Abstract: Vascular complications arising from multiple environmental and genetic factors are responsible for many of the disabilities and short life expectancy associated with diabetes mellitus. Here we provide the first direct in vivo evidence that interactions between advanced glycation end products (AGEs; nonenzymatically glycosylated protein derivatives formed during prolonged hyperglycemic exposure) and their receptor, RAGE, lead to diabetic vascular derangement. We created transgenic mice that... Show More
Full-text available · Article · Aug 2001 · Journal of Clinical Investigation
Abstract: Proteasomal dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD). We examined the effect of a selective proteasomal inhibitor, epoxomicin, on primary cultured mesencephalic neurons. Exposing rat cultured mesencephalic neurons to epoxomicin for 24 h resulted in neurotoxicity in a dose-dependent manner. Epoxomicin caused mitochondrial dysfunction, reduction in reduced glutathione (GSH), and increased generation of free radicals. Neuronal damage was significantly... Show More
Abstract: Glycation, one of the post-translational modifications of proteins, is a nonenzymatic reaction initiated by the primary addition of a sugar aldehyde or ketone to the amino groups of proteins. In the early stage of glycation, the synthesis of intermediates leading to the formation of Amadori compounds occurs. In the late stage, advanced glycation end products (AGE) are irreversibly formed after a complex cascade of reactions. Several AGEs have been characterized chemically, while other new... Show More
Abstract: A dysfunctional ubiquitin-proteasome system recently has been proposed to play a role in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). We have shown previously that spinal motor neurons are more vulnerable to proteasome inhibition-induced neurotoxicity, using a dissociated culture system. To confirm this toxicity, we used organotypic slice cultures from rat neonatal spinal cords, which conserve the structure of the spinal cord in a horizontal... Show More
Full-text available · Article · Nov 2005 · Journal of Neuroscience Research
Abstract: Melanin, which is responsible for virtually all visible skin, hair, and eye pigmentation in humans, is synthesized, deposited, and distributed in subcellular organelles termed melanosomes. A comprehensive determination of the protein composition of this organelle has been obstructed by the melanin present. Here, we report a novel method of removing melanin that includes in-solution digestion and immobilized metal affinity chromatography (IMAC). Together with in-gel digestion, this method has... Show More
Full-text available · Article · Dec 2006 · Journal of Proteome Research
Abstract: We examined the effects of 2 calcium channel blockers, benidipine (T-, L-, and N-type) and amlodipine (L- and N-type), on renal, inflammatory, oxidative, and atherosclerosis markers in hypertensive patients with mild chronic kidney disease (CKD).
Forty hypertensive patients with CKD were assigned randomly to either of the 2 treatments: 8 mg benidipine once daily (n = 20, group A) or 5 mg amlodipine once daily (n = 20, group B). Treatment was continued for 12 months. Blood pressure, serum... Show More
Article · Feb 2010 · The American Journal of the Medical Sciences
Abstract: Diabetes is associated with a marked increased risk of atherosclerotic vascular disorders, including coronary, cerebrovascular, and peripheral artery disease. Cardiovascular disease (CVD) could account for disabilities and high mortality rates in patients with diabetes. Conventional risk factors, including hyperlipidemia, hypertension, smoking, obesity, lack of exercise, and a positive family history, contribute similarly to macrovascular complications in type 2 diabetic patients and... Show More
Abstract: To investigate the effect of glyceraldehyde-derived advanced glycation end-products (Glycer-AGEs) on hepatocellular carcinoma (HCC) cells.
Two HCC cell lines (Hep3B and HepG2 cells) and human umbilical vein endothelial cells (HUVEC) were used. Cell viability was determined using the WST-8 assay. Western blotting, enzyme linked immunosorbent assay, and real-time reverse transcription-polymerase chain reactions were used to detect protein and mRNA. Angiogenesis was evaluated by assessing the... Show More
Article · Apr 2012 · World Journal of Gastroenterology
An outline of the organotypic culture is presented in Figure 1. The procedures for the organotypic slice cultures of the central nervous system, in which the tissue slices were maintained on a Millicell-CM membrane for more than several months at the interface between the air and the culture medium (Stoppini et al., 1991; Tsuji et al., 2005), were modified for adipose tissue culture in our experiment. Six-week-old male Sprague–Dawley rats were purchased from Charles River Laboratories Japan, Inc. (Kanagawa, Japan) and, under deep anesthesia with isoflurane, were euthanized by exsanguination from the abdominal aorta.
[Show abstract] [Hide abstract] ABSTRACT: The precise localization and biological characteristics of the adipose progenitor cells are still a focus of debate. In this study, the localization of the adipose progenitor cells was determined using an organotypic culture system of adipose tissue slices. The tissue slices of subcutaneous white adipose tissue from rats were placed on a porous membrane and cultured at the interface between air and the culture medium for up to 5 days with or without adipogenic stimulation. The structure of adipose tissue components was sufficiently preserved during the culture and, following adipogenic stimulation with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine, numerous multilocular adipocytes appeared in the interstitium among the mature adipocytes. Histomorphological 3-D observation using confocal laser microscopy revealed the presence of small mesenchymal cells containing little or no fat residing in the perivascular region and on the mature adipocytes and differentiation from the pre-existing mesenchymal cells to multilocular adipocytes. Immunohistochemistry demonstrated that these cells were initially present within the fibronectin-positive extracellular matrix (ECM). The adipose differentiation of the mesenchymal cells was confirmed by the enhanced expression of C/EBP-β suggesting adipose differentiation and the concurrent advent of CD105-expressing mesenchymal cells within the interstitium of the mature adipocytes. Based on the above, the mesenchymal cells embedded in the ECM around the mature adipocytes were confirmed to be responsible for adipogenesis because the transition of the mesenchymal cells to the stem state contributed to the increase in the number of adipocytes in rat adipose tissue.
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Previous research has reported that ubiquitination of misfolded proteins is also a common hallmark of a variety of age-related neurodegenerative diseases including PD (Zhang et al., 2005;Bhat et al., 2014;Hromadkova et al., 2015;Squitieri and de Yebenes, 2015). And it has been reported that dysfunction of UPP induced by proteasome inhibitors, such as MG132 and epoxomicin, led to dopaminergic degeneration in both cell cultures and animal models (Kikuchi et al., 2003;Sun et al., 2006), indicating the importance of UPP in PD. In the present study, MG132 treatment induced the upregulation of exogenous Hapln2 in MES23.5 cells, indicating that Hapln2 may be degraded by ubiquitin degradation pathway.
[Show abstract] [Hide abstract] ABSTRACT: Parkinson's disease (PD), the second most common age-associated progressive neurodegenerative disorder, is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SN). The pathogenesis of PD and the mechanisms underlying the degeneration of DA neurons are still not fully understood. Our previous quantitative proteomics study revealed that hyaluronan and proteoglycan binding link protein 2 (Hapln2) is one of differentially expressed proteins in the substantia nigra tissues from PD patients and healthy control subjects. However, the potential role of Hapln2 in PD pathogenesis remains elusive. In the present study, we characterized the expression pattern of Hapln2. In situ hybridization revealed that Hapln2 mRNA was widely expressed in adult rat brain with high abundance in the substantia nigra. Immunoblotting showed that expression levels of Hapln2 were markedly upregulated in the substantia nigra of either human subjects with Parkinson's disease compared with healthy control. Likewise, there were profound increases in Hapln2 expression in neurotoxin 6-hydroxydopamine-treated rat. Overexpression of Hapln2 in vitro increased vulnerability of MES23.5 cells, a dopaminergic cell line, to 6-hydroxydopamine. Moreover, Hapln2 overexpression led to the formation of cytoplasmic aggregates which were co-localized with ubiquitin and E3 ligases including Parkin, Gp78, and Hrd1 in vitro. Endogenous α-synuclein was also localized in Hapln2-containing aggregates and ablation of Hapln2 led to a marked decrease of α-synuclein in insoluble fraction compared with control. Thus, Hapln2 is identified as a novel factor contributing to neurodegeneration in PD. Our data provides new insights into the cellular mechanism underlying the pathogenesis in PD.
Inflammation plays some important roles in the pathogenesis of DN. Leukocytes, macrophages and monocytes all involve in the process of DN [4, 5], and proinflammatory cytokines and inflammatory markers are strongly associated with the development of DN [6, 7]. High-sensitivity C-reactive protein (Hs-CRP), which is a marker of inflammation, has been reported to be associated with development of DN .
[Show abstract] [Hide abstract] ABSTRACT: Background
Interleukin-19 (IL-19) is a newly discovered cytokine belonging to the Interleukin-10(IL-10) family. IL-19 have indispensable functions in many inflammatory processes and also can induce the angiogenic potential of endothelial cells. The purpose of present study was to investigate the relation of serum interleukin-19 (IL-19) levels with diabetic nephropathy (DN). Methods
Two hundred study groups of patients with type 2 diabetes mellitus (T2DM) (109 males and 91 females) were recruited, included normoalbuminuria(n = 102), microalbuminuria(n = 72) and macroalbuminuria(n = 26) . The 50 healthy blood donors were enrolled for the control group. All subjects were assessed for: IL-19, High-sensitivity C-reactive protein (Hs-CRP), Cystatin C, urinary albumin excretion rate (UAE) and glycosylated hemoglobin A1c(HbA1c). ResultsThe serum IL-19 levels in DN patients were found to be significantly higher compared to controls. IL-19 levels were significantly positively correlated with Hs-CRP, Cystatin C, UAE and HbA1c(r = 0.623, 0.611,0.591 and 0.526 respectively, P < 0.01). Multivariable logistic regression analysis showed IL-19 levels (P = 0.01) were found to be independently associated with patients with DN. ConclusionsIL-19 is significantly positive correlated with UAE and Cystatin C. IL-19 may play an important role that contributes to the progression of diabetic nephropathy.
Hence, we did not compare the incidences of withdrawals due to adverse effects among the different treatment groups because it would likely result in bias. Several reports [13,16,18,20,21,23,24,27] used figures to present results, so the raw data were re-extracted using the Origin 8.6 program. We also attempted to contact the authors of the included twenty-four studies.
[Show abstract] [Hide abstract] ABSTRACT: BACKGROUND: High blood pressure can cause kidney damage, which can increase blood pressure, leading to a vicious cycle. It is not clear whether the protective effects of T-type calcium channel blockers (T-type CCBs) on renal function are better than those of L-type CCBs or renin-angiotensin system (RAS) antagonists in patients with hypertension. METHODS AND FINDINGS: PUBMED, MEDLINE, EMBASE, OVID, Web of Science, Cochrane, CNKI, MEDCH, VIP, and WANFANG databases were searched for clinical trials published in English or Chinese from January 1, 1990, to December 31, 2013. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated and reported. A total of 1494 reports were collected, of which 24 studies with 1,696 participants (including 809 reports comparing T-type CCBs versus L-type CCBs and 887 reports comparing T-type CCB versus RAS antagonists) met the inclusion criteria. Compared with L-type CCBs, T-type CCBs resulted in a significant decline in aldosterone (mean difference = -15.19, 95% CI -19.65 - -10.72, p
These diverse findings may be related to the difference of study design such as the selection of cell type and the method for AGE preparation and detection. Glyceraldehyde-derived AGE was also shown to display tumor-promoting effect on cancer cells from liver  and oral cavity . The study showed that CML a model of RAGE ligand , is abundantly found in glyceraldehyde-derived AGE  .
[Show abstract] [Hide abstract] ABSTRACT: In recent years, glycative stress from exogenous or endogenous advanced glycation end products (AGEs) and highly reactive dicarbonyls has gained great attention for its putative effects on cancer development. AGEs are a group of compounds formed from the complex chemical reaction of reducing sugars with compounds containing an amino group. AGEs bind to and activate the receptor for AGEs (RAGE), which is a predominant modulator of inflammation-associated cancer, and AGEs induce reactive oxygen species (ROS) that are an important regulator of the hallmarks of cancer. Dicarbonyls, which are formed during glycolysis, lipid oxidation or protein degradation, include glyoxal, methylglyoxal and 3-deoxyglucosone and are regarded as major precursors of AGEs. These dicarbonyls not only fuel the AGE pool in living organisms but also evoke carbonyl stress, which may contribute to the carbonylative damage of carbohydrates, lipids, proteins or DNA. Carbonylative damage then leads to many lesions, some of which are implicated in the pathogenesis of cancer. In this review, studies regarding the effects of AGEs and dicarbonyls on cancer onset or progression are systematically discussed, and the utilization of AGE inhibitors and dicarbonyl scavengers in cancer therapy are noted. This article is protected by copyright. All rights reserved
It is also one of the post translational modification processes between the sugars and the free amino groups of proteins (Monnier and Cerami, 1981). The research on glycation began with the discovery by Maillard (1912) who observed that heating of amino acids with a reducing sugar results in yellowish brown colour products (Kikuchi et al., 2003). Glycation reaction occurs in three stages: (i) the early, (ii) the intermediate and (iii) the late stage (Ahmed, 2005; Singh et al., 2014).
[Show abstract] [Hide abstract] ABSTRACT: The non enzymatic reaction between the carbonyl group of sugars and amino group of proteins, lipids and nucleic acids is termed as glycation. It has been linked to various diseases such as diabetes, cataract, Alzheimer’s, dialysis related amyloidosis, atherosclerosis, Parkinson’s as well as physiological ageing. In the present study, the progress of glycation was assessed, using methods for the measurement of browning, periodate, fructosamine and carbonyl content. It was found that phenolic acids (gallic acid, cinnamic acid and ferulic acid) caused a decrease in the production of amadori products and carbonyl content and had no significant effect on browning of glucoselysine mixture, standard glycation reaction. When the effect of gallic acid was checked on the glycated DNA sample, it caused the DNA damage alone and did not enhance the damage of glycated DNA sample. This study is significant as far as understanding the mechanism of phenolic acids on in vitro glycation is concerned.
Full-text · Article · Dec 2016 · Patient Education and Counseling
Suboptimal diabetes self-management increases the risk of diabetes-related complications [3,4]. As such, a substantial number of people living with diabetes are at risk for hyperlipidemia , hypertension, and macro vascular complications . Diabetes treatment and care are associated with considerably higher lifetime treatment costs, particularly when treatment involves poor adherence to self-management behaviors [3,6].
[Show abstract] [Hide abstract] ABSTRACT: Objectives:
The management of type 2 diabetes (T2D) requires complex behavior changes and treatment regimens to achieve optimal outcomes. Interventions including motivational interviewing (MI) have been explored to help patients achieve behavior change and outcomes; this study aimed to explore evidence and gaps in the literature for MI interventions and outcomes in adults with T2D.
A modified Cochrane method structured the search strategy among databases including MEDLINE, CINAHL, PsycINFO, and others. Inclusion criteria included randomized controlled trials that assessed the effects of MI on behavior changeoutcomes and resultant clinical outcomes in adults with T2D.
Of the initial 159 studies identified, 14 were eligible for retention. Behavior targets in the retained studies included dietary changes, physical activity, smoking cessation, and alcohol reduction. MI had significant impact on some dietary behaviors and on weight loss. MI intervention structures were heterogeneous across studies; fidelity assessment was infrequent.
The effects of MI interventions on outcomes in T2D showed promising results for dietary behaviors. Clinical change outcomes from MI-based interventions were most favorable for weight management in T2D.
Behavior-specific MI interventions may positively influence study outcomes. Assessment of MI intervention fidelity will enhance treatment integrity and claims for validity.
Premelanosomes contain all the proteins and enzymes required for their maturation to the fully functional specialised membrane-bound organelles called melanosomes, which are the sites of biosynthesis of melanin [26, 27]. The fully functional melanosomes contain all the proteins and enzymes required for biosynthesis of melanin, and the structural matrix proteins form an internal scaffold both to support the architecture of the melanosomes and to serve as a nidus for melanin deposition .
[Show abstract] [Hide abstract] ABSTRACT: In the mouth, melanin is produced by melanocytes residing in the basal cell layer of the oral epithelium. Melanin influences the colour of the oral mucosa and provides protection against reactive oxygen species and bacterial-derived enzymes and toxins and acts as a physical barrier to both microorganisms invading the oral epithelium and to other microenvironmental stressors. The functional activity of epithelial melanocytes is regulated by biological agents in the microenvironment, including proopiomelanocortin-derived peptides, and by reciprocal interactions between melanocytes on the one hand and neighbouring keratinocytes and signals from the underlying lamina propria on the other hand. Oral mucosal melanin hyperpigmentation is common and may be physiological or pathological, and in either case the pattern of distribution and the intensity of the melanosis are variable. Physiological melanin hyperpigmentation is the result of increased melanin biosynthesis by melanocytes in the basal cell layer of the oral epithelium, but pathological melanin pigmentation may be the result of increased number of normal melanocytes or atypical melanocytes, of increased melanogenic activity of normal or atypical melanocytes, or of both. Oral mucosal melanin hyperpigmentation may be secondary to disease, medications, or smoking, and physiological oral melanin hyperpigmentation may be clinically and histopathologically similar so that the differentiation between pathological and physiological oral melanosis can at times be difficult.
Chapter · Mar 2017 · Patient Education and Counseling