation was correlated with a significant reduction in CK (MD: -23.07 IU/L, 95 %CI: -34.27, -11.86), LDH (WMD: -27.21 IU/L, 95 %CI: -28.23, -14.32), Mb (MD: -7.09 ng/ml; 95 %CI: -11.35, -2.83) and MDA (WMD: -0.17 µmol/l, 95 %CI: -0.29, -0.05) serum levels. Using SMD analysis, "very large" effects on LDH and "moderate" effects on CK and MDA were noted, albeit nonsignificant for other outcomes. CONCLUSION: CoQ10 supplementation may be effective in reducing biomarkers of EIMD and oxidative stress in adults. Nevertheless, given the preponderance of studies conducted in Asia, the generalizability of these findings warrants caution. Further RCTs, particularly in non-Asian populations with large sample sizes and extended supplementation durations, are essential to substantiate these observations.

Enhancing Antibody-Specific Productivity: Unraveling the Impact of XBP1s Overexpression and Glutamine Availability in SP2/0 Cells.

Augmentation of glycoprotein synthesis requirements induces endoplasmic reticulum (ER) stress, activating the unfolded protein response (UPR) and triggering unconventional XBP1 splicing. As a result, XBP1s orchestrates the expression of essential genes to reduce stress and restore homeostasis. When this mechanism fails, chronic stress may lead to apoptosis, which is thought to be associated with exceeding a threshold in XBP1s levels. Glycoprotein assembly is also affected by glutamine (Gln) availability, limiting nucleotide sugars (NS), and preventing compliance with the increased demands. In contrast, increased Gln intake synthesizes ammonia as a by-product, potentially reaching toxic levels. IgA2m(1)-producer mouse myeloma cells (SP2/0) were used as the cellular mammalian model. We explored how IgA2m(1)-specific productivity (qIgA2m(1)) is affected by (i) overexpression of human XBP1s (h-XBP1s) levels and (ii) Gln availability, evaluating the kinetic behavior in batch cultures. The study revealed a two and a five-fold increase in qIgA2m(1) when lower and higher levels of XBP1s were expressed, respectively. High h-XBP1s overexpression mitigated not only ammonia but also lactate accumulation. Moreover, XBP1s overexpressor showed resilience to hydrodynamic stress in serum-free environments. These findings suggest a potential application of h-XBP1s overexpression as a feasible and cost-effective strategy for bioprocess scalability.

Chlorella Supplementation Reduces Blood Lactate Concentration and Increases O2 Pulse during Submaximal and Maximal Cycling in Young Healthy Adults.

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

Probiotic Lactobacillus spp. improves Drosophila memory by increasing lactate dehydrogenase levels in the brain mushroom body neurons.

Probiotics are live microorganisms that offer potential benefits to their hosts and can occasionally influence behavioral responses. However, the detailed mechanisms by which probiotics affect the behavior of their hosts and the underlying biogenic effects remain unclear. Lactic acid bacteria, specifically Lactobacillus spp. are known probiotics. Drosophila melanogaster, commonly known as the fruit fly, is a well-established model organism for investigating the interaction between the host and gut microbiota in translational research. Herein, we showed that 5-day administration of Lactobacillus acidophilus (termed GMNL-185) or Lacticaseibacillus rhamnosus (termed GMNL-680) enhances olfactory-associative memory in Drosophila. Moreover, a combined diet of GMNL-185 and GMNL-680 demonstrated synergistic effects on memory functions. Live brain imaging revealed a significant increase in calcium responses to the training odor in the mushroom body ß and γ lobes of flies that underwent mixed feeding with GMNL-185 and GMNL-680. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and whole-mount brain immunohistochemistry revealed significant upregulation of lactate dehydrogenase (LDH) expression in the fly brain following the mixed feeding. Notably, the genetic knockdown of Ldh in neurons, specifically in mushroom body, ameliorated the beneficial effects of mixed feeding with GMNL-185 and GMNL-680 on memory improvement. Altogether, our results demonstrate that supplementation with L. acidophilus and L. rhamnosus enhances memory functions in flies by increasing brain LDH levels.

Empowering mitochondrial metabolism: Exploring L-lactate supplementation as a promising therapeutic approach for metabolic syndrome.

Mitochondrial dysfunction plays a critical role in the pathogenesis of metabolic syndrome (MetS), affecting various cell types and organs. In MetS animal models, mitochondria exhibit decreased quality control, characterized by abnormal morphological structure, impaired metabolic activity, reduced energy production, disrupted signaling cascades, and oxidative stress. The aberrant changes in mitochondrial function exacerbate the progression of metabolic syndrome, setting in motion a pernicious cycle. From this perspective, reversing mitochondrial dysfunction is likely to become a novel and powerful approach for treating MetS. Unfortunately, there are currently no effective drugs available in clinical practice to improve mitochondrial function. Recently, L-lactate has garnered significant attention as a valuable metabolite due to its ability to regulate mitochondrial metabolic processes and function. It is highly likely that treating MetS and its related complications can be achieved by correcting mitochondrial homeostasis disorders. In this review, we comprehensively discuss the complex relationship between mitochondrial function and MetS and the involvement of L-lactate in regulating mitochondrial metabolism and associated signaling pathways. Furthermore, it highlights recent findings on the involvement of L-lactate in common pathologies of MetS and explores its potential clinical application and further prospects, thus providing new insights into treatment possibilities for MetS.

NIR-Activatable Heterostructured Nanoadjuvant CoP/NiCoP Executing Lactate Metabolism Interventions for Boosted Photocatalytic Hydrogen Therapy and Photoimmunotherapy.

Near-infrared (NIR) laser-induced photoimmunotherapy has aroused great interest due to its intrinsic noninvasiveness and spatiotemporal precision, while immune evasion evoked by lactic acid (LA) accumulation severely limits its clinical outcomes. Although several metabolic interventions have been devoted to ameliorate immunosuppression, intracellular residual LA still remains a potential energy source for oncocyte proliferation. Herein, an immunomodulatory nanoadjuvant based on a yolk-shell CoP/NiCoP (CNCP) heterostructure loaded with the monocarboxylate transporter 4 inhibitor fluvastatin sodium (Flu) is constructed to concurrently relieve immunosuppression and elicit robust antitumor immunity. Under NIR irradiation, CNCP heterojunctions exhibit superior photothermal performance and photocatalytic production of reactive oxygen species and hydrogen. The continuous heat then facilitates Flu release to restrain LA exudation from tumor cells, whereas cumulative LA can be depleted as a hole scavenger to improve photocatalytic efficiency. Subsequently, potentiated photocatalytic therapy can not only initiate systematic immunoreaction, but also provoke severe mitochondrial dysfunction and disrupt the energy supply for heat shock protein synthesis, in turn realizing mild photothermal therapy. Consequently, LA metabolic remodeling endows an intensive cascade treatment with an optimal safety profile to effectually suppress tumor proliferation and metastasis, which offers a new paradigm for the development of metabolism-regulated immunotherapy.

Zinc lactate alleviates oxidative stress by modulating crosstalk between constitutive androstane receptor signaling pathway and gut microbiota profile in weaned piglets.

This study aimed to determine the regulatory mechanism of dietary zinc lactate (ZL) supplementation on intestinal oxidative stress damage in a paraquat (PQ)-induced piglet model. Twenty-eight piglets (mean body weight 9.51 ± 0.23 kg) weaned at 28 d of age were randomly divided into control, ZL, PQ, and ZL + PQ groups (n = 7 in each group). The ZL-supplemented diet had little effect on growth performance under normal physiological conditions. However, under PQ challenge, ZL supplementation significantly improved average daily gain (P < 0.05) and reduced the frequency of diarrhea. ZL improved intestinal morphology and ultrastructure by significantly increasing the expression level of the jejunal tight junction protein, zonula occludens-1 (ZO-1) (P < 0.05), and intestinal zinc transport and absorption in PQ-induced piglets, which reduced intestinal permeability. ZL supplementation also enhanced the expression of antioxidant and anti-inflammatory factor-related genes and decreased inflammatory cytokine expression and secretion in PQ-induced piglets. Furthermore, ZL treatment significantly inhibited the activation of constitutive androstane receptor (CAR) signaling (P < 0.01) in PQ-induced piglets and altered the structure of the gut microbiota, especially by significantly increasing the abundance of beneficial gut microbes, including UCG_002, Ruminococcus, Rikenellaceae_RC9_gut_group, Christensenellaceae_R_7_group, Treponema, unclassified_Christensenellaceae, and unclassified_Erysipelotrichaceae (P < 0.05). These data reveal that pre-administration of ZL to piglets can suppress intestinal oxidative stress by improving antioxidant and anti-inflammatory capacity and regulating the crosstalk between CAR signaling and gut microbiota.

Naturally Bicarbonated Water Supplementation Does Not Improve Anaerobic Cycling Performance or Blood Gas Parameters in Active Men and Women.

The completion of high-intensity exercise results in robust perturbations to physiologic homeostasis, challenging the body's natural buffering systems to mitigate the accumulation of metabolic by-products. Supplementation with bicarbonate has previously been used to offset metabolic acidosis, leading to improvements in anaerobic exercise performance. PURPOSE: The purpose of this study was to investigate the presence of ergogenic properties in naturally occurring low-dose bicarbonated water and their effects on anaerobic cycling performance and blood gas kinetics in recreationally active men and women. METHODS: Thirty-nine healthy, recreationally active men and women (28.1 ± 8.0 years, 169.8 ± 11.7 cm, 68.9 ± 10.8 kg, 20.1 ± 7.9% fat, V˙O2peak: 42.8 ± 7.6 mL/kg/min) completed two separate testing sessions consisting of 15 cycling sprints (10 s sprint, 20 s active rest) against 7.5% of their body mass. Using a randomized, double-blind, placebo-controlled, parallel group study design, study participants consumed a 10 mL/kg dose of either spring water (SW) or bicarbonated mineral water (BMW) (delivering ~3 g/day of bicarbonate) for 7 days. Venous blood was collected before, immediately after, and 5 and 10 min after the sprint protocol and was analyzed for lactate and a series of blood gas components. After the completion of 15 cycling sprints, averages of peak and mean power for bouts 1-5, 6-10, and 11-15, along with total work for the entire cycling protocol, were calculated. All performance and blood gas parameters were analyzed using a mixed-factorial ANOVA. RESULTS: pH was found to be significantly higher in the BMW group immediately after (7.17 ± 0.09 vs. 7.20 ± 0.11; p = 0.05) and 10 min post exercise (7.21 ± 0.11 vs. 7.24 ± 0.09; p = 0.04). A similar pattern of change was observed 5 min post exercise wherein pH levels in the SW group were lower than those observed in the BMW group; however, this difference did not achieve statistical significance (p = 0.09). A statistical trend (p = 0.06) was observed wherein lactate in the BMW group tended to be lower than in the SW group 5 min post exercise. No significant main effect for time (p > 0.05) or group × time interactions (p > 0.05) for the total work, average values of peak power, or average values of mean power were observed, indicating performance was unchanged. CONCLUSION: One week of consuming water with increased bicarbonate (10 mL/kg; ~3 g/day bicarbonate) showed no effect on anaerobic cycling performance. BMW decreased blood lactate concentrations 5 min after exercise and increased blood pH immediately and 10 min after exercise.

Evidence of the Beneficial Impact of Three Probiotic-Based Food Supplements on the Composition and Metabolic Activity of the Intestinal Microbiota in Healthy Individuals: An Ex Vivo Study.

Scientific evidence has increasingly supported the beneficial effects of probiotic-based food supplements on human intestinal health. This ex vivo study investigated the effects on the composition and metabolic activity of the intestinal microbiota of three probiotic-based food supplements, containing, respectively, (1) Bifidobacterium longum ES1, (2) Lactobacillus acidophilus NCFM®, and (3) a combination of L. acidophilus NCFM®, Lactobacillus paracasei Lpc-37™, Bifidobacterium lactis Bi-07™, and Bifidobacterium lactis Bl-04™. This study employed fecal samples from six healthy donors, inoculated in a Colon-on-a-plate® system. After 48 h of exposure or non-exposure to the food supplements, the effects were measured on the overall microbial fermentation (pH), changes in microbial metabolic activity through the production of short-chain and branched-chain fatty acids (SCFAs and BCFAs), ammonium, lactate, and microbial composition. The strongest effect on the fermentation process was observed for the combined formulation probiotics, characterized by the significant stimulation of butyrate production, a significant reduction in BCFAs and ammonium in all donors, and a significant stimulatory effect on bifidobacteria and lactobacilli growth. Our findings suggest that the combined formulation probiotics significantly impact the intestinal microbiome of the healthy individuals, showing changes in metabolic activity and microbial abundance as the health benefit endpoint.

Prognostic nutritional index and serum lactate dehydrogenase predict the prognosis of nasopharyngeal carcinoma patients who received intensity-modulated radiation therapy.

PURPOSE: This research aimed to evaluate the prognostic significance of baseline prognostic nutritional index (PNI) and lactate dehydrogenase (LDH) for the outcome of individuals diagnosed with non-metastatic nasopharyngeal carcinoma (NPC). METHODS: A retrospective analysis was conducted on data from 810 patients with non-metastatic NPC who underwent intensity-modulated radiation therapy (IMRT) with or without chemotherapy. The best cut-offs for PNI and LDH were identified by X-tile software to be 48.5 and 150, respectively. To find the independent prognostic factors for survival outcomes, univariate and multivariate regression analyses were conducted, and AUCs were used to compare their prognostic values. RESULTS: Multivariate analysis revealed that patients with PNI > 48.5 had better overall survival (OS) (HR: 0.502, P < 0.001), progression-free survival (PFS) (HR: 0.618, P < 0.001), and distant metastasis-free survival (DMFS) (HR: 0.637, P = 0.005). Higher LDH was associated with poorer OS (HR: 1.798, P < 0.001), PFS (HR: 1.671, P < 0.001), and DMFS (HR: 1.756, P < 0.001). The combination of low PNI and high LDH in non-metastatic NPC patients was correlated with poor OS (P < 0.001), PFS (P < 0.001), and DMFS (P < 0.001). The combination of PNI and LDH had the highest AUCs for predicting OS, PFS, and DMFS. CONCLUSIONS: PNI and LDH might become valuable predictors of the prognosis of non-metastatic NPC patients undergoing IMRT with or without chemotherapy. Prognostic accuracy can be enhanced by combining PNI and LDH.

Lactate promotes survival and hepatocyte differentiation of human induced pluripotent stem cells in a medium without glucose and supplemented with galactose.

Human induced pluripotent stem (iPS) cells initiate hepatocyte differentiation in a medium without glucose and supplemented with galactose, oncostatin M and small molecules [hepatocyte differentiation inducer (HDI)]. To clarify the metabolic differences between iPS cells in HDI and ReproFF (undifferentiated state), a metabolome analysis was performed. iPS cells were cultured in a medium without glucose and supplemented with galactose, as well as 1 mM of calcium lactate, sodium lactate or lactic acid. After 7 days of culture, the cells were subjected to reverse transcription-quantitative PCR analysis. The galactose-1-phosphate concentration was significantly higher in cells cultured in HDI than in those cultured with ReproFF. The lactate concentration in the HDI group was significantly lower than that in the ReproFF group. The expression levels of α-feto protein and albumin were significantly higher in the groups cultured with calcium lactate, sodium lactate and lactic acid as compared with ReproFF. It was suggested that lactate promoted the survival of iPS cells cultured in a medium without glucose and supplemented with galactose. Under these conditions, iPS cells begin to differentiate into a hepatocyte lineage. Lactate may be applied to produce hepatocytes from iPS cells more efficiently.

Candidatus Accumulibacter use fermentation products for enhanced biological phosphorus removal.

Previous research suggested that two major groups of polyphosphate-accumulating organisms (PAOs), i.e., Ca. Accumulibacter and Tetrasphaera, play cooperative roles in enhanced biological phosphorus removal (EBPR). The fermentation of complex organic compounds by Tetrasphaera provides carbon sources for Ca. Accumulibacter. However, the viability of the fermentation products (e.g., lactate, succinate, alanine) as carbon sources for Ca. Accumulibacter and their potential effects on the metabolism of Ca. Accumulibacter were largely unknown. This work for the first time investigated the capability and metabolic details of Ca. Accumulibacter cognatus clade IIC strain SCUT-2 (enriched in a lab-scale reactor with a relative abundance of 42.8%) in using these fermentation products for EBPR. The enrichment culture was able to assimilate lactate and succinate with the anaerobic P release to carbon uptake ratios of 0.28 and 0.36 P mol/C mol, respectively. In the co-presence of acetate, the uptake of lactate was strongly inhibited, since two substrates shared the same transporter as suggested by the carbon uptake bioenergetic analysis. When acetate and succinate were fed at the same time, Ca. Accumulibacter assimilated two carbon sources simultaneously. Proton motive force (PMF) was the key driving force (up to 90%) for the uptake of lactate and succinate by Ca. Accumulibacter. Apart from the efflux of proton in symport with phosphate via the inorganic phosphate transport system, translocation of proton via the activity of fumarate reductase contributed to the generation of PMF, which agreed with the fact that PHV was a major component of PHA when lactate and succinate were used as carbon sources, involving the succinate-propionate pathway. Metabolic models for the usage of lactate and succinate by Ca. Accumulibacter for EBPR were built based on the combined physiological, biochemical, metagenomic, and metatranscriptomic analyses. Alanine was shown as an invalid carbon source for Ca. Accumulibacter. Instead, it significantly and adversely affected Ca. Accumulibacter-mediated EBPR. Phosphate release was observed without alanine uptake. Significant inhibitions on the aerobic phosphate uptake was also evident. Overall, this study suggested that there might not be a simply synergic relationship between Ca. Accumulibacter and Tetrasphaera. Their interactions would largely be determined by the kind of fermentation products released by the latter.

Iron Deficiency Anemia Presenting With Pancytopenia: A Study From India.

INTRODUCTION: Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. IDA is commonly associated with thrombocytosis and normal or slightly decreased leukocyte count. Sometimes it can present with thrombocytopenia, but rarely present with pancytopenia. Here we are presenting six cases of severe iron deficiency presenting with pancytopenia, which responded to iron replenishment. METHODS:  This 12-month observational study was conducted in the Department of General Medicine at a tertiary care Centre in India. All cases of pancytopenia (after exclusion of other causes) with IDA were included. IDA was established with the help of a complete blood count (CBC), peripheral smear examination, serum iron studies, and serum ferritin.  Results: In our study, CBC at four weeks later of iron transfusion without other supplementation showed significant improvement in hematological parameters. CONCLUSION:  Severe iron deficiency is a reversible etiology of pancytopenia. It should be kept as a differential diagnosis of pancytopenia if common causes of pancytopenia are ruled out.

Recognizing and Managing a Metabolic Crisis.

In some relatively common inborn errors of metabolism there can be the accumulation of toxic compounds including ammonia and organic acids such as lactate and ketoacids, as well as energy deficits at the cellular level. The clinical presentation is often referred to as a metabolic emergency or crisis. Fasting and illness can result in encephalopathy within hours, and without appropriate recognition and intervention, the outcome may be permanent disability or death. This review outlines easy and readily available means of recognizing and diagnosing a metabolic emergency as well as general guidelines for management. Disease-specific interventions focus on parenteral nutrition to reverse catabolism, toxin removal strategies, and vitamin/nutrition supplementation.

Effect of low-level laser therapy on quadriceps and foot muscle fatigue in children with spastic diplegia: a randomized controlled study.

Spastic diplegia is the most common form of cerebral palsy; children with spastic diplegia are suffering from muscle fatigue and spasticity which lead to decreasing power of muscles, impaired motor control, and many functional abilities. The effect of low-level laser (LLL) has a good result as it improves muscles pain and spasticity and in decreasing lactate levels. Forty children were selected with spastic diplegia and were divided into two groups: A and B. Group A received low-level laser treatment (LLLT) with physiotherapy treatment. Group B got physiotherapy sessions. Pain intensity was assessed by the visual analog scale (VAS) of pain which is reliable from age 5, before treatment and after 1-month follow-up. Muscle fatigue and power were assessed by maximum voluntary isometric contraction (MVIC) before treatment and after 1-month follow-up. Also, we tested blood lactate level in both groups; all evaluations were done before treatment and after 1-month follow-up. We found a significant difference between the two groups in VAS and MVIC and blood lactate level test regarding low-level therapy after 1-month follow-up. There is a good effect of low-level laser in increasing muscle power, decreasing blood lactate level, and improving pain.

Effect of vitamin B1 supplementation on blood creatinine and lactate levels and clinical outcomes in patients in intensive care units: a systematic review and meta-analysis of randomized controlled trials.

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).

Effects of lactate, super-GDF9, and low oxygen tension during bi-phasic in vitro maturation on the bioenergetic profiles of mouse cumulus-oocyte complex†.

In vitro maturation (IVM) is an alternative assisted reproductive technology with reduced hormone-related side effects and treatment burden compared to conventional IVF. Capacitation (CAPA)-IVM is a bi-phasic IVM system with improved clinical outcomes compared to standard monophasic IVM. Yet, CAPA-IVM efficiency compared to conventional IVF is still suboptimal in terms of producing utilizable blastocysts. Previously, we have shown that CAPA-IVM leads to a precocious increase in cumulus cell (CC) glycolytic activity during cytoplasmic maturation. In the current study, considering the fundamental importance of CCs for oocyte maturation and cumulus-oocyte complex (COC) microenvironment, we further analyzed the bioenergetic profiles of maturing CAPA-IVM COCs. Through a multi-step approach, we (i) explored mitochondrial function of the in vivo and CAPA-IVM matured COCs through real-time metabolic analysis with Seahorse analyzer, and to improve COC metabolism (ii) supplemented the culture media with lactate and/or super-GDF9 (an engineered form of growth differentiation factor 9) and (iii) reduced culture oxygen tension. Our results indicated that the pre-IVM step is delicate and prone to culture-related disruptions. Lactate and/or super-GDF9 supplementations failed to eliminate pre-IVM-induced stress on COC glucose metabolism and mitochondrial respiration. However, when performing pre-IVM culture under 5% oxygen tension, CAPA-IVM COCs showed similar bioenergetic profiles compared to in vivo matured counterparts. This is the first study providing real-time metabolic analysis of the COCs from a bi-phasic IVM system. The currently used analytical approach provides the quantitative measures and the rational basis to further improve IVM culture requirements.

The Effects of an Acute Dose of New Zealand Blackcurrant Extract on 5-km Running Performance.

This study investigated the effects of an acute dose (900 mg) of New Zealand Blackcurrant (NZBC) extract on 5-km running performance, alongside associated physiological and metabolic responses. Sixteen trained male runners (age 26 ± 5 years, stature 173.4 ± 7.3 cm, body mass 73.7 ± 6.9 kg, maximal oxygen consumption [V˙O2max] 55.4 ± 6.1 ml·kg-1·min-1) ingested either capsules containing NZBC extract (3 × 300 mg CurraNZ, 315 mg anthocyanins) or a matched placebo (3 × 300 mg gluten-free flour) 2 hr before exercise in a double-blind, randomized, crossover design. Performance time, physiological, and metabolic responses were assessed in a 5-km time trial, preceded by 10-min exercise at the lactate threshold on a treadmill. NZBC extract did not alter the physiological or metabolic responses to exercise at the lactate threshold (oxygen uptake, respiratory exchange ratio, minute ventilation, carbohydrate oxidation, fat oxidation, heart rate, blood lactate, or rating of perceived exertion, p > .05). The 5-km time trial was completed in a faster time in the NZBC extract condition compared with placebo (NZBC: 1,308.96 ± 122.36 s, placebo: 1,346.33 ± 124.44, p = .001, d = -0.23, confidence interval range = [-0.46, 0.00 s]). No differences in physiological or metabolic responses were apparent between conditions for the 5-km time trial (p > .05). Ingesting 900 mg of NZBC extract as an acute dose improves performance in trained male runners without altering physiological or metabolic responses to exercise. Further research is needed to assess a wider range of possible mechanisms (e.g., cardiovascular function, metabolite profiles) to advance insight into improved performance following supplementation.

Royal jelly acid suppresses hepatocellular carcinoma tumorigenicity by inhibiting H3 histone lactylation at H3K9la and H3K14la sites.

BACKGROUND AND PURPOSE: Human hepatocellular carcinoma (HCC) features include enhanced glycolysis and elevated lactate concentrations. Accumulation of lactate during metabolism provides a precursor for histone lysine modification. This study was designed to determine whether royal jelly acid (RJA) acts against HCC through the lactate modification pathway. EXPERIMENTAL APPROACH: The effects of RJA on Hep3B and HCCLM3 cell invasion, migration, proliferation, and apoptosis were investigated using cell scratching, colony formation assay, flow cytometry, western blotting, and real-time qPCR, gas chromatography, and RNA sequencing to determine the pathways and molecular targets involved. Tumor xenografts were used to evaluate the anti-HCC effects of RJA in vivo. In-cell Western blotting and expression correlation analysis were applied to confirm the associations between H3 histone lactylation and the antitumor effects of RJA. KEY RESULTS: RJA has good antitumor effects in vivo and in vitro. Multi-omics analysis with metabolome and transcriptome determined that the glycolytic metabolic pathway provided the principle antitumor effect of RJA. Further mechanistic studies showed that RJA inhibited HCC development by interfering with lactate production and inhibiting H3 histone lactylation at H3K9la and H3K14la sites. CONCLUSIONS AND IMPLICATIONS: This study first demonstrated that RJA exerts antitumor effects by affecting the glycolytic pathway. RJA could regulate the lactylation of H3K9la and H3K14la sites on H3 histone using lactate as a clue in the glycolytic pathway. Therefore, the lactylation of H3 histone is vital in exerting the antitumor effect of RJA, providing new evidence for screening and exploring antitumor drug mechanisms in the later stage.