Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.358
Filtrar
1.
Cytokine ; 159: 156026, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36084603

RESUMO

BACKGROUND: Meteorin-like (Metrnl) is a novel adipokine that is highly expressed in white adipose tissues. Whether Metrnl plays a role in rheumatoid arthritis (RA) remains unclear. In this study, sera from 159 RA patients, 28 osteoarthritis (OA) patients, and 50 healthy individuals were included. The serum levels of Metrnl were measured using an enzyme-linked immunosorbent assay. Clinical parameters, including disease activity score 28 (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), antibodies to cyclic citrulline peptide (anti-CCP), inflammatory cytokines, and blood biochemical indices were collected. RESULTS: Metrnl levels were higher in RA patients compared to OA patients and controls. In the RA group, serum Metrnl levels were positively correlated with DAS28, RF, and CRP levels. However, in the RA group, serum Metrnl levels were not correlated with ESR, anti-CCP, immunoglobulins, and blood biochemical indices. CONCLUSION: This study showed that Metrnl is involved in the pathogenesis of RA. Increase in serum Metrnl levels is closely related to RA activity.


Assuntos
Artrite Reumatoide , Osteoartrite , Adipocinas , Anticorpos Anti-Proteína Citrulinada , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Citrulina , Citocinas , Humanos , Peptídeos Cíclicos , Fator Reumatoide
2.
Nutrients ; 14(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36079738

RESUMO

Supplementation with Citrulline (Cit) has been shown to have a positive impact on aerobic exercise performance and related outcomes such as lactate, oxygen uptake (VO2) kinetics, and the rate of perceived exertion (RPE), probably due to its relationship to endogenous nitric oxide production. However, current research has shown this to be controversial. The main objective of this systematic review and meta-analysis was to analyze and assess the effects of Cit supplementation on aerobic exercise performance and related outcomes, as well as to show the most suitable doses and timing of ingestion. A structured literature search was carried out by the PRISMA® (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and PICOS guidelines in the following databases: Pubmed/Medline, Scopus, and Web of Science (WOS). A total of 10 studies were included in the analysis, all of which exclusively compared the effects of Cit supplementation with those of a placebo group on aerobic performance, lactate, VO2, and the RPE. Those articles that used other supplements and measured other outcomes were excluded. The meta-analysis was carried out using Hedges' g random effects model and pooled standardized mean differences (SMD). The results showed no positive effects of Cit supplementation on aerobic performance (pooled SMD = 0.15; 95% CI (-0.02 to 0.32); I2, 0%; p = 0.08), the RPE (pooled SMD = -0.03; 95% CI (-0.43 to 0.38); I2, 49%; p = 0.9), VO2 kinetics (pooled SMD = 0.01; 95% CI (-0.16 to 0.17); I2, 0%; p = 0.94), and lactate (pooled SMD = 0.25; 95% CI (-0.10 to 0.59); I2, 0%; p = 0.16). In conclusion, Cit supplementation did not prove to have any benefits for aerobic exercise performance and related outcomes. Where chronic protocols seemed to show a positive tendency, more studies in the field are needed to better understand the effects.


Assuntos
Citrulina , Exercício Físico , Citrulina/farmacologia , Suplementos Nutricionais , Lactatos
3.
Biomark Med ; 16(13): 993-1004, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36052727

RESUMO

Aim: The aim of this study was to measure serum levels of methylarginine derivatives and related metabolites in patients with gout. Materials & methods: This study enrolled 100 patients with gout and 80 patients in the control group. Serum asymmetric dimethylarginine, symmetric dimethylarginine, L-N-monomethylarginine, arginine, homoarginine, citrulline and ornithine levels were measured with tandem mass spectrometry. Results: Serum ornithine, citrulline and total methylated arginine load levels were statistically significantly higher in patients with gout compared with the control group, while serum arginine and homoarginine levels and global arginine bioavailability ratio were statistically significantly lower. Conclusion: There may be an association between gout, methylarginine levels and hyperuricemia and increased risk of cardiovascular disease.


Assuntos
Gota , Homoarginina , Arginina/metabolismo , Citrulina/metabolismo , Homoarginina/metabolismo , Humanos , Óxido Nítrico/metabolismo , Ornitina
4.
Int J Mol Sci ; 23(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36077232

RESUMO

Citrullination of proteins plays an important role in protein function and it has recently become clear that citrullinated proteins play a role in immune responses. In this study we examined how citrullinated collagen, an extracellular matrix protein, affects T-cell function during the development of autoimmune arthritis. Using an HLA-DR1 transgenic mouse model of rheumatoid arthritis, mice were treated intraperitoneally with either native type I collagen (CI), citrullinated CI (cit-CI), or phosphate buffered saline (PBS) prior to induction of autoimmune arthritis. While the mice given native CI had significantly less severe arthritis than controls administered PBS, mice receiving cit-CI had no decrease in the severity of autoimmune arthritis. Using Jurkat cells expressing the inhibitory receptor leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), Western blot analysis indicated that while CI and cit-CI bound to LAIR-1 with similar affinity, only CI induced phosphorylation of the LAIR ITIM tyrosines; cit-CI was ineffective. These data suggest that cit-CI acts as an antagonist of LAIR-1 signaling, and that the severity of autoimmune arthritis can effectively be altered by targeting T cells with citrullinated collagen.


Assuntos
Artrite Experimental , Artrite Reumatoide , Doenças Autoimunes , Animais , Artrite Reumatoide/metabolismo , Citrulina/metabolismo , Colágeno , Camundongos , Camundongos Transgênicos
5.
Org Lett ; 24(34): 6351-6355, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-35997298

RESUMO

Protein citrullination is one type of protein post-translational modification. Previous methods entail the use of a strongly acidic condition (pH <1), which impedes its exploration under physiological and pathological conditions. Here, we developed a biocompatible method based on o-boron-assisted citrulline modification. We demonstrated that this method enables selective and mainly irreversible modification of citrulline residues under neutral conditions. We expect that it will provide a valuable tool for the study of protein citrullination.


Assuntos
Boro , Citrulina , Citrulina/química , Citrulina/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas
6.
Nutrients ; 14(16)2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36014817

RESUMO

Environmental enteric dysfunction (EED) is an elusive, inflammatory syndrome of the small intestine thought to be associated with enterocyte loss and gut leakiness and lead to stunted child growth. To date, the gold standard for diagnosis is small intestine biopsy followed by histology. Several putative biomarkers for EED have been proposed and are widely used in the field. Here, we assessed in a cross-sectional study of children aged 2-5 years for a large set of biomarkers including markers of protein exudation (duodenal and fecal alpha-1-antitrypsin (AAT)), inflammation (duodenal and fecal calprotectin, duodenal, fecal and blood immunoglobulins, blood cytokines, C-reactive protein (CRP)), gut permeability (endocab, lactulose-mannitol ratio), enterocyte mass (citrulline) and general nutritional status (branched-chain amino acids (BCAA), insulin-like growth factor) in a group of 804 children in two Sub-Saharan countries. We correlated these markers with each other and with anemia in stunted and non-stunted children. AAT and calprotectin, CRP and citrulline and citrulline and BCAA correlated with each other. Furthermore, BCAA, citrulline, ferritin, fecal calprotectin and CRP levels were correlated with hemoglobin levels. Our results show that while several of the biomarkers are associated with anemia, there is little correlation between the different biomarkers. Better biomarkers and a better definition of EED are thus urgently needed.


Assuntos
Biomarcadores , Doença Ambiental , Enteropatias , Intestino Delgado , África ao Sul do Saara , Biomarcadores/análise , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Pré-Escolar , Citrulina/análise , Estudos Transversais , Doença Ambiental/diagnóstico , Doença Ambiental/metabolismo , Transtornos do Crescimento , Humanos , Enteropatias/diagnóstico , Enteropatias/etiologia , Enteropatias/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Complexo Antígeno L1 Leucocitário
7.
Curr Opin Struct Biol ; 75: 102423, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35834948

RESUMO

The specific association between antibodies to citrullinated proteins and rheumatoid arthritis (RA) has centered interest on understanding why citrullinated proteins become immunogenic in this disease, which is believed to inform the origins of autoimmunity in RA. Since citrullination is a physiologic post-translational modification (PTM), one theory is that conditions promoting abnormal citrullination are initiators of self-reactive immune responses to citrullinated proteins in RA. Foremost candidates that dysregulate the normal balance of citrullination are microbial agents, which can exploit citrullination as an effector mechanism to subvert host antimicrobial activities and maximize their progeny. Here, we will use the host-pathogen interface as a unifying model to link microbe-induced citrullination and the loss of immunological tolerance to citrullinated antigens in RA.


Assuntos
Artrite Reumatoide , Citrulina , Artrite Reumatoide/metabolismo , Autoimunidade , Citrulinação , Citrulina/metabolismo , Humanos , Processamento de Proteína Pós-Traducional
8.
Nutrients ; 14(14)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35889869

RESUMO

The amino acid L-arginine is crucial for nitric oxide (NO) synthesis, an important molecule regulating vascular tone. Considering that vascular dysfunction precedes cardiovascular disease, supplementation with precursors of NO synthesis (e.g., L-arginine) is warranted. However, supplementation of L-citrulline is recommended instead of L-arginine since most L-arginine is catabolized during its course to the endothelium. Given that L-citrulline, found mainly in watermelon, can be converted to L-arginine, watermelon supplementation seems to be effective in increasing plasma L-arginine and improving vascular function. Nonetheless, there are divergent findings when investigating the effect of watermelon supplementation on vascular function, which may be explained by the L-citrulline dose in watermelon products. In some instances, offering a sufficient amount of L-citrulline can be impaired by the greater volume (>700 mL) of watermelon needed to reach a proper dose of L-citrulline. Thus, food technology can be applied to reduce the watermelon volume and make supplementation more convenient. Therefore, this narrative review aims to discuss the current evidence showing the effects of watermelon ingestion on vascular health parameters, exploring the critical relevance of food technology for acceptable L-citrulline content in these products. Watermelon-derived L-citrulline appears as a supplementation that can improve vascular function, including arterial stiffness and blood pressure. Applying food technologies to concentrate bioactive compounds in a reduced volume is warranted so that its ingestion can be more convenient, improving the adherence of those who want to ingest watermelon products daily.


Assuntos
Citrullus , Arginina/farmacologia , Citrulina/farmacologia , Citrullus/química , Ingestão de Alimentos , Tecnologia de Alimentos , Tecnologia
9.
Mol Genet Metab ; 136(4): 330-336, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35798653

RESUMO

BACKGROUND: Citrin deficiency is an autosomal recessive disorder caused by variants of the SLC25A13 gene. Although newborn screening (NBS) provides an opportunity for its early diagnosis and treatment, citrin deficiency detection rates remain lower than those estimated. METHODS: Before 2018, NBS for citrin deficiency was based on citrulline levels alone. In June 2018, a second-tier molecular test was implemented to detect 11 common variants of the SLC25A13 gene and improve the NBS detection rates. This study compares the incidence rates and costs before and after the second-tier implementation. RESULTS: Prior to 2018, five subjects were diagnosed via NBS, and 12 of 555,449 newborns screened were missed. In comparison, 11 subjects were diagnosed out of 198,071 newborns screened after 2018, and there were no false-negatives. The citrin deficiency detection rate increased from 1/32,673 to 1/18,006 after the second-tier test was implemented, with only a minimal increase in the total cost. The number of false-positive in our cohort was tolerable. Subjects with citrin deficiency may present with borderline elevated citrulline levels; these can remain slightly elevated or increase considerably on retest. Four patients (80%) detected prior to second-tier testing and six patients (55%) detected after it was implemented were identified based on the citrulline levels alone. However, at the time of second blood sampling, the normal citrulline level of five subjects did not exclude a citrin deficiency diagnosis. CONCLUSIONS: Our study shows that it is vital and cost-effective to employ second-tier molecular testing to improve the detection of citrin deficiency by NBS.


Assuntos
Citrulinemia , Citrulina , Citrulinemia/diagnóstico , Citrulinemia/epidemiologia , Citrulinemia/genética , Humanos , Recém-Nascido , Proteínas de Transporte da Membrana Mitocondrial/genética , Mutação , Triagem Neonatal
10.
Mol Cancer Ther ; 21(9): 1449-1461, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-35793453

RESUMO

Valine-citrulline is a protease-cleavable linker commonly used in many drug delivery systems, including antibody-drug conjugates (ADC) for cancer therapy. However, its suboptimal in vivo stability can cause various adverse effects such as neutropenia and hepatotoxicity, leading to dose delays or treatment discontinuation. Here, we report that glutamic acid-glycine-citrulline (EGCit) linkers have the potential to solve this clinical issue without compromising the ability of traceless drug release and ADC therapeutic efficacy. We demonstrate that our EGCit ADC resists neutrophil protease-mediated degradation and spares differentiating human neutrophils. Notably, our anti-HER2 ADC shows almost no sign of blood and liver toxicity in healthy mice at 80 mg kg-1. In contrast, at the same dose level, the FDA-approved anti-HER2 ADCs Kadcyla and Enhertu show increased levels of serum alanine aminotransferase and aspartate aminotransferase and morphologic changes in liver tissues. Our EGCit conjugates also exert greater antitumor efficacy in multiple xenograft tumor models compared with Kadcyla and Enhertu. This linker technology could substantially broaden the therapeutic windows of ADCs and other drug delivery agents, providing clinical options with improved efficacy and safety.


Assuntos
Antineoplásicos , Imunoconjugados , Ado-Trastuzumab Emtansina , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Citrulina , Humanos , Imunoconjugados/metabolismo , Imunoconjugados/farmacologia , Camundongos , Peptídeo Hidrolases , Índice Terapêutico
11.
Anaesthesiol Intensive Ther ; 54(2): 141-149, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35792110

RESUMO

INTRODUCTION: Vasopressors increase arterial pressure but they may have deleterious effects on mesenteric blood flow. We aimed to evaluate the response of gut biomarkers and superior mesenteric blood flow to different vasopressors with and without dobutamine. MATERIAL AND METHODS: Thirty New Zealand rabbits were included and randomly allocated to 5 groups: group A - sham group; group B - norepinephrine; group C - norepinephrine plus dobutamine; group D - vasopressin; and group E - vasopressin plus dobutamine. Mean arterial pressure (MAP) target was greater than 60 mmHg. Endotoxic shock was induced by intra-venous injection of lipopolysaccharide (LPS) in four of the five groups. Aortic blood flow (Qao), superior mesenteric artery flow (QSMA) and lactate were measured after LPS injection. Enterocyte damage was evaluated by measurements of serum citrulline and intestinal fatty acid-binding protein (I-FABP) after 4 h. RESULTS: The largest reduction in Qao occurred in group D (64 ± 17.3 to 38 ± 7.5 mL min-1; P = 0.04). QSMA also declined significantly in groups D and E and remained lower than in the other groups over 4 h (group D - baseline: 65 ± 31; 1 h: 37 ± 10; 2 h: 38 ± 10; 3 h: 46 ± 26; and 4 h: 48 ± 15 mL min-1; P < 0.005; group E - baseline: 73 ± 14; 1 h: 28 ± 4.0; 2 h: 37 ± 6.4; 3 h: 40 ± 11; and 4 h: 48 ± 11; P < 0.005; all in mL min-1). Serum citrulline was significantly lower in groups D (P = 0.014) and E (P = 0.019) in comparison to group A. The fluid administration regimen was similar in all groups. CONCLUSIONS: Vasopressin seems to negatively impact gut enterocyte function during endotoxic shock despite the association of an inodilator and adequate fluid replacement.


Assuntos
Dobutamina , Choque Séptico , Animais , Citrulina , Dobutamina/farmacologia , Dobutamina/uso terapêutico , Hemodinâmica , Humanos , Lipopolissacarídeos/farmacologia , Norepinefrina/farmacologia , Coelhos , Choque Séptico/tratamento farmacológico , Vasoconstritores/farmacologia , Vasopressinas/farmacologia
12.
Int Immunopharmacol ; 110: 109010, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35785731

RESUMO

OBJECTIVE: Post-translational modifications of extracellular matrix proteins such as fibrinogen may lead to tolerance loss and have been implicated in rheumatoid arthritis (RA) pathogenesis. The purpose of this study was to determine whether fibrinogen (FIB) modified with citrulline (CIT), malondialdehyde-acetaldehyde (MAA) or both leads to altered macrophage polarization, peptidyl arginine deiminase (PAD) expression, or production of citrullinated proteins. METHODS: PMA-treated U-937 cells (M0 cells) were stimulated with MAA, CIT or MAA-CIT modified FIB. Macrophage (M1/M2) phenotypes were evaluated by flow cytometry, RT-PCR, and ELISA. PAD enzyme expression and protein citrullination was evaluated using RT-PCR and Western Blot. RESULTS: Flow cytometry revealed that M0 macrophages stimulated with FIB-MAA-CIT resulted in mixed M1/M2 phenotypes as demonstrated by cell surface expression and mRNA levels of CD14, CD192, CD163, and CD206 (p < 0.001 vs. others), and the release of IL-18, IP-10, CCL22, and IL-13 (p < 0.001 vs. others). While FIB-MAA treated M0 cells demonstrated a mixed M1/M2 phenotype, cytokine and cell surface markers differed from FIB-MAA-CIT. Finally, M0 cells treated with FIB-CIT demonstrated markers and cytokines consistent with only the M1-like phenotype. Exposure of M0 cells to FIB-MAA-CIT (at 48 h) and FIB-MAA (at 24 h) led to increased mRNA expression and protein expression of PAD2 (p < 0.001) with increased protein citrullination. CONCLUSION: These findings suggest that MAA-modification and citrullination of FIB, in isolation or combination, yield specific effects on macrophage polarization, PAD expression and citrullination that ultimately may induce inflammatory and fibrotic responses associated with RA.


Assuntos
Artrite Reumatoide , Fibrinogênio , Acetaldeído , Citrulina/metabolismo , Fibrinogênio/metabolismo , Humanos , Hidrolases , Macrófagos/metabolismo , Malondialdeído , Desiminases de Arginina em Proteínas/metabolismo , RNA Mensageiro
13.
Mol Genet Genomic Med ; 10(9): e2007, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35726796

RESUMO

INTRODUCTION: Citrullinemia Type 1 (CTLN1) is an autosomal recessive disorder caused by variants in the ASS1 gene. This study intends to clarify the etiology of false positives in newborn screening for citrullinemia. METHOD: Newborns who had elevated dried-blood spot citrulline levels were enrolled, and medical records were reviewed retrospectively. Common ASS1 variants were screened using high-resolution melting analysis. RESULT: Between 2011 and 2021, 130 newborns received confirmatory testing for citrullinemia, 4 were found to be patients for CTLN1; 11 were patients with citrin deficiency; and 49 newborns were confirmed to be carrying one pathogenic ASS1 variant. The incidence of CTLN1 was 1 in 188,380 (95% confidence interval: 1 in 73,258 to 1 in 484,416). All ASS1 variants studied in this cohort were located in exons 11 to 15, which encode the tetrameric interface regions of the ASS1 protein. Among 10 ASS1 carriers with elevated citrulline levels and complete sequence data, four (40%) revealed additional non-benign ASS1 variants; in contrast, only 2 of the 26 controls (7.7%), with normal citrulline levels, had additional ASS1 variants. CONCLUSION: Heterozygote ASS1 variants may lead to a mild elevation of blood citrulline levels: about 2-6 times the population mean. Molecular testing and family studies remain critical for precise diagnosis, genetic counseling, and management.


Assuntos
Citrulinemia , Argininossuccinato Sintase/genética , Argininossuccinato Sintase/metabolismo , Citrulina/genética , Citrulina/metabolismo , Citrulinemia/diagnóstico , Citrulinemia/genética , Heterozigoto , Humanos , Recém-Nascido , Estudos Retrospectivos
14.
Bone Marrow Transplant ; 57(9): 1373-1381, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35661156

RESUMO

Earlier studies have suggested that severe intestinal mucositis (IM; citrulline < 10 µmol/L) is an independent risk factor for bloodstream infections (BSI) after cytotoxic therapy. Our aim was to grade IM in patients receiving commonly used chemotherapy and conditioning regimens, and characterize its relationship with BSI incidence. In a retrospective analysis of remission induction (RI) chemotherapy, or conditioning for autologous and allogeneic hematopoietic stem cell transplantation (HSCT; myeloablative conditioning [MAC] and non-myeloablative and reduced-intensity conditioning [NMA/RIC]), data were collected on central venous catheter (CVC) characteristics and BSI. The relationship between BSI occurrence and the degree of IM (determined by citrulline levels) and neutropenia was analyzed. In 626 CVC episodes, 268 (42.8%) laboratory-confirmed BSIs (LCBIs) occurred, classified as mucosal barrier injury (MBI)-LCBIs in 179 (28.6%) episodes, central line-associated BSIs in 113 (18.1%) episodes, and catheter-related BSIs in 55 (8.8%) episodes. In NMA/RIC, the mean duration of hypocitrullinemia was 0.77 days, with LCBI and MBI-LCBI occurring in 11.1% and 4.8% of episodes. In autologous HSCT, RI, and MAC allogeneic HSCT, LCBI and MBI-LCBI occurred frequently (40.0-63.8% and 22.8-53.2% of episodes, respectively) and the mean duration of hypocitrullinemia was significantly higher (9.2-13.8 days). There was a strong correlation between LCBI and the duration of hypocitrullinemia (Pearson's correlation coefficient R = 0.96), as opposed to the relationship between LCBI and the duration of neutropenia (R = 0.42). We conclude that citrulline can be used to grade BSI risk for commonly used intensive treatment regimens.


Assuntos
Bacteriemia , Infecções Relacionadas a Cateter , Transplante de Células-Tronco Hematopoéticas , Infecções , Mucosite , Neutropenia , Sepse , Bacteriemia/etiologia , Biomarcadores , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/etiologia , Citrulina , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Infecções/etiologia , Mucosite/etiologia , Neutropenia/etiologia , Estudos Retrospectivos
15.
Immunobiology ; 227(4): 152233, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35667151

RESUMO

Protein citrullination is one of the processes of post-translational modification of proteins and peptides, playing a crucial role in the homeostasis of important processes, however also leading to pathological processes in autoimmune and neoplastic disorders. Citrullination regulates epidermal function, reproduction being also involved in NET formation. Nowadays, the knowledge about citrullination spreads and opens up a new field for investigation of compounds that potentially be used as a treatment. Inhibitors of PADI are currently being tested in various diseases. As these enzymes play an essential role in the disease progression, one should also look for the basics of regulation of their expression in the cell as well as focus on environmental factors like air pollution or smoking, which can augment the process of citrullination. Despite its pathological properties, citrullination can be a prognostic marker of diseases and a good target for therapies. In this revision, we used PubMed, PubMed Central (PMC), and Google Scholar to collect data which presents information from severalarticles, reviews, case reports, case studies, cohort studies, and clinical trials. Studies conducted in vitro, in vivo on mouse models, postmortem tissue models of animal and human origin were included and non-english articles were excluded. We mainly used keywords like "PAD", Peptidylarginine deiminases", "citrullination" or "deimination" in the search. This revision contains description using both original and review papers can be useful for doctors, scientists, and patients.


Assuntos
Citrulina , Hidrolases , Animais , Citrulinação , Citrulina/metabolismo , Humanos , Hidrolases/metabolismo , Camundongos , Processamento de Proteína Pós-Traducional , Desiminases de Arginina em Proteínas/genética , Desiminases de Arginina em Proteínas/metabolismo
16.
J Vector Borne Dis ; 59(1): 45-51, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35708403

RESUMO

BACKGROUND & OBJECTIVES: Malaria affects around 228 million people all over the globe. Malaria causing parasite Plasmodium infection leads to activation of immune responses. The growth of parasite and immune activation requires semi essential amino acids like L-arginine. Malaria infection leads to condition of hyperargininemia and low availability of nitric oxide. However, the effect of L-arginine supplementation in malaria infected mice has not been explored in in-vivo studies. In this study we have compared the effect of oral supplementation of nitric oxide donor, L-arginine and L-citrulline, in malaria infected mice Methods: To examine the effect of oral supplementation of L-arginine and L-citrulline, Plasmodium berghei infected mice were divided in different groups and respective groups were fed with L- arginine and L-citrulline, parasitemia was measured on different days. Mice was sacrificed and immunophenotyping was done on 10 days post infection. RESULTS: our results show that supplementation of L-arginine induces conducive environment for Plasmodium growth due to which the infected mice dies earlier than control wild type infected mice whereas L-citrulline supplementation inhibits parasite growth and mice survives for longer period of time. Flow cytometric analysis shows that supplementation of L-arginine increases cTLA-4 on T cell population, increases Treg cells leading to immunosuppression while supplementation of L-citrulline does not have effect on T cells population and number of Treg cell decrease compared to P. berghei infected mice. INTERPRETATION & CONCLUSION: our results show that L-citrulline can be a better alternative than L-arginine because of lower expression of inhibitory molecules and lower parasitemia as well as increased survival of infected mice.


Assuntos
Citrulina , Malária , Animais , Arginina/metabolismo , Arginina/farmacologia , Citrulina/metabolismo , Citrulina/farmacologia , Humanos , Malária/prevenção & controle , Camundongos , Parasitemia/prevenção & controle , Plasmodium berghei , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia
17.
Eur J Immunol ; 52(9): 1464-1473, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35712879

RESUMO

Rheumatoid arthritis (RA) is associated with HLA-DRB1 alleles expressing the "shared epitope." RA is usually preceded by the emergence of anti-citrullinated protein autoantibodies (ACPAs). ACPAs recognize citrulline residues on numerous proteins. Conversion of arginine into citrulline is performed by enzymes called peptidyl arginine deiminases (PADs). We have previously demonstrated that C3H mice immunized with PADs can produce ACPAs by a hapten-carrier mechanism. Here, we address the influence of HLA-DR alleles in this model in mice expressing RA-associated HLA-DRB1*04:01 (KO/KI*04:01), HLA-DRB1*04:04 (KO/KI*04:04), or non-RA-associated HLA-DRB1*04:02 (KO/KI*04:02) after murine PAD2 immunization. Immunization with mPAD2 triggers production of ACPAs in wild-type (WT) and HLA-DR4 C57BL/6 mice. Both I-Ab and HLA-DR are involved in the activation of mPAD2-specific T lymphocytes. Among HLA-DR4 mice, mice expressing RA-associated HLA-DRB1*04:01 are the best responders to mPAD2 and the best anti-citrullinated peptide antibody producers.


Assuntos
Artrite Reumatoide , Antígeno HLA-DR4 , Alelos , Animais , Arginina , Autoanticorpos , Citrulina/metabolismo , Antígeno HLA-DR4/genética , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/metabolismo , Imunização , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL
18.
Molecules ; 27(12)2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35744973

RESUMO

Metformin (N,N-dimethylguanylguanidine) is one of the most prescribed drugs with pleiotropic, exerted in part by not fully elucidated mechanisms of action. We developed and validated a gas chromatography-mass spectrometry (GC-MS) method for the quantitative analysis of metformin (metformin-d0) in 10-µL aliquots of human serum and urine using N,N-[dimethylo-2H6]guanylguanidine (metformin-d6) as the internal standard. The method involves evaporation of the samples to dryness, derivatization with pentafluoropropionic (PFP) anhydride in ethyl acetate (30 min, 65 °C), and extraction into toluene. The negative-ion chemical ionization GC-MS spectra of the PFP derivatives contain a single intense ion with mass-to-charge (m/z) ratios of m/z 383 for metformin-d0 and m/z 389 for metformin-d6. Our results suggest that all amine/imine groups of metformin-d0 and metformin-d6 are converted to their N,N,N-tripentafluoropropionyl derivatives, which cyclize to form a symmetric triazine derivative, of which the non-ring amine group is amidated. Quantification was performed by selected-ion monitoring (SIM) of m/z 383 and m/z 389. Upon validation, the method was applied to determine serum and urine metformin concentrations in 19 patients with Becker muscular dystrophy (BMD). Serum and urine samples were collected at baseline (Visit I), after six weeks of supplementation (Visit II) with metformin (3 × 500 mg/d; metformin group; n = 10) or l-citrulline (3 × 1500 mg/d; citrulline group; n = 9) followed by a six-week supplementation with 3 × 500 mg/d of metformin plus 3 × 1500 mg/d l-citrulline. At Visit I, the metformin concentration in the serum and urine was very low in both groups. The metformin concentrations in the serum and urine of the patients who first took metformin (MET group) were higher at Visit II and Visit III. The metformin concentration in the serum and urine samples of the patients who first took l-citrulline (CITR group) were higher at Visit III. The serum and urine concentrations of metformin were insignificantly lower in the CITR group at Visit III. The mean fractional excretion (FE) rate of metformin was 307% (Visit II) and 322% (Visit III) in the MET group, and 290% in the CITR group (Visit III). This observation suggests the accumulation of metformin in the kidney and its secretion in the urine. The GC-MS is suitable to measure reliably circulating and excretory metformin in clinical settings.


Assuntos
Metformina , Distrofia Muscular de Duchenne , Aminas , Citrulina , Fluorcarbonetos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Isótopos , Metformina/uso terapêutico , Distrofia Muscular de Duchenne/tratamento farmacológico
19.
Nitric Oxide ; 125-126: 31-39, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35705144

RESUMO

Aging is associated with a decline in physiological function and exercise performance. These effects are mediated, at least in part, by an age-related decrease in the bioavailability of nitric oxide (NO), a ubiquitous gasotransmitter and regulator of myriad physiological processes. The decrease in NO bioavailability with aging is especially apparent in sedentary individuals, whereas older, physically active individuals maintain higher levels of NO with advancing age. Strategies which enhance NO bioavailability (including nutritional supplementation) have been proposed as a potential means of reducing the age-related decrease in physiological function and enhancing exercise performance and may be of interest to a range of older individuals including those taking part in competitive sport. In this brief review we discuss the effects of aging on physiological function and endurance exercise performance, and the potential role of changes in NO bioavailability in these processes. We also provide a summary of current evidence for dietary supplementation with substrates for NO production - including inorganic nitrate and nitrite, l-arginine and l-citrulline - for improving exercise capacity/performance in older adults. Additionally, we discuss the (limited) evidence on the effects of (poly)phenols and other dietary antioxidants on NO bioavailability in older individuals. Finally, we provide suggestions for future research.


Assuntos
Citrulina , Óxido Nítrico , Idoso , Envelhecimento , Atletas , Citrulina/farmacologia , Suplementos Nutricionais , Exercício Físico/fisiologia , Humanos , Nitratos/farmacologia
20.
J Am Soc Mass Spectrom ; 33(7): 1176-1186, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35621259

RESUMO

The use of tandem mass spectrometry (MS/MS) is a fundamental prerequisite of reliable protein identification and quantification in mass-spectrometry-based proteomics. In bottom-up and middle-down proteomics, proteins are identified by the characteristic fragments of their constituting peptides. Post-translational modifications (PTMs) often further complicate proteome analyses. Citrullination is an increasingly studied PTM converting arginines to citrullines (Cit, X) and is implicated in several autoimmune and neurological diseases as well as different types of cancer. Confirmation of citrullination is known to be very challenging since it results in the same molecular mass change as Asn/Gln deamidation. In this study, we explore which MS/MS characteristics can be used for the reliable identification of citrullination. We synthesized several peptides incorporating Cit residues that model enzymatic cleavages of different proteins with verified or putative citrullination. Collision-induced dissociation was used to investigate the energy dependence of Byonic and Mascot scores and confirmed sequence coverage (CSC) along with the neutral loss of HNCO characteristic to citrulline side chains. We found that although the recommended values (19-45 V) for ramped collision energy settings cover the optimal Mascot, Byonic, or %CSC scores effectively, the diagnostic HNCO loss from precursors and fragments may reach their maximum intensities at lower and higher collision energies, respectively. Therefore, we suggest broadening the ramp range to ∼5-60 V to obtain more favorable identification rates for citrullinated peptides. We also found that Byonic was more successful in correctly identifying citrullinated peptides with deamidated residues than Mascot.


Assuntos
Peptídeos , Espectrometria de Massas em Tandem , Citrulina/química , Peptídeos/química , Processamento de Proteína Pós-Traducional , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...