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The role of lactate dehydrogenase A (LDHA) expression in differentiated thyroid cancer (DTC), especially in radioiodine-refractory DTC, remains unclear. The aim of this study was to analyse the relationships and the prognostic value of LDHA, glycolysis, and radioactive iodine (RAI) avidity in DTC. DTC patients who underwent 18F-FDG PET/CT and subsequent total thyroidectomy or metastasectomy were enroled. The expression levels of LDHA, glucose transporters (Glut) and Ki67 proteins in tumour tissue were measured using immunohistochemistry. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of 18F-FDG PET/CT were measured. A radioiodine whole body scan was used to determine lesion radioiodine avidity. 69 patients with DTC were enroled in this study, including 37 women (53.6%) and 32 men (46.4%), with a median age of 52 years (11 to 77 years). Regarding the pathological category, papillary thyroid cancer was documented in 50 patients (72.5%), while follicular and poorly differentiated thyroid cancer were found in 12 patients (17.4%) and seven patients (10.1%), respectively. Distant metastases were observed in 27 (39.1%) patients; 34 (49.3%) were classified as stage I, 16 (23.2%) as stage II, and 3 (4.3%) and 16 (23.2%) patients in stages III and IV, respectively. LDHA expression levels were correlated with Glut3 expression levels (r = 0.395, P = 0.003) and SUVmax (r = 0.408, P = 0.002). The median LDHA expression and lesion SUVmax of the RAI avidity group were lower than those of the non-RAI avidity group (200 vs. 285, P = 0.036; 3.06 vs. 8.38, P = 0.038, respectively). Elevated SUVmax (P = 0.004), MTV (P = 0.014), TLG (P = 0.001) and LDHA expression (P = 0.048) led to shorter time to progression (TTP); Cox regression analysis revealed that TLG (HR: 4.773, P = 0.047) was an independent prognostic factor of TTP. Elevated LDHA is correlated with increased glucose metabolism, decreased radioiodine avidity, and accelerated disease progression. Moreover, 18F-FDG PET/CT acting as "in vivo pathology" is an excellent predictor of DTC prognosis. [ABSTRACT FROM AUTHOR]

Identification of cues originating from skeletal muscle that govern bone formation is essential for understanding the crosstalk between muscle and bone and for developing therapies for degenerative bone diseases. Here, we identified that skeletal muscle secreted multiple extracellular vesicles (Mu-EVs). These Mu-EVs traveled through the bloodstream to reach bone, where they were phagocytized by bone marrow mesenchymal stem/stromal cells (BMSCs). Mu-EVs promoted osteogenic differentiation of BMSCs and protected against disuse osteoporosis in mice. The quantity and bioactivity of Mu-EVs were tightly correlated with the function of skeletal muscle. Proteomic analysis revealed numerous proteins in Mu-EVs, some potentially regulating bone metabolism, especially glycolysis. Subsequent investigations indicated that Mu-EVs promoted the glycolysis of BMSCs by delivering lactate dehydrogenase A into these cells. In summary, these findings reveal that Mu-EVs play a vital role in BMSC metabolism regulation and bone formation stimulation, offering a promising approach for treating disuse osteoporosis. [Display omitted] • Skeletal muscle secretes Mu-EVs, which can travel via blood vessels to bone • Supplementation with Mu-EVs alleviates disuse osteoporosis after muscle atrophy • Mu-EVs promote osteogenic differentiation of BMSCs by enhancing glycolysis • Glycolic profiles transported by Mu-EVs function as non-canonical myokines In their study, Ma et al. demonstrate that skeletal muscle secretes abundant extracellular vesicles (Mu-EVs). These Mu-EVs promote glycolysis in BMSCs by delivering glycolic profiles to enhance bone formation. The quantity and bioactivity of Mu-EVs are found to correlate with skeletal muscle function. Importantly, supplementation with Mu-EVs is shown to alleviate disuse osteoporosis following muscle atrophy, suggesting a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

We have previously reported the toxicity of microcystin-LR (MC-LR) to the male reproductive system, which results in functional changes in mouse testes. In this study, mice were orally exposed to MC-LR at 1, 7.5, 15, or 30 μg/L daily for 180 days. We found an increase in germ cell apoptosis in the seminiferous tubules and low-quality sperm in the epididymis. A decrease in lactate dehydrogenase A (Ldha) expression in testes through high-throughput sequencing was observed. We validated that MC-LR disrupted lactate production in Sertoli cells by suppressing the expression of Ldha. Further studies identified that methyltransferase 3 (Mettl3) catalysed N6-methyladenosine (m6A) methylation of Ldha mRNA. Mettl3 was downregulated in Sertoli cells following exposure to MC-LR, decreasing m6A levels of Ldha. The stability of Ldha mRNA decreased when m6A levels of Ldha were inhibited. In conclusion, these results showed that MC-LR inhibits the expression of Ldha in an m6A-dependent manner, which might result in the apoptosis of spermatogenic cells and a decline in sperm quality. Our work provides a new perspective to understanding MC-LR-induced male infertility. [Display omitted] • The MC-LR-mediated disruption of energy metabolism plays a vital role in germ cell apoptosis. • MC-LR disrupts lactate production in Sertoli cells by suppressing the expression of Ldha. • MC-LR inhibits m6A modification of Ldha mRNA by suppressing Mettl3 expression, • Igf2bp3 enhances the stability of Ldha mRNA in an m6A-dependent manner. [ABSTRACT FROM AUTHOR]

Sufficient evidence has linked many different types of cancers and T2D through shared risk factors; however, the underlying mechanisms are not fully understood. α-Hydroxybutyrate (α-HB), a byproduct metabolite increased in diabetes and cancer, including colorectal cancer (CRC), triggers lactate dehydrogenase A (LDHA) nuclear translocation. Nuclear LDHA markedly extends NF-κB nuclear retention by interacting with phosphorylated p65, leading to an increase in TNF-α production, impaired insulin secretion and the exacerbation of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC and high-fat diet (HFD)-induced type 2 diabetes. Furthermore, metformin interrupted this process by inhibiting the transcription of FOXM1 and c-MYC, the resultant downregulation of LDHA expression and α-HB-induced LDHA nuclear translocation. Thus, the results reveal the elevated α-HB level could be a novel shared risk factor of linking CRC, diabetes and the use of metformin treatment, as well as highlight the importance of preventing NF-κB activation for protecting against cancer and diabetes. • α-HB accelerates the development of colorectal cancer and type 2 diabetes. • α-HB prolongs the nuclear retention of NF-κB via LDHA. • Metformin inhibits nuclear LDHA-induced NF-κB nuclear retention. [ABSTRACT FROM AUTHOR]

Spatholobus suberectus (SS) is an excellent functional and medicinal food source of dietary procyanidins, which have numerous health benefits. Ten procyanidin fractions with different polymerization degrees were prepared from SS. For the first time, trimers to 11-mers were detected in SS extracts, and their compositions were elucidated through thiolysis, ESI-MS and MALDI-TOF-MS analyses. The results determined that the mean polymerization degree (mDP) of the crude SS procyanidins was 5.2 and that the mass distribution of the monomer and the oligomers (mDP of 1.0–5.7) was 70.4%, whereas that of the polymers (mDP of 6.2–11.8) was 25.6%. Catechin and epicatechin were the main monomeric units with minor quantities of epigallocatechin and gallocatechin. The observed interflavan linkages were both A-type (minor type) and B-type (major type). The fractions enriched in the monomer and oligomers showed the highest activities, including antioxidant activity and inhibitory activities on both the proliferation of MCF-7 breast cancer cells and lactate dehydrogenase A (LDH-A). These results suggested that the monomer- and oligomer-enriched procyanidin fractions from SS could undergo further development to become a beneficial source of antioxidants, LDH-A inhibitors, and potential inhibitors of breast cancer. [ABSTRACT FROM AUTHOR]

The article focuses on the scientific content of lactate dehydrogenase A4 (LDH-A4). This was purified for yak skeletal muscle. Michaelis constant (Km) analysis showed that yak LDH-A4 for pyruvate was significantly higher than that of cattle, cDNA cloning of LDH-A revealed two amino acid substitutions between yak and cattle.

Background Emerging studies suggest that enhanced glycolysis accompanies inflammatory responses. Virtually nothing is known about the relevance of glycolysis in patients with allergic asthma. Objectives We sought to determine whether glycolysis is altered in patients with allergic asthma and to address its importance in the pathogenesis of allergic asthma. Methods We examined alterations in glycolysis in sputum samples from asthmatic patients and primary human nasal cells and used murine models of allergic asthma, as well as primary mouse tracheal epithelial cells, to evaluate the relevance of glycolysis. Results In a murine model of allergic asthma, glycolysis was induced in the lungs in an IL-1–dependent manner. Furthermore, administration of IL-1β into the airways stimulated lactate production and expression of glycolytic enzymes, with notable expression of lactate dehydrogenase A occurring in the airway epithelium. Indeed, exposure of mouse tracheal epithelial cells to IL-1β or IL-1α resulted in increased glycolytic flux, glucose use, expression of glycolysis genes, and lactate production. Enhanced glycolysis was required for IL-1β– or IL-1α–mediated proinflammatory responses and the stimulatory effects of IL-1β on house dust mite (HDM)–induced release of thymic stromal lymphopoietin and GM-CSF from tracheal epithelial cells. Inhibitor of κB kinase ε was downstream of HDM or IL-1β and required for HDM-induced glycolysis and pathogenesis of allergic airways disease. Small interfering RNA ablation of lactate dehydrogenase A attenuated HDM-induced increases in lactate levels and attenuated HDM-induced disease. Primary nasal epithelial cells from asthmatic patients intrinsically produced more lactate compared with cells from healthy subjects. Lactate content was significantly higher in sputum supernatants from asthmatic patients, notably those with greater than 61% neutrophils. A positive correlation was observed between sputum lactate and IL-1β levels, and lactate content correlated negatively with lung function. Conclusions Collectively, these findings demonstrate that IL-1β/inhibitory κB kinase ε signaling plays an important role in HDM-induced glycolysis and pathogenesis of allergic airways disease. [ABSTRACT FROM AUTHOR]