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Abstract The benefits of physical exercise on human health make it desirable to identify new approaches that would mimic or potentiate the effects of exercise to treat metabolic diseases. However, whether far-infrared (FIR) hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regulation, and its underling mechanisms remain unclear. Here, a specific far-infrared (FIR) rays generated from graphene-based hyperthermia devices might promote exercise capacity and metabolisms. The material characterization showed that the graphene synthesized by chemical vapour deposition (CVD) was different from carbon fiber, with single-layer structure and high electrothermal transform efficiency. The emission spectra generated by graphene-FIR device would maximize matching those adsorbed by tissues. Graphene-FIR enhanced both core and epidermal temperatures, leading to increased blood flow in the femoral muscle and the abdominal region. The combination of microbiomic and metabolomic analysis revealed that graphene-FIR modulates the metabolism of the gut-muscle axis. This modulation was characterized by an increased abundance of short-chain fatty acids (SCFA)-producing bacteria and AMP, while lactic acid levels decreased. Furthermore, the principal routes involved in glucose metabolism, such as glycolysis and gluconeogenesis, were found to be altered. Graphene-FIR managed to stimulate AMPK activity by activating GPR43, thus enhancing muscle glucose uptake. Furthermore, a microbiota disorder model also demonstrated that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4. Our results provided convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis. These novel findings regarding the therapeutic effects of graphene-FIR suggested its potential utility as a mimetic agent in clinical management of metabolic disorders.

Glucose catabolism, one of the essential pathways sustaining cellular bioenergetics, has been widely studied in the context of tumors. Nevertheless, the function of various branches of glucose metabolism that stem from ‘classical’ glycolysis have only been partially explored. This review focuses on discussing general mechanisms and pathological implications of glycolysis and its branching pathways in the biology of B cell malignancies. We summarize here what is known regarding pentose phosphate, hexosamine, serine biosynthesis, and glycogen synthesis pathways in this group of tumors. Despite most findings have been based on malignant B cells themselves, we also discuss the role of glucose metabolism in the tumor microenvironment, with a focus on T cells. Understanding the contribution of glycolysis branching pathways and how they are hijacked in B cell malignancies will help to dissect the role they have in sustaining the dissemination and proliferation of tumor B cells and regulating immune responses within these tumors. Ultimately, this should lead to deciphering associated vulnerabilities and improve current therapeutic schedules.

Alzheimer's disease (AD) is an increasingly important public health concern due to the increasing proportion of older individuals within the general population. The impairment of processes responsible for adequate brain energy supply primarily determines the early features of the aging process. Restricting brain energy supply results in brain hypometabolism prior to clinical symptoms and is anatomically and functionally associated with cognitive impairment. The present study investigated changes in metabolic profiles induced by intracerebroventricular‐streptozotocin (ICV‐STZ) in an AD‐like animal model. To this end, male Wistar rats received a single injection of STZ (3 mg·kg−1) by ICV (2.5 μL into each ventricle for 5 min on each side). In the second week after receiving ICV‐STZ, rats were tested for cognitive performance using the Morris Water Maze test and subsequently prepared for positron emission tomography (PET) to confirm AD‐like symptoms. Tandem Mass Spectrometry (MS/MS) analysis was used to detect amino acid changes in cerebrospinal fluid (CFS) samples. Our metabolomics study revealed a reduction in the concentrations of various amino acids (alanine, arginine, aspartic acid, glutamic acid, glycine, isoleucine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine) in CSF of ICV‐STZ‐treated animals as compared to controls rats. The results of the current study indicate amino acid levels could potentially be considered targets of nutritional and/or pharmacological interventions to interfere with AD progression.

Abstract Background There are contradictory effects regarding the effect of NAD + precursor on glucose metabolism and liver enzymes. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of NAD + precursor supplementation on glucose metabolism, C-reactive protein (CRP), and liver enzymes. Methods PubMed/MEDLINE, Web of Science, SCOPUS, and Embase databases were searched using standard keywords to identify all controlled trials investigating the glucose metabolism, CRP, and liver enzymes effects of NAD + precursor. Pooled weighted mean difference (WMD) and 95% confidence intervals (95% CI) were achieved by random-effects model analysis for the best estimation of outcomes. Results Forty-five articles with 9256 participants’ were included in this article. The pooled findings showed that NAD + precursor supplementation had a significant increase in glucose (WMD: 2.17 mg/dL, 95% CI: 0.68, 3.66, P = 0.004) and HbA1c (WMD: 0.11, 95% CI: 0.06, 0.16, P

Abstract High sugar consumption is associated with cardiovascular diseases and diabetes. Current sugar substitutes may cause taste sensations and gastrointestinal symptoms. ENSO 16 is a combination of 16 different sugar substitutes and plant fibers and has been designed as a sugar alternative. The impact on plasma glucose metabolism as well as on gastrointestinal tolerance has not been investigated yet. 17 healthy participants were enrolled in this randomized, double-blind trial. Participants received a single oral dose of 30 g glucose or 30 g ENSO 16 and crossed over to the alternate treatment after a 7 day wash out period. The study endpoint was the effect on plasma glucose, insulin, C-peptide concentrations and gastrointestinal disorders. A questionnaire regarding gastrointestinal symptoms was used for individual subjective scoring. The mean baseline adjusted plasma glucose AUC0–180 min was significantly greater after glucose administration compared to ENSO 16 (n = 15, p = 0.0128, paired t-test). Maximum plasma glucose elevation over baseline was 117 mg*dl−1 and 20 mg*dl−1 after oral glucose or ENSO 16, respectively. Insulin and C-peptide AUC0−180 min were significantly greater after glucose compared to ENSO 16 intake (p

Abstract Hypoxia can cause a variety of diseases, including ischemic stroke and neurodegenerative diseases. Within a certain range of partial pressure of oxygen, cells can respond to changes in oxygen. Changes in oxygen concentration beyond a threshold will cause damage or even necrosis of tissues and organs, especially for the central nervous system. Therefore, it is very important to find appropriate measures to alleviate damage. MiRNAs can participate in the regulation of hypoxic responses in various types of cells. MiRNAs are involved in regulating hypoxic responses in many types of tissues by activating the hypoxia-inducible factor (HIF) to affect angiogenesis, glycolysis and other biological processes. By analyzing differentially expressed miRNAs in hypoxia and hypoxia-related studies, as well as the HT22 neuronal cell line under hypoxic stress, we found that the expression of miR-18a was changed in these models. MiR-18a could regulate glucose metabolism in HT22 cells under hypoxic stress by directly regulating the 3’UTR of the Hif1a gene. As a small molecule, miRNAs are easy to be designed into small nucleic acid drugs, so this study can provide a theoretical basis for the research and treatment of nervous system diseases caused by hypoxia. Graphical Abstract

Abstract The β‐cell relies predominantly on glucose utilization to generate adenosine triphosphate, which is crucial for both cell viability and insulin secretion. The β‐cell has evolved remarkable metabolic flexibility to productively respond to shifts in environmental conditions and changes in glucose availability. Although these adaptive responses are important for maintaining optimal cellular function, there is emerging evidence that the resulting changes in cellular metabolites can impact the epigenome, causing transient and lasting alterations in gene expression. This review explores the intricate interplay between metabolism and the epigenome, providing valuable insights into the molecular mechanisms leading to β‐cell dysfunction in diabetes. Understanding these mechanisms will be critical for developing targeted therapeutic strategies to preserve and enhance β‐cell function, offering potential avenues for interventions to improve glycemic control in individuals with diabetes.

Au@Pt nanozyme, a bimetallic core–shell structure Au and Pt nanoparticle, has attracted significant attention due to its excellent catalytic activity and stability. Here, we propose that Au@Pt improves glucose tolerance and reduces TG after four weeks administration. The transcriptomic analysis of mouse liver tissues treated with Au@Pt nanozyme showed changes in genes related to glucose and lipid metabolism signaling pathways, including glycolysis/gluconeogenesis, pyruvate metabolism, PPAR signaling, and insulin signaling. Moreover, analysis of fecal samples from mice treated with Au@Pt nanozyme showed significant changes in the abundance of beneficial gut microbiota such as Dubosiella, Parvibacter, Enterorhabdus, Monoglobus, Lachnospiraceae_UCG-008, Lachnospiraceae_UCG-006, Lachnospiraceae_UCG-001, and Christensenellaceae_R-7_group. Combined multi-omics correlation analyses revealed that the modulation of glucose and lipid metabolism by Au@Pt was strongly correlated with changes in hepatic gene expression profiles as well as changes in gut microbial profiles. Overall, our integrated multi-omics analysis demonstrated that Au@Pt nanozyme could modulate glucose and lipid metabolism by regulating the expression of key genes in the liver and altering the composition of gut microbiota, providing new insights into the potential applications of Au@Pt nanozyme in the treatment of metabolic disorder. [ABSTRACT FROM AUTHOR]

Background: Ectoine as an amino acid derivative is widely applied in many fields, such as the food industry, cosmetic manufacturing, biologics, and therapeutic agent. Large-scale production of ectoine is mainly restricted by the cost of fermentation substrates (e.g., carbon sources) and sterilization. Results: In this study, Halomonas cupida J9 was shown to be capable of synthesizing ectoine using xylose as the sole carbon source. A pathway was proposed in H. cupida J9 that synergistically utilizes both WBG xylose metabolism and EMP glucose metabolism for the synthesis of ectoine. Transcriptome analysis indicated that expression of ectoine biosynthesis module was enhanced under salt stress. Ectoine production by H. cupida J9 was enhanced by improving the expression of ectoine biosynthesis module, increasing the intracellular supply of the precursor oxaloacetate, and utilizing urea as the nitrogen source. The constructed J9U-P8EC achieved a record ectoine production of 4.12 g/L after 60 h of xylose fermentation. Finally, unsterile production of ectoine by J9U-P8EC from either a glucose-xylose mixture or corn straw hydrolysate was demonstrated, with an output of 8.55 g/L and 1.30 g/L of ectoine, respectively. Conclusions: This study created a promising H. cupida J9-based cell factory for low-cost production of ectoine. Our results highlight the potential of J9U-P8EC to utilize lignocellulose-rich agriculture waste for open production of ectoine. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM), prediabetes, and insulin resistance are highly prevalent in patients with ischemic stroke (IS). DM is associated with higher risk for poor outcomes after IS. Objective: Investigate the risk of recurrent vascular events and mortality associated with impaired glucose metabolism compared to normoglycemia in patients with IS and transient ischemic attack (TIA). Methods: Systematic literature search was performed in PubMed, Embase, Cochrane Library on 21st March 2024 and via citation searching. Studies that comprised IS or TIA patients and exposures of impaired glucose metabolism were eligible. Study Quality Assessment Tool was used for risk of bias assessment. Covariate adjusted outcomes were pooled using random-effects meta-analysis. Main outcomes: Recurrent stroke, cardiac events, cardiovascular and all-cause mortality and composite of vascular outcomes. Results: Of 10,974 identified studies 159 were eligible. 67% had low risk of bias. DM was associated with an increased risk for composite events (pooled HR (pHR) including 445,808 patients: 1.58, 95% CI 1.34–1.85, I2 = 88%), recurrent stroke (pHR including 1.161.527 patients: 1.42 (1.29–1.56, I2 = 92%), cardiac events (pHR including 443,863 patients: 1.55, 1.50–1.61, I2 = 0%), and all-cause mortality (pHR including 1.031.472 patients: 1.56, 1.34–1.82, I2 = 99%). Prediabetes was associated with an increased risk for composite events (pHR including 8,262 patients: 1.50, 1.15–1.96, I2 = 0%) and recurrent stroke (pHR including 10,429 patients: 1.50, 1.18–1.91, I2 = 0), however, not with mortality (pHR including 9,378 patients, 1.82, 0.73–4.57, I2 = 78%). Insulin resistance was associated with recurrent stroke (pHR including 21,363 patients: 1.56, 1.19–2.05, I2 = 55%), but not with mortality (pHR including 21,363 patients: 1.31, 0.66–2.59, I2 = 85%). Discussion: DM is associated with a 56% increased relative risk of death after IS and TIA. Risk estimates regarding recurrent events are similarly high between prediabetes and DM, indicating high cardiovascular risk burden already in precursor stages of DM. There was a high heterogeneity across most outcomes. [ABSTRACT FROM AUTHOR]

Background: Abiotic stress seriously affects the growth and yield of crops. It is necessary to search and utilize novel abiotic stress resistant genes for 2.0 breeding programme in quinoa. In this study, the impact of drought stress on glucose metabolism were investigated through transcriptomic and metabolomic analyses in quinoa seeds. Candidate drought tolerance genes on glucose metabolism pathway were verified by qRT-PCR combined with yeast expression system. Results: From 70 quinoa germplasms, drought tolerant material M059 and drought sensitive material M024 were selected by comprehensive evaluation of drought resistance. 7042 differentially expressed genes (DEGs) were indentified through transcriptomic analyses. Gene Ontology (GO) analysis revealed that these DEGs were closely related to carbohydrate metabolic process, phosphorus-containing groups, and intracellular membrane-bounded organelles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis detected that DEGs were related to pathways involving carbohydrate metabolisms, glycolysis and gluconeogenesis. Twelve key differentially accumulated metabolites (DAMs), (D-galactose, UDP-glucose, succinate, inositol, D-galactose, D-fructose-6-phosphate, D-glucose-6-phosphate, D-glucose-1-phosphate, dihydroxyacetone phosphate, ribulose-5-phosphate, citric acid and L-malate), and ten key candidate DEGs (CqAGAL2, CqINV, CqFrK7, CqCELB, Cqbg1x, CqFBP, CqALDO, CqPGM, CqIDH3, and CqSDH) involved in drought response were identified. CqSDH, CqAGAL2, and Cqβ-GAL13 were candidate genes that have been validated in both transcriptomics and yeast expression screen system. Conclusion: These findings provide a foundation for elucidating the molecular regulatory mechanisms governing glucose metabolism in quinoa seeds under drought stress, providing insights for future research exploring responses to drought stress in quinoa. [ABSTRACT FROM AUTHOR]

Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle‐aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age‐related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3‐adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18‐month‐old) C57BL/6JN mice. Sustained β3‐AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a favorable adipokine profile. At the cellular level, CL treatment increased uncoupling protein 1 (UCP1)‐dependent thermogenesis in brown adipose tissue (BAT). However, in white adipose tissue (WAT) depots, CL treatment increased glycerol and lipid de novo lipogenesis (DNL) and turnover suggesting the activation of the futile substrate cycle of lipolysis and reesterification in a UCP1‐independent manner. Increased lipid turnover was also associated with the simultaneous upregulation of proteins involved in glycerol metabolism, fatty acid oxidation, and reesterification in WAT. Further, a dose‐dependent impact of CL treatment on inflammation was observed, particularly in subcutaneous WAT, suggesting a potential mismatch between fatty acid supply and oxidation. These findings indicate that chronic β3‐AR stimulation activates distinct cellular mechanisms that increase energy expenditure in BAT and WAT to improve systemic metabolism in aged mice. Considering that people lose BAT with aging, activation of futile lipid cycling in WAT presents a novel strategy for improving age‐related metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) has become a thorny problem in the treatment of breast cancer because of its high invasiveness, metastasis and recurrence. Although immunotherapy has made important progress in TNBC, immune escape caused by many factors, especially metabolic reprogramming, is still the bottleneck of TNBC immunotherapy. Regrettably, the mechanisms responsible for immune escape remain poorly understood. Exploring the mechanism of TNBC immune escape at the metabolic level provides a target and direction for follow-up targeting or immunotherapy. In this review, we focus on the mechanism that TNBC affects immune cells and interstitial cells through hypoxia, glucose metabolism, lipid metabolism and amino acid metabolism, and changes tumor metabolism and tumor microenvironment. This will help to find new targets and strategies for TNBC immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Ubiquitin-specific protease 15 (USP15) exhibits amplifications in various tumors, including gastric cancer (GC), yet its biological function and mechanisms in GC progression remain elusive. Methods: Here, we established stable USP15 knockdown or overexpression GC cell lines and explored the potential mechanism of USP15 in GC. Besides, we also identified interacting targets of USP15. Results: USP15 knockdown significantly impeded cell proliferation, invasion, epithelial-mesenchymal transition, and distal colonization in xenograft models, while enhancing oxaliplatin's antitumor effect. USP15 was involved in ubiquitination modification of glycolytic regulators. Silencing of USP15 suppressed glycolytic activity and impaired mitochondrial functions. Interference with USP15 expression reversed tumor progression and distal colonization in vivo. HKDC1 and IGF2BP3 were found as core interacting targets of USP15, and HKDC1 was identified as a substrate for ubiquitination modification by USP15, whereby USP15 regulated glucose metabolism activity by inhibiting the ubiquitination degradation of HKDC1. Conclusions: Our study unveiled aberrantly high expression of USP15 in GC tissues, correlating with malignant progression and nonresponse to neoadjuvant therapy. USP15 inhibitors, if developed, could be effective in promoting chemotherapy through glucose metabolism remodeling. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes (T2D) is the predominant form of diabetes mellitus and is among the leading causes of death with an increasing prevalence worldwide. However, the pathological mechanism underlying T2D remains complex and unclear. An increasing number of studies have suggested an association between circadian clock disruption and high T2D prevalence. Method: This review explores the physiological and genetic evidence underlying T2D symptoms associated with circadian clock disturbances, including insulin secretion and glucose metabolism. Results and Discussion: Notably, circadian clock disruption reduces insulin secretion and insulin sensitivity and negatively affects glucose homeostasis. The circadian clock regulates the hypothalamic-pituitary-adrenal axis, an important factor that regulates glucose metabolism and influences T2D progression. Therefore, circadian clock regulation is an attractive, novel therapeutic approach for T2D, and various circadian clock stabilizers play therapeutic roles in T2D. Lastly, this review suggests novel therapeutic and preventive approaches using circadian clock regulators for T2D. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) infection is the primary risk factor for the pathogenesis of gastric cancer (GC). N6‐methyladenosine (m6A) plays pivotal roles in mRNA metabolism and hnRNPA2B1 as an m6A reader is shown to exert m6A‐dependent mRNA stabilization in cancer. This study aims to explore the role of hnRNPA2B1 in H. pylori‐associated GC and its novel molecular mechanism. Multiple datasets and tissue microarray are utilized for assessing hnRNPA2B1 expression in response to H. pylori infection and its clinical prognosis in patients with GC. The roles of hnRNPA2B1 are investigated through a variety of techniques including glucose metabolism analysis, m6A‐epitranscriptomic microarray, Ribo‐seq, polysome profiling, RIP‐seq. In addition, hnRNPA2B1 interaction with poly(A) binding protein cytoplasmic 1 (PABPC1) is validated using mass spectrometry and co‐IP. These results show that hnRNPA2B1 is upregulated in GC and correlated with poor prognosis. H. pylori infection induces hnRNPA2B1 upregulation through recruiting NF‐κB to its promoter. Intriguingly, cytoplasm‐anchored hnRNPA2B1 coordinated PABPC1 to stabilize its relationship with cap‐binding eIF4F complex, which facilitated the translation of CIP2A, DLAT and GPX1 independent of m6A modification. In summary, hnRNPA2B1 facilitates the non‐m6A translation of epigenetic mRNAs in GC progression by interacting with PABPC1‐eIF4F complex and predicts poor prognosis for patients with GC. [ABSTRACT FROM AUTHOR]

Application of stable isotopically labelled (SIL) molecules in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) over a series of time points allows the temporal and spatial dynamics of biochemical reactions to be tracked in a biological system. However, these large kinetic MSI datasets and the inherent variability of biological replicates presents significant challenges to the rapid analysis of the data. In addition, manual annotation of downstream SIL metabolites involves human input to carefully analyse the data based on prior knowledge and personal expertise. To overcome these challenges to the analysis of spatiotemporal MALDI-MSI data and improve the efficiency of SIL metabolite identification, a bioinformatics pipeline has been developed and demonstrated by analysing normal bovine lens glucose metabolism as a model system. The pipeline consists of spatial alignment to mitigate the impact of sample variability and ensure spatial comparability of the temporal data, dimensionality reduction to rapidly map regional metabolic distinctions within the tissue, and metabolite annotation coupled with pathway enrichment modules to summarise and display the metabolic pathways induced by the treatment. This pipeline will be valuable for the spatial metabolomics community to analyse kinetic MALDI-MSI datasets, enabling rapid characterisation of spatio-temporal metabolic patterns from tissues of interest. [ABSTRACT FROM AUTHOR]

Cataracts are the world's leading cause of blindness, and diabetes is the second leading risk factor for cataracts after old age. Despite this, no preventative treatment exists for cataracts. The altered metabolism of excess glucose during hyperglycaemia is known to be the underlying cause of diabetic cataractogenesis, resulting in localised disruptions to fibre cell morphology and cell swelling in the outer cortex of the lens. In rat models of diabetic cataracts, this damage has been shown to result from osmotic stress and oxidative stress due to the accumulation of intracellular sorbitol, the depletion of NADPH which is used to regenerate glutathione, and the generation of fructose metabolites via the polyol pathway. However, differences in lens physiology and the metabolism of glucose in the lenses of different species have prevented the translation of successful treatments in animal models into effective treatments in humans. Here, we review the stresses that arise from hyperglycaemic glucose metabolism and link these to the regionally distinct metabolic and physiological adaptations in the lens that are vulnerable to these stressors, highlighting the evidence that chronic oxidative stress together with osmotic stress underlies the aetiology of human diabetic cortical cataracts. With this information, we also highlight fundamental gaps in the knowledge that could help to inform new avenues of research if effective anti-diabetic cataract therapies are to be developed in the future. [ABSTRACT FROM AUTHOR]

High-Protein Mulberry is a novel strain of mulberry. High-Protein Mulberry leaves (HPM) were the subject of this study, which aimed to investigate its efficacy and underlying mechanisms in modulating glucose and lipid metabolism. A six-week intervention using db/db mice was carried out to assess the effects of HPM on serum lipid levels, liver function, and insulin (INS) levels. qRT-PCR and Western Blotting were employed to measure key RNA and protein expressions in the PI3K/Akt and PPARα/CPT-1 pathways. UHPLC-MS and the Kjeldahl method were utilized to analyze the component content and total protein. Additionally, network pharmacology was employed to predict regulatory mechanism differences between HPM and Traditional Mulberry leaves. The results of the study revealed significant improvements in fasting blood glucose, glucose tolerance, and insulin resistance in mice treated with HPM. HPM notably reduced serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and INS, while increasing high-density lipoprotein cholesterol (HDL-C) levels. The treatment also effectively mitigated liver fatty lesions, inflammatory infiltration, and islet atrophy. HPM activation of the PI3K/Akt/PPARα/CPT-1 pathway suggested its pivotal role in the regulation of glucose and lipid metabolism. With its rich composition and pharmacodynamic material basis, HPM displayed a greater number of targets associated with glucose and lipid metabolism pathways, underscoring the need for further research into its potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Giardia lamblia, the cause of giardiasis, significantly impacts patients with metabolic disorders related to insulin resistance (IR). Both giardiasis and metabolic disorders share elements such as chronic inflammation and intestinal dysbiosis, which substantially affect the metabolic and cytokine profiles of patients. This review discusses the mechanisms of virulence of G. lamblia, its influence on the immune system, and its association with metabolic disorders. The review aims to show how G. lamblia invasion acts on the immune system and the glucose and lipid metabolism. Key findings reveal that G. lamblia infection, by disrupting intestinal permeability, alters microbiota composition and immune responses, potentially impairing metabolic status. Future research should focus on elucidating the specific mechanisms by which G. lamblia influences the metabolism, exploring the long-term consequences of chronic infection, and developing targeted therapeutic strategies that include both parasitic and metabolic aspects. These insights underscore the need for a multidisciplinary approach to the treatment of giardiasis in patients with metabolic disorders. [ABSTRACT FROM AUTHOR]

Women typically have less muscle mass and more fat mass than men, while at the same time possessing similar or even greater whole‐body insulin sensitivity. Our study aimed to investigate the molecular factors in primarily adipose tissue, but also in skeletal muscle, contributing to this sex difference. In healthy, moderately active premenopausal women and men with normal weight (28 ± 5 and 23 ± 3 years old; BMI 22.2 ± 1.9 and 23.7 ± 1.7) and in healthy, recreationally active women and men with overweight (32.2 ± 6 and 31.0 ± 5 years old; BMI 29.8 ± 4.3 & 30.9 ± 3.7) matched at age, BMI, and fitness level, we assessed insulin sensitivity and glucose tolerance with a hyperinsulinemic–euglycemic clamp or oral glucose tolerance test and studied subcutaneous adipose tissue and skeletal muscle samples with western blotting. Additionally, we traced glucose‐stimulated glucose disposal in adipose tissues of female and male C57BL/6J littermate mice aged 16 weeks and measured glucose metabolic proteins. Our findings revealed greater protein expression related to glucose disposal in the subcutaneous adipose tissue (AKT2, insulin receptor, glucose transport 4) and skeletal muscle (hexokinase II, pyruvate dehydrogenase) in women compared to matched men with normal weight and with overweight. This increased protein capacity for glucose uptake extended to white adipose tissues of mice accompanied with ~2‐fold greater glucose uptake compared to male mice. Furthermore, even in the obese state, women displayed better glucose tolerance than matched men, despite having 46% body fat and 20 kg less lean mass. In conclusion, our findings suggest that the superior potential for glucose disposal in female subcutaneous adipose tissue and skeletal muscle, driven by greater expression of various glucose metabolic proteins, compensates for their lower muscle mass. This likely explains women's superior glucose tolerance and tissue insulin sensitivity compared to men. [ABSTRACT FROM AUTHOR]

Background: Obesity in pregnancy is linked to adverse clinical outcomes such as gestational diabetes. Recently, a risk score calculated by different ceramide concentrations was recognized as a new way to investigate cardiovascular risk. The aim was to analyze if the ceramide risk score and cardiometabolic risk vary between normal-weight, obese, and females with prior Roux-en-Y bypass surgery (RYGB) during pregnancy. Methods: Three cohorts were investigated: first, 25 pregnant females with a history of RYGB; second, 19 with preconception BMI ≥ 35 kg/m2; and third, 19 normal-weight (preconception BMI < 25 kg/m2). Around the 24th to 28th weeks of gestation routine laboratory assessments, 3 h 75 g oral and intravenous glucose tolerance tests were carried out. The correlation of ceramide risk scores and ceramide ratios (Cer(d18:1/18:0)/Cer(d18:1/16:0)) with metabolic parameters was analyzed via Pearson correlation. The cohorts were compared via ANOVA and unpaired t-tests. Results: The RYGB cohort had lower ceramide risk scores and ratios compared to obese pregnant females (7.42 vs. 9.34, p = 0.025; 0.33 vs. 0.47, p < 0.001). Ceramide risk score and ratio were found to correlate negatively with insulin sensitivity (measured with the Matsuda (r = −0.376, p = 0.031; r = −0.455, p = 0.008) and calculated sensitivity index (r = −0.358, p = 0.044; r = −0.621, p < 0.001) in females without RYGB. The ceramide risk score correlated positively with body fat in RYGB females (r = 0.650, p = 0.012). Conclusions: We found that females after RYGB have lower ceramide risk scores and ceramide ratios compared to obese pregnant females, possibly indicating lower metabolic risk. [ABSTRACT FROM AUTHOR]

Intermittent religious fasting increases the risk of hypo- and hyperglycemia in individuals with diabetes, but its impact on those without diabetes has been poorly investigated. The aim of this preliminary study 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, TRE, or control group. Continuous glucose monitoring and food intake documentation were conducted before and during the 19 days of the intervention, and the 24 h mean glucose and glycemic variability indices were assessed. The 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 comparisons (BF vs. control: p = 0.010; TRE vs. BF: p = 0.022). However, there were no alterations of the 24 h mean glucose, intra- and inter-day glycemic variability indices in any group. The proportions of time above and below the range (70–180 mg/dL) remained unchanged. BF and TRE do not exhibit negative effects on glycemic control and variability in subjects without diabetes. [ABSTRACT FROM AUTHOR]

Before the absorption in the intestine, glucose encounters gut bacteria, which may serve as a barrier against hyperglycemia by metabolizing glucose. In the present study, we compared the capacity of enterobacterial strains to lower glucose levels in an in vitro model of nutrient-induced bacterial growth. Two probiotic strains, Hafnia alvei HA4597 (H. alvei) and Escherichia coli (E. coli) Nissle 1917, as well as E. coli K12, were studied. To mimic bacterial growth in the gut, a planktonic culture was supplemented twice daily by the Luria Bertani milieu with or without 0.5% glucose. Repeated nutrient provision resulted in the incremental growth of bacteria. However, in the presence of glucose, the maximal growth of both strains of E. coli but not of H. alvei was inhibited. When glucose was added to the culture medium, a continuous decrease in its concentration was observed during each feeding phase. At its highest density, H. alvei displayed more efficient glucose consumption accompanied by a more pronounced downregulation of glucose transporters' expression than E. coli K12. Thus, the study reveals that the probiotic strain H. alvei HA4597 is more resilient to maintain its growth than E. coli in the presence of 0.5% glucose accompanied by more efficient glucose consumption. This experimental approach offers a new strategy for the identification of probiotics with increased glucose metabolizing capacities potentially useful for the prevention and co-treatment of type 2 diabetes. [ABSTRACT FROM AUTHOR]

In order to provide theoretical support for diabetes prevention and therapy, this study investigated the regulatory effect of Berberis dasystachya Maxim. Polysaccharide (BDP) on glucose and lipid metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetic model rats were randomly assigned to the model control group, low-dose polysaccharide group (BDP-L, 10 mg/kg), mid-dose polysaccharide group (BDP-M, 200 mg/kg), and high-dose group (BDP-H, 400 mg/kg). Blood lipid levels, lipid metabolic enzyme activity, and antioxidant enzyme activity served as evaluation markers. Results showed that after 28 days of administering yellow thorn polysaccharide, the BDP-treated groups exhibited significantly (P<0.05) lower blood glucose and lipid levels compared to the model group, with a remarkable 39.16% reduction in blood glucose in the high-dose group (P<0.01). In contrast, serum insulin levels and hepatic glycogen (HG) levels increased in the BDP-treated groups (P<0.05 or P<0.01), with a 1.28-fold increase in serum insulin (P<0.01) and an 89.79% increase in HG (P<0.01) in the high-dose group. Furthermore, compared to the model group, serum and pancreatic levels of catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH-Px) were significantly elevated (P<0.05 or P<0.01), while malondialdehyde (MDA) levels were considerably reduced (P<0.05) in a dose-dependent manner following BDP treatment. In conclusion, BDP effectively improved glucolipid metabolism in diabetic rats by alleviating oxidative stress, ultimately safeguarding pancreatic β-cell integrity in type I diabetes. [ABSTRACT FROM AUTHOR]

Polygonatum sibiricum, a plant homologous to both medicine and food, is of significant importance. Its primary active components include polysaccharides, saponin, flavonoids, polyphenols, and alkaloids. These constituents are known for their roles in enhancing immune function, combating fatigue, providing anti-oxidative benefits, reducing blood sugar, and offering anti-inflammatory effects. Consequently, P. sibiricum presents wide-ranging prospects in health food and pharmaceutical research and development. This paper provides a comprehensive summary of research advancements in the polysaccharides, flavonoids, saponins, and solomonseal rhizome extract of P. sibiricum, particularly in metabolic regulation. It delves into the mechanisms by which the main active substances of P. sibiricum influence glucose and lipid metabolism. Simultaneously, the paper analyzes current patents and the state of industrial development related to P. sibiricum, aiming to provide a reference for future research and development of metabolic regulation functional products based on this plant. [ABSTRACT FROM AUTHOR]

Because of the advent of genome-editing technology, gene knockout (KO) hamsters have become attractive research models for diverse diseases in humans. This study established a new KO model of diabetes by disrupting the insulin receptor substrate-2 (Irs2) gene in the golden (Syrian) hamster. Homozygous KO animals were born alive but with delayed postnatal growth until adulthood. They showed hyperglycemia, high HbA1c, and impaired glucose tolerance. However, they normally responded to insulin stimulation, unlike Irs2 KO mice, an obese type 2 diabetes (T2D) model. Consistent with this, Irs2 KO hamsters did not increase serum insulin levels upon glucose administration and showed β-cell hypoplasia in their pancreas. Thus, our Irs2 KO hamster provide a unique T2D animal model that is distinct from the obese T2D models. This model may contribute to a better understanding of the pathophysiology of human non-obese T2D with β-cell dysfunction, the most common type of T2D in East Asian countries, including Japan. [ABSTRACT FROM AUTHOR]

Abnormal glucose metabolism in microglial is closely associated with Alzheimer's disease (AD). Reprogramming of microglial glucose metabolism is centered on regulating the way in which microglial metabolize glucose to alter microglial function. Therefore, reprogramming microglial glucose metabolism is considered as a therapeutic strategy for AD. Huanshaodan (HSD) is a Chinese herbal compound which shows significant efficacy in treating AD, however, the precise mechanism by which HSD treats AD remains unclear. This study is aim to investigate whether HSD exerts anti-AD effects by regulating the metabolic reprogramming of microglial through the mTOR/HIF-1α signaling pathway. SAMP8 mice and BV2 cells were used to explore the alleviative effect of HSD on AD and the molecular mechanism in vivo and in vitro. The pharmacodynamic effects of HSD was evaluated by behavioral tests. The pathological deposition of Aβ in brain of mice was detected by immunohistochemistry. ELISA method was used to measure the activity of HK2 and the expression of PKM2, IL-6 and TNF-α in hippocampus and cortex tissues of mice. Meanwhile, proteins levels of p-mTOR, mTOR, HIF-1α, CD86, Arg1 and IL-1β were detected by Western-blot. LPS-induced BV2 cells were treated with HSD-containing serum. The analysis of the expression profiles of the CD86 and CD206 markers by flow cytometry allows us to distinguish the BV2 polarization. Glucose, lactic acid, ATP, IL-6 and TNF-α levels, as well as lactate dehydrogenase and pyruvate dehydrogenase activities were evaluated in the BV2. Western-blot analysis was employed to detect mTOR, p-mTOR, HIF-1α and IL-1β levels in BV2. And the mTOR agonist MHY1485 (MHY) was chosen to reverse validate. In this study, it is found that HSD improved cognitive impairment in SAMP8 mice and reduced Aβ deposition, suppressed the levels of glycolysis and neuroinflammation in mice. In LPS-induced BV2 cells, HSD also regulated glycolysis and neuroinflammation, and suppressed the mTOR/HIF-1α signaling pathway. More importantly, these effects were reversed by MHY. It is demonstrated that HSD regulated microglial glucose metabolism reprogramming by inhibiting the mTOR/HIF-1α signaling pathway, alleviated neuroinflammation, and exerted anti-AD effects. This study provided scientific evidence for the clinical application of HSD for treating AD. [ABSTRACT FROM AUTHOR]

Recent research has extensively explored the intricate mechanisms that underlie the effectiveness of acupuncture, highlighting the importance of stimulating acupoints, the role of acupuncture techniques in managing diseases, and the interaction between meridian pathways and molecular processes. Studies have underscored the crucial role of acupuncture in activating neurons, modulating the immune system, and influencing vascular activity, all of which contribute significantly to its therapeutic benefits across a wide range of symptoms and conditions. Utilization of imaging modalities enables the identification of changes in cerebral blood flow, brain function, and regional glucose metabolism following acupuncture sessions. The interstitial fluid circulation network within meridians adheres to specific laws that facilitate the transportation of materials. Acupuncture initiates the release of neurotransmitters, neuropeptides, and immune factors, impacting pain perception, inflammation, and physiological functions. It influences the complex neuro–endocrine–immune network by activating pathways involving the nervous system, the hypothalamic-pituitary-adrenal axis, and immune responses. Moreover, acupuncture induces molecular modifications such as phosphorylation, methylation, and histone modification, leading to key molecular changes that ultimately result in anti-inflammatory effects and the regulation of immune responses. [ABSTRACT FROM AUTHOR]

Background: Magnesium plays a crucial role in glucose metabolism and insulin action. This study aimed to evaluate serum magnesium levels in patients with type 2 diabetes mellitus (T2DM) and explore its relationship with glycemic control and treatment modalities. Methods: This case-control study included 50 T2DM patients and 50 non-diabetic controls. Serum magnesium levels were measured and compared between groups. The association between magnesium levels and glycemic control, as well as the impact of different treatment types, was analyzed. Results: T2DM patients had significantly lower mean serum magnesium levels compared to controls (1.72 ± 0.28 mg/dL vs 2.14 ± 0.22 mg/dL, p<0.001). Hypomagnesemia (<1.5 mg/dL) was more prevalent in T2DM patients (40%) than in controls (2%). T2DM patients were 32.066 times more likely to have hypomagnesemia (p<0.001). Uncontrolled diabetics had lower magnesium levels than controlled diabetics (1.14 ± 0.12 mg/dL vs 1.91 ± 0.32 mg/dL, p<0.001). Insulin-treated patients showed lower magnesium levels compared to those on oral hypoglycemic agents (1.35 ± 0.21 mg/dL vs 2.06 ± 0.26 mg/dL, p<0.001). Conclusion: This study demonstrates a significant association between T2DM and lower serum magnesium levels. Poor glycemic control and insulin treatment were associated with lower magnesium levels. These findings suggest the potential importance of monitoring serum magnesium in T2DM management and warrant further investigation into the role of magnesium in diabetes care. [ABSTRACT FROM AUTHOR]

The central nervous system regulates feeding, weight and glucose homeostasis in rodents and humans, but the site-specific mechanisms remain unclear. The dorsal vagal complex in the brainstem that contains the nucleus of the solitary tract (NTS) and area postrema (AP) emerges as a regulatory center that impacts energy and glucose balance by monitoring hormonal and nutrient changes. However, the specific mechanistic metabolic roles of the NTS and AP remain elusive. This mini-review highlights methods to study their distinct roles and recent findings on their metabolic differences and similarities of growth differentiation factor 15 (GDF15) action and glucose sensing in the NTS and AP. In summary, future research aims to characterize hormonal and glucose sensing mechanisms in the AP and/or NTS carries potential to unveil novel targets that lower weight and glucose levels in obesity and diabetes. [ABSTRACT FROM AUTHOR]

To investigate the effects of Pseudomonas monteilii SX001 on various parameters of cucumber plants under salt stress, the salt-sensitive cucumber variety "Jinyou No. 4" was used as the test material, and coconut bran was used to simulate salt stress by applying NaCl solution. The results indicated that salt stress significantly reduced the morphological structure, relative growth rate, root morphology, and photosynthetic parameters of the cucumber plants. Leaf starch, soluble sugar, and sucrose contents significantly increased, whereas their levels in roots decreased. Cell membrane damage leads to the accumulation of reactive oxygen species and malondialdehyde, with notable increases in the activities of major antioxidant enzymes such as SOD, CAT, and POD. Nitrogen metabolism was disrupted, as evidenced by a significant decrease in nitrate nitrogen content and an increase in ammonium nitrogen content, as well as a significant reduction in the activity of NR enzymes involved in nitrogen metabolism. The enzyme activity in the cucumber rhizosphere soil decreased. However, Pseudomonas monteilii SX001 significantly enhanced the growth of cucumber seedlings under salt stress, improved photosynthetic efficiency, and facilitated sugar transformation and transport via glucose metabolism. Additionally, Pseudomonas monteilii SX001 reduced the reactive oxygen content and increased antioxidant enzyme activity. It also increased the activity of substrate enzymes and decreased the diversity of rhizosphere soil microorganisms but also increased the abundance of Asticcacaulis, Acinetobacter, Brevundimonas, Pseudomonas, and Enterobacter. These findings demonstrate that Pseudomonas monteilii SX001 is a promising bioinoculant for alleviating salt stress in cucumber production and improving soil health. [ABSTRACT FROM AUTHOR]

Introduction: Human chemerin is an adipokine that regulates chemotaxis, inflammation, and glucose metabolism. In addition, accumulating evidence suggests that chemerin promotes apoptosis, autophagy, and pyroptosis. However, there are no data on its impact on eryptosis. The current study aimed to analyze the effects of human active Glu-Ser chemerin on eryptosis in vitro. Materials and Methods: Human chemerin 0-2-10-50 µg/mL was incubated for 24 h with human erythrocytes (hematocrit 0.4%) obtained from eight healthy individuals. Flow cytometry-based determination of phospholipid scrambling, reactive oxygen species (ROS) production, and intracellular Ca levels was performed. To supplement data on ROS and Ca signaling in chemerin-mediated eryptosis, incubation in the presence or absence of antioxidants vitamin C and N-acetylcysteine and Ca-binding agent EGTA was carried out, respectively. Confocal microscopy-based techniques were used to detect reactive nitrogen species (RNS) generation, involvement of caspase-3 and caspase-8, as well as the state of lipid order in cell membranes of erythrocytes exposed to human Glu-Ser chemerin. Results: Our observations suggest that human Glu-Ser chemerin had no impact on eryptosis parameters at 2 µg/mL. However, chemerin stimulated phosphatidylserine externalization, ROS production, and Ca accumulation at higher concentrations suggesting activation of eryptosis. Ca uptake turned out to be at least partly required for chemerin-mediated eryptosis. Chemerin-mediated erythrotoxicity was additionally mediated by RNS, caspase-3, and caspase-8. Moreover, Glu-Ser chemerin promoted reduction in the liquid-ordered phase of cell membranes in erythrocytes. Conclusions: The present study first discloses that human chemerin can induce eryptosis via Ca-dependent mechanisms at concentrations noticeably exceeding circulating levels. Thus, chemerin-induced eryptosis can hardly contribute to eryptosis-mediated anemia in diseases associated with enhanced levels of chemerin in blood. [ABSTRACT FROM AUTHOR]

Filamentous algae have potential application to wastewater treatment, in particular for efficient recovery of nutrients into biomass. However, supplying inorganic carbon is a major limiting factor. The utilisation of organic carbon present in wastewater may reduce the constraints in carbon supply, however there is little knowledge of mixotrophic growth amongst filamentous algae. This study investigated the utilisation of organic carbon sources relevant to wastewater by the filamentous xanthophyte alga Tribonema. Algae growth was compared in the absence of organic carbon (autotrophic) and in presence of 0.2 g-C L-1 glucose, ethanol or acetate under mixotrophic (presence of organic carbon and light) or heterotrophic (presence of organic carbon and absence of light) conditions. To investigate direct utilisation of organic carbon and indirect utilisation via bacterial CO2-genesis, cultivation was performed under both axenic and non-axenic conditions. Tribonema was found to directly utilise glucose, which increased mixotrophic productivity and maintained growth under heterotrophic conditions. In contrast, acetate was only indirectly utilised mixotrophically in the presence of bacteria, whereas ethanol was not utilised under any conditions. The underlying mechanisms of glucose utilisation by Tribonema were also investigated by analysing its photosynthetic rate and respiration rate under glucose concentrations ranging from 0 – 100 g L-1. Based on the results, enhancements to metabolic pathways and reduced CO2 requirements provided by glucose utilisation were proposed. Despite the positive results with respect to glucose utilisation, out competition for this resource by bacteria suggest that Tribonema is more suitable for treatment of wastewater with low organic carbon concentrations, such as secondary-treated wastewater effluent. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is the predominant metabolic epidemic posing a major threat to global health. Growing evidence indicates that gut microbiota (GM) may critically influence the progression from normal glucose tolerance, to pre-diabetes, to T2D. On the other hand, regular exercise contributes to the prevention and/or treatment of the disease, and evidence suggests that a possible way regular exercise favorably affects T2D is by altering GM composition toward health-promoting bacteria. However, research regarding this potential effect of exercise-induced changes of GM on T2D and the associated mechanisms through which these effects are accomplished is limited. This review presents current data regarding the association of GM composition and T2D and the possible critical GM differentiation in the progression from normal glucose, to pre-diabetes, to T2D. Additionally, potential mechanisms through which GM may affect T2D are presented. The effect of exercise on GM composition and function on T2D progression is also discussed. [ABSTRACT FROM AUTHOR]

Prior studies have extensively investigated the essential oil derived from the Mediterranean cypress, Cupressus sempervirens. However, the 'Stricta' variety, known for its ornamental value, has received less attention in terms of its oil composition and potential health benefits. The objective of this research was to comprehensively analyze the chemical components and medicinal properties of the essential oil extracted from C. sempervirens 'Stricta' (CSSLEO) grown in Egypt. Utilizing gas chromatography–mass spectrometry (GC–MS), the investigation identified 22 compounds within CSSLEO, with α-pinene and δ-3-carene being predominant, accounting for 96.01% of the oil. In vitro assays evaluated CSSLEO's cytotoxic effects on cancer cell lines, revealing notable anticancer potential. Additionally, the oil displayed antidiabetic properties by impeding crucial enzymes involved in glucose metabolism. Complementary in silico network pharmacology and molecular docking studies provided insights into the possible interactions between CSSLEO's key compounds and essential proteins and pathways in cancer treatment. The results underscored CSSLEO's intricate composition and its promising applications in cancer prevention and diabetes management. The conclusions drawn from this research underscore the need for further investigation to validate CSSLEO's clinical effectiveness and to gain a deeper understanding of its therapeutic mechanisms, with a view to harnessing its potential in oncology and endocrinology. [ABSTRACT FROM AUTHOR]

Objective: This study utilized a data-driven Bayesian model to automatically identify distinct latent disease factors represented by overlapping glucose metabolism patterns from 18F-Fluorodeoxyglucose PET (18F-FDG PET) to analyze heterogeneity among patients with TLE. Methods: We employed unsupervised machine learning to estimate latent disease factors from 18F-FDG PET scans, representing whole-brain glucose metabolism patterns in seventy patients with TLE. We estimated the extent to which multiple distinct factors were expressed within each participant and analyzed their relevance to epilepsy burden, including seizure onset, duration, and frequency. Additionally, we established a predictive model for clinical prognosis and decision-making. Results: We identified three latent disease factors: hypometabolism in the unilateral temporal lobe and hippocampus (factor 1), hypometabolism in bilateral prefrontal lobes (factor 2), and hypometabolism in bilateral temporal lobes (factor 3), variably co-expressed within each patient. Factor 3 demonstrated the strongest negative correlation with the age of onset and duration (r = − 0.33, − 0.38 respectively, P < 0.05). The supervised classifier, trained on latent disease factors for predicting patient-specific antiepileptic drug (AED) responses, achieved an area under the curve (AUC) of 0.655. For post-surgical seizure outcomes, the AUC was 0.857, and for clinical decision-making, it was 0.965. Conclusions: Decomposing 18F-FDG PET-based phenotypic heterogeneity facilitates individual-level predictions relevant to disease monitoring and personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]

M1/M2 macrophage polarization plays an important role in regulating the balance of the microenvironment within tissues. Moreover, macrophage polarization involves the reprogramming of metabolism, such as glucose and lipid metabolism. Transcriptional coactivator B‐cell lymphoma‐3 (Bcl‐3) is an atypical member of the IκB family that controls inflammatory factor levels in macrophages by regulating nuclear factor kappa B pathway activation. However, the relationship between Bcl‐3 and macrophage polarization and metabolism remains unclear. In this study, we show that the knockdown of Bcl‐3 in macrophages can regulate glycolysis‐related gene expression by promoting the activation of the nuclear factor kappa B pathway. Furthermore, the loss of Bcl‐3 was able to promote the interferon gamma/lipopolysaccharide‐induced M1 macrophage polarization by accelerating glycolysis. Taken together, these results suggest that Bcl‐3 may be a candidate gene for regulating M1 polarization in macrophages. [ABSTRACT FROM AUTHOR]

Objective: Half of ALS patients are cognitively and/or behaviourally impaired. As cognition/behaviour and cerebral glucose metabolism can be correlated by means of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET), we aimed to utilise FDG-PET, first, to replicate group-level differences in glucose metabolism between non-demented ALS patients separated into non-impaired (ALSni), cognitively impaired (ALSci), behaviourally impaired (ALSbi), and cognitively and behaviourally impaired (ALScbi) groups; second, to investigate glucose metabolism and performance in various cognitive domains; and third, to examine the impact of partial volume effects correction (PVEC) of the FDG-PET data on the results. Methods: We analysed neuropsychological, clinical, and imaging data from 67 ALS patients (30 ALSni, 21 ALSci, 5 ALSbi, and 11 ALScbi). Cognition was assessed with the Edinburgh Cognitive and Behavioural ALS Screen, and two social cognition tests. FDG-PET and structural MRI scans were acquired for each patient. Voxel-based statistical analyses were undertaken on grey matter volume (GMV) and non-corrected vs. PVE-corrected FDG-PET scans. Results: ALSci and ALScbi had lower cognitive scores than ALSni. In contrast to both ALSni and ALSci, ALScbi showed widespread hypometabolism in the superior- and middle-frontal gyri in addition to the right temporal pole. Correlations were observed between the GMV, the FDG-PET signal, and various cognitive scores. The FDG-PET results were largely unaffected by PVEC. Interpretation: Our study identified widespread differences in hypometabolism in the ALScbi-ni but not in the ALSci-ni group comparison, raising the possibility that cerebral metabolism may be more closely related to the presence of behavioural changes than to mild cognitive deficits. [ABSTRACT FROM AUTHOR]

Background: Cancer-derived exosomes facilitate chemoresistance by transferring RNAs, yet their role in exosomal microRNA-221-3p (miR-221-3p) regulation of adriamycin resistance in breast cancer (BC) remains unclear. Methods: Adriamycin-resistant BC cells were developed from MCF-7 and MDA-MB-231 cells by incremental adriamycin exposure. The miR-221-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction. Subsequently, exosomes were isolated and incubated with BC cells, and exosome-mediated adriamycin sensitivity was evaluated using Cell Counting Kit-8, colony formation, and flow cytometry assays. Sensitive cells were cocultured with miR-221-3p inhibitor-treated cells to assess adriamycin resistance. Moreover, the interaction between miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was validated using a dual luciferase reporter gene assay. Mimics and inhibitors were used to determine the effects of miR-221-3p on adriamycin resistance. Results: Elevated levels of miR-221-3p expression were observed in adriamycin-resistant BC cells and exosomes. Sensitive cells were cocultured with exosomes from resistant cells, resulting in increased half-maximal inhibitory concentration value and proliferation, and reduced adriamycin-induced apoptosis. However, the effects of coculturing sensitive cells with adriamycin-resistant cells were significantly weakened by miR-221-3p inhibitor transfection in adriamycin-resistant cells. PIK3R1 was found to be a target of miR-221-3p, and miR-221-3p mimics enhanced adriamycin resistance in sensitive cells. miR-221-3p inhibitors increased the expression of PIK3R1, p-AKT, c-Myc, HK2, and PKM2, decreased FOXO3 expression, and weakened the adriamycin resistance in resistant cells. Conclusions: miR-221-3p can be transferred between BC cells through exosomes. High levels of miR-221-3p were found to target PIK3R1 and promoted adriamycin resistance in BC cells. [ABSTRACT FROM AUTHOR]

Globally, type 2 diabetes mellitus (T2DM) is a major threat to the public's health, particularly in low- and middle-income countries (LMICs). The production of short-chain fatty acids (SCFAs) by the gut microbiota has been reported to have the potential to reduce the prevalence of T2DM, particularly in LMICs where the disease is becoming more common. Dietary fibers are the primary source of SCFAs; they can be categorized as soluble (such as pectin and inulin) or insoluble (such as resistant starches). Increased consumption of processed carbohydrates, in conjunction with insufficient consumption of dietary fiber, has been identified as a significant risk factor for type 2 diabetes (T2DM). However, there are still controversies over the therapeutic advantages of SCFAs on human glucose homeostasis, due to a lack of studies in this area. Hence, a few questions need to be addressed to gain a better understanding of the beneficial link between SCFAs and glucose metabolism. These include the following: What are the biochemistry and biosynthesis of SCFAs? What role do SCFAs play in the pathology of T2DM? What is the most cost-effective strategy that can be employed by LMICs with limited laboratory resources to enhance their understanding of the beneficial function of SCFAs in patients with T2DM? To address the aforementioned questions, this paper aims to review the existing literature on the protective roles that SCFAs have in patients with T2DM. This paper further discusses possible cost-effective and accurate strategies to quantify SCFAs, which may be recommended for implementation by LMICs as preventive measures to lower the risk of T2DM. [ABSTRACT FROM AUTHOR]

The growing incidence of diabetes mellitus (DM) and depression is a global public health issue. Alpiniae oxyphyllae Fructus (AOF) is a kind of medicinal and edible plant which be found with anti-diabetic property, and could improve depression-like symptoms. This study aimed to screen active targets and potential mechanisms of AOF in treating DM with depression. Injection of streptozotocin (STZ) and exposure to chronic unpredictable mild stress (CUMS) for 4 weeks were used to conduct the DM with depression mice model. Behavioral tests, indexes of glucose metabolism, monoamine neurotransmitters, inflammatory cytokine and oxidative stress were measured. Histopathological change of hippocampus tissue was observing by HE and Nissl staining. UPLC-Q-Exactive Orbitrap/MS, network pharmacology and molecular docking were used to explore the chemical components and mechanisms of AOF on the DM with depression. AOF showed a reversed effect on body weight in DM with depression mice. Glucose metabolism and insulin resistance could be improved by treatment of AOF. In addition, AOF could alleviate depression-like behaviors based on the results of behavior tests and monoamine neurotransmitters. AOF also attenuated STZ-CUMS induced neuron injury in hippocampus. Next, a total of 61 chemical components were identified in the UPLC-Q-Exactive Orbitrap/MS analysis of the extract of AOF. Network pharmacology analysis suggested that 12 active components and 227 targets were screened from AOF, and 1802 target genes were screened from DM with depression, finally 126 intersection target genes were obtained. Drug-disease targets network was constructed and implied that the top five components with a higher degree value includes quercetin, nootkatone, baicalein, (-)-epicatechin and nootkatol. Protein-protein interaction (PPI) network showed that MAPK1, FOS, AKT1, IL6 and TP53 may be the core intersection targets. The mechanism of the effect of AOF on DM with depression was analyzed through gene ontology (GO), and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, mainly involved in AGE/RAGE, PI3K/AKT, and MAPK signaling pathways. The results of molecular docking indicated that quercetin, nootkatone, baicalein, (-)-epicatechin and nootkatol all had good binding to the core intersection targets. Overall, our experimental researches have demonstrated that AOF could exert the dual effects of anti-diabetic and anti-depression on DM with depression mice, through multi-targets and multi-pathways. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is characterized by the dysregulation of glucose homeostasis, resulting in hyperglycemia. However, concerns have been raised about the safety and efficacy of current hypoglycemic drugs due to undesirable side effects. Increasing studies have shown that whole grains (WG) consumption is inversely associated with the risk of T2DM and its subsequent complications. Thus, dietary strategies involving functional components from the WG provide an intriguing approach to restoring and maintaining glucose homeostasis. This review provides a comprehensive understanding of the major functional components derived from WG and their positive effects on glucose homeostasis, demonstrates the underlying molecular mechanisms targeting hepatic glucose metabolism, and discusses the unclear aspects according to the latest viewpoints and current research. Improved glycemic response and insulin resistance were observed after consumption of WG-derived bioactive ingredients, which are involved in the integrated, multi-factorial, multi-targeted regulation of hepatic glucose metabolism. Promotion of glucose uptake, glycolysis, and glycogen synthesis pathways, while inhibition of gluconeogenesis, contributes to amelioration of abnormal hepatic glucose metabolism and insulin resistance by bioactive components. Hence, the development of WG-based functional food ingredients with potent hypoglycemic properties is necessary to manage insulin resistance and T2DM. [ABSTRACT FROM AUTHOR]

Summary: This study investigated the impact of comprehensive sleep patterns on glycaemic parameters and endothelial function in adolescents and young adults with type 1 diabetes (T1D). Thirty subjects with type 1 diabetes (aged 13–25) without chronic complications participated. For 1 week, glucose levels were monitored by real‐time continuous glucose monitoring (CGM) and sleep was simultaneously assessed by actigraphy. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Flow‐mediated dilatation (FMD) measured endothelial function at the brachial artery. Insulin sensitivity was determined by calculated estimated glucose disposal rate (eGDR). Glycaemic control was assessed using haemoglobin A1C (HbA1C) levels. To address potential confounding by metabolic syndrome on the FMD results, three affected subjects were excluded from FMD correlation analyses. Participants with PSQI scores >5 had a lower %FMD compared with those with scores ≤5 (4.6 ± 3.7% vs. 7.6 ± 3.0%, p = 0.03). Multivariate analysis indicated that lower sleep efficiency and higher sleep duration variability were associated with higher HbA1C levels (β = −0.076, 95%CI [−0.145, −0.008], p = 0.029; β = 0.012, 95%CI [0.001, 0.023], p = 0.033). Irregular sleep timing and lower sleep efficiency were related to decreased insulin sensitivity (sleep midpoint irregularity β = −1.581, 95%CI [−2.661, −0.502], p = 0.004, and sleep efficiency β = 0.147, 95%CI [0.060, 0.235], p = 0.001). No significant associations were found between glycaemic parameters and FMD. Our study demonstrated that sleep irregularity in type 1 diabetes was associated with glycaemic control and insulin resistance, while poor subjective sleep quality was linked to endothelial dysfunction. Promoting healthy sleep habits, including consistent sleep timing could benefit metabolic and cardiovascular health in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder that primarily manifests itself by progressive memory loss and cognitive decline, thus significantly affecting memory functions and quality of life. In this review, we proceed from the understanding that the canonical amyloid‐β hypothesis, while significant, has faced setbacks, highlighting the need to adopt a broader perspective considering the intricate interplay of diverse pathological pathways for effective AD treatments. Sex differences in AD offer valuable insights into a better understanding of its pathophysiology. Fluctuation of the levels of ovarian sex hormones during perimenopause is associated with changes in glucose metabolism, as a possible window of opportunity to further understand the roles of sex steroid hormones and their associated receptors in the pathophysiology of AD. We review these dimensions, emphasizing the potential of estrogen receptors (ERs) to reveal mitochondrial functions in the search for further research and therapeutic strategies for AD pharmacotherapy. Understanding and addressing the intricate interactions of mitochondrial dysfunction and ERs potentially pave the way for more effective approaches to AD therapy. [ABSTRACT FROM AUTHOR]

Cancer and senescent cells share many metabolic features that contribute to their common and unique cellular states. Senescent cells alter both glucose and non-glucose metabolism, including glycolysis, mitochondrial respiration, fatty acid oxidation, and glutaminolysis, to meet their bioenergetic, biosynthetic, and redox homeostatic needs. Senescent cells sustain metabolic signaling pathways in a hardwired manner to direct their metabolic alterations toward pathological anabolic processes. Senescent cells may rely on protein degradation pathways to mitigate errors caused by their hyperactivated anabolism, such as the senescence-associated secretory phenotype (SASP). Targeting senescence metabolism, analogous to targeting cancer metabolism, sensitizes senescent cells or suppresses the SASP, thereby serving as a new therapeutic modality for senotherapy. Cellular metabolism is a flexible and plastic network that often dictates physiological and pathological states of the cell, including differentiation, cancer, and aging. Recent advances in cancer metabolism represent a tremendous opportunity to treat cancer by targeting its altered metabolism. Interestingly, despite their stable growth arrest, senescent cells – a critical component of the aging process – undergo metabolic changes similar to cancer metabolism. A deeper understanding of the similarities and differences between these disparate pathological conditions will help identify which metabolic reprogramming is most relevant to the therapeutic liabilities of senescence. Here, we compare and contrast cancer and senescence metabolism and discuss how metabolic therapies can be established as a new modality of senotherapy for healthy aging. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a common disease during pregnancy that has adverse effects on both the mother and fetus. There are currently rare researches on the effect of vitamin supplementation on GDM pregnant mother and their offspring on animal and cell levels systematically. This work supplemented the GDM pregnant mouse model with vitamin D and found that vitamin D can effectively alleviate the hyperglycemia in GDM pregnant mice, increase blood insulin and adiponectin concentrations, and improve GTT and ITT in pregnant mice. In addition, vitamin D can reduce the incidence of death and high birth weight of offspring caused by GDM. The offspring of GDM pregnant mice had higher blood glucose levels in the first 5 weeks after birth compared to the normal group, and then returned to normal levels. Vitamin D can alleviate abnormal glucose metabolism in newborn mice. The therapeutic effect exhibited by vitamin D may be due to their anti-inflammatory effects, as vitamin D supplementation significantly reduces the levels of TFN-α, MCP-1, IL-1β and IL-8 in the blood. Vitamin D also regulates liver lipid metabolism, resulting in a decrease in liver lipid accumulation and a decrease in blood triglycerides (TG) and cholesterol (CHO). The results of this study demonstrate that vitamin D supplementation can serve as an effective treatment strategy for alleviating GDM symptoms. [ABSTRACT FROM AUTHOR]

Human gut microorganisms consume proteins and amino acids to make many chemicals, including branched-chain fatty acids, phenolic, indole, and sulfur compounds, many of which are harmful to the host. In the distal colon, where symptoms of diseases including Ulcerative Colitis (UC) and Colo-Rectal Cancer (CRC) frequently manifest, bacteria mostly ferment amino acids and proteins. The Gut Microbiota's (GM) proteolytic metabolism hasn't been studied as much as its glucose metabolism. With low molecular weight, volatile molecules make up a large portion of metabolites. This research's goal is to give a general indication of the use of analysis techniques to identify and evaluate substances to comprehend the connections among several dietary protein substrates, their related metabolites, and their effects on gastrointestinal health. [ABSTRACT FROM AUTHOR]

A study on 81 individuals (18–75 years old) with mildly impaired fasting blood glucose (FBG) concentrations (98–125 mg/dL) was undertaken to investigate the tolerability of a food supplement (FS) based on Zea mays and Gymnema sylvestre extracts, zinc, and chromium and its efficacy on glucose and lipid metabolism. The subjects were randomized into three groups (27 in each group) and supplemented with one or two tablet(s)/day of FS (groups 1 and 2, respectively), or two tablets/day of placebo (group 3). Blood sampling was carried out at baseline (t0) and after a 3-month treatment (t1), and biochemical parameters associated with glucose and lipid metabolism and kidney and liver toxicity were evaluated. Compared to the placebo, FBG and glycated haemoglobin (HbA1c) were significantly (p < 0.001) reduced in group 1 subjects. In contrast, at the doses of one and two tablet(s)/day, the FS exerted no effect on the other parameters examined. We conclude that in subjects with slightly impaired FBG, ingestion of a FS based on Z. mays and G. sylvestre extracts, zinc, and chromium over 3 months lowers FBG and modulates glucose homeostasis by improving glucose metabolism. These beneficial effects occur in the absence of biochemical evidence of kidney and liver toxicity. [ABSTRACT FROM AUTHOR]

The present study, as one part of a larger project that aimed to investigate the effects of dietary berberine (BBR) on fish growth and glucose regulation, mainly focused on whether miRNAs involve in BBR's modulation of glucose metabolism in fish. Blunt snout bream Megalobrama amblycephala (average weight of 20.36 ± 1.44 g) were exposed to the control diet (NCD, 30% carbohydrate), the high-carbohydrate diet (HCD, 43% carbohydrate) and the berberine diet (HCB, HCD supplemented with 50 mg/kg BBR). After 10 weeks' feeding trial, intraperitoneal injection of glucose was conducted, and then, the plasma and liver were sampled at 0 h, 1 h, 2 h, 6 h, and 12 h. The results showed the plasma glucose levels in all groups rose sharply and peaked at 1 h after glucose injection. Unlike the NCD and HCB groups, the plasma glucose in the HCD group did not decrease after 1 h, while remained high level until at 2 h. The NCD group significantly increased liver glycogen content at times 0–2 h compared to the other two groups and then liver glycogen decreased sharply until at times 6–12 h. To investigate the role of BBR that may cause the changes in plasma glucose and liver glycogen, miRNA high-throughput sequencing was performed on three groups of liver tissues at 2 h time point. Eventually, 20 and 12 differentially expressed miRNAs (DEMs) were obtained in HCD vs NCD and HCB vs HCD, respectively. Through function analyzing, we found that HCD may affect liver metabolism under glucose loading through the NF-κB pathway; and miRNAs regulated by BBR mainly play roles in adipocyte lipolysis, niacin and nicotinamide metabolism, and amino acid transmembrane transport. In the functional exploration of newly discovered novel:Chr12_18892, we found its target gene, adenylate cyclase 3 (adcy3), was widely involved in lipid decomposition, amino acid metabolism, and other pathways. Furthermore, a targeting relationship of novel:Chr12_18892 and adcy3 was confirmed by double luciferase assay. Thus, BBR may promote novel:Chr12_18892 to regulate the expression of adcy3 and participate in glucose metabolism. [ABSTRACT FROM AUTHOR]