• Inflammatory bowel disease
• colectomy
• hospitalisation
• hydrocortisone
• inflammation

• Adult
• Female
• Humans
• Male
• Acute Disease
• Albumins/administration & dosage
• Albumins/therapeutic use
• Anti-Inflammatory Agents/administration & dosage
• Colectomy/methods
• Colitis, Ulcerative/diet therapy
• Colitis, Ulcerative/drug therapy
• Colitis, Ulcerative/therapy
• Combined Modality Therapy/methods
• Enteral Nutrition/methods
• Hydrocortisone/administration & dosage
• Hydrocortisone/blood
• Infusions, Intravenous
• Steroids/administration & dosage
• Steroids/therapeutic use
• Treatment Outcome
• Severity of Illness Index

• 55/4/11/CARE-ID/2018-NCD-II Centre for Advanced Research and Excellence in intestinal diseases

• Latina
• Nonalcoholic fatty liver disease
• White
• fibrosis
• noninvasive scores
• women

• Adult
• Female
• Humans
• Middle Aged
• Hispanic or Latino
• Liver Cirrhosis/ethnology
• Liver Cirrhosis/pathology
• Models, Biological
• Non-alcoholic Fatty Liver Disease/ethnology
• Non-alcoholic Fatty Liver Disease/pathology
• White

• Humans
• Fluorescent Dyes/chemistry
• Fluorescent Dyes/chemical synthesis
• Serum Albumin, Human/analysis
• Serum Albumin, Human/metabolism
• Molecular Docking Simulation
• Molecular Structure
• Optical Imaging

• caspase 3
• inflammatory mediators
• kidney transplant
• renal injury
• transcription factor

• Biomarker for oxidative stress
• Colorimetric assay
• Cys34 reactivity
• Cysteine reactivity
• Oxidized albumin
• Serum albumin

• Animals
• Humans
• Biomarkers/blood
• Mammals/blood
• Oxidation-Reduction
• Oxidative Stress
• Serum Albumin/analysis
• Spectrophotometry

• albumin binding capacity
• human mercaptalbumin
• human nonmercaptalbumin-1
• human nonmercaptalbumin-2
• neutrophil function

• Humans
• End Stage Liver Disease/drug therapy
• Serum Albumin
• Liver Cirrhosis/drug therapy
• Liver Cirrhosis/metabolism
• Oxidative Stress
• Oxidation-Reduction

• KLI 741 Austrian Science Fund FWF
• Albus Award 2016 Grifols

• D‐dimer
• VEGF
• ovarian hyperstimulation syndrome
• peritoneal effusion
• venous thromboembolism

• albumin
• carbonyl stress
• hemoglobin
• metal-binding centers
• nitrosative stress
• oxidative stress
• thiols

• Metals/chemistry
• Metals/metabolism
• Oxidative Stress
• Oxidation-Reduction
• Protein Processing, Post-Translational

• Anti-inflammatory
• Apoptosis
• Cardioprotective
• Oxidative stress
• Traditional Chinese medicine

• Myocytes, Cardiac/drug effects
• Myocytes, Cardiac/metabolism
• Myocytes, Cardiac/radiation effects
• Myocardium/cytology
• Myocardium/metabolism
• Myocardium/pathology
• Heart/radiation effects
• Rats, Sprague-Dawley
• Animals, Newborn
• Primary Cell Culture
• Animals
• Rats
• Cell Survival/drug effects
• Cell Survival/radiation effects
• Phenanthrenes/pharmacology
• Drugs, Chinese Herbal/pharmacology
• Salvia miltiorrhiza/chemistry
• Oxidative Stress/drug effects
• Oxidative Stress/radiation effects
• Cardiotonic Agents/pharmacology
• Antioxidants/pharmacology
• Anti-Inflammatory Agents, Non-Steroidal/pharmacology
• Cardiotoxicity/drug therapy
• Cardiotoxicity/etiology
• Cardiotoxicity/pathology
• Disease Models, Animal
• Specific Pathogen-Free Organisms
• p38 Mitogen-Activated Protein Kinases/metabolism
• MAP Kinase Signaling System/drug effects

• Differentiated thyroid cancer
• Ferroptosis
• Lipid peroxidation
• Radioactive iodine therapy
• Serum albumin

• Humans
• Thyroid Neoplasms/genetics
• Thyroid Neoplasms/drug therapy
• Cysteine/metabolism
• Retrospective Studies
• Iodine Radioisotopes/therapeutic use
• Ferroptosis/genetics
• Serum Albumin, Human/metabolism
• Oxidation-Reduction
• Adenocarcinoma

• biomarker
• diabetes mellitus
• human mercaptalbumin
• human nonmercaptalbumin
• human serum albumin
• oxidative stress

• Humans
• Glycated Hemoglobin
• Diabetes Mellitus, Type 1
• Serum Albumin, Human/metabolism
• Diabetes Mellitus, Type 2
• Serum/metabolism
• Oxidative Stress
• Oxidation-Reduction

• KLI 1076 Austrian Science Fund FWF

• NETs
• ROS
• chemotaxis
• cirrhosis
• neutrophils
• phagocytosis

• albumin
• binding capacity
• critical care
• electron paramagnetic resonance
• intensive care medicine
• sepsis
• septic shock
• spin-probe technique

• Humans
• Shock, Septic/diagnosis
• Pilot Projects
• Critical Illness
• Prospective Studies
• Sepsis/diagnosis
• Albumins
• Critical Care

• Acute decompensation
• Binding properties
• Chronic liver failure
• Dansylsarcosine
• Effective albumin
• Human serum albumin
• Oxidative modification
• electron paramagnetic resonance

• Biomarkers
• Bottom-up
• Human serum albumin
• Liver diseases
• Posttranslational modifications
• Top-down

• FXa inhibitors
• apixaban
• betrixaban
• commercially available FXa inhibitors
• direct oral FXa inhibitors
• edoxaban
• fluorescence
• human serum albumin
• isothermal titration calorimetry
• molecular modeling
• rivaroxaban

• Humans
• Anticoagulants
• Binding Sites
• Calorimetry/methods
• Molecular Docking Simulation
• Protein Binding
• Serum Albumin, Human/chemistry
• Spectrometry, Fluorescence
• Thermodynamics
• Venous Thromboembolism
• Factor X/antagonists & inhibitors

The liver is the site of synthesis of the majority of circulating proteins. Besides initial polypeptide synthesis, sophisticated machinery is involved in the further processing of proteins by removing parts of them and/or adding functional groups and small molecules tailoring the final molecule to suit its physiological purpose. Posttranslational modifications (PTMs) design a network of molecules with the common protein ancestor but with slightly or considerably varying activity/localization/purpose. PTMs can change under pathological conditions, giving rise to aberrant or overmodified proteins. Undesired changes in the structure of proteins most often accompany undesired changes in their function, such as reduced activity or the appearance of new effects. Proper protein processing is essential for the reactions in living beings and crucial for the overall quality control. Modifications that occur on proteins synthesized in the liver whose PTMs are cirrhosis-related are oxidation, nitration, glycosylation, acetylation, and ubiquitination. Some of them predominantly affect proteins that remain in liver cells, whereas others predominantly occur on proteins that leave the liver or originate from other tissues and perform their function in the circulation. Altered PTMs of certain proteins are potential candidates as biomarkers of liver-related diseases, including cirrhosis. This review will focus on PTMs on proteins whose structural changes in cirrhosis exert or are suspected to exert the most serious functional consequences.

• Liver cirrhosis
• Post-translational modifications
• Circulation
• Protein function
• Protein structure
• Chronic liver disease

• Acetylation
• Humans
• Liver Cirrhosis
• Peptides/metabolism
• Phosphorylation
• Protein Processing, Post-Translational
• Proteins/metabolism

Bladder cancer has been increasing globally. Urinary cytology is considered a major screening method for bladder cancer, but it has poor sensitivity. This study aimed to utilize clinical laboratory data and machine learning methods to build predictive models of bladder cancer. A total of 1336 patients with cystitis, bladder cancer, kidney cancer, uterus cancer, and prostate cancer were enrolled in this study. Two-step feature selection combined with WEKA and forward selection was performed. Furthermore, five machine learning models, including decision tree, random forest, support vector machine, extreme gradient boosting (XGBoost), and light gradient boosting machine (GBM) were applied. Features, including calcium, alkaline phosphatase (ALP), albumin, urine ketone, urine occult blood, creatinine, alanine aminotransferase (ALT), and diabetes were selected. The lightGBM model obtained an accuracy of 84.8% to 86.9%, a sensitivity 84% to 87.8%, a specificity of 82.9% to 86.7%, and an area under the curve (AUC) of 0.88 to 0.92 in discriminating bladder cancer from cystitis and other cancers. Our study provides a demonstration of utilizing clinical laboratory data to predict bladder cancer.

Mitochondria are entrusted with the challenging task of providing energy through the generation of ATP, the universal cellular currency, thereby being highly flexible to different acute and chronic nutrient demands of the cell. The fact that mitochondrial diseases (genetic disorders caused by mutations in the nuclear or mitochondrial genome) manifest through a remarkable clinical variation of symptoms in affected individuals underlines the far-reaching implications of mitochondrial dysfunction. The study of mitochondrial function in genetic or non-genetic diseases therefore requires a multi-angled approach. Taking into account that the liver is among the organs richest in mitochondria, it stands to reason that in the process of unravelling the pathogenesis of liver-related diseases, researchers give special focus to characterizing mitochondrial function. However, mitochondrial dysfunction is not a uniformly defined term. It can refer to a decline in energy production, increase in reactive oxygen species and so forth. Therefore, any study on mitochondrial dysfunction first needs to define the dysfunction to be investigated. Here, we review the alterations of mitochondrial function in liver cirrhosis with emphasis on acutely decompensated liver cirrhosis and acute-on-chronic liver failure (ACLF), the latter being a form of acute decompensation characterized by a generalized state of systemic hyperinflammation/immunosuppression and high mortality rate. The studies that we discuss were either carried out in liver tissue itself of these patients, or in circulating leukocytes, whose mitochondrial alterations might reflect tissue and organ mitochondrial dysfunction. In addition, we present different methodological approaches that can be of utility to address the diverse aspects of hepatocyte and leukocyte mitochondrial function in liver disease. They include assays to measure metabolic fluxes using the comparatively novel Biolog’s MitoPlates in a 96-well format as well as assessment of mitochondrial respiration by high-resolution respirometry using Oroboros’ O2k-technology and Agilent Seahorse XF technology.

• acute decompensation
• cirrhosis
• immunometabolism
• mitochondrial dysfunction
• organ failure
• systemic inflammation

• ACLF
• Acute-on-chronic liver failure
• Ascites
• Cirrhosis
• DAMP
• Hepatic encephalopathy
• Organ failure
• PAMP
• Tissue injury
• Variceal bleeding

Human serum albumin (HSA) constitutes the primary transporter of fatty acids, bilirubin, and other plasma compounds. The binding, transport, and release of its cargos strongly depend on albumin conformation, which is affected by bound ligands induced by physiological and pathological conditions. HSA is both highly oxidized and heavily loaded with fatty acids and bilirubin in chronic liver disease. By employing small-angle X-ray scattering we show that HSA from the plasma of chronic liver disease patients undergoes a distinct opening compared to healthy donors. The extent of HSA opening correlates with clinically relevant variables, such as the model of end-stage liver disease score, bilirubin, and fatty acid levels. Although the mild oxidation of HSA in vitro does not alter overall structure, the alteration of patients’ HSA correlates with its redox state. This study connects clinical data with structural visualization of albumin dynamicity in solution and underlines the functional importance of albumin’s inherent flexibility.

Paar et al. propose a SAXS-based approach to study conformations of human serum albumin (HSA) from patients with liver disease and a structural understanding of HSA dynamicity and its correlation with clinical variables are provided. Using it on real clinical samples, this study has concrete practical implications too.

• albumin
• biomarker
• oxidative stress
• serum albumin redox state

• Albumin
• Free radicals
• Glaucoma
• Open-angle glaucoma
• Vitreous

Introduction: Crohn’s disease (CD) is characterized by chronic and relapsing inflammation of the gastro-intestinal tract. It is assumed that oxidative stress contributes to CD pathogenesis, but systemic biomarkers for oxidative stress in CD are not yet identified. A reduction in free thiol groups in plasma proteins (“plasma free thiols”) reflects systemic oxidative stress since they are prime substrates for reactive oxygen species. Here, we determined the concentrations of plasma free thiols in CD patients and healthy controls and studied the putative correlation with disease parameters.

Methods: Free thiols were quantified in plasma of patients with CD in clinical remission [according to the Harvey Bradshaw Index (HBI)] and healthy controls and adjusted for plasma albumin. Albumin-adjusted free thiol concentrations were analyzed for associations with clinical and biochemical disease markers.

Results: Mean plasma free thiol concentrations were significantly lower in patients with CD (n = 51) compared to healthy controls (n = 27) (14.7 ± 2.4 vs. 17.9 ± 1.8 μmol/g albumin; P < 0.001). Patients with CD with above-average free thiols had significantly lower CRP levels (median 1.4 [interquartile range] [0.4; 2.6] vs. 3.6 [0.6; 7.0] mg/L; P < 0.05) and BMI (23.6 ± 4.8 vs. 27.1 ± 5.2 kg/m²; P < 0.05). Patients with CD having solely colonic disease demonstrated markedly reduced plasma free thiol concentrations compared to patients with ileocolonic involvement (13.2 ± 1.8 vs. 15.2 ± 2.2 μmol/g; P < 0.05). Finally, plasma free thiol concentrations negatively correlated with biomarkers of inflammation, including hsCRP, SAA, IL-17A (all P < 0.05), and VEGF.

Conclusion: Plasma free thiols are reduced in patients with CD in clinical remission compared to healthy controls. Thus, subclinical CD disease activity is reflected by systemic oxidative stress and plasma free thiols may be a relevant therapeutic target and biomarker to monitor disease activity in CD.

• Crohn’s disease
• biomarker
• disease activity
• free thiols
• oxidative stress
• redox status

Liver cirrhosis yearly causes 1.2 million deaths worldwide, ranking as the 10th leading cause of death in the most developed countries. High susceptibility to infections along with a significant risk for infection-related mortality justifies the description of liver cirrhosis as the world's most common immunodeficiency syndrome. Liver cirrhosis is an end-stage organic disease hallmarked by a multifaceted immune dysfunction due to deterioration of antimicrobial recognition and elimination mechanisms in macrophages along with an impaired antigen presentation ability in circulating monocytes. Bacterial translocation supports—and is supported by—uncontrolled activation of immune cell responses and/or loss of toll-like receptor (TLR) tolerance, which can turn exaggerated inflammatory responses to systemic inflammation. Lipopolysaccharide (LPS) or endotoxin boosts systemic inflammatory activity through activation of TLR-2- and TLR-4-dependent pathways and facilitate a massive production of cytokines. This, in turn, results into elevated secretion of reactive oxygen species (ROS), which further enhances intestinal hyperpermeability and thus sustains a vicious circle of events widely known as “leaky gut.” Albumin can be of particular benefit in cirrhotic patients with spontaneous bacterial peritonitis and/or hepatorenal syndrome type of acute kidney injury (HRS-AKI) due to anti-inflammatory and antioxidative stress as well as volume-expanding properties and endothelial-stabilizing attributes. However, presence of autoantibodies against albumin in patients with liver cirrhosis has been described. Although previous research suggested that these antibodies should be regarded as naturally occurring antibodies (NOA), the origin of the antialbumin immune response is obscure. High occurrence of NAO/albumin complexes in patients with liver disease might reflect a limited clearance capacity due to bypassing portal circulation. Moreover, high burden of oxidized albumin is associated with less favorable outcome in patients with liver cirrhosis. To date, there is no data available as to whether oxidized forms of albumin result in neoepitopes recognized by the immune system. Nevertheless, it is reasonable to hypothesize that these alterations may have the potential to induce antialbumin immune responses and thus favor systemic inflammation.

Neutrophil extracellular traps (NETs) promote cancer metastasis in preclinical models following massive exogenous inflammatory stimuli. It remains unknown whether cancer hosts under physiologic conditions experience NETosis and consequent metastasis. Here we show that plasma redox imbalance caused by albumin oxidation promotes inflammation-independent NETosis. Albumin is the major source of free thiol that maintains redox balance. Oxidation of albumin-derived free thiol is sufficient to trigger NETosis via accumulation of reactive oxygen species within neutrophils. The resultant NETs are found predominantly within lungs where they contribute to the colonization of circulating tumor cells leading to pulmonary metastases. These effects are abrogated by pharmacologic inhibition of NET formation. Moreover, albumin oxidation is associated with pulmonary metastasis in a cohort of head and neck cancer patients. These results implicate plasma redox balance as an endogenous and physiologic regulator of NETosis and pulmonary cancer metastasis, providing new therapeutic and diagnostic opportunities for combatting cancer progression.

Neutrophil extracellular traps (NETs) are known to promote metastasis in mouse models. Here the authors show plasma redox imbalance caused by albumin oxidation to induce inflammation-independent NETosis and lung metastasis, and albumin oxidation and reduced plasma free thiol to be associated with lung metastasis in a cohort of head and neck cancer patients.

• Humans
• Albumins
• Cytokines
• Inflammation
• Leukocytes
• Liver Cirrhosis
• p38 Mitogen-Activated Protein Kinases

• R01 DK044234 NIDDK NIH HHS
• R01 AA022601 NIAAA NIH HHS
• R01 DK111678 NIDDK NIH HHS

• Albumin
• Cirrhosis
• Inflammation
• Leukocytes

The redox state of plasma albumin shifts in response to dietary protein intake in growing rats, and the shift is more sensitive than that of plasma albumin level, a classical marker of protein nutritional status. While it has been suggested that plasma albumin redox state could be useful as a novel marker of protein nutritional status, the above animal model is highly sensitive to dietary protein intake and the observation may not be extrapolated widely to humans. This study aimed to investigate whether albumin redox state also reflects protein nutritional status in adult rats, which have a lower dietary protein requirement and are less responsive to protein intake. Male adult rats were placed on AIN-93M diet (14% casein), or AIN-93M-based low protein diets (10 or 5% casein) ad libitum for 24 weeks. Whereas there was no significant difference in body weight between the groups at the end of the experimental period, the 5% casein diet group had the smallest gastrocnemius muscle weight among the groups, which was significantly lower than that of the 10% casein diet group. Plasma albumin level was also lower in the 5% casein diet group compared with the other groups, but the differences were limited and inconsistent during the experimental period. Among the albumin redox isoforms such as mercaptalbumin, non-mercaptalbumin-1, and non-mercaptalbumin-2, the ratio of non-mercaptalbumin-1 among total albumin was significantly higher in the 5% casein diet group, and the increase remained constant throughout the experimental period. Increased non-mercaptalbumin-1 ratio would thus demonstrate the presence of potential protein undernutrition in adult rats, as manifested only by a decreased gain in a specific type of skeletal muscle; non-mercaptalbumin-1 among total albumin ratio could be useful as a robust marker of protein nutritional status, contributing to prevention of protein undernutrition-related diseases such as frailty and sarcopenia.

• adult rat
• dietary protein intake
• low protein diet
• mercaptalbumin
• non-mercaptalbumin
• plasma albumin
• protein undernutrition
• redox state of plasma albumin

• Albumin
• Effective albumin concentration
• Liver cirrhosis
• Posttranslational changes

• Branched-chain amino acids
• Hepatic encephalopathy
• Lactulose
• Probiotics
• Rifaximin
• Treatment

• Amino Acids, Branched-Chain/therapeutic use
• Anti-Bacterial Agents/therapeutic use
• Disease Management
• Fecal Microbiota Transplantation
• Gastrointestinal Agents/therapeutic use
• Hepatic Encephalopathy/drug therapy
• Hepatic Encephalopathy/therapy
• Humans
• Lactulose/therapeutic use
• Probiotics/therapeutic use
• Rifamycins/therapeutic use
• Rifaximin

• Hepatic encephalopathy
• Hyperammonemia
• Intestinal
• Mannitol
• Stress oxidative

A commercially available styryl based fluorophore in the near-IR region shows exceptional turn-on emission for serum albumins.

Albumin is the major protein in the serum of mammals. It is synthesized exclusively in the liver, before being secreted into the circulation. Similar to skeletal muscle protein, albumin synthesis is stimulated by dietary amino acids and proteins as well as exercise. Albumin has three isoforms based on the redox states of the free cysteine residue at position 34. The redox state of serum albumin has long been extensively investigated in terms of oxidative stress-related chronic diseases, with the redox state of serum albumin having been regarded as a marker of systemic oxidative stress. However, according to recent animal studies, the redox state of serum albumin is modulated by albumin turnover and may also reflect amino acid/protein nutritional status. Furthermore, as the redox state of serum albumin is modulated by exercise training, measuring the pre- and post-exercise redox states of serum albumin in athletes may be useful in assessing amino acid/protein nutritional status and exercise-induced oxidative stress, which are closely associated with skeletal muscle adaptive responses. This article extensively reviews serum albumin and the redox state of albumin in the context of amino acid/protein nutritional status and exercise training.

• amino acids
• exercise
• oxidative stress
• protein
• redox state of serum albumin
• skeletal muscle

• Amino Acids/administration & dosage
• Amino Acids/metabolism
• Animals
• Biomarkers/blood
• Dietary Proteins/administration & dosage
• Dietary Proteins/metabolism
• Exercise/physiology
• Humans
• Nutritional Status
• Oxidation-Reduction
• Oxidative Stress
• Serum Albumin, Human/metabolism
• Time Factors

Ellagic acid has been proven to have anticancer, antimutation, antimicrobial and antiviral functions. The present study investigated whether treatment with ellagic acid was able to prevent tetrachloride (CCl4)-induced cirrhosis through the inhibition of reactive oxygen species (ROS) formation and angiogenesis. CCl₄ diluted in olive oil at a final concentration of 10% was used to induce a cirrhosis model. A total of 40 mice were random allocated into four groups, as follows: Control, cirrhosis model, 7.5 mg/kg ellagic acid and 15 mg/kg ellagic acid groups. In the control group, mice were given normal saline. The results indicated that ellagic acid exerted a protective effect, evidently preventing CCl₄-induced cirrhosis. In addition, treatment with ellagic acid significantly inhibited collagen I and inducible nitric oxide synthase protein expression levels in CCl₄-induced cirrhosis mice. Oxidative stress and ROS formation were also significantly reduced by ellagic acid treatment. The protein expression levels of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2), and the caspase-3 activity were significantly inhibited by treatment with ellagic acid. In conclusions, these results suggest that ellagic acid exerted protective effects against CCl₄-induced cirrhosis through the inhibition of ROS formation and angiogenesis.

• ellagic acid
• tetrachloride-induced cirrhosis

• Chronic hepatitis B infection
• IMAR
• fibrosis
• ischemia-modified albumin

• Human serum albumin
• Liquid chromatography–mass spectrometry
• Liver cirrhosis
• Non-oncotic properties
• Post-translational modifications
• Spectroscopic methods

Type I interferons are major players against viral infections and mediate their function by the induction of Interferon regulated genes (IRGs). Recently, it became obvious that these cytokines have a multitude of additional functions. Due to the unique features of the chickens’ immune system, available data from mouse models are not easily transferable; hence we performed an extensive analysis of chicken IRGs.

A broad database search for homologues to described mammalian IRGs (common IRGs, cIRGs) was combined with a transcriptome analysis of spleen and lung at different time points after application of IFNα. To apply physiological amounts of IFN, half-life of IFN in the chicken was determined. Interestingly, the calculated 36 min are considerably shorter than the ones obtained for human and mouse. Microarray analysis revealed many additional IRGs (newly identified IRGs; nIRGs) and network analysis for selected IRGs showed a broad interaction of nIRGs among each other and with cIRGs. We found that IRGs exhibit a highly tissue and time specific expression pattern as expression quality and quantity differed strongly between spleen and lung and over time. While in the spleen for many affected genes changes in RNA abundance peaked already after 3 h, an increasing or plateau-like regulation after 3, 6 and 9 h was observed in the lung.

The induction or suppression of IRGs in chickens is both tissue and time specific and beside known antiviral mechanisms type I IFN induces many additional cellular functions. We confirmed many known IRGs and established a multitude of so far undescribed ones, thus providing a large database for future research on antiviral mechanisms and additional IFN functions in non-mammalian species.

The online version of this article (doi:10.1186/s12864-017-3641-6) contains supplementary material, which is available to authorized users.

• Chicken
• Expression profile
• Half-life
• IFNα
• IRG

• albumin
• biomarker
• cysteine-34
• diabetes mellitus
• kidney disease
• ligand binding
• liver disease
• oxidative stress
• posttranslational modification