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Scars, Burns & Healing 2016With ageing, the skin gradually loses its youthful appearance and functions like wound healing and scar formation. The pathophysiological theory of Advanced Glycation... (Review)
Review
INTRODUCTION
With ageing, the skin gradually loses its youthful appearance and functions like wound healing and scar formation. The pathophysiological theory of Advanced Glycation End products (AGEs) has gained traction during the last decade. This review aims to document the influence of AGEs on the mechanical and physiologic properties of the skin, how they affect dermal wound healing and scar formation in high-AGE populations like elderly patients and diabetics, and potential therapeutic strategies.
METHODS
This systematic literature study involved a structured search in Pubmed and Web of Science with qualitative analysis of 14 articles after a three-staged selection process with the use of in- and exclusion criteria.
RESULTS
Overall, AGEs cause shortened, thinned, and disorganized collagen fibrils, consequently reducing elasticity and skin/scar thickness with increased contraction and delayed wound closure. Documented therapeutic strategies include dietary AGE restriction, sRAGE decoy receptors, aminoguanidine, RAGE-blocking antibodies, targeted therapy, thymosin β4, anti-oxidant agents and gold nanoparticles, ethyl pyruvate, Gal-3 manipulation and metformin.
DISCUSSION
With lack of evidence concerning scars, no definitive conclusions can yet be made about the role of AGEs on possible appearance or function of scar tissue. However, all results suggest that scars tend to be more rigid and contractile with persistent redness and reduced tendency towards hypertrophy as AGEs accumulate.
CONCLUSION
Abundant evidence supports the pathologic role of AGEs in ageing and dermal wound healing and the effectiveness of possible therapeutic agents. More research is required to conclude its role in scar formation and scar therapy.
PubMed: 29799552
DOI: 10.1177/2059513116676828 -
PloS One 2016Galactose-deficient IgA1 was evaluated in patients with IgA nephropathy(IgAN) and controls in order to determine the predictive value of galactose-deficient IgA1 in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Galactose-deficient IgA1 was evaluated in patients with IgA nephropathy(IgAN) and controls in order to determine the predictive value of galactose-deficient IgA1 in cases of IgA nephropathy.
METHODS
PubMed, EMBASE, Cochrane central register of controlled trials, CNKI, CBM disc, and VIP database were searched to identify eligible studies that evaluated a difference in aberrant IgA1 glycosylation in IgAN patients compared with controls. A meta-analysis was conducted to evaluate the impact of galactose-deficient IgA1(Gd-IgA1) levels in different groups.
RESULTS
A total of 22 studies (n = 1657) met inclusion criteria. The mean Newcastle-Ottawa Scale (NOS) score was 7.2 and ranged from 6 to 8. The standard mean difference(SMD) in the meta-analysis of 20 studies of the level of Gd-IgA1 in the serum and/or supernatant of cultured cells was higher in the IgAN group compared with healthy controls as well as in those with other renal diseases (SMD = 1.76, 95% CI = 1.18-2.34, P<0.00001; SMD = 1.05, 95% CI = 0.05-2.04, P = 0.04). The data synthesis suggested that IgAN patients had similar levels of serum Gd-IgA1, with no significant differences, compared with first-degree relatives and Henoch-Schonlein purpura nephritis (HSPN) patients (MD = 0.04, 95% CI = 0.00-0.08, P = 0.05; MD = -46.03, 95% CI = -217.70-125.64, P = 0.60). In addition, the combined MD of 5 studies indicated that there were no significant differences in Gd-IgA1 levels among patients with varying severities of IgAN (MD = 0.02, 95% CI = -0.02-0.05, P = 0.28).
CONCLUSIONS
The pooled evidence suggests that the level of Gd-IgA1 in the serum or supernatant of cultured cells from peripheral blood or tonsils may be a useful biomarker for predicting IgA nephropathy, though the level of Gd-IgA1 was not significantly associated with disease severity.
Topics: Biomarkers; Early Diagnosis; Female; Galactose; Glomerulonephritis, IGA; Glycosylation; Humans; Immunoglobulin A; Male; Randomized Controlled Trials as Topic
PubMed: 27870872
DOI: 10.1371/journal.pone.0166700 -
International Archives of... Oct 2016High mobility group box 1 is a versatile protein involved in gene transcription, extracellular signaling, and response to inflammation. Extracellularly, high mobility... (Review)
Review
High mobility group box 1 is a versatile protein involved in gene transcription, extracellular signaling, and response to inflammation. Extracellularly, high mobility group box 1 binds to several receptors, notably the receptor for advanced glycation end-products. Expression of high mobility group box 1 and the receptor for advanced glycation end-products has been described in many cancers. To systematically review the available literature using PubMed and Web of Science to evaluate the clinical value of high mobility group box 1 and the receptor for advanced glycation end-products in head and neck squamous cell carcinomas. A total of eleven studies were included in this review. High mobility group box 1 overexpression is associated with poor prognosis and many clinical and pathological characteristics of head and neck squamous cell carcinomas patients. Additionally, the receptor for advanced glycation end-products demonstrates potential value as a clinical indicator of tumor angiogenesis and advanced staging. In diagnosis, high mobility group box 1 demonstrates low sensitivity. High mobility group box 1 and the receptor for advanced glycation end-products are associated with clinical and pathological characteristics of head and neck squamous cell carcinomas. Further investigation of the prognostic and diagnostic value of these molecules is warranted.
PubMed: 27746844
DOI: 10.1055/s-0036-1583168 -
Biochimica Et Biophysica Acta Apr 2015Galectins are a family of proteins that bind to specific glycans thereby deciphering the information captured within the glycome. In the last two decades, several... (Review)
Review
Galectins are a family of proteins that bind to specific glycans thereby deciphering the information captured within the glycome. In the last two decades, several galectin family members have emerged as versatile modulators of tumor progression. This has initiated the development and preclinical assessment of galectin-targeting compounds. With the first compounds now entering clinical trials it is pivotal to gain insight in the diagnostic and prognostic value of galectins in cancer as this will allow a more rational selection of the patients that might benefit most from galectin-targeted therapies. Here, we present a systematic review of galectin expression in human cancer patients. Malignant transformation is frequently associated with altered galectin expression, most notably of galectin-1 and galectin-3. In most cancers, increased galectin-1 expression is associated with poor prognosis while elevated galectin-9 expression is emerging as a marker of favorable disease outcome. The prognostic value of galectin-3 appears to be tumor type dependent and the other galectins require further investigation. Regarding the latter, additional studies using larger patient cohorts are essential to fully unravel the diagnostic and prognostic value of galectin expression. Furthermore, to better compare different findings, consensus should be reached on how to assess galectin expression, not only with regard to localization within the tissue and within cellular compartments but also regarding alternative splicing and genomic variations. Finally, linking galectin expression and function to aberrant glycosylation in cancer cells will improve our understanding of how these versatile proteins can be exploited for diagnostic, prognostic and even therapeutic purposes in cancer patients.
Topics: Alternative Splicing; Biomarkers, Tumor; Blood Proteins; Cell Transformation, Neoplastic; Galectin 1; Galectin 3; Galectins; Gene Expression Regulation, Neoplastic; Genomics; Humans; Neoplasms; Prognosis
PubMed: 25819524
DOI: 10.1016/j.bbcan.2015.03.003 -
Food & Function Oct 2014while antiglycative capacity has been attributed to (poly)phenols, the exact mechanism of action remains unclear. Studies so far are often relying on supra-physiological... (Review)
Review
BACKGROUND
while antiglycative capacity has been attributed to (poly)phenols, the exact mechanism of action remains unclear. Studies so far are often relying on supra-physiological concentrations and use of non-bioavailable compounds.
METHODS
to inform the design of a physiologically relevant in vitro study, we carried out a systematic literature review of dietary interventions reporting plasma concentrations of polyphenol metabolites. Bovine Serum Albumin (BSA) was pre-treated prior to in vitro glycation: either no treatment (native), pre-oxidised (incubated with 10 nM H2O2, for 8 hours) or incubated with a mixture of phenolic acids at physiologically relevant concentrations, for 8 hours). In vitro glycation was carried out in the presence of (i) glucose only (0, 5 or 10 mM), (ii) glucose (0, 5 or 10 mM) plus H2O2 (10 nM), or (iii) glucose (0, 5 or 10 mM) plus phenolic acids (10-160 nM). Fructosamine was measured using the nitro blue tetrazolium method.
RESULTS
following (high) dietary polyphenol intake, 3-hydroxyphenylacetic acid is the most abundant phenolic acid in peripheral blood (up to 338 μM) with concentrations of other phenolic acids ranging from 13 nM to 200 μM. The presence of six phenolic acids with BSA during in vitro glycation did not lower fructosamine formation. However, when BSA was pre-incubated with phenolic acids, significantly lower concentration of fructosamine was detected under glycoxidative conditions (glucose 5 or 10 mM plus H2O2 10 nM) (p < 0.001 vs. native BSA).
CONCLUSION
protein pre-treatment, either with oxidants or phenolic acids, is an important regulator of subsequent glycation in a physiologically relevant system. High quality in vitro studies under conditions closer to physiology are feasible and should be employed more frequently.
Topics: Animals; Databases, Factual; Fructosamine; Glucose; Glycosylation; Humans; Hydrogen Peroxide; Models, Molecular; Phenylacetates; Polyphenols; Proteins; Serum Albumin, Bovine
PubMed: 25170687
DOI: 10.1039/c4fo00568f -
Expert Review of Molecular Diagnostics Mar 2014Congenital disorders of N-glycosylation (CDG) form a rapidly growing group of more than 20 inborn errors of metabolism. Most patients are identified at the pediatric age... (Review)
Review
Congenital disorders of N-glycosylation (CDG) form a rapidly growing group of more than 20 inborn errors of metabolism. Most patients are identified at the pediatric age with multisystem disease. There is no systematic review on the long-term outcome and clinical presentation in adult patients. Here, we review the adult phenotype in 78 CDG patients diagnosed with 18 different forms of N-glycosylation defects. Characteristics include intellectual disability, speech disorder and abnormal gait. After puberty, symptoms might remain non-progressive and patients may lead a socially functional life. Thrombosis and progressive symptoms, such as peripheral neuropathy, scoliosis and visual demise are specifically common in PMM2-CDG. Especially in adult patients, diagnostic glycosylation screening can be mildly abnormal or near-normal, hampering diagnosis. Features of adult CDG patients significantly differ from the pediatric phenotype. Non-syndromal intellectual disability, or congenital malformations in different types of CDG and decreasing sensitivity of screening might be responsible for the CDG cases remaining undiagnosed until adulthood.
Topics: Abnormalities, Multiple; Adult; Ataxia; Cataract; Congenital Disorders of Glycosylation; Female; Glycosylation; Humans; Male; Phenotype; Scoliosis; Thrombosis; Young Adult
PubMed: 24524732
DOI: 10.1586/14737159.2014.890052 -
Seminars in Arthritis and Rheumatism Oct 2013Hydroxychloroquine (HCQ) is a widely used medication for the treatment of rheumatoid arthritis and systemic lupus erythematosus. An increasing body of evidence supports... (Review)
Review
OBJECTIVES
Hydroxychloroquine (HCQ) is a widely used medication for the treatment of rheumatoid arthritis and systemic lupus erythematosus. An increasing body of evidence supports actions of this drug that are not directly related to its immunosuppressive or anti-rheumatic properties. The objective of this systematic review is to characterize the spectrum of conditions that might be responsive to treatment with HCQ.
METHODS
PubMed was searched using the MeSH for HCQ with relevant subheadings and the limits of human topics and English language. Four-hundred and fifty-six abstracts from this search were examined individually to exclude those that were not focused on the objectives of this review. The resulting 76 articles were grouped according to topic areas and reviewed in detail.
RESULTS
HCQ has been reported to have therapeutic effects in a wide array of conditions, including diabetes mellitus, dyslipidemias, coagulopathies, infectious diseases and malignancies. Mechanisms of action responsible for these effects likely include altered signaling through cellular receptors, post-glycosylation modifications of infectious agents, changes in levels of inflammatory mediators and inhibition of autophagy. Many of the pathways are likely dependent on drug-induced changes in intra-endosomal acidity.
CONCLUSIONS
The use of, and interest in, HCQ has spread into many areas of medicine. Actions of this drug may be directly beneficial to patients with non-rheumatic conditions such as diabetes mellitus or viral infections. Further understanding of underlying mechanisms has potential to reveal modifiable pathogenic pathways that might elucidate approaches to the design of more effective therapeutics for many chronic diseases.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Hydroxychloroquine; Lupus Erythematosus, Systemic
PubMed: 23481418
DOI: 10.1016/j.semarthrit.2013.01.001 -
Nutricion Hospitalaria 2012Incretins are a cluster of hormones which are secreted and released into the bloodstream after food intake by gut enteroendocrine cells, reaching to pancreas where... (Meta-Analysis)
Meta-Analysis Review
Incretins are a cluster of hormones which are secreted and released into the bloodstream after food intake by gut enteroendocrine cells, reaching to pancreas where produce a potentiating effect on insulin release. The aim of this study was to perform a systematic review of incretins gene expression mediated by nutrients using specific search equations in the PubMed database. The two most relevant incretins are GLP-1 and GIP, which come from proglucagon and proGIP precursor respectively. GLP-1 is mainly synthesized and released by ileum and colon L cells, in contrast to GIP which does it by K cells in duodenum and proximal jejunum. It has been shown that canonical Wnt signalling pathway is closely related to the production of these hormones, since transcription factor TCF7L2 affects proglucagon and proGIP gene expression in L and K enteroendocrine cells. On the other hand, it has been shown that the hexosamine biosynthetic pathway can produce N-linked glycosylation of -catenin, an essential component of canonical Wnt signalling. This process hinders β-catenin phosphorylation and, thereby prevents proteasome degradation. Increasing glucose concentration enhances the hexosamine pathway and thus β-catenin glycosylation. This causes a β-catenin cytoplasmic accumulation allowing entry into nucleus, where it exerts its action by binding to a clump of molecules and transcription factors, allowing to express the target genes, including the incretin hormones. There is also evidence that glucose, through the hexosamine pathway, can induces autocrine activation of Wnt signalling pathway by stimulating secretion of Wnt proteins.
Topics: Animals; Gene Expression; Gene Expression Regulation; Hexosamines; Humans; Incretins; Nutritional Physiological Phenomena; Wnt Proteins
PubMed: 22566303
DOI: 10.1590/S0212-16112012000100006 -
Diabetic Medicine : a Journal of the... Sep 2010To describe the association between lung function and Type 2 diabetes mellitus. (Review)
Review
AIMS
To describe the association between lung function and Type 2 diabetes mellitus.
METHODS
We identified English language studies evaluating the association between lung function and diabetes mellitus in the MEDLINE database from 1 January 1975 to 31 December 2009. We evaluated study quality based on established criteria (54 studies were reviewed, 34 met the inclusion criteria).
RESULTS
Cross-sectional studies showed that adults with diabetes mellitus have lower forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), with reductions in FVC more consistent than FEV1 and lower diffusion capacity (DLCO) compared with their non-diabetic counterparts. The reduced lung function in patients with diabetes is inversely related to blood glucose levels, duration of diabetes and its severity and is independent of smoking or obesity. Findings in cohort studies have been less consistent, with only a few studies identifying an increased rate of lung function decline in adults with diabetes. In addition, other cohort studies have reported an association between decreased lung function and incident insulin resistance and diabetes. Studies evaluating biological mechanisms to explain the association between lung impairment and diabetes identified microangiopathy of the alveolar capillaries and pulmonary arterioles, chronic inflammation, autonomic neuropathy involving the respiratory muscles, loss of elastic recoil secondary to collagen glycosylation of lung parenchyma, hypoxia-induced insulin resistance and low birthweight, as being associated with both insulin resistance and impaired lung function.
CONCLUSIONS
There is an association between diabetes mellitus and decreased lung function, but the definitive direction as well as the exact pathophysiological mechanism to explain this association requires further investigation.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Forced Expiratory Volume; Humans; Insulin Resistance; Lung Diseases; Respiratory Function Tests
PubMed: 20722670
DOI: 10.1111/j.1464-5491.2010.03073.x -
Molecular Genetics and Metabolism 2010Hydrops fetalis (HF) is characterized by an accumulation of fluid in the extracellular compartments and in body cavities. Non-immune HF (NIHF) is caused by a wide... (Review)
Review
Hydrops fetalis (HF) is characterized by an accumulation of fluid in the extracellular compartments and in body cavities. Non-immune HF (NIHF) is caused by a wide variety of disorders and overall, 20-25% of NIHF remain unexplained. Inborn errors of metabolism, mostly lysosomal storage diseases have been estimated to account for 1-2% of cases, leading to HF by anemia or liver failure. Very few cases of NIHF and Congenital Disorder of Glycosylation (CDG) have been reported. We present here a case of recurrence of HF in a non-related couple in which the diagnosis of CDG type I was suspected at fetal pathological examination then confirmed at the enzymatic and molecular levels, as well as on a characteristic CDG I serum transferrin profile at 30weeks of gestation. We also provide a systematic review of reported cases with CDG type I and NIHF reported thus far. When NIHF remains unexplained despite exhaustive obstetrical screening, analysis of PMM activity in the parents' leucocytes is possible and might be performed easily during pregnancy. The accurate diagnosis is important in terms of counseling during pregnancy or later, in order to allow an early molecular prenatal diagnosis for the following pregnancies.
Topics: Congenital Disorders of Glycosylation; Female; Humans; Hydrops Fetalis; Lysosomal Storage Diseases; Phosphotransferases (Phosphomutases); Pregnancy
PubMed: 20638314
DOI: 10.1016/j.ymgme.2010.06.009