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Xiao-Bin Fang, Ying-Qi Xu, Hon-Fai Chan, Chun-Ming Wang, Qing Zheng, Fei Xiao, Mei-Wan Chen
Hepatocellular carcinoma (HCC) is an aggressive malignancy and the second leading cause of cancer death worldwide. Most current therapeutic agents lack the tumor-targeting efficiency and result in a nonselective biodistribution in the body. In our previous study, we identified a peptide Ala-Pro-Asp-Thr-Lys-Thr-Gln (APDTKTQ) that can selectively bind to the receptor of advanced glycation end-products (RAGE), an immunoglobulin superfamily cell surface molecule overexpressed during HCC malignant progression. Here, we report the design of a mixed micelles system modified with this peptide to target HCC cells...
October 21, 2016: Molecular Pharmaceutics
Helena Lenasi, Markos Klonizakis
Diabetes mellitus (DM) is associated with cardiovascular complications. Impairment of glycemic control induces noxious glycations, an increase in oxydative stress and dearangement of various metabolic pathways. DM leads to dysfunction of micro and macrovessels, connected to metabolic, endothelial and autonomic nervous system. Thus, assessing vascular reactivity might be one of the clinical tools to evaluate the impact of harmful effects of DM and potential benefit of treatment; skin and skeletal muscle microcirculation have usually been tested...
October 18, 2016: Clinical Hemorheology and Microcirculation
L Blonde, P Chava, T Dex, J Lin, E Nikonova, R Goldenberg
AIMS: To explore the treatment outcomes in adult patients with type 2 diabetes (T2D) enrolled in the GetGoal trials of lixisenatide (LIXI), and the predictive effects of baseline characteristics on outcomes. METHODS: This study was a pooled analysis of patient-level data from LIXI GetGoal studies comparing LIXI and placebo. Patients were divided into baseline therapy groups: oral antihyperglycaemic drugs (OADs) at baseline (n = 2,760) or basal insulin at baseline (n = 1,198)...
October 21, 2016: Diabetes, Obesity & Metabolism
Kailash Prasad, Abdullah Sarkar, Mohammad A Zafar, Ahmed Shoker, Hamdi Ei Moselhi, Maryann Tranquilli, Bulat A Ziganshin, John A Elefteriades
BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of thoracic aortic aneurysms (TAAs). Cytokines [Interleukin (IL)-Iβ, IL-2, IL-6, and TNF-α)] increase the expression of MMP-2 and -3. Advanced glycation end products (AGEs) interact with cell receptors to increase the release of cytokines. Circulating soluble receptors for AGEs (sRAGE) and endogenous secretory RAGE (esRAGE) compete with membrane bound RAGE for binding with AGEs and reduce the production of cytokines...
February 2016: Aorta (Stamford, Conn.)
Dora M Gorman, Carel W le Roux, Neil G Docherty
Bariatric surgery, initially intended as a weight-loss procedure, is superior to standard lifestyle intervention and pharmacological therapy for type 2 diabetes in obese individuals. Intensive medical management of hyperglycemia is associated with improved microvascular outcomes. Whether or not the reduction in hyperglycemia observed after bariatric surgery translates to improved microvascular outcomes is yet to be determined. There is substantial heterogeneity in the data relating to the impact of bariatric surgery on diabetic retinopathy (DR), the most common microvascular complication of diabetes...
October 2016: Diabetes & Metabolism Journal
Min-Soo Kim, Ji Hye Bang, Jun Lee, Jung-Soo Han, Tae Gon Baik, Won Kyung Jeon
BACKGROUND: Ginkgo biloba extract (GBE)-a widely used nutraceutical-is reported to have diverse functions, including positive effects on memory and vasodilatory properties. Although numerous studies have assessed the neuroprotective properties of GBE in ischemia, only a few studies have investigated the neuro-pharmacological mechanisms of action of GBE in chronic cerebral hypoperfusion (CCH). PURPOSE: In the present study, we sought to determine the effects of GBE on CCH-induced neuroinflammation and cholinergic dysfunction in a rat model of bilateral common carotid artery occlusion (BCCAo)...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Simona Arena, Giovanni Renzone, Chiara D'Ambrosio, Anna Maria Salzano, Andrea Scaloni
Heating of milk and dairy products is done using various technological processes with the aim of preserving microbiological safety and extending shelf-life. These treatments result in chemical modifications in milk proteins, mainly generated as a result of the Maillard reaction. Recently, different bottom-up proteomic methods have been applied to characterize the nature of these structural changes and the modified amino acids in model protein systems and/or isolated components from thermally-treated milk samples...
March 15, 2017: Food Chemistry
Herman G Sprenger, Wouter F Bierman, Melanie I Martes, Reindert Graaff, Tjip S Van Der Werf, Andries J Smit
OBJECTIVE: HIV-1 infection is associated with an increased cardiovascular disease (CVD) risk. Advanced glycation end products (AGEs) are formed as stable markers of glycemic and oxidative stress. Skin autofluorescence (SAF) as marker of accumulated AGEs is increased and predictive of CVD events in diabetes mellitus, chronic kidney disease (CKD) and pre-existing CVD. We determined SAF levels in HIV-1 infected patients, testing the hypothesis that SAF predicts CVD events in HIV infection...
October 18, 2016: AIDS
Alice P S Kong, Kai Chow Choi, Jihui Zhang, Andrea Luk, Siu Ping Lam, Michael H M Chan, Ronald C W Ma, Juliana C N Chan, Yun Kwok Wing
AIMS: We aimed to explore the associations of sleep patterns during weekdays and weekends with glycemic control in patients with type 2 diabetes. METHODS: We examined the association between indices of glycemic control [glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG)] and sleep parameters (sleep duration, bedtime, and differences of sleep duration during weekdays and weekends) from adults with type 2 diabetes recruited in a prospective cohort enrolling from hospital medical clinics...
October 19, 2016: Acta Diabetologica
Zhong'e Zhou, Yong Tang, Xian Jin, Chengjun Chen, Yi Lu, Liang Liu, Chengxing Shen
Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects...
2016: Journal of Diabetes Research
Somayeh Atari-Hajipirloo, Neda Valizadeh, Mohammad-Hassan Khadem-Ansari, Yousef Rasmi, Fatemeh Kheradmand
BACKGROUND: The altered levels of some essential trace elements and antioxidant minerals have been observed in diabetic patients. OBJECTIVES: The aim of the present study was to compare the concentrations of essential trace elements, copper (Cu), zinc (Zn), and iron (Fe) in the serum of patients who have type 2 diabetes mellitus (T2DM) with those of their non-diabetic first-degree relatives (FDR) and control subjects. The association between glycated hemoglobin (HbA1c) and levels of metals was also evaluated...
April 2016: International Journal of Endocrinology and Metabolism
Nabanita Das, Varun Dewan, Peter M Grace, Robin J Gunn, Ryo Tamura, Netanel Tzarum, Linda R Watkins, Ian A Wilson, Hang Yin
Infectious and sterile inflammatory diseases are correlated with increased levels of high mobility group box 1 (HMGB1) in tissues and serum. Extracellular HMGB1 is known to activate Toll-like receptors (TLRs) 2 and 4 and RAGE (receptor for advanced glycation endproducts) in inflammatory conditions. Here, we find that TLR5 is also an HMGB1 receptor that was previously overlooked due to lack of functional expression in the cell lines usually used for studying TLR signaling. HMGB1 binding to TLR5 initiates the activation of NF-κB signaling pathway in a MyD88-dependent manner, resulting in proinflammatory cytokine production and pain enhancement in vivo...
October 18, 2016: Cell Reports
Marie-Julie Nokin, Florence Durieux, Paul Peixoto, Barbara Chiavarina, Olivier Peulen, Arnaud Blomme, Andrei Turtoi, Brunella Costanza, Nicolas Smargiasso, Dominique Baiwir, Jean L Scheijen, Casper G Schalkwijk, Justine Leenders, Pascal De Tullio, Elettra Bianchi, Marc Thiry, Koji Uchida, David A Spiegel, James R Cochrane, Craig A Hutton, Edwin De Pauw, Philippe Delvenne, Dominique Belpomme, Vincent Castronovo, Akeila Bellahcène
Metabolic reprogramming toward aerobic glycolysis unavoidably induces methylglyoxal (MG) formation in cancer cells. MG mediates the glycation of proteins to form advanced glycation end products (AGEs). We have recently demonstrated that MG-induced AGEs are a common feature of breast cancer. Little is known regarding the impact of MG-mediated carbonyl stress on tumor progression. Breast tumors with MG stress presented with high nuclear YAP, a key transcriptional co-activator regulating tumor growth and invasion...
October 19, 2016: ELife
Ejiofor T Ugwu, Casmir Jg Orjioke, Ekenechukwu E Young
BACKGROUND: Self monitoring of blood glucose (SMBG) is a useful adjunct to lifestyle modification and medications for optimal management of type 2 diabetes mellitus (DM). This study was aimed at evaluating the practice, cost and associations of SMBG in subjects with type 2 DM in Enugu, Nigeria. METHODS: In a cross-sectional survey conducted at the diabetes clinic in three hospitals, 366 type 2 diabetic subjects aged 18-65 years were consecutively interviewed. Socio-demographic and clinical information were documented and glycated hemoglobin was performed for all the participants...
October 14, 2016: Current Diabetes Reviews
Eda Cengiz, Peiyao Cheng, Katrina J Ruedy, Craig Kollman, William V Tamborlane, Georgeanna J Klingensmith, Robin L Gal, Janet Silverstein, Joyce Lee, Maria J Redondo, Roy W Beck
OBJECTIVE: Current data are limited on the course of type 1 diabetes (T1D) in children and adolescents through the first few years of diabetes. The Pediatric Diabetes Consortium T1D new onset (NeOn) Study was undertaken to prospectively assess natural history and clinical outcomes in children treated at 7 US diabetes centers from the time of diagnosis. This paper describes clinical outcomes in the T1D NeOn cohort during the first 3 years postdiagnosis. RESULTS: A total of 1048 participants (mean age 9...
October 19, 2016: Pediatric Diabetes
Suzanne Miller, Amanda P Henry, Emily Hodge, Alexander K Kheirallah, Charlotte K Billington, Tracy L Rimington, Sangita K Bhaker, Ma'en Obeidat, Erik Melén, Simon K Merid, Caroline Swan, Catherine Gowland, Carl P Nelson, Ceri E Stewart, Charlotte E Bolton, Iain Kilty, Anders Malarstig, Stuart G Parker, Miriam F Moffatt, Andrew J Wardlaw, Ian P Hall, Ian Sayers
INTRODUCTION: Genome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Receptor (AGER, encoding RAGE). We aimed to (i) characterise RAGE expression in the lung, (ii) identify AGER transcripts, (iii) ascertain if SNP rs2070600 (Gly82Ser C/T) is associated with lung function and serum sRAGE levels and (iv) identify whether the Gly82Ser variant is functionally important in altering sRAGE levels in an airway epithelial cell model...
2016: PloS One
Jan Filipovsky, Jitka Seidlerova, Otto Mayer, Petra Karnosova
OBJECTIVE: Accumulation of advanced glycation end-products (AGE) has been suggested to be involved in several pathophysiological processes in the vessel wall. Soluble isoform of receptor for AGE (sRAGE) acts as a decoy for capturing circulating AGE, thus preventing them from binding to the cell-surface receptor (RAGE) and protecting against the RAGE-AGE axis-elicited processes. We hypothesized that low sRAGE levels might be associated with increased arterial stiffness. DESIGN AND METHOD: In a cross-sectional design, we analyzed 1077 subjects, aged 25 to 64 years, from the Czech population-based study ("Post-MONICA")...
September 2016: Journal of Hypertension
Hiroshi Itoh
Many hypertension guidelines have been published mainly from Western countries to standardize the management of hypertension all over the world, however, the significance of hypertension, along with other cardio-metabolic risks, such as obesity, diabetes or dyslipidemia should differ among different races. This paper compares the relevance of hypertension, one of the most important cardio-metabolic risk factors, in Asian and Western societies.1) Low target level of blood pressure control for diabetic hypertensives in JapanIn the Japanese Society of Hypertension Guidelines for the management of Hypertension (JSH2014), the target of blood pressure (BP) control in hypertensive patients with diabetes was set as < 130/80 mmHg...
September 2016: Journal of Hypertension
Asrul Akmal Shafie, Chin Hui Ng, Yui Ping Tan, Nathorn Chaiyakunapruk
BACKGROUND: Insulin analogues have a pharmacokinetic advantage over human insulin and are increasingly used to treat diabetes mellitus. A summary of their cost effectiveness versus other available treatments was required. OBJECTIVE: Our objective was to systematically review the published cost-effectiveness studies of insulin analogues for the treatment of patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). METHODS: We searched major databases and health technology assessment agency reports for economic evaluation studies published up until 30 September 2015...
October 17, 2016: PharmacoEconomics
Margarita G Skalnaya, Anatoly V Skalny, Vasily V Yurasov, Vasily A Demidov, Andrei R Grabeklis, Ivan V Radysh, Alexey A Tinkov
The primary aim of the research was to assess the level of trace elements and electrolytes in serum of postmenopausal diabetic women. Sixty-four postmenopausal women with type 2 diabetes mellitus (DM2) and 64 age- and body mass index-matched controls were examined. Serum trace elements were assessed using inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). Fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) levels were evaluated using Randox kits. The obtained data demonstrate that DM2 patients were characterized by 42 and 34 % higher FPG and HbA1c levels, respectively (p < 0...
October 18, 2016: Biological Trace Element Research
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