Hexokinase Activity Research Articles

Investigating the Phytochemistry and Underlying Glycemic Control Mechanisms of Litchi chinensis Sonn. (Litchi) Peel Ethyl Acetate Extract in a Fructose/Streptozotocin Diabetic Model of Rats

The glycemic control potential and flavonoid profile of litchi have been documented for its hydroalcoholic extracts, while there is scarce information regarding its ethyl acetate extract. This study investigated the flavonoid profile, as well as the ameliorative potential and possible underlying mechanisms of litchi peel ethyl acetate extract on type 2 diabetes-related pathologies in a fructose/streptozotocin (STZ) model of diabetic rats. Sprague Dawley rats were induced with diabetes by administering 10% fructose for 2 weeks and a single i.p. injection of low-dose (40 mg/kg bw) STZ. Thereafter, the animals were orally administered with a low-dose (150 mg/kg bw) and high-dose (300 mg/kg bw) of the peel extract (LDPE and HDPE, respectively) and metformin (200 mg/kg bw). Compared to untreated diabetic rats (AUC = 1004 mg.h/dL), the HDPE significantly (p < 0.05) improved glucose tolerance (AUC = 847 mg.h/dL), which was statistically comparable (p ˃ 0.05) to the effect of metformin (AUC = 903 mg.h/dL). Serum insulin and pancreatic histology data showed that the STZ-induced pancreatic damage and insulin depletion was improved by the HDPE, which could be linked to the observed ameliorative effect of the extract on pancreatic lipid peroxidation and SOD and catalase activity. The extract further improved liver and muscle glycogen storage, as well as muscle hexokinase activity and Akt phosphorylation, suggesting that the extract exerts glycemic control by enhancing glycogen storage and modulating insulin-mediated signaling of glucose uptake and utilization. LC-MS data and documented reports suggest that flavonoids, such as epicatechin, cinnamtannin B2, procyanidin B5, and proanthocyanidin A2, are the possible influencing compounds. The ethyl acetate extract of litchi peel could be a source of bioactive flavonoids that can potentiate glycemic control in diabetes and mitigate oxidative stress-related pathologies.

Turmeric as a therapeutic agent against arsenic-induced metabolic dysregulation in rat models

Ethnopharmacological relevanceHealth hazards stemming from metalloid consumption, such as arsenic, pose a global concern. This study aimed to assess the protective effects of turmeric against arsenic-induced alterations in lipid profiles and energy metabolism in rats. MethodsThirty male rats were divided into three groups over a 90–180-day exposure period: Group 1 (Control) received standard rat chow; Group 2 received an arsenic diet; and Group 3 received arsenic plus turmeric supplemented diet. Blood and liver tissue samples were collected for lipid profiles, glucose levels, energy metabolism parameters, and PPAR-α mRNA expression using qRT-PCR. Statistical analysis was performed (p<0.05). ResultsResults indicated significant (p<0.05) increases in lipid profiles among arsenic-exposed rats after 180 days, elevating the risk of coronary artery diseases. Both arsenic and turmeric-exposed groups showed heightened total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) levels at 90 and 180 days, with nuanced differences suggesting dyslipidemia and atherosclerosis. Blood glucose observations revealed hypoglycemia initially in arsenic-exposed rats, progressing to hyperglycemia by 180 days. Arsenic significantly (p<0.05) inhibited pyruvate kinase, hexokinase, and isocitrate dehydrogenase activities in the liver after 180 days, while turmeric exposure showed no significant (p<0.05) changes. Additionally, both arsenic and turmeric groups exhibited downregulation of PPAR-α expression at 180 days. In-silico analysis identified curcumin as a promising component for anti-atherosclerosis and arsenic-related conditions due to its strong binding affinities and multiple hydrogen bond formations. ConclusionIn conclusion, long-term turmeric consumption may mitigate arsenic-induced oxidative damage associated with early hyperglycemia, diabetes mellitus, cardiovascular diseases, and atherosclerosis. These findings underscore turmeric’s potential therapeutic role against arsenic toxicity, suggesting avenues for future research and public health interventions.

Taurine reduces glycolysis of pig skeletal muscle by inhibiting HIF-1α signaling.

The aim of this study was to investigate the effect of taurine on skeletal muscle glycolysis in pigs. The results showed that dietary supplementation of taurine significantly reduced the activities of hexokinase (HK), phosphofructose kinase (PFK), and pyruvate kinase (PK) in finishing pigs. Meanwhile, taurine reduced the protein and mRNA expression levels of hypoxia inducible factor 1α (HIF-1α) and the mRNA expression of glycolytic enzyme related genes (such as HK type II, HK Ⅱ; pyruvate kinase M2, PKM2; lactate dehydrogenase A, LDHA). In addition, taurine reduced the expression of HIF-1α, lactate content, and the expression of glycolysis related genes in porcine myotubes. These results suggest that taurine may regulate glycolysis in skeletal muscle of finishing pigs through the HIF-1α signaling pathway. To further investigate the mechanism by which taurine affects skeletal glycolysis, HIF-1α activator dimethyloxalyl glycine (DMOG) was used to treat porcine myotubes, our results showed that DMOG significantly increased the protein and mRNA expression levels of HIF-1α, lactate content, and glycolytic enzyme (HK, PFK, PK, and LDH) activity, but taurine treatment significantly inhibited this effect. Taken together, these results of in vivo and in vitro experiments revealed that taurine reduces skeletal muscle glycolysis by inhibiting HIF-1α signaling.

Improving sugar and respiratory metabolism in pear wounds by postharvest dipping with chitosan and chitooligosaccharide

Chitosan (CTS) and its degradation product, chitooligosaccharide (COS), promote fruit healing by activating phenylpropanoid metabolism. This study investigates their effects on sucrose metabolism in pear wounds. CTS and COS were found to activate neutral invertase, acid invertase, sucrose synthase, and sucrose phosphate synthase, increasing sucrose, glucose, and fructose levels in fruit wounds. They also enhanced sorbitol dehydrogenase activity and promoted sorbitol accumulation. In addition, CTS and COS improved the activities of hexokinase, phosphofructokinase, and pyruvate kinase, increasing phosphoenolpyruvate and ATP production. They activated glucose-6-phosphate dehydrogenase and increased erythrose-4-phosphate, NADPH, and shikimic acid levels. In conclusion, CTS and COS support the formation of the healing closing layer by supplying carbon skeletons, energy, and reducing power through the activation of sugar and respiratory metabolism during the healing process. Compared to CTS, COS was superior in activating the above metabolisms, which is expected to be widely used as a chitin product in postharvest fruit and vegetable preservation and provide new insights into preserving pear freshness.

Potent Biological Activity of Fluorinated Derivatives of 2-Deoxy-d-Glucose in a Glioblastoma Model.

One defining feature of various aggressive cancers, including glioblastoma multiforme (GBM), is glycolysis upregulation, making its inhibition a promising therapeutic approach. One promising compound is 2-deoxy-d-glucose (2-DG), a d-glucose analog with high clinical potential due to its ability to inhibit glycolysis. Upon uptake, 2-DG is phosphorylated by hexokinase to 2-DG-6-phosphate, which inhibits hexokinase and downstream glycolytic enzymes. Unfortunately, therapeutic use of 2-DG is limited by poor pharmacokinetics, suppressing its efficacy. To address these issues, we synthesized novel halogenated 2-DG analogs (2-FG, 2,2-diFG, 2-CG, and 2-BG) and evaluated their glycolytic inhibition in GBM cells. Our in vitro and computational studies suggest that these derivatives modulate hexokinase activity differently. Fluorinated compounds show the most potent cytotoxic effects, indicated by the lowest IC50 values. These effects were more pronounced in hypoxic conditions. 19F NMR experiments and molecular docking confirmed that fluorinated derivatives bind hexokinase comparably to glucose. Enzymatic assays demonstrated that all halogenated derivatives are more effective HKII inhibitors than 2-DG, particularly through their 6-phosphates. By modifying the C-2 position with halogens, these compounds may overcome the poor pharmacokinetics of 2-DG. The modifications seem to enhance the stability and uptake of the compounds, making them effective at lower doses and over prolonged periods. This research has the potential to reshape the treatment landscape for GBM and possibly other cancers by offering a more targeted, effective, and metabolically focused therapeutic approach. The application of halogenated 2-DG analogs represents a promising advancement in cancer metabolism-targeted therapies, with the potential to overcome current treatment limitations.

Targeting insulin resistance: myricetin and isorhamnetin from Hardwickia binata, and luteolin from Hedysarum alpinum enhance glucose uptake and AMPK signaling in HepG2 cells

This study examined five plants (Xylopia aethiopica, Agave sisalana, Hardwickia binata, Hedysarum alpinum, and Toxicodendron vernicifluum) for their potential to address insulin resistance in type 2 diabetes. In-vitro assays showed that H. binata leaves and H. alpinum flowers inhibited α-glucosidase and α-amylase while enhancing glucose uptake in normal and insulin-resistant HepG2 cells. Phytochemical screening and SPE purification identified the key constituents responsible for the effects. The chromatographic and spectral analysis confirmed flavonoids in H. binata (myricetin, isorhamnetin, quercetin, kaempferol, and catechin) and H. alpinum (luteolin, quercetin, kaempferol, and apigenin). Myricetin, isorhamnetin, and luteolin significantly increased glucose uptake, enhanced hexokinase and pyruvate kinase activities, and promoted IRec and IRS-1 phosphorylation, modulating insulin signalling. They activated AMPK and Akt, with molecular docking confirming strong AMPK binding. These findings suggest that H. binata, H. alpinum, and their flavonoids are promising candidates for managing insulin resistance and type 2 diabetes, warranting further research.

Polysaccharides from Tremella Fuciformis Enhance Glucose and Lipid Metabolism in HepG2 Cells Through Activating the AMPK Signaling Pathway.

Polysaccharides have gained substantial attention for their diverse biological activities. The present study was conucted to elucidate the effects and molecular mechanisms of Tremella fuciformis-derived polysaccharides (PTP-3a) on glucose and lipid metabolism in palmitic acid (PA) - treated HepG2 cells. Multiple parameters were assessed following PTP-3a treatment, including lipid accumulation, glycogen content, glucose consumption, and enzyme activities, including pyruvate kinase (PK) and hexokinase (HK). Additionally, the expression levels of genes associated with glucose and lipid metabolism was evaluated using western blot analysis. PTP-3a effectively inhibited lipid accumulation, promoted the glucose consumption, increased the amount of cellular glycogen, and enhanced PK and HK activities in PA-treated cells. Furthermore, PTP-3a induced a significant increase in the p-AMPK/AMPK ratio and the expression level of PPARa, while decreasing the expression levels of SREBP, FAS, ACC, and SOCS3. In conclusion, these findings suggested that PTP-3a exerted beneficial effects on glucose and lipid metabolism by activating the AMPK signaling pathway, resulting in the inhibition of lipogenesis, promotion of fatty acid oxidation, and enhancement of cellular glycogen synthesis and glycolysis. These findings hold clinical relevance and provide a foundation for potential treatments for non-alcoholic fatty liver disease (NAFLD) and and related metabolic disorders.

Efficient nata de coco production of Komagataeibacter nataicola driven by microbiota-fermented coconut water: Biological and structural characteristics

Nata de coco is a traditional fermented food, chemically known as bacterial cellulose (BC), widely used in the food industry, personal care, and biomaterial areas. In the nata de coco industry, microbiota-fermented coconut water (FCW) has been regarded as a highly efficient medium for improving BC synthesis by Komagataeibacter spp. However, its effects on the biological properties of the strains of Komagataeibacter and structural characteristics of BC remain unknown, resulting in unstable production and BC quality. This study aimed to explore the biological properties of K. nataicola, the characteristics of BC structure and reasons for the efficiency under the effect of FCW. The results showed that FCW could increase the BC yield of K. nataicola by 2.03–4.75 times, the uridine diphosphate glucose pyrophosphorylase activity by 10–45.3 times, and the hexokinase, phosphofructokinase, or pyruvate kinase activities by 2 times. The extracellular metabolite profile of K. nataicola showed that its glycolysis/gluconeogenesis pathway was significantly stimulated and the utilization of erythritol obviously increased. These phenomena might be attributed to the use of ethanol, lactate, xylitoland mannitol in FCW by K. nataicola. In addition, the structural characteristics of BC produced in FCW included higher number of hydrogen bonds, thinner fibrils, a looser three-dimensional network, improved porosity and greater mechanical strength. This study offered novel insights into the BC synthesis of K. nataicola and the BC structural characteristics cultivated in FCW, providing valuable references for the efficient production and potential applications of both nata de coco and BC.

Toxicogenomic assessment of hydroxylated metabolites of PBDEs on cetaceans: An in vitro study

Despite their ban, polybrominated diphenyl ethers (PBDEs) are frequently detected in various environmental compartments including marine and coastal ecosystems due to their persistence, bio-accumulative, high production volumes, and widespread use. One of the major concerns from PBDEs is the transformation products, such as hydroxylated polybrominated diphenyl ethers (OH-BDEs), which are more bioactive than the parent compounds. For example, 6-hydroxy-2,2′,4’,4-tetrabromodiphenyl ether (6-OH-BDE-47) is a typical metabolite of PBDEs and cause endocrine system disruption, developmental toxicity, and neurotoxicity in different species. Despite being widely detected in marine environments, investigations on the toxicological mechanisms of 6-OH-BDE-47 in cetaceans remain scarce. High concentrations of PBDEs accumulate in cetaceans due to the long lifespan and large fat reserve. The accumulated PBDEs have become the major source of OH-BDEs in cetaceans. We exposed immortalized fibroblast cell lines from the skin of pygmy killer whales (PKW-LWHT) and Indo-Pacific finless porpoises (FP-LWHT) to 6-OH-BDE-47 and analyzed changes in cellular function using transcriptomic data, along with enzymatic activity. Exposure to the body-relevant body burdens of 6-OH-BDE-47 (250 and 500 ng mL−1) significantly decreased cell viability. Differentially expressed genes in FP-LWHT exposed to 6-OH-BDE-47 were primarily enriched in the pathways associated with steroid metabolism. Total cholesterol was decreased by 6-OH-BDE-47, whereas low-density lipoprotein cholesterol and triglyceride levels were significantly increased in FP-LWHT cells. In contrast, glycolysis was the main enriched function of differentially expressed genes in PKW-LWHT cells exposed to 6-OH-BDE-47, and the enzyme activity of phosphofructokinase and hexokinase was upregulated. Thus, even though the cell viability of both cell lines from these two species was significantly suppressed by 6-OH-BDE-47, the cellular response or affected cellular function was different between the Pygmy killer whale and the Indo-Pacific Finless Porpoise, suggesting a diverse response towards OH-BDEs exposure.

Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model.

Diisononyl phthalate (DiNP) has been associated with the development of allergies, asthma, and allergic airway inflammation. Through a complex interplay of signals and feedback mechanisms, the lungs communicate with the heart to ensure maintenance of homeostasis and supporting the body's metabolic demands. In the current study, we assessed the crosstalk between DiNP-induced asthma and cardiac cellular respiration, oxidative stress, apoptotic potential, and induction of oncogenic factors. Ten male BALB/c mice with a weight range of 20-30g were divided into two groups, each comprising five mice. Group 1 (control), was administered saline orally for a duration of 30days. In contrast, group 2 (DiNP group), received 50mg/kg of DiNP to induce asthma. After the final administration and asthma induction, the mice were euthanized, and their hearts were excised, processed, and subjected to biochemical analyses. The DiNP group had downregulated (P < 0.05) activities of the enzymes of glycolysis, tricyclic acid cycle, and electron transport chain except the hexokinase and succinate dehydrogenase activity which were upregulate relative to control. Also, oxidative distress markers (GSH, CAT, and MDA and SOD) were also perturbed. Biomarkers of inflammation (MPO and NO) were considerably higher (P < 0.05) in the heart of DiNP-induced asthma mice as compared with the control group. Furthermore, DiNP-induced asthma group has an increased cardiac caspase-3, Bax, c-Myc and K-ras, and p53 while the Bcl2 decreased when compared with control. Overall, the findings indicate that DiNP-induced asthma impairs cardiac functions by induction of key cardiac oncogenes, downregulation of cardiac energy, transduction of enzymes, and promotion of oxidative stress and cellular death.

The antagonistic activity of Streptomyces spiroverticillatus (No. HS1) against of poplar canker pathogen Botryosphaeria dothidea

BackgroundPoplar canker caused by Botryosphaeria dothidea is one of the most severe plant disease of poplars worldwide. In our study, we aimed to investigate the modes of antagonism by fermentation broth supernatant (FBS) of Streptomyces spiroverticillatus HS1 against B. dothidea.ResultsIn vitro, the strain and FBS of S. spiroverticillatus HS1 significantly inhibited mycelial growth and biomass accumulation, and also disrupted the mycelium morphology of B. dothidea. On the 3rd day after treatment, the inhibition rates of colony growth and dry weight were 80.72% and 52.53%, respectively. In addition, FBS treatment damaged the plasma membrane of B. dothidea based on increased electrical conductivity in the culture medium, and malondialdehyde content of B. dothidea mycelia. Notably, the analysis of key enzymes in glycolysis pathway showed that the activity of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK), Ca2+Mg2+-ATPase were significantly increased after FBS treatment. But the glucose contents were significantly reduced, and pyruvate contents were significantly increased in B. dothidea after treatment with FBS.ConclusionsThe inhibitory mechanism of S. spiroverticillatus HS1 against B. dothidea was a complex process, which was associated with multiple levels of mycelial growth, cell membrane structure, material and energy metabolism. The FBS of S. spiroverticillatus HS1 could provide an alternative approach to biological control strategies against B. dothidea.

Repeated marine heatwaves aggravate the adverse effects of nano-TiO2 on physiological metabolism of the thick-shelled mussel Mytilus coruscus

Global climate change is a major trigger of unexpected temperature fluctuations. The impacts of marine heatwaves (MHWs) and nano-titanium dioxide (nano-TiO2) on marine organisms have been extensively investigated. However, the potential mechanisms underlying their interactive effects on physiological processes and metabolism remain poorly understood, especially regarding periodic MHWs in real-world conditions. In this study, the effects of nano-TiO2 (at concentrations of 0, 25, and 250 μg/L) and periodic MHWs on the condition index (CI) and underlying metabolic mechanisms were investigated in mussels (Mytilus coruscus). The results showed that mussels try to upregulate their respiration rate (RR) to enhance aerobic metabolism (indicated by elevated succinate dehydrogenase) under short-term nano-TiO2 exposure. However, even at ambient concentration (25 μg/L), prolonged nano-TiO2 exposure inhibited ingestion ability (decreased clearance rate) and glycolysis (inhibited pyruvate kinase, hexokinase, and phosphofructokinase activities), which led to an insufficient energy supply (decreased triglyceride, albumin, and ATP contents). Repeated thermal scenarios caused more severe physiological damage, demonstrating that mussels are fragile to periodic MHWs. MHWs decreased the zeta potential of the nano-TiO2 particles but increased the hydrodynamic diameter. Additionally, exposure to nano-TiO2 and periodic MHWs further affected aerobic respiration (inhibited lactate dehydrogenase and succinate dehydrogenase activities), metabolism (decreased RR, activities of respiratory metabolism-related enzymes, and expressions of PEPCK, PPARγ, and ACO), and overall health condition (decreased ATP and CI). These findings indicate that the combined stress of these two stressors exerts more detrimental impact on the physiological performance and energy metabolism of mussels, and periodic MHWs exacerbate the toxicological effects of ambient concentration nano-TiO2. Given the potential worsening of nanoparticle pollution and the increase in extreme heat events in the future, the well-being of mussels in the marine environment may face further threats.

Asiaticoside ameliorates type 2 diabetes mellitus in rats by modulating carbohydrate metabolism and regulating insulin signaling

Objective: To evaluate the effect of asiaticoside on streptozotocin (STZ) and nicotinamide (NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats. Methods: Asiaticoside (50 and 100 mg/kg body weight) was administered to STZ-NAD-induced diabetic rats for 45 days, and its effects on hyperglycaemic, carbohydrate metabolic, and insulin signaling pathway markers were examined. Results: Asiaticoside increased insulin production, lowered blood glucose levels, and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities. Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity. Furthermore, asiaticoside upregulated the mRNA expressions of IRS-1, IRS-2, and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal. Conclusions: Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis, gluconeogenesis, and insulin signaling pathways.

Hypoxia-acclimation adjusts skeletal muscle anaerobic metabolism and burst swim performance in a marine fish

Red drum, Sciaenops ocellatus, are a marine teleost native to the Gulf of Mexico that routinely experiences periods of low oxygen (hypoxia). Recent work has demonstrated this species has the capacity to improve aerobic performance in hypoxia through respiratory acclimation. However, it remains unknown how hypoxia acclimation impacts anaerobic metabolism in red drum, and the consequences of exhaustive exercise and recovery. Juvenile fish were acclimated to normoxia (n = 15, DO 90.4 ± 6.42 %) or hypoxia (n = 15, DO 33.6 ± 7.2 %) for 8 days then sampled at three time points: at rest, after exercise, and after a 3 h recovery period. The resting time point was used to characterize the acclimated phenotype, while the remaining time points demonstrate how this phenotype responds to exhaustive exercise. Whole blood, red muscle, white muscle, and heart tissues were sampled for metabolites and enzyme activity. The resting phenotype was characterized by lower pHe and changes to skeletal muscle ATP. Exhaustive exercise increased muscle lactate, and decreased phosphocreatine and ATP with no effect of acclimation. Interestingly, hypoxia-acclimated fish had higher pHe and pHi than control in all exercise time points. Red muscle ATP was lower in hypoxia-acclimated fish versus control at each sample period. Moreover, acclimated fish increased lactate dehydrogenase activity in the red muscle. Hypoxia acclimation increased white muscle ATP and hexokinase activity, a glycolytic enzyme. In a gait-transition swim test, hypoxia-acclimated fish recruited anaerobic-powered burst swimming at lower speeds in normoxia compared to control fish. These data suggest that acclimation increases reliance on anaerobic metabolism, and does not benefit recovery from exhaustive exercise.

Extraction, purification, chemical characterization, and in vitro hypoglycemic activity of polysaccharides derived from Rosa laevigata Michx.

This study aimed to optimize the extraction process of polysaccharides from Rosa laevigata Michx. (RLMP) using an ultrasound-microwave-assisted method and investigate its in vitro hypoglycemic activity. Key factors affecting RLMP yield were identified using a Plackett–Burman design, followed by a Box–Behnken design and response–surface methodology, to determine the optimal extraction conditions. RLMP was purified using DEAE-52 cellulose, yielding two homogeneous fractions: RLMP-1 and RLMP-2. Monosaccharide composition was analyzed by gas chromatography, and structural characterization of RLMP, RLMP-1, and RLMP-2 was performed using FT-IR, SEM, and TEM. Methylation analysis and NMR were used to elucidate the sugar-chain structure of RLMP-1. In vitro hypoglycemic activity analysis showed that RLMP improved the glucose consumption and glycogen synthesis and enhanced the activities of pyruvate kinase and hexokinase in IR-HepG2 cells. Moreover, RLMP significantly increased the activities of antioxidant enzymes, such as CAT, SOD, and GSH-Px and decreased those of ROS and MDA. Western blotting analysis confirmed that RLMP enhances glucose and lipid metabolism and reduces oxidative stress by activating the PI3K/Akt/GLUT-4 signaling pathway, thereby exerting its hypoglycemic effect. These findings suggest that RLMP is a promising candidate for developing novel antioxidant agents or hypoglycemic drugs.

Excitation–contraction coupling reflects the metabolic profile of mantle muscle in young cuttlefish (Sepia officinalis)

AbstractThe mantle muscle of common cuttlefish, Sepia officinalis, is responsible both for high‐magnitude and rapid movements for locomotion, as well as sustained ventilation, which require specific metabolic, electrophysiological, and structural organization. Young cuttlefish have a highly oxidative phenotype and a rapid growth rate. Here, we show high rates of oxygen consumption and protein synthesis in juveniles, and these rates decay exponentially over the first few weeks of growth. This is associated with considerable citrate synthase activity (relative to larger cuttlefish) but a lack of glucose metabolism based on zero uptake of glucose by isolated muscle sheets and minimal activity of hexokinase (similar to larger animals). In contrast to glucose metabolism in the heart, glucose metabolism in these muscle sheets was not stimulated by extracellular taurine. Previous research revealed an unusual ion channel complement in mantle myocytes, the most notable feature of which is the lack of a Na+ current during depolarization. Because this adaptation is not consistent across the coleoid clade, we investigated excitation–contraction coupling. Here, mantle energetics and contractility, including the individual components of the total Ca2+ flux driving contraction, were studied. Results indicate that the majority of Ca2+ current underlying contractile stress development capacity in cuttlefish juveniles is not mediated by dihydropyridine‐sensitive L‐type channels, in contrast to their adult counterparts, and the sarcoplasmic reticulum contributes little to routine contractility. We had previously noted an influence of physiological levels of taurine in limiting cardiac contractility but found no analogous sensitivity in mantle muscle. Finally, transmission electron microscopy of subcellular architecture revealed the presence of sarcoplasmic tubular aggregates, suggesting that oxidative inhibition of sarcoplasmic reticulum function limits its role in this life stage.

Electrostatic ethanol fermentation: Experimental study and kinetic-based metabolic modeling

Due to the electrical nature of the cell, it is possible to modulate its behavior through the application of non-lethal external electric fields to improve fermentation processes. In this work, a microbial cell system with a chamber and two electrodes inside and connected to a voltage source was used. One of the electrodes was kept isolated to create an electric field without the flow of current. Cultures with two ethanol-producing microbial strains (Saccharomyces cerevisiae and Zymomonas mobilis) were conducted in this device. The application of voltages between 0 and 18 V was evaluated to determine the impact of the generated electric field on ethanol production. To analyze the possible effect of the field on the central carbon metabolism in each strain, biochemical-based kinetic models were formulated to describe the experimental fermentation kinetics obtained.It was found that low applied voltages did not have significant effects on growth rate in either strain, but all voltages evaluated increased substrate consumption and ethanol production rate in Z. mobilis, while only 18 V affected these rates in S. cerevisiae, indicating that Z. mobilis was the most sensitive to the electric field. At the end of the fermentation, significant increases in ethanol yields of 10.7% and 19.5% were detected for S. cerevisiae and Z. mobilis, respectively. The proposed mathematical models showed that substrate transport through the membrane catalyzed by the phosphotransferase system (PTS) for Z. mobilis and hexose transport proteins mechanism and hexokinase (HK) activity for S. cerevisiae and the transformation of pyruvate to ethanol, catalyzed by the decarboxylase (PDC) and alcohol dehydrogenase (ADH) enzymes, were the reactions most affected by the application of the external field.

Effect of Ca2+ signal on the activity of key enzymes of carbon metabolism and related gene expression in yeast under high sugar fermentation.

Saccharomyces cerevisiae is a fungus widely used in the food industry and biofuel industry, whereas it is usually exposed to high sugar stress during the fermentation process. Ca2+ is a key second messenger of the cell, it can regulate cell metabolism. The present study investigated the effect of the Ca2+ signal on the activity of key enzymes of carbon metabolism and related gene expression in yeast under high sugar fermentation. The expression of genes encoding hexokinase was up-regulated in the high sugar environment, the activity of hexokinase was increased, glucose transmembrane transport capacity was enhanced, the ability of glucose to enter into glycolytic metabolism was increased, and the expression of genes related to pentose phosphate metabolism, glycerol metabolism and trehalose metabolism was up-regulated in the high glucose with Ca2+ group. Ca2+ signal regulates the cellular metabolism of glycerol and trehalose and optimizes the allocation of carbon flow by regulating the key enzymes and related gene expression to enhance the resistance of yeast to high sugar stress. © 2024 Society of Chemical Industry.

Macrophage metabolic reprogramming-based diabetic infected bone defect/bone reconstruction though multi-function silk hydrogel with exosome release

Diabetic infected bone defects (DIBD) with abnormal immune metabolism are prone to the hard-to-treat bacterial infections and delayed bone regeneration, which present significant challenges in clinic. Control of immune metabolism is believed to be important in regulating fundamental immunological processes. Here, we developed a macrophage metabolic reprogramming hydrogel composed of modified silk fibroin (Silk-6) and poly-l-lysine (ε-PL) and further integrated with M2 Macrophage-derived Exo (M2-Exo), named Silk-6/ε-PL@Exo. This degradable hydrogel showed a broad-spectrum antibacterial performance against both Gram-positive and -negative bacteria. More importantly, the release of M2-Exo from Silk-6/ε-PL@Exo could target M1 macrophages, modulating the activity of the key enzyme hexokinase II (HK2) to control the inflammation-related NF-κB pathway, alleviate lactate accumulation, and inhibit glycolysis to normalize the cycle, thereby promoting M1-to-M2 balance. Using a rat model of DIBD, Silk-6/ε-PL@Exo hydrogel promoted infection control, balanced immune responses and accelerated the bone defect healing. Overall, this study demonstrates that this Silk-6/ε-PL @Exo is a promising filler biomaterial with multi-function to treat DIBD and emphasizes the importance of metabolic reprogramming in bone regeneration.

Identification and molecular mechanism of novel hypoglycemic peptide in ripened pu-erh tea: Molecular docking, dynamic simulation, and cell experiments

Ripened pu-erh tea is known to have beneficial hypoglycemic properties. However, it remains unclear whether the bioactive peptides produced during fermentation are also related to hypoglycemic potential. This study aimed to identify hypoglycemic peptides in ripened pu-erh tea and to elucidate their bioactive mechanisms using physicochemical property prediction, molecular docking, molecular dynamics simulations, and cell experiments. Thirteen peptides were identified by liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS). Among them, AADTDYRFS (AS-9) and AGDGTPYVR (AR-9) exhibited high α-glucosidase inhibitory activity, with half-maximal inhibitory concentration (IC50) values of 0.820 and 3.942 mg/mL, respectively. Molecular docking and dynamics simulations revealed that hydrogen bonding, hydrophobic interactions, and van der Waals forces assist peptides AS-9 and AR-9 in forming stable and tight complexes with α-glucosidase. An insulin-resistance (IR)-HepG2 cell model was established. AS-9 was non-toxic to IR-HepG2 cells and significantly increased the glucose consumption capacity, hexokinase, and pyruvate kinase activities of IR-HepG2 cells (p < 0.05). AS-9 alleviated glucose metabolism disorders and ameliorated IR by activating the IRS-1/PI3K/Akt signaling pathway and increasing the expression levels of MDM2, IRS-1, Akt, PI3K, GLUT4, and GSK3β genes. In addition, no hemolysis of mice red blood cells red blood cells occurred at concentrations below 1 mg/mL. This work first explored hypoglycemic peptides in ripened pu-erh tea, providing novel insights for enhancing its functional value.