Corrigendum: Alcohol Intake Is Associated With Elevated Serum Levels of Selenium and Selenoprotein P in Humans

Selenoprotein P is a hepatokine with antioxidative properties that eliminate a physiologic burst of reactive oxygen species required for intracellular signal transduction. Serum levels of selenoprotein P are elevated during aging and in people with type 2 diabetes, non-alcoholic fatty liver disease, and hepatitis C. However, how serum levels of full-length selenoprotein P are regulated largely remains unknown, especially in the general population. To understand the significance of serum selenoprotein P levels in the general population, we evaluated intrinsic and environmental factors associated with serum levels of full-length selenoprotein P in 1,183 subjects participating in the Shika-health checkup cohort. Serum levels of selenium were positively correlated with liver enzymes and alcohol intake and negatively correlated with body mass index. Serum levels of selenoprotein P were positively correlated with age, liver enzymes, and alcohol intake. In multiple regression analyses, alcohol intake was positively correlated with serum levels of both selenium and selenoprotein P independently of age, gender, liver enzymes, and fatty liver on ultrasonography. In conclusion, alcohol intake is associated with elevated serum levels of selenium and selenoprotein P independently of liver enzyme levels and liver fat in the general population. Moderate alcohol intake may exert beneficial or harmful effects on health, at least partly by upregulating selenoprotein P. These findings increase our understanding of alcohol-mediated redox regulation and form the basis for the adoption of appropriate drinking guidelines.

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The Cytoskeletal Elements MAP2 and NF-L Show Substantial Alterations in Different Stroke Models While Elevated Serum Levels Highlight Especially MAP2 as a Sensitive Biomarker in Stroke Patients

Molecular Neurobiology ◽

10.1007/s12035-021-02372-3 ◽

2021 ◽

Author(s):

Bianca Mages ◽

Thomas Fuhs ◽

Susanne Aleithe ◽

Alexandra Blietz ◽

Constance Hobusch ◽

...

Keyword(s):

Animal Models ◽

Neuronal Damage ◽

Degradation Products ◽

Focal Cerebral Ischemia ◽

Elevated Serum ◽

Serum Levels ◽

Ultrastructural Level ◽

Stroke Patients ◽

Protein Levels ◽

Cytoskeletal Elements

AbstractIn the setting of ischemic stroke, the neurofilament subunit NF-L and the microtubule-associated protein MAP2 have proven to be exceptionally ischemia-sensitive elements of the neuronal cytoskeleton. Since alterations of the cytoskeleton have been linked to the transition from reversible to irreversible tissue damage, the present study investigates underlying time- and region-specific alterations of NF-L and MAP2 in different animal models of focal cerebral ischemia. Although NF-L is increasingly established as a clinical stroke biomarker, MAP2 serum measurements after stroke are still lacking. Therefore, the present study further compares serum levels of MAP2 with NF-L in stroke patients. In the applied animal models, MAP2-related immunofluorescence intensities were decreased in ischemic areas, whereas the abundance of NF-L degradation products accounted for an increase of NF-L-related immunofluorescence intensity. Accordingly, Western blot analyses of ischemic areas revealed decreased protein levels of both MAP2 and NF-L. The cytoskeletal alterations are further reflected at an ultrastructural level as indicated by a significant reduction of detectable neurofilaments in cortical axons of ischemia-affected areas. Moreover, atomic force microscopy measurements confirmed altered mechanical properties as indicated by a decreased elastic strength in ischemia-affected tissue. In addition to the results from the animal models, stroke patients exhibited significantly elevated serum levels of MAP2, which increased with infarct size, whereas serum levels of NF-L did not differ significantly. Thus, MAP2 appears to be a more sensitive stroke biomarker than NF-L, especially for early neuronal damage. This perspective is strengthened by the results from the animal models, showing MAP2-related alterations at earlier time points compared to NF-L. The profound ischemia-induced alterations further qualify both cytoskeletal elements as promising targets for neuroprotective therapies.

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Sustained high expression of multiple APOBEC3 cytidine deaminases in systemic lupus erythematosus

Scientific Reports ◽

10.1038/s41598-021-87024-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Danielle Perez-Bercoff ◽

Hélène Laude ◽

Morgane Lemaire ◽

Oliver Hunewald ◽

Valérie Thiers ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Cell Death ◽

Lupus Erythematosus ◽

Immunosuppressive Treatment ◽

Elevated Serum ◽

Serum Levels ◽

Chronic Inflammatory Disease ◽

Mrna Levels ◽

Systemic Lupus ◽

Inflammatory Conditions

AbstractAPOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.

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Type 3 Deiodinase Role on Central Thyroid Hormone Action Affects the Leptin-Melanocortin System and Circadian Activity

Endocrinology ◽

10.1210/en.2016-1680 ◽

2016 ◽

Vol 158 (2) ◽

pp. 419-430 ◽

Cited By ~ 11

Author(s):

Zhaofei Wu ◽

M. Elena Martinez ◽

Donald L. St. Germain ◽

Arturo Hernandez

Keyword(s):

Energy Balance ◽

Elevated Serum ◽

Serum Levels ◽

Leptin Resistance ◽

Melanocortin System ◽

White Adipocyte ◽

Pituitary Thyroid Axis ◽

Thyroid Axis ◽

The Central Nervous System ◽

Type 3

Abstract The role of thyroid hormones (THs) in the central regulation of energy balance is increasingly appreciated. Mice lacking the type 3 deiodinase (DIO3), which inactivates TH, have decreased circulating TH levels relative to control mice as a result of defects in the hypothalamic-pituitary-thyroid axis. However, we have shown that the TH status of the adult Dio3−/− brain is opposite that of the serum, exhibiting enhanced levels of TH action. Because the brain, particularly the hypothalamus, harbors important circuitries that regulate metabolism, we aimed to examine the energy balance phenotype of Dio3−/− mice and determine whether it is associated with hypothalamic abnormalities. Here we show that Dio3−/− mice of both sexes exhibit decreased adiposity, reduced brown and white adipocyte size, and enhanced fat loss in response to triiodothyronine (T3) treatment. They also exhibit increased TH action in the hypothalamus, with abnormal expression and T3 sensitivity of genes integral to the leptin-melanocortin system, including Agrp, Npy, Pomc, and Mc4r. The normal to elevated serum levels of leptin, and elevated and repressed expression of Agrp and Pomc, respectively, suggest a profile of leptin resistance. Interestingly, Dio3−/− mice also display elevated locomotor activity and increased energy expenditure. This occurs in association with expanded nighttime activity periods, suggesting a disrupted circadian rhythm. We conclude that DIO3-mediated regulation of TH action in the central nervous system influences multiple critical determinants of energy balance. Those influences may partially compensate each other, with the result likely contributing to the decreased adiposity observed in Dio3−/− mice.

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Elevated Serum Transforming Growth Factor β1 Levels in Epstein-Barr Virus-Associated Diseases and Their Correlation with Virus-Specific Immunoglobulin A (IgA) and IgM

Journal of Virology ◽

10.1128/jvi.74.5.2443-2446.2000 ◽

2000 ◽

Vol 74 (5) ◽

pp. 2443-2446 ◽

Cited By ~ 30

Author(s):

Jingwu Xu ◽

Ali Ahmad ◽

James F. Jones ◽

Riccardo Dolcetti ◽

Emanuela Vaccher ◽

...

Keyword(s):

Growth Factor ◽

Epstein Barr Virus ◽

Transforming Growth Factor ◽

Immunoglobulin A ◽

Elevated Serum ◽

Transforming Growth Factor Β ◽

Serum Levels ◽

Barr Virus ◽

Associated Diseases ◽

Epstein Barr

ABSTRACT Transforming growth factor β (TGF-β) is an immunosuppressive cytokine which can induce immunoglobulin A (IgA) switch and Epstein-Barr virus (EBV) replication in latently infected cells. Here we report elevated serum levels of TGF-β in various EBV-associated diseases correlating positively with EBV-specific IgA titers and negatively with IgM titers, suggesting a role for this cytokine in the pathogenesis of these diseases.

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MAPK/AP-1-Targeted Anti-Inflammatory Activities of Xanthium strumarium

The American Journal of Chinese Medicine ◽

10.1142/s0192415x16500622 ◽

2016 ◽

Vol 44 (06) ◽

pp. 1111-1125 ◽

Cited By ~ 10

Author(s):

Muhammad Jahangir Hossen ◽

Mi-Yeon Kim ◽

Jae Youl Cho

Keyword(s):

Mouse Model ◽

Therapeutic Potential ◽

Inflammatory Diseases ◽

Elevated Serum ◽

Human Monocyte ◽

Serum Levels ◽

Mitogen Activated Protein Kinase ◽

Xanthium Strumarium ◽

U937 Cells ◽

Anti Inflammatory

Xanthium strumarium L. (Asteraceae), a traditional Chinese medicine, is prescribed to treat arthritis, bronchitis, and rhinitis. Although the plant has been used for many years, the mechanism by which it ameliorates various inflammatory diseases is not yet fully understood. To explore the anti-inflammatory mechanism of methanol extracts of X. strumarium (Xs-ME) and its therapeutic potential, we used lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells and human monocyte-like U937 cells as well as a LPS/D-galactosamine (GalN)-induced acute hepatitis mouse model. To find the target inflammatory pathway, we used holistic immunoblotting analysis, reporter gene assays, and mRNA analysis. Xs-ME significantly suppressed the up-regulation of both the activator protein (AP)-1-mediated luciferase activity and the production of LPS-induced proinflammatory cytokines, including interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor (TNF)-[Formula: see text]. Moreover, Xs-ME strongly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW264.7 and U937 cells. Additionally, these results highlighted the hepatoprotective and curative effects of Xs-ME in a mouse model of LPS/D-GalN-induced acute liver injury, as assessed by elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and histological damage. Therefore, our results strongly suggest that the ethnopharmacological roles of Xs-ME in hepatitis and other inflammatory diseases might result from its inhibitory activities on the inflammatory signaling of MAPK and AP-1.

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Serum Soluble Triggering Receptor Expressed on Myeloid Cells-1 and Procalcitonin Can Reflect Sepsis Severity and Predict Prognosis: A Prospective Cohort Study

Mediators of Inflammation ◽

10.1155/2014/641039 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 12

Author(s):

Zhenyu Li ◽

Hongxia Wang ◽

Jian Liu ◽

Bing Chen ◽

Guangping Li

Keyword(s):

Sofa Score ◽

Prognostic Significance ◽

Elevated Serum ◽

Myeloid Cells ◽

Serum Levels ◽

Clinical Severity ◽

Apache Ii ◽

Apache Ii Score ◽

Survival Group ◽

Severity Scores

Objective. To investigate the prognostic significance of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), procalcitonin (PCT), N-terminal probrain natriuretic peptide (NT-pro-BNP), C-reactive protein (CRP), cytokines, and clinical severity scores in patients with sepsis.Methods. A total of 102 patients with sepsis were divided into survival group (n=60) and nonsurvival group (n=42) based on 28-day mortality. Serum levels of biomarkers and cytokines were measured on days 1, 3, and 5 after admission to an ICU, meanwhile the acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were calculated.Results. Serum sTREM-1, PCT, and IL-6 levels of patients in the nonsurvival group were significantly higher than those in the survival group on day 1 (P<0.01). The area under a ROC curve for the prediction of 28 day mortality was 0.792 for PCT, 0.856 for sTREM-1, 0.953 for SOFA score, and 0.923 for APACHE II score. Multivariate logistic analysis showed that serum baseline sTREM-1 PCT levels and SOFA score were the independent predictors of 28-day mortality. Serum PCT, sTREM-1, and IL-6 levels showed a decrease trend over time in the survival group (P<0.05). Serum NT-pro-BNP levels showed the predictive utility from days 3 and 5 (P<0.05).Conclusion. In summary, elevated serum sTREM-1 and PCT levels provide superior prognostic accuracy to other biomarkers. Combination of serum sTREM-1 and PCT levels and SOFA score can offer the best powerful prognostic utility for sepsis mortality.

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Increased Serum Interleukin 22 in Patients with Rheumatoid Arthritis and Correlation with Disease Activity

The Journal of Rheumatology ◽

10.3899/jrheum.111027 ◽

2012 ◽

Vol 39 (7) ◽

pp. 1320-1325 ◽

Cited By ~ 60

Author(s):

LAURINDO FERREIRA da ROCHA ◽

ÂNGELA LUZIA BRANCO PINTO DUARTE ◽

ANDRÉA TAVARES DANTAS ◽

HENRIQUE ATAÍDE MARIZ ◽

IVAN da ROCHA PITTA ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Mononuclear Cells ◽

Activity Index ◽

Elevated Serum ◽

Serum Levels ◽

Peripheral Blood Mononuclear ◽

Additional Tool ◽

Bone Erosions ◽

Interleukin 22

Objective.To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA).Methods.IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for 28 joints (DAS28)], serological markers, bone erosions, and demographic factors were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA and 14 controls were purified and stimulatedin vitrowith phorbol myristate acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated by ELISA.Results.IL-22 levels were increased in patients with RA compared with controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity was correlated with higher levels of IL-22 in patients with RA (mean 575.08 pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22 levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels of IL-22 in patients with RA than controls but this was not significant (mean 584.75 pg/ml and 295.57 pg/ml; p = 0.553).Conclusion.IL-22 is elevated in the serum of patients with established RA. Elevated serum IL-22 allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RF antibodies and longterm disease. IL-22 is associated with bone-destructive disease.

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