Glycolysis Process Research Articles

ASIC1a mediated nucleus pulposus cells pyroptosis and glycolytic crosstalk as a molecular basis for intervertebral disc degeneration.

One of the etiologic components of degenerative spinal illnesses is intervertebral disc degeneration (IVDD), and the accompanying lower back pain is progressively turning into a significant public health problem. Important pathologic characteristics of IVDD include inflammation and acidic microenvironment, albeit it is unclear how these factors contribute to the disease. To clarify the functions of inflammation and the acidic environment in IVDD, identify the critical connections facilitating glycolytic crosstalk and nucleus pulposus cells (NPCs) pyroptosis, and offer novel approaches to IVDD prevention and therapy. By developing keywords search strategy, literature was found and screened using databases such as PUBMED, Google Scholar, Web of Science, China National Knowledge Infrastructure, and others. Hub genes, protein interaction networks, clinical transcriptome data validation, and enrichment analysis were used to further validate relevant biological pathways. It is clear that disc degeneration is associated with apoptosis or pyroptosis, inflammation, and an acidic environment based on literature review. The process of IVDD is intimately associated with pyroptosis, inflammation, and an acidic environment. The precise mechanism may entail the regulation of key genes such NLRP3, ASIC1a, IL1β, TNF-a, and GSDMD. While the acidic environment exacerbated extracellular matrix degradation and promoted cellular senescence and inflammatory factor expression, it was found to be unfavorable for NPCs survival and proliferation. Moreover, NPCs pyroptosis in an acidic environment, the molecular mechanism behind this phenomenon may be connected to ASIC1a mediated Ca + influx. On the other hand, IVDD can be constantly promoted by the interaction between the degenerating disc's acidic and inflammatory environments through "crosstalk" between anaerobic glycolysis and positive feedback. In summary, the inflammatory process in NPCs is made worse by the buildup of glucose brought on by metabolic problems, such as anaerobic glycolytic processes, and pyroptosis caused by excessive glucose may be mitigated by inhibiting endoplasmic reticulum stress. A new therapeutic approach for IVDD will involve using ASIC1a as a regulatory target to enhance the inflammatory environment and decrease the incidence of NPCs pyroptosis. Following this, anaerobic glycolysis will be regulated, lactic acid generation will be reduced, and the degenerative vicious loop will be blocked.

The impact of apoptosis-inducing MAPK and glycolytic pathways modulated by Aloe vera and royal jelly in lung and colorectal cancer

Lung and colon cancer are among the most commonly diagnosed and fatal cancer types in the world. Due to their metastatic properties, they complicate the treatment process and pose a great threat to human health. These aggressive types of cancer are resistant to chemotherapy drugs. Therefore, it is extremely important to investigate the therapeutic effects of natural compounds. In our previous study, effective doses of Royal Jelly (RJ) (100 mg/mL) and Aloe vera (AVE) (20 µg/mL) were determined and tested separately and in combination on lung and colorectal cancer cells. Glycolytic capacities were determined using the Seahorse XFe24 Analyzer, total transcriptome profiles were sequenced using NovaSeq 6000, and BAX and BCL-2 gene levels were determined using RT-qPCR. It was seen that RJ and RJ + AVE affected glycolytic capacity and more genes in lung cancer cells. In HT29, AVE alone was seen to reduce glycolytic capacity and RJ + AVE combination was seen to reduce the expression level of genes related to cell proliferation and cycle. After RJ + AVE treatments, the apoptotic process which is triggered via MAPK pathway was found in lung cancer. Moreover, BAX levels increased and BCL-2 levels decreased both lung and colorectal cancer cells. It was observed that the combination of RJ and AVE affected the glycolysis process, cell cycle, proliferation and apoptosis on lung and colorectal cancer. In particular, the combination of RJ + AVE was found to be more effective on lung cancer.

Bibliometric analysis of glycolysis and prostate cancer research from 2004 to 2024

BackgroundProstate cancer (PCa) ranks as the second most common disease among men and the fourth most prevalent cancer worldwide. Enhanced glycolysis and excessive lactate secretion are recognized as critical factors driving the progression of various cancers. This study systematically investigated the research trends associated with glycolysis in PCa through bibliometric analysis.MethodIn this study, we conducted a systematic search of the Web of Science and PubMed databases for literature pertaining to the glycolysis of PCa that was published between January 1, 2004, and June 30, 2024. To achieve this objective, we employed CiteSpace software to generate visualizations that illustrate countries/regions, institutions, journals, and keywords. Additionally, we extracted pertinent quantitative data. Furthermore, we utilized VOSviewer software to create a collaboration network map among various journals.ResultsBetween 2004 and 2024, a total of 408 research articles on glycolysis in PCa were published, indicating a consistent upward trend in the annual publication rate. In this field, the United States not only leads in the volume of research papers but also has the highest degree of centrality. The journal "Cancer Research" is recognized as the most influential in the field, whereas "Prostate and Cancer" serves as a significant platform for disseminating research related to glycolysis in PCa. Keyword analysis has identified four primary research directions that have dominated this field over the past two decades. The role of glycolysis and its associated enzymes in PCa underpins this research. Glycolysis has also demonstrated significant clinical value in the diagnosis and prognosis of PCa. Moreover, drugs targeting glycolytic inhibitors and natural products have exhibited therapeutic potential against this disease. By modulating glycolytic mechanisms, there is potential to increase resistance in PCa. Currently, leading research in this area encompasses the application of nanotechnology to PCa glycolysis, the roles of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) in this metabolic pathway, and the interactions between glycolysis and other biological processes in PCa.ConclusionThis study employs bibliometric analysis to provide a comprehensive overview of research on glycolysis in PCa over the past two decades. It highlights the current state of knowledge in this field, identifies key research hotspots, and explores emerging frontiers, particularly nanotechnology, lncRNA, and miRNA, which are driving innovative research directions.

Comparison of behavioral responses, respiratory metabolism-related enzyme activities, and metabolomics of the juvenile Chinese mitten crab Eriocheir sinensis with different tolerance to air exposure

Air exposure is a common stressor for Chinese mitten crab (Eriocheir sinensis) during rearing and transport, and air exposure tolerance can serve as a crucial indicator for assessing the quality of juvenile E. sinensis. In this study, juvenile E. sinensis were divided into two groups based on their behavioral responses: Group S, which exhibited strong tolerance to air exposure, and Group W, which exhibited weak tolerance. Immersed crabs, not exposed to air, served as a control group (Group C). Whole body morphological characteristics and enzyme activities related to respiratory metabolism in the hemolymph and anterior gills were compared among the three groups. Non-targeted LC-MS metabolomic analysis was conducted on anterior gills. The results showed that, independent of developmental stage, crabs that were larger and had higher condition factor were more tolerant to air exposure. Additionally, compared to Group W, air exposure had a relatively small effect on glycolysis and anaerobic respiratory metabolic processes in the hemolymph and anterior gills of Group S. In response to air exposure, E. sinensis experienced increased energy demand, and switched from aerobic to anaerobic respiration to increase energy supply. Simultaneously, air exposure induced oxidative stress in the hemolymph and anterior gills. This study enhances our understanding of the response mechanism of E. sinensis to air exposure and provides a theoretical reference for the identification of high-quality juvenile E. sinensis.

SUCLG1 promotes aerobic respiration and progression in plexiform neurofibroma.

Plexiform neurofibromas (PNFs) are benign tumors that affect 20‑50% of patients with type I neurofibromatosis (NF1). PNF carries a risk of malignancy. There is no effective cure for PNF. Its onset may be associated with genetic and metabolic abnormalities, but the exact mechanisms remain unclear. Succinate‑CoA ligase GDP/ADP‑Forming Subunit α(SUCLG1), a catalytic enzyme in the tricarboxylic acid cycle, is highly expressed in PNF. The present study aimed to explore the role of SUCLG1 in function and metabolism of PNF cells. SUCLG1 expression was verified using western blotting and immunofluorescence. After inducing SUCLG1 knockdown and overexpression, functional changes in PNF cells were assessed, as well as effects of SUCLG1 on cell respiration and glucose metabolism. Quantitative PCR, WB, electron microscopy and Flow cytometry demonstrated that SUCLG1 enhanced mitochondrial quality and promoted mitochondrial fusion, thereby driving proliferation and migration of tumor cells, inhibiting apoptosis and altering the cell cycle. A Seahorse assay showed that elevated SUCLG1 expression enhanced cell aerobic respiration without affecting the glycolytic process. This suggests that SUCLG1 upregulation in PNF does not trigger the Warburg effect associated with malignant tumors. This study also demonstrated the positive regulation of cellular function by promoting the expression level of the SLC25A1 gene when SUCLG1 expression was elevated. In conclusion, SUCLG1 altered the mechanism of mitochondrial quality control to enhance cell aerobic respiration, thereby driving the pathogenesis of PNF. Thus, SUCLG1 can serve as a potential target in future therapeutic strategies.

Aerobic Training Alleviates Muscle Atrophy by Promoting the Proliferation of Skeletal Muscle Satellite Cells in Myotonic Dystrophy Type 1 by Inhibiting Glycolysis via the Upregulation of MBNL1.

Skeletal muscle atrophy in myotonic dystrophy type 1 (DM1) is caused by abnormal skeletal muscle satellite cell (SSC) proliferation due to increased glycolysis, which impairs muscle regeneration. In DM1, RNA foci sequester muscleblind-like protein 1 (MBNL1) in the nucleus, inhibiting its role in regulating SSC proliferation. Aerobic training reduces glycolysis and increases SSC proliferation and muscle fiber volume. This study aimed to investigate whether aerobic training prevents muscle atrophy in DM1 through the regulation of glycolysis via MBNL1. In this study, we used the HSALR transgenic mice (DM1 mice model) to investigate the effects of aerobic training on skeletal muscle atrophy and its molecular mechanisms. HSALR mice were subjected to 4 weeks of aerobic training. After aerobic training, hindlimb grip, and myofiber mean cross-sectional area (CSA) detected by haematoxylin and eosin (HE) staining were performed. In DM1 primary SSCs, cell proliferation was assessed using Pax7 and MyoD immunofluorescence and CCK-8 assays, RNA foci were detected by RNA fluorescence in situ hybridization, and total MBNL1 expression was measured by western blot. We also used lentivirus to knock down MBNL1 in DM1 primary SSCs and performed RNA sequencing and extracellular acidification rate (ECAR). Furthermore, glycolysis detected by ECAR and oxygen consumption rate (OCR) assays were performed in WT, Sedentary, and Training group SSCs. Glycolysis was inhibited with shikonin, a glycolysis inhibitor, and the proliferation of DM1 SSCs was subsequently evaluated. Finally, we engineered an adeno-associated virus specifically targeting MBNL1 to knock down MBNL1 in DM1 mice. Subsequently, we assessed hindlimb grip strength and CSA in vivo, as well as the glycolytic capacity and proliferative capacity of DM1 SSCs in vitro. Aerobic training increased hindlimb grip strength and the average myofiber CSA in DM1 mice. Additionally, aerobic training reduced RNA foci, upregulated MBNL1, and promoted SSC proliferation. Gene-set enrichment analysis (GSEA) indicated that glycolytic processes were enriched following the knockdown of MBNL1. Furthermore, ECAR showed glycolysis was enhanced after the knockdown of MBNL1. Aerobic training reduced elevated glycolysis in DM1 mice and primary SSCs. Treatment with shikonin promoted DM1 SSC proliferation. However, MBNL1 knockdown was shown to abolish the reduced glycolysis and increased proliferation capability of SSCs due to aerobic training. Taken together, aerobic training suppresses glycolysis in SSCs via the upregulation of MBNL1, thereby enhancing SSC proliferation and alleviating muscle atrophy.

Electrochemiluminescence Detecting and Imaging of Yeast Metabolism Indicated by Endogenetic Co-reactant.

Glycolysis, a pivotal step in yeast metabolism, plays an indispensable role as a carbohydrate utilization process crucial for cellular survival. Developing advanced technologies to elucidate this fundamental physiological process holds significant scientific implications. Electrochemiluminescence (ECL) imaging exhibits the advantage of negligible background interference and facilitates straightforward visualization, thereby conferring significant value in biomolecular observation. In this study, we present an ECL imaging method for investigating yeast metabolism by utilizing the endogenetic NADH as an efficient coreactant for ECL generation. The yeast glycolysis process drives the conversion of NAD+ to NADH, resulting in enhanced ECL response as well as the increased brightness of ECL images that can be used for quantification of yeast activity. There was a linear correlation between the reciprocal of both the gray value of ECL image and yeast concentration within the range of 6.25 × 106 - 6.25 × 108 CFU/mL. Due to the highly efficient coreactant behavior of NADH, our method demonstrated excellent selectivity with minimal interference. Furthermore, we employed this approach to investigate some toxic inhibitors on yeast metabolism, yielding reliable results. This ECL imaging method not only avoids the use of additional coreactants but also provides a sensitive and intuitive approach for monitoring yeast metabolism, demonstrating great potential in revealing various complex biological processes.

Hypoxic mesenchymal stem cell-derived exosomal circDennd2a regulates granulosa cell glycolysis by interacting with LDHA

BackgroundPremature ovarian insufficiency (POI) is an ovarian dysfunction disorder that significantly impacts female fertility. Ovarian granulosa cells (GCs) are crucial somatic components supporting oocyte development that rely on glycolysis for energy production, which is essential for follicular growth. Hypoxia-induced exosomal circRNAs regulate glycolysis, but their biological functions and molecular mechanisms in POI are largely unexplored. The present comprehensive investigation revealed a substantial reduction in ovarian glycolysis levels in POI rats. Notably, hypoxia-induced exosomes originating from mesenchymal stem cells (HM-Exs) exhibit a remarkable capacity to enhance ovarian glycolysis, mitigate GCs apoptosis, reinstate disrupted estrous cycles, modulate sex hormone levels, and curtail the presence of atretic follicles. These restorative actions collectively contribute to fostering fertility revival in POI-afflicted rats.MethodsCyclophosphamide was administered for 2 weeks to induce POI rat model, and POI rats were randomly divided into three groups and treated with PBS, NM-Exs and HM-Exs, respectively. Ovarian function and fertility were assessed at the end of the study and ovarian tissues were collected for analysis of energy metabolites. The relationship between circDennd2a and POI was explored in vitro by qRT-PCR, Western blotting, CCK-8 assay, EdU staining, TUNEL staining, extracellular acidification rate (ECAR) measurements, and ATP, lactate and pyruvate level assays.ResultsOur findings revealed depletion of circDennd2a in serum samples and GCs from individuals suffering from POI. The introduction of HM-Exs-derived circDennd2a (HM-Exs-circDennd2a) effectively counteracted GCs apoptosis by enhancing glycolytic processes and driving cellular proliferation. CircDennd2a interacted with lactate dehydrogenase A (LDHA), which served as a catalyst to increase LDHA enzymatic activity and facilitate the conversion of NADH to NAD+. This biochemical cascade worked synergistically to sustain glycolytic function within GCs.ConclusionThis study revealed that HM-Exs-circDennd2a promoted LDHA activity and enhanced GCs glycolytic capacity, both of which support its use as a potential clinical diagnostic and therapeutic target for POI.

PKC phospho-activated PFK1 is required for PBAN regulated sex pheromone biosynthesis in Helicoverpa armigera.

The enzyme 6-phosphofructokinase-1 (PFK1) acts as the primary rate-limiting enzyme in glycolysis, catalyzing the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. This glycolytic process provides essential substrates for the synthesis of sex pheromones. However, the specific function of PFK1 in sex pheromone biosynthesis remains unidentified. This study aimed to investigate the detailed mechanism by which PFK1 influences pheromone biosynthesis activating neuropeptide (PBAN)-regulated sex pheromone biosynthesis in Hecoverpa armigera. Findings revealed the presence of two PFK genes in pheromone glands (PGs). Further investigation demonstrated that RNAi-mediated knockdown of PFK1 significantly reduced sex pheromone production, mating success and the female ability to attract males, whereas PFK2 did not influence sex pheromone biosynthesis. Importantly, PFK1 was activated by PBAN in both isolated PGs and Sf9 cells. However, PBAN-induced activation of PFK1 could be attenuated by chelerythrine chloride (CC), a specific inhibitor of protein kinase C (PKC). Furthermore, the phosphorylation levels of PFK1 significantly increased in response to PBAN challenge, while CC treatment significantly mitigated this phosphorylation. PFK1 activity was found to depend on phosphorylation at the S135 and S676 sites in response to PBAN stimulation. Mutants at these sites abolished PFK1 phosphorylation and its activity. Overall, our findings unveil a critical mechanism by which the PBAN signaling recruits PKC to phosphorylate PFK1 at S135 and S676 sites, thereby activating PFK1. This activation ensures the normal progression of the glycolysis pathway, ultimately facilitating sex pheromone biosynthesis.

Metformin improves insulin resistance to enhance the glycolysis process by activating SIRT2 of granulosa cells in PCOS rats

Metformin improves insulin resistance to enhance the glycolysis process by activating SIRT2 of granulosa cells in PCOS rats

Enhancing Student Comprehension of Glucose Metabolism Visualization Through Virtual Simulation Platform: An Educational Approach.

With the rapid progression of biotechnology, the significance translational research on glycolysis in molecular pharmacology has become increasingly evident. To deepen students' understanding of glycolytic processes and facilitate their comprehension of drug action mechanisms, we have developed a visual virtual simulation platform dedicated glycolysis. The educational approach commenced with theoretical lectures on glycolysis, followed by practical laboratory sessions where students measured glycolysis-related parameters such as hexokinase, pyruvate kinase, and lactate. Students then engaged with the virtual simulation training platform to explore glycolytic stress tests and positron emission tomography/computed tomography (PET/CT) imaging, with their progress tracked through an assessment mode. The study involved 67 s-year undergraduate students majoring in biomedical sciences, all of whom had received instruction in glucose metabolism theories and completed the associated questionnaires. The results showed that the students gained a deeper understanding of glycolysis and the clinical application of PET/CT imaging in the context of glycolysis. The majority also agreed that the integration of scientific and clinical cases in teaching is beneficial and that the project sparked their interest in scientific research. These findings align with existing literature that emphasizes the importance of innovative educational tools in enhancing student engagement and understanding of the underlying theories of the curriculum. This project designed an innovative glycolytic metabolism teaching system encompassing the monitoring of traditional glycolytic indicators, glycolytic stress tests, and PET/CT imaging based on glycolysis. The visual virtual simulation platform for glycolysis can serve as an innovative educational tool in the molecular pharmacology curriculum or other courses involving glycolysis, assisting students in deeply understanding the molecular mechanisms of glycolysis and its significance in disease and drug action.

Histone lactylation mediated by Fam172a in POMC neurons regulates energy balance

Glycolysis-derived lactate was identified as substrate for histone lactylation, which has been regarded as a significant role in transcriptional regulation in many tissues. However, the role of histone lactylation in the metabolic center, the hypothalamus, is still unknown. Here, we show that hypothalamic pro-opiomelanocortin (POMC) neuron-specific deletion of family with sequence similarity 172, member A (Fam172a) can increase histone lactylation and protect mice against diet-induced obesity (DIO) and related metabolic disorders. Conversely, overexpression of Fam172a in POMC neurons led to an obesity-like phenotype. Using RNA-seq and CUT&Tag chromatin profiling analyzes, we find that knockdown of Fam172a activates the glycolytic process and increases peptidylglycine α-amidating monooxygenase (PAM), which affects the synthesis of α-MSH, via H4K12la (histone lactylation). In addition, pharmacological inhibition of lactate production clearly abrogates the anti-obesity effect of PFKO (POMC-Cre, Fam172aloxP/loxP, POMC neurons Fam172a knockout). These findings highlight the importance of Fam172a and lactate in the development of obesity and our results mainly concern male mice.

METTL3/YTDHF1 Stabilizes CSRP1 mRNA to Regulate Glycolysis and Promote Acute Myeloid Leukemia Progression.

CSRP1 (Cysteine and Glycine-Rich Protein 1) is a protein often overactivated in various cancers, promoting cell proliferation and survival, making it a key factor in cancer development. However, it is worth noting that the effect of this protein on the glycolysis process in Acute Myeloid Leukemia (AML) has not yet been studied. This study aims to investigate the role of the METTL3/YTHDF1 axis in regulating Glycolysis and its impact on AML progression by stabilizing CSRP1 mRNA. We analyzed CSRP1 expression in AML tissues and cell lines using quantitative real-time PCR (qRT-PCR) and Western blotting. Functional assays, including cell viability, colony formation, glycolysis related indicators, were performed to assess the impact of CSRP1 knockdown or overexpression on AML cells. RNA immunoprecipitation (RIP) and RNA stability assays were conducted to elucidate the mechanism of METTL3/YTHDF1-mediated regulation of CSRP1 mRNA. CSRP1 was significantly upregulated in AML tissues and cell lines. Knockdown of CSRP1 inhibited AML cell proliferation and glycolysis. Overexpression of CSRP1 promoted AML cell survival. Mechanistically, METTL3 enhanced CSRP1 mRNA stability via m6A modification, recognized and bound by YTHDF1, preventing mRNA degradation. The METTL3/YTHDF1/ CSRP1 axis plays a critical role in AML progression by regulating glycolysis. Targeting this pathway may provide a novel therapeutic strategy for AML treatment.

Valorization of the Isocyanate-Derived Fraction from Polyurethane Glycolysis by Synthesizing Polyureas and Polyamides.

The isocyanate-derived fraction resulting as the bottom phase from the split-phase glycolysis of conventional polyurethane flexible foams has been given a new life based on the formation of amine-based polymers (polyureas and polyamides). For that purpose, the bottom phase was first hydrolyzed, producing toluenediamine and diethylene glycol, and further subjected to controlled vacuum distillation in order to recover both products separately. The hydrolysis reaction and the separation process conditions were determined and optimized, obtaining products with a purity comparable to that of commercial ones. Then, the recovered diethylene glycol was used in a new glycolysis process, obtaining a split-phase product with properties similar to those obtained using commercial diethylene glycol. Finally, the recovered toluenediamine was used in the synthesis of polyureas and polyamides. Both syntheses were modified with respect to the state of the art, replacing benzene with limonene in the synthesis of polyamides, which implies environmental improvements.

Low-temperature chemical upcycling of poly(ethylene terephthalate) waste to recyclable polyurethane thermosets using biomass-derived materials

Addressing the global challenge of plastic waste, particularly poly(ethylene terephthalate) (PET), requires innovative chemical upcycling strategies. In this study, we report a sustainable approach for transforming PET waste into chemically recyclable polyurethane (PU) thermosets. Using a low-temperature glycolysis process with potassium carbonate, 1,4-butanediol and chlorobenzene, bis(4-hydroxybutyl) terephthalate (BHBT) was obtained with a conversion rate exceeding 99 % and an isolated yield of 55.4 %. The BHBT was subsequently used to synthesize PU thermosets with bio-based pentamethylene diisocyanate trimer and 2-methyltetrahydrofuran as a solvent. The resulting thermosets demonstrated excellent mechanical properties, including a tensile strength of 21.8 MPa, elongation at break of 151 %, and a Young’s modulus of 279 MPa. The PU thermosets were chemically recyclable, enabling a closed-loop process where BHBT was recovered with 84.5 % yield via glycolysis. Furthermore, the BHBT-based PU thermosets were successfully applied to carbon fiber-reinforced polymer composites, maintaining their mechanical integrity after recycling. This work highlights a promising route for the upcycling of PET waste, contributing to the development of sustainable polymer materials and supporting the principles of a circular economy.

Effect of cold atmospheric plasma (CAP) on the energy metabolism in HeLa cells through miRNA regulation

Abstract Cold atmospheric plasma (CAP) is an emerging tool for tumor treatment because it can inhibit cancer cell proliferation primarily through oxidative stress due to CAP-induced reactive oxygen species (ROS). Among various ROS targeting molecules in cancer cells, microRNAs (miRNAs) are one kind of important targets that can be stimulated by ROS, and many studies have shown that miRNAs are involved in the metabolism regulation of cancer cells. In this study, we applied helium-CAP (He-CAP) to HeLa cells, and observed that the ROS induced by He-CAP could modulate the miRNAs related to energy metabolism, leading to the changes of proliferation, glycolysis, tricarboxylic acid (TCA) cycling and oxidative phosphorylation (OXPHOS) in the HeLa cells, and affected the related hypoxia-inducible factor 1, p53, phosphoinositide 3-kinase signaling pathways. In addition, the analysis of miRNAs in the metabolic network revealed that the expressions of the miRNAs responsible for the promotion of energy metabolism increased, and correspondingly, the involved mRNA and protein expression decreased. As such, this study has not only demonstrated that CAP treatment could significantly change the miRNAs expression of cancer cells, but also provided a more in-depth understanding of the CAP effects on glycolysis, TCA cycling and OXPHOS processes in the cells through the comprehensive analysis of the miRNAs regulation.

Role of the PGAM5-CypD mitochondrial pathway in methylglyoxal-induced bone loss in diabetic osteoporosis

Diabetic osteoporosis (DOP) is a skeletal complication with a high rate of disability. It results in a great burden to the patient's family and society. Methylglyoxal (MG) is a toxic by-product of the glycolytic process that occurs during diabetic conditions. It causes osteoblastic injury and con-tributes to the initiation and development of DOP. Disruption of mitochondrial homeostasis has been implicated as a cause of dysregulated osteo-blastogenesis, an essential step in bone formation. It is unclear whether mitochondrial dysfunction is involved in MG-induced osteoblast dysfunction. In this study, we showed that mitochondrial dysfunction contributes to MG-induced MC3T3-E1 cell apoptosis and impaired differentiation. A significant reduction of mitochondrial membrane potential (MMP) and ATP production occurred in MG-induced osteoblasts as well as increasing mitochondrial reactive oxygen species (mtROS) and intracellular Ca2+. Classical antioxidant N-Acetylcysteine (NAC) significantly attenuated mitochondrial dysfunction as well as osteoblast apoptosis and osteogenic differentiation damage induced by MG. More importantly, we found that activating phosphoglycerate mutase family member 5 (PGAM5) and cyclophilin D (CypD), which contributes to mitochondrial homeostasis, is involved in MG-induced osteoblast injury. Both PGAM5 and CypD knockdown effectively reversed osteoblast viability and function, whereas PGAM5 or CypD overexpression aggravated osteoblast injury caused by MG. Moreover, the result of co-transfection revealed that PGAM5 is an upstream signaling molecule of CypD. By constructing type I diabetes mouse models, we further found that the expression of PGAM5 and CypD were both increased in the femur along with a reduction of ATP and increased TUNEL-positive cells. These results, for the first time, suggest that MG-induced mitochondrial dysfunction induces osteoblast injury through the PGAM5-CypD pathway. This study provides insight into the prevention and treatment of DOP. Lay summaryThis study highlights the role of mitochondria in regulating osteoblast viability and function under conditions of diabetic osteoporosis (DOP). We found that the PGAM5-CypD mitochondrial pathway is activated following glycolytic by-product methylglyoxal (MG) treatment, which contributes to mitochondrial dysfunction and osteogenic dysfunction. This mechanism implicates mitochondria as a potential therapeutic target for osteoporosis.

Nampt/SIRT2/LDHA pathway-mediated lactate production regulates follicular dysplasia in polycystic ovary syndrome

Decreased nicotinamide adenine dinucleotide (NAD+) content has been shown to contribute to metabolic dysfunction during aging, including polycystic ovary syndrome (PCOS). However, the effect of NAD+ on ovulatory dysfunction in PCOS by regulating glycolysis has not been reported. Based on the observations of granulosa cells (GCs) transcriptome data from the Gene Expression Omnibus (GEO) database, the signal pathways including glycolysis and nicotinate-nicotinamide metabolism were significantly enriched, and most genes of the above pathway like LDHA and SIRT2 were down-regulated in PCOS patients. Therefore, the PCOS rat model was established by combining letrozole with a high-fat diet (HFD), we demonstrate that in vivo supplementation of nicotinamide mononucleotide (NMN) significantly improves the ovulatory dysfunction by facilitating the follicular development, promoting luteal formation, as well the fertility in PCOS rats. Furthermore, target energy metabolomics and transcriptome results showed that NMN supplementation ameliorates the lactate production by activating glycolytic process in the ovary. In vitro, when NAD+ synthesis and SIRT2 expression were inhibited, lactate content in KGN cells was decreased and LDHA expression was significantly inhibited. We confirmed that FK866 can enhance the acetylation of LDHA on 293T cells by Co-immunoprecipitation (Co-IP) assay. We also observed that inhibition of NAD+ synthesis can reduce the activity and increase the apoptosis of KGN cells. Overall, these benefits of NMN were elucidated and the Nampt/SIRT2/LDHA pathway mediated lactate production in granulosa cells played an important role in the improvement of follicular development disorders in PCOS. This study will provide experimental evidence for the clinical application of NMN in the treatment of PCOS in the future.

Targeting PGK1: A New Frontier in Breast Cancer Therapy Under Hypoxic Conditions.

Breast cancer represents one of the most prevalent malignant neoplasms affecting women, and its pathogenesis has garnered significant scholarly interest. Research indicates that the progression of breast cancer is intricately regulated by glucose metabolism. Under hypoxic conditions within the tumor microenvironment, breast cancer cells generate ATP and essential biosynthetic precursors for growth via the glycolytic pathway. Notably, phosphoglycerate kinase 1 (PGK1) is intimately associated with the regulation of hypoxia-inducible factors in breast cancer and plays a crucial role in modulating glycolytic processes. Further investigation into the role of PGK1 in breast cancer pathogenesis is anticipated to identify novel therapeutic targets and strategies. This review consolidates current research on the regulation of glucose metabolism and the function of PGK1 in breast cancer within hypoxic conditions. It aims to offer a significant theoretical foundation for elucidating the mechanisms underlying breast cancer progression and metastasis, thereby facilitating the development of innovative treatment approaches.

A new mechanism for the kinetics of simultaneous depolymerization reaction inside and outside poly (ethylene terephthalate) particles

The depolymerization and recycling of PET is important for waste reduction, resource efficiency and production cost reduction. However, among the industrialized methods for recycling waste PET, the main challenge applicable to the PET glycolysis strategy is the low efficiency and low purity in recovering polyester, which is mainly due to the imperfections in the reaction kinetics model. In this study, we developed a kinetic model for PET glycolysis at different reaction temperatures by investigating the glycolysis process of PET chips at different reaction temperatures to discover new PET glycol depolymerization mechanisms. It was found that the zinc acetate-catalyzed PET glycolysis followed a first-order reversible kinetic model at higher temperature (206–210 °C). However, at lower temperatures (180 °C–205 °C), the experimental curve of the kinetic model is similar to the theoretical curve of the nucleation-controlled model, and in this temperature range, EG depolymerized PET in a manner that internal and external depolymerization proceeded simultaneously. This finding is expected to guide the establishment of a more efficient PET depolymerization process, which is an important guide for recycling waste PET.