This study aims to explore the mechanism of Yanghe Decoction(YHD) against subcutaneous tumor in pulmonary metastasis from breast cancer, which is expected to lay a basis for the treatment of breast carcinoma with YHD. The chemical components of medicinals in YHD, and the targets of the components were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The disease-related targets were searched from GeneCards and Online Mendelian Inheritance in Man(OMIM). Excel was employed to screen the common targets and plot the Venn diagram. The protein-protein interaction network was constructed. R language was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. A total of 53 female SPF Bablc/6 mice were randomized into normal group(same volume of normal saline, ig), model group(same volume of normal saline, ig), and low-dose and high-dose YHD groups(YHD, ig, 30 days), with 8 mice in normal group and 15 mice in each of the other groups. Body weight and tumor size was measured every day. Curves for body weight variation and growth of tumor in situ were plotted. In the end, the subcutaneous tumor sample was collected and observed based on hematoxylin and eosin(HE) staining. The mRNA and protein levels of hypoxia inducible factor-1α(HIF-1α), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and glucose transporter type 1(GLUT1) were detected by PCR and Western blot. A total of 213 active components of YHD and 185 targets against the disease were screened out. The hypothesis that YHD may regulate glycolysis through HIF-1α signaling pathway to intervene in breast cancer was proposed. Animal experiment confirmed that the mRNA and protein levels of HIF-1α, PKM2, LDHA, and GLUT1 in the high-and low-dose YHD groups were lower than those in the model group. YHD has certain inhibitory effect on subcutaneous tumor in pulmonary metastasis from breast cancer in the early stage, which may intervene pulmonary metastasis from breast cancer by regulating glycolysis through HIF-1α signaling pathway.
Female ; Mice ; Animals ; Glucose Transporter Type 1/genetics* ; Network Pharmacology ; Animal Experimentation ; Saline Solution ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Signal Transduction ; Glycolysis ; RNA, Messenger ; Neoplasms/drug therapy* ; Molecular Docking Simulation

OBJECTIVE: To explore the pathogenesis of erythrocytosis by detecting the key enzymes of glucose metabolism and glucose transporter in bone marrow erythrocytes of chronic mountain sickness (CMS), and analyzing its correlation with hemoglobin. METHODS: Twenty CMS patients hospitalized in Qinghai Provincial People's Hospital from January 2019 to December 2020 were selected as CMS group. Twenty males with leukocyte count > 3.5×10⁹/L who had accepted bone marrow aspiration and had normal result were taken as control group. The mRNA and protein expression of key enzymes and glucose transporter in glucose metabolism in bone marrow CD71⁺ erythrocytes were detected by real time qPCR and Western blot, respectively. Glucose, lactic acid and 2,3-diphosphoglycerate in the bone marrow supernatant and serum were tested by ELISA. The mRNA and protein expression of key enzymes and glucose transporter, glucose, lactic acid and 2,3-diphosphoglycerate of the two groups were compared. Pearson correlation was used to analyze the correlation between key enzymes, glucose transporter in glucose metabolism in bone marrow CD71⁺ erythrocytes and hemoglobin. RESULTS: The expression of HK2, GLUT1 and GLUT2 mRNA in the CMS group were higher than those in the control group (P<0.001), while the expression of HK1, OGDH and COX5B mRNA were not different. The expression of HK2, GLUT1 and GLUT2 protein in the CMS group were higher than those in the control group (P<0.05). The levels of glucose and lactic acid in the bone marrow supernatant and serum in the CMS group were not different from those in the control group, while the level of 2,3-diphosphoglycerate was higher (P<0.001). Both HK2 and GLUT2 proteins were positively correlated with hemoglobin (r=0.511, 0.717). CONCLUSION CMS patients may increase glycolysis by increasing the expression of HK2, and promote the utilization of glucose through high expression of GLUT1 and GLUT2 to meet the need of energy supply.
Male ; Humans ; Altitude Sickness/metabolism* ; Glucose Transporter Type 1 ; 2,3-Diphosphoglycerate ; Hemoglobins ; Chronic Disease ; RNA, Messenger ; Phenotype ; Glucose

OBJECTIVE: To analyze the clinical phenotype and variant of SLC2A1 gene in a Chinese pedigree affected with glucose transporter type 1 deficiency syndrome (GLUT1-DS). METHODS: Clinical data of a child who was treated due to delayed motor and language development and his family members were collected. DNA was extracted from peripheral blood samples and subjected to high-throughput medical exome sequencing. Candidate variant was verified by Sanger sequencing of his parents and sister. The genotype-phenotype correlation was explored. RESULTS: The child, his mother and sister had common manifestations such as delayed mental and motor development, poor exercise tolerance, easy fatigue and paroxysmal dystonia, but the difference was that the child and his mother had microcephaly and seizures, while his sister did not. A heterozygous missense SLC2A1 c.191T>C (p.L64P) variant was identified in all affected members, which was unreported previously. CONCLUSION The missense SLC2A1 c.191T>C (p.L64P) variant probably underlay the disease in the proband and his mother and sister. Variability of the clinical phenotypes has reflected the genetic and phenotypic diversity of GLUT1-DS. Detection of the novel variant has enriched the spectrum of GLUT1-DS mutations.
Carbohydrate Metabolism, Inborn Errors ; China ; Glucose Transporter Type 1/genetics* ; Humans ; Monosaccharide Transport Proteins/deficiency* ; Mutation ; Pedigree ; Phenotype

Because of the unobvious early symptoms and low 5-year survival rate, the early diagnosis and treatment is of great significance for patients with non-small cell lung cancer. Glucose transporter-1 is the most widely distributed glucose transporters in various tissue cells in the human body, whose expression in non-small cell lung cancer is closely related to the histological types, lymph node metastasis, degree of differentiation, progression and prognosis.
Carcinoma, Non-Small-Cell Lung/diagnostic imaging* ; Fluorodeoxyglucose F18 ; Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 1 ; Humans ; Lung Neoplasms/diagnostic imaging* ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Radiopharmaceuticals

OBJECTIVES: To analyze the expressions and distributions of hypoxia-inducible factor-1α (HIF-1α), CD147, and glucose transporter 1 (GLUT1) in epidermis from psoriasis vulgaris and normal people, and to explore the associations among these proteins and their roles in hypoxic HaCaT cell line. METHODS: The expression levels of HIF-1α, CD147, and GLUT1 were determined by immunohistochemistry staining in skin biopsies from 48 psoriasis vularis patients and 33 healthy subjects. Cobalt chloride (CoCl RESULTS: HIF-1α, CD147, and GLUT1 were highly expressed and the glycolytic capacity was increased in lesions of psoriasis vulgaris; HIF-1α upregulated the expression of CD147 and GLUT1, increased the lactate production and decreased the ATP level in CoCl CONCLUSIONS Glycolytic capacity increases in the injured keratinocytes of psoriasis vulgaris, suggesting that HIF-1α, CD147, and GLUT1 are associated with glycolysis, which can be considered as the promising targets for psoriasis therapy.
Basigin ; Glucose Transporter Type 1 ; Glycolysis ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Psoriasis/genetics* ; Transcriptional Activation ; Up-Regulation

Hyperglycemia induces chronic low-grade inflammation (inflammaging), which is a newly identified contributor to diabetes-related tissue lesions, including the inflammatory bone loss in periodontitis. It is also a secondary senescent pattern mediated by an increased burden of senescent cells and senescence-associated secretory phenotype (SASP). Macrophage is a key SASP-spreading cell and may contribute to the maintenance of SASP response in the periodontal microenvironment. Using a transgenic diabetic model (BLKS/J-Lepr
Animals ; Cellular Senescence ; Diabetes Mellitus, Experimental ; Glucose Transporter Type 1 ; Inflammation ; Macrophages ; Mice

It is reported that energy metabolism is the core feature of tumor cells. This study is aimed to investigate the regulatory effect of two flavonoids( glabridin and quercetin) on energy supply and glycolysis of breast cancer cells,and provide reference for developing some anticancer herbal drugs with the function of regulating tumor energy metabolism. Based on the characteristics of each pathway during energy metabolism,in the present study,the triple negative breast cancer tumor cells( MDA-MB-231) were selected to investigate the effects of glabridin and quercetin on the energy metabolism of breast cancer cells and discuss the possible mechanisms from the following five potential targets: glucose uptake,protein expression of glucose transporter 1( GLUT1),adenosine triphosphate( ATP) level,lactate dehydrogenase( LDH) activity,and lactic acid( LD) concentration. The results showed that both quercetin and glabridin could decrease the glucose uptake capacity of breast cancer cells by down-regulating the protein expression of GLUT1. Quercetin had no significant effect on LDH activity and LD concentration; it did not affect the glycolysis process,but increased the intracellular ATP level. Glabridin decreased the activity of LDH and reduced LD concentration,thereby inhibiting the glycolysis metabolism of breast cancer cells. Therefore,both quercetin and glabridin can regulate the energy metabolism of breast cancer cells and can be used as potential anticancer agents or anti-cancer adjuvants.
Breast Neoplasms ; metabolism ; Cell Line, Tumor ; Energy Metabolism ; Glucose ; metabolism ; Glucose Transporter Type 1 ; metabolism ; Humans ; Isoflavones ; pharmacology ; Phenols ; pharmacology ; Quercetin ; pharmacology

The interplay between mechanoresponses and a broad range of fundamental biological processes, such as cell cycle progression, growth and differentiation, has been extensively investigated. However, metabolic regulation in mechanobiology remains largely unexplored. Here, we identified glucose transporter 1 (GLUT1)-the primary glucose transporter in various cells-as a novel mechanosensitive gene in orthodontic tooth movement (OTM). Using an in vivo rat OTM model, we demonstrated the specific induction of Glut1 proteins on the compressive side of a physically strained periodontal ligament. This transcriptional activation could be recapitulated in in vitro cultured human periodontal ligament cells (PDLCs), showing a time- and dose-dependent mechanoresponse. Importantly, application of GLUT1 specific inhibitor WZB117 greatly suppressed the efficiency of orthodontic tooth movement in a mouse OTM model, and this reduction was associated with a decline in osteoclastic activities. A mechanistic study suggested that GLUT1 inhibition affected the receptor activator for nuclear factor-κ B Ligand (RANKL)/osteoprotegerin (OPG) system by impairing compressive force-mediated RANKL upregulation. Consistently, pretreatment of PDLCs with WZB117 severely impeded the osteoclastic differentiation of co-cultured RAW264.7 cells. Further biochemical analysis indicated mutual regulation between GLUT1 and the MEK/ERK cascade to relay potential communication between glucose uptake and mechanical stress response. Together, these cross-species experiments revealed the transcriptional activation of GLUT1 as a novel and conserved linkage between metabolism and bone remodelling.
Animals ; Biomechanical Phenomena ; Blotting, Western ; Bone Remodeling ; drug effects ; Cells, Cultured ; Glucose Transporter Type 1 ; antagonists & inhibitors ; genetics ; Humans ; Hydroxybenzoates ; pharmacology ; Immunohistochemistry ; MAP Kinase Signaling System ; drug effects ; Mice ; Mice, Inbred C57BL ; Osteoprotegerin ; metabolism ; Periodontal Ligament ; cytology ; RANK Ligand ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Tooth Movement Techniques ; Transcriptional Activation

In the present study, we compared the cell-specific expression and changes protein levels in the glucose transporters (GLUTs) 1 and 3, the major GLUTs in the mouse and gerbil brains using immunohistochemistry and Western blot analysis. In both mouse and gerbils, GLUT1 immunoreactivity was mainly found in the blood vessels in the dentate gyrus, while GLUT3 immunoreactivity was detected in the subgranular zone and the molecular layer of the dentate gyrus. GLUT1-immunoreactivity in blood vessels and GLUT1 protein levels were significantly decreased with age in the mice and gerbils, respectively. In addition, few GLUT3-immunoreactive cells were found in the subgranular zone in aged mice and gerbils, but GLUT3-immunoreactivity was abundantly found in the polymorphic layer of dentate gyrus in mice and gerbils with a dot-like pattern. Based on the double immunofluorescence study, GLUT3-immunoreactive structures in gerbils were localized in the glial fibrillary acidic protein-immunoreactive astrocytes in the dentate gyrus. Western blot analysis showed that GLUT3 expression in the hippocampal homogenates was slightly, although not significantly, decreased with age in mice and gerbils, respectively. These results indicate that the reduction in GLUT1 in the blood vessels of dentate gyrus and GLUT3 in the subgranular zone of dentate gyrus may be associated with the decrease in uptake of glucose into brain and neuroblasts in the dentate gyrus. In addition, the expression of GLUT3 in the astrocytes in polymorphic layer of dentate gyrus may be associated with metabolic changes in glucose in aged hippocampus.
Aging* ; Animals ; Astrocytes ; Blood Vessels ; Blotting, Western ; Brain ; Dentate Gyrus* ; Fluorescent Antibody Technique ; Gerbillinae* ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 1 ; Glucose* ; Hippocampus ; Immunohistochemistry ; Mice*

The management of type 2 diabetes mellitus should comprise healthy lifestyle modifications along with tailored pharmacologic treatment. Traditionally, the American Diabetes Association (ADA)'s Diabetes Management Guidelines have not prioritized specific anti-diabetic drugs over others with regard to cardiovascular disease (CVD) and mortality prevention. Recently, two novel anti-diabetic medications proved to be significantly protective against future CVD and mortality, regardless of the glycemic levels achieved in type 2 diabetic patients with pre-existing CVD. The 2018 ADA Guidelines recommend SGLT2 inhibitor and/or GLP-1 receptor agonist be used for type 2 diabetes patients with atherosclerotic CVD after metformin monotherapy failure. Considering the value of CVD protection in the management of diabetes mellitus, this minor guideline adjustment could have far-reaching implications.
Cardiovascular Diseases ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide-1 Receptor ; Humans ; Life Style ; Metformin ; Mortality ; Sodium-Glucose Transporter 2