STUDY DESIGN: A retrospective observational study was performed. PURPOSE: We investigated the prevalence of sarcopenia in dropped head syndrome (DHS), and the relationship between biochemical markers, including major advanced glycation end products (AGEs), pentosidine, and DHS in older women. OVERVIEW OF LITERATURE: AGEs have been implicated in the pathogenesis of sarcopenia. METHODS: We studied 13 elderly women with idiopathic DHS (mean age, 77.2 years) and 20 healthy volunteers (mean age, 74.8 years). We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass [kg]/[height (m)]2). Cervical sagittal plane alignment, including C2–C7 sagittal vertical axis (C2–C7SVA), C2–C7 angle, and C2 slope (C2S), was measured. Biochemical markers, such as serum and urinary pentosidine, serum homocysteine, 1, 25-dihydroxyvitamin D, and 25-hydroxyvitamin D, were measured. The level of each variable was compared between DHS and controls. The relationship between biochemical markers and DHS was examined. RESULTS: Sarcopenia (SMI < 5.75) was observed at a high prevalence in participants with DHS (77% compared to 22% of healthy controls). Height, weight, femoral bone mineral density, appendicular lean mass, total lean mass, and SMI all had significantly lower values in the DHS group. Serum and urinary pentosidine, and serum homocysteine were significantly higher in the DHS group compared to controls. Analysis of cervical alignment revealed a significant positive correlation of serum pentosidine with C2–C7SVA and C2S. CONCLUSIONS: Sarcopenia was involved in DHS, and high serum pentosidine levels are associated with severity of DHS in older women.
Aged ; Biomarkers ; Body Composition ; Bone Density ; Electric Impedance ; Female ; Glycosylation End Products, Advanced ; Head ; Healthy Volunteers ; Homocysteine ; Humans ; Muscle, Skeletal ; Neck Muscles ; Observational Study ; Prevalence ; Retrospective Studies ; Sarcopenia

Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs. Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.
Cell Cycle ; Cell Cycle Checkpoints ; Cell Proliferation ; Connective Tissue Growth Factor* ; Connective Tissue* ; Cyclin D1 ; Extracellular Matrix* ; Fibrosis ; Genes, Regulator ; Glycosylation End Products, Advanced ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Muscle, Smooth, Vascular* ; Phosphotransferases ; RNA, Messenger ; Vascular System Injuries

OBJECTIVE: This study examined the effects on mortality and cell death after biomass charcoal combustion, in which carbon monoxide (CO) emissions were reduced using a biomass combustion improver in mice. METHODS: The biomass (glycerin) charcoal (Biomass CharCoal by Pusan National University, BCCP) was generated in the Power Generation System laboratory, Pusan National University. The effects and molecular mechanisms of biomass charcoal in carbon monoxide poisoning were examined by analyzing the mouse mortality, circulating leukocytes, carboxyhemoglobin (COHb), and expression of the inflammation-related genes, and cleaved capase-3 using enzyme-linked-immunosorbent-assays, real-time polymerase chain reaction, or Western blotting. RESULTS: The mortality rates were lower in the BCCP-exposed mice than in the raw charcoal-exposed mice. The circulating leukocytes were lower in the BCCP-exposed mice than in the raw charcoal-exposed mice. On the other hand, there was no significantly difference in the levels of COHb between both mice. Interestingly, the expression of the apoptosis-related gene, cleaved-capase 3, and the inflammation and tissue necrosis-related gene and receptor for the advanced glycation end products were reduced markedly in the BCCP-exposed mice compared to the raw charcoal-exposed mice. Decreased inflammation and tissue necrotic factors could be molecular mechanisms for the decreased mortality rates after BCCP burning. CONCLUSION: Biomass charcoal (BCCP) reduced the mortality rates and inflammation and tissue necrotic factors by 30%–40%. These results suggest that the biomass charcoal (BCCP) could reduce the incidence of suicide and CO-associated delayed symptoms after charcoal burning. Furthermore, it could extend the time for rescue in suicide attempts using charcoal burning.
Animals ; Biomass* ; Blotting, Western ; Burns* ; Busan ; Carbon Monoxide Poisoning ; Carbon Monoxide* ; Carbon* ; Carboxyhemoglobin ; Cell Death ; Charcoal* ; Glycosylation End Products, Advanced ; Hand ; Incidence ; Inflammation ; Leukocytes ; Mice* ; Mortality* ; Real-Time Polymerase Chain Reaction ; Suicide

In cases of chronic hyperglycemia, advanced glycation end-products (AGEs) are actively produced and accumulated in the circulating blood and various tissues. AGEs also accelerate the expression of receptors for AGEs, and they play an important role in the development of diabetic vascular complications through various mechanisms. Active interventions for glucose and related risk factors may help improve the clinical course of patients by reducing AGEs. This review summarizes recent updates on AGEs that have a significant impact on diabetic vascular complications.
Diabetes Complications ; Diabetic Angiopathies* ; Glucose ; Glycosylation End Products, Advanced* ; Humans ; Hyperglycemia ; Risk Factors

The present study was designed to evaluate the therapeutic potential of bioactive compounds from chloroform extract of the leaves of Hylocereus undatus in the formation of advanced glycation end products (AGEs) in vitro. Bioactivity-guided fractionation of chloroform extract from Hylocereus undatus afforded two novel 12-ursen-type triterpenes, 3β, 16α, 23-trihydroxy-urs-12- en-28-oic acid (1) and 3β, 6β, 19α, 22α-tetrahydroxy-urs-12-en-28-oic acid (2), as well as four known triterpenes 2α, 3β, 23-tetrahydroxy-urs-11-en-28-oic acid (3), 3β-acetoxy-28-hydroxyolean-12-ene (4), 3β, 16α-dihidroxyolean-12-ene (5) and 3β-acetoxy-olean-12-ene (6). Our results revealed that triterpenes 1-3 were able to inhibit the formation of AGEs in all tested assays. The data indicated that the triterpenes had inhibitory activity at the múltiple stages of glycation and that there might be a high potential for decreasing protein oxidation and protein glycation that can enhance glycative stress in diabetic complications.
Cactaceae ; chemistry ; Glycation End Products, Advanced ; chemistry ; Glycosylation ; drug effects ; Molecular Structure ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; Plant Leaves ; chemistry ; Triterpenes ; chemistry ; isolation & purification ; pharmacology

No abstract available.
Glycosylation End Products, Advanced* ; Lysine*

This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity. A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study. Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups. We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO₂) and arterial partial pressure of carbon dioxide (PaCO₂), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores. Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO₂, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO₂, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment. This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients.
Animals ; Asthma ; Carbon Dioxide ; Cats ; Eosinophils ; Forced Expiratory Volume ; Glycosylation End Products, Advanced ; Humans ; Hydrogen-Ion Concentration ; Immunoglobulin E ; Immunoglobulins ; Inspiratory Capacity ; Lipocalins ; Lung Diseases, Obstructive ; Neutrophils ; Nitric Oxide* ; Oxygen ; Partial Pressure ; Peroxidase ; Plasma ; Pulmonary Disease, Chronic Obstructive ; Pulmonary Surfactant-Associated Protein A ; Residual Volume ; Sputum ; Total Lung Capacity ; Vital Capacity

Hemodialysis (HD) patients experience vascular calcification, ultimately leading to high mortality rates. Previously, we reported associations between soluble receptor for advanced glycation end products (sRAGEs) and extracellular newly identified RAGE-binding protein S100A12 (EN-RAGE) and vascular calcification. Here, we extended our observations, investigating whether these biomarkers may be useful for predicting cardiovascular morbidity and mortality in these subjects. Thus, we evaluated the relationship between sRAGE and S100A12 and mortality in long-term HD patients. This was a prospective observational cohort study in 199 HD patients from an extended analysis of our previous study. Plasma sRAGE, S100A12, comorbidities, and other traditional risk factors were investigated. The cumulative incidences for death using Cox proportional hazards regression were evaluated in multivariable analyses. The observation period was 44 months. During the observation period, 27 (13.6%) patients died. Univariate analysis demonstrated that S100A12 was correlated with diabetes (P = 0.040) and high-sensitivity C-reactive protein (hsCRP) (P = 0.006). In multivariable analyses, plasma sRAGE (hazard ratio [HR] = 1.155; 95% confidence interval [CI] = 0.612–2.183; P = 0.656) and S100A12 (HR = 0.960; 95% CI = 0.566–1.630; P = 0.881) were not associated with mortality in HD patients, although traditional predictors of mortality, including age, history of cardiovascular diseases (CVDs), and serum levels of albumin and hsCRP were related to mortality. Powerful predictors of mortality were age, CVD, and albumin levels. Plasma sRAGE and S100A12 may be weak surrogate markers for predicting all-cause mortality in patients undergoing HD, although S100A12 was partly related to diabetes and inflammation.
Biomarkers ; C-Reactive Protein ; Cardiovascular Diseases ; Cohort Studies ; Comorbidity ; Glycosylation End Products, Advanced* ; Humans ; Incidence ; Inflammation ; Mortality* ; Plasma ; Prospective Studies ; Renal Dialysis* ; Risk Factors ; S100A12 Protein* ; Vascular Calcification

Methylglyoxal (MGO) is a highly reactive metabolite of glucose which is known to cause damage and induce apoptosis in endothelial cells. Endothelial cell damage is implicated in the progression of diabetes-associated complications and atherosclerosis. Hypericin, a naphthodianthrone isolated from Hypericum perforatum L. (St. John’s Wort), is a potent and selective inhibitor of protein kinase C and is reported to reduce neuropathic pain. In this work, we investigated the protective effect of hypericin on MGO-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Hypericin showed significant anti-apoptotic activity in MGO-treated HUVECs. Pretreatment with hypericin significantly inhibited MGO-induced changes in cell morphology, cell death, and production of intracellular reactive oxygen species. Hypericin prevented MGO-induced apoptosis in HUVECs by increasing Bcl-2 expression and decreasing Bax expression. MGO was found to activate mitogen-activated protein kinases (MAPKs). Pretreatment with hypericin strongly inhibited the activation of MAPKs, including P38, JNK, and ERK1/2. Interestingly, hypericin also inhibited the formation of AGEs. These findings suggest that hypericin may be an effective regulator of MGO-induced apoptosis. In conclusion, hypericin downregulated the formation of AGEs and ameliorated MGO-induced dysfunction in human endothelial cells.
Apoptosis ; Atherosclerosis ; Cell Death ; Endothelial Cells* ; Glucose ; Glycosylation End Products, Advanced ; Human Umbilical Vein Endothelial Cells ; Humans* ; Hypericum ; Mitogen-Activated Protein Kinases ; Neuralgia ; Protein Kinase C ; Pyruvaldehyde ; Reactive Oxygen Species

PURPOSE: Diabetic complications are a major concern to manage progression of diabetes. Production of advanced glycation end products (AGEs) due to high blood glucose is one of the mechanisms leading to diabetic complications. Multiple pharmacologic AGE inhibitory agents are currently under development, but clinical applications are still limited due to safety issues. Thus, it is necessary to identify a safe anti-glycation agent. It is known that burdock roots have antioxidant, anti-inflammatory, and anti-cancer activities. The objective of the present study was to investigate the inhibitory role of burdock roots on the formation of high glucose-induced glycation of bovine serum albumin (BSA). METHODS: In this study, glycation of BSA by glucose, galactose, or fructose at 37℃ for 3 weeks was assessed based on levels of α-dicarbonyl compounds (early-stage glycation products), fructosamine (intermediate products of glycation), and fluorescent AGEs (late-stage glycation products). In order to compare the inhibitory actions of burdock root extract in AGE formation, aminoguanidine (AG), a pharmacological AGE inhibitor, was used as a positive control. RESULTS: BSA glycation by glucose, fructose, and galatose was dose- and time-dependently produced. Burdock root extract at a concentration of 4 mg/mL almost completely inhibited glucose-induced BSA glycation. The results demonstrate that burdock root extract inhibited AGE formation with an IC₅₀ value of 1.534 mg/mL, and inhibitory activity was found to be more effective than the standard anti-glycation agent aminoguanidine. This study identified a novel function of burdock root as a potential anti-glycation agent. CONCLUSION: Our findings suggest that burdock root could be beneficial for preventing diabetic complications.
Arctium* ; Blood Glucose ; Diabetes Complications ; Fructosamine ; Fructose ; Galactose ; Glucose ; Glycosylation End Products, Advanced ; Hyperglycemia ; Serum Albumin, Bovine