Assessing metal-induced glycation in French fries.

Non-enzymatic glycation is the chemical reaction between the amine group of an amino acid and the carbonyl group of a reducing sugar. The final products of this reaction, advanced glycation end-products (AGEs), are known to play a key role in aging and many chronic diseases. The kinetics of the AGE formation reaction depends on several factors, including pH, temperature, and the presence of prooxidant metals, such as iron and copper.

New metabolic signature for Chagas disease reveals sex steroid perturbation in humans and mice.

The causative agent of Chagas disease (CD), , claims thousands of lives each year. Current diagnostic tools are insufficient to ensure parasitological detection in chronically infected patients has been achieved. A host-derived metabolic signature able to distinguish CD patients from uninfected individuals and assess antiparasitic treatment efficiency is introduced.

Detection of Fusobacterium nucleatum subspecies in the saliva of pre-colorectal cancer patients, using tandem mass spectrometry.

Objective: Rising evidence links Fusobacterium nucleatum (F. nucleatum) with its four subspecies; nucleatum, polymorphum, animalis, and vincentii, with the development of colorectal cancer (CRC) and its precursor colorectal adenoma (CRA). This study aims to optimize a technique for and explore the capability of matrix-assisted laser-desorption ionization-tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS) to detect F.

Protein Targets of Acetaminophen Covalent Binding in Rat and Mouse Liver Studied by LC-MS/MS.

Acetaminophen (APAP) is a mild analgesic and antipyretic used commonly worldwide. Although considered a safe and effective over-the-counter medication, it is also the leading cause of drug-induced acute liver failure. Its hepatotoxicity has been linked to the covalent binding of its reactive metabolite, -acetyl -benzoquinone imine (NAPQI), to proteins.

Site-Specific Alkylation of the Islet Amyloid Polypeptide Accelerates Self-Assembly and Potentiates Perturbation of Lipid Membranes.

The accumulation of insoluble amyloids in the pancreatic islets is a pathological hallmark of type II diabetes and correlates closely with the loss of β-cell mass. The predominant component of these amyloid deposits is the islet amyloid polypeptide (IAPP). The factors contributing to the conversion of IAPP from a monomeric bioactive peptide hormone into insoluble amyloid fibrils remain partially elusive.

Fecal host biomarkers predicting severity of Clostridioides difficile infection.

Clostridioides difficile is a major cause of health care-associated diarrhea. Severity ranges from mild to life-threatening, but this variability remains poorly understood. Microbiologic diagnosis of C.

A Procedure for Analyzing the Proteomic Proteomics Profile of Schistosoma mansoni Cercariae.

Schistosomiasis is one of the most important helminthic parasitic infections in the world, with over 700 million people at risk of infection. Species of Schistosoma have a complex life cycle involving the infection of freshwater snails before infecting their mammalian definitive host. Taking about 130,000 lives per annum, S.

Plant-derived virus-like particle vaccines drive cross-presentation of influenza A hemagglutinin peptides by human monocyte-derived macrophages.

A growing body of evidence supports the importance of T cell responses to protect against severe influenza, promote viral clearance, and ensure long-term immunity. Plant-derived virus-like particle (VLP) vaccines bearing influenza hemagglutinin (HA) have been shown to elicit strong humoral and CD4 T cell responses in both pre-clinical and clinical studies. To better understand the immunogenicity of these vaccines, we tracked the intracellular fate of a model HA (A/California/07/2009 H1N1) in human monocyte-derived macrophages (MDMs) following delivery either as VLPs (H1-VLP) or in soluble form.

Apolipoprotein A1 and Fibronectin Fragments as Markers of Cure for the Chagas Disease.

Chagas disease (CD), endemic from Latin America, affects more than 8 million people, and the disease keeps spreading around the world due to population migrations. The treatment options for CD are currently limited to two drugs, benznidazole (BZ) and nifurtimox (Nfx), which are often unsatisfactory in chronically infected patients. To date, the only accepted marker of the cure is seroconversion (the disappearance of Trypanosoma cruzi antibodies in the patient's serum), which can take decades to occur, if ever.

Peptidyl-prolyl cis-trans isomerase A - A novel biomarker of multi-episodic (recurrent) ocular toxoplasmosis.

Ocular toxoplasmosis (OT) is the most common etiology of posterior uveitis. The high incidence of macular scarring associated with OT is a leading cause of visual morbidity. Serum biomarkers of the disease would aid in its diagnosis.

Proteomic fingerprinting in HIV/HCV co-infection reveals serum biomarkers for the diagnosis of fibrosis staging.

Background: Hepatic complications of hepatitis C virus (HCV), including fibrosis and cirrhosis are accelerated in human immunodeficiency virus (HIV)-infected individuals. Although, liver biopsy remains the gold standard for staging HCV-associated liver disease, this test can result in serious complications and is subject to sampling errors. These challenges have prompted a search for non-invasive methods for liver fibrosis staging.

Increased serotransferrin and ceruloplasmin turnover in diet-controlled patients with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is associated with oxidative stress and perturbed iron metabolism. Serotransferrin (Trf) and ceruloplasmin (Cp) are two key proteins involved in iron metabolism and anti-oxidant defense. Non-enzymatic glycation and oxidative modification of plasma proteins are known to occur under hyperglycemia and oxidative stress.

Glycation Reduces the Stability of ApoAI and Increases HDL Dysfunction in Diet-Controlled Type 2 Diabetes.

Context: Hyperglycemia plays a key role in the pathogenesis of cardiovascular complications of diabetes. Type 2 diabetes mellitus (T2DM) is associated with high-density lipoprotein (HDL) dysfunction and increased degradation of apolipoprotein I (ApoAI). The mechanism(s) of these changes is largely unknown.

Novel bi-allelic splice mutations in CARD9 causing adult-onset Candida endophthalmitis.

CARD9 deficiency (CANDF2; OMIM# 212050) is an autosomal-recessive monogenic inborn error of immunity conferring susceptibility to invasive fungal diseases, including the very distinct syndrome of spontaneous central nervous system candidiasis, in which opportunistic yeast of the genus Candida infect the central nervous system (either brain parenchyma and/or meninges) in the absence of trauma, chemotherapy or underlying systemic disease. We present a patient with spontaneous endophthalmitis of the right eye due to Candida albicans; further investigations revealed concomitant cerebral abscess. She had a history of left endophthalmitis due to the dematiaceous mould, Aureobasidium pullulans, 15 years earlier.

Effects of oxidative post-translational modifications on structural stability and self-assembly of λ6 immunoglobulin light chain.

Light chain amyloidosis (AL) originates from the deposition of immunoglobulin light chains (LCs) as amyloid fibrils in the extracellular space of vital organs. Although non-enzymatic post-translational modifications (PTMs) have been shown to contribute to protein misfolding diseases, little is known about their contributions to LC amyloidogenicity. In this study, we investigated the effects of three oxidative PTMs, carbonylation by hydroxynonenal (HNE), oxidation and nitration, on the structure, thermodynamic stability and self-assembly propensity of a LC variable domain from the λ6 germline, Wil.

Identification of 4-hydroxynonenal protein targets in rat, mouse and human liver microsomes by two-dimensional liquid chromatography/tandem mass spectrometry.

Rationale: 4-Hydroxynonenal (HNE), endogenously generated through peroxidation and breakdown of polyunsaturated fatty acids, has been linked to a number of adverse biological effects through carbonylation of essential biomolecules. Covalent binding of HNE to proteins can alter their structure and functions, causing cell damage as well as adverse immune responses. The liver plays a predominant role in metabolic transformations and hepatic proteins are often targeted by reactive metabolites.

A Covalent Cysteine-Targeting Kinase Inhibitor of Ire1 Permits Allosteric Control of Endoribonuclease Activity.

The unfolded protein response (UPR) initiated by the transmembrane kinase/ribonuclease Ire1 has been implicated in a variety of diseases. Ire1, with its unique position in the UPR, is an ideal target for the development of therapies; however, the identification of specific kinase inhibitors is challenging. Recently, the development of covalent inhibitors has gained great momentum because of the irreversible deactivation of the target.

Identification of Acetaminophen Adducts of Rat Liver Microsomal Proteins using 2D-LC-MS/MS.

Xenobiotic metabolism in the liver can give rise to reactive metabolites that covalently bind to proteins, and determining which proteins are targeted is important in drug discovery and molecular toxicology. However, there are difficulties in the analysis of these modified proteins in complex biological matrices due to their low abundance. In this study, an analytical approach was developed to systematically identify target proteins of acetaminophen (APAP) in rat liver microsomes (RLM) using two-dimensional chromatography and high-resolution tandem mass spectrometry.

Dataset from proteomic analysis of rat, mouse, and human liver microsomes and S9 fractions.

Rat, mouse and human liver microsomes and S9 fractions were analyzed using an optimized method combining ion exchange fractionation of digested peptides, and ultra-high performance liquid chromatography (UHPLC) coupled to high resolution tandem mass spectrometry (HR-MS/MS). The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.

Covalent binding of 4-hydroxynonenal to matrix metalloproteinase 13 studied by liquid chromatography-mass spectrometry.

Osteoarthritis (OA) is caused by the degradation of articular cartilage and affects approximately 80% of people over the age of 65. Matrix metalloproteinases (MMPs) belong to a group of zinc endopeptidases that degrade extracellular matrix (ECM) proteins in cartilage. MMP-13, also known as collagenase 3, cleaves type II collagen more rapidly than other MMPs and therefore is an important target for the treatment of OA.

Optimized proteomic analysis of rat liver microsomes using dual enzyme digestion with 2D-LC-MS/MS.

Unlabelled: A systematic approach was developed to optimize the analysis of rat liver microsomes combining ion exchange fractionation with reverse-phase chromatography coupled to high resolution quadrupole-time-of-flight mass spectrometry. A comparison was performed with several conditions to select the most efficient solubilization and proteolysis protocol to achieve highest proteome coverage. Optimal trypsin digestion conditions were achieved with SDS and heat to increase solubilization of microsomal samples, with an increase from 621 to 686 identified proteins when SDS and heat were applied.