Glucose Metabolism-related Genes Research Articles

Postprandial regulation of glucose metabolism and insulin signaling pathways in Macrobrachium rosenbergii

To better understand postprandial glucose metabolic mechanisms in crustaceans, the pathways involved in glucose transport, breakdown, synthesis, and regulation were investigated in the giant freshwater prawn Macrobrachium rosenbergii after feeding. Prawns were fasted for 48 hours and then refed to satiation. Glucose and glycogen contents, along with the transcriptional levels of glucose metabolism-related genes, were measured at 0, 1, 3, 6, and 10 hours after feeding (HAF). Plasma glucose levels peaked at 3 HAF and returned to basal levels by 6–10 HAF. Hepatopancreas glucose followed a similar trend, except for a notable increase at 10 HAF, suggesting gluconeogenesis at this time point. Expression analysis of glucose transporter genes in hepatopancreas revealed a significant upregulation of GLUT1 at 3, 6, and 10 HAF, while GLUT2 showed significant decreases only at 6 HAF. Glycolysis-related genes (GK and PK) exhibited transient increases post-feeding, whereas the gluconeogenesis-related gene FBP was initially suppressed, with expression recovering from 6 HAF onward. The glycogenesis-related gene GS was significantly upregulated at 3, 6, and 10 HAF, correlating with increased glycogen levels in the hepatopancreas. Conversely, the expression of the glycogenolysis-related gene GDE was inhibited after feeding, along with a decrease in the glycogenesis inhibitory gene GSK3. Genes in the insulin signaling pathway (ILP, PI3KCa, and AKT) were upregulated post-feeding, peaking at 3 HAF and subsequently declining. These results suggest that feeding stimulates the insulin signaling pathway and GLUT1 to transport excess glucose, inducing glycolysis and hepatopancreatic glycogenesis, while inhibiting gluconeogenesis and glycogenolysis.

GLUT1 and cerebral glucose hypometabolism in human focal cortical dysplasia is associated with hypermethylation of key glucose regulatory genes.

Focal cortical dysplasia (FCD) is recognized as a significant etiological factor in pharmacoresistant intractable epilepsy, linked with disturbances in neurovascular metabolism. Our study investigated regulation of glucose-transporter1 (GLUT1) and cerebral hypometabolism within FCD subtypes. Surgically excised human brain specimens underwent histopathological categorization. A subset of samples (paired with matching blood) was assessed for DNA methylation changes of glucose metabolism-related genes. We evaluated GLUT1, VEGFα, MCT2, and mTOR expression by western blot analysis, measured glucose-lactate concentrations, and established correlations with patients' demographic and clinical profiles. Furthermore, we investigated the impact of DNA methylation inhibitor decitabine and hypometabolic condition on the uptake of [3H]-2-deoxyglucose and ATPase in epileptic brain endothelial cells (EPI-EC). We observed hypermethylation of GLUT1 and glucose metabolic genes in FCD brain/blood samples and could distinguish FCDIIa/b from mMCD, MOGHE and non-lesional types in brain. Low GLUT1 and glucose-lactate ratios corresponded to elevated VEGFα and MCT2 in FCDIIa/b vs non-lesional tissues, independent of age, gender, seizure-onset, or duration of epilepsy. Increased mTOR signaling in FCDIIa/b tissues was evident. Decitabine stimulation increased GLUT1, decreased VEGFα expression, restored glucose uptake and ATPase activity in EPI-ECs and reduced mTOR and MCT2 levels in HEK cells. We demonstrated: 1) hypermethylation of glucose regulatory genes distinguish FCDIIa/b from mMCD, MOGHE and non-lesional types, 2) glucose uptake reduction is due to GLUT1 suppression mediated possibly by a GLUT1-mTOR mechanism; and 3) DNA methylation regulates cellular glucose update and metabolism. Together, these studies may lead to GLUT1-mediated biomarkers, glucose metabolism and identify early intervention strategies in FCD.

Transcriptional expression of SLC16A7 as a biomarker of occult lymph node metastases in patients with head and neck squamous cell carcinoma.

Glucose is the main energy substrate of tumor cells. This study aims to assess whether the transcriptional expression of glucose metabolism-related genes is associated with occult lymph node metastases in head and neck squamous cell carcinoma (HNSCC) patients. We examined the transcriptional expression of a panel of glucose metabolism-related genes in a cohort of 53 patients with HNSCC without cervical lymph node involvement at the time of diagnosis (cN0) and subsequently treated with elective neck dissection. Occult lymph node metastases were found in 37.7% (n = 20) of the patients. Among the analyzed genes, SLC16A7 exhibited the strongest association with the presence of occult lymph node metastases. Patients with occult lymph node metastases (cN0/pN +) had significantly lower SLC16A7 expression values (p = 0.001). Patients with low SLC16A7 expression (n = 17, 32.1%) had a frequency of occult lymph node metastases of 76.5%, while for patients with high SLCA16A7 expression (n = 36, 67.9%) it was 19.4% (P = 0.0001). A multivariable analysis showed that patients with low expression of SLC16A7 had a 12.6 times higher risk of developing occult lymph node metastases. cN0 HNSCC patients with low SLC16A7 expression had a higher risk of occult lymph node metastases.

SlNAP1 promotes tomato fruit ripening by regulating carbohydrate metabolism

Many studies showed NAC transcription factors play an important role in fruit ripening. Moreover, sucrose and starch metabolism is also closely related to fruit ripening. However, there are a few studies focus on whether NAC regulates sucrose and starch metabolism to influence fruit ripening. In this study, virus-induced gene silencing (VIGS) of SlNAP1 suppressed fruit ripening and delayed color transformation. The chlorophyll (including Chla, Chlb, and Chla + b) degradation and carotenoid synthesis in SlNAP1-silenced fruits were dramatically suppressed. Silencing SlNAP1 decreased soluble sugar and reducing sugar accumulation in fruits, and increased starch content. The activity of starch degrading enzymes, including α amylase (AMY) and β amylase (BAM) was significantly lower in SlNAP1-silenced fruits than in the control fruits, whereas denosine diphosphoglucose pyrophosphorylase (AGP) activity was significantly higher. In addition, the expression of starch degradation-related genes (SlAMY1, SlAMY2, SlBAM1, SlBAM7, SlGWD, SlPWD) in SlNAP1-silenced fruits was significantly suppressed, while starch synthesis-related genes (SlAGPase1, SlAGPase2) was significantly increased. Compared with the control fruits, SlNAP1-silenced fruits showed significantly lower sucrose and glucose content. The expression level of sucrose and glucose metabolism-related genes such as Slsus1, Slsus3, SlSPS, SlHxk1, SlHxk2, SlPK1, and SlPK2 was significantly lower in SlNAP1-silenced fruits than in the control fruits. Overall, this study revealed that SlNAP1 gene might positively regulate fruit ripening by influencing carbohydrate metabolism.

Effects of parental nutritional programming on the hatching parameters, metabolome, glucose metabolism-related gene expressions, and global DNA methylation in larvae of yellow catfish Tachysurus fulvidraco

Effects of parental nutritional programming on the hatching parameters, metabolome, glucose metabolism-related gene expressions, and global DNA methylation in larvae of yellow catfish Tachysurus fulvidraco

Domestication Gene Mlx and Its Partner Mondo Are Involved in Controlling the Larval Body Size and Cocoon Shell Weight of Bombyx mori.

Bombyx mori was domesticated from Bombyx mandarina. The long-term domestication of the silkworm has brought about many remarkable changes to its body size and cocoon shell weight. However, the molecular mechanism underlying the improvement in the economic characteristics of this species during domestication remains unclear. In this study, we found that a transposable element (TE)-Bm1-was present in the upstream regulatory region of the Mlx (Max-like protein X) gene in wild silkworms but not in all domesticated silkworms. The absence of Bm1 caused an increase in the promoter activity and mRNA content of Mlx. Mlx and its partner Mondo belong to the bHLHZ transcription factors family and regulate nutrient metabolism. RNAi of Mlx and Mondo decreased the expression and promoter activity of glucose metabolism-related genes (trehalose transport (Tret), phosphofructokinase (PFK), and pyruvate kinase (PK)), lipogenic genes (Acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS)), and glutamine synthesis gene (Glutamine synthase 2, (GS2)). Furthermore, the transgenic overexpression of Mlx and Mondo in the fat body of silkworms increased the larval body size, cocoon shell weight, and egg number, but the silencing of the two genes resulted in the opposite phenotypes. Our results reveal the molecular mechanism of Mlx selection during domestication and its successful use in the molecular breeding of Bombyx mori.

GATA6 inhibits the biological function of non-small cell lung cancer by modulating glucose metabolism

PurposeThis study aims to explore the role of GATA6 in lung cancer, with a focus on its impact on metabolic processes.MethodsWe assessed GATA6 expression in lung cancer tissues and its association with patient prognosis. In vitro cell function experiments were conducted to investigate the effects of altered GATA6 levels on lung cancer cell proliferation and migration. Mechanistic insights were gained by examining GATA6's influence on glucose metabolism-related genes, particularly its effect on c-Myc mRNA expression.ResultsOur study revealed significant down-regulation of GATA6 in lung cancer tissues, and this down-regulation was strongly correlated with unfavorable patient prognosis. Elevating GATA6 levels effectively inhibited the proliferation and migration of lung cancer cells in our cell function experiments. Mechanistically, we found that GATA6 suppressed the expression of c-Myc mRNA, impacting genes related to glucose metabolism. As a result, glucose uptake and metabolism in lung cancer cells were disrupted, ultimately impeding their malignant behaviors.ConclusionOur study provides crucial insights into the metabolic regulation of GATA6 in lung cancer cells. These findings have the potential to offer a solid theoretical foundation for the development of novel clinical treatments for lung cancer.

Errate: Dysregulation of Inflammation, Oxidative Stress, and Glucose Metabolism-Related Genes and miRNAs in Visceral Adipose Tissue of Women with Type 2 Diabetes Mellitus.

The authors informed the journal that errors occurred in their manuscript, and were not noticed by the authors during the proofreading. Corrections: 1. Figure 1, top entry: "Predipocytes" should read "Preadipocytes". 2. Figure 3, chart "TIGAR": "-9" value on y axis should read "-8". 3. Figure 4, chart "let-7g-5p": the upper "-4" value on y axis should read "0". 4. Figure 5: the title of the bottom right chart should read "TIGAR". 5. Figure 6, chart "miR-26a-5p": the values on y axis should read from the top: 2, 1, 0, -1, -2. 6. Figure 6, chart "miR-374a-5p": the values on y axis should read from the top: 0, -1, -2, -3, -4. 7. Table 4., in the 6 rows from the bottom: in column "miRNAs", "hsa-miR-21-5" should read "hsa-miR-21-5p". 8. Supplementary Table1, 1st column on the left: "TG-HDL" should read "TG/HDL" Reference: Adam Wróblewski, Justyna Strycharz, Katarzyna Oszajca, Piotr Czarny, Ewa Świderska, Tomasz Matyjas, Andrzej Zieleniak, Monika Rucińska, Lech Pomorski, Józef Drzewoski, Agnieszka Śliwińska, Janusz Szemraj: Dysregulation of Inflammation, Oxidative Stress, and Glucose Metabolism-Related Genes and miRNAs in Visceral Adipose Tissue of Women with Type 2 Diabetes Mellitus. Med Sci Monit, 2023; 29: e939299. DOI: 10.12659/MSM.939299.

FGF2, LIF, and IGF-1 supplementation improves mouse oocyte in vitro maturation via increased glucose metabolism†.

Chemically defined oocyte maturation media supplemented with FGF2, LIF, and IGF-1 (FLI medium) enabled significantly improved oocyte quality in multiple farm animals, yet the molecular mechanisms behind such benefits were poorly defined. Here, we first demonstrated that FLI medium enhanced mouse oocyte quality assessed by blastocyst formation after in vitro fertilization and implantation and fetal development after embryo transfer. We then analyzed the glucose concentrations in the spent media; reactive oxygen species concentrations; mitochondrial membrane potential; spindle morphology in oocytes; and the abundance of transcripts of endothelial growth factor-like factors, cumulus expansion factors, and glucose metabolism-related genes in cumulus cells. We found that FLI medium enabled increased glucose metabolism through glycolysis, pentose phosphate pathway, and hexosamine biosynthetic pathway, as well as more active endothelial growth factor-like factor expressions in cumulus cells, resulting in improved cumulus cell expansion, decreased spindle abnormality, and overall improvement in oocyte quality. In addition, the activities of MAPK1/3, PI3K/AKT, JAK/STAT3, and mTOR signaling pathways in cumulus cells were assessed by the phosphorylation of MAPK1/3, AKT, STAT3, and mTOR downstream target RPS6KB1. We demonstrated that FLI medium promoted activations of all these signaling pathways at multiple different time points during in vitro maturation.

Metformin treatment of juvenile mice alters aging-related developmental and metabolic phenotypes in sex-dependent and sex-independent manners.

Metformin has attracted increasing interest for its potential benefits in extending healthspan and longevity. This study examined the effects of early-life metformin treatment on the development and metabolism of C57BL/6J (B6) mice, with metformin administered to juvenile mice from 15 to 56days of age. Metformin treatment led to decreased body weight in both sexes (P < 0.05, t-test). At 9weeks of age, mice were euthanized and organ weights were recorded. The relative weight of retroperitoneal fat was decreased in females, while relative weights of perigonadal and retroperitoneal fat were decreased, and relative liver weight was increased in males (P < 0.05, t-test). Glucose and insulin tolerance tests (GTT and ITT) were conducted at the age of 7weeks. ANOVA revealed a significant impairment in insulin sensitivity by the treatment, and a significantly interactive effect on glucose tolerance between sex and treatment, underscoring a disparity in GTT between sexes in response to the treatment. Metformin treatment reduced circulating insulin levels in fasting and non-fasting conditions for male mice, with no significant alterations observed in female mice. qRT-PCR analysis of glucose metabolism-related genes (Akt2, Glut2, Glut4, Irs1, Nrip1, Pi3k, Pi3kca, Pkca) in the liver and skeletal muscle reveals metformin-induced sex- and organ-specific effects on gene expression. Comparison with previous studies in heterogeneous UM-HET3 mice receiving the same treatment suggests that genetic differences may contribute to variability in the effects of metformin treatment on development and metabolism. These findings indicate that early-life metformin treatment affects development and metabolism in both sex- and genetics-dependent manners.

Resveratrol attenuates high glucose-induced inflammation and improves glucose metabolism in HepG2 cells

Diabetes mellitus (DM) is characterized by impaired glucose and insulin metabolism, resulting in chronic hyperglycemia. Hyperglycemia-induced inflammation is linked to the onset and progression of diabetes. Resveratrol (RES), a polyphenol phytoalexin, is studied in diabetes therapeutics research. This study evaluates the effect of RES on inflammation and glucose metabolism in HepG2 cells exposed to high glucose. Inflammation and glucose metabolism-related genes were investigated using qPCR. Further, inflammatory genes were analyzed by applying ELISA and Bioplex assays. High glucose significantly increases IKK-α, IKB-α, and NF-kB expression compared to controls. Increased NF-kB expression was followed by increased expression of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-β, and COX2. RES treatment significantly reduced the expression of NF-kB, IKK-α, and IKB-α, as well as pro-inflammatory cytokines. High glucose levels reduced the expression of TGFβ1, while treatment with RES increased the expression of TGFβ1. As glucose levels increased, PEPCK expression was reduced, and GCK expression was increased in HepG2 cells treated with RES. Further, HepG2 cells cultured with high glucose showed significant increases in KLF7 and HIF1A but decreased SIRT1. Moreover, RES significantly increased SIRT1 expression and reduced KLF7 and HIF1A expression levels. Our results indicated that RES could attenuate high glucose-induced inflammation and enhance glucose metabolism in HepG2 cells.

FpOGT is required for fungal growth, stress response, and virulence of Fusarium proliferatum by affecting the expression of glucokinase and other glucose metabolism-related genes

O-GlcNAcylation, an important post-translational modification catalyzed by O-GlcNAc transferase (OGT), plays critical roles in several biological processes. In this study, we present our findings on the function of FpOGT in regulating physiological processes and pathogenicity of Fusarium proliferatum (Fp), the alfalfa root rot fungus. The deletion of FpOGT impaired mycelial growth and altered macroconidia morphology in Fp. Furthermore, ΔFpOGT mutant displayed altered tolerance to various stressors, including cell wall perturbing agents, osmotic stressors, metal ionic stressors, and fungicides. Deletion of FpOGT significantly decreased Fp virulence toward alfalfa. The transcriptome analysis demonstrated that FpOGT plays a regulatory role in glucose metabolic pathways, including glycolysis, tricarboxylic acid (TCA) cycle, and hexosamine biosynthesis pathway (HBP), by influencing the expression of relevant genes. The downregulation of the glucokinase gene, FpGCK, was observed in ΔFpOGT, and the disruption of FpGCK led to a decrease in Fp virulence. Additionally, FpOGT affected the expression levels of the FpGCK-AS1 isoform, thereby impacting glucokinase function. The molecular docking analysis elucidated the plausible physical interaction between FpOGT and FpGCK, thereby offering valuable insights into their interrelationship. These findings underscore the indispensable involvement of FpOGT, the sole O-GlcNAc transferase in Fp, in various biological processes and the pathogenicity through its regulation of fundamental metabolic processes. Consequently, this study emphasizes the significance and elucidates the molecular mechanism underlying the role of O-GlcNAc transferase in diverse fundamental biological processes and the pathogenicity of phytopathogenic fungi.

Prognostic Value of IGFBP6 in Breast Cancer: Focus on Glucometabolism.

IGFBP6, a member of the IGF binding protein (IGFBP) family, is a specific inhibitor of insulin-like growth factor II (IGF-II) and can inhibit the growth of malignant tumors overexpressing IGF-II. Type 2 diabetes (T2D) is a basic disorder of glucose metabolism that can be regulated by IGF-related pathways. We performed bioinformatics analysis of the TCGA database to explore the possible mechanism of IGFBP6 in breast cancer (BC) metabolism and prognosis and collected clinical samples from BC patients with and without T2D to compare and verify the prognostic effect of IGFBP6. In our study, the levels of IGFBP1-6 were positively correlated with overall survival (OS) in patients with breast cancer. IGFBP6 was upregulated in estrogen receptor (ER)-positive BC, and ER-positive and progesterone receptor (PR) positive patients had a higher expression level of IGFBP6 than ER-negative and PR-negative patients. IGFBP6 could be used as an independent prognostic factor in BC. The expression of IGFBP6 was decreased in BC tissue, and BC tissue from patients with T2D had lower IGFBP6 expression levels than BC tissue from patients without T2D. IGFBP6 is mainly involved in the PI3K-Akt and TGF-β signaling pathways and tumor microenvironment regulation. In terms of metabolism, the expression of IGFBP6 was negatively correlated with that of most glucose metabolism-related genes. IGFBP6 expression was mainly correlated with mutations in TP53, PIK3CA, CDH1, and MAP3K1. In addition, the upregulation of IGFBP6 in BC increased the drug sensitivity to docetaxel, paclitaxel and gemcitabine. Overall, these results indicated that high expression of IGFBP6 is associated with a good prognosis in BC patients, especially in those without T2D. It is not only involved in the maintenance of the tumor microenvironment in BC but also inhibits the energy metabolism of cancer cells through glucose metabolism-related pathways. These findings may provide a new perspective on IGFBP6 as a potential prognostic marker for BC.

Metabolome and microbiome analyses of the anti-fatigue mechanism of Acanthopanax senticosus leaves.

Acanthopanax senticosus leaves, widely used as a vegetable and tea, are reported to be beneficial in treating neurological disorders. At present, their anti-fatigue effect remains to be established. In this study, we analyzed the composition of the extracts from A. senticosus leaves and confirmed their antioxidant and anti-inflammatory properties at the cellular level. In mice subjected to exhaustive running on a treadmill, supplementation with A. senticosus leaf extracts enhanced exercise performance and alleviated fatigue via the reversal of exercise-induced 5-HT elevation, metabolic waste accumulation, organ damage, and glucose metabolism-related gene expression. The collective findings from microbiome and metabolomic analyses indicate that A. senticosus leaf extracts increase α-diversity, regulate microbial composition, and reverse exercise-mediated disruption of carbohydrate, creatine, amino acid, and trimethylamine metabolism. This study provides preliminary evidence for the utility of A. senticosus leaves as a promising anti-fatigue food and offers insights into the underlying mechanism.

Ferroptosis-related gene glutathione peroxidase 4 promotes reprogramming of glucose metabolism via Akt-mTOR axis in intrahepatic cholangiocarcinoma.

The role of the ferroptosis-related gene glutathione peroxidase 4 (GPX4) in oncology has been extensively investigated. However, the clinical implications of GPX4 in patients with intrahepatic cholangiocarcinoma (ICC) remain unknown. This study aimed to evaluate the prognostic impact of GPX4 and its underlying molecular mechanisms in patients with ICC. Fifty-seven patients who underwent surgical resection for ICC between 2010 and 2017 were retrospectively analyzed. Based on the immunohistochemistry, patients were divided into GPX4 high (n = 15) and low (n = 42) groups, and clinical outcomes were assessed. Furthermore, the roles of GPX4 in cell proliferation, migration and gene expression were analyzed in ICC cell lines in vitro and in vivo. The results from clinical study showed that GPX4 high group showed significant associations with high SUVmax on 18F-fluorodeoxyglucose-positron emission tomography (≥8.0, P = 0.017), multiple tumors (P = 0.004), and showed glucose transporter 1 (GLUT1) high expression with a trend toward significance (P = 0.053). Overall and recurrence-free survival in the GPX4 high expression group were significantly worse than those in the GPX4 low expression group (P = 0.038 and P < 0.001, respectively). In the experimental study, inhibition of GPX4 attenuated cell proliferation and migration in ICC cell lines. Inhibition of GPX4 also decreased the expression of glucose metabolism-related genes, such as GLUT1 or HIF1α. Mechanistically, these molecular changes are regulated in Akt-mechanistic targets of rapamycin axis. In conclusion, this study suggested the pivotal value of GPX4 serving as a prognostic marker for patients with ICC. Furthermore, GPX4 can mediate glucose metabolism of ICC.

Constructing a prognostic model for head and neck squamous cell carcinoma based on glucose metabolism related genes.

Glucose metabolism (GM) plays a crucial role in cancer cell proliferation, tumor growth, and survival. However, the identification of glucose metabolism-related genes (GMRGs) for effective prediction of prognosis in head and neck squamous cell carcinoma (HNSC) is still lacking. We conducted differential analysis between HNSC and Normal groups to identify differentially expressed genes (DEGs). Key module genes were obtained using weighted gene co-expression network analysis (WGCNA). Intersection analysis of DEGs, GMRGs, and key module genes identified GMRG-DEGs. Univariate and multivariate Cox regression analyses were performed to screen prognostic-associated genes. Independent prognostic analysis of clinical traits and risk scores was implemented using Cox regression. Gene set enrichment analysis (GSEA) was used to explore functional pathways and genes between high- and low-risk groups. Immune infiltration analysis compared immune cells between the two groups in HNSC samples. Drug prediction was performed using the Genomics of Drug Sensitivity in Cancer (GDSC) database. Quantitative real-time fluorescence PCR (qRT-PCR) validated the expression levels of prognosis-related genes in HNSC patients. We identified 4973 DEGs between HNSC and Normal samples. Key gene modules, represented by black and brown module genes, were identified. Intersection analysis revealed 76 GMRG-DEGs. Five prognosis-related genes (MTHFD2, CDKN2A, TPM2, MPZ, and DNMT1) were identified. A nomogram incorporating age, lymph node status (N), and risk score was constructed for survival prediction in HNSC patients. Immune infiltration analysis showed significant differences in five immune cell types (Macrophages M0, memory B cells, Monocytes, Macrophages M2, and Dendritic resting cells) between the high- and low-risk groups. GDSC database analysis identified 53 drugs with remarkable differences between the groups, including A.443654 and AG.014699. DNMT1 and MTHFD2 were up-regulated, while MPZ was down-regulated in HNSC. Our study highlights the significant association of five prognosis-related genes (MTHFD2, CDKN2A, TPM2, MPZ, and DNMT1) with HNSC. These findings provide further evidence of the crucial role of GMRGs in HNSC.

Identification of genes related to glucose metabolism and analysis of the immune characteristics in Alzheimer's disease

ObjectiveGlucose metabolism plays a crucial role in the progression of Alzheimer's disease (AD). The purpose of this study is to identify genes related to glucose metabolism in AD by bioinformatics, construct an early AD prediction model from the perspective of glucose metabolism, and analyze the characteristics of immune cell infiltration. MethodsAD-related modules and genes were screened by weighted gene co-expression network analysis (WGCNA). The GO and KEEG enrichment analysis were used to explore the potential biological functions of glucose metabolism related genes (GMRGs) in AD. The Least Absolute Shrinkage Selection Operator (LASSO) method was used to construct an early AD prediction model based on GMRGs. Then, the receiver operating characteristic curve (ROC) and nomogram were introduced to evaluate the effectiveness of this model. Finally, CIBERSORT and single-cell analysis were applied for illustrating the immune characteristics in AD patients. ResultsA total of 462 differential expressed genes (DEGs) were obtained between Non-Alzheimer's disease (ND,) and AD groups. The genes in the blue module had the highest correlation with AD by WGCNA analysis. We found 18 intersected genes among DEGs, blue model genes and GMRGs according to the Venn diagram. The GO and KEEG enrichment analysis showed that these 18 genes were mainly involved in the production of metabolites and energy, glycolysis, amino acid biosynthesis and so on. The early AD prediction model including ENO2, TPI1, AEBP1, HERC1, PCSK1, PREPL, SLC25A4, UQCRC2, CHST6, DDIT4, ACSS1 and SUCLA2 was constructed by LASSO analysis. The area under the curve (AUC) of this model in brain tissues was 0.942. Then, we draw the nomogram of this model and the C-index was 0.942. The model was further validated in blood samples and the AUC was 0.644. Immune cell infiltration analysis showed that the proportion of plasma cells, T cells follicular helper and activated NK cells in AD group were significantly lower than ND group, while the proportion of M1 macrophages, neutrophils, T cells CD4 naive and γ-δ T cells was significantly increased when compared with the ND group. Additionally, the specific GMRGs such as ENO2, DDIT4, and SUCLA2 are significantly correlated with certain immune cells such as plasma cells, follicular helper T cells, and M1 macrophages. Single-cell analysis results suggested that the increased macrophages in AD was associated with the up-regulation of AEBP1, DDIT4 and ACSS1. ConclusionsThe diagnosis model based on the twelve GMRGs has strong predictive ability and can be used as early diagnosis biomarkers for AD. In addition, these GMRGs closely associate with AD development by influencing the glucose metabolism of immune cells.

Haloxyfop-P-methyl induces immunotoxicity and glucose metabolism disorders and affects the Nrf2/ARE pathway mediated antioxidant system in Chiromantes dehaani

Haloxyfop-P-methyl is used extensively in agricultural production, and its metabolites in soil have potentially toxic effects on aquatic ecosystems. In this study, we explored the toxicity of haloxyfop-P-methyl on Chiromantes dehaani. The results of the 21-day toxicity test showed that haloxyfop-P-methyl decreased the weight gain (WG), specific growth rate (SGR) and hepatosomatic index (HSI). In glucose metabolism, haloxyfop-P-methyl reduced pyruvate, lactate, lactate dehydrogenase and succinate dehydrogenase, but enhanced glucose-6-phosphate dehydrogenase and hexokinase. Furthermore, expression of glucose metabolism-related genes was upregulated. We cloned the full-length CdG6PDH gene, which contains a 1587 bp ORF that encoded a 528 amino acid polypeptide. In antioxidant system, haloxyfop-P-methyl increased glutathione, thioredoxin reductase and thioredoxin peroxidase activities and activated the Nrf2/ARE pathway through upregulation of ERK, JNK, PKC and Nrf2. In immunity, low concentrations haloxyfop-P-methyl, or short-term exposure, upregulated the expression of immune-related genes and enhanced immune-related enzymes activity, while high concentrations or long-term exposure inhibited immune function. In summary, haloxyfop-P-methyl inhibited the growth performance, disrupted glucose metabolism, activated the antioxidant system, and led to immunotoxicity. The results deepen our understanding of the toxicity mechanism of haloxyfop-P-methyl and provide basic biological data for the comprehensive assessment of the risk of haloxyfop-P-methyl to the environment and humans.

Transcriptome profiling of A549 non-small cell lung cancer cells in response to Trichinella spiralis muscle larvae excretory/secretory products.

Trichinella spiralis (T. spiralis) muscle-larva excretory/secretory products (ML-ESPs) is a complex array of proteins with antitumor activity. We previously demonstrated that ML-ESPs inhibit the proliferation of A549 non-small cell lung cancer (NSCLC) cell line. However, the mechanism of ML-ESPs against A549 cells, especially on the transcriptional level, remains unknow. In this study, we systematically investigated a global profile bioinformatics analysis of transcriptional response of A549 cells treated with ML-ESPs. And then, we further explored the transcriptional regulation of genes related to glucose metabolism in A549 cells by ML-ESPs. The results showed that ML-ESPs altered the expression of 2,860 genes (1,634 upregulated and 1,226 downregulated). GO and KEGG analysis demonstrated that differentially expressed genes (DEGs) were mainly associated with pathway in cancer and metabolic process. The downregulated genes interaction network of metabolic process is mainly associated with glucose metabolism. Furthermore, the expression of phosphofructokinase muscle (PFKM), phosphofructokinase liver (PFKL), enolase 2 (ENO2), lactate dehydrogenase B (LDHB), 6-phosphogluconolactonase (6PGL), ribulose-phosphate-3-epimerase (PRE), transketolase (TKT), transaldolase 1 (TALDO1), which genes mainly regulate glycolysis and pentose phosphate pathway (PPP), were suppressed by ML-ESPs. Interestingly, tricarboxylic acid cycle (TCA)-related genes, such as pyruvate dehydrogenase phosphatase 1 (PDP1), PDP2, aconitate hydratase 1 (ACO1) and oxoglutarate dehydrogenase (OGDH) were upregulated by ML-ESPs. In summary, the transcriptome profiling of A549 cells were significantly altered by ML-ESPs. And we also provide new insight into how ML-ESPs induced a transcriptional reprogramming of glucose metabolism-related genes in A549 cells.

Modulation of glucose metabolism-related genes in diabetic rats treated with herbal synthetic anti-diabetic compound (α-HSA): insights from transcriptomic profiling.

Eugenia jambolana is a medicinal plant traditionally used for treating diabetes. The bioactive compound FIIc, which is derived from the fruit pulp of E. jambolana, has been identified and purified as α-HSA. Previous studies have demonstrated that administration of α-HSA for 6 weeks improved glycemic index and dyslipidemia in rats with T2D. This study investigated the molecular mechanism underlying the potential therapeutic effects of α-HSA in experimentally induced diabetic rats. Male Wistar rats were divided into four groups: diabetic control, diabetic treated with FIIc, diabetic treated with α-HSA, and diabetic treated with glibenclamide. Over a 6-week experimental period, transcriptomic analysis was conducted on liver, skeletal, and pancreatic tissue samples collected from the rats. The study findings revealed significant upregulation of genes associated with glucose metabolism and insulin signaling in the groups treated with FIIc and α-HSA, compared to the diabetic control group. Moreover, pro-inflammatory genes were downregulated in these treatment groups. These results indicate that α-HSA has the potential to modulate key metabolic pathways, improve glucose homeostasis, enhance insulin sensitivity, and alleviate inflammation. This study provides compelling scientific evidence supporting the potential of α-HSA as a therapeutic agent for diabetes treatment. The observed upregulation of genes related to glucose metabolism and insulin signaling, along with the downregulation of pro-inflammatory genes, aligns with the pharmacological activity of α-HSA in controlling glucose homeostasis and improving insulin sensitivity. These findings suggest that α-HSA holds promise as a novel therapeutic approach for managing diabetes and its associated complications.