Glucose-sensitive films were prepared by the layer-by-layer (LbL) deposition of poly(ethyleneimine) (H-PEI) solution and DNA solution (containing glucose oxidase (GOx)). H-PEI/DNA+GOx multilayer films were constructed using electrostatic interactions. The (H-PEI/DNA+GOx)5 film was then partially decomposed by hydrogen peroxide (H2O2). The mechanism for the decomposition of the LbL film was considered to involve a more reactive oxygen species (ROS) that was formed by the reaction of hemin and H2O2, which then caused nonspecific DNA cleavage. GOx present in the LbL films reacts with glucose to generate hydrogen peroxide. Therefore, decomposition of the H-PEI/DNA+GOx)5 film was observed when the thin film was immersed in a glucose solution. A (H-PEI/DNA+GOx)5 film exposed to a glucose solution for periods of 24, 48 72, and 96 h indicated decomposition of the film increased with the time. The rate of LbL film decomposition increased with the glucose concentration. At pH and ionic strength close to physiological conditions, it was possible to slowly decompose the LbL film at a sub-millimolar glucose concentration.

Nanocomposite hydrogels offer remarkable potential for applications in bone tissue engineering. They are synthesized through the chemical or physical crosslinking of polymers and nanomaterials, allowing for the enhancement of their behaviour by modifying the properties and compositions of the nanomaterials involved. However, their mechanical properties require further enhancement to meet the demands of bone tissue engineering. Here, we present an approach to improve the mechanical properties of nanocomposite hydrogels by incorporating polymer grafted silica nanoparticles into a double network inspired hydrogel (gSNP Gels). The gSNP Gels were synthesised via a graft polymerization process using a redox initiator. gSNP Gels were formed by grafting 2-acrylamido-2-methylpropanesulfonic acid (AMPS) as the first network gel followed by a sequential second network acrylamide (AAm) onto amine functionalized silica nanoparticles (ASNPs). We utilized glucose oxidase (GOx), to create an oxygen-free atmosphere during polymerization resulting in higher polymer conversion compared to argon degassing. The gSNP Gels showed excellent compressive strengths of 13.9 ± 5.5 MPa, a strain of 69.6 ± 6.4%, and a water content of 63.4% ± 1.8. The synthesis technique demonstrates a promising approach to enhance the mechanical properties of hydrogels, which can have significant implications for bone tissue engineering and other soft tissue applications.

In this work, an enzymatic sensor, based on a bionanocomposite film consisting of a polyelectrolyte complex (PEC) [Chitosan/kappa-carrageenan] doped with gold nanoparticles (AuNPs) encapsulating glucose oxidase (GOD) deposited on a gold electrode (Au) for glucose sensing, is described. Using the electrocatalytic synergy of AuNPs and GOD as a model of enzyme, the variation of the current (µA) as a function of the log of the glucose concentration (log [glucose]), shows 3 times higher sensitivity for the modified electrode (283.9) compared to that of the PEC/GOD modified electrode (93.7), with a detection limit of about 5 µM and a linearity range between 10µM and 7mM. The response of the PEC/AuNPs/GOD based biosensor also presents good reproducibility, stability and negligible interfering effects from ascorbic acid, uric acid, urea and creatinine. The applicability of the PEC/AuNPs/GOD based biosensor was tested in glucose-spiked saliva samples and acceptable recovery rates were obtained.

Graphene-based composites have been widely explored for electrode and electrocatalyst materials for electrochemical energy systems. In this paper, a novel composite material of the reduced graphene oxide nanosheets (rGON) with gold nanoparticles (NPs) (rGON-AuNP) is synthesized, and its morphology, structure and composition are characterized by SEM, HRTEM, XRD, EDX, FTIR, Raman, and UV-Vis techniques. To confirm this material’s electrochemical activity, a glucose oxidase (GOD) is chosen as the target reagent to modify the rGON-AuNP layer to form GOD/rGON-AuNP/glassy carbon (GC) electrode. Two pairs of distinguishable redox peaks, corresponding to the redox processes of two different conformational GOD on AuNP, are observed on the cyclic voltammograms of GOD/rGON-AuNP/GC electrode. Both cyclic voltammetry and electrochemical impedance spectroscopy are employed to study the mechanism of direct electron transfer from GOD to GC electrode on the rGON-AuNP layer. In addition, this GOD/rGON-AuNP/GC electrode shows catalytic activity toward glucose oxidation reaction.

In this study, we designed a new biosensing membrane for the development of an electrochemical glucose biosensor. To proceed, we used a chitosan-based hydrogel that entraps glucose oxidase enzyme (GOx) and we crosslinked the whole matrix using glutaraldehyde, which is known for its quick and reactive crosslinking behavior. Then, the stability of the designed biosensors was investigated over time according to different storage conditions (in PBS solution at temperatures of 4 °C and 37 °C and in the presence or absence of glucose). In some specific conditions, we found that our biosensor is capable to keep its stability for more than six months of storage. We also included catalase to protect the biosensing membranes from the enzymatic reaction by-products (e.g., hydrogen peroxide). This design protects the biocatalytic activity of GOx and enhances the biosensor lifetime.

Diabetes is a major health concern that the next-generation of on-demand insulin releasing implants may overcome for personalized therapy. Therein, 3D-printed phenylboronic acid-containing subcutaneous implants with on-demand glucose-triggered drug release abilities are produced using high resolution stereolithography technology. To that end, the methacrylation of phenylboronic acid is targeted following a two-step reaction. The resulting photocurable phenylboronic acid derivative is accordingly incorporated within bioinert polyhydroxyethyl methacrylate-based hydrogels at varying loadings. The end result are sub-centimeter scaled 3D-printed bionert implants that can be remotely activated with 1,2-diols and 1,3-diols such as glucose for on-demand drug administration such as insulin. As a proof of concept, varying glucose concentration from hypoglycemia to hyperglycemia levels readily allow the release of pinacol, i.e. a model molecule with similar release properties than insulin, at respectively low and high rates. In addition, the results demonstrated that adjusting the geometry and size of the 3D-printed part is a simple and suitable method for tailoring the release behavior and dosage.

Oxidoreductase (OXR) enzymes are in high demand for biocatalytic applications in food industry and cosmetics: glucose oxidase (GOx), cellobiose dehydrogenase (CBDH), bioremediation: horseradish peroxidase (HRP), laccase (LAC), and medicine for biosensors and miniature biofuel cells (GOx, CBDH, LAC, HRP). They can be used in a soluble form and/or within the yeast cell walls expressed as chimeras on the surface of yeast cells (YSD), such as P. pastoris and S. cerevisiae. However, most of the current studies suffer from either low yield for soluble enzyme expression or low enzyme activity when expressed as chimeric proteins using YSD. This is always the case in studies dealing with heterologous expression of oxidoreductase enzymes, since there is requirement not only for multiple OXR genes integrations into the yeast genome (super transformations), and codon optimization, but also very careful design of fermentation media composition, and fermentation conditions during expression due to need for adding transition metals (copper, iron), and metabolic precursors of FAD and heme. Therefore, scientists are still trying to find optimal formula using above mentioned approaches, and most recently also using protein engineering and directed evolution for additional increase in the yield of recombinant enzyme production. In this review article we will cover all the current state of the art technologies and most recent advances in the field that yielded high expression level for some of these enzymes in specially designed expression/fermentation systems. We will also tackle and discuss new possibilities for further increase in fermentation yield by the cutting-edge technologies such are directed evolution, protein and strain engineering, high-throughput screening methods based on in vitro compartmentalization, flow cytometry and microfluidics.

L-gulonolactone oxidase enzyme (GULO) catalyzes the last step of L-ascorbic acid (vitamin C) biosynthesis. This enzymatic activity is lost in primates. The full-length rat GULO has been previously produced in plants and demonstrated to be active. In this study, we compare activity of two variants of GULO produced in Escheriachia coli cells, full-length rat GULO (fGULO) and its C-terminal catalytic domain (cGULO). The expression and purification of the recombinant proteins were optimised and their biological activity was confirmed by two methods, the GULO activity assay in the protein extracts and the ‘in-gel’ staining for GULO activity. Both variants of recombinant GULO were biologically active in both assays. However, cGULO is more promising than fGULO for ascorbic acid production because it is more efficiently produced by bacteria.

Glucose is a simple sugar molecule. The sugar molecule is chemically symbolised as C6H12O6. This means that the glucose molecule contains 6 carbon atoms (C), 12 hydrogen atoms (H) and 6 oxygen atoms (O). In human blood, the molecule glucose circulates as blood sugar. Normally after eating or drinking, our body breaks down the sugars in food and uses them to obtain energy for our cells. To do this, our pancreas produces insulin. Insulin "pulls" sugar from the blood and puts it into the cells for use. If someone has diabetes, their pancreas can't produce enough insulin. As a result, the level of glucose in the blood rises. This can lead one to many potential complications, including blindness, disease, nerve damage, amputation, stroke, heart attack and damage to blood vessels etc. In this study, a non-invasive method for monitoring blood glucose has been developed and is therefore easily usable. The device developed can measure the glucose level continuously and eliminates the disadvantages of the invasive system. Near-IR sensors (optical sensors) were used to estimate the concentration of glucose in the blood; these sensors have a wavelength of 940 nm. The sensor is placed on the tip of the finger and the output of the optical sensor is then connected to the microcontroller at the analogue input. Another sensor used, but only to provide more medical information was the heartbeat sensor. After processing and regression analysis, the glucose level is predicted, and data is sent via the Bluetooth network to a developed APP. The results of the implemented device were compared with available invasive methods. The study consists of a hardware platform inserted into an armband and then a small black parallelepiped-shaped box in which the optical sensors are inserted. The hardware consists of a microcontroller, a Near-IR optical sensor, a heartbeat sensor and a Bluetooth module.

Background: Several kinds of research say that adjuvant blood glucose and blood pressure are usual, but an efficient solution for medical application count remains. This review analyzes the pandemic blood pressure and blood glucose to identify the publications which tell about the clinical practices and research gaps in systematic research.Methods: A study guides to identify the research of Blood Pressure (BP) and Blood Glucose. In order to analyze the recent innovations and research on BP and Blood glucose, the relevant publications and literature from journals were identified.Results: Co-morbidity of BP and Blood glucose is reported as very high. The commonness of blood pressure is thrice as high in type I diabetes patients and almost two times higher in type II diabetes patients when compared to others without Diabetes. The pervasiveness of getting depression is more in the female when compared with men. A detailed study about the linkage of BP and blood glucose tells that the relationship between them is not exactly clear.Limitations: Nearly all reviews providing the linkage of BP and blood glucose are with some limitations and they are not providing any clear conclusion.Conclusions: Present research tells that people having high blood glucose will have a greater chance of getting high blood pressure. More research is needed to state the linkage between BP, blood glucose, and the growth of diabetes mellitus issues and to provide support for managing Diabetes.

Resveratrol is a well-known natural polyphenol with a plethora of pharmacological activities. As a potent antioxidant, resveratrol is highly oxidizable, and readily reacts with reactive oxygen species (ROS). Such a reaction not only leads to a decrease in ROS levels in a biological environ-ment but may also generate a wide range of metabolites with altered bioactivities. Inspired by this notion, in the current study, our aim was to take a diversity-oriented chemical approach to study the chemical space of oxidized resveratrol metabolites. Chemical oxidation of resveratrol and a bioactivity-guided isolation strategy using xanthine oxidase (XO) and radical scavenging activities led to the isolation of a diverse group of compounds, including a chlorine-substituted compound (2), two iodine-substituted compounds (3 and 4), two viniferins (5 and 6), an eth-oxy-substituted compound (7) two ethoxy-substituted dimers (8 and 9). Compounds 4, 7, 8 and 9 are reported here for the first time. All compounds without ethoxy-substitution exerted stronger XO inhibition than their parent compound, resveratrol. By enzyme kinetic and in silico docking studies compounds 2, 3 and 4 were identified as potent competitive inhibitors of the enzyme while the viniferins acted as mixed-type inhibitors. Further, compounds 2 and 9 had better DPPH scavenging activity and oxygen radical absorbing capacity than resveratrol. Our results suggest that the antioxidant activity of resveratrol is modulated by the effect of a cascade of chemically stable oxidized metabolites, several of which have significantly altered target specificity as compared to their parent compound.

We have designed cell penetrating peptides that target the leucine zipper transcription factors ATF5, CE-BPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not normal cells, in vitro and in vivo. While such peptides have the potential for clinical application, their mechanisms of action are not fully understood. Here, we show that one such peptide, Dpep, compromises glucose uptake and glycolysis in a cell-context-dependent manner (in about 2/3 of cancer lines assessed). These actions are dependent on induction of tumor suppressor TXNIP (thioredoxin interacting protein) mRNA and protein. Knockdown studies show that TXNIP significantly contributes to apoptotic death in those cancer cells in which it is induced by Dpep. The metabolic actions of Dpep on glycolysis led us to explore combinations of Dpep with clinically approved drugs metformin and atovaquone that inhibit oxidative phosphorylation and that are in trials for cancer treatment. Dpep showed additive to synergistic activities in all lines tested. In summary, we find that Dpep induces TXNIP in a cell-context-dependent manner that in turn sup-presses glucose uptake and glycolysis and contributes to apoptotic death of a range of cancer cells.

There is growing interest in the discovery of novel xanthine oxidase inhibitors for gout prevention and treatment with fewer side effects. This study aimed to identify the xanthine oxidase (XO) inhibitory potential and drug-likeness of the metabolites present in the methanolic leaves extract of Anastatica (A.) hierochuntica L. using in vitro and in silico models. The extract-derived metabolites were identified by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Molecular docking predicted the XO inhibitory activity of the identified metabolites and validated the best scored in vitro XO inhibitory activities for experimental verification as well as predictions of their anticancer, pharmacokinetic and toxic properties, oral bioavailability, and endocrine disruption using SwissADMET, PASS, ProTox-II and Endocrine Disruptome web servers. A total of 12 metabolites with a majority of flavonoids were identified. Rutin, quercetin and luteolin flavonoids demonstrated the highest ranked docking score of -12.39, -11.15 and -10.43, respectively, while the half-maximal inhibitory concentration (IC50) values of these metabolites against XO activity were 11.35 µM, 11.1 µM and 21.58 µM, respectively. In addition, SwissADMET generated data related to physicochemical properties and drug-likeness of the metabolites. Similarly, PASS, ProTox-II and Endocrine Disruptome prediction models stated the safe and potential use of these natural compounds. However, in vivo studies are necessary to support the development of prominent and promising therapeutic use of A. hierochuntica methanolic leaves extract-derived metabolites as XO inhibitors for the prevention and treatment of hyperuricemic and gout patients. Furthermore, the predicted findings of the present study open a new paradigm for these extract-derived metabolites by revealing novel oncogenic targets for the potential treatment of human malignancies.

The GLUT members belong to a family of glucose transporter proteins that facilitate glucose transport across the cell membrane. The mammalian GLUT family consists of thirteen members (GLUTs 1-12 and HMIT). Humans have a recently duplicated GLUT member, GLUT14. Avians express the majority of GLUT members. The arrangement of multiple GLUTs across all somatic tissues signifies the important role of glucose across all organisms. Defects in glucose transport have been linked to metabolic disorders, insulin resistance and diabetes. Despite the essential importance of these transporters, our knowledge regarding GLUT members in avians is fragmented. It has been clear that there are no chicken orthologs of mammalian GLUT4 and GLUT7. Our examination of GLUT members in the chicken revealed that some chicken GLUT members do not have corresponding orthologs in mammals. We review the information regarding GLUT orthologs and their function and expression in mammals and birds, with emphasis on chickens and humans.

Background. Transferrin receptor 1 (TfR1), glucose transporter 1 (GLUT1), and CD98hc are candidates for targeted therapy at the blood-brain barrier (BBB). Our objective was to challenge the expression of TfR1, GLUT1, and CD98hc in brain capillaries by the histone deacetylase inhibitor (HDACi) valproic acid (VPA). Methods. Primary mouse brain capillary endothelial cells (BCECs) and brain capillaries isolated from mice injected intraperitoneally with VPA were examined using RT-qPCR and ELISA. Targeting to the BBB was performed by injecting monoclonal anti-TfR1 (Ri7217)-conjugated gold nanoparticles measured using ICP-MS. Results. In BCECs co-cultured with glial cells, Tfrc mRNA expression was significantly higher after 6 h VPA returning to baseline after 24 h. In vivo Glut1 mRNA expression was significantly higher in males, but not females', receiving VPA, whereas Cd98hc mRNA expression was unaffected by VPA. TfR1 increased significantly in vivo after VPA, whereas GLUT1 and CD98hc were unchanged. Uptake of anti-TfR1-conjugated nanoparticles was unaltered by VPA in spite upregulated TfR expression. Conclusions. VPA upregulates TfR1 in brain endothelium in vivo and in vitro. VPA does not increase GLUT1 and CD98hc proteins. The increase in TfR1 does not result in higher anti-TfR1 antibody targetability, suggesting targeting sufficiently occurs with available transferrin receptors without further contribution from accessory VPA-induced TfR1.

Postprandial glucose levels between 4 and 7.9 hours (PPG4–7.9h) correlate with mortality from various diseases including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4–7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4–7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4–7.9h predicted using this model. Receiver operating characteristic curve analysis showed that predicted PPG4–7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. Simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4–7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4–7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants.

Salidroside, a valuable phenylethanoid glycoside, is obtained from plants belonging to the Rhodiola genus, known for its diverse biological properties. At present, salidroside is still far from large-scale industrial production due to the lower titer and higher process cost. In this study, we constructed a biosynthetic pathway from L-tyrosine to salidroside in Saccharomyces cerevisiae. To increase sali-droside production, we for the first time constructed an in vivo UDP-glucose regeneration system that sucrose synthase GmSUS worked in conjunction with UDP-glucose transferase RrUGT33 to improve the UDP-glucose availability with inexpensive sucrose as the consumed substrate. Finally, the molar conversion rate of L-tyrosine could reach 95%. To further reduce the cost, co-culture with E. coli that synthesized L-tyrosine de novo resulted in an 81% reduction in the final substrate cost per 1 kg of salidroside compared to the initial cost. The final titer of salidroside obtained 3.8 g/L and was the highest titer achieved at the Shake-Flask-Level in the existing reports. And this marked the first successful synthesis of salidroside in an in situ enhanced UDP-glucose system using sucrose. This accomplishment laid a robust groundwork for further investigations into the synthesis of other notable glycosides and natural compounds.

Intermittent religious fasting increases a risk of hypo- and hyperglycemia in individuals with diabetes, but its impact in those without diabetes is poorly investigated. The study aim was to examine the effects of religious Bahá'í fasting (BF) on glycemic control and variability and compare these effects with time-restricted eating (TRE). In a three-arm randomized controlled trial, 16 subjects without diabetes were assigned to a BF, 16:8 TRE or control group. Continuous glucose monitoring and food intake documentation was conducted before and during the 19 days of intervention, and 24-hour mean glucose, glycemic variability indices, and glucotypes were assessed. BF and TRE groups, but not the control group, markedly reduced the daily eating window while maintaining macronutrient composition. Only the BF group decreased caloric intake (-677.8 ± 357.6 kcal, p=0.013), body weight (-1.92 ± 0.95 kg, p=0.011) and BMI (-0.65 ± 0.28 kg, p=0.006). Higher maximum glucose values were observed during BF in the within-group (+1.41 ± 1.04, p=0.039) and between-group comparison (BF vs. Control: p= 0.010 and TRE vs. BF: p= 0.022). However, there were no alterations of 24-hour mean glucose, intra- and inter-day glycemic variability indices, or glucotypes in any group. Proportions of time above and below range (70-180mg/dl) and HbA1c values remained unchanged. BF and TRE do not exhibit negative effects on glycemic control and variability in subjects without diabetes.

Global warming and the associated increasing frequency of heatwaves are on the rise leading to numerous health complications. Diabetic patients are more vulnerable to heat exposure than healthy individuals, owing to their impaired sweating ability, however, little is known about how heat exposure may impact the function of skin cells, commonly keratinocytes. Our recent report provided the first proof-of-concept revealing that the metabolic composition of sweat EVs is associated with metabolic changes in healthy individuals and type 2 diabetes patients. Given this and the shared cellular proprieties of eccrine sweat glands with keratinocytes, we questioned whether the metabolic changes in sweat EVs may mirror the responses of keratinocytes upon heat exposure. To this, we exposed HaCat, which were maintained in low (mimicking healthy condition) and high glucose (mimicking diabetes condition) to acute (90 min), chronic (48 h), and repetitive heat exposure at 40 ⁰C. Through conducting a set of experiments including a targeted metabolomics approach, Greiss assay, western blotting analysis, and electron microscopy studies. The data demonstrate that heat exposure results in substantial changes of metabolite levels belonging to amino acids, pyrimidine metabolism, and glycolysis pathways in high glucose maintained HaCat cells when compared to those noted in low glucose condition. Exploring the molecular mechanisms through which heat exposure may impact the metabolic composition in keratinocytes, our discoveries highlight nitric oxide (NO) as a novel biomarker that the level is correlated with heat duration and frequency. Furthermore, data reveal that the HSP-70 protein levels and mitochondrial morphology are consequently altered. This study provides evidence of shared metabolic alterations in keratinocytes and sweat EVs collected from clinical study and proposes, for the first time, NO as a novel biomarker for monitoring changes in health and diabetes upon heat exposure.

BACKGROUND This study investigated the association of postprandial plasma glucose (PPG) with cancer mortality using a general cohort of US adults. METHODS This cohort study included 14,860 US adults who attended the third National Health and Nutrition Examination Survey from 1988 to 1994, with mortality being followed up to December 31, 2019. The experimental exposures were levels of plasma glucose, including PPG with a fasting time of 0-3.9 h (PPG_0-3.9h) and 4-7.9 h (PPG_4-7.9h), plasma glucose with a fasting time ≥ 8 h (PG_fasting), and plasma glucose at 2 h after oral glucose tolerance test (PG_2hOGTT). Plasma glucose-associated cancer mortality risk was assessed using Cox proportional hazards models. RESULTS A 1-natural-log-unit increase in PPG_4-7.9h was associated with a higher multivariate-adjusted risk for cancer mortality [hazard ratio (HR), 3.24; 95% confidence interval (CI), 1.50-7.00]. However, PPG_0-3.9h, PG_fasting, PG_2hOGTT, hemoglobin A_1c, and insulin were not significantly associated with cancer mortality. The positive association of PPG_4-7.9h with cancer mortality remained in those without a prior diagnosis of cancer. CONCLUSIONS High PPG_4-7.9h is associated with a higher cancer mortality risk in US adults. Lowering PPG_4-7.9h may reduce cancer mortality.

Keywords: CYP5122A1; ERG25; Leishmania; Sterol; Demethylase.

Aim: Aging is companied by deteriorations of insulin resistance (IR) and insulin secretion. However, little is known about the roles of aging on different phases of insulin secretion (ISEC); i.e., the first- and second-phase of insulin secretion (FPIS, SPIS) and glucose effectiveness (GE). Methods: Totally 169 individuals (43 men and 126 women) with the similar fasting plasma glucose (FPG: 90 mg/dL) and BMI (men: 23 kg/m2, women 22 kg/m2) were enrolled. IR, FPIS, SPIS, and GE were estimated using our previously developed equations shown below. Pearson correlation analysis was conducted to assess the correlations between age and four diabetes factors (DFs: IR, FPIS, SPIS and GE). The equations that are used to calculate the DF in the present study were built and published by our group. Results: The age of the participants ranged from 18- to 78-year-old. Men had higher FPIS but lower HDL-C levels than women (2.067±0.159, 1.950±0.186 μU/min and 1.130±0.306, 1.348±0.357 mmol/dl, accordingly). The results of Pearson correlation revealed that age was negatively related to IR and GE in both genders (IR: r = -0.39, p < 0.001 for men, r = -0.24, p < 0.003 for women; GE: r = 0.66, p < 0.001 for men, r = 0.78, p < 0.001 for women). In the meanwhile, FPIS was also only found to be negatively correlated with age in female (r = -0.238, p = 0.003). But there was no different with SPIS and age in both of genders. Conclusions: We have found that in Chinese with normal FPG level (90 mg/dl) and body mass index (men: 23 kg/m2, women: 22: kg/m2), age is negatively related to IR and GE in both genders. At the same time, only FPIS was found to be negatively related to age in women. The tightness of their relationships, from the highest to the lowest are, GE, FPIS and IR accordingly. The importance of GE should be re-evaluated. These results should be interpreted with caution because of the small sample size.

The present protocol described extraction of active polyphenol oxidase and peroxidase from a plant rich in phenolics and chlorophylls in the post-harvest browning syndrome of B. myrtifolia. Initially, general optimisation using conventional enzyme extractions was performed. However, along with membrane-bound proteins, chlorophylls and phenols were also released with Triton X (TTX). With a view to obtaining high enzymatic activity, removal of the released chlorophylls and phenols by formation of TTX-114 micelles in the detergent rich phase after high-temperature induced phase separation was tested.

Collagen, the most abundant structural protein found in mammals, plays a vital role as a constituent of the extracellular matrix (ECM) that surrounds cells. Collagen fibrils are strengthened through the formation of covalent cross-links, which involve complex enzymatic and non-enzymatic reactions. Lysyl oxidase (LOX) is responsible for catalyzing the oxidative deamination of lysine and hydroxylysine residues, resulting in the production of aldehydes, allysine, and hydroxyallysine. These intermediates undergo spontaneous condensation reactions, leading to the formation of immature cross-links, which are the initial step in the development of mature covalent cross-links. Additionally, non-enzymatic glycation contributes to the formation of abnormal cross-linking in collagen fibrils. During glycation, specific lysine and arginine residues in collagen are modified by reducing sugars, leading to the creation of Advanced Glycation End-products (AGEs). These AGEs have been associated with changes in the mechanical properties of collagen fibers. Interestingly, various studies have reported that plant polyphenols possess amine oxidase-like activity and can act as potent inhibitors of protein glycation. This review article focuses on compiling literature describing polyphenols with amine oxidase-like activity and antiglycation properties. Specifically, we explore the molecular mechanisms by which specific flavonoids impact or protect the normal collagen cross-linking process. Furthermore, we discuss how these dual activities can be harnessed to generate properly cross-linked collagen molecules, thereby promoting the stabilization of highly organized collagen fibrils.

Plant sulfite oxidase )SO( is a molybdo-enzyme responsible for the oxidation of excess SO₂/sulfite into non-toxic sulfate. The effect of toxic sulfite level on leaves and fruits was studied in tomato plants with different SO expression levels: wild-type (WT), SO overexpression (OE) and SO RNA interference (Ri) plants. Leaf discs and ripe fruit of plants lacking SO were more susceptible, whereas SO OE plants were more resistant as revealed by remaining chlorophyll content and tissue damage levels. Application of molybdenum further enhanced the tolerance of leaf discs to sulfite by enhancing SO activity in SO OE lines, but not in WT or Ri plants. Notably, incubation with tungsten, the molybdenum antagonist, overturned the effect of molybdenum spray in SO OE plants, revealed by remaining chlorophyll content and SO activity. The results indicate that SO determines, in tomato leaves and ripe fruits, the resistance to toxic sulfite and the application of molybdenum enhances sulfite resistance in OE plants by increasing SO activity. The results suggest that overexpressing SO mechanism can be employed in agriculture with or without molybdenum application, for the development of more tolerate crops and vegetables to higher concentrations of sulfite/SO₂ containing postharvest treatments.

To make low-cost catalytic materials that mimic the activity of tyrosinase enzymes (Catechol oxidase) is an exciting challenge of biochemical technology. Herein, we report the synthesis of a series of acylhydrazone-pyrazoles based biomolecule materials (L1-L7) with superior catecholase activity. These biomolecules were synthesized by a one pot chemical condensation between 5-methyl-1H-pyrazole-3-carbohydrazide and benzaldehyde derivatives. The X-ray single crystal diffraction (XRD) for two ligands L1 and L2 have been studied and the molecular structures were optimized and confirmed using the density functional theory (DFT/B3LYP) method. Copper (II) complexes of the biomolecules (L1-L7), generated in-situ, and were studied for their catalytic activities towards the oxidation reaction of catechol to ortho-quinone according to two parameters: the nature of the ligand and the nature of counter anion. The L7-CuSO4 was found to have an excellent catalytic activity (105.42 μmol·L−1·min−1) among the catalysts recently reported in the existing literature.

Activity of the Nox1 centered NADPH oxidase complex depends on the activator NoxA1 and the organizer NoxO1. NoxO1 itself is not involved in electron transfer for superoxide formation. Instead, by creating proximity of all components in the right place NoxO1 enables a constitutive formation of reactive oxygen species by that complex. All subunits should form the complex in a 1:1:1 ratio. When analyzing different cell lines in this study, we found an unequal expression of the component on mRNA level with an excess of NoxO1. Even with plasmid-based overexpression of individual components of Nox1 centered NADPH oxidase complex results in different expression of their mRNA, with NoxO1 mRNA being best expressed. Despite an unchanged high level of NoxO1 mRNA over a wide range of transfected plasmid, protein expression is increased with accelerating plasmid concentrations. We thought to analyze the ability of NoxO1 to induce ROS formation, when present in different ratio to Nox1 and NoxA1. To this end, we used Hek293 cells with constitutive expression of Nox1 and NoxA1 transfected with increasing concentrations of NoxO1. Our results suggest that ROS formation by the Nox1 centered NADPH oxidase strongly depends on the level of NoxO1 and a surplus of NoxO1 further increases the activity of the complex.

The cyclic AMP-responsive element-binding protein H (CREBH, encoded by CREB3L3) is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins upregulating LPL activity. A deficiency of CREBH in mice leads to severe hypertriglyceridemia. CREBH, in synergy with PPARα, has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis. CREBH binds to and functions as a co-activator for both PPARα and LXRα in regulating gene expression of lipid metabolism. Furthermore, intestinal CREBH in overexpression reduces cholesterol absorption and suppresses high-cholesterol diet-induced fatty liver. Conversely, a deficiency of CrebH in mice fed on various high-fat diets leads to severe fatty liver. Thus, CREBH could be a therapeutic target in the treatment of metabolic diseases.

Background: Diet is a risk factor for gestational diabetes mellitus (GDM). There are few studies on women´s diet and glucose tolerance test (GTT) results. Objective: To evaluate the relationship between previous diet and the number of abnormal values on the diagnostic GTT in women with GDM. We hypothesized there would be an inverse relation between antioxidant micronutrient consumption and the number of abnormal GTT values. Methods: This cross-sectional study included 60 women diagnosed with GDM (2-hours, 75g-GTT). Shortly after diagnosis, participants answered a validated food frequency questionnaire to assess food consumption in the last 6 months. Mann-Whitney´s test was used to compare the dietary intake of participants with one (group 1) versus two-three (group 2) abnormal GTT values. Results: Participant characteristics were similar. There were no significant differences between groups in median intake of total calories, carbohydrates, lipids and proteins. Participants in group 1 had significantly higher intakes of fiber (11.9 vs. 11.0 g/day p= 0.049), vitamin D (40.6 vs. 40.4 mcg/day p= 0.049) and vitamin C (180.0 vs. 151.0 mg/day p= 0.008) than those in group 2. Conclusion: Results suggest a possible association between consumption of fiber and some antioxidant micronutrients and GDM severity at the time of diagnosis.

Diabetic patients need long-term and frequent glucose monitoring to assist in insulin intake. The current finger-prick devices are painful and costly which make noninvasive glucose sensors highly demanded. In this review paper, we discuss several advanced electromagnetic (EM) wave based technologies for noninvasive glucose measurement, including infrared (IR) spectroscopy, photoacoustic (PA) spectroscopy, Raman spectroscopy, fluorescence, optical coherent tomography (OCT) and microwave sensing. Development and progress of each method are discussed regarding fundamental principle, system setup and experimental results. Despite the promising achievements reported previously, there is no established product to obtain FDA approval or survive marketing test. Limitations and prospects of these techniques are discussed at the end of this review.

Background: Study to assess glucose levels of people with type 1 diabetes (T1D) overnight based on insulin type and timing. Methods: Real-world, retrospective study in T1D using multiple daily insulin injections. Contin-uous glucose monitoring and insulin injections data were collected for ten hours after dinner us-ing the Insulclock® connected cap. Meal events were identified using ROC detection methodology. The timing of rapid insulin, second injections, and the type of insulin analogs used were evaluat-ed. Results: Nocturnal profiles (n=775, 49 subjects) were analyzed. Higher glucose AUC over 180mg/dL was observed in delayed injections (number; %; mg/dL x h): -45-15min (n=136; 17.5%, 175.9 ±271.0); -15-0min (n= 231; 29.8%, 164.0 ±237.1); 0+45min (n= 408; 52.6%, 203.6 ±260.9), (p 0.049). The use of ultrarapid (FiAsp®) (URI) vs rapid insulin analogs (RI) was associated with less hypoglycemia events (7.1 vs 13.6%; p 0.005) and TBR70 (1.7 +6.9 vs 4.6 +13.9%; p 0.003). Us-ers of glargine U300 vs degludec had higher TIR (70.7 vs 58.5 %) (Adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n= 144, 18.6%) was associated with higher hypoglycemia events (18.1 vs 9.5%; p 0.003), TBR70 (5.5 +14.2 vs 3.0 +11.1%; p 0.003), glucose AUC over 180 mg/dL (226.1 +257.8 vs 178.0 +255.3 mg/dL x h; p 0.001), and lower TIR (56.0 +27.4 vs 62.7 +29.6 mg/dL x h; p 0.004). Conclusions: Dinner rapid insulin timing, insulin types and correction injections affect nocturnal glucose profile in T1D.

Background/objectives: The health benefits of resistant starch are well known, but there have not been many studies available documenting the effect of basmati rice products containg resistant starch upon blood glucose level and lipid profile in vivo efficacy. Methods: Common cooking methods were used to prepare basmati rice products including two boiling methods viz. boiling 1 (boiling by absorption), boiling 2 (boiling in extra amount of water), frying and pressure cooking. The cooked rice were held at various temperatures and times: it was made fresh (T1), kept at room temperature (20–22°C) for 24 h (T2), kept at 4°C for 24 h (T3), and then reheated after being kept at 4°C for 24 h(T4). Next, the products' proximate composition, total dietary fibre (soluble and insoluble), resistant starch (RS), and In vitro starch digestion rate (rapidly and slowly digested starch) were examined. The effect of RS on blood glucose and lipid profile were measured in humans and rats. Histopathological study of liver and pancreas in rats were also observed. Results: The basmati rice prepared by boiling 1 and stored with T3 was found more effective to control blood glucose and lipid profile. Similarly in rats, the blood glucose level, cholesterol, triglycerides and LDL were reduced about 29.7, 37.9, 31.3 and 30.5% respectively, after consumption of basmsti rice prepared by boiling 1 and stored at T3. Conclusion: Rice products stored at 4⁰C have a high amount of resistant starh, insoluble dietary fibre, slowly digestible starch and low glycemic index. Thus helps to inhibit glycogen and lipid synthesis.

In solid cancer surgery, oxidative stress (OS) is of particular interest because both the malignancy itself and the surgical intervention are major contributors to the modulation of OS levels. This study aimed to investigate the effects of solid cancer surgery on OS levels. Because solid cancer is often accompanied by intense cell death, the study specifically focused on the pathway leading to uric acid formation, (i.e. adenosine deaminase (ADA) and xanthine oxidase (XO). Ische-mia-modified albumin (IMA), a recognized marker of oxidative stress, and plasma redox poten-tial (RP) were also measured. Thirty-six patients undergoing major solid cancer surgery (median age 68 years (58-76), 23 men and 13 women) and thirty controls (62 years (51-80)) were included. During the surgical procedure, serum ADA levels did not change significantly (10.4 International Units (IU) (6.9 – 13.7) vs. 8 IU (6 – 12); p = 0.47). In contrast, XO (IU), IMA (Arbitrary Units(AU)) and redox potential (mV) decreased significantly (22.5 IU (11 – 63) vs. 8.4 IU (5 – 27); p = 0.0041, 89 AU (69 – 105) vs. 74 AU (66 – 80); p = 0.01 and 98 mV (78 – 118) vs. 79 mV (65 – 101); p = 0.033). The correlation between XO and IMA or redox potential was positive (Spearman’s r = 0.32 ; p = 0.007, and r = 0.58; p < 0.001, respectively). XO was negatively correlated with ADA (r = -0.26; p = 0.03). Redox potential was positively correlated with IMA (r = 0.26; p = 0.04) and nega-tively correlated with ADA (r = -0.25 ;p = 0.04). We found that a major source of OS in solid cancer could be the result of an increase in xanthine oxidase activity and that the global effect of solid cancer surgery is a significant decrease in OS levels. We also found that ADA and XO were inversely correlate, suggesting the existence of a negative retrocontrol between the production of free radicals and the production of their sub-strate. Finally, our study highlights the potential value of XO inhibitors as adjuvant therapy in solid tumor surgery.

Hyperuricemia is mainly caused by the overproduction of uric acid (UA) catalyzed from xanthine by xanthine oxidase (XO) in abnormal purine metabolism in human body. There is an increasing demand for developing novel XO inhibitors of plant origins. The inhibition kinetics and type as well as actions of hesperetin against XO were investigated in vitro using multi-spectroscopic methods including UV-Vis absorption, Fourier transform infrared spectroscopy (FT-IR), fluorescence spectroscopy and molecular docking simulation. Results indicated that hesperetin reversibly inhibited XO in a competitive manner with an inhibition constant (Ki) value of (2.15 ± 0.05) × 10-6 mol/L. Hesperetin had a higher scavenging rate against O2- radical generated by the XO reaction system. The binding of hesperetin to the active site of XO altered the protein’s secondary structure as demonstrated by FT-IR and fluorescence spectra. Molecular docking study revealed that hesperetin had highly affinity to XO and the bonding of hesperetin to the molybdopterin (Mo-pt) active center inhibited not only substrate entry, but also prevented oxygen binding to flavin adenine dinucleotide (another active center in XO). Additionally, hydrophobic interactions and hydrogen bonds contributed to the stabilization of the hesperetin-XO complex. The results suggested that hesperetin be a promising natural XO inhibitor to alleviate hyperuricemia and gout.

The objective of this pilot study was to compare glucose concentrations in capillary blood (CB) samples analysed in a laboratory by a validated method and glucose concentrations measured in the interstitial fluid (ISF) by continuous glucose monitoring under different physical activity levels in a postprandial state in healthy and active subjects without diabetes. Ten healthy, active subjects (26±4 years, 67±11 kg bodyweight (BW), 11±3 h) were included in the study. Within 14 days, they underwent six tests consisting of a) resting fasted (R/Fast), b) resting after intake of 1 g glucose/kg BW (R/Glc) and c) running for 60 minutes at moderate (65/Glc) and d) high (85/Glc) intensity after intake of 1 g glucose/kg BW. Data were collected in the morning, following a standardised dinner before test day. Sensor-based glucose concentrations were compared to simultaneous capillary blood glucose concentrations. Pearson’s r correlation coefficient was highest for R/Glc (.92, p<.001) compared to R/Fast (.45, p<.001), 65/Glc (.60, p<.001) and 85/Glc (.70, p<.001). Mean absolute relative deviation (MARD) and standard deviation (SD) was smallest for resting fasted and similar between all other conditions (R/Fast: 8±6%, R/Glc: 17±12%, 65/Glc: 22 ± 24%, 85/Glc: 18±17%). However, Bland-Altman plot analysis showed a higher range between lower and upper limits of agreement (95% confidence interval) of paired data under exercising compared to resting conditions. Under resting fasted conditions, both methods produce similar outcomes. Under resting postprandial and exercising conditions, respectively, there are differences between both methods. However, further data in healthy subjects need to be gathered considering physical activity and nutrition status.

Background/Objectives: To assess the prevalence of diamine oxidase (DAO) enzyme deficiency caused by single nucleotide polymorphisms (SNPs) of the AOC1 gene in a sample of patients with symptoms of insomnia. Methods: A total of 167 adult patients (&gt; 18 years of age) with symptoms of insomnia attended in a specialized institute for healthy sleep, in Barcelona (Spain) between May and November 2023, underwent genotyping analysis of the four most relevant SNP variants, including c.691G&gt;7 (rs2052129), c.47C&gt;T (rs10156191), c.995C&gt;T (rs1049742), and c.1990C&gt;G (rs1049793). Results: Genetic DAO deficiency was present in 138 patients, with a prevalence rate of 82.6% (95% CI 76-88.1%). Difficulties in staying asleep was the most common complaint in 88% of patients followed by trouble falling asleep in 60.5%. More than half of patients suffered from insomnia symptoms every day. Also, 99.4% reported daytime consequences of insomnia, with fatigue (79.6%), mood changes (72.5%), and impaired concentration in 70.1%. When patients were grouped by DAO-score, which reflected the number of heterozygous and homozygous SNPs variants, the group with a DAO-score ≥ 4 vs. 1 showed higher percentages of insomnia-related symptoms, in particular trouble staying asleep and early morning awakening. These two symptoms were also more common in the presence of the c.1990C&gt;G (rs1049793) variant. Conclusions: This preliminary real-world study presents novel evidence of a potential link between DAO enzyme deficiency of genetic origin and clinical symptoms of insomnia may suggest the potential benefit of DAO supplementation to improve the quality of sleep in these subjects.

The redox chemistry of copper(II) is strongly modulated by the coordination to amyloid-β peptides and by the stability of the resulting complexes. Amino terminal copper and nickel binding motifs (ATCUN) identified in truncated Aβ sequences starting with Phe4 show very high affinity for copper(II) ions. Herein, we study the oxidase activity of [Cu-Aβ4-x] and [Cu-Aβ1-x] complexes toward dopamine and other catechols. The results show that the CuII-ATCUN site is not redox-inert, the reduction of the metal is induced by coordination of catechol to the metal and occurs through an inner sphere reaction. The generation of a ternary [CuII-Aβ-catechol] species determines the efficiency of the oxidation, although the reaction rate is ruled by re-oxidation of the CuI complex. In addition to the N-terminal coordination site, the two vicinal histidines, His13 and His14, provide a second Cu-binding motif. Catechol oxidation studies together with structural insight from the mixed dinuclear complexes Ni/Cu-Aβ4-x reveal that the His-tandem is able to bind CuII ions independently of the ATCUN site, but the N-terminal metal complexation reduces the conformational mobility of the peptide chain, preventing the binding and oxidative reactivity toward catechol of CuII bound to the secondary site.

As lung cancer shows the highest mortality in cancer related death, serum biomarkers are demanded for the lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS-MS proteomic analysis. Quescin sulfhydryl oxidase(QSOX1) was selected as a biomarker candidate from the proteins enriched in the secretion of lung cancer cells. QSOX1levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p<0.05, AUC=0.89), when measured by multiple reaction monitoring(MRM). Higher levels of QSOX1 are also uniquely detected in lung cancer tissues among several other solid cancers by immunohistochemistry. QSOX1 knock-downed Lewis lung cancer (LLC) cells was less viable from oxidative stress and had reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

Background/Objectives: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Cardiovascular disease (CVD) is the leading cause of mortality in MASLD patients, therefore, the therapeutic interventions for MASLD should improve coronary risk factors such as obesity, diabetes and dyslipidemia, in addition to improving liver function. The evidence on effect of sodium-glucose cotransporter 2 inhibitors (SGLT2is) which have beneficial pharmacological properties for MASLD, especially the long-term effects, on the progression of MASLD in Asian population is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at the National Center for Global Health and Medicine, Kohnodai Hospital, Japan. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between April 1, 2014 and March 31, 2018. We collected the data on metabolic parameters, including blood tests and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. The 3-year-SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein-cholesterol, triglyceride and non-high-density lipoprotein-cholesterol (HDL-C) and significantly increased HDL-C. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, the long-term SGLT2is treatment may be an ideal therapy for MASLD patients.

Rho guanosine triphosphatases (GTPases) are key regulators in a number of cellular functions, including actin cytoskeleton remodeling and vesicle traffic. Traditionally, Rho GTPases are studied because of their function in cell migration and cancer, while their roles in metabolism are less documented. However, emerging evidence implicates Rho GTPases as regulators of processes of crucial importance for maintaining metabolic homeostasis. Thus, the time is now ripe for reviewing Rho GTPases in the context of metabolic health. Rho GTPase-mediated key processes include the release of insulin from pancreatic β-cells, glucose uptake into skeletal muscle and adipose tissue, and muscle mass regulation. Through the current review, we cast light on the important role of Rho GTPases in skeletal muscle, adipose tissue, and the pancreas and mechanisms by which Rho GTPases act to regulate glucose metabolism in health and disease. We also describe challenges and goals for future research.

The aim of this study was to investigate the relationship between postprandial glycemic levels based on flash-monitoring and the production of intestinal hydrogen (H2) and methane (CH4) gases based on measurement of the amount of these gases in exhaled air. We studied 14 subjects with type 2 diabetes mellitus (T2DM) and 10 individuals without diabetes (control) with 3 food-load tests with simultaneous determination of gases in exhaled air and assessment of glucose levels. In 15.4% of patients with T2DM, there was a non-significant increase in exhaled H2. How-ever, all subjects in the control group had significant increase in exhaled H2. Moreover, the level of H2 in exhaled breathafter food load in patients with T2DM was lower than in normoglycemic subjects. Also, in normoglycemic subjects there was an inverse correlation between maximum glucose rise and maximum H2 in exhaled air after food load. At the same time in patients with T2DM the level of CH4 in exhaled air directly correlated with the parameters of postprandial glycemia in the test with lactulose. Confirmation of a causal relationship between decreased H2 production, increased intestinal CH4 production, and more severe postprandial glycemia may identify new therapeutic targets in the correction of postprandial glycemia in patients with T2DM.

Enzymes reliant on pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B6 is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells by pyridoxal kinase (PLK) and pyridox-(am)-ine 5'-phosphate oxidase (PNPOx). The flavin mononucleotide dependent PNPOx enzyme converts pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate into PLP. PNPOx is vital for both biosynthesis and salvage pathways in organisms producing B6 vitamers. However, for those depending on vitamin B6 as nutrient, PNPOx participates only in the salvage pathway. Transferring PLP produced by PNPOx to client apo-enzymes is indispensable for their catalytic function, proper folding and targeting to specific organelles. PNPOx activity deficiencies due to inborn errors lead to severe neurological pathologies, particularly neonatal epileptic encephalopathy. PNPOx enzymes from different organisms maintain PLP homeostasis through highly regulated mechanisms, including structural alterations throughout the catalytic cycle and allosteric PLP binding influencing substrate transformation at the active site. Despite shared features, species-specific regulations are evident among PNPOx enzymes.

Increased activity of transforming growth factor-beta (TGF-β) is a key factor mediating kidney impairment in diabetes. Glomerular podocytes, the crucial component of the renal filter, are a direct target of TGF-β action, resulting in irreversible cell loss and progression of chronic kidney disease (CKD). Urolithin A (UA) is a member of the family of polyphenol metabolites produced by gut microbiota from ellagitannins and ellagic acid-rich foods. The broad spectrum of biological ac-tivities of UA makes it a promising candidate for the treatment of podocyte disorders. In this in vitro study, we investigated whether UA influences the changes exerted in podocytes by TGF-β and high glucose. Following a 7-day incubation in normal (NG, 5.5 mM) or high (HG, 25 mM) glucose the cells were treated with UA and/or TGF-β1 for 24 hours. HG and TGF-β1, each independent and in concert reduced expression of nephrin, increased podocyte motility and up-regulated expression of b3 integrin and fibronectin. These typical for epithelial-to-mesenchymal transition (EMT) effects were inhibited by UA in both HG and NG conditions. UA also reduced the typically elevated in HG expression of TGF-β receptors and activation of TGF-β signal transducer Smad2. Our results indicate that in podocytes cultured in conditions mimicking diabetic milieu, UA inhibits and reverses changes underlying podocytopenia in diabetic kidneys. Hence, UA should be considered as a po-tential therapeutic agent in podocytopathies.

Objectives and Background: Gestational diabetes (GDM) is a common pregnancy complication, defined as a glucose intolerance diagnosis during pregnancy. GDM is strongly associated with adverse fetal and maternal outcomes. In Germany, to screen and diagnose GDM we use a 1-hour 50g oGCT (oral glucose challenge test) followed by a 2-hour 75g oGTT if the first was pathological. This analysis examines the correlation of 75g oGTT glucose levels and fetomaternal outcome. Methods: Data of 1664 patients from a gestational diabetes consultation clinic at the Charité University hospital in Berlin, Germany, were analyzed retrospectively from 2015 until 2022. The 75g oGTT blood glucose levels were categorized into isolated fasting hyperglycemia (GDM-IFH), isolated post-load hyperglycemia (GDM-IPH) and combined hyperglycemia (GDM-CH), using the levels of the fasting, 1-hour and 2-hour values after glucose application. These subtypes were compared regarding baseline characteristics as well as fetal and maternal outcome. Results: GDM-IFH and GDM-CH women displayed higher preconceptional BMI and required insulin therapy more frequently (p<0,001). The GDM-IFH group was at higher risk of having a primary cesarean section (p=0,047), while GDM-IPH women were significantly more likely to have an emergent cesarean section (p=0,013). The offspring of GDM-IFH and GDM-CH women were born with a significantly higher mean birthweight (p<0,001) and birth weight percentiles (p<0,001) and were at increased risk of being large for gestational age (LGA) (p=0,004). Women from the GDM-IPH group delivered significantly more neonates who were small for gestational age (p=0,027) or with low fetal weight <30th percentile (p=0,003). Conclusion: This analysis shows a strong association between glucose response pattern in the 75g oGTT and adverse perinatal fetomaternal outcome. The differences among the subgroups, specifically concerning insulin therapy, mode of delivery and fetal growth, suggest an individualized approach in prenatal care after a GDM diagnosis.

Increased chronic glucose is associated with pandemic diseases. To date, there is not a practical, as well as accurate sample for reflecting that level. We measured earwax glucose in 37 controls. They provided standard serum samples, Glycated Haemoglobin (HbA1c) and earwax samples on two time-points, one month a part. The specimens measured baseline fasting glucose, a follow-up postprandial glucose level and a between sample chronic glucose, calculated using the average level on the two occasions. The baseline earwax sample was obtained using a clinical method and the follow-up using a novel self-sampling earwax device. The earwax analytic time was significantly faster using the novel device in comparison to the clinical use of the syringe. Earwax accurately reflected glucose at both assessments with stronger correlations than HbA1c. Follow-up postprandial concentrations were more significant than their respective fasting baseline concentrations, reflecting differences in fasting and postprandial glycaemia and more efficient standardisation at follow up. Earwax demonstrated to be more predictable than HbA1c in reflecting systemic fasting, postprandial and long-term glucose levels and immune by confounders. Earwax glucose was approximately 60% more predictable than HbA1c in reflecting glycaemia over a month. The self-sampling device provided a sample that might accurately reflect chronic glycaemia.

Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed, but appears to have tissue-specific roles. Earlier studies have focused on the role of hypothlamic FTO in the regulation of metabolism. However, it appears that FTO plays a role in the regulation of metabolism in a tissue-specific manner. Recent studies suggest that expression of hepatic FTO is regulated by metabolic signals such as nutrients and hormones and altered FTO levels in liver affects glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.

When a large artery becomes occluded, hemodynamic changes stimulate remodeling of arterial networks to form collateral arteries in a process termed arteriogenesis. However, the structural changes necessary for collateral remodeling have not been defined. We hypothesize that decon-struction of the extracellular matrix is essential to the remodeling of smaller arteries into effective collaterals. Using multiphoton microscopy, we analyzed collagen and elastin structure in maturing collateral arteries isolated from ischemic rat hindlimbs. Collateral arteries harvested at different timepoints showed progressive diameter expansion associated with striking rearrangement of in-ternal elastic lamina (IEL) into a loose fibrous mesh, a pattern persisting at 8 weeks. Despite a 2.5-fold increase in luminal diameter, total elastin content remained unchanged in collaterals compared with control arteries. Among the collateral midzones, baseline elastic fiber content is low. Outward remodeling of these vessels with a 10-20 fold diameter increase was associated with fractures of the elastic fibers and evidence of increased wall tension as demonstrated by straight-ening of the adventitial collagen. Inhibition of lysyl oxidase (LOX) function with β-aminopropionitrile resulted in severe fragmentation or complete loss of continuity of the IEL in developing collaterals. Collateral artery development is associated with permanent redistribution of existing elastic fibers to accommodate diameter growth. We found no evidence of new elastic fiber formation. Stabilization of the arterial wall during outward remodeling is necessary and dependent on LOX activity.

The actions of many drugs involve enzyme inhibition. This is exemplified by the inhibitors of monoamine oxidases (MAO) and the cholinsterases (ChE) that have been used for several pharmacological purposes. This review describes key principles and approaches for the reliable determination of enzyme activities and inhibition as well as some of the methods that are in current use for such studies with these two enzymes. Their applicability and potential pitfalls arising from their inappropriate use are discussed. Since inhibitor potency is frequently assessed in terms of the quantity necessary to give 50% inhibition (the IC50 value), the relationships between this and the mode of inhibition is also considered, in terms of the misleading information that it may provide. Incorporation of more than one functionality into the same molecule to give a multi-target-directed ligands (MTDLs) requires careful assessment to ensure that the specific target effects are not significantly altered and that the kinetic behaviour remains as favourable with the MTDL as it does with the individual components. Such factors will be considered in terms of recently developed MTDLs that combine MAO and ChE inhibitory functions.

Protein–nanoparticle hybridization can ideally lead to novel biological entities characterized by emerging properties, which can sensibly differ from those of the parent components. Herein, the effect of ionic strength on the biological functions of recombinant, His-tagged spermine oxidase (i.e., SMOX) was studied for the first time. Moreover, SMOX was integrated to colloidal surface active maghemite nanoparticles (SAMNs) by direct self-assembly, leading to a biologically active nano-enzyme (i.e., SAMN@SMOX). The hybrid was subjected to an in-depth chemical-physical characterization highlighting that protein structure was perfectly preserved. The catalytic activity of the nanostructured hybrid (SAMN@SMOX) was assessed by extracting kinetics parameters using spermine as substrate and compared to the soluble enzyme as a function of ionic strength. Results revealed that the catalytic function was dominated by electrostatic interactions and that they were drastically modified upon hybridization with colloidal ɣ-Fe2O3. Noteworthy, the affinity of SMOX toward spermine was significantly higher for the nanohybrid at low salinity. The present study supports the vision of using protein–nanoparticle conjugation as a mean for modulating biological functions.

Thyroid hormones regulate tissue metabolism establishing an energy balance in the cell, in particular by affecting oxidative phosphorylation. Their long-term impact is mainly associated with changes in gene expression, while the short-term effects may differ in mechanism. Our work is devoted to short-term effects of hormones T2, T3, and T4 on mitochondrial cytochrome c oxidase (CcO) mediated by a direct contact with the enzyme. The data obtained indicate the existence of two separate sites of CcO interaction with thyroid hormones differing in location, affinity and specificity to hormone binding. It is shown that T3 and T4 but not T2 inhibit oxidase activity of CcO in solution and on membrane preparations with Кi≈100–200 M. In solution, T3 and T4 compete in a 1:1 ratio with the detergent dodecyl-maltoside for binding to the enzyme. Peroxidase and catalase partial activities of CcO are not sensitive to hormones while electron transfer from heme a to the oxidized binuclear center is affected. We believe that T3 and T4 are ligands of the Bile Acid Binding Site found in the 3D structure of CсO by Ferguson-Miller’s group, and hormone induced inhibition is associated with dysfunction of the K- proton channel. Similar conclusion we made recently with regard to steroid-like compounds. It is found that T2, T3, and T4 inhibit superoxide generation by oxidized CcO in the presence of excess Н2О2. Inhibition is characterized by Ki values of 0.3 – 5 M and apparently affects the formation of О2• at the protein surface. The second binding site for thyroid hormones presumably coincides with the point of tight T2 binding on the Va subunit described in the literature.

Increased sugar intake is implicated in Type-2 diabetes and fatty liver disease. Mechanisms by which glucose and fructose components promote these conditions are unclear. We hypothesize that alterations in intestinal metabolite and microbiota profiles specific to each monosaccharide are involved. Two groups of six adult C57BL/6 mice were fed for 10-weeks with a diet where either glucose or fructose was the sole carbohydrate component (G and F, respectively). A third group was fed with normal chow (N). Fecal metabolites were profiled every 2-weeks by ¹H NMR and microbial composition was analysed by real-time PCR (qPCR). Glucose tolerance was also periodically assessed. N, G and F mice had similar weight gains and glucose tolerance. Multivariate analysis of NMR profiles indicated that F mice were separated from both N and G, with decreased butyrate and glutamate and increased fructose, succinate, taurine, tyrosine and xylose. Compared to N and G, F mice showed a shift in microbe populations from gram-positive Lactobacillus spp. to gram-negative Enterobacteria species. Substitution of normal chow carbohydrate mixture by either pure glucose or fructose for 10 weeks did not alter adiposity or glucose tolerance. However, F G and N mice generated distinctive fecal metabolite signatures with incomplete fructose absorption as a dominant feature of F mice.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

The kidney and the heart work together in balancing the body circulation and although their physiology is based on strict inter dependence, their performance fulfills different aims. While the heart can rapidly increase its own oxygen consumption to comply with the wide changes in metabolic demand linked to body function, the kidney physiology is primarily designed to maintain a stable metabolic rate and has limited capacity to cope with any steep increase in renal metabolism. In the kidneys the glomerular population filters a large amount of blood and the tubular system has been programmed to reabsorb 99% of filtrate by reabsorbing sodium together with other filtered substances including all glucose molecules. Glucose reabsorption involves the sodium-glucose cotransporters SGLT2 and SGLT1 on the apical membrane in the proximal tubular section; it also enhances bicarbonate formation so as to preserve the acid-base balance. The complex work of reabsorption in the kidney is the main factor in renal oxygen consumption; analysis of renal glucose transport in disease states is providing better understanding of the renal physiology changes that occur when clinical conditions alter the neurohormonal response leading to an increase in glomerular filtration pressure. In this circumstance glomerular hyperfiltration occurs, imposing a higher metabolic demand on kidney physiology and causing progressive renal impairment. Albumin urination is the warning signal of renal engagement over-exertion and most frequently heralds heart failure development, regardless of disease etiology. The review analyzes the mechanisms linked to renal oxygen consumption, focusing on sodium-glucose management.

Background. Cardiorespiratory fitness (CRF) is a predictor of chronic disease that is impractical to routinely measure in primary care settings. We used a new estimated cardiorespiratory fitness (eCRF) algorithm that uses information routinely documented in electronic health care records to predict abnormal blood glucose incidence. Methods: Participants were adults (17.8% female) 20-81 years old at baseline from the Aerobics Center Longitudinal Study between 1979 and 2006. eCRF was based on sex, age, body mass index, resting heart rate, resting blood pressure, and smoking status. CRF was measured by maximal treadmill testing. Cox proportional hazards regression models were established using eCRF and CRF as independent variables predicting the abnormal blood glucose incidence while adjusting for covariates. Results: Of 8,602 participants at risk at baseline, 3,580 (41.6%) developed abnormal blood glucose during an average of 4.9 years follow-up. The average eCRF of 12.03 ± 1.75 METs was equivalent to the CRF of 12.15 ± 2.40 METs within the 10% equivalence limit. In fully adjusted models, the estimated risks were the same (HRs = 0.96), eCRF (95% CIs = 0.93−0.99), and CRF (95% CI of 0.94−0.98). Each 1-MET increase was associated with a 4% reduced risk. Conclusion: Higher eCRF is associated with a lower risk of abnormal glucose. eCRF can be a vital sign used for research and prevention.

Various efforts have been made to detect minimum value of glucose in any medium like water or body buffer solutions with high-sensitivity, accurate, and low-cost sensors in order to enhance life style. Therefore, the present study was done to investigate reliability of two-dimensional plasmonic structure by circular dichroism (CD) and ellipsometry tools in different concentrations of glucose. Our results confirmed a dependency of the CD signal on glucose concentrations and also a very good sensitivity based on the phase difference between each polarization in ellipsometry parameters with the help of an achiral plasmonic structure.

A human organism depends on stable glucose blood levels in order to maintain the metabolic needs. Glucose is considered as the most important energy source and glycolysis is postulated as a backbone pathway. However, when glucose supply is limited, ketone bodies and amino acids can be used to produce enough ATP. In contrast, for the functioning of pentose phosphate pathway (PPP) glucose is essential and cannot be substituted by other metabolites. PPP generates and maintains levels of NADPH needed for reduction of oxidized glutathione and protein thiols, synthesis of lipids and DNA as well as for xenobiotic detoxification, regulatory redox signaling and counteracting infections. Flux of glucose into a PPP, particularly under extreme oxidative and toxic challenges is critical for survival, whereas the glycolytic pathway is primarily activated when glucose is abundant, and there is lack of NADP⁺ that is required for activation of glucose-6 phosphate dehydrogenase. An important role of glycogen stores in resistance to oxidative challenges is discussed. Current evidences explain disruptive metabolic effects and detrimental health consequences of chronic nutritional carbohydrate overload and provides new insights into positive metabolic effects of intermittent fasting, caloric restriction, exercise, and ketogenic diet through modulation of redox homeostasis.

Plant Cysteine Oxidase (PCO) is a plant O2-sensing enzyme of catalyzing oxidation of cysteine to Cys-sulfinic acid at the N-termini of target proteins. To better understand the Brassica napus PCO gene family, PCO genes in B. napus and related species were analyzed. In this study, 20, 7 and 8 PCO genes were identified in Brassica napus, Brassica rapa and Brassica oleracea, respectively. According to phylogenetic analysis, the PCOs were divided into five groups: PCO1, PCO2, PCO3, PCO4 and PCO5. Gene organization and motif distribution analysis suggested that PCO gene family was relatively conserved during evolution. Expression analysis showed that PCO genes were expressed in different tissues at different developmental stages. Interestingly, most of the Bna/Br/BoPCO5 members were expressed in leaves, roots, flowers, buds and siliques, suggesting an important role in both vegetative and reproductive development. Expression of BnaPCO was induced by various abiotic stress, especially waterlogging stress, which was consistent with the result of cis-element analysis. In this study, the PCO gene family of Brassicaceae was analyzed for the first time, which contributes to a comprehensive understanding of the origin and evolution of PCO genes in Brassicaceae and the function of BnaPCO in regulating plant responses to abiotic stresses.

Kaempferia parviflora Wall. ex Baker (KP), Krachaidam in Thai or Thai ginseng, is an herbal medicine that has many potential pharmacological effects. This study focused on the oral glucose tolerance test and pharmacokinetic study in healthy volunteers administered with KP extract (90 and 180 mg/day, placebo). The oral glucose tolerance tests were performed at baselines and 28-days of administration. The pharmacokinetics were determined after a single dose administration of the tested products using 3,5,7,3,4-pentamethoxyflavone (PMF) and 5,7,4-trimethoxylfavone (TMF) as markers. The results showed that glucose metabolism via oral glucose tolerance test was not affected by KP extract. The results of pharmacokinetics study revealed that only TMF and PMF, but not DMF levels could be detected in human blood. The given doses of KP extract at 90 and 180 mg/day showed a linear dose-relationship of blood PMF concentration whereas blood TMF was detected only at high given dose (180 mg/day). The half-lives of PMF and TMF were 2–3 h. The Cmax, AUC and Tmax values of PMF and TMF estimated for the 180 mg/day dose were 85.3711.31, 73.2329.93 mg/ml; 291.8948.23, 412.20203.69 mg.h/ml; and 3.890.37, 4.500.96 h, respectively. PMF was quickly eliminated with higher Ke and Cl than TMF at the dose of 180 mg/day of KP extract. In conclusion, the results demonstrated that KP extract had no effect on glucose tolerance test. In addition, this is the first demonstration of the pharmacokinetic parameters of methoxyflavones of KP extract in healthy volunteers in a phase I study in drug development. The data suggest the safety of the KP extract and will be of benefit for further clinical trials using KP extract as food and sport supplements as well as a drug in health product development.

A key response to glucose stress is an increased production of unsaturated fatty acids to balance the increase of saturated fatty acids in the membrane. The C. elegans homolog of stearoyl-CoA desaturase, FAT-7, introduces the first double bond into saturated C18 fatty acids yielding oleic acid and is a critical regulatory point for surviving cold and glucose stress. Here, we incorporated 13C stable isotopes into the diet of nematodes and quantified the 13C-labelled fatty acid by GC-MS and HPLC/MS-MS to track the metabolic response to various concentrations of glucose. Previous work has analyzed membrane composition of C. elegans when responding to mild glucose stress and showed few alterations in overall fatty acid composition in the membrane. Here, in nematodes exposed to higher concentrations of glucose, a specific reduction of oleic acid and linoleic acid was observed. Using time courses and stable isotope tracing, the response of fatty acid me-tabolism to increasing levels of glucose stress has been characterized, revealing a funneling of monounsaturated fatty acids to preserve polyunsaturated fatty acid abundance. Taken together, higher levels of glucose unveil a specific reduction of oleic and linolenic acid in the metabolic re-wiring required to survive glucose stress.

As an option to deal with the insulin-dependent disease, a recent commuted PD control strategy is designed and carefully analyzed for different clinic diabetic patients. This controller approach is mainly conceived to stabilize the glucose blood concentration in a diabetic patient around its basal value, hence avoiding extreme situations such as hypoglycemia and hyperglycemia. This control strategy receives two inputs carefully tuned to actuate when the measured variable is out of a prescribed healthy zone. Therefore, one of these variables is invoked to decrease the glucose concentration to insulin injection, and the other is employed to increase the glucose absorption, both by using a proper PD controller. According to our numerical experiments, our controller approach performs well, even when there is an external disturbance in the controlled system.

Pathogens and adulterants in human feeding consumables can be readily identified according to their electrical properties. Electrical bioimpedance analysis (BIA) has been widely used for body contents characterization, such as blood, urine, lactate and sweat. If the blood glucose concentration alters the electrical properties of the blood medium, then the impedance spectrum obtained by BIA can be used to measure glycemia. In some applications, artificial neural networks allows the correlation of these parameters (impedance and glucose concentration) by means of symbolic and statistical rules. According to our literature review, there is any physical model that allows the interpretation of the relationship between blood’s electrical properties, obtained by BIA, and the concentration of glucose in the blood plasma. This article proposes a simplified physical model for blood electrical conductivity as a function of glucose concentration, based on Bruggeman’s effective medium theory. The equations of this model were obtained considering an insulating phase distribution diffused in a conductive matrix, in which red blood cells are represented by macroscopic insulating nuclei and glucose molecules by microscopic insulating particles. The impedance spectrum for different glucose concentrations (4.0 to 6.8 mmol/L) in a blood sample, published by Kamat Bagul (2014), were compared with the proposed model. The results showed a significant correlation with the experimental data, showing a maximum error of 5.2%. The proposed model might be useful in the design of noninvasive blood glucose monitoring systems.

Non-enzymatic glucose sensing is a crucial field of study because of the current market demand. This study proposes a novel design of glucose sensor with enhanced selectivity and sensitivity by using graphene Schottky diodes, which is composed of Graphene/Platinum Oxide/n-Silicon heterostructure. The sensor was tested with different glucose concentrations and interfering solutions to investigate its sensitivity and selectivity. Different structures of the device were studied by adjusting the platinum oxide film thickness to investigate its catalytic activity. It was found that the film thickness plays a significant role in the efficiency of glucose oxidation and hence in overall device sensitivity. Moreover, theoretical investigations were conducted using Density Function Theory (DFT) to better understand the detection method and the origins of selectivity. The working principle of the sensors puts it in a competitive position with other non-enzymatic glucose sensors. DFT calculations provided a qualitative explanation of the charges distributed across the graphene sheet within a system of a platinum substrate with D-glucose molecules above. The proposed graphene/PtO/n-Si heterostructure has proven to satisfy these factors, which opens the door for further developments of more reliable non-enzymatic glucometers for continuous glucose monitoring systems.

Calorie restriction (CR) has been shown to prolong the lifespan of humans, but enforcing long-term CR is difficult. Therefore, a compound that reproduces the effect of CR without CR is needed. In this review, we summarize the current knowledge on compounds with CR mimetic (CRM) effects. More than 10 compounds have been listed as CRMs, some of which are conventionally categorized as upstream-type CRMs showing glycolytic inhibition while the others are categorized as downstream-type CRMs that regulate or genetically modulate intracellular signaling proteins. Among these, we focus on upstream-type CRMs and propose their classification as compounds with energy metabolism inhibition effects, particularly glucose metabolism modulation effects. The upstream-type CRMs reviewed include chitosan, acarbose, sodium-glucose cotransporter 2 inhibitors, and hexose analogs such as 2-deoxy-D-glucose, D-glucosamine, and D-allulose, which show anti-aging and longevity effects. Finally, we discuss the molecular definition of upstream-type CRMs.

The prevalence of diabetes mellitus (DM), considered one of the most common metabolic disorders, has dramatically increased and resulted in higher rate of morbidity and mortality around the world, in the past decade. It is well known that insulin resistance in target tissues and a deficiency in insulin secretion from pancreatic β-cells are the main characteristic of type 2 diabetes. The aim of this study was the bio-evaluation of compounds isolated from three selected plant species; namely, Salvia africana-lutea, Leonotis ocymifolia and Plectranthus madagascariensis, for their glucose uptake ability. Methanolic extracts were produced from the arterial part of each plant. Compounds were identified using different spectroscopic techniques. The glucose uptake ability of each compound was then evaluated in mammalian cells using 2-deoxyglucose-6-phosphate. The cytotoxicity of each compound was established via the MTT assay. Chromatographic purification of the three plant species yielded fifteen pure terpenoids. Compounds 1 (p = 0.0031), 8 (p = 0.0053), and 6 (p = 0.0086), showed a marked increase in glucose uptake, with p values of p=0.0031, p=0.0053 and p=0.0086, respectively. Additionally, 1, 4 and 6 exhibited cytotoxicity toward mammalian tissue with a decrease in cell viability of ~70%, ~68% and ~67%, respectively. The results suggested that several compounds demonstrated a marked increase in glucose uptake while two of the compounds exhibited signs of cytotoxicity. It may, therefore, be suggested that these compounds be considered as potential candidates for novel plant-derived alternative therapies in the treatment of type 2 diabetes.

Many marine animals use chemicals to defend themselves and their eggs from predators. Beyond their ecologically relevant functions, these chemicals may also have properties that make them beneficial for humans, including with biomedical and industrial applications. For example, some chemical defenses are also powerful antimicrobial or anti-tumor agents with relevance to human health and disease. One such chemical defense, Escapin, an L–amino acid oxidase in the defensive ink of the sea hare Aplysia californica, and related proteins have been investigated for their biomedical properties. This review details our current understanding of Escapin’s antimicrobial activity, including the array of chemicals generated by Escapin’s oxidation of its major substrates, L–lysine and L–arginine, and mechanisms underlying these molecules’ bactericidal and bacteriostatic effects on planktonic cells and the prevention of formation and removal of bacterial biofilms. Models of Escapin’s effects are presented, and future directions are proposed.

Postprandial plasma glucose between 4 and 7.9 hours is associated with the diagnosis of diabetes, diabetes mortality, and cardiovascular mortality. However, it is unknown whether 2-hour plasma glucose during the oral glucose tolerance test conducted in this postprandial period (4–7.9 hours), termed as 2-h PGOGTT@4–7.9h, can accurately classify diabetes diagnosis and predict mortality risks. This study aimed to address these questions using 2,347 adult participants. Diabetes was defined as HbA1c ≥6.5%, and the ability of 2-h PGOGTT@4–7.9h to classify diabetes was analyzed using receiver operating characteristic curves. Cox proportional hazards models were employed to estimate mortality hazard ratios (HRs) and 95% confidence intervals (CIs). The results showed that 2-h PGOGTT@4–7.9h could classify diabetes with 92% accuracy. Participants were followed up for a mean of 21.4 years. A 1-natural-log higher 2-h PGOGTT@4–7.9h was associated with an increased risk of mortality from diabetes (adjusted HR, 21.1; 95% CI, 9.2–48.0) and cardiovascular disease (adjusted HR, 1.47; 95% CI, 1.13–1.91). Simulation analysis indicated that future studies may require at least 100 participants to investigate 2-h PGOGTT@4–7.9h for diabetes diagnosis. In conclusion, 2-h PGOGTT@4–7.9h may be useful for diabetes classification and prediction of mortality risk.

Biomimetic compounds are an alternative for to the limited action and fragile nature of enzymes. This work deals with the synthesis, characterization and evaluation of catalytic activity of two new biomimetic models for the active centers of ascorbate oxidase and catalase. [Cu3(S,S(+)cpse)3(H2O)3][Cu3(R,R(-)cpse)3(H2O)3]·17H2O (model for ascorbate oxidase, 1), and [Mn2(S,S(+)Hcpse)4(NaClO4)2(NaOH)(CH4O)]n·[(C2H6O)2]n·[(CH4O)2]n (model for catalase, 2) were prepared through the synchronic method (yields > 78%). The compound 1 has electronic and optical characteristics for racemic compound. The magnetic properties and electrochemical behavior evidence electronic transfer between metal centers. Meanwhile, the compound 2 showed polymeric properties in solid state and dimeric behavior in solution. Compound 1 was able to effectively catalyze the oxidation of ascorbic acid to dehydroascorbic acid (65.6% and 78.24% for racemic and enantiomeric pure compounds) showing structural and functional similarity to the natural enzyme. Besides, Compound 2 catalyzed the decomposition of hydrogen peroxide toward oxygen and water molecules (45%), evidencing that the prepared complex mimics the action of catalases. These two biomimetic models are relationship between them for the structural ligands, the coordination form to metal center and the catalytic activity as oxidase. This research shows the relationship with the design, evaluation, and comprehension of fundamentals aspects for the biomimetic models of active center of metalloenzymes that have importance for biological and industrial processes.

A cuprous oxide (Cu₂O) thin layer served as the base for a non-enzymatic glucose sensor in an alkaline medium, 0.1 NaOH solution, with a linear range of 50-200 mg/dL using differential pulse voltammetry (DPV) measurement. An X-ray photoelectron spectroscopy (XPS) study confirmed the formation of the cuprous oxide layer on the thin gold film sensor prototype. Quantitative detection of glucose in both phosphate-buffered saline (PBS) and undiluted human serum were carried out. Neither ascorbic acid nor uric acid even at a relatively high concentration level of 100mg/dL in serum interfered with the glucose detection, demonstrating the excellent selectivity of this non-enzymatic cuprous oxide thin layer based glucose sensor. Chronoamperometry (CA) and single potential amperometric voltammetry were used to verify the measurements obtained by differential pulse voltammetry (DPV), and the positive results validated that the detection of glucose in a 0.1 M NaOH alkaline medium by DPV measurement was effective. Nickel, platinum and copper are commonly used metals for non-enzymatic glucose detection. The performance of these metal-based sensors for glucose detection using DPV were also evaluated. Cuprous oxide (Cu₂O) thin layer based sensor showed the best sensitivity for glucose detection among the sensors evaluated.

Millions of people worldwide are affected by diabetes, a chronic disease that continuously grows due to abnormal glucose concentration levels present in the blood. Monitoring blood glucose concentrations is therefore an essential diabetes indicator to aid in the management of the disease. Enzymatic electrochemical glucose sensors presently account for the bulk of glucose sensors in the market. However, their disadvantages are that they are expensive and are dependent on environmental conditions, hence affecting their performance and sensitivity. To meet the increasing demand, non-enzymatic glucose sensors based on chemically modified electrodes for the direct electrocatalytic oxidation of glucose are a good alternative to the costly enzymatic-based sensors currently on the market, and the research thereof continues to grow. Nanotechnology-based biosensors have been explored for their electronic and mechanical properties, resulting in enhanced biological signalling through the direct oxidation of glucose. Copper oxide and copper sulfide exhibit attractive attributes for sensor application, due to their non-toxic nature, abundance, and their unique properties. Thus, in this review, copper oxide and copper sulfide-based materials, are evaluated based on their chemical structure, morphology, and fast electron mobility as suitable electrode materials for non-enzymatic glucose sensors. The review highlights the present challenges of non-enzymatic glucose sensors that have limited their deployment into the market.

The heat and matter transfer during glucose catabolism in living systems and their relation with entropy production are a challenging subject of the classical thermodynamics applied to biology. In this respect, an analogy between mechanics and thermodynamics has been performed via the definition of the entropy density acceleration expressed by the time derivative of the rate of entropy density and related to heat and matter transfer in minimum living systems. Cells are regarded as open thermodynamic systems that exchange heat and matter resulting from irreversible processes with the intercellular environment. Prigogine’s minimum energy dissipation principle is reformulated using the notion of entropy density acceleration applied to glucose catabolism. It is shown that, for out-of-equilibrium states, the calculated entropy density acceleration is finite and negative and approaches as a function of time a zero value at global thermodynamic equilibrium for heat and matter transfer independently of the cell type and the metabolic pathway. These results could be important for a deeper understanding of entropy generation and its correlation with heat transfer in cell biology with special regard to glucose catabolism representing the prototype of irreversible reactions and a crucial metabolic pathway in stem cells and cancer stem cells.

Pentagalloyl glucose (PGG) is currently being investigated as a non-surgical treatment for abdominal aortic aneurysms (AAA); however molecular mechanisms of action of PGG on the AAA matrix components and the intra-luminal thrombus (ILT) still need to be better understood. To assess these interactions, we utilized peptide fingerprinting and molecular docking simulations to predict the binding of PGG to vascular proteins in normal and aneurysmal aorta, including matrix metalloproteinases (MMPs), cytokines and fibrin. We performed PGG diffusion studies in pure fibrin gels and human ILT samples. PGG was predicted to bind with high affinity to most vascular proteins, the active sites of MMPs, and several cytokines known to be present in AAA. Finally, despite potential binding to fibrin, PGG was shown to diffuse readily through thrombus at physiologic pressures. In conclusion, PGG can bind to all the normal and aneurysmal aorta protein components with high affinity, potentially protecting the tissue from degradation and exerting anti-inflammatory activities. Diffusion studies showed that thrombus presence in AAA is not a barrier to endovascular treatment. Together, these results provide a deeper understanding of the clinical potential of PGG as a non-surgical treatment of AAA.

External stressors strongly increase cardiovascular activity and induce metabolic changes that ensure the availability of glucose and oxygen as part of a co-ordinated stress response. Exposure to stress during early life appears to have an exaggerated long-term effect on this response, leading to an increased risk or cardiometabolic disorders. Here we demonstrate that acute stress induced glucose release is impacted by the early life environment in rodent maternal deprivation and early-life infection models and this was validated in our EpiPath human early-life adversity cohort. In all three models differences in baseline blood glucose levels after ELA exposure were sex dependent. The human ELA model showed higher levels of basal glucose in females, similar to the mouse infection and rat maternal deprivation models. We anticipated that the stress induced glucose rise would be a GC dependent process. However, the kinetics of stress-induced glucose release, peaking 15-28 minutes before cortisol suggest that it is a GC-independent process. We confirmed this by administering an escalating dose of cortisol to a health human cohort, and the inability of an intravenous GC bolus induce a glucose rise in man confirms that it is a rapid, GC independent, process.In conclusion, we provide a novel perspective on the mechanisms behind stress related metabolic changes and highlights the importance of collecting early life data as a measure to understand an individual’s metabolic status in a better light.

Lung cancer, globally recognized as the leading cause of cancer-related mortality, presents a pressing need for innovative treatment strategies. Increasing evidence points towards the potential of monoamine oxidase (MAO) inhibitors in modulating cancer progression, primarily due to their role in regulating cellular metabolism and apoptotic pathways. This extraordinary study delves into the multifaceted therapeutic implications of MAO inhibitors in lung cancer management, elucidating their ability to pave the way for clinical advancement via novel targets and pathways. Capitalizing on recent advances in molecular biology, this research explores the molecular mechanisms underlying the anticancer actions of MAO inhibitors. By examining their impact on cell proliferation, migration, invasion, and apoptosis in lung cancer cell lines, we provide insight into the intricate signaling pathways and biochemical processes modulated by these compounds. The study also investigates the synergistic effects of MAO inhibitors in combination with established chemotherapeutic agents, elucidating their potential to enhance treatment efficacy and reduce cytotoxicity. Furthermore, we delve into the implications of MAO inhibitors on the tumor microenvironment, evaluating their influence on angiogenesis, immune regulation, and the epithelial-mesenchymal transition. This comprehensive analysis enables the identification of novel molecular targets, which hold promise for the development of advanced therapeutics tailored for specific lung cancer subtypes. To substantiate our findings, in this review, we thoroughly analyze the existing literature using state-of-the-art bioinformatics tools." in vivo orthotopic lung cancer models, and clinical patient cohorts. This robust and multidisciplinary approach permits the generation of clinical evidence supporting the integration of MAO inhibitors in lung cancer management. Conclusion: This ground-breaking study establishes the therapeutic potential of monoamine oxidase inhibitors in lung cancer management by unearthing novel pathways and targets for clinical advancement. The outcomes open doors for the development of innovative treatment strategies and inspire continued research efforts to combat the global burden of lung cancer.

Ethylene is an essential plant hormone critical in various physiological processes. These processes include seed germination, leaf senescence, fruit ripening, and the plant's response to environmental stressors. Ethylene biosynthesis is tightly regulated by two key enzymes, namely 1-aminocyclopropane-1-carboxylate synthase (ACS) and 1-aminocyclopropane-1-carboxylate oxidase (ACO). Initially, the prevailing hypothesis suggested that ACS is the limiting factor in the ethylene biosynthesis pathway. Nevertheless, accumulating evidence from various studies has demonstrated that ACO, under specific circumstances, acts as the rate-limiting enzyme in ethylene production. Under normal developmental processes, ACS and ACO collaborate to maintain balanced ethylene production, ensuring proper plant growth and physiology. However, under abiotic stress conditions, such as drought, salinity, extreme temperatures, or pathogen attack, the regulation of ethylene biosynthesis becomes critical for plants’ survival. This review highlights the structural characteristics, examines the transcriptional, post-transcriptional, and post-translational regulation of ACS and ACO, and their role under abiotic stress conditions. Reviews on the role of ethylene signaling in abiotic stress adaptation are available. However, a review that delineates the role of ACS and ACO in abiotic stress acclimation is not available.

Advanced Glycation End Products (AGEs) represent a set of substances that contribute directly to the triggering and/or aggravation of pathologies associated with ageing. AGEs are produced by the reaction between reducing sugars (or α-dicarbonyl compounds) proteins and amino acid residues. Current methodologies require an incubation period of 1-3 weeks to generate AGEs. In this study the reaction time for the formation of AGEs (48 and 3 hours) is significantly reduced by coupling and adapting procedures already existing in the literature to the free radical generation system called the hypoxanthine/xanthine oxidase assay. The capacity of different classes and chemical compounds (aminoguanidine, chlorogenic acid, rutin, extracts of Hancornia speciosa Gomes) were evaluated to inhibit the protein glycation process, acting as capturing agents of α-dicarbonyl species. Aminoguanidine, rutin and the leaf extracts of Hancornia speciosa Gomes show a high capacity to act as α-dicarbonyl compound scavengers (RCS-trapping) and resulting in the inhibition of AGEs formation.

Background: Novel technologies like continuous glucose monitor (CGM) systems are improving diabetes management by means of real-time sensor glucose levels, retrospective course of glucose and trend arrows. Continuous Glucose Monitoring (CGM) offers real-time alerts for (prognostic) hypo- and hyperglycemia, fast dropping or increasing glucose, and hence improving glycaemia under unstable conditions like during meals, physical activity and exercise management. Complex CGM systems challenge people with diabetes and health care professionals in interpreting rapid changes, sensor delay (~10-minute difference between interstitial and plasma glucose), and malfunctions. Enhanced prediction models are necessary for optimal insulin dosing, daily activities, and especially for future fully closed-loop systems. Methods: The aim of this study was to investigate the efficacy of three different predictive models for glucose responses: 1) an autoregressive integrated moving average model (ARIMA), 2) logistic regression, 3)and long short-term memory networks (LSTM), in predicting glucose levels after 15 minutes and one hour. We compared and evaluated the performance of these models in predicting hypoglycemia (<70 mg/dL), euglycemia (70-180 mg/dL), and hyperglycemia (>180 mg/dL). In more detail, by assessing metrics such as precision, recall, F1-score, and accuracy, we specifically assessed which model provided the most accurate and reliable predictions for glucose levels Results: As expected, ARIMA showed the worst accuracy especially predicting hypoglycaemia withing 1-hour (7.3%). The accuracy of the logistic regression model, predicting hypoglycemia during the first 15 min was higher (98%), comparing to LSTM (88%). However, the LSTM model (87%) exceeded the accuracy of hypoglycemia prediction of the logistic regression (83%) during an hour prognosis. The same pattern observed in hyperglycemia - ARIMA model (60%, 1 hour), logistic regression (96%, 15 minutes) and LSTM (85%, 1 hour) Conclusions: These findings suggest that different models may have varying strengths and weaknesses in predicting glucose levels, and the choice of model should be carefully considered based on the specific requirements and context of the clinical application. The logistic regression model was more accurate for the next 15 minutes, especially predicting hypoglycemia. However, the LSTM model exceeded logistic regression for the next one hour prediction. Future research could explore hybrid models or ensemble approaches that combine the strengths of multiple models to further improve the accuracy and reliability of glucose predictions.

Magnesium supplementation has recently attracted attention as effective in the management of diabetes and its related complications though its mechanisms of action is yet to be fully unraveled. This study was carried out to determine the effects of magnesium supplementation on body weight, fasting blood sugar, Oral glucose tolerance (OGTT 2 and OGTT 4), glucose transporter isoform 2 (GLUT2), GLUT4 and insulin receptor (INSR) mRNA expressions in streptozotocin-nicotinamide induced diabetic Sprague dawley rats. A total of 24 Sprague dawley rats (Four groups of six rats each) were used for this study, and the treatment was for 28 days. Group 1: Normal control rats were given distilled water; Group 2: Metformin treated rats were given 100 mg/kg body weight; Group 3: Metformin + Magnesium treated rats were given 100 mg/kg and 1000 mg/kg body weight respectively; Group 4: Diabetic untreated rats given distilled water. Data were analyzed statistically using Analysis of Variance (ANOVA) and graphically by Graph pad prism. The GLUT4 and INSR gene expressions of Group 3 were significantly (p<0.05) upregulated when compared with Group 4. There was significant (p<0.05) decrease fasting blood sugar and GLUT2 mRNA level in the treated diabetic rats but the metformin-magnesium supplement treated group showed more decrease (p<0.05) when compared with the group treated with metformin only. This study demonstrates that magnesium may mediate effective metabolic control by stimulating insulin sensitivity, and upregulating mRNA levels of GLUT4, INSR as well as improving glucose tolerance in diabetic rats. Therefore, magnesium supplementation appears to have a beneficial role and improves glucose uptake by cells in those at high risks of diabetes. Magnesium supplementation, Metformin, INSR, GLU4, glucose tolerance.

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Contributing pathophysiologic factors include endothelial dysfunction caused by excessive production of reactive oxygen species (ROS), increased activity of nuclear factor kB (NFkB), altered macrophage polarization, and reduced synthesis of endothelial progenitor cells (EPC). Consequently, there can be a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque, leading to increased cardiovascular mortality. Management is aimed at prevention, early diagnosis, and treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial function, inflammatory markers, markers of oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of trials that evaluated the cardiovascular safety of these drugs and found them to be safe from the CV standpoint.

NiFe alloy nanoparticles/graphene oxide hybrid (NiFe/GO) was prepared for electrochemical glucose sensing. The as-prepared NiFe/GO hybrid was characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD). The results indicated that NiFe alloy nanoparticles can be successfully deposited on GO. The electrochemical glucose sensing performance of the as-prepared NiFe/GO was studied by cyclic voltammetry and amperometric measurement. Results showed that NiFe/GO modified glassy carbon electrode had sensitivity of 173 μA mM⁻¹cm⁻² for glucose sensing with a linear range up to 5 mM, which was superior to commonly used Ni nanoparticles. Furthermore, high selectivity for glucose detection can be achieved by NiFe/GO. All the results demonstrated that NiFe/GO hybrid was promising for using in electrochemical glucose sensing.

The microglia, displaying diverse phenotypes, play a significant regulatory role in the development, progression, and prognosis of Parkinson's disease. Research has established that glycolytic reprogramming serves as a critical regulator of inflammation initiation in pro-inflammatory macrophages. Furthermore, the modulation of glycolytic reprogramming has the potential to reverse the polarized state of these macrophages. Previous studies have shown that levetistilide A (LA), a phthalide component derived from Angelica sinensis, possesses a range of pharmacological effects, including anti-inflammatory, antioxidant, and neuroprotective properties. In our study, we have examined the impact of LA on inflammatory cytokines and glucose metabolism in microglia induced by lipopolysaccharide (LPS). Furthermore, we explored the effects of LA on the AMPK/mTOR pathway and assessed its neuroprotective potential both in vitro and in vivo. The findings revealed that LA notably diminished the expression of M1 pro-inflammatory factors induced by LPS in microglia, while leaving M2 anti-inflammatory factor expression unaltered. Additionally, it reduced ROS production and suppressed IκB-α phosphorylation levels as well as NF-κB p65 nuclear translocation. Notably, LA exhibited the ability to reverse microglial glucose metabolism reprogramming and modulate the phosphorylation levels of AMPK/mTOR. In vivo experiments further corroborated these findings, demonstrating that LA mitigated the death of TH-positive dopaminergic neurons and reduced microglia activation in the ventral SNpc brain region of the midbrain and the striatum. In summary, LA exhibited neuroprotective benefits by modulating the polarization state of microglia and altering glucose metabolism, highlighting its therapeutic potential.

Olfactory Receptors (ORs) are a large family of G protein coupled receptors predominantly expressed by the main olfactory epithelium at nasal level and are responsible for the generation of smelling sense. Microarray and deep sequencing analyses, however, have demonstrated that ORs are ectopically expressed in various human tissues including testis, kidneys, adipose tissue and liver and their biological functions become to be unrevealed. Molecular and pharmacological approaches have shown that some of these ORs modulate glucose and lipid metabolism at multiple interfaces, suggesting that ORs might be part of the large family of nutrient sensors. i.e. molecular/ cellular machines that respond to a specific nutrient component. By using nutrients- derived agonists it has been shown that ORs effectively modulates glucose and lipid metabolism raising interest on their possible therapeutic application in the treatment of metabolic disorders including dyslipidemia, obesity and metabolic syndrome.

This case report examines the impact of a novel Combined Neuromuscular Electrical Stimulation (Comb-NMES) regimen on muscle glucose signaling, fiber type distribution, and metabolic function in a patient with acute spinal cord injury (SCI) and lower motor neuron lesions (LMNLs). A 32-year-old male with complete T9 SCI underwent a ten-session Comb-NMES intervention targeting the quadriceps. Muscle biopsies and blood samples were analyzed pre- and post-intervention to evaluate changes in muscle fiber types, key metabolic proteins, fasting insulin, glucose, and lipid profiles. The intervention led to a 74.7%, and 28.2% reduction in fasting insulin and glucose, respectively. Muscle analysis showed significant increases in CaMK II, Hexokinase II, and IRS-1, indicating improved glucose metabolism. Comb-NMES training markedly improved metabolic control and muscle glucose metabolism in a patient with acute SCI and LMNLs. Enhanced insulin sensitivity and glucose utilization were evidenced by upregulated metabolic proteins which suggests Comb-NMES is a promising intervention for improving muscle and metabolic health in SCI patients with LMNLs. Further studies are needed to confirm these benefits and explore long-term effects.

The study aimed to determine the relationship between glucose, C-peptide, BDNF, and leptin between mother and fetus and neonatal weight. Methods: In the prospective observational cohort study, we included 66 women with T1DM. According to the z-score for neonatal weight, patients were divided into Healthy weight neonates (n=42) and Overweight neonates (n=24). The maternal blood samples were taken during pregnancy and cesarean section when the umbilical vein blood sample was also withdrawn. The maternal vein sera were analyzed for fasting glucose, CRP, leptin, BDNF, TSH, FT3, and FT4. The umbilical vein sera were analyzed for glucose, C-peptide, leptin, TSH, FT3, FT4, and BDNF concentration. The neonatologist measured the skinfold thickness on the third day of neonatal life. Results: A strong correlation was confirmed between maternal and umbilical vein glucose concentration and maternal glucose and C-peptide in umbilical vein blood. A negative correlation was found between the concentration of BDNF in the umbilical vein and glucose in maternal blood. A strong correlation was seen between BMI and maternal blood leptin concentration, neonatal fat body mass, and umbilical vein blood leptin concentration. Increased odds for Overweight neonates were BMI, BDNF, and TSH in the first trimester of pregnancy. Maternal leptin concentration decreased the odds of Overweight neonates. Conclusions: Maternal glucose concentrations affect the fetus’s glucose, C-peptide, and BDNF concentrations. Leptin levels increase in maternal blood due to increased body mass index, and in the neonate, its fat body mass is responsible for increased leptin concentrations.

: Increased glucose and choline uptake are hallmarks of cancer. We investigated if the uptake and conversion of [2H9]choline alone and together with that of [6,6’ 2H2]glucose can be assessed in subcutaneous tumors by deuterium metabolic imaging (DMI) after bolus administration of these compounds. Therefore tumors with human renal carcinoma cells were grown subcutaneously in mice up to ~0.5 cm3. Mice were anesthetized with isoflurane and IV infused in the MR magnet for ~20 sec with ~0.2 ml solutions containing either [2H9]choline (0.05g/kg) alone or together with [6,6’ 2H2]glucose (1.3g/kg). 2H MR was performed on a 11.7T MR system with a home-built 2H/1H coil using a 900 excitation pulse and 400ms repetition time. 3D DMI was recorded at high resolution (2x2x2mm) in 37 min or at low resolution (3.7x3.7x3.7mm) in 2:24 min. Absolute tissue concentrations were calculate assuming initial [HOD]=13.7mM. Within 5 minutes after [2H9]choline infusion its signal appeared in tumor spectra representing concentration increasing up to 0.3–1.2 mM and then slowly decreased or remained constant over 100 minutes. In plasma [2H9]choline disappeared within 15 minutes post-infusion implying that its tumor signal arises from tissue and not blood. After infusing a mixture of [2H9]choline and [6,6’ 2H2]glucose their signals were observed separately in tumor 2H spectra. Over time the [2H9]choline signal broadened, possibly due to conversion to other choline compounds, [[6,6’ 2H2]glucose] declined, [HOD] increased and a lactate signal appeared, reflecting glycolysis. Metabolic maps of all 2H compounds were reconstructed from high resolution DMIs. As choline infusion and glucose DMI is feasible in patients, their simultaneous detection has clinical potential for tumor characterization.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally used for diabetes mellitus, are gaining more popularity for other indications owing to their positive cardiovascular and renal effects. Initially, SGLT2 inhibitors were shown to reduce heart failure (HF) hospitalization and improve cardiovascular outcomes in patients with type 2 diabetes. Later, SGLT2 inhibitors were evaluated in patients with HF with reduced ejection fraction (HFREF) and had beneficial effects independent of the presence of diabetes. Recently, reduction in cardiovascular outcomes were also observed in patients with HF with preserved ejection fraction (HFPEF). SGLT2 inhibitors also reduced renal outcomes in patients with chronic kidney disease. Overall, these drugs have an excellent safety profile with a negligible risk of genitourinary tract infections and ketoacidosis. In this review, we discuss the current data regarding SGLT2 inhibitors in special populations including acute myocardial infarction, acute HF, right ventricular (RV) failure, patients with left ventricular assist device (LVAD), and patients with type1 diabetes. We also discuss the potential mechanisms behind the cardiovascular benefits of these drugs.

Like 18F-FDG, 99mTc-1-thio-D-glucose (99mTc-TG) also binds to GLUT receptors. The aim of this Phase I study was to evaluate the safety, biodistribution and dosimetry of 99mTc-TG. Twelve lym-phoma patients were injected with 729±102 MBq 99mTc-TG. Whole-body planar imaging was per-formed in 10 patients at 2, 4, 6 and 24 h after injection. In all 12 patients SPECT/CT (at 2 h) and SPECT (at 4 and 6 h) imaging was performed. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection. 99mTc-TG injections were well tolerated and no side effects or alterations in blood and urine analyses data were observed. The highest absorbed dose was in the kidneys and urinary bladder wall, followed by the adrenals, prostate, bone mar-row, lungs, myocardium, ovaries, uterus, liver and gall bladder wall. 99mTc-TG SPECT/CT re-vealed foci of high activity uptake in the lymph nodes of all nine patients with known nodal le-sions. Extranodal lesions were detected in all nine cases. In one patient, a lesion in the humerus head, which was not detected by CT, was visualized using 99mTc-TG. Potentially, 99mTc-TG SPECT can be considered as an additional diagnostic method for imaging GLUT receptors in lymphoma patients.

The aim of this study was to establish the blood glucose response to different cooking methods of pasta. Participants consumed three identical meals in a random order that were freshly cooked (hot), cooled and reheated. Blood glucose concentrations were assessed before, and every 15 minutes after ingestion of each meal for 120 minutes. There was a significant interaction between temperature and time (F_{(8.46-372.34)} = 2.75, p = 0.005), with the reheated (90 minutes) condition returning to baseline faster than both cold (120 minutes) and hot conditions. Blood glucose AUC was significantly lower in the reheated (703 ± 56 mmol L^-1 min^-1) compared with the hot condition (735 ± 77 mmol L^-1 min^-1, t(92) = -3.36, pbonferroni = 0.003), with no significant difference with the cold condition (722 ± 62 mmol L^-1 min^-1). To our knowledge, the current study is the first to show that reheating pasta causes changes in post-prandial glucose response, with a quicker return to fasting levels in both the reheated and cooled conditions compared with the hot condition. The mechanisms behind the changes in post-prandial blood glucose seen in this study are most likely related to changes in starch structure and how these changes influence glycaemic response.

This study aimed to examine the association of blood triglyceride levels with fasting blood glucose levels and type 2 diabetes (T2D) prevalence in Chinese adults with normal triglyceride levels (<1.7 mmol/L), using linear regression and binary logistic regression, respectively. This cross-sectional study included 16,706 Chinese adults, among which 1,067 had T2D. Triglycerides were positively associated with fasting plasma glucose after multivariate adjustment (β=0.034, P<0.001). One natural log unit increase in blood triglycerides was associated with a 61% higher multivari-ate-adjusted risk of T2D (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.19-2.17; P=0.002). The positive associations remained when participants who were treated with lipid-lowering or an-ti-diabetic drugs were excluded. The optimal cut-off of triglycerides for T2D was 1.09 mmol/L (obtained using Receiver Operating Characteristic curve analysis). Participants with triglycerides of ≥1.09 mmol/L had a 28% higher risk of T2D (OR, 1.28; 95% CI, 1.07-1.53; P=0.006) compared to those with triglycerides below the cut-off. In conclusion, this study showed that, in people with normal triglyceride levels, triglycerides at the upper normal range correlated with increased T2D diagnosis risk, with an optimal cut-off of 1.09 mmol/L. Therefore, adults with high “normal” triglyceride levels (1.09-1.69 mmol/L) may need to be closely monitored for the development of T2D.

Background: Nonalcoholic fatty liver disease (NAFLD) is regarded as a component of metabolic syndrome, which has insulin resistance (IR) as the primary physiopathological event. The aim of study was to establish the association between IR, assessed using triglyceride and glucose index (TyG), and histopathological features of NAFLD lesions. Methods: The study included patients with metabolic syndrome. Fasting plasma glucose (FPG), fasting lipid profiles and liver enzymes were measured. IR was assessed by TyG index. Liver biopsy was performed for assessment steatosis and fibrosis. Results: TyG index had a mean value of 8.93 ± 1.45, with a higher value in the patients with overweight (p=0.002) and obesity (p=0.004) than in the patients with normal weight. TyG index mean value of 8.78 ± 0.65 in subjects without NASH, 8.91 ± 0.57 in patients with borderline NASH and 9.13 ± 0.55 in patients with definite NASH. Significant difference was found between subjects without NASH and the ones with definite NASH (p=0.004). The analysis of the area under the ROC curve proved that TyG index is a predictor for NASH (p=0.043). Conclusion: TyG index is a facile tool used to identify individuals at risk for NAFLD, but not for the progression of liver lesions.

In order to improve the performance of soft plantation wood, an environmentally friendly inorganic-organic hybrid wood modifier was developed. First, using urea and melamine as crosslinking agents, the waterborne glucose silicone resin (MUG) was prepared with glucose under the catalysis of inorganic acid and metal ions. Then MUG resin was diluted to 10% and 20% mass fraction, and compounded with sodium silicate (S) of 20% and 10% mass fraction, so the inorganic-organic hybrid G10S20 and G20S10 wood modifier were obtained respectively. Then plantation poplar wood (Populus tomentosa) were impregnated and modified with them. Their physical and mechanical properties were tested and compared with those of the wood treated with S of 20% mass fraction (S20). Infrared analysis showed that amino resin characteristic structure (CO-NH-) existed in MUG resin. The resin has good permeability. Compared with S20 modified wood, the degree of shrinkage of G10S20 or G20S10 modified wood is reduced, their moisture absorption is reduced, and their dimensional stability is improved. Waterborne glucose silicone modifier can effectively improve the wood density, modulus of elasticity, modulus of rapture and compression strength. SEM analysis showed that the cell wall of G20S10 modified wood was significantly thicker than the untreated wood, and there were columnar and granular solid substances attached in some cell cavities, ducts and corners, etc. EDX showed that the number of Si elements on the cell wall was significantly increased compared with the control, indicating that the modifier effectively entered the wood cell wall. The waterborne glucose silicone resin can greatly improve the physical and mechanical properties of wood through organic-inorganic hybridization. It is a green, non-formaldehyde, eco-friendly, low cost, compound wood modifier with broad application prospects.

Evolutionary psychology theories propose that contact with green, natural environments may benefit physical health, but little comparable evidence exists for brown, natural environments, such as the desert. In this study, we examined the association between “brownness” and “greenness” with fasting glucose among young residents of El Paso, Texas. We defined brownness as the surface not covered by vegetation or impervious land within Euclidian buffers around participants’ homes. Fasting glucose along with demographic and behavioral data was obtained from the Nurse Engagement and Wellness Study (N = 517). We found that residential proximity to brownness was not associated with fasting glucose when modeled independently. In contrast, we found that residential greenness was associated with decreased levels of fasting glucose, despite the relatively low levels of greenness within the predominantly desert environment of El Paso. A difference between the top and bottom greenness exposure quartiles within a 250 m buffer was associated with a 3.5 mg/dL decrease in fasting glucose levels (95% confidence interval: -6.2, -0.8). Our results suggest that within the understudied context of the desert, green vegetation may be health-promoting to a degree that is similar to other, non-desert locations in the world that have higher baselines levels of green.

Glucose-6-phosphatase (G6Pase), an enzyme found mostly in the kidneys and the liver, acting significant role of supplying glucose through starvation. This study includes (84) subjects, their age ranged from (40 to 54) years. (20) subjects were healthy chosen as control group and (64) patients with type 2 diabetes mellitus were divided into three groups according to their type of anti diabetic therapy : (23) newly diagnosed group without therapy (Group1), (20) with metformin therapy (Group2) and (21) with metformin plus glibenclamide therapies( Group3). The study found that G-6-Pase activity is increased, thereby leading to an increase in endogenous glucose production (EGP) in patients with type 2 diabetes and, therefore FPG will increase. The result found that increasing G-6-Pase activity will increase the concentration of glucose in the blood and that will increase the long-term glycemic control (HbA1c%).

Diabetes is one of the metabolic syndromes that demands the great concern affecting millions of people all over the world. Viral infections were also considered as responsible for diabetes. Though, variety of medications for prevention and treatment of diabetes are available, numerous limitations are also prevailing that cannot be neglected. Precise drug-targetability, controlled drug-release, oral bioavailability, minimizing side effects are a few to consider. To address most of these shortcomings of traditional drug-delivery models, nanoformulation has been employed therein a wide range of nanoformulation models are developed. The pharmacology of a drug can be greatly enhanced through nanoformulation models in diabetes treatment in terms of enhanced bioavailability, prolonged and sustained drug-lease, maintain maximum drug concentration in serum, higher intestinal absorption, and protection from enzymatic degradation. In this review work, recently designed nanoformulation models for efficient insulin delivery and the other properties concerning diabetes such as reducing blood glucose level, total cholesterol, triglycerides, lipid profile, wound healing, elevating antioxidant enzymes etc. are discussed. Classification of the nanoformulation models is done based on the nature of the fabricating material employed in nanoformulation. This review may be helpful in designing a more efficient nanoformulation model for diabetes treatment.

Our findings indicate that all five phytocannabinoids reduce HG-HL-induced -cell loss likely through reducing apoptosis and pyroptosis. The protective effects of CBD, THCV, CBC, and CBN were seen in the GSIS impairment by HG-HL. Although all five phytocannabinoids tested in this research demonstrated the capability to inhibit β-cell dedifferentiation induced by HG-HL, CBD seems to be more effective compared to the other phytocannabinoids, as indicated by the specific biomarker responses of β-cells and progenitor cells to CBD.

Persistent organic pollutants (POPs) accumulation and hypoxia are two factors proposed to adversely alter adipose tissue (AT) functions in the context of excess adiposity. Studies have shown that preadipocytes exposure to dioxin and dioxin-like POPs have the greatest deleterious impact on rodent and immortalized human preadipocyte differentiation, but evidence on human preadipocytes is lacking. Also, hypoxia is known to strongly interfere with the dioxin-response pathway. Therefore, we tested the effects of pre-differentiation polychlorinated biphenyl (PCB)126 exposure and subsequent differentiation under hypoxia on human subcutaneous adipocytes (hSA) differentiation, glucose uptake and expression of selected metabolism- and inflammation-related genes. Pre-differentiation PCB126 exposure lowered the ATP content, glucose uptake and leptin expression of mature adipocytes but had limited effects on differentiation under normoxia (21% O2). Under hypoxia (3% O2), preadipocytes ability to differentiate was significantly reduced as reflected by significant decreased lipid accumulation and downregulation of key adipocyte genes such as PPARγ and adiponectin. Hypoxia increased glucose uptake and GLUT1 expression but abolished the adipocytes insulin response and GLUT4 expression. Expression of pro-inflammatory adipokine IL-6 was slightly increased by both PCB126 and hypoxia, while IL-8 expression was significantly increased only following the PCB126-hypoxia sequence. These observations suggest that PCB126 do not affect human preadipocyte differentiation, but do affect the subsequent adipocytes population, as reflected by lower ATP levels and absolute glucose uptake. On the other hand, PCB126 and hypoxia exert additive effects on AT inflammation, an important player in the development of chronic diseases such as type 2 diabetes and cardiovascular diseases.

The integration of metal nanoparticles and solid carriers can achieve ideal stability, high load and good conductivity. In this work, copper nanoparticles (Cu NPs) were sequentially deposited on a cobalt metal-organic framework (Co-MOF) by bonding with exposed imino groups, followed by a reduction reaction to prepare a new Cu@Co-MOF composite. Cu@Co-MOF acts as a non-enzymatic electrochemical sensor to detect glucose (Glu) in an alkaline medium. The composite working electrode of Cu@Co-MOF/GCE (GCE = glassy carbon electrode) improves the electrocatalytic activity for Glu oxidation. Cu@Co-MOF/GCE shows excellent electrocatalytic performances in Glu concentration ranging 0.005~1.8 mmol∙L⁻¹ (mM): the sensitivities are 282.89 μA∙mM⁻¹∙cm⁻² in 0.005-0.4 mM Glu and 113.15 μA∙mM⁻¹∙cm⁻² in 0.4-1.8 mM Glu respectively with low detection limit of 1.6 μM (S/N = 3) and high selectivity and stability.

Gestational Diabetes Mellitus (GDMs) is worldly wide pregnancy complication. Gestational Diabetes can significantly impact the fetus development. However, the effects of high glucose on embryological development post-fertilization are yet to be researched. Danio rerio embryos are great model to study the embryonic development. In this study, the effects on embryological (morphological and genetic) development were examined in the presence of a high glucose environment that mimic the developing fetus in pregnant women with GMD. Fertilized Zebrafish embryos were treated with normal media and high glucose for 5 days from 3 hours post-fertilization(hpf) to 96hpf respectively as control and experimental groups. Morphological changes are recorded with Microscope images. Hatch rate and heart rate are compared between groups in set up time points. RNA-Seq is performed to examine the gene changes in experimental group. Glucose delayed the zebrafish embryo development by slowing the hatch rate about 24 hours. The brain, heart, and tail started showing morphology smaller in the glucose group compared to the control group at 24 hpf. Heart rate is faster in the glucose group compared to the control group on day 2 and 3 with a statistically significant difference. Among zebrafish whole genome, the significantly changed genes are 556 genes up-regulated and 1118 genes down-regulated respectively in high glucose group. The metabolic and Wnt pathways are altered under high glucose condition. These conditions contribute to significant physiological differences that may provide insight on functionality post-embryological development.

The hyperactivation of the sympathetic nervous system (SNS) is linked to obesity, hypertension, and type 2 diabetes, with elevated norepinephrine (NE) levels being a key feature. Previous research has shown increased sodium-glucose cotransporter 1 (SGLT1) protein in kidneys of hypertensive rodents, prompting investigation into SGLT1 expression in other tissues such as skeletal muscle. This study aimed to assess: i) whether skeletal muscle cells and tissue express SGLT1 and SGLT2 protein; ii) if NE increases SGLT1 in skeletal muscle cells and iii) whether skeletal muscle of neurogenically hypertensive mice exhibits increased SGLT1 expression. We found that i) skeletal muscle cells and tissue are a novel source of SGLT2 protein and ii) NE significantly elevated SGLT1 in skeletal muscle cells. As SGLT2 inhibition (SGLT2i) with Empagliflozin increased SGLT1, in vivo studies with the dual SGLT1/2i, Sotagliflozin were warranted. Treatment of neurogenically hypertensive mice with Sotagliflozin significantly reduced blood pressure. Our findings suggest that SNS activity upregulates the therapeutic target, SGLT1 in skeletal muscle, potentially worsening cardiometabolic control. As clinical trial data suggests cardiorenal benefits with SGLT2i, future studies should aim to utilize sole SGLT1i which may offer a therapeutic strategy for conditions with heightened SNS activity, such as hypertension, diabetes and obesity.

. Background. Hypoxic-ischemic brain injury is one primary cause of long-term neurological disability, morbidity, and death worldwide. The decrease in blood flow and oxygen concentration leads to insufficient nutrient supply to the brain, energy depletion, increased free radical generation, and mitochondrial dysfunction. Perinatal asphyxia — the oxygen supply suspension near birth-time — causes hypoxic-ischemic brain injury and is a major risk factor for neurodevelopmental damage. In pathological scenarios, raloxifene, a selective estrogen receptor modulator, has shown neuroprotective effects. Purpose. To examine whether raloxifene showed neuroprotection in an oxygen-glucose deprivation/reoxygenation astrocyte cell model. Methods. T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37ºC in a hypoxia chamber with 1% O2 for 3, 6, 12, and 24 hours. Cultures were supplemented with raloxifene 1, 10, and 100 nM during both glucose and oxygen deprivation and reoxygenation periods. Results. Raloxifene 100 nM and 10 nM improved cell survival — 65.34% and 70.56% — respectively compared to the control cell groups. Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifene cotreatment. Raloxifene cotreatment reduced superoxide production by 72.72% and peroxide production by 57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-hour oxygen-glucose deprivation followed by 3, 6, and 9 hours of reoxygenation, respectively. Conclusions. Raloxifene improved cell survival and mitochondrial membrane potential, and reduced lipid peroxidation and reactive oxygen species (ROS) production, suggesting a direct effect on mitochondria. Raloxifene protected the oxygen-glucose-deprived astrocyte cells used to mimic hypoxic-ischemic brain injury in this study.

Background and Objectives: Mycobacterium bovis Bacillus Calmette–Guérin (BCG) vaccine administration has been suggested to prevent glucose metabolism abnormalities and fatty liver in genetically obese ob/ob mice; however, it is not clear whether the beneficial effects of BCG are also observed in the progression of glucose intolerance induced by a high-fat diet (HFD). Therefore, the effects of BCG vaccination on changes in glucose tolerance and insulin response were investigated in HFD-fed C57BL/6 mice. Materials and Methods: We used the BCG Tokyo 172 strain to determine its effects on abnormalities in glucose metabolism. For vaccination, five-week-old male mice were injected intraperitoneally with BCG and maintained on an HFD three weeks later. The mice were regularly subjected to intraperitoneal glucose tolerance and insulin tolerance tests (IGTT and ITT). These tests were also performed in mice transplanted with bone marrow cells from BCG-vaccinated donor mice. Results: Significant effects of BCG vaccination on blood glucose levels in IGTT and ITT were observed from week 12 of the experiment. BCG vaccination significantly improved changes in fasting glucose and insulin levels, insulin resistance indexes, and glucagon-to-insulin ratios by HFD at the end of the experiment. Significant inhibitory effects in IGTT and ITT on glucose intolerance were also observed by transplantation with bone marrow cells derived from BCG-vaccinated donor mice. Conclusions: BCG vaccination significantly delayed glucose intolerance progression, suggesting a beneficial effect of BCG on the pathogenesis of type 2 diabetes. It has also been demonstrated that the effects of BCG vaccination may be at least partially due to an immune memory (trained immunity) for hematopoietic stem and progenitor cells of the bone marrow.