Enzymatic craftsmanship in collagen glycosylation.

Collagen IV, a key structural protein of basement membranes, is vital for the development and survival of multicellular life forms. Its maturation relies on specific post-translational O- glycosylation, primarily mediated by lysyl hydroxylase-3 (LH3) and other glycosyltransferases, which sculpt collagen by modifying the hydroxylysine residues with sugar moieties.

Decoding elegant interplay among different stereo-electronic effects due to the ancient prolyl-4-hydroxylation stabilizing collagenous helicity.

Prolyl-4-hydroxylation is an ancient evolutionarily conserved post-translational modification (PTM) critical for both structural and regulatory functions in multicellular life forms. This PTM plays a pivotal role in stabilizing collagen's triple helix by influencing the puckering of the pyrrolidine ring. The elegant interplay between ring pucker, torsional angles, peptide bond isomerization, and charge-transfer interactions (O···C=O n→π∗ and σ→σ∗) attaining the helical stability remains underappreciated.

The theatrics of collagens in the myocardium: the supreme architect of the fibrotic heart.

Heart failure (HF) mediated by cardiac fibrosis (CF) is characterized by an excessive accumulation of collagen-based extracellular matrix (ECM) in the myocardium. CF is a common pathophysiological condition in many heart diseases and can be distinctly categorized into two types: replacement and interstitial. In ischemic heart diseases, sudden loss of cardiomyocytes leads to the replacement of CF to prevent ventricular rupture.

Proteomics-guided Biomarker Discovery, Validation, and Pathway Perturbation in Infection-related Acute Decompensation of Cirrhosis.

Background & Aims: Inappropriate treatment of infections fuels drug resistance, organ failures, and costs in cirrhosis. We explored proteomics to improve infection diagnosis and management in acutely decompensated (AD) cirrhosis.

Methods: We enrolled 391 patients with AD cirrhosis (92% males, median-age: 41 years), 84 in the discovery cohort (54 infected, 30 non-infected), 147 in the validation cohort I (106 infected, 41 non-infected), and 160 in the validation cohort II (108 infected, 52 non-infected).

Tissue fibrosis in cardiorenal syndrome: crosstalk between heart and kidneys.

Cardiorenal syndrome (CRS) is represented as an intricate dysfunctional interplay between the heart and kidneys, marked by cardiorenal inflammation and fibrosis. Unlike other organs, the repair process in cardiorenal injury involves a regenerative phase characterized by proliferation and polyploidization, followed by a subsequent pathogenic phase of fibrosis. In CRS, acute or chronic cardiorenal injury leads to hyperactive inflammation and fibrotic remodeling, associated with injury-mediated immune cell (macrophages, monocytes and T cells) infiltration and myofibroblast activation.

ColPTMScape: An open access knowledge base for tissue-specific collagen PTM maps.

Collagen is a key component of the extracellular matrix (ECM). In the remodeling of ECM, a remarkable variation in collagen post-translational modifications (PTMs) occurs. This makes collagen a potential target for understanding extracellular matrix remodeling during pathological conditions.

Elucidation of Site-Specific Ubiquitination on Chaperones in Response to Mutant Huntingtin.

Huntington's disease (HD) is one of the prominent neurodegenerative diseases, characterized by the progressive decline of neuronal function, due to the accumulation and aggregation of misfolded proteins. Pathological progression of HD is hallmarked by the aberrant aggregation of the huntingtin protein (HTT) and subsequent neurotoxicity. Molecular chaperones (heat shock proteins, HSPs) play a pivotal role in maintaining proteostasis by facilitating protein refolding, degradation, or sequestration to limit the accumulation of misfolded proteins during neurotoxicity.

Urinary Apolipoprotein A1 and Neutrophil Gelatinase-associated Lipocalin in Children with Idiopathic Nephrotic Syndrome.

Urinary biomarkers are a promising diagnostic modality whose role was explored in nephrotic syndrome (NS). We estimated urinary apolipoprotein A1 (Apo A1) and neutrophil gelatinase-associated lipocalin (NGAL) in children with first-episode NS (FENS) and controls with a longitudinal follow-up to see the serial changes during remission. The study groups comprised 35 children with FENS and an equal number of age- and sex-matched controls.

A Comprehensive Insight and Mechanistic Understanding of the Lipidomic Alterations Associated With DCM.

Dilated cardiomyopathy (DCM) is one of the major causes of heart failure characterized by the enlargement of the left ventricular cavity and contractile dysfunction of the myocardium. Lipids are the major sources of energy for the myocardium. Impairment of lipid homeostasis has a potential role in the pathogenesis of DCM.

A comprehensive review of acute cardio-renal syndrome: need for novel biomarkers.

Cardiorenal syndrome represents a wide-spectrum disorder involving the heart and kidneys as the primary affected organs. India has an increasingly high burden of acute CRS, coinciding with the rise in global statistics. Up to 2022, approximately 46.

Exploring the cardiac ECM during fibrosis: A new era with next-gen proteomics.

Extracellular matrix (ECM) plays a critical role in maintaining elasticity in cardiac tissues. Elasticity is required in the heart for properly pumping blood to the whole body. Dysregulated ECM remodeling causes fibrosis in the cardiac tissues.

Comprehensive Mapping and Dynamics of Site-Specific Prolyl-Hydroxylation, Lysyl-Hydroxylation and Lysyl O-Glycosylation of Collagens Deposited in ECM During Zebrafish Heart Regeneration.

Cardiac fibrosis-mediated heart failure (HF) is one of the major forms of end-stage cardiovascular diseases (CVDs). Cardiac fibrosis is an adaptive response of the myocardium upon any insult/injury. Excessive deposition of collagen molecules in the extracellular matrix (ECM) is the hallmark of fibrosis.

A Comprehensive Outlook on Dilated Cardiomyopathy (DCM): State-Of-The-Art Developments with Special Emphasis on OMICS-Based Approaches.

Dilated cardiomyopathy (DCM) remains an enigmatic cardiovascular disease (CVD) condition characterized by contractile dysfunction of the myocardium due to dilation of the ventricles. DCM is one of the major forms of CVD contributing to heart failure. Dilation of the left or both ventricles with systolic dysfunction, not explained by known causes, is a hallmark of DCM.

Purified Splenic amastigotes of Leishmania donovani-Immunoproteomic approach for exploring Th1 stimulatory polyproteins.

Visceral leishmaniasis (VL) represents one of the most challenging infectious diseases worldwide. The reason that once infected, patient develops immunity against Leishmania parasite has paved way to develop prophylactic vaccines against disease, but only some of these have moved ahead for clinical trials. Herein, the study to explore novel and potential vaccine candidates was extended to pathogenic form of parasite, that is, amastigote form which is less explored due to complexity of its purification process.

Urinary EPCR and dermcidin as potential novel biomarkers for severe adult OSA patients.

Background: Due to low predictive values of obstructive sleep apnea (OSA) screening tools, there is a need for biomarker for screening of OSA patients at an early stage. The aim of the study was to evaluate differentially expressed proteins in blood and urine samples of OSA patients.

Methods: In this study, we used isobaric tagging for relative and absolute quantification (iTRAQ) based proteomics approach to identify differentially expressed proteins, which were subsequently verified and validated using enzyme-linked immunosorbent assay (ELISA) technique in adult OSA patients.

The Extracellular Matrix Receptor Discoidin Domain Receptor 1 Regulates Collagen Transcription by Translocating to the Nucleus.

Background: The discoidin domain receptor 1 (DDR1) is activated by collagens, upregulated in injured and fibrotic kidneys, and contributes to fibrosis by regulating extracellular matrix production, but how DDR1 controls fibrosis is poorly understood. DDR1 is a receptor tyrosine kinase (RTK). RTKs can translocate to the nucleus a nuclear localization sequence (NLS) present on the receptor itself or a ligand it is bound to.

Plasma Free Homocysteine Levels in Children with Idiopathic Nephrotic Syndrome.

Altered metabolism of homocysteine in children with idiopathic nephrotic syndrome leads to raised plasma-free homocysteine levels. Elevated free homocysteine causes endothelial cell dysfunction and promotes early atherosclerosis and glomerulosclerosis. In this analytical study with a longitudinal follow-up, 29 children with first episode of nephrotic syndrome (FENS) aged 1-16 years along with 30 age andgender-matched healthy controls were enrolled.

Quantitative proteomic profiling of extracellular matrix and site-specific collagen post-translational modifications in an model of lung fibrosis.

Lung fibrosis is characterized by excessive deposition of extracellular matrix (ECM), in particular collagens, by fibroblasts in the interstitium. Transforming growth factor-β1 (TGF-β1) alters the expression of many extracellular matrix (ECM) components produced by fibroblasts, but such changes in ECM composition as well as modulation of collagen post-translational modification (PTM) levels have not been comprehensively investigated. Here, we performed mass spectrometry (MS)-based proteomics analyses to assess changes in the ECM deposited by cultured lung fibroblasts from idiopathic pulmonary fibrosis (IPF) patients upon stimulation with transforming growth factor β1 (TGF-β1).

Hydrolysis of homocysteine thiolactone results in the formation of Protein-Cys-S-S-homocysteinylation.

An increased level of homocysteine, a reactive thiol amino acid, is associated with several complex disorders and is an independent risk factor for cardiovascular disease. A majority (>80%) of circulating homocysteine is protein bound. Homocysteine exclusively binds to protein cysteine residues via thiol disulfide exchange reaction, the mechanism of which has been reported.

Proteolytic processing of lysyl oxidase-like-2 in the extracellular matrix is required for crosslinking of basement membrane collagen IV.

Lysyl oxidase-like-2 (LOXL2) is an enzyme secreted into the extracellular matrix that crosslinks collagens by mediating oxidative deamination of lysine residues. Our previous work demonstrated that this enzyme crosslinks the 7S domain, a structural domain that stabilizes collagen IV scaffolds in the basement membrane. Despite its relevant role in extracellular matrix biosynthesis, little is known about the structural requirements of LOXL2 that enable collagen IV crosslinking.

Quantitative proteomic changes during post myocardial infarction remodeling reveals altered cardiac metabolism and Desmin aggregation in the infarct region.

Unlabelled: Myocardial infarction is one of the leading causes of cardiac dysfunction, failure and sudden death. Post infarction cardiac remodeling presents a poor prognosis, with 30%-45% of patients developing heart failure, in a period of 5-25years. Oxidative stress has been labelled as the primary causative factor for cardiac damage during infarction, however, the impact it may have during the process of post infarction remodeling has not been well probed.