Telomere length may be maintained by telomerase nucleoprotein complex and shelterin complex, namely TRF1, TRF2, TIN2, TPP1, POT1 and RAP1 proteins and modulated by TERRA expression. Telomere loss is observed during progression of chronic myeloid leukemia (CML) from the chronic phase (CML-CP) to the blastic phase (CML-BP). The introduction of tyrosine kinase inhibitors (TKIs), such as imatinib (IM), has changed outcome for majority of patients, however, a number of patients treated with TKIs may develop drug resistance. The molecular mechanisms underlying this phenomenon are not fully understood and require further investigation. In the present study, we demonstrate that IM-resistant BCR::ABL1 gene-positive CML K-562 and MEG-A2 cells are characterized by decreased telomere length, lowered protein levels of TRF2 and RAP1 and increased expression of TERRA in comparison to corresponding IM-sensitive CML cells and BCR::ABL1 gene-negative HL-60 cells. Furthermore, enhanced activity of glycolytic pathway was observed in IM-resistant CML cells. A negative correlation between a telomere length and advanced glycation end products (AGE) was also revealed in CD34+ cells isolated from CML patients. In conclusion, we suggest that affected expression of shelterin complex proteins, namely TRF2 and RAP1, TERRA levels, and glucose consumption rate may promote telomere dysfunction in IM-resistant CML cells.

BACKGROUND: The accumulation of tissue-advanced glycation end products in skin results from complex and consecutive reactions and can be measured by skin autofluorescence (SAF) reader devices. This overview discusses studies evaluating the utilization of SAF in screening renal and cardiac disease.
METHODS: Literature search was performed using Google Scholar, PubMed, Springer, Ovid, and ScienceDirect.
RESULTS: SAF was an independent predictor of progression of chronic kidney disease (CKD) and was elevated in subjects on hemodialysis and peritoneal dialysis. Furthermore, SAF was significantly associated with cardiovascular events, cardiovascular mortality, and all-cause mortality in CKD patients. Other studies revealed a correlation between SAF and arterial stiffness, vascular damage, and subclinical atherosclerosis. A vegetarian diet was associated with lower SAF levels, whereas malnutrition was correlated with higher levels and increased mortality.
CONCLUSIONS: SAF measurement may be useful in managing renal and cardiac disease. Future studies are needed to clarify the specific role of SAF in the management of CKD and its noninvasive office utilization to identify comorbidities in inflammatory diseases, such as psoriasis.

OBJECTIVE: Degenerative rotator cuff tears do not heal spontaneously, necessitating surgical intervention. This makes prevention crucial, but effective prophylactic measures are currently lacking. Oxidative stress has recently been implicated as a cause of degenerative rotator cuff tears, while mitochondrial injury has been reported in the development of age-related rotator cuff degeneration. Taurine, which has antioxidant properties, has been found to be effective in the treatment of various mitochondrial abnormalities. This prompted us to investigate the inhibitory effect of taurine and some other antioxidants against rotator cuff degeneration using tenocytes.
METHODS: Hydrogen peroxide (H2O2, 2 mM) was added to tenocytes in medium with 0.8 µM taurine (Group TAU), medium with 100 µM α-tocopherol (Group E), and medium with 150 µM ascorbic acid (Group C), then each medium was cultured for 24 h. Tenocytes supplemented with 2 mM H2O2 alone were similarly cultured for 24 h (Group H2O2). In each group, immunostaining was performed for the oxidative stress marker 8-hydroxy-2\'-deoxyguanosine and advanced glycation end products (AGE), which contribute to the development of age-related rotator cuff degeneration. In addition, levels of reactive oxygen species were measured using a cell-based assay kit, and results were compared. Immunostaining was also performed for indices of apoptosis (caspase-9, cleaved caspase-3 and Bcl-2), and Western blotting was used to quantify activation of caspase-9 at an early stage in each group.
RESULTS: Oxidative stress and AGE levels were decreased in the E and C groups. Levels of all parameters were reduced in the TAU group.
CONCLUSIONS: Taurine showed preventative effects against rotator cuff degeneration. The simple method of administration and paucity of side effects make clinical application easy, and the clear potential as a novel prophylactic strategy against degenerative rotator cuff tear warrants further study.

Interaction of advanced glycation end products (AGE) with their receptor i.e. receptor for advanced glycation end products (RAGE), better understood as AGE-RAGE axis, generates oxidative and inflammatory stress. The generated stress extent, in turn aggravates the AGE and RAGE levels through a vicious self propagation cycle. The associated oxidation and inflammation culminates in modifications and subsequent detrimental state of cellular macromolecules, including nucleic acids and proteins, manifesting multiple diseased conditions. Under normal physiological state, fewer carbonyl group(s) and glutathione, a tripeptide antioxidant may be added to proteins during post-translational modifications, recognized as carbonylation and glutathionylation, respectively. However, under oxidative and inflammatory stress conditions, protein carbonylation and glutathionylation are caused to considerably greater extents, leading to numerous diseased complications. Thereby, increased protein carbonylation and glutathionylation could be used as predictive markers of oxidative and inflammatory stress. The AGE-RAGE axis generated oxidatively modified proteins can be screened via assessing the protein carbonylation and glutathionylation. The present article focuses on most widely used protein carbonylation and glutathionylation based assays for quantifying the AGE-RAGE axis mediated oxidative and inflammatory stress.

Glycation and glycosylation are non-enzymatic and enzymatic reactions, respectively, of glucose, glucose metabolites, and other reducing sugars with different substrates, such as proteins, lipids, and nucleic acids. Increased availability of glucose is a recognized risk factor for the onset and progression of diabetes-mellitus-associated disorders, among which cardiovascular diseases have a great impact on patient mortality. Both advanced glycation end products, the result of non-enzymatic glycation of substrates, and O-linked-N-Acetylglucosaminylation, a glycosylation reaction that is controlled by O-N-AcetylGlucosamine (GlcNAc) transferase (OGT) and O-GlcNAcase (OGA), have been shown to play a role in cardiovascular remodeling. In this review, we aim (1) to summarize the most recent data regarding the role of glycation and O-linked-N-Acetylglucosaminylation as glucose-related pathogenetic factors and disease markers in cardiovascular remodeling, and (2) to discuss potential common mechanisms linking these pathways to the dysregulation and/or loss of function of different biomolecules involved in this field.

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder in women in their reproductive age. In recent years, the role of advanced glycation end products (AGEs) in PCOS has gained great attention. AGEs are highly reactive molecules that can be assumed by diet or endogenously synthesized as by-products of metabolic processes. AGE deposition increases with aging, hyperglycemia, insulin resistance, and glycotoxin-rich diet. Therefore, it has become imperative to understand the underlying mechanism of AGEs actions and its downstream effects in PCOS pathophysiology. By integrating evidence from human studies and experimental models, the present review points out that altered AGE deposition is a common feature in all PCOS phenotypes. Searching for possible mechanisms involved in the adaptive response against glycation injury in oocytes and ovaries, the role of SIRT1, the main member of the mammalian sirtuin family, has also recently emerged. Therefore, further studies based on anti-AGE interventions could be helpful in creating innovative strategies for counteracting PCOS and its effects on fertility.

The color of a therapeutic monoclonal antibody solution is a critical quality attribute. Consistency of color is typically assessed at time of release and during stability studies against preset criteria for late stage clinical and commercial products. A therapeutic protein solution\'s color may be determined by visual inspection or by more quantitative methods as per the different geographical area compendia. The nature and intensity of the color of a therapeutic protein solution is typically determined relative to calibrated standards. This review covers the analytical methodologies used for determining the color of a protein solution and presents an overview of protein variants and impurities known to contribute to colored recombinant therapeutic protein solutions.

Coronary artery atherosclerosis and atherosclerotic plaque rupture cause coronary artery disease (CAD). Advanced glycation end products (AGE) and its cell receptor RAGE, and soluble receptor (sRAGE) and endogenous secretory RAGE (esRAGE) may be involved in the development of atherosclerosis. AGE and its interaction with RAGE are atherogenic, while sRAGE and esRAGE have antiatherogenic effects. AGE-RAGE stress is a ratio of AGE/sRAGE. A high AGE-RAGE stress results in development and progression of CAD and vice-versa. AGE levels in serum and skin, AGE/sRAGE in patients with CAD, and expression of RAGE in animal model of atherosclerosis were higher, while serum levels of esRAGE were lower in patients with CAD compared with controls. Serum levels of sRAGE in CAD patients were contradictory, increased or decreased. This contradictory data may be due to type of patients used, because the sRAGE levels are elevated in diabetics and end-stage renal disease. AGE/sRAGE ratio is elevated in patients with reduced or elevated levels of serum sRAGE. It is to stress that AGE, RAGE, sRAGE, or esRAGE individually cannot serve as universal biomarker. AGE and sRAGE should be measured simultaneously to assess the AGE-RAGE stress. The treatment of CAD should be targeted at reduction in AGE levels, prevention of AGE formation, degradation of AGE in vivo, suppression of RAGE expression, blockade of RAGE, elevation of sRAGE, and use of antioxidants. In conclusion, AGE-RAGE stress would initiate the development and progression of atherosclerosis. Treatment modalities would prevent, regress, and slow the progression of CAD.

Sarcopenia is common in chronic kidney disease (CKD), and it is independently associated with morbidity and mortality. Advanced glycation end products (AGE) are mainly known as aging products. In CKD, AGE accumulate due to increased production and reduced kidney excretion. The imbalance between oxidant/antioxidant capacities in CKD patients is one of the main factors leading to AGE synthesis. AGE can, in turn, promote CKD progression and CKD-related complications by increasing reactive oxygen species generation, inducing inflammation, and promoting fibrosis. All these derangements can further increase AGE and uremic toxin accumulation and promote loss of muscle mass and function. Since the link between AGE and sarcopenia in CKD is far from being fully understood, we revised hereby the data supporting the potential contribution of AGE as mediators of oxidative stress in the pathogenesis of sarcopenia. Understanding how AGE and oxidative stress impact the onset of sarcopenia in CKD may help to identify new potential markers of disease progression and/or therapeutic targets.

This review focuses on the role of advanced glycation end products (AGEs) and its cell receptor (RAGE) and soluble receptor (sRAGE) in the pathogenesis of chronic lower limb ischemia (CLLI) and its treatment. CLLI is associated with atherosclerosis in lower limb arteries. AGE-RAGE axis which comprises of AGE, RAGE, and sRAGE has been implicated in atherosclerosis and restenosis. It may be involved in atherosclerosis of lower limb resulting in CLLI. Serum and tissue levels of AGE, and expression of RAGE are elevated, and the serum levels of sRAGE are decreased in CLLI. It is known that AGE, and AGE-RAGE interaction increase the generation of various atherogenic factors including reactive oxygen species, nuclear factor-kappa B, cell adhesion molecules, cytokines, monocyte chemoattractant protein-1, granulocyte macrophage-colony stimulating factor, and growth factors. sRAGE acts as antiatherogenic factor because it reduces the generation of AGE-RAGE-induced atherogenic factors. Treatment of CLLI should be targeted at lowering AGE levels through reduction of dietary intake of AGE, prevention of AGE formation and degradation of AGE, suppression of RAGE expression, blockade of AGE-RAGE binding, elevation of sRAGE by upregulating sRAGE expression, and exogenous administration of sRAGE, and use of antioxidants. In conclusion, AGE-RAGE stress defined as a shift in the balance between stressors (AGE, RAGE) and antistressor (sRAGE) in favor of stressors, initiates the development of atherosclerosis resulting in CLLI. Treatment modalities would include reduction of AGE levels and RAGE expression, RAGE blocker, elevation of sRAGE, and antioxidants for prevention, regression, and slowing of progression of CLLI.