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Article ; Online: Response to: "Relationship Between Ventricular Arrhythmias, Conduction Disorders, and Myocardial Fibrosis in Patients With Systemic Sclerosis: the Role of Cardiac Magnetic Resonance" by De Luca Giacomo, Campochiaro Corrado, Cavalli Giulio, Dagna Lorenzo.

Muresan, Lucian / Rednic, Simona

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

2020 Volume 26, Issue 2, Page(s) e36–e37

MeSH term(s)	Arrhythmias, Cardiac ; Cardiac Conduction System Disease ; Fibrosis ; Humans ; Magnetic Resonance Spectroscopy ; Scleroderma, Systemic
Language	English
Publishing date	2020-02-04
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1283266-2
ISSN	1536-7355 ; 1076-1608
ISSN (online)	1536-7355
ISSN	1076-1608
DOI	10.1097/RHU.0000000000000791
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Article ; Online: An Update on the Effects of Vitamin D on the Immune System and Autoimmune Diseases.

Sîrbe, Claudia / Rednic, Simona / Grama, Alina / Pop, Tudor Lucian

International journal of molecular sciences

2022 Volume 23, Issue 17

Abstract: Vitamin D intervenes in calcium and phosphate metabolism and bone homeostasis. Experimental studies have shown that 1,25-dihydroxyvitamin D (calcitriol) generates immunologic activities on the innate and adaptive immune system and endothelial membrane ... ...

Abstract	Vitamin D intervenes in calcium and phosphate metabolism and bone homeostasis. Experimental studies have shown that 1,25-dihydroxyvitamin D (calcitriol) generates immunologic activities on the innate and adaptive immune system and endothelial membrane stability. Low levels of serum 25-hydroxyvitamin D (25(OH)D) are associated with an increased risk of developing immune-related diseases such as psoriasis, type 1 diabetes, multiple sclerosis, and autoimmune diseases. Various clinical trials describe the efficacy of supplementation of vitamin D and its metabolites for treating these diseases that result in variable outcomes. Different disease outcomes are observed in treatment with vitamin D as high inter-individual difference is present with complex gene expression in human peripheral blood mononuclear cells. However, it is still not fully known what level of serum 25(OH)D is needed. The current recommendation is to increase vitamin D intake and have enough sunlight exposure to have serum 25(OH)D at a level of 30 ng/mL (75 nmol/L) and better at 40-60 ng/mL (100-150 nmol/L) to obtain the optimal health benefits of vitamin D.
MeSH term(s)	Autoimmune Diseases/complications ; Autoimmune Diseases/drug therapy ; Humans ; Leukocytes, Mononuclear/metabolism ; Vitamin D ; Vitamin D Deficiency/complications ; Vitamins
Chemical Substances	Vitamins ; Vitamin D (1406-16-2)
Language	English
Publishing date	2022-08-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23179784
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Article ; Online: Immune Profiling of Patients with Systemic Sclerosis through Targeted Proteomic Analysis.

Szabo, Iulia / Badii, Medeea / Gaál, Ildikó O / Szabo, Robert / Sîrbe, Claudia / Humiță, Oana / Joosten, Leo A B / Crișan, Tania O / Rednic, Simona

International journal of molecular sciences

2023 Volume 24, Issue 24

Abstract: High-throughput proteomic analysis could offer new insights into the pathogenesis of systemic sclerosis (SSc) and reveal non-invasive biomarkers for diagnosis and severity. This study aimed to assess the protein signature of patients with SSc compared to ...

Abstract	High-throughput proteomic analysis could offer new insights into the pathogenesis of systemic sclerosis (SSc) and reveal non-invasive biomarkers for diagnosis and severity. This study aimed to assess the protein signature of patients with SSc compared to that of healthy volunteers, decipher various disease endotypes using circulating proteins, and determine the diagnostic performance of significantly expressed plasma analytes. We performed targeted proteomic profiling in a cohort of fifteen patients with SSc and eighteen controls using the Olink
MeSH term(s)	Humans ; Proteomics ; Scleroderma, Systemic/pathology ; Inflammation ; Immunity, Innate ; Proteins ; Biomarkers
Chemical Substances	Proteins ; Biomarkers
Language	English
Publishing date	2023-12-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242417601
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Article ; Online: Detection of Novel Biomarkers in Pediatric Autoimmune Hepatitis by Proteomic Profiling.

Sîrbe, Claudia / Badii, Medeea / Crişan, Tania O / Bența, Gabriel / Grama, Alina / Joosten, Leo A B / Rednic, Simona / Pop, Tudor Lucian

International journal of molecular sciences

2023 Volume 24, Issue 8

Abstract: Autoimmune hepatitis (AIH) is characterized by immune-mediated hepatocyte injury resulting in the destruction of liver cells, causing inflammation, liver failure, and fibrosis. Pediatric (AIH) is an autoimmune inflammatory disease that usually requires ... ...

Abstract	Autoimmune hepatitis (AIH) is characterized by immune-mediated hepatocyte injury resulting in the destruction of liver cells, causing inflammation, liver failure, and fibrosis. Pediatric (AIH) is an autoimmune inflammatory disease that usually requires immunosuppression for an extended period. Frequent relapses after treatment discontinuation demonstrate that current therapies do not control intrahepatic immune processes. This study describes targeted proteomic profiling data in patients with AIH and controls. A total of 92 inflammatory and 92 cardiometabolic plasma markers were assessed for (i) pediatric AIH versus controls, (ii) AIH type 1 versus type 2, (iii) AIH and AIH-autoimmune sclerosing cholangitis overlapping syndrome and (iv) correlations with circulating vitamin D levels in AIH. A total of 16 proteins showed a nominally significant differential abundance in pediatric patients with AIH compared to controls. No clustering of AIH subphenotypes based on all protein data was observed, and no significant correlation of vitamin D levels was observed for the identified proteins. The proteins that showed variable expression include CA1, CA3, GAS6, FCGR2A, 4E-BP1 and CCL19, which may serve as potential biomarkers for patients with AIH. CX3CL1, CXCL10, CCL23, CSF1 and CCL19 showed homology to one another and may be coexpressed in AIH. CXCL10 seems to be the central intermediary link for the listed proteins. These proteins were involved in relevant mechanistic pathways for liver diseases and immune processes in AIH pathogenesis. This is the first report on the proteomic profile of pediatric AIH. The identified markers could potentially lead to new diagnostic and therapeutic tools. Nevertheless, considering the complex pathogenesis of AIH, more extensive studies are warranted to replicate and validate the present study's findings.
MeSH term(s)	Humans ; Child ; Hepatitis, Autoimmune/diagnosis ; Proteomics ; Liver Diseases ; Cholangitis, Sclerosing/therapy ; Biomarkers ; Vitamin D
Chemical Substances	Biomarkers ; Vitamin D (1406-16-2)
Language	English
Publishing date	2023-04-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24087479
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Article ; Online: Enhanced Innate and Acquired Immune Responses in Systemic Sclerosis Primary Peripheral Blood Mononuclear Cells (PBMCs).

Szabo, Iulia / Badii, Medeea / Gaál, Ildikó O / Szabo, Robert / Popp, Radu A / Joosten, Leo A B / Crişan, Tania O / Rednic, Simona

International journal of molecular sciences

2023 Volume 24, Issue 19

Abstract: Chronic immune activation in systemic sclerosis is supported by the production of a plethora of cytokines with proven regulatory activities of the immune responses. This study aimed to explore PBMCs' cytokine profiles in SSc patients versus controls, as ... ...

Abstract	Chronic immune activation in systemic sclerosis is supported by the production of a plethora of cytokines with proven regulatory activities of the immune responses. This study aimed to explore PBMCs' cytokine profiles in SSc patients versus controls, as well as to investigate the balance between pro- and anti-inflammatory cytokines in association with disease duration. PBMCs were isolated from 18 SSc patients and 17 controls and further subjected to in vitro stimulation with lipopolysaccharide and heat-killed
MeSH term(s)	Humans ; Leukocytes, Mononuclear ; Interleukin-10 ; Interleukin-17/pharmacology ; Interleukin 1 Receptor Antagonist Protein/pharmacology ; Interleukin-6/pharmacology ; Pilot Projects ; Cytokines ; Tumor Necrosis Factor-alpha/pharmacology ; Immunity ; Scleroderma, Systemic
Chemical Substances	Interleukin-10 (130068-27-8) ; Interleukin-17 ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-6 ; Cytokines ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2023-09-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241914438
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Article ; Online: GWAS-identified hyperuricemia-associated IGF1R variant rs6598541 has a limited role in urate mediated inflammation in human mononuclear cells.

Gaal, Orsolya I / Liu, Ruiqi / Marginean, Dragoș / Badii, Medeea / Cabău, Georgiana / Hotea, Ioana / Nica, Valentin / Colcear, Doina / Pamfil, Cristina / Merriman, Tony R / Rednic, Simona / Popp, Radu A / Crișan, Tania O / Joosten, Leo A B

Scientific reports

2024 Volume 14, Issue 1, Page(s) 3565

Abstract: Gout is a common autoinflammatory joint diseases characterized by deposition of monosodium urate (MSU) crystals which trigger an innate immune response mediated by inflammatory cytokines. IGF1R is one of the loci associated with both urate levels and ... ...

Abstract	Gout is a common autoinflammatory joint diseases characterized by deposition of monosodium urate (MSU) crystals which trigger an innate immune response mediated by inflammatory cytokines. IGF1R is one of the loci associated with both urate levels and gout susceptibility in GWAS to date, and IGF-1-IGF-1R signaling is implicated in urate control. We investigate the role of IGF-1/IGF1R signaling in the context of gouty inflammation. Also, we test the gout and urate-associated IGF1R rs6598541 polymorphism for association with the inflammatory capacity of mononuclear cells. For this, freshly isolated human peripheral blood mononuclear cells (PBMCs) were exposed to recombinant IGF-1 or anti-IGF1R neutralizing antibody in the presence or absence of solubilized urate, stimulated with LPS/MSU crystals. Also, the association of rs6598541 with IGF1R and protein expression and with ex vivo cytokine production levels after stimulation with gout specific stimuli was tested. Urate exposure was not associated with IGF1R expression in vitro or in vivo. Modulation of IGF1R did not alter urate-induced inflammation. Developing urate-induced trained immunity in vitro was not influenced in cells challenged with IGF-1 recombinant protein. Moreover, the IGF1R rs6598541 SNP was not associated with cytokine production. Our results indicate that urate-induced inflammatory priming is not regulated by IGF-1/IGF1R signaling in vitro. IGF1R rs6598541 status was not asociated with IGF1R expression or cytokine production in primary human PBMCs. This study suggests that the role of IGF1R in gout is tissue-specific and may be more relevant in the control of urate levels rather than in inflammatory signaling in gout.
MeSH term(s)	Humans ; Uric Acid/metabolism ; Hyperuricemia/complications ; Insulin-Like Growth Factor I/genetics ; Insulin-Like Growth Factor I/metabolism ; Leukocytes, Mononuclear/metabolism ; Genome-Wide Association Study ; Gout/genetics ; Gout/complications ; Inflammation/metabolism ; Cytokines/metabolism ; Receptor, IGF Type 1/genetics ; Receptor, IGF Type 1/metabolism
Chemical Substances	Uric Acid (268B43MJ25) ; Insulin-Like Growth Factor I (67763-96-6) ; Cytokines ; IGF1R protein, human ; Receptor, IGF Type 1 (EC 2.7.10.1)
Language	English
Publishing date	2024-02-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-53209-7
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Article: Insights into the Relationship between Periodontitis and Systemic Sclerosis Based on the New Periodontitis Classification (2018): A Cross-Sectional Study.

Ciurea, Andreea / Stanomir, Alina / Șurlin, Petra / Micu, Iulia Cristina / Pamfil, Cristina / Leucuța, Daniel Corneliu / Rednic, Simona / Rasperini, Giulio / Soancă, Andrada / Țigu, Adrian Bogdan / Roman, Alexandra / Picoș, Andrei / Delean, Ada Gabriela

Diagnostics (Basel, Switzerland)

2024 Volume 14, Issue 5

Abstract: 1) Background: This study aimed to assess the periodontitis burden in systemic sclerosis patients and the possible association between them, and the degree to which some potential risk factors and two potential diagnostic biomarkers may account for this ...

Abstract	(1) Background: This study aimed to assess the periodontitis burden in systemic sclerosis patients and the possible association between them, and the degree to which some potential risk factors and two potential diagnostic biomarkers may account for this association. (2) Methods: This cross-sectional study included a test group (systemic sclerosis patients) and a control group (non-systemic sclerosis patients). Both groups benefited from medical, periodontal examination and saliva sampling to determine the salivary flow rate and two inflammatory biomarkers (calprotectin, psoriasin). A systemic sclerosis severity scale was established. (3) Results: In the studied groups, comparable periodontitis rates of 88.68% and 85.85%, respectively, were identified. There were no significant differences in the severity of periodontitis among different systemic sclerosis severity, or in the positivity for anti-centromere and anti-SCL70 antibodies. Musculoskeletal lesions were significantly more common in stage III/IV periodontitis (
Language	English
Publishing date	2024-03-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics14050540
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Article: Novel Concepts in Systemic Sclerosis Pathogenesis: Role for miRNAs.

Szabo, Iulia / Muntean, Laura / Crisan, Tania / Rednic, Voicu / Sirbe, Claudia / Rednic, Simona

Biomedicines

2021 Volume 9, Issue 10

Abstract: Systemic sclerosis (SSc) is a rare connective tissue disease with heterogeneous clinical phenotypes. It is characterized by the pathogenic triad: microangiopathy, immune dysfunction, and fibrosis. Epigenetic mechanisms modulate gene expression without ... ...

Abstract	Systemic sclerosis (SSc) is a rare connective tissue disease with heterogeneous clinical phenotypes. It is characterized by the pathogenic triad: microangiopathy, immune dysfunction, and fibrosis. Epigenetic mechanisms modulate gene expression without interfering with the DNA sequence. Epigenetic marks may be reversible and their differential response to external stimuli could explain the protean clinical manifestations of SSc while offering the opportunity of targeted drug development. Small, non-coding RNA sequences (miRNAs) have demonstrated complex interactions between vasculature, immune activation, and extracellular matrices. Distinct miRNA profiles were identified in SSc skin specimens and blood samples containing a wide variety of dysregulated miRNAs. Their target genes are mainly involved in profibrotic pathways, but new lines of evidence also confirm their participation in impaired angiogenesis and aberrant immune responses. Research approaches focusing on earlier stages of the disease and on differential miRNA expression in various tissues could bring novel insights into SSc pathogenesis and validate the clinical utility of miRNAs as biomarkers and therapeutic targets.
Language	English
Publishing date	2021-10-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9101471
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Article ; Online: Regulation of SOCS3-STAT3 in urate-induced cytokine production in human myeloid cells.

Badii, Medeea / Klück, Viola / Gaal, Orsolya / Cabău, Georgiana / Hotea, Ioana / Nica, Valentin / Mirea, Andreea M / Bojan, Anca / Zdrenghea, Mihnea / Novakovic, Boris / Merriman, Tony R / Liu, Zhaoli / Li, Yang / Xu, Cheng-Jian / Pamfil, Cristina / Rednic, Simona / Popp, Radu A / Crişan, Tania O / Joosten, Leo A B

Joint bone spine

2024 Volume 91, Issue 3, Page(s) 105698

Abstract: Objective: Hyperuricaemia is necessary for gout. High urate concentrations have been linked to inflammation in mononuclear cells. Here, we explore the role of the suppressor of cytokine signaling 3 (SOCS3) in urate-induced inflammation.: Methods: ... ...

Abstract	Objective: Hyperuricaemia is necessary for gout. High urate concentrations have been linked to inflammation in mononuclear cells. Here, we explore the role of the suppressor of cytokine signaling 3 (SOCS3) in urate-induced inflammation. Methods: Peripheral blood mononuclear cells (PBMCs) from gout patients, hyperuricemic and normouricemic individuals were cultured for 24h with varying concentrations of soluble urate, followed by 24h restimulation with lipopolysaccharides (LPS)±monosodium urate (MSU) crystals. Transcriptomic profiling was performed using RNA-Sequencing. DNA methylation was assessed using Illumina Infinium® MethylationEPIC BeadChip system (EPIC array). Phosphorylation of signal transducer and activator of transcription 3 (STAT3) was determined by flow cytometry. Cytokine responses were also assessed in PBMCs from patients with JAK2 V617F tyrosine kinase mutation. Results: PBMCs pre-treated with urate produced more interleukin-1beta (IL-1β) and interleukin-6 (IL-6) and less interleukin-1 receptor anatagonist (IL-1Ra) after LPS simulation. In vitro, urate treatment enhanced SOCS3 expression in control monocytes but no DNA methylation changes were observed at the SOCS3 gene. A dose-dependent reduction in phosphorylated STAT3 concomitant with a decrease in IL-1Ra was observed with increasing concentrations of urate. PBMCs with constitutively activated STAT3 (JAK2 V617F mutation) could not be primed by urate. Conclusion: In vitro, urate exposure increased SOCS3 expression, while urate priming, and subsequent stimulation resulted in decreased STAT3 phosphorylation and IL-1Ra production. There was no evidence that DNA methylation constitutes a regulatory mechanism of SOCS3. Elevated SOCS3 and reduced pSTAT3 could play a role in urate-induced hyperinflammation since urate priming had no effect in PBMCs from patients with constitutively activated STAT3.
MeSH term(s)	Humans ; Suppressor of Cytokine Signaling 3 Protein/metabolism ; Suppressor of Cytokine Signaling 3 Protein/genetics ; Uric Acid/pharmacology ; STAT3 Transcription Factor/metabolism ; Cytokines/metabolism ; Gout/genetics ; Gout/metabolism ; Cells, Cultured ; Male ; Myeloid Cells/metabolism ; Myeloid Cells/drug effects ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/drug effects ; Hyperuricemia/metabolism ; Female ; Middle Aged ; DNA Methylation ; Janus Kinase 2/metabolism
Chemical Substances	Suppressor of Cytokine Signaling 3 Protein ; Uric Acid (268B43MJ25) ; STAT3 Transcription Factor ; SOCS3 protein, human ; Cytokines ; STAT3 protein, human ; Janus Kinase 2 (EC 2.7.10.2)
Language	English
Publishing date	2024-02-01
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020487-5
ISSN	1778-7254 ; 1297-319X
ISSN (online)	1778-7254
ISSN	1297-319X
DOI	10.1016/j.jbspin.2024.105698
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Zs.A 4590: Show issues

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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Article ; Online: Hyperuricemia remodels the serum proteome toward a higher inflammatory state.

Cabău, Georgiana / Gaal, Orsolya / Badii, Medeea / Nica, Valentin / Mirea, Andreea-Manuela / Hotea, Ioana / Pamfil, Cristina / Popp, Radu A / Netea, Mihai G / Rednic, Simona / Crișan, Tania O / Joosten, Leo A B

iScience

2023 Volume 26, Issue 10, Page(s) 107909

Abstract: Gout is an autoinflammatory disease triggered by a complex innate immune response to MSU crystals and inflammatory triggers. While hyperuricemia is an obligatory risk factor for the development of gout, the majority of individuals with hyperuricemia ... ...

Abstract	Gout is an autoinflammatory disease triggered by a complex innate immune response to MSU crystals and inflammatory triggers. While hyperuricemia is an obligatory risk factor for the development of gout, the majority of individuals with hyperuricemia never develop gout but have an increased risk of developing cardiometabolic disorders. Current management of gout aims at MSU crystal dissolution by lowering serum urate. We apply a targeted proteomic analysis, using Olink inflammation panel, to a large group of individuals with gout, asymptomatic hyperuricemia, and normouricemic controls, and we show a urate-driven inflammatory signature. We add
Language	English
Publishing date	2023-09-14
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107909
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