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Glucose meters provide a rapid blood glucose status for evidence-based diagnosis, monitoring, and treatment of diabetes mellitus. We aimed to evaluate the commutability of processed blood materials (PBMs) and their use in the performance evaluation of glucose meters. Two PBMs obtained by the fixed-cell method were analyzed for homogeneity, stability, and commutability. The compatibility of ten pairs between mass spectrometry and each glucose meter was categorized as compatible (mean paired difference ≤ 5%) and incompatible (mean paired difference > 5%). The performance of glucose meter 1 (n = 767) and glucose meter 2 (n = 266) was assessed. The glucose in the PBMs remained homogenized and stable for at least 180 days. Six out of ten pairs had commutable PBMs. Commutability of PBMs was observed in both well-compatible and incompatible glucose results. Target glucose values from mass spectrometry were significantly different (p ≤ 0.05) from consensus values in one group of glucose meters. When commutable PBMs were used, glucose meter 1 showed better performance than glucose meter 2, and the percentage of satisfaction was associated when using target values for glucose from mass spectrometry and consensus values, but the performance of glucose meter 2 was not associated. PBM from a fixed-cell method could be mass produced with acceptable homogeneity and stability. Commutability testing of PBMs is required prior to use in the performance evaluation of glucose meters, as the commutability of glucose in the PBMs obtained by a fixed-cell method was variable and depended on the individual glucose meter. [ABSTRACT FROM AUTHOR]

Sialidases (neuraminidases) catalyze the removal of terminal sialic acid residues from glycoproteins. Novel enzymes from non-clinical isolates are of increasing interest regarding their application in the food and pharmaceutical industry. The present study aimed to evaluate the participation of carbon catabolite repression (CCR) in the regulation of cold-active sialidase biosynthesis by the psychrotolerant fungal strain Penicillium griseofulvum P29, isolated from Antarctica. The presence of glucose inhibited sialidase activity in growing and non-growing fungal mycelia in a dose- and time-dependent manner. The same response was demonstrated with maltose and sucrose. The replacement of glucose with glucose-6-phosphate also exerted CCR. The addition of cAMP resulted in the partial de-repression of sialidase synthesis. The CCR in the psychrotolerant strain P. griseofulvum P29 did not depend on temperature. Sialidase might be subject to glucose repression by both at 10 and 25 °C. The fluorescent assay using 4MU-Neu5Ac for enzyme activity determination under increasing glucose concentrations evidenced that CCR may have a regulatory role in sialidase production. The real-time RT-PCR experiments revealed that the sialidase gene was subject to glucose repression. To our knowledge, this is the first report that has studied the effect of CCR on cold-active sialidase, produced by an Antarctic strain. [ABSTRACT FROM AUTHOR]

H-Beta zeolite is a solid acid catalyst commonly utilized in the catalytic conversion of biomass resources. In this study, H-Beta zeolite was calcined at different temperatures (350, 550, 750, and 1000 °C) to explore the effects of high temperature-induced dealumination on its physicochemical properties and its catalytic ability to convert glucose into 5-hydroxymethylfurfural (HMF). It was shown that as the calcination temperature increased, the Si-O-Al bond of H-Beta zeolite was broken and its dealumination effect was enhanced. Dealumination led to the collapse of the framework of H-Beta zeolite and a reduction in the number of acid sites, which in turn reduced its catalytic performance and the efficiency of HMF formation from glucose. Furthermore, H-Beta zeolite exhibited an extraordinary catalytic ability for the production of HMF from carbohydrates. Using glucose and cellulose as substrates, superior HMF yields of 91% and 46%, respectively, were achieved under optimal reaction conditions. Further, calcination removes carbon deposits in the recovered H-Beta zeolite, but it affects the cycling stability of the catalyst. Meanwhile, the by-products formed during the synthesis of HMF from glucose catalyzed by H-Beta zeolite catalyst were also clearly detected. [ABSTRACT FROM AUTHOR]

Ethyl (S)-4-chloro-3-hydroxybutyrate ((S)-CHBE) is an important chiral intermediate in the synthesis of the cholesterol-lowering drug atorvastatin. Studying the use of SpyTag/SpyCatcher and SnoopTag/SnoopCatcher systems for the asymmetric reduction reaction and directed coupling coenzyme regeneration is practical for efficiently synthesizing (S)-CHBE. In this study, Spy and Snoop systems were used to construct a double-enzyme directed fixation system of carbonyl reductase (BsCR) and glucose dehydrogenase (BsGDH) for converting 4-chloroacetoacetate (COBE) to (S)-CHBE and achieving coenzyme regeneration. We discussed the enzymatic properties of the immobilized enzyme and the optimal catalytic conditions and reusability of the double-enzyme immobilization system. Compared to the free enzyme, the immobilized enzyme showed an improved optimal pH and temperature, maintaining higher relative activity across a wider range. The double-enzyme immobilization system was applied to catalyze the asymmetric reduction reaction of COBE, and the yield of (S)-CHBE reached 60.1% at 30 °C and pH 8.0. In addition, the double-enzyme immobilization system possessed better operational stability than the free enzyme, and maintained about 50% of the initial yield after six cycles. In summary, we show a simple and effective strategy for self-assembling SpyCatcher/SnoopCatcher and SpyTag/SnoopTag fusion proteins, which inspires building more cascade systems at the interface. It provides a new method for facilitating the rapid construction of in vitro immobilized multi-enzyme complexes from crude cell lysate. [ABSTRACT FROM AUTHOR]

Inverted fatty acid β-oxidation represents a versatile biochemical platform for biosynthesis by the engineered microbial strains of numerous value-added chemicals from convenient and abundant renewable carbon sources, including biomass-derived sugars. Although, in recent years, significant progress has been made in the production through this pathway of n-alcohols, 1,3-diols, and carboxylic acids and its 2,3-unsaturated derivatives, the potential of the pathway for the biosynthesis of 3-hydroxycarboxylic acids remained almost undisclosed. In this study, we demonstrate the microaerobic production of even-chain-length C4–C8 3-hydroxycarboxylic acids from glucose through the inverted fatty acid β-oxidation by engineered E. coli strains. The notable accumulation of target compounds was achieved upon the strong constitutive expression of the genes atoB, fadA, fadB, fadE/fabI, and tesB, which code for the key enzymes catalysing reactions of aerobic fatty acid β-oxidation and thioesterase II, in strains devoid of mixed-acid fermentation pathways and lacking nonspecific thioesterase YciA. The best performing recombinants were able to synthesise up to 14.5 mM of 3-hydroxycarboxylic acids from glucose with a total yield of 0.34 mol/mol and a C4/C6/C8 ratio averaging approximately 63/28/9. The results provide a framework for the development of highly efficient strains and processes for the bio-based production of valuable 3-hydroxycarboxylates from renewable raw materials. [ABSTRACT FROM AUTHOR]

The global rise in obesity and related health issues, such as type 2 diabetes and cardiovascular disease, is alarming. Gaining a deeper insight into the central neural pathways and mechanisms that regulate energy and glucose homeostasis is crucial for developing effective interventions to combat this debilitating condition. A significant body of evidence from studies in humans and rodents indicates that brain-derived neurotrophic factor (BDNF) signaling plays a key role in regulating feeding, energy expenditure, and glycemic control. BDNF is a highly conserved neurotrophin that signals via the tropomyosin-related kinase B (TrkB) receptor to facilitate neuronal survival, differentiation, and synaptic plasticity and function. Recent studies have shed light on the mechanisms through which BDNF influences energy and glucose balance. This review will cover our current understanding of the brain regions, neural circuits, and cellular and molecular mechanisms underlying the metabolic actions of BDNF and TrkB. [ABSTRACT FROM AUTHOR]

Simple Summary: Cisplatin-based resistance is an old concern for advanced urothelial bladder cancer (UBC) patients. This work aimed to study the metabolic profiles of three pairs of cisplatin-sensitive (CS) and cisplatin-resistant (CR) UBC cell lines. A tendency was observed towards an intensified glycolytic metabolism in two of the CR cell lines, especially in the CR cells showing higher levels of cisplatin resistance. However, in this cell line, a shift towards alternative metabolic routes involving lactate uptake, lipid biosynthesis and glutamate metabolism occurred with time. The remaining cell line seemed to engage in a metabolic reprogramming, recovering the preference for oxygen consumption. Thus, CR UBC cells displayed deep metabolic alterations that likely depended on their molecular backgrounds. Advanced urothelial bladder cancer (UBC) patients are tagged by a dismal prognosis and high mortality rates, mostly due to their poor response to standard-of-care platinum-based therapy. Mediators of chemoresistance are not fully elucidated. This work aimed to study the metabolic profile of advanced UBC, in the context of cisplatin resistance. Three isogenic pairs of parental cell lines (T24, HT1376 and KU1919) and the matching cisplatin-resistant (R) sublines were used. A set of functional assays was used to perform a metabolic screening on the cells. In comparison to the parental sublines, a tendency was observed towards an exacerbated glycolytic metabolism in the cisplatin-resistant T24 and HT1376 cells; this glycolytic phenotype was particularly evident for the HT1376/HT1376R pair, for which the cisplatin resistance ratio was higher. HT1376R cells showed decreased basal respiration and oxygen consumption associated with ATP production; in accordance, the extracellular acidification rate was also higher in the resistant subline. Glycolytic rate assay confirmed that these cells presented higher basal glycolysis, with an increase in proton efflux. While the results of real-time metabolomics seem to substantiate the manifestation of the Warburg phenotype in HT1376R cells, a shift towards distinct metabolic pathways involving lactate uptake, lipid biosynthesis and glutamate metabolism occurred with time. On the other hand, KU1919R cells seem to engage in a metabolic rewiring, recovering their preference for oxidative phosphorylation. In conclusion, cisplatin-resistant UBC cells seem to display deep metabolic alterations surpassing the Warburg effect, which likely depend on the molecular signature of each cell line. [ABSTRACT FROM AUTHOR]

Ginkgo biloba L. (ginkgo) is a widely used medicinal plant around the world. Its leaves, which have been used as a traditional Chinese medicine, are rich in various bioactive components. However, most of the research and applications of ginkgo leaves have focused on terpene trilactones and flavonol glycosides, thereby overlooking the other active components. In this study, a lipophilic extract (GL) was isolated from ginkgo leaves. This extract is abundant in lipids and lipid-like molecules. Then, its effect and potential mechanism on glucose uptake and insulin resistance in C2C12 myotubes were investigated. The results showed that GL significantly enhanced the translocation of GLUT4 to the plasma membrane, which subsequently promoted glucose uptake. Meanwhile, it increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream targets. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor compound C reversed these effects. Additionally, GL ameliorated palmitate-induced insulin resistance by enhancing insulin-stimulated glucose uptake, increasing the phosphorylation of protein kinase B (PKB/AKT), and restoring the translocation of GLUT4 from the cytoplasm to the membrane. However, pretreatment with compound C abolished these beneficial effects of GL. In conclusion, GL enhances basal glucose uptake in C2C12 myotubes and improves insulin sensitivity in palmitate-induced insulin resistant myotubes through the AMPK pathway. [ABSTRACT FROM AUTHOR]

We describe the creation of a conductive microcavity based on the assembly of two pieces of carbon nanotube buckypaper for the entrapment of two enzymes, horseradish peroxidase (HRP) and glucose oxidase (GOx), as well as a redox mediator: 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS). The hollow electrode, employing GOx, HRP, and the mediator, as an electrochemical enzyme cascade model, is utilized for glucose sensing at a potential of 50 mV vs. Ag/AgCl. This bienzyme electrode demonstrates the ability to oxidize glucose by GOx and subsequently convert H2O2 to water via the electrical wiring of HRP by ABTS. Different redox mediators (ABTS, potassium hexacyanoferrate (III), and hydroquinone) are tested for HRP wiring, with ABTS being the best candidate for the electroenzymatic reduction of H2O2. To demonstrate the possibility to optimize the enzyme cascade configuration, the enzyme ratio is studied with 1 mg HRP combined with variable amounts of GOx (1–4 mg) and 2 mg GOx combined with variable amounts of HRP (0.5–2 mg). The bienzyme electrode shows continuous operational stability for over a week and an excellent storage stability in phosphate buffer, with a decay of catalytic current by only 29% for 1 mM glucose after 100 days. [ABSTRACT FROM AUTHOR]

The Co3O4 is a typical p-type metal oxide semiconductor (MOS) that attracted great attention for hydrogen detection. In this work, porous, urchin-like Co3O4 was synthesized using a hydrothermal method with the assistance of glucose and a subsequent calcination process. Urchin-like Co3O4 has a large specific surface area of 81.4 m2/g. The response value of urchin-like Co3O4 to 200 ppm hydrogen at 200 °C is 36.5 (Rg/Ra), while the low-detection limit is as low as 100 ppb. The obtained Co3O4 also exhibited good reproducibility, long-term stability, and selectivity towards various gases (e.g., ammonia, hydrogen, carbon monoxide, and methane). Porous, urchin-like Co3O4 is expected to become a potential candidate for low-concentration hydrogen-sensing materials with the above advantages. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive malignancy with a lack of reliable diagnostic biomarkers. Protein induced by vitamin K absence (PIVKA-II) is a protein increased in various cancers (particularly in hepatocellular carcinoma), and it has recently exhibited superior diagnostic performance in PDAC detection compared to other biomarkers. The aim of our research was to identify an in vitro model to study PIVKA-II production, distribution, and release in PDAC. We examined the presence of PIVKA-II protein in a panel of stabilized pancreatic cancer cell lines by Western blot analysis and indirect immunofluorescence (IFA). After quantitative evaluation of PIVKA-II in PaCa 44, H-Paf II, Capan-1, and PANC-1, we adopted the latter as a reference model. Subsequently, we analyzed the effect of glucose addiction on PIVKA-II production in a PANC-1 cell line in vitro; PIVKA-II production seems to be directly related to an increase in glucose concentration in the culture medium. Finally, we evaluated if PIVKA-II released in the presence of increasing doses of glucose is concomitant with the expression of two well-acknowledged epithelial–mesenchymal transition (EMT) markers (Vimentin and Snail). According to our experimental model, we can speculate that PIVKA-II release by PANC-1 cells is glucose-dependent and occurs jointly with EMT activation. [ABSTRACT FROM AUTHOR]

In arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication. The defined endpoint was the assessment of circulating metabolites using a nuclear magnetic resonance-based metabolomics approach. Univariate and multivariate analyses were used to evaluate the systemic metabolic alterations caused by cholecalciferol. In comparison with normotensive controls, hypertensive patients presented overall decreased expression of several amino acids (p < 0.05), including amino acids with ketogenic and glucogenic properties as well as aromatic amino acids. Following cholecalciferol supplementation, increases were observed in glutamine (p < 0.001) and histidine levels (p < 0.05), with several other amino acids remaining unaffected. Glucose (p < 0.05) and acetate (p < 0.05) decreased after 24 weeks in the group taking the supplement, and changes in the saturation of fatty acids (p < 0.05) were also observed, suggesting a role of liposoluble vitamin D in lipid metabolism. Long-term cholecalciferol supplementation in chronically obese and overweight hypertensives induced changes in the blood serum metabolome, which reflected systemic metabolism and may have fostered a new microenvironment for cell proliferation and biology. Of note, the increased availability of glutamine may be relevant for the proliferation of different T-cell subsets. [ABSTRACT FROM AUTHOR]

Unbalanced blood glucose levels may cause inflammation within the central nervous system (CNS). This effect can be reversed by the action of a natural neuroprotective compound, resveratrol (RSV). The study aimed to investigate the anti-inflammatory effect of RSV on astrocyte cytokine profiles within an in vitro model of the blood–brain barrier (BBB) under varying glucose concentrations (2.2, 5.0, and 25.0 mmol/L), corresponding to hypo-, normo-, and hyperglycemia. The model included co-cultures of astrocytes (brain compartment, BC) and endothelial cells (microvascular compartment, MC), separated by 0.4 µm wide pores. Subsequent exposure to 0.2 μM LPS in the brain compartment (BC) and 50 μM RSV in the microvascular compartment (MC) of each well was carried out. Cytokine levels (IL-1 α, IL-1 β, IL-2, IL-4, IL-6, IL-8) in the BC were assessed using a Multi-Analyte ELISArray Kit before and after the addition of LPS and RSV. Statistical analysis was performed to determine significance levels. The results demonstrated that RSV reduced the concentration of all studied cytokines in the BC, regardless of glucose levels, with the most substantial decrease observed under normoglycemic conditions. Additionally, the concentration of RSV in the BC was highest under normoglycemic conditions compared to hypo- and hyperglycemia. These findings confirm that administration of RSV in the MC exerts anti-inflammatory effects within the BC, particularly under normoglycemia-simulating conditions. Further in vivo studies, including animal and human research, are warranted to elucidate the bioavailability of RSV within the central nervous system (CNS). [ABSTRACT FROM AUTHOR]

Background: Sodium glucose cotransporter-2 inhibitors (SGLT2is) represent an emerging class of drugs with diverse indications. Despite their therapeutic potential, concerns regarding safety, particularly diabetic ketoacidosis (DKA), remain contentious, with uncertainty regarding differences among various SGLT2is. This study aimed to conduct a network meta-analysis and meta-regression to evaluate the risk of SGLT2i-induced DKA and associated factors. Methods: We systematically searched electronic databases for randomized clinical trials assessing SGLT2is across indications, reporting incidences of DKA. Mixed treatment comparison pooled estimates (MTCPEs) were calculated, and odds ratios (OR) with 95% confidence intervals (95% CI) served as effect estimates. We analyzed differences across dose categories (low, medium, and high) and conducted a meta-regression analysis to identify risk factors. The strength of evidence for key comparisons was determined. Results: Our analysis included 73 articles encompassing 85,997 participants assessing the risk of DKA. SGLT2is were associated with a heightened risk of DKA compared to placebo/control interventions (OR: 1.83; 95% CI: 1.35, 2.46), a finding confirmed by bootstrap analysis. Among SGLT2is, dapagliflozin (OR: 1.9; 95% CI: 1.17, 3.08), sotagliflozin (OR: 1.93; 95% CI: 1.14, 3.25), canagliflozin (OR: 1.11; 95% CI: 1.11, 12.45), and ertugliflozin (OR: 3.92; 95% CI: 1.04, 14.77) exhibited increased DKA risk. No significant differences were observed among specific SGLT2is. Sub-group analyses revealed a high risk of DKA with low (OR: 1.98; 95% CI: 1.3, 2.95) and high doses (OR: 2.4; 95% CI: 1.7, 3.3), type 1 diabetes (OR: 3.6; 95% CI: 1.6, 8.1), type 2 diabetes (OR: 1.6; 95% CI: 1.3, 2.4), as well as a diabetes duration exceeding 10 years (OR: 3.4; 95% CI: 1.1, 10.8). The evidence of certainty for most comparisons was moderate. Conclusions: SGLT2 inhibitors (SGLT2is) have been found to elevate the risk of DKA. The key factors that significantly predict the likelihood of DKA include the presence of diabetes (whether T1D or T2D) and the duration of diabetes. Based on these findings, standard treatment guidelines should advise taking specific precautions against DKA in patients identified as high-risk. [ABSTRACT FROM AUTHOR]

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of glucose-lowering agents widely used for the treatment of type 2 diabetes mellitus. A number of clinical trials in type 2 diabetic patients with different degrees of renal impairment have clearly demonstrated that SGLT2 inhibitors reduce the progression rate of diabetic kidney disease. Furthermore, recent studies have shown that SGLT2 inhibitors also exert a protective effect in the case of non-diabetic kidney disease. Consequently, it has been hypothesized that the nephroprotective activity of these drugs could exceed the canonical impact on glycemic control and that the resulting beneficial effects could be the consequence of their pleiotropic properties (proven reduction of inflammation, fibrosis, oxidative stress and sympathetic nervous activity) both at systemic and tissue levels, suggesting that the efficacy of these drugs could also be extended to non-diabetic nephropathies. This review focuses on the nephroprotective effects of SGLT2 inhibitors in different experimental models of non-diabetic kidney disease. The different glucose-independent mechanisms potentially implemented by SGLT2 inhibitors to ultimately protect the non-diabetic kidney are described in detail, and conflicting results, when present, are discussed. [ABSTRACT FROM AUTHOR]

Our purpose in this study was to identify the role played by oxidative stress in the changes to proteoglycans that occur under hyperglycemic conditions, using primary rat retinal microvascular endothelial cells (RRMEC) and cultured ophthalmic arteries. The cells and blood vessels obtained from rats were cultured in normal glucose (5.6 mM) and high glucose (25 mM) with or without N-acetylcysteine (NAC), an antioxidant. Intracellular oxidative stress was determined by measuring dihydroethidium (DHE) fluorescence and malondialdehyde (MDA)-modified protein levels. mRNA and protein levels were evaluated using quantitative real-time polymerase chain reaction and immunoblot, respectively. High glucose increased levels of glypican-1 mRNA and protein. The level of syndecan-1 mRNA also was increased, but its protein level was decreased, by high glucose. Evaluation of DHE and MDA showed that high glucose increased oxidative stress. These changes caused by high glucose were significantly reversed by NAC treatment. Matrix metalloproteinase-9 (MMP-9) levels, which increased under high glucose conditions, were suppressed by NAC treatment. Oxidative stress caused by hyperglycemia may be responsible for significant changes to the ocular endothelial glycocalyx. [ABSTRACT FROM AUTHOR]

Pathogens have to cope with oxidative, iron- and carbon(glucose)-limitation stresses in the human body. To understand how combined iron–carbon limitation alters oxidative stress responses, Aspergillus fumigatus was cultured in glucose–peptone or peptone containing media supplemented or not with deferiprone as an iron chelator. Changes in the transcriptome in these cultures were recorded after H2O2 treatment. Responses to oxidative stress were highly dependent on the availability of glucose and iron. Out of the 16 stress responsive antioxidative enzyme genes, only the cat2 catalase–peroxidase gene was upregulated in more than two culturing conditions. The transcriptional responses observed in iron metabolism also varied substantially in these cultures. Only extracellular siderophore production appeared important regardless of culturing conditions in oxidative stress protection, while the enhanced synthesis of Fe-S cluster proteins seemed to be crucial for oxidative stress treated iron-limited and fast growing (glucose rich) cultures. Although pathogens and host cells live together in the same place, their culturing conditions (e.g., iron availability or occurrence of oxidative stress) can be different. Therefore, inhibition of a universally important biochemical process, like Fe-S cluster assembly, may selectively inhibit the pathogen growth in vivo and represent a potential target for antifungal therapy. [ABSTRACT FROM AUTHOR]

The salt–tolerant yeast Zygosaccharomyces rouxii is a typical aroma–producing yeast used in food brewing, but its mechanism of high temperature tolerance is still unclear. In this study, the response mechanism of Z. rouxii to glucose under high temperature stress at 40 °C was explored, based on the total synthetic lowest–nutrient medium. The results of the growth curves and scanning electron microscopy showed that high glucose was necessary for Z. rouxii to restore growth under high temperature stress, with the biomass at 300 g/L of glucose (OD600, 120h = 2.44 ± 0.26) being 8.71 times higher than that at 20 g/L (OD600, 120h = 0.28 ± 0.08). The results of the transcriptome analysis, combined with RT–qPCR, showed that the KEGG analysis of differentially expressed genes was enriched in pathways related to glucose metabolism, and high glucose (300 g/L) could effectively stimulate the gene expression of glucose transporters, trehalose synthesis pathways, and xylitol synthesis pathways under a high temperature, especially the expression of the glucose receptor gene RGT2 (up–regulated 193.7 times at 12 h). The corresponding metabolic characteristics showed that the contents of intracellular metabolites, such as glucose (Cmax, 6h = 6.50 ± 0.12 mg/g DCW), trehalose (Cmax, 8h = 369.00 ± 17.82 μg/g DCW), xylitol (Cmax, 8h = 1.79 ± 0.27 mg/g DCW), and glycerol (Cmax, 8h = 268.10 ± 44.49 μg/g DCW), also increased with time. The accumulation of acetic acid, as the main product of overflow metabolism under high temperature stress (intracellular Cmax, 2h = 126.30 ± 10.96 μg/g DCW; extracellular Cmax, 12h = 499.63 ± 27.16 mg/L), indicated that the downstream glycolysis pathway was active. Compared with the normal physiological concentration of glucose, a high glucose concentration can effectively stimulate the gene expression and metabolism of salt–tolerant Z. rouxii under high–temperature conditions to restore growth. This study helps to deepen the current understanding of the thermoadaptive growth mechanism of salt–tolerant Z. rouxii. [ABSTRACT FROM AUTHOR]

As a crucial enzyme for cellulose degradation, β-glucosidase finds extensive applications in food, feed, and bioethanol production; however, its potential is often limited by inadequate thermal stability and glucose tolerance. In this study, a functional gene (lq-bg5) for a GH1 family β-glucosidase was obtained from the metagenomic DNA of a hot spring sediment sample and heterologously expressed in E. coli and the recombinant enzyme was purified and characterized. The optimal temperature and pH of LQ-BG5 were 55 °C and 4.6, respectively. The relative residual activity of LQ-BG5 exceeded 90% at 55 °C for 9 h and 60 °C for 6 h and remained above 100% after incubation at pH 5.0–10.0 for 12 h. More importantly, LQ-BG5 demonstrated exceptional glucose tolerance with more than 40% activity remaining even at high glucose concentrations of 3000 mM. Thus, LQ-BG5 represents a thermophilic β-glucosidase exhibiting excellent thermal stability and remarkable glucose tolerance, making it highly promising for lignocellulose development and utilization. [ABSTRACT FROM AUTHOR]

Micropillar array electrodes represent a promising avenue for enhancing detection sensitivity and response current. However, existing methods for depositing electrode materials on micropillar arrays often result in uneven distribution, with the thin sidewall layer being less conductive and prone to corrosion. In addressing this issue, this study introduces electroplating to enhance the copper layer on the sidewall of micropillar array electrodes. These electrodes, fabricated through standard microelectronics processes and electroplating, are proposed for non-enzymatic glucose detection, with the copper layer deposited via electroplating significantly enhancing sensitivity. Initially, the impact of cetyltrimethylammonium bromide (CTAB) concentration as an inhibitor on the surface morphology and sensitivity of the plated layer was investigated. It was discovered that CTAB could decrease surface roughness, hinder the development of large and coarse grains, generate small particles, and boost sensitivity. Compared to the uncoated electrode and plating without CTAB, sensitivity was elevated by a factor of 1.66 and 1.62, respectively. Subsequently, the alterations in plating morphology and detection performance within a range of 0.3 ASD to 3 ASD were examined. Sensitivity demonstrated a tendency to increase initially and then decrease. The electrode plated at 0.75 ASD achieved a maximum sensitivity of 3314 μA·mM−1·cm−2 and a detection limit of 15.9 μM. Furthermore, a potential mechanism explaining the impact of different morphology on detection performance due to CTAB and current density was discussed. It was believed that the presented effective strategy to enhance the sensitivity of micropillar array electrodes for glucose detection would promote the related biomedical detection applications. [ABSTRACT FROM AUTHOR]

The rat model of perinatal stress (PRS), in which exposure of pregnant dams to restraint stress reduces maternal behavior, is characterized by a metabolic profile that is reminiscent of the "metabolic syndrome". We aimed to identify plasma metabolomic signatures linked to long-term programming induced by PRS in aged male rats. This study was conducted in the plasma and frontal cortex. We also investigated the reversal effect of postpartum carbetocin (Cbt) on these signatures, along with its impact on deficits in cognitive, social, and exploratory behavior. We found that PRS induced long-lasting changes in biomarkers of secondary bile acid metabolism in the plasma and glutathione metabolism in the frontal cortex. Cbt treatment demonstrated disease-dependent effects by reversing the metabolite alterations. The metabolomic signatures of PRS were associated with long-term cognitive and emotional alterations alongside endocrinological disturbances. Our findings represent the first evidence of how early life stress may alter the metabolomic profile in aged individuals, thereby increasing vulnerability to CNS disorders. This raises the intriguing prospect that the pharmacological activation of oxytocin receptors soon after delivery through the mother may rectify these alterations. [ABSTRACT FROM AUTHOR]

Metformin is a well-established drug for the treatment of type 2 diabetes; however, the mechanism of action has not been well described and many aspects of how it truly acts are still unknown. Moreover, regarding in vitro experiments, the glycaemic status when metformin is used is generally not considered, which, added to the suprapharmacological drug concentrations that are commonly employed in research, has resulted in gaps of its mechanism of action. The aim of this study was to determine how glucose and metformin concentrations influence cell culture. Considering that diabetic retinopathy is one of the most common complications of diabetes, a retinal pigment epithelial cell line was selected, and cell viability and proliferation rates were measured at different glucose and metformin concentrations. As expected, glucose concentration by itself positively influenced cell proliferation rates. When the metformin was considered, results were conditioned, as well, by metformin concentration. This conditioning resulted in cell death when high concentrations of metformin were used under physiological concentrations of glucose, while this did not happen when clinically relevant concentrations of metformin were used independently of glucose status. Our study shows the importance of in vitro cell growth conditions when drug effects such as metformin's are being analysed. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major public health concern with significant consequences across various domains. Following the primary event, secondary injuries compound the outcome after TBI, with disrupted glucose metabolism emerging as a relevant factor. This narrative review summarises the existing literature on post-TBI alterations in glucose metabolism. After TBI, the brain undergoes dynamic changes in brain glucose transport, including alterations in glucose transporters and kinetics, and disruptions in the blood–brain barrier (BBB). In addition, cerebral glucose metabolism transitions from a phase of hyperglycolysis to hypometabolism, with upregulation of alternative pathways of glycolysis. Future research should further explore optimal, and possibly personalised, glycaemic control targets in TBI patients, with GLP-1 analogues as promising therapeutic candidates. Furthermore, a more fundamental understanding of alterations in the activation of various pathways, such as the polyol and lactate pathway, could hold the key to improving outcomes following TBI. [ABSTRACT FROM AUTHOR]

While glucose is the primary fuel for fetal growth, the placenta utilizes the majority of glucose taken up from the maternal circulation. Of the facilitative glucose transporters in the placenta, SLC2A8 (GLUT8) is thought to primarily function as an intracellular glucose transporter; however, its function in trophoblast cells has not been determined. To gain insight into the function of SLC2A8 in the placenta, lentiviral-mediated RNA interference (RNAi) was performed in the human first-trimester trophoblast cell line ACH-3P. Non-targeting sequence controls (NTS RNAi; n = 4) and SLC2A8 RNAi (n = 4) infected ACH-3P cells were compared. A 79% reduction in SLC2A8 mRNA concentration was associated with an 11% reduction (p ≤ 0.05) in ACH-3P glucose uptake. NTS RNAi and SLC2A8 RNAi ACH-3P mRNA were subjected to RNAseq, identifying 1525 transcripts that were differentially expressed (|log2FC| > 1 and adjusted p-value < 0.05), with 273 transcripts derived from protein-coding genes, and the change in 10 of these mRNAs was validated by real-time qPCR. Additionally, there were 147 differentially expressed long non-coding RNAs. Functional analyses revealed differentially expressed genes involved in various metabolic pathways associated with cellular respiration, oxidative phosphorylation, and ATP synthesis. Collectively, these data indicate that SLC2A8 deficiency may impact placental uptake of glucose, but that its likely primary function in trophoblast cells is to support cellular respiration. Since the placenta oxidizes the majority of the glucose it takes up to support its own metabolic needs, impairment of SLC2A8 function could set the stage for functional placental insufficiency. [ABSTRACT FROM AUTHOR]

Simple Summary: Chickens are sensitive to different stressors such as emotional stressors, feed reduction or restraint. These may influence physiological parameters including those related to metabolism, growth and development. The choice of reliable markers of stress is essential to evaluate poultry welfare. Therefore, the objective of this study was to examine whether measuring glucose and insulin levels could be useful for establishing the short-term effects of stress. Additionally, we measured the changes in Met-enkephalin, an endogenous opioid, and corticosterone, hormones responsible for the stress response. Our results show that restraint is a severe stressor stimulating both the hypothalamo–pituitary–adrenocortical axis and the opioid system activity, together with influencing carbohydrate metabolism. This study examined the effects of acute restraint stress in the presence or absence of naltrexone on the circulating concentrations of insulin, glucose, Met-enkephalin and corticosterone in 14-week-old chickens [design: 2 sex × 2 stress/non-stress × 2 +/− naltrexone]. In chickens (five male and five females per treatment) subjected to restraint for 30 min, there were increases in the plasma concentrations of corticosterone and Met-enkephalin. The plasma concentrations of insulin and glucose were also increased in the chickens during restraint. Moreover, there were increases in the plasma concentrations of insulin and glucose in the chickens. The patterns of expression of the proenkephalin gene (PENK) in both the anterior pituitary gland and the adrenal gland were very similar to that of plasma Met-enkephalin. There were relationships between the plasma concentrations of corticosterone, Met-enkephalin, insulin and glucose after 30 min of restraint. The effects of naltrexone treatment on both untreated and stressed chickens were also examined, with naltrexone attenuating the stress-induced increases in the plasma concentrations of corticosterone, Met-enkephalin and glucose but not in those of insulin. The present study demonstrates that stress increases insulin secretion in chickens but also induces insulin resistance. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the association between glucose dysregulation and delirium after non-cardiac surgery. Among a total of 203,787 patients who underwent non-cardiac surgery between January 2011 and June 2019 at our institution, we selected 61,805 with available preoperative blood glucose levels within 24 h before surgery. Patients experiencing glucose dysregulation were divided into three groups: hyperglycemia, hypoglycemia, and both. We compared the incidence of postoperative delirium within 30 days after surgery between exposed and unexposed patients according to the type of glucose dysregulation. The overall incidence of hyperglycemia, hypoglycemia, and both was 5851 (9.5%), 1452 (2.3%), and 145 (0.2%), respectively. The rate of delirium per 100 person-months of the exposed group was higher than that of the unexposed group in all types of glucose dysregulation. After adjustment, the hazard ratios of glucose dysregulation in the development of delirium were 1.35 (95% CI, 1.18–1.56) in hyperglycemia, 1.36 (95% CI, 1.06–1.75) in hypoglycemia, and 3.14 (95% CI, 1.27–7.77) in both. The subgroup analysis showed that exposure to hypoglycemia or both to hypo- and hyperglycemia was not associated with delirium in diabetic patients, but hyperglycemia was consistently associated with postoperative delirium regardless of the presence of diabetes. Preoperative glucose dysregulation was associated with increased risk of delirium after non-cardiac surgery. Our findings may be helpful for preventing postoperative delirium, and further investigations are required to verify the association and mechanisms for the effect we observed. [ABSTRACT FROM AUTHOR]

The binding of ubiquitous serum ligands (free fatty acids) to human serum albumin (HSA) or its glycation can affect thiol group reactivity, thus influencing its antioxidant activity. The effects of stearic acid (SA) and glucose binding on HSA structural changes and thiol group content and reactivity were monitored by fluoroscopy and the Ellman method during a 14-day incubation in molar ratios to HSA that mimic pathophysiological conditions. Upon incubation with 5 mM glucose, HSA glycation was the same as HSA without it, in three different HSA:SA molar ratios (HSA:SA-1:1-2-4). The protective effect of SA on the antioxidant property of HSA under different glucose regimes (5-10-20 mM) was significantly affected by molar ratios of HSA:SA. Thiol reactivity was fully restored with 5–20 mM glucose at a 1:1 HSA:SA ratio, while the highest thiol content recovery was in pathological glucose regimes at a 1:1 HSA:SA ratio. The SA affinity for HSA increased significantly (1.5- and 1.3-fold, p < 0.01) with 5 and 10 mM glucose compared to the control. These results deepen the knowledge about the possible regulation of the antioxidant role of HSA in diabetes and other pathophysiological conditions and enable the design of future HSA-drug studies which, in turn, is important for clinicians when designing information-based treatments. [ABSTRACT FROM AUTHOR]

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here, we studied the effect of 12 weeks of drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined, as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males, with slightly higher adipocyte area values in both males and females under clozapine treatment. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol-medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine treatment. IR-ß expression changed sex-specifically in the clozapine-medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-treated females. Taken together, clozapine and haloperidol had a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined, and probably in their effect on liver metabolism. [ABSTRACT FROM AUTHOR]

Previously, we demonstrated that renal denervation in pigs reduces renal glucose release during a hypoglycemic episode. In this study we set out to examine changes in side-dependent renal net glucose release (SGN) through unilateral low-frequency stimulation (LFS) of the renal plexus with a pulse generator (2–5 Hz) during normoglycemia (60 min) and insulin-induced hypoglycemia ≤3.5 mmol/L (75 min) in seven pigs. The jugular vein, carotid artery, renal artery and vein, and both ureters were catheterized for measurement purposes, blood pressure management, and drug and fluid infusions. Para-aminohippurate (PAH) and inulin infusions were used to determine side-dependent renal plasma flow (SRP) and glomerular filtration rate (GFR). In a linear mixed model, LFS caused no change in SRP but decreased sodium excretion (p < 0.0001), as well as decreasing GFR during hypoglycemia (p = 0.0176). In a linear mixed model, only hypoglycemic conditions exerted significant effects on SGN (p = 0.001), whereas LFS did not. In a Wilcoxon signed rank exact test, LFS significantly increased SGN (p = 0.03125) and decreased sodium excretion (p = 0.0017) and urinary flow rate (p = 0.0129) when only considering the first instance LFS followed a preceding period of non-stimulation during normoglycemia. To conclude, this study represents, to our knowledge, the first description of an induction of renal gluconeogenesis by LFS. [ABSTRACT FROM AUTHOR]

The ambulatory glucose profile (AGP) lacks sufficient statistical metrics and insightful graphs; indeed, it is missing important information on the temporal patterns of glucose variations. The AGP graph is difficult to interpret due to the overlapping metrics and fluctuations in glucose levels over 14 days. The objective of this proposed work is to overcome these challenges, specifically the lack of insightful information and difficulty in interpreting AGP graphs, to create a platform for decision assistance. The present work proposes 20 findings built from decision rules that were developed from a combination of AGP metrics and additional statistical metrics, which have the potential to identify patterns and insightful information on hyperglycemia and hypoglycemia. The "CGM Trace" webpage was developed, in which insightful metrics and graphical representations can be used to make inferences regarding the glucose data of any user. However, doctors (endocrinologists) can access the "Findings" tab for a summarized presentation of their patients' glycemic control. The findings were implemented for 67 patients' data, in which the data of 15 patients were collected from a clinical study and the data of 52 patients were gathered from a public dataset. The findings were validated by means of MANOVA (multivariate analysis of variance), wherein a p value of < 0.05 was obtained, depicting a strong significant correlation between the findings and the metrics. The proposed work from "CGM Trace" offers a deeper understanding of the CGM data, enhancing AGP reports for doctors to make treatment adjustments based on insightful information and hidden patterns for better diabetic management. [ABSTRACT FROM AUTHOR]

This article introduces an algorithm for detecting glucose and silicon levels in solution. The research focuses on addressing the critical need for accurate and efficient glucose monitoring, particularly in the context of diabetic management. Understanding and monitoring silicon levels in the body is crucial due to its significant role in various physiological processes. Silicon, while often overshadowed by other minerals, plays a vital role in bone health, collagen formation, and connective tissue integrity. Moreover, recent research suggests its potential involvement in neurological health and the prevention of certain degenerative diseases. Investigating silicon levels becomes essential for a comprehensive understanding of its impact on overall health and well-being and paves the way for targeted interventions and personalized healthcare strategies. The approach presented in this paper is based on the integration of hyperspectral data and artificial intelligence techniques. The algorithm investigates the effectiveness of two distinct models utilizing SVMR and a perceptron independently. SVMR is employed to establish a robust regression model that maps input features to continuous glucose and silicon values. The study outlines the methodology, including feature selection, model training, and evaluation metrics. Experimental results demonstrate the algorithm's effectiveness at accurately predicting glucose and silicon concentrations and showcases its potential for real-world application in continuous glucose and silicon monitoring systems. [ABSTRACT FROM AUTHOR]

Nanofiber technology is leading the revolution of wearable technology and provides a unique capability to fabricate smart textiles. With the novel fabrication technique of electrospinning, nanofibers can be fabricated and then manufactured into a durable conductive string for the application of smart textiles. This paper presents an electrospun nanofiber mesh-based (NF-Felt) string electrode with a conducting polymer coating for an electrochemical enzymatic glucose sensor. The surface area of a nanofiber matrix is a key physical property for enhanced glucose oxidase (GOx) enzyme binding for the development of an electrochemical biosensor. A morphological characterization of the NF-Felt string electrode was performed using scanning electron microscopy (SEM) and compared with a commercially available cotton–polyester (Cot-Pol) string coated with the same conducting polymer. The results from stress–strain testing demonstrated high stretchability of the NF-Felt string. Also, the electrochemical characterization results showed that the NF-Felt string electrode was able to detect a glucose concentration in the range between 0.0 mM and 30.0 mM with a sensitivity of 37.4 μA/mM·g and a detection limit of 3.31 mM. Overall, with better electrochemical performance and incredible flexibility, the NF-Felt-based string electrode is potentially more suitable for designing wearable biosensors for the detection of glucose in sweat. [ABSTRACT FROM AUTHOR]

In this article, we demonstrate an improved efficient fibre sensor with a high sensitivity to measure glucose concentrations in the physiological range of human beings, operating in a broad spectral bandwidth from the near- to mid-infrared. The sensor consists of a dual-peak long period grating (DPLPG) with a period of 150 μm inscribed in an optical fibre with a diameter of 80 μm. The investigation of sensing for refractive index results in a sensitivity of ~−885.7 nm/refractive index unit (RIU) and ~2008.6 nm/RIU in the range of 1.30–1.44. The glucose measurement is achieved by the immobilisation of a layer of enzyme of glucose oxidase (GOD) onto the fibre surface for the selective enhancement of sensitivity for glucose. The sensor can measure glucose concentrations with a maximum sensitivity of −36.25 nm/(mg/mL) in the range of 0.1–3.0 mg/mL. To the best of our knowledge, this is the highest sensitivity ever achieved for a measurement of glucose with a long period grating-based sensor, indicating its potential for many applications including pharmaceutical, biomedical and food industries. [ABSTRACT FROM AUTHOR]

A pellet-forming as-catalyst, CuO/Al2O3, was prepared by the precipitation–tablet molding method and characterized by the Brunner–Emmet–Teller (BET), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM) techniques and TEM. The characterization results showed that the formed CuO/Al2O3 was in situ reduced to Cu/Al2O3 and Cu2O/ Al2O3 catalysts in the reaction system. The catalytic performance of catalyzing hydrogenation starch into glucose was investigated in an autoclave over CuO/Al2O3. The yield of glucose reached 83.16% at a temperature of 160 °C, a pressure of 1.8 MPa, a 100 g starch solution of 15 wt%, a catalyst dosage of 2.25%, a reaction time of 4 h, and a rotational speed of 630 r/min. The reusability of the catalyst was evaluated, and the glucose yield did not decrease obviously even after being reused for five consecutive cycles. Starch was converted into glucose through the synergistic action of Cu+ and Cu0 catalysis. This work is expected to provide valuable insights into the design of catalysts and the hydrogenation process for efficient starch hydrogenation. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the potential effects of natural polyphenol antioxidant (Cabanin® CSD provided by R2 Agro, Denmark)-supplemented diets on the growth performance and biochemical and antioxidant responses of Nile tilapia (Oreochromis niloticus). The fish were fed two control diets (low and high levels of vitamin C and vitamin E without added Cabanin® CSD) and two experimental diets with Cabanin® CSD supplementation for 10 weeks. After the trial, the specific growth rate, feed utilization, and survival rate were observed. The blood biochemical parameters, consisting of superoxide dismutase activity, malondialdehyde, cortisol, and glucose, were measured. The presence of malondialdehyde in the flesh meat of the tilapia was also evaluated during refrigerated storage. The fish was then challenged with 60 mg/L ammonia for 168 h. The survival rate and biochemical parameters of the blood (glucose and cortisol) were recorded after exposure to ammonia. The results show that the growth performance of tilapia was significantly improved by Cabanin® CSD supplementation (p < 0.05), while the survival rates were similar between control and Cabanin® CSD-supplemented diet groups. Superoxide dismutase activity and malondialdehyde levels in the blood serum were significantly different between the control and Cabanin® CSD-supplemented diet groups (p < 0.05). The malondialdehyde levels were significantly higher in the control group in comparison with the Cabanin® CSD-supplemented groups at day 1 and day 7 of refrigerated storage (p < 0.05). In the ammonia challenge test, the highest survival rate was observed in the Cabanin® CSD-supplemented diet groups compared to the control group. The fish serum glucose and cortisol levels increased in all the Cabanin® CSD-supplemented diet groups. In general, diets featuring Cabanin® CSD supplementation were found to exert beneficial effects on the growth performance, antioxidant capacity, and biochemical activity of tilapia under ammonia stress. [ABSTRACT FROM AUTHOR]

The use of continuous glucose monitors (CGMs) in individuals living without diabetes is increasing. The purpose of this study was to profile various CGM metrics around nutritional intake, sleep and exercise in a large cohort of physically active men and women living without any known metabolic disease diagnosis to better understand the normative glycemic response to these common stimuli. A total of 12,504 physically active adults (age 40 ± 11 years, BMI 23.8 ± 3.6 kg/m2; 23% self-identified as women) wore a real-time CGM (Abbott Libre Sense Sport Glucose Biosensor, Abbott, USA) and used a smartphone application (Supersapiens Inc., Atlanta, GA, USA) to log meals, sleep and exercise activities. A total of >1 M exercise events and 274,344 meal events were analyzed. A majority of participants (85%) presented an overall (24 h) average glucose profile between 90 and 110 mg/dL, with the highest glucose levels associated with meals and exercise and the lowest glucose levels associated with sleep. Men had higher mean 24 h glucose levels than women (24 h—men: 100 ± 11 mg/dL, women: 96 ± 10 mg/dL). During exercise, the % time above >140 mg/dL was 10.3 ± 16.7%, while the % time <70 mg/dL was 11.9 ± 11.6%, with the remaining % within the so-called glycemic tight target range (70–140 mg/dL). Average glycemia was also lower for females during exercise and sleep events (p < 0.001). Overall, we see small differences in glucose trends during activity and sleep in females as compared to males and higher levels of both TAR and TBR when these active individuals are undertaking or competing in endurance exercise training and/or competitive events. [ABSTRACT FROM AUTHOR]

Hyperglycemia, lipotoxicity, and insulin resistance are known to increase the secretion of extracellular matrix from cardiac fibroblasts as well as the activation of paracrine signaling from cardiomyocytes, immune cells, and vascular cells, which release fibroblast-activating mediators. However, their influences on vascular smooth muscle cells (vSMCs) have not been well examined. This study aimed to investigate whether contractile vascular vSMCs could develop a more synthetic phenotype in response to hyperglycemia. The results showed that contractile and synthetic vSMCs consumed high glucose in different ways. Lactate/GPR81 promotes the synthetic phenotype in vSMCs in response to high glucose levels. The stimulation of high glucose was associated with a significant increase in fibroblast-like features: synthetic vSMC marker expression, collagen 1 production, proliferation, and migration. GPR81 expression is higher in blood vessels in diabetic patients and in the high-glucose, high-lipid diet mouse. The results demonstrate that vSMCs assume a more synthetic phenotype when cultured in the presence of high glucose and, consequently, that the high glucose could trigger a vSMC-dependent cardiovascular disease mechanism in diabetes via lactate/GPR81. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDDs) are mainly induced by oxidative stress which produces excessive reactive oxygen species (ROS). Quercetin (QU) is a potent antioxidant with some effects on NDDs. This study prepared and characterized a novel glucose-modified QU liposome (QU–Glu–Lip), aiming not only to overcome QU's poor water solubility and bioavailability but also to deliver more QU to brain tissue to enhance its neuroprotective effect. QU–Glu–Lip possessed encapsulation efficiency (EE) of 89.9%, homogenous particle sizes (116–124 nm), small PDI value (<0.3), zeta value −1.363 ± 0.437 mV, proper pH and salt stability, and proper cytotoxicity. The glucose-modified liposome penetrated the blood–brain barrier (BBB) mediated via the glucose transporter 1 (GLUT1) and was taken by neuronal cells more efficiently than liposome without glucose, according to bEnd.3 and PC12 cell tests. QU–Glu–Lip attenuated H2O2-induced oxidative damage to PC12 with higher cell viability (88.42%) and lower intracellular ROS compared to that of QU. QU–Glu–Lip had higher brain target ability and delivered more QU to neuronal cells, effectively exerting the antioxidative neuroprotection effect. There is potential for the QU–Glu–Lip application for more effective treatment of NDDs. [ABSTRACT FROM AUTHOR]

Impaired skeletal muscle glucose uptake is a key feature in the development of insulin resistance and type 2 diabetes. Skeletal muscle glucose uptake can be enhanced by a variety of different stimuli, including insulin and contraction as the most prominent. In contrast to the clearance of glucose from the bloodstream in response to insulin stimulation, exercise-induced glucose uptake into skeletal muscle is unaffected during the progression of insulin resistance, placing physical activity at the center of prevention and treatment of metabolic diseases. The two Rab GTPase-activating proteins (RabGAPs), TBC1D1 and TBC1D4, represent critical nodes at the convergence of insulin- and exercise-stimulated signaling pathways, as phosphorylation of the two closely related signaling factors leads to enhanced translocation of glucose transporter 4 (GLUT4) to the plasma membrane, resulting in increased cellular glucose uptake. However, the full network of intracellular signaling pathways that control exercise-induced glucose uptake and that overlap with the insulin-stimulated pathway upstream of the RabGAPs is not fully understood. In this review, we discuss the current state of knowledge on exercise- and insulin-regulated kinases, hypoxia, nitric oxide (NO) and bioactive lipids that may be involved in the regulation of skeletal muscle glucose uptake. [ABSTRACT FROM AUTHOR]

Differentiation-inducing factor 1 (DIF-1), found in Dictyostelium discoideum, has antiproliferative and glucose-uptake-promoting activities in mammalian cells. DIF-1 is a potential lead for the development of antitumor and/or antiobesity/antidiabetes drugs, but the mechanisms underlying its actions have not been fully elucidated. In this study, we searched for target molecules of DIF-1 that mediate the actions of DIF-1 in mammalian cells by identifying DIF-1-binding proteins in human cervical cancer HeLa cells and mouse 3T3-L1 fibroblast cells using affinity chromatography and liquid chromatography–tandem mass spectrometry and found mitochondrial malate dehydrogenase (MDH2) to be a DIF-1-binding protein in both cell lines. Since DIF-1 has been shown to directly inhibit MDH2 activity, we compared the effects of DIF-1 and the MDH2 inhibitor LW6 on the growth of HeLa and 3T3-L1 cells and on glucose uptake in confluent 3T3-L1 cells in vitro. In both HeLa and 3T3-L1 cells, DIF-1 at 10–40 μM dose-dependently suppressed growth, whereas LW6 at 20 μM, but not at 2–10 μM, significantly suppressed growth in these cells. In confluent 3T3-L1 cells, DIF-1 at 10–40 μM significantly promoted glucose uptake, with the strongest effect at 20 μM DIF-1, whereas LW6 at 2–20 μM significantly promoted glucose uptake, with the strongest effect at 10 μM LW6. Western blot analyses showed that LW6 (10 μM) and DIF-1 (20 μM) phosphorylated and, thus, activated AMP kinase in 3T3-L1 cells. Our results suggest that MDH2 inhibition can suppress cell growth and promote glucose uptake in the cells, but appears to promote glucose uptake more strongly than it suppresses cell growth. Thus, DIF-1 may promote glucose uptake, at least in part, via direct inhibition of MDH2 and a subsequent activation of AMP kinase in 3T3-L1 cells. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) stands as one of the extensively investigated iron-binding glycoproteins within milk, exhibiting diverse biological functionalities. The global demand for LF has experienced consistent growth. Biotechnological strategies aimed at enhancing LF productivity through microbial expression systems offer substantial cost-effective advantages and exhibit fewer constraints compared to traditional animal bioreactor technologies. This study devised a novel recombinant plasmid, wherein the AOX1 promoter was replaced with a glucose-inducible G1 promoter (PG1) to govern the expression of recombinant porcine LF (rpLF) in Pichia pastoris GS115. High-copy-number PG1-rpLF yeast clones were meticulously selected, and subsequent induction with 0.05 g/L glucose demonstrated robust secretion of rpLF. Scaling up production transpired in a 5 L fermenter, yielding an estimated rpLF productivity of approximately 2.8 g/L by the conclusion of glycerol-fed fermentation. A three-step purification process involving tangential-flow ultrafiltration yielded approximately 6.55 g of rpLF crude (approximately 85% purity). Notably, exceptional purity of rpLF was achieved through sequential heparin and size-exclusion column purification. Comparatively, the present glucose-inducible system outperformed our previous methanol-induced system, which yielded a level of 87 mg/L of extracellular rpLF secretion. Furthermore, yeast-produced rpLF demonstrated affinity for ferric ions (Fe3+) and exhibited growth inhibition against various pathogenic microbes (E. coli, S. aureus, and C. albicans) and human cancer cells (A549, MDA-MB-231, and Hep3B), similar to commercial bovine LF (bLF). Intriguingly, the hydrolysate of rpLF (rpLFH) manifested heightened antimicrobial and anticancer effects compared to its intact form. In conclusion, this study presents an efficient glucose-inducible yeast expression system for large-scale production and purification of active rpLF protein with the potential for veterinary or medical applications. [ABSTRACT FROM AUTHOR]

Diabetes patients need to monitor blood glucose all year round. In this article, a novel scheme is proposed for blood glucose detection. The proposed sensor is based on a U-shaped microfiber prepared using hydrogen-oxygen flame-heating technology, and then 3-aminopropyltriethoxysilane (APTES) and glucose oxidase (GOD) are successively coated on the surface of the U-shaped microfiber via a coating technique. The glucose reacts with the GOD of the sensor surface to produce gluconic acid, which changes the effective refractive index and then shifts the interference wavelength. The structure and morphology of the sensor were characterized via scanning electron microscope (SEM) and confocal laser microscopy (CLM). The experimental results show that the sensitivity of the sensor is as high as 5.73 nm/(mg/mL). Compared with the glucose sensor composed of the same material, the sensitivity of the sensor increased by 329%. The proposed sensor has a broad application prospect in blood glucose detection of diabetic patients due to the advantages of miniaturization, high sensitivity, and good stability. [ABSTRACT FROM AUTHOR]

This research investigates the difference between products obtained through two hydrothermal carbonization treatments. Our aim is to synthesize metal-free, carbon-based catalysts for the oxygen reduction reaction (ORR) to serve as efficient and cost-effective alternatives to platinum-based catalysts. Catalysts synthesized using the traditional hydrothermal approach exhibit a higher electrocatalytic activity for ORR in alkaline media, despite their more energy-intensive production process. The superior performance is attributed to differences in the particle morphology and the chemical composition of the particle surfaces. The presence of functional groups on the surfaces of catalysts obtained via a traditional approach significantly enhances ORR activity by facilitating deprotonation reactions in an alkaline environment. Our research aims to provide a reference for future investigations, shifting the focus to the fine-tuning of surface chemical compositions and morphologies of metal-free catalysts to enhance ORR activity. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is associated with various complications, mainly caused by the chronic exposure of the cells to high glucose (HG) concentrations. The effects of long-term HG exposure in vitro accompanied by lipopolysaccharide (LPS) application on astrocytes are relatively unknown. We used cell medium with normal (NG, 5.5 mM) or high glucose (HG, 25 mM) for rat astrocyte cultures and measured the release of NO, IL-6, β-hexosaminidase and cell survival in response to LPS. We first demonstrated that HG long-term incubation of astrocytes increased the release of β-hexosaminidase without decreasing MTT-detected cell survival, suggesting that there is no cell membrane damage or astrocyte death but could be lysosome exocytosis. Different from what was observed for NG, all LPS concentrations tested at HG resulted in an increase in IL-6, and this was detected for both 6 h and 48 h treatments. Interestingly, β-hexosaminidase level increased after 48 h of LPS and only at HG. The NO release from astrocytes also increased with LPS application at HG but was less significant. These data endorsed the original hypothesis that long-term hyperglycemia increases proinflammatory activation of astrocytes, and β-hexosaminidase could be a specific marker of excessive activation of astrocytes associated with exocytosis. [ABSTRACT FROM AUTHOR]

Trichophyton rubrum is the leading causative agent of dermatophytosis worldwide. Keratinocytes are the first line of defense that drives an immune response against fungal invasion. Host-specific pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs) to trigger immunological pathways. Fungal cell wall components are the primary sources of fungal PAMPs, and some pathogens increase cell wall rearrangement to evade the immune system. Glycolysis and enhanced lactate levels are critical for improving host immune responses to fungal infections. Using reverse transcription–quantitative polymerase chain reaction (RT-qPCR), we evaluated the transcriptional responses of human genes involved in fungal recognition and glycolytic metabolism and fungal cell-wall-related genes in a co-culture model of human keratinocytes with T. rubrum. We observed the upregulation of several Toll-like receptors (TLRs), NOD-like receptors (NLRs), and glycolytic genes. Complementarily, we measured intra- and extracellular glucose levels and the increase in lactate production in the co-culture supernatant. We noted a distinct transcriptional regulation pattern of fungal cell-wall-related genes from fungal growth on keratin as the primary carbon source compared to co-culture with human keratinocytes. Our results showed new insights into the transcriptional adaptation of keratinocytes, particularly in regulating genes involved in sensing and metabolic processes, during the interaction with T. rubrum. [ABSTRACT FROM AUTHOR]

Simple Summary: Iodine is an essential trace element for thyroid hormone synthesis and plays a key role in extrathyroidal tissues. Recently, diabetes mellitus type 2 and elevated blood glucose have been associated with iodine excess. This study aims to elucidate the effect of iodine in mature adipocytes and pancreatic beta cells. Background: Epidemiological clinical reports have shown an association between iodine excess with diabetes mellitus type 2 and higher blood glucose. However, the relationship between iodine, the pancreas, adipose tissue, and glucose transport is unclear. The goal of this study was to analyze the effect of iodine concentrations (in Lugol solution) on glucose transport, insulin secretion, and its cytotoxic effects in mature 3T3-L1 adipocytes and pancreatic beta-TC-6 cells. Methods: Fibroblast 3T3-L1, mature adipocytes, and pancreatic beta-TC-6 cells were treated with 1 to 1000 µM of Lugol (molecular iodine dissolved in potassium iodide) for 30 min to 24 h for an MTT proliferation assay. Then, glucose uptake was measured with the fluorescent analog 2-NBDG, insulin receptor, Akt protein, p-Akt (ser-473), PPAR-gamma, and Glut4 by immunoblot; furthermore, insulin, alpha-amylase, oxidative stress, and caspase-3 activation were measured by colorimetric methods and the expression of markers of the apoptotic pathway at the RNAm level by real-time PCR. Results: Low concentrations of Lugol significantly induce insulin secretion and glucose uptake in pancreatic beta-TC-6 cells, and in adipose cells, iodine-induced glucose uptake depends on the serine-473 phosphorylation of Akt (p-Akt) and Glut4. Higher doses of Lugol lead to cell growth inhibition, oxidative stress, and cellular apoptosis dependent on PPAR-gamma, Bax mRNA expression, and caspase-3 activation in pancreatic beta-TC-6 cells. Conclusions: Iodine could influence glucose metabolism in mature adipocytes and insulin secretion in pancreatic beta cells, but excessive levels may cause cytotoxic damage to pancreatic beta cells. [ABSTRACT FROM AUTHOR]

Simple Summary: During pregnancy, especially the perinatal period, cows are often in a state of negative energy balance due to the imbalance of glucose metabolism. As the main energy substrate to promote fetal development, glucose is mainly obtained from the mother through the placenta and the provision of glucose to the fetus depends on the activity of glucose transporters distributed within the placental tissue. As the basic component of placental tissue, placental trophoblast cells participate in nutrient supply and metabolism between mother and fetus. However, a noticeable void exists in the study of the function and potential regulation mechanism of placental trophoblast cells in ruminants. In light of this, the bovine placental trophoblast cells were treated with different dose-concentration glucose and the gene expression of glucose transport carriers and enzymes related to glucose metabolism were detected. Moreover, the signaling pathway of placental-sensing energy level changes were studied to explore the mechanism of placenta mediating energy metabolism transmission between mother and fetus. The results showed that glucose regulates cellular glucose transport and metabolism by mediating the mTOR signaling pathway in bovine placental trophoblast cells. It has been confirmed that improving the energy level of the diet contributed to the greater reproductive performance and birth weight of calves in periparturient dairy cows. To investigate the effect of glucose on nutrient transport during fetal development, the bovine placental trophoblast cells (BPTCs) were cultured in media with different glucose concentrations (1, 2, 4, 8, or 16 mg/mL). Subsequently, the BPTCs were cultured in media with 1, 8 mg/mL glucose and 8 mg/mL glucose plus 100 nmol/L rapamycin (the inhibitor of mTOR pathway). Compared with the 1 mg/mL glucose, the addition of 8 mg/mL glucose stimulated cell proliferation, upregulated the mRNA abundance of the glucose transporter GLUT1 and GLUT4, and increased the activity of glucose metabolism-related enzyme glucose-6-phosphate dehydrogenease (G6PD), lactate dehydrogenase (LDHA) and phosphoglycerate kinase 1 (PGK1), as well as adenosine-triphosphate (ATP) content (p < 0.05).Furthermore, compared with the treatment of 1 mg/mL glucose, adding 8 mg/mL of glucose-upregulated gene expression in the mTOR signaling pathway, including phosphatidylinositol3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR) and 70 kDa ribosomal protein S6 kinase 2 (P70S6K) (p < 0.05).The supplementation of rapamycin downregulated the gene and protein expression of the mTOR signaling pathway, including mTOR, P70S6K, EIF4E-binding protein 1 (4EBP1), hypoxia-inducible factor 1-alpha (HIF-1α) and gene expression of glucose transporter upregulated by 8 mg/mL glucose (p < 0.05). Thus, these results indicated that the addition of 8 mg/mL glucose regulated the glucose transport and metabolism in BPTCs through the mTOR signaling pathway, thereby promoting the supply of nutrients to fetus. [ABSTRACT FROM AUTHOR]

In this work, we investigated the effect of multi-walled carbon nanotubes (MWCNTs) and bio-graphene (bG) on the structure and activity of glucose oxidase (GOx), as well as on the performance of the respective electrochemical glucose biosensors. Various spectroscopic techniques were applied to evaluate conformational changes in GOx molecules induced by the presence of MWCNTs and bG. The results showed that MWCNTs induced changes in the flavin adenine dinucleotide (FAD) prosthetic group of GOx, and the tryptophan residues were exposed to a more hydrophobic environment. Moreover, MWCNTs caused protein unfolding and conversion of α-helix to β-sheet structure, whereas bG did not affect the secondary and tertiary structure of GOx. The effect of the structural changes was mirrored by a decrease in the activity of GOx (7%) in the presence of MWCNTs, whereas the enzyme preserved its activity in the presence of bG. The beneficial properties of bG over MWCNTs on GOx activity were further supported by electrochemical data at two glucose biosensors based on GOx entrapped in chitosan gel in the presence of bG or MWCNTs. bG-based biosensors exhibited a 1.33-fold increased sensitivity and improved reproducibility for determining glucose over the sweat-relevant concentration range of glucose. [ABSTRACT FROM AUTHOR]

Metformin is the most prescribed glucose-lowering drug worldwide; globally, over 100 million patients are prescribed this drug annually. Some different action mechanisms have been proposed for this drug, but, surprisingly, no metabolite of metformin has ever been described. It was considered interesting to investigate the possible reaction of metformin with glucose following the Maillard reaction pattern. The reaction was first performed in in vitro conditions, showing the formation of two adducts that originated by the condensation of the two molecular species with the losses of one or two water molecules. Their structures were investigated by liquid chromatography coupled with mass spectrometry (HPLC-MS), tandem mass spectrometry (MS/MS) and accurate mass measurements (HRMS). The species originated via the reaction of glucose and metformin and were called metformose and dehydrometformose, and some structural hypotheses were conducted. It is worth to emphasize that they were detected in urine samples from a diabetic patient treated with metformin and consequently they must be considered metabolites of the drug, which has never been identified before now. The glucose-related substructure of these compounds could reflect an improved transfer across cell membranes and, consequently, new hypotheses could be made about the biological targets of metformin. [ABSTRACT FROM AUTHOR]

Diet-related lipotoxic stress is a significant driver of skeletal muscle insulin resistance (IR) and type 2 diabetes (T2D) onset. β2-adrenergic receptor (β-AR) agonism promotes insulin sensitivity in vivo under lipotoxic stress conditions. Here, we established an in vitro paradigm of lipotoxic stress using palmitate (Palm) in rat skeletal muscle cells to determine if β-AR agonism could cooperate with double C-2-like domain beta (DOC2B) enrichment to promote skeletal muscle insulin sensitivity under Palm-stress conditions. Previously, human T2D skeletal muscles were shown to be deficient for DOC2B, and DOC2B enrichment resisted IR in vivo. Our Palm-stress paradigm induced IR and β-AR resistance, reduced DOC2B protein levels, triggered cytoskeletal cofilin phosphorylation, and reduced GLUT4 translocation to the plasma membrane (PM). By enhancing DOC2B levels in rat skeletal muscle, we showed that the deleterious effects of palmitate exposure upon cofilin, insulin, and β-AR-stimulated GLUT4 trafficking to the PM and glucose uptake were preventable. In conclusion, we revealed a useful in vitro paradigm of Palm-induced stress to test for factors that can prevent/reverse skeletal muscle dysfunctions related to obesity/pre-T2D. Discerning strategies to enrich DOC2B and promote β-AR agonism can resist skeletal muscle IR and halt progression to T2D. [ABSTRACT FROM AUTHOR]