12 research outputs found
Metal complex formation and anticancer activity of cu(I) and cu(ii) complexes with metformin
Metformin has been used for decades in millions of type 2 diabetes mellitus patients. In this
time, correlations between metformin use and the occurrence of other disorders have been noted, as
well as unpredictable metformin side effects. Diabetes is a significant cancer risk factor, but unexpectedly,
metformin-treated diabetic patients have lower cancer incidence. Here, we show that metformin
forms stable complexes with copper (II) ions. Both copper(I)/metformin and copper(II)/metformin
complexes form adducts with glutathione, the main intracellular antioxidative peptide, found at
high levels in cancer cells. Metformin reduces cell number and viability in SW1222 and K562 cells,
as well as in K562-200 multidrug-resistant cells. Notably, the antiproliferative effect of metformin is
enhanced in the presence of copper ions
What doesn't kill you makes you stronger: Future applications of amyloid aggregates in biomedicine
Amyloid proteins are linked to the pathogenesis of several diseases including Alzheimer’s
disease, but at the same time a range of functional amyloids are physiologically important in humans.
Although the disease pathogenies have been associated with protein aggregation, the mechanisms
and factors that lead to protein aggregation are not completely understood. Paradoxically, unique
characteristics of amyloids provide new opportunities for engineering innovative materials with
biomedical applications. In this review, we discuss not only outstanding advances in biomedical
applications of amyloid peptides, but also the mechanism of amyloid aggregation, factors aecting
the process, and core sequences driving the aggregation. We aim with this review to provide a useful
manual for those who engineer amyloids for innovative medicine solutions
New Advances in Fast Methods of 2D NMR Experiments
Although nuclear magnetic resonance spectroscopy is a potent analytical tool for identification, quantification, and structural elucidation, it suffers from inherently low sensitivity limitations. This chapter focuses on recently reported methods that enable quick acquisition of NMR spectra, as well as new methods of faster, efficient, and informative two-dimensional (2D) NMR methods. Fast and efficient data acquisition has risen in response to an increasing need to investigate chemical and biological processes in real time. Several new techniques have been successfully introduced. One example of this is band-selective optimized-flip-angle short-transient (SOFAST) NMR, which has opened the door to studying the kinetics of biological processes such as the phosphorylation of proteins. The fast recording of NMR spectra allows researchers to investigate time sensitive molecules that have limited stability under experimental conditions. The increasing awareness that molecular structures are dynamic, rather than static, has pushed some researchers to find alternatives to standard, time-consuming methods of 15N relaxation observables acquisition
Undercover Toxic Ménage à Trois of Amylin, Copper (II) and Metformin in Human Embryonic Kidney Cells
In recent decades, type 2 diabetes complications have been correlated with amylin aggregation,
copper homeostasis and metformin side effects. However, each factor was analyzed
separately, and only in some rare cases copper/amylin or copper/metformin complexes were
considered. We demonstrate for the first time that binary metformin/amylin and tertiary copper
(II)/amylin/metformin complexes of high cellular toxicity are formed and lead to the formation
of aggregated multi-level lamellar structures on the cell membrane. Considering the increased
concentration of amylin, copper (II) and metformin in kidneys of T2DM patients, our findings on the
toxicity of amylin and its adducts may be correlated with diabetic nephropathy development
Living with the enemy: from protein-misfolding pathologies we know, to those we want to know
Conformational diseases are caused by the aggregation of misfolded proteins. The risk for such pathologies
develops years before clinical symptoms appear, and is higher in people with alpha-1 antitrypsin (AAT) polymorphisms.
Thousands of people with alpha-1 antitrypsin deficiency (AATD) are underdiagnosed. Enemyaggregating
proteins may reside in these underdiagnosed AATD patients for many years before a pathology
for AATD fully develops. In this perspective review, we hypothesize that the AAT protein could exert a new and
previously unconsidered biological effect as an endogenous metal ion chelator that plays a significant role in
essential metal ion homeostasis. In this respect, AAT polymorphism may cause an imbalance of metal ions, which
could be correlated with the aggregation of amylin, tau, amyloid beta, and alpha synuclein proteins in type 2
diabetes mellitus (T2DM), Alzheimer’s and Parkinson’s diseases, respectively
Natural Polysaccharides as Preventive and Therapeutic Horizon for Neurodegenerative Diseases
Neurodegenerative diseases are a serious and widespread global public health burden amongst aging populations. The total estimated worldwide global cost of dementia was US by 2030. While advances have been made to understand different neurodegenerative disease mechanisms, effective therapeutic strategies do not generally exist. Several drugs have been proposed in the last two decades for the treatment of different types of neurodegenerative diseases, with little therapeutic benefit, and often with severe adverse and side effects. Thus, the search for novel drugs with higher efficacy and fewer drawbacks is an ongoing challenge in the treatment of neurodegenerative disease. Several natural compounds including polysaccharides have demonstrated neuroprotective and even therapeutic effects. Natural polysaccharides are widely distributed in plants, animals, algae, bacterial and fungal species, and have received considerable attention for their wide-ranging bioactivity, including their antioxidant, anti-neuroinflammatory, anticholinesterase and anti-amyloidogenic effects. In this review, we summarize different mechanisms involved in neurodegenerative diseases and the neuroprotective effects of natural polysaccharides, highlighting their potential role in the prevention and therapy of neurodegenerative disease
Therapeutic Properties of Vanadium Complexes
Vanadium is a hard, silver-grey transition metal found in at least 60 minerals and fossil fuel deposits. Its oxide and other vanadium salts are toxic to humans, but the toxic effects depend on the vanadium form, dose, exposure duration, and route of intoxication. Vanadium is used by some life forms as an active center in enzymes, such as the vanadium bromoperoxidase of ocean algae and nitrogenases of bacteria. The structure and biochemistry of vanadate resemble those of phosphate, hence vanadate can be regarded as a phosphate competitor in a variety of biochemical enzymes such as kinases and phosphatases. In this review, we describe the biochemical pathways regulated by vanadium compounds and their potential therapeutic benefits for a range of disorders including type 2 diabetes, cancer, cardiovascular disease, and microbial pathology
P166 Flow DSA-XM assay, will it explain the doubt of conventional flow cytometry crossmatch
Therapeutic Properties of Vanadium Complexes
Vanadium is a hard, silver-grey transition metal found in at least 60 minerals and fossil fuel deposits. Its oxide and other vanadium salts are toxic to humans, but the toxic effects depend on the vanadium form, dose, exposure duration, and route of intoxication. Vanadium is used by some life forms as an active center in enzymes, such as the vanadium bromoperoxidase of ocean algae and nitrogenases of bacteria. The structure and biochemistry of vanadate resemble those of phosphate, hence vanadate can be regarded as a phosphate competitor in a variety of biochemical enzymes such as kinases and phosphatases. In this review, we describe the biochemical pathways regulated by vanadium compounds and their potential therapeutic benefits for a range of disorders including type 2 diabetes, cancer, cardiovascular disease, and microbial pathology