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PloS One 2022Glycation process refers to reactions between reduction sugars and amino acids that can lead to formation of advanced glycation end products (AGEs) which are related to...
Glycation process refers to reactions between reduction sugars and amino acids that can lead to formation of advanced glycation end products (AGEs) which are related to changes in chemical and functional properties of biological structures that accumulate during aging and diseases. The aim of this study was to perform and analyze in vitro glycation by fructose and methylglyoxal (MGO) using salivary fluid, albumin, lysozyme, and salivary α-amylase (sAA). Glycation effect was analyzed by biochemical and spectroscopic methods. The results were obtained by fluorescence analysis, infrared spectroscopy (total attenuated reflection-Fourier transform, ATR-FTIR) followed by multivariate analysis of principal components (PCA), protein profile, immunodetection, enzymatic activity and oxidative damage to proteins. Fluorescence increased in all glycated samples, except in saliva with fructose. The ATR-FTIR spectra and PCA analysis showed structural changes related to the vibrational mode of glycation of albumin, lysozyme, and salivary proteins. Glycation increased the relative molecular mass (Mr) in protein profile of albumin and lysozyme. Saliva showed a decrease in band intensity when glycated. The analysis of sAA immunoblotting indicated a relative reduction in intensity of its correspondent Mr after sAA glycation; and a decrease in its enzymatic activity was observed. Carbonylation levels increased in all glycated samples, except for saliva with fructose. Thiol content decreased only for glycated lysozyme and saliva with MGO. Therefore, glycation of salivary fluid and sAA may have the potential to identify products derived by glycation process. This opens perspectives for further studies on the use of saliva, an easy and non-invasive collection fluid, to monitor glycated proteins in the aging process and evolution of diseases.
Topics: Adult; Albumins; Female; Fructose; Glycation End Products, Advanced; Glycosylation; Healthy Volunteers; Humans; Male; Muramidase; Oxidative Stress; Pyruvaldehyde; Saliva; Salivary Proteins and Peptides; Spectrometry, Fluorescence
PubMed: 35061788
DOI: 10.1371/journal.pone.0262369 -
Transfusion and Apheresis Science :... Jun 2021Alzheimer's disease (AD) is a neurodegenerative process that inexorably leads to progressive deterioration of cognition function and, ultimately, death. Central... (Review)
Review
Alzheimer's disease (AD) is a neurodegenerative process that inexorably leads to progressive deterioration of cognition function and, ultimately, death. Central pathophysiologic features of AD include the accumulation of extracellular plaques comprised of amyloid-β peptide (Aβ) and the presence of intraneuronal neurofibrillary tangles. However, a large body of evidence suggests that oxidative stress and inflammation are major contributors to the pathogenesis and progression of AD. To date, available pharmacologic treatments are only symptomatic. Clinical trials focused on amyloid and non-amyloid-targeted treatments with small molecule pharmacotherapy and immunotherapies have accumulated a long list of failures. Considering that around 90 % of the circulating Aβ is bound to albumin, and that a dynamic equilibrium exists between peripheral and central Aβ, plasma exchange with albumin replacement has emerged as a new approach in a multitargeted AD therapeutic strategy (AMBAR Program). In plasma exchange, a patient's plasma is removed by plasmapheresis to eliminate toxic endogenous substances, including Aβ and functionally impaired albumin. The fluid replacement used is therapeutic albumin, which acts not only as a plasma volume expander but also has numerous pleiotropic functions (e.g., circulating Aβ- binding capacity, transporter, detoxifier, antioxidant) that are clinically relevant for the treatment of AD. Positive results from the AMBAR Program (phase 1, 2, an 2b/3 trials), i.e., slower decline or stabilization of disease symptoms in the most relevant clinical efficacy and safety endpoints, offer a glimmer of hope to both AD patients and caregivers.
Topics: Albumins; Alzheimer Disease; Humans; Models, Molecular; Plasma Exchange
PubMed: 34083161
DOI: 10.1016/j.transci.2021.103164 -
Nephrology, Dialysis, Transplantation :... Oct 2018Aggressive removal of middle molecules or larger low-molecular-weight proteins (LMWPs) has been a growing concern following studies on their harmful effects on the... (Review)
Review
Aggressive removal of middle molecules or larger low-molecular-weight proteins (LMWPs) has been a growing concern following studies on their harmful effects on the mortality and morbidity of chronic dialysis patients. To remove larger LMWPs and some protein-bound uremic toxins (PBUTs), high- and medium-cutoff (HCOs and MCOs, respectively) membranes, convective therapy and protein adsorptive membranes are available. When we use HCO or MCO membranes for convective therapy, we have to take care to avoid massive albumin leakage during a dialysis session. Convection volume is an important element to increase middle molecule removal; however, a larger convection volume has a risk of larger leakage of albumin. Predilution hemodiafiltration is a useful measurement to increase larger LMWPs without massive albumin leakage. β2-microglobulin (B2M), α1-microglobulin (A1M) and albumin leakage during a dialysis session are useful parameters for assessing middle-molecule removal. Reduction ratios of B2M >80% and of A1M >35% are favorable to improve severe dialysis-related symptoms. The efficacy of middle molecule removal should be evaluated in comparison with clinical outcomes, mortality, morbidity and the improvement of dialysis-related symptoms. Recently some dialysis-related symptoms such as sleep disturbance, skin itchiness and dialysis hypotension have been recognized as good surrogate makers for mortality. Further studies to evaluate the relationship between middle molecule or PBUTs removal and the improvement of patient symptoms should be performed in well-designed randomized controlled trials.
Topics: Albumins; Animals; Hemodiafiltration; Humans; Membranes, Artificial; Molecular Weight; Renal Dialysis; Toxins, Biological; beta 2-Microglobulin
PubMed: 30281129
DOI: 10.1093/ndt/gfy224 -
Genes Mar 2022The common non-synonymous mutation of the glucokinase regulator () gene, namely rs1260326, is widely reported to have pleiotropic effects on cardio-metabolic traits and...
BACKGROUND
The common non-synonymous mutation of the glucokinase regulator () gene, namely rs1260326, is widely reported to have pleiotropic effects on cardio-metabolic traits and hematological parameters.
OBJECTIVE
This study aimed to identify whether other variants may have pleiotropic effects independent of the rs1260326 genotypes.
METHODS
In total, 81,097 Taiwan Biobank participants were enrolled for the regional plot association studies and candidate variant analysis of the region around the gene.
RESULTS
The initial candidate variant approach showed the significant association of the rs1260326 genotypes with multiple phenotypes. Regional plot association analysis of the gene region further revealed genome-wide significant associations between variants and serum total and low-density lipoprotein cholesterol; triglyceride, uric acid, creatinine, aspartate aminotransferase, γ-Glutamyl transferase, albumin, and fasting plasma glucose levels; estimated glomerular filtration rate; leukocyte and platelet counts; microalbuminuria, and metabolic syndrome, with rs1260326 being the most common lead polymorphism. Serial conditional analysis identified genome-wide significant associations of two low-frequency exonic mutations, rs143881585 and rs8179206, with high serum triglyceride and albumin levels. In five rare exonic non-synonymous or nonsense mutations available for analysis, rs146175795 showed an independent association with serum triglyceride and albumin levels and rs150673460 showed an independent association with serum triglyceride levels. Weighted genetic risk scores from the combination of rs143881585 and rs146175795 revealed a significant association with metabolic syndrome.
CONCLUSION
In addition to the rs1260326 variant, low-frequency and rare exonic mutations exhibit pleiotropic effects on serum triglyceride and albumin levels and the risk of metabolic syndrome. These results provide evidence that both common and rare variants may play a critical role in predicting the risk of cardiometabolic disorders.
Topics: Adaptor Proteins, Signal Transducing; Albumins; Blood Glucose; Cardiovascular Diseases; Genetic Pleiotropy; Humans; Metabolic Syndrome; Mutation; Phenotype; Polymorphism, Single Nucleotide; Triglycerides
PubMed: 35328045
DOI: 10.3390/genes13030491 -
The Journal of Organic Chemistry Sep 2022A modular synthetic process enables two or four shielding arms to be appended strategically over the fluorochromes of near-infrared cyanine heptamethine dyes to create...
A modular synthetic process enables two or four shielding arms to be appended strategically over the fluorochromes of near-infrared cyanine heptamethine dyes to create hydrophilic analogs of clinically approved indocyanine green. A key synthetic step is the facile substitution of a heptamethine 4'-Cl atom by a phenol bearing two triethylene glycol chains. The lead compound is a heptamethine dye with four shielding arms, and a series of comparative spectroscopy studies showed that the shielding arms (a) increased dye photostability and chemical stability and (b) inhibited dye self-aggregation and association with albumin protein. In mice, the dye cleared from the blood primarily through the renal pathway rather than the biliary pathway for . This change in biodistribution reflects the much smaller hydrodynamic diameter of the shielded hydrophilic analog compared to the 67 kDa size of the /albumin complex. An attractive feature of versatile synthetic chemistry is the capability to systematically alter the dye's hydrodynamic diameter. The sterically shielded hydrophilic dye platform is well-suited for immediate incorporation into dynamic contrast-enhanced (DCE) spectroscopy or imaging protocols using the same cameras and detectors that have been optimized for .
Topics: Albumins; Animals; Fluorescent Dyes; Hydrophobic and Hydrophilic Interactions; Indocyanine Green; Mice; Tissue Distribution
PubMed: 35950971
DOI: 10.1021/acs.joc.2c01229 -
BMC Surgery Apr 2022A meta-analysis of randomized controlled trials was recently published in BMC Surgery that compared the use of human albumin with 6% hydroxyethyl starches 130/0.4 for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A meta-analysis of randomized controlled trials was recently published in BMC Surgery that compared the use of human albumin with 6% hydroxyethyl starches 130/0.4 for cardiopulmonary bypass prime and perioperative fluid management in pediatric and adult cardiac surgery patients. The two plasma expanding solutions are described as equivalent for efficacy and safety outcomes, and, on that basis, the preferential use of hydroxyethyl starches 130/0.4 was recommended for economic reasons because of the higher unit costs of human albumin solutions.
RESULTS
In addition to the fact that trials were mostly small, single-center studies and the number of total participants was low, making the meta-analysis underpowered for several outcomes, selective reporting of data for ICU length of stay was identified. Re-calculation of statistics at higher precision showed that ICU length of stay of patients in the human albumin group was significantly shorter than that of patients in the 6% hydroxyethyl starches 130/0.4 group (standard mean difference - 0.181, 95% confidence interval - 0.361 to - 0.001, P = 0.049), which may offset any proposed economic advantage of using 6% hydroxyethyl starches 130/0.4. At the same time, the renal safety of 6% hydroxyethyl starches 130/0.4 in surgical patients is under regulatory review.
CONCLUSIONS
Underpowered trials and selective reporting may impair the validity of the meta-analysis. A more cautious conclusion about the interchangeability between human albumin and 6% hydroxyethyl starches 130/0.4 in cardiac surgery should have been reached.
Topics: Adult; Albumins; Cardiac Surgical Procedures; Child; Humans; Hydroxyethyl Starch Derivatives; Plasma Substitutes; Serum Albumin, Human
PubMed: 35410195
DOI: 10.1186/s12893-022-01588-x -
Scientific Reports Jun 2023This study aimed to evaluate the change of white blood cell count, serum concentration of cortisol, C-reactive protein, albumin and globulin fractions in horse after...
This study aimed to evaluate the change of white blood cell count, serum concentration of cortisol, C-reactive protein, albumin and globulin fractions in horse after road transport, and to assess the linkage among hypothalamic-pituitary-adrenal axis (HPA) and inflammatory reaction. From 10 horses blood samples were collected at rest, before road transport (218 km) (BT); after unloaded (AT), 30 and 60 min after unloaded (AT30 and AT60) in order to assess white blood cell count (WBC), serum cortisol, C-reactive protein (CRP), total proteins, albumin, α1-, α-2, β1-, β2- and γ-globulins. WBC, cortisol, CRP, α1-, α-2 and β2-globulins values increased after road transport than rest condition (p < 0.001). Albumin and A/G ratio showed lower values after road transport than rest (p < 0.001). Pearson's test showed a negative correlation between cortisol and the values of WBC, CRP, α1-, α2-, β1-, β2- globulins, and a positive correlation between WBC and serum concentration of CRP, α1- and α2-, β1-, β2-globulins at AT and AT30. The results showed that road transport evokes an inflammatory like-status in horses. Moreover, the activation of HPA and the onset of acute phase reaction in response to road transport seem to be interconnected with effects on horse's immune status.
Topics: Horses; Animals; Hydrocortisone; C-Reactive Protein; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Globulins; Albumins
PubMed: 37330619
DOI: 10.1038/s41598-023-37069-1 -
International Journal of Molecular... Oct 2022Age-dependent conformational stability of human serum albumin was determined by the method of fluorescent bilayer liposome assay. After pre-heating at 80 °C, albumin in...
Age-dependent conformational stability of human serum albumin was determined by the method of fluorescent bilayer liposome assay. After pre-heating at 80 °C, albumin in the sera of 74-year-old healthy subjects exhibited hydrophobic effects on liposomes and made liposomal membrane phospholipids more susceptible to hydrolysis by the lipolytic enzyme phospholipase A2. In contrast, albumin in the sera of 24-year-old individuals was stable at 80 °C and displayed no increased hydrophobic effects on liposomes. The results suggest that albumin in the sera of 74-year-old subjects is more easily converted to a misfolded form in which its protein structure is altered when compared to albumin in the sera of 24-year-old individuals. Misfolded albumin can lose its ability to carry out its normal homeostatic functions and may promote alterations in membrane integrity under inflammatory conditions. However, our investigation has limitations that include the lack of testing sera from large numbers of individuals across a broad range of age to validate our preliminary observations of age-dependent differences in albumin stability and its interactions with liposomes.
Topics: Aged; Aging; Albumins; Humans; Liposomes; Phospholipases A2; Phospholipids; Protein Folding; Proteins; Serum Albumin, Human; Young Adult
PubMed: 36232977
DOI: 10.3390/ijms231911675 -
Toxins Jan 2023End-stage renal disease (ESRD) patients rely on renal replacement therapies to survive. Hemodialysis (HD), the most widely applied treatment, is responsible for the... (Review)
Review
End-stage renal disease (ESRD) patients rely on renal replacement therapies to survive. Hemodialysis (HD), the most widely applied treatment, is responsible for the removal of excess fluid and uremic toxins (UTs) from blood, particularly those with low molecular weight (MW < 500 Da). The development of high-flux membranes and more efficient treatment modes, such as hemodiafiltration, have resulted in improved removal rates of UTs in the middle molecular weight range. However, the concentrations of protein-bound uremic toxins (PBUTs) remain essentially untouched. Due to the high binding affinity to large proteins, such as albumin, PBUTs form large complexes (MW > 66 kDa) which are not removed during HD and their accumulation has been strongly associated with the increased morbidity and mortality of patients with ESRD. In this review, we describe adsorption- and displacement-based approaches currently being studied to enhance the removal of PBUTs. The development of mixed matrix membranes (MMMs) with selective adsorption properties, infusion of compounds capable of displacing UTs from their binding site on albumin, and competitive binding membranes show promising results, but the road to clinical application is still long, and further investigation is required.
Topics: Humans; Uremic Toxins; Uremia; Adsorption; Protein Binding; Toxins, Biological; Renal Dialysis; Kidney Failure, Chronic; Albumins
PubMed: 36828424
DOI: 10.3390/toxins15020110 -
Applied Spectroscopy Sep 2023The ultraviolet resonance Raman (UVRR) spectra of the two proteins bovine serum albumin (BSA) and human serum albumin (HSA) in an aqueous solution are compared with the...
The ultraviolet resonance Raman (UVRR) spectra of the two proteins bovine serum albumin (BSA) and human serum albumin (HSA) in an aqueous solution are compared with the aim to distinguish between them based on their very similar amino acid composition and structure and to obtain signals from tryptophan that has only very few residues. Comparison of the protein spectra with solutions of tryptophan, tyrosine, and phenylalanine in comparative ratios as in the two proteins shows that at an excitation wavelength of 220 nm, the spectra are dominated by the strong resonant contribution from these three amino acids. While the strong enhancement of two and one single tryptophan residue in BSA and HSA, respectively, results in pronounced bands assigned to fundamental vibrations of tryptophan, its weaker overtones and combination bands do not play a major role in the spectral range above 1800 cm. There, the protein spectra clearly reveal the signals of overtones and combination bands of phenylalanine and tyrosine. Assignments of spectral features in the range of Raman shifts from 3800 to 5100 cm to combinations comprising fundamentals and overtones of tyrosine were supported by spectra of amino acid mixtures that contain deuterated tyrosine. The information in the high-frequency region of the UVRR spectra could provide information that is complementary to near-infrared absorption spectroscopy of the proteins.
Topics: Humans; Serum Albumin; Tryptophan; Vibration; Serum Albumin, Bovine; Tyrosine; Phenylalanine; Spectrum Analysis, Raman
PubMed: 37415516
DOI: 10.1177/00037028231183728