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Article ; Online: Therapeutic Lowering of C-Reactive Protein.

Jimenez, Rachel V / Szalai, Alexander J

2021 Volume 11, Page(s) 619564

Abstract: In the blood of healthy individuals C-reactive protein (CRP) is typically quite scarce ...

Abstract	In the blood of healthy individuals C-reactive protein (CRP) is typically quite scarce, whereas its blood concentration can rise robustly and rapidly in response to tissue damage and inflammation associated with trauma and infectious and non-infectious diseases. Consequently, CRP plasma or serum levels are routinely monitored in inpatients to gauge the severity of their initial illness and injury and their subsequent response to therapy and return to health. Its clinical utility as a faithful barometer of inflammation notwithstanding, it is often wrongly concluded that the biological actions of CRP (whatever they may be) are manifested only when blood CRP is elevated. In fact over the last decades, studies done in humans and animals (e.g. human CRP transgenic and CRP knockout mice) have shown that CRP is an important mediator of biological activities even in the absence of significant blood elevation, i.e. even at baseline levels. In this review we briefly recap the history of CRP, including a description of its discovery, early clinical use, and biosynthesis at baseline and during the acute phase response. Next we overview evidence that we and others have generated using animal models of arthritis, neointimal hyperplasia, and acute kidney injury that baseline CRP exerts important biological effects. In closing we discuss the possibility that therapeutic lowering of baseline CRP might be a useful way to treat certain diseases, including cancer.
MeSH term(s)	Animals ; C-Reactive Protein ; Humans
Chemical Substances	C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2021-01-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.619564
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Article ; Online: Persistently High Procalcitonin and C-Reactive Protein Are Good Predictors of Infection in Acute Necrotizing Pancreatitis: A Systematic Review and Meta-Analysis.

Tarján, Dorottya / Szalai, Eszter / Lipp, Mónika / Verbói, Máté / Kói, Tamás / Erőss, Bálint / Teutsch, Brigitta / Faluhelyi, Nándor / Hegyi, Péter / Mikó, Alexandra

International journal of molecular sciences

2024 Volume 25, Issue 2

Abstract: ... Within the first 72 hours (h) after admission, the AUC of C-reactive protein (CRP) was 0.69 (confidence interval ...

Abstract	Infected necrotizing pancreatitis (INP) is associated with an increased risk of organ failure and mortality. Its early recognition and timely initiation of antibiotic therapy can save patients' lives. We systematically searched three databases on 27 October 2022. In the eligible studies, the presence of infection in necrotizing pancreatitis was confirmed via a reference test, which involved either the identification of gas within the necrotic collection through computed tomography imaging or the examination of collected samples, which yielded positive results in Gram staining or culture. Laboratory biomarkers compared between sterile necrotizing pancreatitis and INP were used as the index test, and our outcome measures included sensitivity, specificity, the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Within the first 72 hours (h) after admission, the AUC of C-reactive protein (CRP) was 0.69 (confidence interval (CI): 0.62-0.76), for procalcitonin (PCT), it was 0.69 (CI: 0.60-0.78), and for white blood cell count, it was 0.61 (CI: 0.47-0.75). After the first 72 h, the pooled AUC of CRP showed an elevated level of 0.88 (CI: 0.75-1.00), and for PCT, it was 0.86 (CI: 0.60-1.11). The predictive value of CRP and PCT for infection is poor within 72 h after hospital admission but seems good after the first 72 h. Based on these results, infection is likely in case of persistently high CRP and PCT, and antibiotic initiation may be recommended.
MeSH term(s)	Humans ; Anti-Bacterial Agents/therapeutic use ; Biomarkers/blood ; C-Reactive Protein/analysis ; Pancreatitis, Acute Necrotizing/blood ; Pancreatitis, Acute Necrotizing/diagnosis ; Procalcitonin/blood ; ROC Curve
Chemical Substances	Anti-Bacterial Agents ; Biomarkers ; C-Reactive Protein (9007-41-4) ; Procalcitonin
Language	English
Publishing date	2024-01-20
Publishing country	Switzerland
Document type	Meta-Analysis ; Systematic Review ; 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/ijms25021273
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Article ; Online: The C-Terminus and Third Cytoplasmic Loop Cooperatively Activate Mouse Melanopsin Phototransduction.

Valdez-Lopez, Juan C / Petr, Stephen T / Donohue, Matthew P / Bailey, Robin J / Gebreeziabher, Meheret / Cameron, Evan G / Wolf, Julia B / Szalai, Veronika A / Robinson, Phyllis R

Biophysical journal

2020 Volume 119, Issue 2, Page(s) 389–401

Abstract: ... deactivation have been characterized (i.e., C-terminal phosphorylation and β-arrestin binding), but a detailed ... adjacent to the proximal C-terminal region of mouse melanopsin in the inactive conformation, which is ... a high degree of steric freedom at the third cytoplasmic loop, which is increased upon C-terminus ...

Abstract	Melanopsin, an atypical vertebrate visual pigment, mediates non-image-forming light responses including circadian photoentrainment and pupillary light reflexes and contrast detection for image formation. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells are characterized by sluggish activation and deactivation of their light responses. The molecular determinants of mouse melanopsin's deactivation have been characterized (i.e., C-terminal phosphorylation and β-arrestin binding), but a detailed analysis of melanopsin's activation is lacking. We propose that an extended third cytoplasmic loop is adjacent to the proximal C-terminal region of mouse melanopsin in the inactive conformation, which is stabilized by the ionic interaction of these two regions. This model is supported by site-directed spin labeling and electron paramagnetic resonance spectroscopy of melanopsin, the results of which suggests a high degree of steric freedom at the third cytoplasmic loop, which is increased upon C-terminus truncation, supporting the idea that these two regions are close in three-dimensional space in wild-type melanopsin. To test for a functionally critical C-terminal conformation, calcium imaging of melanopsin mutants including a proximal C-terminus truncation (at residue 365) and proline mutation of this proximal region (H377P, L380P, Y382P) delayed melanopsin's activation rate. Mutation of all potential phosphorylation sites, including a highly conserved tyrosine residue (Y382), into alanines also delayed the activation rate. A comparison of mouse melanopsin with armadillo melanopsin-which has substitutions of various potential phosphorylation sites and a substitution of the conserved tyrosine-indicates that substitution of these potential phosphorylation sites and the tyrosine residue result in dramatically slower activation kinetics, a finding that also supports the role of phosphorylation in signaling activation. We therefore propose that melanopsin's C-terminus is proximal to intracellular loop 3, and C-terminal phosphorylation permits the ionic interaction between these two regions, thus forming a stable structural conformation that is critical for initiating G-protein signaling.
MeSH term(s)	Animals ; Light ; Light Signal Transduction ; Mice ; Phosphorylation ; Retinal Ganglion Cells/metabolism ; Rod Opsins/genetics ; Rod Opsins/metabolism
Chemical Substances	Rod Opsins ; melanopsin
Language	English
Publishing date	2020-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2020.06.013
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Article ; Online: C-Reactive Protein Promotes the Expansion of Myeloid Derived Cells With Suppressor Functions.

Jimenez, Rachel V / Kuznetsova, Valeriya / Connelly, Ashley N / Hel, Zdenek / Szalai, Alexander J

Frontiers in immunology

2019 Volume 10, Page(s) 2183

Abstract: Previously we established that human C-reactive protein (CRP) exacerbates mouse acute kidney injury ...

Abstract	Previously we established that human C-reactive protein (CRP) exacerbates mouse acute kidney injury and that the effect was associated with heightened renal accumulation of myeloid derived cells with suppressor functions (MDSC). Herein we provide direct evidence that CRP modulates the development and suppressive actions of MDSCs
MeSH term(s)	Animals ; C-Reactive Protein/immunology ; Humans ; Immunity, Innate/immunology ; Inflammation/immunology ; Mice ; Mice, Inbred C57BL ; Myeloid-Derived Suppressor Cells/immunology
Chemical Substances	C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2019-09-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.02183
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Article ; Online: An about-face for C-reactive protein?

Szalai, Alexander J

Clinical chemistry

2011 Volume 57, Issue 10, Page(s) 1351–1353

MeSH term(s)	Animals ; C-Reactive Protein/physiology ; Complement Activation ; Humans ; Male ; Scavenger Receptors, Class E/physiology
Chemical Substances	Scavenger Receptors, Class E ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2011-08-05
Publishing country	England
Document type	Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1373/clinchem.2011.172296
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Article ; Online: C-reactive protein and arteriosclerosis.

Torzewski, Jan / Fan, Jianglin / Schunkert, Heribert / Szalai, Alexander / Torzewski, Michael

Mediators of inflammation

2014 Volume 2014, Page(s) 646817

MeSH term(s)	Animals ; Arteriosclerosis/metabolism ; C-Reactive Protein/metabolism ; Humans
Chemical Substances	C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2014-05-26
Publishing country	United States
Document type	Editorial ; Introductory Journal Article
ZDB-ID	1137605-3
ISSN	1466-1861 ; 0962-9351
ISSN (online)	1466-1861
ISSN	0962-9351
DOI	10.1155/2014/646817
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Article: Arguments for and against the whole-genome sequencing of newborns.

Szalai, Csaba

American journal of translational research

2023 Volume 15, Issue 10, Page(s) 6255–6263

Abstract: Recent decades have brought enormous progress in both genetics and genomics, as well as in information technology (IT). The sequence of the human genome is now known, and although our knowledge is far from complete, great progress has been made in ... ...

Abstract	Recent decades have brought enormous progress in both genetics and genomics, as well as in information technology (IT). The sequence of the human genome is now known, and although our knowledge is far from complete, great progress has been made in understanding how the genome works. With the developments in storage capacity, artificial intelligence, and learning algorithms, we are now able to learn and interpret complex systems such as the human genome in a very short time. Perhaps the most important goal of learning about the human genome is to understand diseases better: how they develop; how their processes can be prevented or slowed down; and after diseases have developed, how they can be cured or their symptoms alleviated. The vast majority of diseases have a genetic background, i.e., genes, sequence variations, and gene-gene interactions play a role in most diseases to a greater or lesser extent. Accordingly, the first step is to discover which genes, or genomic variants, cause or contribute to the development of a particular disease in a given patient. Given that an individual's genome remains virtually unchanged throughout their life (with one or two exceptions, such as in the case of cancer, which is caused by somatic mutations), it might be considered advantageous to sequence the genome of every person at birth. In this paper, we set out to show the possible benefits of sequencing the entire genome of every human being at birth, while also discussing the main arguments against it.
Language	English
Publishing date	2023-10-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2471058-1
ISSN	1943-8141
ISSN	1943-8141
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Article ; Online: Novel automated immune turbidimetric assay for routine urinary cystatin-C determinations.

Szirmay, Balázs / Kustán, Péter / Horváth-Szalai, Zoltán / Ludány, Andrea / Lakatos, Ágnes / Mühl, Diána / Wittmann, István / Miseta, Attila / Kovács, Gábor L / Kőszegi, Tamás

Bioanalysis

2018 Volume 10, Issue 6, Page(s) 377–384

Abstract: Aim: There is no commercially available urinary cystatin-C (u-CYSC) test in the market ...

Abstract	Aim: There is no commercially available urinary cystatin-C (u-CYSC) test in the market. Therefore, we optimized and validated an automated immune turbidimetric test for u-CYSC measurements and investigated u-CYSC concentrations in acute and chronic diseases which might lead to renal tubular disorders. Materials & methods: A particle-enhanced immune turbidimetric assay was adapted and validated on a Cobas 8000/c502 analyzer. Urine samples of different patient groups were also analyzed. Results: Our method showed excellent analytical performance. U-CYSC/u-creatinine (u-CREAT) was higher in sepsis-related acute kidney injury group (p < 0.001) compared with controls and to patients with chronic hypertension and Type 2 diabetes. Conclusion: We validated a fast, sensitive, fully automated u-CYSC assay which is ideal for routine use and might be a potential complementary laboratory test to evaluate renal tubular function.
MeSH term(s)	Cystatin C/urine ; Humans ; Nephelometry and Turbidimetry/methods
Chemical Substances	Cystatin C
Language	English
Publishing date	2018-02-16
Publishing country	England
Document type	Journal Article
ISSN	1757-6199
ISSN (online)	1757-6199
DOI	10.4155/bio-2017-0228
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Article: C-Reactive Protein Impairs Dendritic Cell Development, Maturation, and Function: Implications for Peripheral Tolerance.

Jimenez, Rachel V / Wright, Tyler T / Jones, Nicholas R / Wu, Jianming / Gibson, Andrew W / Szalai, Alexander J

Frontiers in immunology

2018 Volume 9, Page(s) 372

Abstract: C-reactive protein (CRP) is the prototypical acute phase reactant, increasing in blood ...

Abstract	C-reactive protein (CRP) is the prototypical acute phase reactant, increasing in blood concentration rapidly and several-fold in response to inflammation. Recent evidence indicates that CRP has an important physiological role even at low, baseline levels, or in the absence of overt inflammation. For example, we have shown that human CRP inhibits the progression of experimental autoimmune encephalomyelitis (EAE) in CRP transgenic mice by shifting CD4
MeSH term(s)	Animals ; C-Reactive Protein/genetics ; C-Reactive Protein/metabolism ; CD11c Antigen/metabolism ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Dendritic Cells/physiology ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Humans ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Multiple Sclerosis/immunology ; Peripheral Tolerance ; Receptors, IgG/genetics
Chemical Substances	CD11c Antigen ; FCGR2B protein, human ; Receptors, IgG ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2018-03-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.00372
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Article ; Online: A Selective Inhibitor of Human C-reactive Protein Translation Is Efficacious In Vitro and in C-reactive Protein Transgenic Mice and Humans.

Jones, Nicholas R / Pegues, Melissa A / McCrory, Mark A / Singleton, Walter / Bethune, Claudette / Baker, Brenda F / Norris, Daniel A / Crooke, Rosanne M / Graham, Mark J / Szalai, Alexander J

Molecular therapy. Nucleic acids

2012 Volume 1, Page(s) e52

Abstract: ... correlation between C-reactive protein (CRP) blood concentration and worsening of RA symptoms ...

Abstract	Observational studies of patients with established rheumatoid arthritis (RA) document a positive correlation between C-reactive protein (CRP) blood concentration and worsening of RA symptoms, but whether this association is causal or not is not known. Using CRP transgenic mice (CRPTg) with collagen-induced arthritis (CIA; a rodent model of RA), we explored causality by testing if CRP lowering via treatment with antisense oligonucleotides (ASOs) targeting human CRP mRNA was efficacious and of clinical benefit. We found that in CRPtg with established CIA, ASO-mediated lowering of blood human CRP levels improved the clinical signs of arthritis. In addition, in healthy human volunteers the ASO was well tolerated and efficacious i.e., treatment achieved significant CRP lowering. ASOs targeting CRP should provide a specific and effective way to lower human CRP levels, which might be an effective therapy in patients with established RA.Molecular Therapy - Nucleic Acids (2012) 1, e52; doi:10.1038/mtna.2012.44; published online 13 November 2012.
Language	English
Publishing date	2012-11-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2662631-7
ISSN	2162-2531 ; 2162-2531
ISSN (online)	2162-2531
ISSN	2162-2531
DOI	10.1038/mtna.2012.44
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