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The nature of the post-translational modifications of the autoantigen LL37 influences the autoreactive T-helper cell phenotype in psoriasis.

Psoriasis is a chronic skin disease evolving to psoriatic arthritis (PsA) in 30% of cases. LL37 is a psoriasis T-cell autoantigen and, in complex with self-DNA/RNA, a trigger of type I interferon (IFN-I) and pro-inflammatory factors in dendritic cells. LL37 can undergo irreversible post-translational modifications (PTMs), namely, citrullination and carbamylation, which are linked to a neutrophil-dominated inflammation. Notably, in PsA, carbamylated and citrullinated LL37 (carb-LL37 and cit-LL37) become antibody targets. Here, we analyze the presence of, and the T-cell and antibody reactivity t…

Biochemical characterization of peptidylarginine deiminase-like orthologs from thermotolerant Emericella dentata and Aspergillus nidulans.

Peptidylarginine deiminases (PADs) are a group of hydrolases, mediating the deimination of peptidylarginine residues into peptidyl-citrulline. Equivocal protein citrullination by PADs of fungal pathogens has a strong relation to the progression of multiple human diseases, however, the biochemical properties of fungal PADs remain ambiguous. Thus, this is the first report exploring the molecular properties of PAD from thermotolerant fungi, to imitate the human temperature. The teleomorph Emericella dentata and anamorph Aspergillus nidulans have been morphologically and molecularly identified, wi…

Biological importance of arginine: A comprehensive review of the roles in structure, disorder, and functionality of peptides and proteins.

Arginine shows Jekyll and Hyde behavior in several respects. It participates in protein folding via ionic and H-bonds and cation-pi interactions; the charge and hydrophobicity of its side chain make it a disorder-promoting amino acid. Its methylation in histones; RNA binding proteins; chaperones regulates several cellular processes. The arginine-centric modifications are important in oncogenesis and as biomarkers in several cardiovascular diseases. The cross-links involving arginine in collagen and cornea are involved in pathogenesis of tissues but have also been useful in tissue engineering a

Удаление Pad2 вызывает тревогу, подобное поведению и дефициту памяти у мышей.

Цитуллинация, деимитация педицидильгининовых остатков в пептидилцитруллин, катализированная пептидилагинином (PADs), была подтверждена в качестве уникальной формы посттранслатальной модификации белков. Среди пяти изоформ PAD PAD2 является основным ферментом PAD, выраженным в центральной нервной системе (CNS). Предыдущие исследования показали, что цитруллинированные белки, катализированные PAD2, все чаще ассоциируются с такими неврологическими расстройствами, как болезнь Альцгеймера, прионовая болезнь и множественный склероз. Однако физиологическая роль PAD2 в CNS до сих пор недостаточно ясна.

Совпадение в аннотации оригинала
Citrullination, the deimination of peptidylarginine residues into peptidylcitrulline catalyzed by the peptidylarginine deiminase (PADs), has been confirmed as a unique form of posttranslational modification of proteins. Among the five isoforms of PADs, PAD2 is a main PAD enzyme expressed in central nervous system (CNS). Previous studies reported that citrull…

Increased Serum Levels of Dickkopf-1 and Sclerostin as WNT Signaling Pathway Inhibitors in Celiac Disease Patients.

BACKGROUND: Celiac disease (CD) is an autoimmune enteropathy. The WNT signaling pathway acts in adult intestinal epithelium maintenance. AIM: To evaluate the level of two WNT antagonists, including dikkopf-1 (Dkk-1) and sclerostin, in CD patients compared to controls. METHODS: A total of 43 cases and 45 controls were enrolled in this case-control study. The serum levels of Dkk-1, sclerostin, citrulline, and parathyroid hormone (PTH) were measured using the ELISA method. Moreover, the levels of vitamin D3 were measured using the HPLC method. RESULT: Our findings illustrated an elevation of b

Antigen-specific T-cell frequency and phenotype mirrors disease activity in DRB1*04:04+ rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is associated with high-risk HLA class II alleles known as the "RA shared epitope." Among prevalent shared epitope alleles, study of DRB1*04:04 has been limited. To define relevant epitopes, we identified citrullinated peptide sequences from synovial antigens that were predicted to bind to HLA-DRB1*04:04 and utilized a systematic approach to confirm their binding and assess their recognition by CD4 T cells. After confirming the immunogenicity of 13 peptides derived from aggrecan, cartilage intermediate layer protein (CILP), α-enolase, vimentin, and fibrinogen, we asse

Metformin has no impact on nitric oxide production in patients with pre-diabetes.

AIMS/INTRODUCTION: The authors evaluated the impact of different dose of metformin on NO (nitric oxide) production in subjects with pre-diabetes. MATERIALS AND METHODS: The metformin-naïve patients from one Diabetic Center with newly diagnosed pre-diabetes, without cardio-vascular diseases, were randomized (based on the identification number, individual for each inhabitant in the country) for treatment with different doses of metformin (group A 3 × 500 mg, group B 3 × 1000 mg) for 12 weeks. Then, the subjects from group B were switched to dose 3 × 500 for the last 3 weeks. The wide panel of L

Free amino acid composition of saliva in patients with healthy periodontium and periodontitis.

OBJECTIVES: To identify and compare the free amino acids in the saliva of periodontitis patients and healthy individuals and to assess their levels in different periodontal disease types. MATERIALS AND METHODS: There were three groups: healthy individuals (control (C); n = 20), Stage III Grade B generalized periodontitis (GP-B; n = 20), and Stage III Grade C generalized periodontitis (GP-C; n = 20). Clinical periodontal parameters were measured. Amino acid analysis of the saliva was accomplished by liquid chromatography-mass spectrometry (LC MS/MS), taking the mean concentration. RESULTS: Ci

The shifted balance of arginine metabolites in acute myocardial infarction patients and its clinical relevance.

The arginine metabolism as a target for cardioprotection in patients with ST-segment elevation myocardial infarction (STEMI) remains insufficiently understood. Arginine, ornithine, citrulline, asymmetric dimethylarginine (ADMA) and proline plasma levels were measured using liquid chromatography and tandem mass spectrometry in 70 consecutive STEMI patients upon admission and at 6-month follow-up and were compared with left ventricular function, volumes, and infarct characteristics determined by cardiac magnetic resonance imaging, and with 5-year clinical outcomes. Baseline median concentration

Characterization of medicinal plant-associated biocontrol Bacillus subtilis (SSL2) by liquid chromatography-mass spectrometry and evaluation of compounds by in silico and in vitro methods.

This study explores the antimicrobial properties of bioactive secondary metabolites extracted from the medicinal plant (Solanum surattense)-associated Bacillus subtilis strain SSL2. The secondary metabolites were extracted from B. subtilis (SSL2) using ethyl acetate, acetone, butanol, chloroform and methanol solvents. The crude extract was tested against two wilt causing pathogens: Ralstonia solanacearum and Fusarium oxysporum. The results revealed that the ethyl acetate extract has maximum inhibition against both the pathogens tested in this study. Furthermore, liquid chromatography-mass spec

l-Arginine metabolism before and after 10 weeks of antipsychotic treatment in first-episode psychotic patients.

Agmatine is an endogenous NMDA (N-methyl-d-aspartate) antagonist which is synthesized from l-Arginine and described as a novel neurotransmitter. Agmatine is considered to play an important role for the development of schizophrenia. The aim of the present study is to explore the role of agmatine and l-arginine metabolism in medication-naive first-episode psychosis (FEP). We conducted a case control study in medication-naive patients with FEP (n = 40). The healthy volunteers with no family history of schizophrenia (n = 35) matched for age, gender and education level were selected as a control gr

Decreased severity of experimental autoimmune arthritis in peptidylarginine deiminase type 4 knockout mice.

BACKGROUND: Peptidylarginine deiminase type 4 (PADI4) has been identified as a susceptibility gene for rheumatoid arthritis (RA) by genome-wide association studies. PADI4 is highly expressed in the bone marrow, macrophages, neutrophils, and monocytes. Peptidyl citrulline is an interesting molecule in RA because it is a target antigen for anti-citrullinated peptide antibodies, and only PADs (translated proteins from PADI genes) can provide peptidyl citrulline via the modification of protein substrates. The aim of this study was to evaluate the importance of the PADI4 gene in the progression of

Is it necessary to combine detection of anticitrullinated protein antibodies in the diagnosis of rheumatoid arthritis?

OBJECTIVE: Antibodies against citrulline-containing epitopes, such as antiperinuclear factor (APF), antikeratin antibodies (AKA), antifilaggrin antibodies, and anticyclic citrullinated peptide (anti-CCP) antibodies, are specific in rheumatoid arthritis (RA). Detection of APF, AKA, and anti-CCP has been widely used in clinical practice. However, studies on combined detection of these anti citrullinated protein antibodies (ACPA) in the significance of diagnosing RA have been limited. We aimed to detect APF, AKA, and anti-CCP antibodies and to evaluate the significance of combined detection of th

An undescribed subset of neonatal intrahepatic cholestasis associated with multiple hyperaminoacidemia.

Five patients of cholestatic jaundice and multiple hyperaminoacidemias were uncovered during neonatal mass screening for homocystinuria. All five patients had increased plasma levels of methionine, citrulline, tyrosine, threonine, phenylalanine, lysine and arginine. Compared with those of age-matched cholestatic disease controls, idiopathic neonatal hepatitis (n=9) and biliary atresia (n=14), plasma levels of three amino acids, citrulline, methionine, and threonine, were significantly greater, respectively (P<0.01). Liver biopsies examined in four patients uniformly showed diffuse hepatic fatt

Rheumatoid arthritis-associated rheumatoid factors post-COVID-19.

OBJECTIVE: Rheumatoid factors (RFs) are a hallmark of rheumatoid arthritis but also arise in infections, including COVID-19. Moreover, infections, again including COVID-19, are associated with rheumatoid arthritis development, positioning RFs as a potential link between infection and rheumatoid arthritis. RFs traditionally have been thought to be relatively uniform in their reactivity across conditions apart from some increased reactivity in rheumatoid arthritis. Recently, however, IgG RFs that bind citrulline- and homocitrulline-containing IgG epitopes were identified in rheumatoid arthritis,

Serum ornithine levels in some ocular disorders.

The fact that Chinese have a high occurrence of myopia and the toxicity of ornithine to retinal epithelial cells raised our interest to investigate the serum ornithine levels in high myopic patients. After analyzing several hundred patients, no significant difference in the serum ornithine level was found between Chinese and non-Chinese. However, patients with various ocular disorders did show higher ornithine levels. Serum citrulline levels in myobes and non-Chinese groups were decreased. The significance of these findings needs further investigation.

Ornithine transcarbamylase deficiency and pancreatitis.

We describe a male patient with a Y202H ornithine transcarbamylase deficiency gene mutation who had pancreatitis while taking a low-protein diet, citrulline, and sodium phenylbutyrate.

Seropositivity of Rheumatoid Arthritis Specific Tests in a Patient With Nephrotic Syndrome: Successful Treatment With Rituximab.

Presentation of rheumatoid arthritis (RA) with renal complications is very rare without articular symptoms. We here report a case of a 23-year-old woman, presenting with the edema of the extremities, no relevant previous medical history, and the features of acute tubular injury in her percutaneous kidney biopsy. Following the incidental notification of a positive rheumatoid factor test, other immunologic tests including anticyclic citrullinated peptide and antimutated citrullinated vimentin were performed, the positive results of which favored the diagnosis of RA. Administration of rituximab l

Hyperammonemia in Marasmic children.

The amino acids citrulline, ornithine and arginine, total serum proteins, serum enzymes glutamic oxalacetic and glutamic pyruvic transaminases, blood ammonia and urea were measured in 20 marasmic children with manifest psychomotor changes, before and after nutritional rehabilitation, as well as in 10 healthy age-matched children. Serum protein levels were significantly low and plasma ammonia concentrations were significantly elevated in marasmic children before refeeding (177 +/- 66 micrograms/dl). Plasma ammonia concentrations decreased significantly after 4 weeks of nutritional rehabilitatio

Derangement of Arginine and Related Amino Acids in Children Undergoing Surgery for Congenital Heart Disease With Cardiopulmonary Bypass.

UNLABELLED: Arginine is a conditionally essential amino acid, the precursor for nitric oxide and a key factor in cell proliferation, protein synthesis, and energy metabolism. When there is increased demand in the setting of inflammation, ischemia-reperfusion injury, and organ dysfunction, endogenous arginine production falls short, and external supplementation may be necessary. The goal of this study was to assess changes in concentrations of plasma arginine, citrulline, ornithine, glutamine, and plasma arginase in infants and children undergoing surgery for congenital heart disease with cardi