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Liu T, Sui M, Tian M, Wu N, Zhao S, Wang Y, Yang Y, Ma S, Jiao D, Wang L, Feng Y, Zhang Y, Qin C, Liu C, Qi J, Zhu Q. Sulfonated albumin from hepatocytes accelerates liver fibrosis in nonalcoholic fatty liver disease through endoplasmic reticulum stress. Free Radic Biol Med 2025; 228:150-162. [PMID: 39743026 DOI: 10.1016/j.freeradbiomed.2024.12.055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 12/15/2024] [Accepted: 12/28/2024] [Indexed: 01/04/2025]
Abstract
BACKGROUND Posttranslational modifications (PTM) of albumin occur in liver diseases; however, little is known about the source and function of sulfonated albumin, a significant modification of albumin occurring in nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the mechanism underlying sulfonated albumin production and its role in the progression of NAFLD-related liver fibrosis. METHODS Serum samples from healthy controls and patients with NAFLD were used to measure the proportion of sulfonated albumin. Mice models with NAFLD fed with high-fat diet (HFD) and methionine choline-deficient diet (MCD) were constructed. RNA sequencing, KEGG analysis, and GSEA were used to explore the mechanism of sulfonated albumin production and its mechanism of activating hepatic stellate cells (HSCs) and promoting the progression of liver fibrosis in NAFLD. RESULTS Sulfonated albumin levels increased significantly in both human and mouse NAFLD serum samples. In vivo studies in mice have shown that the intraperitoneal injection of sulfonated albumin promotes inflammation, hepatic steatosis, and liver fibrosis in NAFLD. In addition, autophagy has been verified as a key mechanism in the regulation of sulfonated albumin production. We also demonstrated that reactive oxygen species (ROS) production depends on the accumulation of damaged mitochondria and affects the production of sulfonated albumin under the regulation of autophagy. Hepatocyte-derived sulfonated albumin activates HSCs through the GAL3 receptor, thereby activating the endoplasmic reticulum (ER) stress pathway and promoting profibrotic activation of HSCs. CONCLUSIONS Our study demonstrated that sulfonated albumin activated HSCs through GAL3, thereby accelerating NAFLD-related liver fibrosis. Serum sulfonated albumin may be a potential diagnostic marker for liver fibrosis and an important target for the treatment of NAFLD-related liver fibrosis.
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Affiliation(s)
- Tiantian Liu
- Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China; Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Minghao Sui
- Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China; Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China; Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Miaomiao Tian
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China; Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Nijin Wu
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China; Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Songbo Zhao
- Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Yingchun Wang
- Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Yinuo Yang
- Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China; Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China; Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Shujun Ma
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China; Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China; Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Deyan Jiao
- Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Le Wang
- Department of Health Care Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Yuemin Feng
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Yahui Zhang
- Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Chengyong Qin
- Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China; Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China
| | - Chenxi Liu
- Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China; Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
| | - Jianni Qi
- Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China; Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
| | - Qiang Zhu
- Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China; Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
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Kronsten VT, Shawcross DL. Clinical Implications of Inflammation in Patients With Cirrhosis. Am J Gastroenterol 2025; 120:65-74. [PMID: 39194320 PMCID: PMC11676607 DOI: 10.14309/ajg.0000000000003056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/19/2024] [Indexed: 08/29/2024]
Abstract
Cirrhosis-associated immune dysfunction refers to the concurrent systemic inflammation and immunoparesis evident across the disease spectrum of chronic liver disease, ranging from the low-grade inflammatory plasma milieu that accompanies compensated disease to the intense high-grade inflammatory state with coexistent severe immune paralysis that defines acute decompensation and acute-on-chronic liver failure. Systemic inflammation plays a crucial role in the disease course of cirrhosis and is a key driver for acute decompensation and the progression from compensated to decompensated cirrhosis. Severe systemic inflammation is fundamental to the development of organ dysfunction and failure and, in its most extreme form, acute-on-chronic liver failure. Systemic inflammation propagates the development of hepatic encephalopathy and hepatorenal syndrome-acute kidney injury. It may also be involved in the pathogenesis of further complications such as hepatocellular carcinoma and mental illness. Those patients with the most profound systemic inflammation have the worst prognosis. Systemic inflammation exerts its negative clinical effects through a number of mechanisms including nitric oxide-mediated increased splanchnic vasodilation, immunopathology, and metabolic reallocation.
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Affiliation(s)
- Victoria T. Kronsten
- Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London
- Institute of Liver Studies, King's College Hospital, Denmark Hill, London
| | - Debbie L. Shawcross
- Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London
- Institute of Liver Studies, King's College Hospital, Denmark Hill, London
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Trebicka J, Garcia-Tsao G. Controversies regarding albumin therapy in cirrhosis. Hepatology 2025; 81:288-303. [PMID: 37540192 PMCID: PMC11643133 DOI: 10.1097/hep.0000000000000521] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 05/26/2023] [Indexed: 08/05/2023]
Abstract
Albumin is the most abundant protein in the human body and is synthetized exclusively by the liver. Therefore, serum albumin levels are reduced in acute and/or chronic liver disease. In cirrhosis, low levels of albumin predict the outcome. In advanced cirrhosis, the quality of albumin is decreased due to high oxidative stress and a proinflammatory state. Therefore, the administration of i.v. albumin would seem to be of pathophysiological relevance and benefit. Yet, the questions that remain are who, when, how much, and how often. While albumin infusion is recommended after large-volume paracentesis, at diagnosis of spontaneous bacterial peritonitis, in acute kidney injury, and in hepatorenal syndrome, the amount and schedule of albumin to be administered require refinement, particularly given complications related to volume overload that have become increasingly apparent. Other indications for albumin such as infections other than spontaneous bacterial peritonitis, hyponatremia, HE, prevention of poor outcomes in hospitalized, and in outpatients with cirrhosis are still debated. The results of studies in these settings are either negative, controversial, or inconclusive. This sheds some doubts regarding the use of albumin as a "one size fits all" strategy. The indication and patient selection are crucial and not always intuitive. The amount and frequency also seem to play a role in the success or failure of albumin. This review will critically discuss the evidence and underline areas where there are indications for albumin use and others where evidence is still insufficient and will have to await the development/results of randomized controlled trials.
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Affiliation(s)
- Jonel Trebicka
- Department of Internal Medicine B, University of Münster, Münster, Germany
- European Foundation for Study of Chronic Liver Failure, EASL-CLIF-Consortium, Barcelona, Spain
- Department of Gastroenterology and Hepatology, University of Southern Denmark, Odense, Denmark
| | - Guadalupe Garcia-Tsao
- Digestive Diseases Section, Department of Medicine, Yale University, New Haven, Connecticut, USA
- Digestive Diseases Section, Department of Medicine, VA-CT Healthcare System, West Haven, Connecticut, USA
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Brown RS, Fisher RA, Subramanian RM, Griesemer A, Fernandes M, Thatcher WH, Stiede K, Curtis M. Artificial Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure: Systematic Review and Meta-Analysis. Crit Care Explor 2025; 7:e1199. [PMID: 39804005 PMCID: PMC11732652 DOI: 10.1097/cce.0000000000001199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2025] Open
Abstract
OBJECTIVES To systematically review the safety and efficacy of nonbiological (NBAL) or biological artificial liver support systems (BAL) and whole-organ extracorporeal liver perfusion (W-ECLP) systems, in adults with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). DATA SOURCES Eligible NBAL/BAL studies from PubMed/Embase searches were randomized controlled trials (RCTs) in adult patients with ALF/ACLF, greater than or equal to ten patients per group, reporting outcomes related to survival, adverse events, transplantation rate, and hepatic encephalopathy, and published in English from January 2000 to July 2023. Separately, we searched for studies evaluating W-ECLP in adult patients with ALF or ACLF published between January1990 and July 2023. STUDY SELECTION AND DATA EXTRACTION Two researchers independently screened citations for eligibility and, of eligible studies, retrieved data related to study characteristics, patients and interventions, outcomes definition, and intervention effects. The Cochrane Risk of Bias 2 tool and Joanna Briggs Institute checklists were used to assess individual study risk of bias. Meta-analysis of mortality at 28-30 days post-support system initiation and frequency of at least one serious adverse event (SAE) generated pooled risk ratios (RRs), based on random (mortality) or fixed (SAE) effects models. DATA SYNTHESIS Of 17 trials evaluating NBAL/BAL systems, 11 reported 28-30 days mortality and five reported frequency of at least one SAE. Overall, NBAL/BAL was not statistically associated with mortality at 28-30 days (RR, 0.85; 95% CI, 0.67-1.07; p = 0.169) or frequency of at least one SAE (RR, 1.15; 95% CI, 0.99-1.33; p = 0.059), compared with standard medical treatment. Subgroup results on ALF patients suggest possible benefit for mortality (RR, 0.67; 95% CI, 0.44-1.03; p = 0.069). From six reports of W-ECLP (12 patients), more than half (58%) of severe patients were bridged to transplantation and survived without transmission of porcine retroviruses. CONCLUSIONS Despite no significant pooled effects of NBAL/BAL devices, the available evidence calls for further research and development of extracorporeal liver support systems, with larger RCTs and optimization of patient selection, perfusion durability, and treatment protocols.
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Affiliation(s)
- Robert S. Brown
- Center for Liver Disease, Weill Cornell Medicine, New York, NY
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Li X, Wu M, Chen M, Liu R, Tao Q, Hu Y, Yu J, Chen D. The Association Between Neutrophil-Percentage-to-Albumin Ratio (NPAR) and Mortality Among Individuals With Cancer: Insights From National Health and Nutrition Examination Survey. Cancer Med 2025; 14:e70527. [PMID: 39831739 PMCID: PMC11744675 DOI: 10.1002/cam4.70527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 11/27/2024] [Accepted: 12/10/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Neutrophils interact with tumor cells, potentially exacerbating cancer progression. Additionally, decreased albumin levels are a marker of poor cancer prognosis. The neutrophil-percentage-to-albumin ratio (NPAR) has been used for prognostic assessment in non-cancerous diseases, but its relationship with mortality risk in cancer patients has not been explored. Therefore, we utilized data from the National Health and Nutrition Examination Survey (NHANES) to investigate the correlation between NPAR and the risks of all-cause mortality and cancer-related mortality among cancer patients. METHODS This study leveraged comprehensive NHANES data spanning 2005-2016. We analyzed the relationship between NPAR and the risks of cancer incidence, all-cause mortality, and cancer-related mortality using weighted Logistic and Cox regression models, as well as trend tests. Restricted cubic spline analysis was employed to investigate NPAR's nonlinear relationship with mortality risk. Furthermore, Kaplan-Meier survival analysis was utilized to assess patient prognoses across varying NPAR levels. RESULTS Elevated NPAR was associated with an increased risk of all-cause mortality and cancer-related mortality in cancer patients (p < 0.05), with higher NPAR values correlating with greater risk (p-trend < 0.05). However, no significant association between NPAR and cancer incidence was observed (p > 0.05). Our analysis further identified a non-linear relationship between NPAR and all-cause mortality risk (p-nonlinear < 0.05), while no non-linear relationship was found with cancer-related mortality risk. The relationship is characterized by an optimal NPAR value, correlating with the lowest hazard ratio (HR). Deviations from this optimal NPAR result in increased all-cause mortality risk (p < 0.05). Kaplan-Meier analysis indicated superior survival rates in patients with lower NPAR values compared to those with higher NPAR values (p < 0.05). CONCLUSIONS According to our study, higher NPAR was associated with an increased risk of all-cause mortality and cancer-related mortality in cancer patients.
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Affiliation(s)
- Xinyang Li
- Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Meng Wu
- Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Minxin Chen
- Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Rufei Liu
- Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Qingxu Tao
- Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Yun Hu
- Department of Radiation OncologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Jinming Yu
- Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
| | - Dawei Chen
- Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandongChina
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Liang S, Sun J, Gu X, Zhao Y, Wang X, Tao H, Wang Z, Zhong Y, Wang J, Han B. Lactobacillus plantarum L11 and Lactobacillus reuteri LR: Ameliorate Obesity via AMPK Pathway. Nutrients 2024; 17:4. [PMID: 39796438 PMCID: PMC11723306 DOI: 10.3390/nu17010004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 12/18/2024] [Accepted: 12/19/2024] [Indexed: 01/13/2025] Open
Abstract
OBJECTIVES The purpose of this study was to find the potential mechanism of two Lactobacillus (Lactobacillus plantarum L11 and Lactobacillus reuteri LR) on ameliorating obesity, including lipid metabolism and gut microbiota. The two isolates have been studied to have good characterization in vitro, but in vivo studies in modulating lipid metabolism and gut microbiota were not studied. METHODS In this study, mice with HFD supplemented with L11 or LR exhibited slower obesity progression, including reduced weight gain, abdominal fat accumulation, liver damage, inflammation, and adipose lesions. RESULTS Total cholesterol (TC) and triglycerides (TG) in the serum were significantly reduced (p < 0.01). The inflammatory marker interleukin-6 (IL-6) notably decreased (p < 0.05). Both Lactobacillus strains altered the gut microbiota composition, increasing the relative abundance of Alistipes and Lactobacillus, while L11 also raised Lachnospiraceae abundance. Results of the Western blot analysis showed that L11 and LR influenced the PPAR and AMPK pathways. CONCLUSIONS L11 and LR can effectively reduce obesity by modulating gut microbiota and activating the PPAR-AMPK pathway, leading to decreased liver injury and systemic inflammation in mice fed with an HFD. In the future, the two probiotics may provide a new way for clinically ameliorating obesity on human beings.
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Affiliation(s)
- Shukun Liang
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China (J.W.)
- School of Veterinary Medicine, China Agricultural University, Beijing 100193, China;
| | - Jintao Sun
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China (J.W.)
| | - Xinshu Gu
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China (J.W.)
| | - Ya Zhao
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China (J.W.)
| | - Xiumin Wang
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China (J.W.)
| | - Hui Tao
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China (J.W.)
| | - Zhenlong Wang
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China (J.W.)
| | - Yougang Zhong
- School of Veterinary Medicine, China Agricultural University, Beijing 100193, China;
| | - Jinquan Wang
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China (J.W.)
| | - Bing Han
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China (J.W.)
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Nishikawa T, Ueyama J, Shimizu S, Shibata Y, Yamada S. Redox state of human serum albumin as a post-discharge prognostic marker in patients hospitalized for heart failure. Int J Cardiol 2024; 416:132497. [PMID: 39214476 DOI: 10.1016/j.ijcard.2024.132497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 08/17/2024] [Accepted: 08/27/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Heart failure (HF) is a global health concern, and oxidative stress has been implicated in its progression. The redox state of human serum albumin, a systemic oxidative biomarker, holds promise as a prognostic marker in HF. This study aimed to investigate the association between the fraction of human mercaptalbumin (fHMA), an indicator of human serum albumin's redox state, and adverse events in HF within a prospective single-hospital-based cohort. METHODS We enrolled patients hospitalized for HF and measured fHMA using high-performance liquid chromatography at discharge. The primary endpoint was the composite of HF rehospitalization and all-cause death within one year after discharge. RESULTS A total of 221 participants (median age:79 years; 35 % female) were included in the study. Over the course of one year, 26.1 % of the patients experienced HF readmission, while 13.1 % died. The low fHMA group divided by median of fHMA (<57.6 %) showed higher composite outcome rates (41.4 % for the low fHMA vs. 24.6 % for the high fHMA, p = 0.0114). Multivariate analysis, accounting for seven potential confounders, identified low fHMA (adjusted HR: 1.79 [1.03-3.11]) and lower hemoglobin as independent predictors of HF prognosis. CONCLUSIONS The findings in this study provide the first evidence that fHMA is a potential novel prognostic biomarker in patients with HF.
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Affiliation(s)
- Taiki Nishikawa
- Department of Biomolecular Sciences, Field of Omics Health Sciences, Nagoya University Graduate School, Nagoya, Japan; Department of Rehabilitation, Japan Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan
| | - Jun Ueyama
- Department of Biomolecular Sciences, Field of Omics Health Sciences, Nagoya University Graduate School, Nagoya, Japan
| | - Shinya Shimizu
- Department of Cardiology, Kariya Toyota General Hospital, Kariya, Japan
| | - Yoshihisa Shibata
- Department of Cardiology, Japan Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan
| | - Sumio Yamada
- Department of Cardiology, Aichi Medical University, Nagakute, Japan.
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Ihira H, Nakano S, Yamaji T, Katagiri R, Sawada N, Inoue M, Tsugane S, Iwasaki M. Plasma albumin, bilirubin, and uric acid and the subsequent risk of cancer: a case-cohort study in the Japan Public Health Center-based Prospective Study. Am J Epidemiol 2024; 193:1460-1469. [PMID: 38808611 DOI: 10.1093/aje/kwae092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 04/02/2024] [Accepted: 05/23/2024] [Indexed: 05/30/2024] Open
Abstract
Several epidemiologic studies have investigated the circulating levels of albumin, bilirubin, and uric acid (UA) in relation to cancer risk; however, they have provided equivocal evidence. In this prospective case-cohort study, we measured the plasma levels of albumin, bilirubin, and UA and investigated their association with cancer incidence in 3584 case patients and 4270 randomly selected participants with a median follow-up of 15.8 years. The adjusted hazard ratios (HRs) and 95% CIs of total cancer for the highest quartile (Q4) versus lowest quartile (Q1) was 0.77 (95% CI, 0.67-0.90; P <.001 for trend) for albumin. This association was attenuated after excluding liver cancer cases with lower plasma albumin levels. Plasma bilirubin levels were positively related to liver cancer but inversely to total cancer after excluding liver cancer with, for Q4 versus Q1, an adjusted HR of 0.86 (95% CI, 0.74-0.99; P = .015 for trend). Plasma UA levels were not dose-responsively associated with total cancer risk. Higher plasma bilirubin levels were associated with a decreased risk of total cancer after excluding liver cancer, which is likely attributed to the antioxidant properties of bilirubin.
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Affiliation(s)
- Hikaru Ihira
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan
- Department of Physical Therapy, School of Health Sciences, Sapporo Medical University, Hokkaido 060-8556, Japan
| | - Shiori Nakano
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan
| | - Taiki Yamaji
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan
| | - Ryoko Katagiri
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan
- Department of Nutritional Epidemiology and Shokuiku, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 566-0002, Japan
| | - Norie Sawada
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan
| | - Manami Inoue
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan
- Division of Prevention Research, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan
| | - Shoichiro Tsugane
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan
- International University of Health and Welfare Graduate School of Public Health, Tokyo 107-8402, Japan
| | - Motoki Iwasaki
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan
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Gambardella G, Notari S, Criscuolo E, Lai O, Nardoni A, Massoud R, Micheli L, Bocedi A, Ricci G. Quantitation of oxidized and reduced albumin in mammals. An intriguing analytical question. Arch Biochem Biophys 2024; 757:110038. [PMID: 38750920 DOI: 10.1016/j.abb.2024.110038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/09/2024] [Accepted: 05/11/2024] [Indexed: 05/21/2024]
Abstract
Oxidized albumin is considered a short-term biomarker of oxidative stress and its measurement in blood contributes to evaluate the impact of diseases, drugs, dialytic treatments, physical activity, environmental contaminants etc. on the red-ox balance of humans as well as of other mammalians. Nevertheless, the most common methods for quantifying the oxidized and reduced albumins are costly and time-consuming. Furthermore, there is a dearth of information regarding the proper ways to store human serum or plasma samples in order to prevent inaccurate quantification of these various albumin forms. This paper explores these aspects and proposes a few spectrophotometric assay procedures which make the quantitation of oxidized and reduced albumin very fast, precise and un-expensive in various mammals.
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Affiliation(s)
- Giorgia Gambardella
- Department of Chemical Sciences and Technologies, University of Rome "Tor Vergata", Via Della Ricerca Scientifica 1, 00133 Rome, Italy
| | - Sara Notari
- Department of Chemical Sciences and Technologies, University of Rome "Tor Vergata", Via Della Ricerca Scientifica 1, 00133 Rome, Italy
| | - Emanuele Criscuolo
- Department of Biomedical Engineering, Eindhoven University of Technology, Institute for Complex Molecular Systems, Eindhoven, Netherlands
| | - Olga Lai
- Istituto Zooprofilattico Sperimentale Del Lazio e Della Toscana 'M. Aleandri', Via Appia Nuova 1411, 00182, Rome, Italy
| | - Antonella Nardoni
- Istituto Zooprofilattico Sperimentale Del Lazio e Della Toscana 'M. Aleandri', Via Appia Nuova 1411, 00182, Rome, Italy
| | - Renato Massoud
- Department of Experimental Medicine, University of Rome "Tor Vergata", Via Montpellier 1, Rome, 00133, Italy; Department of Laboratory Medicine, "Tor Vergata" University Hospital, Viale Oxford 81, Rome, 00133, Italy
| | - Laura Micheli
- Department of Chemical Sciences and Technologies, University of Rome "Tor Vergata", Via Della Ricerca Scientifica 1, 00133 Rome, Italy
| | - Alessio Bocedi
- Department of Chemical Sciences and Technologies, University of Rome "Tor Vergata", Via Della Ricerca Scientifica 1, 00133 Rome, Italy.
| | - Giorgio Ricci
- Department of Chemical Sciences and Technologies, University of Rome "Tor Vergata", Via Della Ricerca Scientifica 1, 00133 Rome, Italy
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Terrill JR, Bautista APR, Tsioutsias I, Grounds MD, Arthur PG. Oxidised Albumin Levels in Plasma and Skeletal Muscle as Biomarkers of Disease Progression and Treatment Efficacy in Dystrophic mdx Mice. Antioxidants (Basel) 2024; 13:720. [PMID: 38929159 PMCID: PMC11201235 DOI: 10.3390/antiox13060720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 06/05/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024] Open
Abstract
Redox modifications to the plasma protein albumin have the potential to be used as biomarkers of disease progression and treatment efficacy in pathologies associated with inflammation and oxidative stress. One such pathology is Duchenne muscular dystrophy (DMD), a fatal childhood disease characterised by severe muscle wasting. We have previously shown in the mdx mouse model of DMD that plasma albumin thiol oxidation is increased; therefore, the first aim of this paper was to establish that albumin thiol oxidation in plasma reflects levels within mdx muscle tissue. We therefore developed a method to measure tissue albumin thiol oxidation. We show that albumin thiol oxidation was increased in both mdx muscle and plasma, with levels correlated with measures of dystropathology. In dystrophic muscle, albumin content was associated with areas of myonecrosis. The second aim was to test the ability of plasma thiol oxidation to track acute changes in dystropathology: we therefore subjected mdx mice to a single treadmill exercise session (known to increase myonecrosis) and took serial blood samples. This acute exercise caused a transient increase in total plasma albumin oxidation and measures of dystropathology. Together, these data support the use of plasma albumin thiol oxidation as a biomarker to track active myonecrosis in DMD.
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Affiliation(s)
- Jessica R. Terrill
- School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia; (J.R.T.); (A.P.R.B.); (I.T.)
| | - Angelo Patrick R. Bautista
- School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia; (J.R.T.); (A.P.R.B.); (I.T.)
| | - Irene Tsioutsias
- School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia; (J.R.T.); (A.P.R.B.); (I.T.)
- School of Human Sciences, The University of Western Australia, Perth, WA 6009, Australia;
| | - Miranda D. Grounds
- School of Human Sciences, The University of Western Australia, Perth, WA 6009, Australia;
| | - Peter G. Arthur
- School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia; (J.R.T.); (A.P.R.B.); (I.T.)
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11
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Biswas B, Dogra S, Sen A, Murugan NA, Dhingra P, Jaswal K, Mondal P, Ghosh S. NIR-I emissive cyanine derived molecular probe for selective monitoring of hepatic albumin levels during hyperglycemia. J Mater Chem B 2024; 12:4441-4450. [PMID: 38639071 DOI: 10.1039/d3tb01938a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2024]
Abstract
In this study, we report a small molecule optical marker BI-CyG derived from the structural engineering of a cyanine scaffold. The developed probe offers suitable advantages over existing cyanine-based albumin specific probes in terms of its excitation and emission wavelengths, which are 760 and 830-832 nm, respectively. Structural tuning of the cyanine architecture leading to extended π-conjugation and resulting in a suitable bathochromic shift in the emission wavelength of the probe is represented in this study. The probe besides emitting in the NIR region, also possesses the desirable characteristics of being a potential target selective optical marker, as established from various biophysical studies. Molecular modelling and simulation studies provided critical insights into the binding of the probe in the protein microenvironment, which was further supported by experimental studies. The probe displayed intracellular albumin selectivity and was utilized for demonstrating alteration in albumin levels in pathological states such as hyperglycemia in hepatic cells. The present study also sheds some light on using BI-CyG as an imaging probe and on the role of metformin as a suitable drug for balancing hyperglycemia-induced reduced intra-hepatic albumin levels. The study, thus, attempts to highlight the structural derivatization of cyanine to afford a potential probe for serum albumin and its deployment to image altering albumin levels in an induced pathological condition, hyperglycemia.
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Affiliation(s)
- Bidisha Biswas
- School of Chemical Sciences, Indian Institute of Technology Mandi, Kamand-175005, Himachal Pradesh, India.
| | - Surbhi Dogra
- School of Bioscience and Bioengineering, Indian Institute of Technology Mandi, Kamand-175005, Himachal Pradesh, India
| | - Aniket Sen
- School of Bioscience and Bioengineering, Indian Institute of Technology Mandi, Kamand-175005, Himachal Pradesh, India
| | - N Arul Murugan
- Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, 110020, India
| | - Pooja Dhingra
- School of Chemical Sciences, Indian Institute of Technology Mandi, Kamand-175005, Himachal Pradesh, India.
| | - Kajal Jaswal
- School of Bioscience and Bioengineering, Indian Institute of Technology Mandi, Kamand-175005, Himachal Pradesh, India
| | - Prosenjit Mondal
- School of Bioscience and Bioengineering, Indian Institute of Technology Mandi, Kamand-175005, Himachal Pradesh, India
- Department of Biological Sciences, Indian Institute of Science Education and Research Berhampur, Berhampur-760010, India.
| | - Subrata Ghosh
- School of Chemical Sciences, Indian Institute of Technology Mandi, Kamand-175005, Himachal Pradesh, India.
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12
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Anouti A, Al Hariri M, VanWagner LB, Lee WM, Mufti A, Pedersen M, Shah J, Hanish S, Vagefi PA, Cotter TG, Patel MS. Early Graft Failure After Living-Donor Liver Transplant. Dig Dis Sci 2024; 69:1488-1495. [PMID: 38381224 DOI: 10.1007/s10620-024-08280-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 01/04/2024] [Indexed: 02/22/2024]
Abstract
BACKGROUND Living-donor liver transplantation (LDLT) has been increasing in the USA. While data exist on longer-term patient and graft outcomes, a contemporary analysis of short-term outcomes is needed. AIM Evaluate short-term (30-day) graft failure rates and identify predictors associated with these outcomes. METHODS Adult (≥ 18) LDLT recipients from 01/2004 to 12/2021 were analyzed from the United States Scientific Registry of Transplant Recipients. Graft status at 30 days was assessed with graft failure defined as retransplantation or death. Comparison of continuous and categorical variables was performed and a multivariable logistic regression was used to identify risk factors of early graft failure. RESULTS During the study period, 4544 LDLTs were performed with a graft failure rate of 3.4% (155) at 30 days. Grafts from male donors (aOR: 0.63, CI 0.44-0.89), right lobe grafts (aOR: 0.40, CI 0.27-0.61), recipients aged > 60 years (aOR: 0.52, CI 0.32-0.86), and higher recipient albumin (aOR: 0.73, CI 0.57-0.93) were associated with superior early graft outcomes, whereas Asian recipient race (vs. White; aOR: 3.75, CI 1.98-7.10) and a history of recipient PVT (aOR: 2.7, CI 1.52-4.78) were associated with inferior outcomes. LDLTs performed during the most recent 2016-2021 period (compared to 2004-2009 and 2010-2015) resulted in significantly superior outcomes (aOR: 0.45, p < 0.001). CONCLUSION Our study demonstrates that while short-term adult LDLT graft failure is uncommon, there are opportunities for optimizing outcomes by prioritizing right lobe donation, improving candidate nutritional status, and careful pre-transplant risk assessment of candidates with known PVT. Notably, a period effect exists whereby increased LDLT experience in the most recent era correlated with improved outcomes.
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Affiliation(s)
- Ahmad Anouti
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
| | | | - Lisa B VanWagner
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
| | - William M Lee
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
| | - Arjmand Mufti
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
| | - Mark Pedersen
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
| | - Jigesh Shah
- Department of Surgery, UT Southwestern Medical Center, 5959 Harry Hines Blvd, HP04.102, Dallas, TX, 75390, USA
| | - Steven Hanish
- Department of Surgery, UT Southwestern Medical Center, 5959 Harry Hines Blvd, HP04.102, Dallas, TX, 75390, USA
| | - Parsia A Vagefi
- Department of Surgery, UT Southwestern Medical Center, 5959 Harry Hines Blvd, HP04.102, Dallas, TX, 75390, USA
| | - Thomas G Cotter
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
| | - Madhukar S Patel
- Department of Surgery, UT Southwestern Medical Center, 5959 Harry Hines Blvd, HP04.102, Dallas, TX, 75390, USA.
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13
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Pompili E, Zaccherini G, Caraceni P. Albumin in hospitalized patients with complications of cirrhosis: Not a suit for all seasons. Indian J Gastroenterol 2024; 43:288-291. [PMID: 38087187 DOI: 10.1007/s12664-023-01487-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/28/2024]
Affiliation(s)
- Enrico Pompili
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via Albertoni 15, 40138, Bologna, Italy
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via Albertoni 15, 40138, Bologna, Italy
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via Albertoni 15, 40138, Bologna, Italy.
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14
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Takahashi H, Asakawa K, Kosakai Y, Lee T, Rokuda M. Comparative effectiveness of sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors on liver function in patients with type 2 diabetes in Japan: A real-world data analysis. Diabetes Obes Metab 2024; 26:997-1007. [PMID: 38086547 DOI: 10.1111/dom.15399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 11/01/2023] [Accepted: 11/17/2023] [Indexed: 12/28/2023]
Abstract
AIM To compare the effects of sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) on liver function in patients with type 2 diabetes (T2D) in Japan. MATERIALS AND METHODS This was a Japanese retrospective cohort study using the RWD Database (1 January 2015 to 24 September 2021). Patients newly treated with an SGLT2i or a DPP4i were matched 1:4 (SGLT2i:DPP4i) using propensity score. The primary endpoint was the change from baseline to 1 year after the index date in alanine aminotransferase (ALT). Secondary endpoints included change from baseline in various laboratory test results, including the Fibrosis-4 (FIB-4) index, aspartate aminotransferase, gamma-glutamyl transpeptidase (GGT), albumin and HbA1c. Endpoints were compared between treatment groups using Welch's t-test in the full population and in subgroups stratified by baseline characteristics. RESULTS Baseline characteristics of 955 and 3063 matched patients newly treated with an SGLT2i and a DPP4i, respectively, were well balanced. Patients receiving an SGLT2i had significantly greater reductions in ALT, FIB-4 index and GGT and a significantly greater increase in albumin than patients receiving a DPP4i. A significantly greater change from baseline in ALT was observed in the SGLT2i group than in the DPP4i group among subgroups with lower baseline FIB-4 index and HbA1c. CONCLUSIONS In this study, improvements in various measures, including ALT, the FIB-4 index, GGT and albumin, were observed with SGLT2is compared with DPP4is, suggesting that SGLT2is may provide hepatoprotective benefits, including the prevention of liver fibrosis, in patients with T2D in Japan.
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Affiliation(s)
- Hirokazu Takahashi
- Liver Center, Saga University Hospital, Saga, Japan
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan
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15
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Stauber RE, Paar M, Balazs I, Horvath A, Feldbacher N, Posch A, Rainer F, Stadlbauer V, Oettl K. Effect of albumin infusion on oxidative albumin modification and albumin binding capacity in chronic liver failure. Basic Clin Pharmacol Toxicol 2024; 134:375-384. [PMID: 38093476 DOI: 10.1111/bcpt.13973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 11/27/2023] [Accepted: 12/11/2023] [Indexed: 12/28/2023]
Abstract
Oxidative albumin modification and impaired albumin binding function have been described both in chronic liver failure and for therapeutic albumin solutions. The aim of the present study was to evaluate the effect of albumin infusion on redox state and binding function of circulating albumin. We studied 20 patients with cirrhosis who routinely received albumin infusions for prevention of post-paracentesis circulatory dysfunction or treatment of hepatorenal syndrome. We measured albumin fractions by redox state of cysteine-34 and albumin binding properties using dansylsarcosine as site II ligand. Therapeutic albumin solutions showed high contents of human nonmercaptalbumin-1 and human nonmercaptalbumin-2, exceeding the respective values in our patients with decompensated cirrhosis. An initial protocol for the first nine patients sampled at baseline, 24 h and 48 h after albumin infusion revealed no significant changes of oxidized albumin species or albumin binding properties. However, a modified protocol for the remaining 11 patients sampled at baseline, <1 h after and 24 h after albumin infusion revealed short-lived changes of oxidized albumin species while no changes in albumin binding properties were observed. In conclusion, therapeutic albumin infusion transiently changed albumin redox state but did not improve binding function of circulating albumin in chronic liver failure.
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Affiliation(s)
- Rudolf E Stauber
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Margret Paar
- Division of Medicinal Chemistry, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria
| | - Irina Balazs
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
- CBmed Center of Biomarker Research in Medicine, Graz, Austria
| | - Angela Horvath
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
- CBmed Center of Biomarker Research in Medicine, Graz, Austria
| | - Nicole Feldbacher
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
- CBmed Center of Biomarker Research in Medicine, Graz, Austria
| | - Andreas Posch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Florian Rainer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Vanessa Stadlbauer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
- CBmed Center of Biomarker Research in Medicine, Graz, Austria
| | - Karl Oettl
- Division of Medicinal Chemistry, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria
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16
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Du L, Xu H, Fang L, Qiao L, Xie Y, Yang C, Ji L, Zhao L, Wang C, Zhang W, Feng X, Chen T, Yuan Q. Albumin-bilirubin score as a predictor of all-cause mortality in patients with hepatitis B virus infection: An analysis of National Health and Nutrition Examination Survey (NHANES) 1999-2018. Prev Med Rep 2024; 39:102639. [PMID: 38357224 PMCID: PMC10865019 DOI: 10.1016/j.pmedr.2024.102639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 01/25/2024] [Accepted: 01/31/2024] [Indexed: 02/16/2024] Open
Abstract
Objectives The Albumin-Bilirubin (ALBI) score has been widely used to assess the prognosis in patients with cirrhosis and hepatocellular carcinoma. This study aimed to analyze the relationship between ALBI score and all-cause mortality in patients with hepatitis B virus (HBV) infection in general. Methods Patients aged ≥ 18 years with previous or current HBV infection from the National Health and Nutrition Examination Survey (NHANES) in the United States between 1999 and 2018 were enrolled in this retrospective cohort study. Weight univariate and multivariate Cox regression models were used to assess the relationship between ALBI score and all-cause mortality. The area under the receiver operating characteristic curve (AUC) was utilized to assess the predictive effect of ALBI score for all-cause mortality. Results A total of 3,666 patients were included, of whom 925 (23.53 %) patients died. Compared with ALBI score ≤ -2.6, HBV-infected patients with ALBI score > -2.6 [hazard ratio (HR) = 1.75; 95 % confidence interval (CI): 1.43-2.14] were corrected with a higher all-cause mortality risk after adjusting for confounders. Stratified analyses showed that higher ALBI score was related to a higher risk of all-cause mortality in different patients with HBV infection (All P < 0.05). Furthermore, the ALBI score had good predictive ability for 1-year (AUC = 0.816, 95 %CI: 0.754-0.878), 3-year (AUC = 0.808, 95 %CI: 0.775-0.841), 5-year (AUC = 0.809, 95 %CI: 0.783-0.835), and 10-year (AUC = 0.806, 95 %CI: 0.784-0.827) all-cause mortality. Conclusion Higher ALBI score was related to a higher risk of all-cause mortality in patients with HBV infection, and the ALBI score showed a good predictive effect for short- and long-term all-cause mortality.
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Affiliation(s)
- Lixia Du
- Department of Infectious Diseases, The First People’s Hospital of Shuangliu District, Chengdu 610020, PR China
- Department of Gastroenterology, Chengdu BOE Hospital, Chengdu 610219, PR China
| | - Hui Xu
- Department of Gastroenterology, Chengdu BOE Hospital, Chengdu 610219, PR China
| | - Li Fang
- Department of Gastroenterology, Chengdu BOE Hospital, Chengdu 610219, PR China
| | - Lijuan Qiao
- Department of Gastroenterology, Chengdu BOE Hospital, Chengdu 610219, PR China
| | - Yu Xie
- Department of Gastroenterology, Chengdu BOE Hospital, Chengdu 610219, PR China
| | - Chunli Yang
- Department of Gastroenterology, Chengdu BOE Hospital, Chengdu 610219, PR China
| | - Linxiu Ji
- Department of Gastroenterology, Chengdu BOE Hospital, Chengdu 610219, PR China
| | - Liqiong Zhao
- Department of Gastroenterology, Chengdu BOE Hospital, Chengdu 610219, PR China
| | - Cong Wang
- Department of Gastroenterology, Chengdu BOE Hospital, Chengdu 610219, PR China
| | - Weilan Zhang
- Department of Gastroenterology, Chengdu BOE Hospital, Chengdu 610219, PR China
| | - Xue Feng
- Department of Gastroenterology, Chengdu BOE Hospital, Chengdu 610219, PR China
| | - Ting Chen
- Department of Gastroenterology, Chengdu BOE Hospital, Chengdu 610219, PR China
| | - Qin Yuan
- Department of Infectious Diseases, The First People’s Hospital of Shuangliu District, Chengdu 610020, PR China
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17
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Liu B, Hu Y, Tian D, Dong J, Li BF. Assessing the effects of tempol on renal fibrosis, inflammation, and oxidative stress in a high-salt diet combined with 5/6 nephrectomy rat model: utilizing oxidized albumin as a biomarker. BMC Nephrol 2024; 25:64. [PMID: 38395806 PMCID: PMC10893674 DOI: 10.1186/s12882-024-03495-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 02/07/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD), prompting the exploration of antioxidants as a potential therapeutic avenue for mitigating disease progression. This study aims to investigate the beneficial impact of Tempol on the progression of CKD in a rat model utilizing oxidized albumin as a biomarker. METHODS After four weeks of treatment, metabolic parameters, including body weight, left ventricle residual weight, kidney weight, urine volume, and water and food intake, were measured. Systolic blood pressure, urinary protein, oxidized albumin level, serum creatinine (Scr), blood urea nitrogen (BUN), 8-OHdG, TGF-β1, and micro-albumin were also assessed. Renal fibrosis was evaluated through histological and biochemical assays. P65-NF-κB was quantified using an immunofluorescence test, while Smad3, P65-NF-κB, and Collagen I were measured using western blot. TNF-α, IL-6, MCP-1, TGF-β1, Smad3, and P65-NF-κB were analyzed by RT-qPCR. RESULTS Rats in the high-salt diet group exhibited impaired renal function, characterized by elevated levels of blood urea nitrogen, serum creatinine, 8-OHdG, urine albumin, and tubulointerstitial damage, along with reduced body weight. However, these effects were significantly ameliorated by Tempol administration. In the high-salt diet group, blood pressure, urinary protein, and oxidized albumin levels were notably higher compared to the normal diet group, but Tempol administration in the treatment group reversed these effects. Rats in the high-salt diet group also displayed increased levels of proinflammatory factors (TNF-α, IL-6, MCP1) and profibrotic factors (NF-κB activation, Collagen I), elevated expression of NADPH oxidation-related subunits (P65), and activation of the TGF-β1/Smad3 signaling pathway. Tempol treatment inhibited NF-κB-mediated inflammation and TGF-β1/Smad3-induced renal fibrosis signaling pathway activation. CONCLUSION These findings suggest that Tempol may hold therapeutic potential for preventing and treating rats undergoing 5/6 nephrectomy. Further research is warranted to elucidate the mechanisms underlying Tempol's protective effects and its potential clinical applications. Besides, there is a discernible positive relationship between oxidized albumin and other biomarkers, such as 8-OHG, urinary protein levels, mALB, Scr, BUN, and TGF-β1 in a High-salt diet combined with 5/6 nephrectomy rat model. These findings suggest the potential utility of oxidized albumin as a sensitive indicator for oxidative stress assessment.
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Affiliation(s)
- Beibei Liu
- College of Life and Health, Nanjing Polytechnic Institute, No.188 Xinle Road, Luhe District, 210048, Nanjing, Nanjing, Jiangsu, China
| | - Yanling Hu
- College of Life and Health, Nanjing Polytechnic Institute, No.188 Xinle Road, Luhe District, 210048, Nanjing, Nanjing, Jiangsu, China
| | - Danyang Tian
- Department of Physiology, Hebei Medical University, Shijiazhuang, China
| | - Jianlong Dong
- Hebei University of Chinese Medicine, The First Affiliated Hospital, Shijiazhuang, China
| | - Bing-Feng Li
- College of Life and Health, Nanjing Polytechnic Institute, No.188 Xinle Road, Luhe District, 210048, Nanjing, Nanjing, Jiangsu, China.
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18
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Lakis R, Sauvage FL, Pinault E, Marquet P, Saint-Marcoux F, El Balkhi S. Absolute Quantification of Human Serum Albumin Isoforms by Internal Calibration Based on a Top-Down LC-MS Approach. Anal Chem 2024; 96:746-755. [PMID: 38166371 DOI: 10.1021/acs.analchem.3c03933] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2024]
Abstract
Well-characterized biomarkers using reliable quantitative methods are essential for the management of various pathologies such as diabetes, kidney, and liver diseases. Human serum albumin (HSA) isoforms are gaining interest as biomarkers of advanced liver pathologies. In view of the structural alterations observed for HSA, insights into its isoforms are required to establish them as reliable biomarkers. Therefore, a robust absolute quantification method seems necessary. In this study, we developed and validated a far more advanced top-down liquid chromatography-mass spectrometry (LC-MS) method for the absolute quantification of HSA isoforms, using myoglobin (Mb) as an internal standard for quantification and for mass recalibration. Two different quantification approaches were investigated based on peak integration from the deconvoluted spectrum and extracted ion chromatogram (XIC). The protein mixture human serum albumin/myoglobin eluted in well-shaped separated peaks. Mb allowed a systematic mass recalibration for every sample, resulting in extremely low mass deviations compared to conventional deconvolution-based methods. In total, eight HSA isoforms of interest were quantified. Specific-isoform calibration curves showing good linearity were obtained by using the deconvoluted peaks. Noticeably, the HSA ionization behavior appeared to be isoform-dependent, suggesting that the use of an enriched isoform solution as a calibration standard for absolute quantification studies of HSA isoforms is necessary. Good repeatability, reproducibility, and accuracy were observed, with better sensitivity for samples with low albumin concentrations compared to routine biochemical assays. With a relatively simple workflow, the application of this method for absolute quantification shows great potential, especially for HSA isoform studies in a clinical context, where a high-throughput method and sensitivity are needed.
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Affiliation(s)
- Roy Lakis
- Pharmacology & Transplantation (P&T), Université de Limoges, INSERM U1248, Limoges 87000, France
| | - François-Ludovic Sauvage
- Pharmacology & Transplantation (P&T), Université de Limoges, INSERM U1248, Limoges 87000, France
| | - Emilie Pinault
- Pharmacology & Transplantation (P&T), Université de Limoges, INSERM U1248, Limoges 87000, France
| | - Pierre Marquet
- Pharmacology & Transplantation (P&T), Université de Limoges, INSERM U1248, Limoges 87000, France
- Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges, Limoges 87000, France
| | - Franck Saint-Marcoux
- Pharmacology & Transplantation (P&T), Université de Limoges, INSERM U1248, Limoges 87000, France
- Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges, Limoges 87000, France
| | - Souleiman El Balkhi
- Pharmacology & Transplantation (P&T), Université de Limoges, INSERM U1248, Limoges 87000, France
- Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges, Limoges 87000, France
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19
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El Balkhi S, Rahali MA, Lakis R, Sauvage FL, Martin M, Janaszkiewicz A, Lawson R, Goncalves R, Carrier P, Loustaud-Ratti V, Guyot A, Marquet P, Di Meo F, Saint-Marcoux F. Early detection of liver injuries by the Serum enhanced binding test sensitive to albumin post-transcriptional modifications. Sci Rep 2024; 14:1434. [PMID: 38228668 PMCID: PMC10791642 DOI: 10.1038/s41598-024-51412-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 01/04/2024] [Indexed: 01/18/2024] Open
Abstract
Early and sensitive biomarkers of liver dysfunction and drug-induced liver injury (DILI) are still needed, both for patient care and drug development. We developed the Serum Enhanced Binding (SEB) test to reveal post-transcriptional modifications (PTMs) of human serum albumin resulting from hepatocyte dysfunctions and further evaluated its performance in an animal model. The SEB test consists in spiking serum ex-vivo with ligands having specific binding sites related to the most relevant albumin PTMs and measuring their unbound fraction. To explore the hypothesis that albumin PTMs occur early during liver injury and can also be detected by the SEB test, we induced hepatotoxicity in male albino Wistar rats by administering high daily doses of ethanol and CCl4 over several days. Blood was collected for characterization and quantification of albumin isoforms by high-resolution mass spectrometry, for classical biochemical analyses as well as to apply the SEB test. In the exposed rats, the appearance of albumin isoforms paralleled the positivity of the SEB test ligands and histological injuries. These were observed as early as D3 in the Ethanol and CCl4 groups, whereas the classical liver tests (ALT, AST, PAL) significantly increased only at D7. The behavior of several ligands was supported by structural and molecular simulation analysis. The SEB test and albumin isoforms revealed hepatocyte damage early, before the current biochemical biomarkers. The SEB test should be easier to implement in the clinics than albumin isoform profiling.
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Affiliation(s)
- Souleiman El Balkhi
- P&T, UMR1248, Inserm, Univ. Limoges, Limoges, France.
- Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges, Limoges, France.
- Pharmacology-Toxicology and Pharmacovigilance Department, Centre de Biologie Et de Recherche en Santé (CBRS), 2, Av. Martin Luther King, 87042, Limoges Cedex, France.
| | - Mohamad Ali Rahali
- P&T, UMR1248, Inserm, Univ. Limoges, Limoges, France
- Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges, Limoges, France
| | - Roy Lakis
- P&T, UMR1248, Inserm, Univ. Limoges, Limoges, France
| | | | | | | | - Roland Lawson
- P&T, UMR1248, Inserm, Univ. Limoges, Limoges, France
| | | | - Paul Carrier
- P&T, UMR1248, Inserm, Univ. Limoges, Limoges, France
- Department of Liver Disease, CHU Limoges, Limoges, France
| | - Veronique Loustaud-Ratti
- P&T, UMR1248, Inserm, Univ. Limoges, Limoges, France
- Department of Liver Disease, CHU Limoges, Limoges, France
| | - Anne Guyot
- Department of Pathology, CHU Limoges, Limoges, France
| | - Pierre Marquet
- P&T, UMR1248, Inserm, Univ. Limoges, Limoges, France
- Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges, Limoges, France
| | | | - Franck Saint-Marcoux
- P&T, UMR1248, Inserm, Univ. Limoges, Limoges, France
- Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges, Limoges, France
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20
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Juanola A, Ma AT, de Wit K, Gananandan K, Roux O, Zaccherini G, Jiménez C, Tonon M, Solé C, Villaseca C, Uschner FE, Graupera I, Pose E, Moreta MJ, Campion D, Beuers U, Mookerjee RP, Francoz C, Durand F, Vargas V, Piano S, Alonso S, Trebicka J, Laleman W, Asrani SK, Soriano G, Alessandria C, Serra-Burriel M, Morales-Ruiz M, Torres F, Allegretti AS, Krag A, Caraceni P, Watson H, Abraldes JG, Solà E, Kamath PS, Hernaez R, Ginès P. Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis. Gut 2023; 73:156-165. [PMID: 37884354 DOI: 10.1136/gutjnl-2023-329923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 09/18/2023] [Indexed: 10/28/2023]
Abstract
BACKGROUND Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications. METHODS We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not. RESULTS Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46). CONCLUSION Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.
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Affiliation(s)
- Adrià Juanola
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
- Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Barcelona, Spain
| | - Ann Thu Ma
- Toronto Centre for Liver Disease Francis Family Liver Clinic, Toronto General Hospital, Toronto, Ontario, Canada
| | - Koos de Wit
- Gastroenterology and Hepatology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
| | - Kohilan Gananandan
- Institute for Liver and Digestive Health, University College London, London, UK
| | - Olivier Roux
- Department of Hepatology, Beaujon Hospital, Clichy, France
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-related Diseases, University of Bologna Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Bologna, Italy
| | - César Jiménez
- Liver Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain
| | - Marta Tonon
- Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Cristina Solé
- Department of Gastroenterology and Hepatology, Consorci Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - Clara Villaseca
- Digestive Disease Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Frank E Uschner
- Department of Internal Medicine B, University of Münster, Munster, Germany
| | - Isabel Graupera
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
- Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Barcelona, Spain
| | - Elisa Pose
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
- Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Barcelona, Spain
| | - Maria José Moreta
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
| | - Daniela Campion
- Division of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy
| | - Ulrich Beuers
- Gastroenterology & Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands
| | - Rajeshawar P Mookerjee
- Institute of Liver and Digestive Health, University College London Medical School, London, UK
| | - Claire Francoz
- Department of Hepatology, Beaujon Hospital, Clichy, France
| | - Francois Durand
- DHU Unity, Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Centre de Référence des Maladies Vasculaires du Foie, Hôpital Beaujon, AP-HP, Clichy, France
- Université Denis Diderot-Paris 7, Paris, France
| | - Victor Vargas
- Liver Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain
| | - Salvatore Piano
- Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Sonia Alonso
- Digestive Disease Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Jonel Trebicka
- Department of Internal Medicine B, University of Münster, Munster, Germany
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Wim Laleman
- Division of Liver and Biliopanreatic Disorders, KU Leuven, University of Leuven, Leuven, Belgium
| | - Sumeet K Asrani
- Division of Hepatology, Department of Medicine, Baylor University Medical Center at Dallas, Dallas, Texas, USA
| | - German Soriano
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy
| | - Miquel Serra-Burriel
- University of Zurich Institute of Epidemiology Biostatistics and Prevention, Zurich, Switzerland
| | - Manuel Morales-Ruiz
- Biochemistry and Molecular Genetics Department-CDB, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Ferran Torres
- Biostatistics and Data Management Core Facility, IDIBAPS, Hospital Clinic Barcelona, Barcelona, Spain
- Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Andrew S Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Aleksander Krag
- Department of Gastroenterology, Odense University Hospital, University of Southern Denmark, Odense, Denmark
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Juan G Abraldes
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, California, USA
| | - Patrick S Kamath
- Gastroenterology and Hepatology, Mayo Medical School, Rochester, Minnesota, USA
| | - Ruben Hernaez
- Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Pere Ginès
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
- Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Barcelona, Spain
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain
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21
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Paar M, Cvirn G, Hoerl G, Reibnegger G, Sourij H, Sourij C, Kojzar H, Oettl K. Albumin of People with Diabetes Mellitus Is More Reduced at Low HbA1c. Int J Mol Sci 2023; 24:16256. [PMID: 38003446 PMCID: PMC10671031 DOI: 10.3390/ijms242216256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 11/08/2023] [Accepted: 11/09/2023] [Indexed: 11/26/2023] Open
Abstract
Oxidative stress is involved in the development, progression, and complications of diabetes mellitus (DM). Oxidative modification of human serum albumin's cysteine-34 is a marker for oxidative stress-related pathological conditions. We aimed to evaluate the redox state of albumin in patients with DM to investigate possible correlations with age, diabetes duration, and disease control status. Plasma aliquots were collected from 52 participants (26 type 1 and 26 type 2 DM). Patients were divided into two groups according to their glycated hemoglobin levels less than or equal to and greater than 58 mmol/L. Albumin redox state was assessed with high-performance liquid chromatography by fractionating it into human mercaptalbumin (HMA) and human nonmercaptalbumin 1 and 2 (HNA1 and HNA2). Albumin redox fractions were differently related to the age of study participants. In age-matched T1DM and T2DM groups, the albumin redox state was essentially the same. Irreversibly oxidized HNA2 was positively correlated with diabetes duration, especially in the T1DM group. HNA was increased in people with an increased HbA1c (>58 mmol/mol). Our results support the hypothesis that oxidative stress plays a crucial role in DM pathogenesis and emphasize the importance of diabetes control on systemic oxidative burden.
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Affiliation(s)
- Margret Paar
- Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010 Graz, Austria; (M.P.); (G.C.); (G.H.); (G.R.)
| | - Gerhard Cvirn
- Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010 Graz, Austria; (M.P.); (G.C.); (G.H.); (G.R.)
| | - Gerd Hoerl
- Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010 Graz, Austria; (M.P.); (G.C.); (G.H.); (G.R.)
| | - Gilbert Reibnegger
- Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010 Graz, Austria; (M.P.); (G.C.); (G.H.); (G.R.)
| | - Harald Sourij
- Division of Endocrinology and Diabetology, Interdisciplinary Metabolic Medicine Trials Unit, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (H.S.); (H.K.)
| | - Caren Sourij
- Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria;
| | - Harald Kojzar
- Division of Endocrinology and Diabetology, Interdisciplinary Metabolic Medicine Trials Unit, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (H.S.); (H.K.)
| | - Karl Oettl
- Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010 Graz, Austria; (M.P.); (G.C.); (G.H.); (G.R.)
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22
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Holte C, Szafranska K, Kruse L, Simon-Santamaria J, Li R, Svistounov D, McCourt P. Highly oxidized albumin is cleared by liver sinusoidal endothelial cells via the receptors stabilin-1 and -2. Sci Rep 2023; 13:19121. [PMID: 37926735 PMCID: PMC10625979 DOI: 10.1038/s41598-023-46462-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 11/01/2023] [Indexed: 11/07/2023] Open
Abstract
Oxidized albumin (oxHSA) is elevated in several pathological conditions, such as decompensated cirrhosis, acute on chronic liver failure and liver mediated renal failure. Patient derived oxidized albumin was previously shown to be an inflammatory mediator, and in normal serum levels of oxHSA are low. The removal from circulation of oxidized albumins is therefore likely required for maintenance of homeostasis. Liver sinusoidal endothelial cells (LSEC) are prominent scavenger cells specialized in removal of macromolecular waste. Given that oxidized albumin is mainly cleared by the liver, we hypothesized the LSEC are the site of uptake in the liver. In vivo oxHSA was cleared rapidly by the liver and distributed to mainly the LSEC. In in vitro studies LSEC endocytosed oxHSA much more than other cell populations isolated from the liver. Furthermore, it was shown that the uptake was mediated by the stabilins, by affinity chromatography-mass spectrometry, inhibiting uptake in LSEC with other stabilin ligands and showing uptake in HEK cells overexpressing stabilin-1 or -2. oxHSA also inhibited the uptake of other stabilin ligands, and a 2-h challenge with 100 µg/mL oxHSA reduced LSEC endocytosis by 60% up to 12 h after. Thus the LSEC and their stabilins mediate clearance of highly oxidized albumin, and oxidized albumin can downregulate their endocytic capacity in turn.
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Affiliation(s)
- Christopher Holte
- Vascular Biology Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
| | - Karolina Szafranska
- Vascular Biology Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway
| | - Larissa Kruse
- Vascular Biology Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway
| | - Jaione Simon-Santamaria
- Vascular Biology Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway
| | - Ruomei Li
- Vascular Biology Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway
| | - Dmitri Svistounov
- Metabolic and Renal Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
| | - Peter McCourt
- Vascular Biology Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway
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23
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Saeidinejad M, Elshabrawi A, Sriphoosanaphan S, Andreola F, Mehta G, Agarwal B, Jalan R. Novel Therapeutic Approaches in Treatment of Acute-on-Chronic Liver Failure. Semin Liver Dis 2023; 43:429-445. [PMID: 38101419 PMCID: PMC10723941 DOI: 10.1055/s-0043-1776773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2023]
Abstract
Acute-on-chronic liver failure (ACLF), a clinical syndrome that can develop at any stage in the progression of cirrhotic liver disease, is characterized by an acute decompensation in liver function with associated multiorgan failure and high short-term mortality. Current evidence points to ACLF being reversible, particularly in those at the lower end of the severity spectrum. However, there are no specific treatments for ACLF, and overall outcomes remain poor. Expedited liver transplantation as a treatment option is limited by organ shortage and a lack of priority allocation for this indication. Other options are therefore urgently needed, and our improved understanding of the condition has led to significant efforts to develop novel therapies. In conclusion, this review aims to summarize the current understanding of the pathophysiological processes involved in the onset, progression, and recovery of ACLF and discuss novel therapies under development.
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Affiliation(s)
- MohammadMahdi Saeidinejad
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Ahmed Elshabrawi
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
- Intensive Care Unit, Endemic Hepatology and Gastroenterology Department, Mansoura University, Mansoura, Egypt
| | - Supachaya Sriphoosanaphan
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok
| | - Fausto Andreola
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Gautam Mehta
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Banwari Agarwal
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
- Intensive Care Unit, Royal Free Hospital, London, United Kingdom
| | - Rajiv Jalan
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
- Hepatology Department, Royal Free Hospital, London, United Kingdom
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
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24
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Liu H, Lyu H, Jiang X, Wang L, Li H, Wei X, Li L, Zhu J, Fan Y, Wang K. Superoxide dismutase 2 as a predictor in patients with hepatitis B virus-associated acute-on-chronic liver failure. Clin Exp Med 2023; 23:2181-2192. [PMID: 36598672 DOI: 10.1007/s10238-022-00979-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 12/11/2022] [Indexed: 01/05/2023]
Abstract
The prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is critical in clinical management. We aimed to assess the prognostic efficacy of superoxide dismutase 2 (SOD2) for 90-day mortality in HBV-ACLF patients. The expression patterns of SOD2 in peripheral blood mononuclear cells (PBMCs) were examined in a derivation set (n = 82) by quantitative real-time polymerase chain reaction (RT-qPCR). The results were further validated in a validation set (n = 35). The expression levels of SOD2 were significantly decreased in the derivation set compared to those with chronic hepatitis B (CHB) or the healthy controls (HCs) (P < 0.001). In HBV-ACLF patients, SOD2 levels were negatively correlated with serum total bilirubin (TBIL) (rs = - 0.43, P < 0.001) and model for end-stage liver disease (MELD) scores (rs = - 0.22, P = 0.047), but positively correlated with alkaline phosphatase (AKP) (rs = 0.23, P = 0.034). SOD2 was identified as an independent risk factor for 90-day mortality in HBV-ACLF patients (hazard ratio: 0.124, 95% confidence interval: 0.059-0.261, P < 0.001). SOD2 yielded a larger area under the receiver operating characteristic curve (AUROC) than the MELD score in predicting 90-day mortality (0.914 vs. 0.712, P < 0.001). Kaplan-Meier analysis revealed a favorable overall survival (OS) for the SOD2 high expression group compared with the SOD2 low expression group in both the derivation and validation sets (P < 0.001). SOD2 has promising potential as a predictor of 90-day mortality in patients with HBV-ACLF.
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Affiliation(s)
- Huihui Liu
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China
| | - Hui Lyu
- Department of Severe Liver Disease, Shandong Public Health Clinical Center of Shandong University, Jinan, 250000, Shandong, China
| | - Xuemei Jiang
- Department of Hepatology, Shandong Public Health Clinical Center of Shandong University, Jinan, 250000, Shandong, China
| | - Li Wang
- Central Laboratory, Qishan Hospital of Yantai, Yantai, 264000, Shandong, China
| | - Haiming Li
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China
| | - Xuefei Wei
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China
| | - Linlin Li
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China
| | - Jinyu Zhu
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China
| | - Yuchen Fan
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China
- Shenzhen Research Institute of Shandong University, Shenzhen, 518000, China
- Institute of Hepatology, Shandong University, Jinan, 250000, Shandong, China
| | - Kai Wang
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China.
- Shenzhen Research Institute of Shandong University, Shenzhen, 518000, China.
- Institute of Hepatology, Shandong University, Jinan, 250000, Shandong, China.
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25
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Butt MF, Jalan R. Review article: Emerging and current management of acute-on-chronic liver failure. Aliment Pharmacol Ther 2023; 58:774-794. [PMID: 37589507 DOI: 10.1111/apt.17659] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/02/2023] [Accepted: 07/24/2023] [Indexed: 08/18/2023]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a clinically and pathophysiologically distinct condition from acutely decompensated cirrhosis and is characterised by systemic inflammation, extrahepatic organ failure, and high short-term mortality. AIMS To provide a narrative review of the diagnostic criteria, prognosis, epidemiology, and general management principles of ACLF. Four specific interventions that are explored in detail are intravenous albumin, extracorporeal liver assist devices, granulocyte-colony stimulating factor, and liver transplantation. METHODS We searched PubMed and Cochrane databases for articles published up to July 2023. RESULTS Approximately 35% of hospital inpatients with decompensated cirrhosis have ACLF. There is significant heterogeneity in the criteria used to diagnose ACLF; different definitions identify different phenotypes with varying mortality. Criteria established by the European Association for the Study of the Liver were developed in prospective patient cohorts and are, to-date, the most well validated internationally. Systemic haemodynamic instability, renal dysfunction, coagulopathy, neurological dysfunction, and respiratory failure are key considerations when managing ACLF in the intensive care unit. Apart from liver transplantation, there are no accepted evidence-based treatments for ACLF, but several different approaches are under investigation. CONCLUSION The recognition of ACLF as a distinct entity from acutely decompensated cirrhosis has allowed for better patient stratification in clinical settings, facilitating earlier engagement with the intensive care unit and liver transplantation teams. Research priorities over the next decade should focus on exploring novel treatment strategies with a particular focus on which, when, and how patients with ACLF should be treated.
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Affiliation(s)
- Mohsin F Butt
- Centre for Neuroscience, Trauma and Surgery, Wingate Institute of Neurogastroenterology, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Liver Failure Group, University College London Medical School, Royal Free Hospital Campus, London, UK
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottinghamshire, UK
| | - Rajiv Jalan
- Liver Failure Group, University College London Medical School, Royal Free Hospital Campus, London, UK
- European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium, Barcelona, Spain
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26
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Lakis R, Sauvage FL, Pinault E, Marquet P, Saint-Marcoux F, El Balkhi S. Semi-synthetic human albumin isoforms: Production, structure, binding capacities and influence on a routine laboratory test. Int J Biol Macromol 2023; 250:126239. [PMID: 37572814 DOI: 10.1016/j.ijbiomac.2023.126239] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 08/02/2023] [Accepted: 08/07/2023] [Indexed: 08/14/2023]
Abstract
Human Serum Albumin (HSA) undergoes Post-Translational-Modifications (PTMs) leading to isoforms affecting its oncotic and non-oncotic properties. HSA is comprised of several isoforms whose abundance may vary with pathologies such as diabetes, kidney and liver diseases. Studying their impact separately may help to understand their sources and potential pathogenicity and further their evaluation as biomarkers. The present study examined semi-synthetic HSA isoforms to investigate independently their structure by means of advanced mass spectrometry techniques (LC-TOF-MS and ICP-MS), influence on the HSA binding/antioxidant activities using a binding capacity test, and potential impact on albumin quantification by a routine immunoturbidimetric assay. Applying different chemical reactions to a commercial HSA solution, we obtained different solutions enriched up to 53 % of native HSA, 78 % of acetylated HSA, 71 % of cysteinylated HSA, 94 % of oxidized HSA, 58 % of nitrosylated HSA and 96 % of glycated HSA, respectively. Moreover, the semi-synthetic isoforms showed differently altered binding capacities for a panel of ligands (Cu, Cd, Au, Ds and L-T4). Furthermore, immunoturbidimetry was found to be insensitive to the presence and abundance of the different isoforms. The fully characterized semi synthetic HSA isoforms obtained should be useful to further investigate their pathogenicity and potential roles as biomarkers.
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Affiliation(s)
- Roy Lakis
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France
| | - François-Ludovic Sauvage
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France
| | - Emilie Pinault
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France
| | - Pierre Marquet
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France; Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges, Limoges, France
| | - Franck Saint-Marcoux
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France; Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges, Limoges, France
| | - Souleiman El Balkhi
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France; Department of Pharmacology, Toxicology and Pharmacovigilance, CHU Limoges, Limoges, France.
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Kosaruk W, Brown JL, Towiboon P, Pringproa K, Punyapornwithaya V, Tankaew P, Kittisirikul N, Toonrongchang W, Janyamathakul T, Muanghong P, Thitaram C. Seasonal patterns of oxidative stress markers in captive Asian elephants in Thailand and relationships to elephant endotheliotropic herpesvirus shedding. Front Vet Sci 2023; 10:1263775. [PMID: 37795017 PMCID: PMC10546319 DOI: 10.3389/fvets.2023.1263775] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 09/06/2023] [Indexed: 10/06/2023] Open
Abstract
Introduction Oxidative stress refers to an imbalance between oxidant and antioxidant activity and accumulation of reactive oxygen species, which can have detrimental effects on animal health. Annual fluctuations in oxidative stress status can occur, increasing disease susceptibility during certain time periods. However, a full understanding of factors related to oxidative stress in Asian elephants and how to mitigate the negative consequences is lacking. Methods This study measured six serum oxidative stress markers [reactive oxygen species (ROS), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), albumin, glutathione peroxidase (GPx), and catalase] and two stress markers [serum cortisol and fecal glucocorticoid metabolites (fGCM)] in 23 captive Asian elephants in Thailand over a 12 months period to examine relationships with age and season. Results Seasonal variations were observed, with several markers exhibiting significantly higher concentrations in the summer (ROS, MDA, 8-OHdG, albumin) and lower values during the rainy/winter seasons (MDA, 8-OHdG, albumin, catalase). By contrast, GPx was the only marker to be highest during the rainy season. For the stress markers, higher fGCM concentrations were noted during the rainy season, which contrasts with earlier studies showing more activity in the winter (tourist season). Positive correlations were found between the temperature-humidity index and ROS, GPx, and fGCM, while a negative correlation was observed with serum albumin. Elephant endotheliotropic herpesvirus (EEHV) shedding events were associated with higher concentrations of ROS and MDA. A moderate negative correlation was observed between 8-OHdG and the PCR threshold cycle of EEHV shedding (Ct), indicating DNA damage may be involved in EEHV shedding in elephants. Discussion Results revealed significant age and seasonal effects on several oxidative stress markers, indicating those factors should be considered in study design and data interpretation. There also may be physiological adaptations in oxidative stress conditions in relation to environmental changes that could impact health outcomes.
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Affiliation(s)
- Worapong Kosaruk
- Doctoral Degree Program in Veterinary Science, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center of Elephant and Wildlife Health, Chiang Mai University Animal Hospital, Chiang Mai, Thailand
- Elephant, Wildlife, and Companion Animals Research Group, Chiang Mai University, Chiang Mai, Thailand
| | - Janine L. Brown
- Center of Elephant and Wildlife Health, Chiang Mai University Animal Hospital, Chiang Mai, Thailand
- Elephant, Wildlife, and Companion Animals Research Group, Chiang Mai University, Chiang Mai, Thailand
- Center for Species Survival, Smithsonian Conservation Biology Institute, Front Royal, VA, United States
| | - Patcharapa Towiboon
- Center of Elephant and Wildlife Health, Chiang Mai University Animal Hospital, Chiang Mai, Thailand
| | - Kidsadagon Pringproa
- Center of Elephant and Wildlife Health, Chiang Mai University Animal Hospital, Chiang Mai, Thailand
- Elephant, Wildlife, and Companion Animals Research Group, Chiang Mai University, Chiang Mai, Thailand
- Department of Veterinary Bioscience and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Veerasak Punyapornwithaya
- Department of Veterinary Bioscience and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Pallop Tankaew
- Central Laboratory, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Narueporn Kittisirikul
- Elephant Hospital, National Elephant Institute, Forest Industry Organization, Lampang, Thailand
| | | | | | | | - Chatchote Thitaram
- Center of Elephant and Wildlife Health, Chiang Mai University Animal Hospital, Chiang Mai, Thailand
- Elephant, Wildlife, and Companion Animals Research Group, Chiang Mai University, Chiang Mai, Thailand
- Department of Companion Animal and Wildlife Clinic, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand
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Grigoryan H, Imani P, Sacerdote C, Masala G, Grioni S, Tumino R, Chiodini P, Dudoit S, Vineis P, Rappaport SM. HSA Adductomics Reveals Sex Differences in NHL Incidence and Possible Involvement of Microbial Translocation. Cancer Epidemiol Biomarkers Prev 2023; 32:1217-1226. [PMID: 37409972 PMCID: PMC10529301 DOI: 10.1158/1055-9965.epi-23-0231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 05/30/2023] [Accepted: 06/28/2023] [Indexed: 07/07/2023] Open
Abstract
BACKGROUND The higher incidence of non-Hodgkin lymphoma (NHL) in males is not well understood. Although reactive oxygen species (ROS) have been implicated as causes of NHL, they cannot be measured directly in archived blood. METHODS We performed untargeted adductomics of stable ROS adducts in human serum albumin (HSA) from 67 incident NHL cases and 82 matched controls from the European Prospective Investigation into Cancer and Nutrition-Italy cohort. Regression and classification methods were employed to select features associated with NHL in all subjects and in males and females separately. RESULTS Sixty seven HSA-adduct features were quantified by liquid chromatography-high-resolution mass spectrometry at Cys34 (n = 55) and Lys525 (n = 12). Three features were selected for association with NHL in all subjects, while seven were selected for males and five for females with minimal overlap. Two selected features were more abundant in cases and seven in controls, suggesting that altered homeostasis of ROS may affect NHL incidence. Heat maps revealed differential clustering of features between sexes, suggesting differences in operative pathways. CONCLUSIONS Adduct clusters dominated by Cys34 oxidation products and disulfides further implicate ROS and redox biology in the etiology of NHL. Sex differences in dietary and alcohol consumption also help to explain the limited overlap of feature selection between sexes. Intriguingly, a disulfide of methanethiol from enteric microbial metabolism was more abundant in male cases, thereby implicating microbial translocation as a potential contributor to NHL in males. IMPACT Only two of the ROS adducts associated with NHL overlapped between sexes and one adduct implicates microbial translocation as a risk factor.
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Affiliation(s)
- Hasmik Grigoryan
- School of Public Health, University of California, Berkeley, California, 94720, United States
| | - Partow Imani
- School of Public Health, University of California, Berkeley, California, 94720, United States
| | - Carlotta Sacerdote
- Unit of Cancer Epidemiology Città della Salute e della Scienza University-Hospital, 10126, Turin, Italy
| | - Giovanna Masala
- Institute of Cancer Research, Prevention and Clinical Network (ISPRO), 50139, Florence, Italy
| | - Sara Grioni
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
| | - Rosario Tumino
- Hyblean Association for Epidemiological Research, AIRE-ONLUS, 97100, Ragusa, Italy
| | - Paolo Chiodini
- Dipartimento di Salute Mentale e Fisica e Medicina Preventiva, Università degli Studi della Campania ‘Luigi Vanvitelli’, 80138, Naples, Italy
| | - Sandrine Dudoit
- School of Public Health, University of California, Berkeley, California, 94720, United States
- Department of Statistics, University of California, Berkeley, CA, 94720, United States
| | - Paolo Vineis
- Unit of Cancer Epidemiology Città della Salute e della Scienza University-Hospital, 10126, Turin, Italy
- MRC-PHE Centre for Environment and Health, Imperial College, Norfolk Place London W21PG, UK
| | - Stephen M. Rappaport
- School of Public Health, University of California, Berkeley, California, 94720, United States
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Liu S, Chen Y, Wang X, Wang S, Bai L, Cheng X, Wan J, Hu Y, Ding Y, Zhang X, Ding M, Li H, Hu M. Plasma metabolomics identifies metabolic alterations associated with the growth and development of cat. Animal Model Exp Med 2023; 6:306-316. [PMID: 37271879 PMCID: PMC10486329 DOI: 10.1002/ame2.12328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 04/09/2023] [Indexed: 06/06/2023] Open
Abstract
BACKGROUND The purpose of our study was to study the composition and content of the feline plasma metabolome revealing the critical metabolites and metabolic pathways associated with age during growth and development. METHODS Blood samples were collected from juvenile and adult groups for blood routine tests and serum biochemistry tests. Non-targeted metabolomics analyses of plasma were also performed to investigate changes in metabolites and metabolic pathways. RESULTS In this study, we found that the red blood cell counts, liver function indexes (albumin and gamma-glutamyl transpeptidase), and the concentration of triglyceride and glucose changed significant with growth and development. The metabolomics results revealed that 1427 metabolites were identified in the plasma of young and adult cats. Most of these metabolites belong to major classes of lipids and lipid-like molecules. The most obvious age-related metabolites include reduced levels of chenodeoxycholate, taurocholate, cholate, and taurochenodeoxycholate but increased levels of L-cysteine and taurocyamine in the adult cat's serum. These metabolites are mainly involved in the primary bile acid biosynthesis pathway, the bile secretion pathway, and the taurine and hypotaurine metabolism pathway. CONCLUSION This study revealed many age-related metabolite alterations in the feline plasma. These age-varying metabolites, especially in the bile acid biosynthesis and secretion metabolism pathways, indicate that the regulation of these pathways is involved in the growth and development of cats. This study promotes our understanding of the mechanism of feline growth and provides new insights into nutrition and medicine for cats of different ages.
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Affiliation(s)
- Shuaiyang Liu
- School of Basic Medical Science, Wuhan UniversityWuhanChina
- Institute of Model Animal, Wuhan UniversityWuhanChina
| | - Yun Chen
- Institute of Model Animal, Wuhan UniversityWuhanChina
- Clinical Trial CentersHuanggang Central HospitalHuanggangChina
| | - Xiaoming Wang
- School of Basic Medical Science, Wuhan UniversityWuhanChina
- Institute of Model Animal, Wuhan UniversityWuhanChina
| | - Shuang Wang
- College of Veterinary Medicine, Huazhong Agricultural UniversityWuhanChina
| | - Lan Bai
- Key Laboratory of Cardiovascular Disease Prevention and Control, Ministry of EducationSchool of Basic Medical Science, Gannan Medical UniversityGanzhouChina
- Gannan Innovation and Translational Medicine Research Institute, Gannan Medical UniversityGanzhouChina
| | - Xu Cheng
- Key Laboratory of Cardiovascular Disease Prevention and Control, Ministry of EducationSchool of Basic Medical Science, Gannan Medical UniversityGanzhouChina
- Gannan Innovation and Translational Medicine Research Institute, Gannan Medical UniversityGanzhouChina
| | - Juan Wan
- Key Laboratory of Cardiovascular Disease Prevention and Control, Ministry of EducationSchool of Basic Medical Science, Gannan Medical UniversityGanzhouChina
- Gannan Innovation and Translational Medicine Research Institute, Gannan Medical UniversityGanzhouChina
| | - Yufeng Hu
- Key Laboratory of Cardiovascular Disease Prevention and Control, Ministry of EducationSchool of Basic Medical Science, Gannan Medical UniversityGanzhouChina
- Gannan Innovation and Translational Medicine Research Institute, Gannan Medical UniversityGanzhouChina
| | - Yi Ding
- College of Veterinary Medicine, Huazhong Agricultural UniversityWuhanChina
| | - Xin Zhang
- Key Laboratory of Cardiovascular Disease Prevention and Control, Ministry of EducationSchool of Basic Medical Science, Gannan Medical UniversityGanzhouChina
- Gannan Innovation and Translational Medicine Research Institute, Gannan Medical UniversityGanzhouChina
| | - Mingxing Ding
- College of Veterinary Medicine, Huazhong Agricultural UniversityWuhanChina
| | - Hongliang Li
- School of Basic Medical Science, Wuhan UniversityWuhanChina
- Institute of Model Animal, Wuhan UniversityWuhanChina
- Gannan Innovation and Translational Medicine Research Institute, Gannan Medical UniversityGanzhouChina
| | - Manli Hu
- Key Laboratory of Cardiovascular Disease Prevention and Control, Ministry of EducationSchool of Basic Medical Science, Gannan Medical UniversityGanzhouChina
- Gannan Innovation and Translational Medicine Research Institute, Gannan Medical UniversityGanzhouChina
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Paar M, Fengler VH, Reibnegger G, Schnurr K, Waterstradt K, Schwaminger SP, Stauber RE, Oettl K. Determination of binding characteristics as a measure for effective albumin using different methods. Biochim Biophys Acta Gen Subj 2023:130427. [PMID: 37454915 DOI: 10.1016/j.bbagen.2023.130427] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/13/2023] [Accepted: 07/13/2023] [Indexed: 07/18/2023]
Abstract
BACKGROUND & AIMS Transport functions of albumin are of clinical and pharmacological interest and are determined by albumin's properties like posttranslational modifications or bound ligands. Both are affected in pathological conditions and in therapeutic grade albumin solutions. The term effective albumin concentration was introduced as a measure of functionally intact albumin. Our aim was to evaluate the impact of ligands and modifications with different approaches as a measure of effective albumin. APPROACH & RESULTS We used a spin labelled fatty acid and dansylsarcosine to characterize binding properties of albumin i) prepared from plasma of patients and healthy control donors, ii) measured directly out of plasma, iii) research grade albumin, iv) in vitro modified albumin, and v) therapeutic infusion solutions before and after removal of stabilizers. Bilirubin is the main determinant for binding function in patients' albumin. In in vitro prepared albumin bound fatty acids correlated with impaired binding. Human nonmercaptalbumin1, not human nonmercaptalbumin2, showed reduced binding properties. Binding and transport function of therapeutic albumin was severely impaired and restored by filtration. Glycation of research grade albumin had no effect on the binding of dansylsarcosine and only a minor effect on fatty acid binding. CONCLUSIONS Our results suggest that effective albumin -in terms of binding properties- is primarily determined by bound ligands and only to a minor extent by posttranslational modifications. Characterizing albumin directly from plasma better reflects the physiological situation whereas in the case of therapeutic grade albumin stabilizers should be removed to make its binding properties accessible.
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Affiliation(s)
- Margret Paar
- Medical University of Graz, Otto Loewi Research Center, Division of Medicinal Chemistry, Neue Stiftingtalstrasse 6, 8010, Graz, Austria
| | - Vera H Fengler
- University of Graz, Institute of Molecular Biosciences, Humboldtstrasse 50, 8010, Graz, Austria
| | - Gilbert Reibnegger
- Medical University of Graz, Otto Loewi Research Center, Division of Medicinal Chemistry, Neue Stiftingtalstrasse 6, 8010, Graz, Austria
| | - Kerstin Schnurr
- MedInnovation GmbH, Wissenschaftsstandort Berlin-Adlershof (WISTA), Groß-Berliner Damm 151, 12487 Berlin, Germany
| | - Katja Waterstradt
- MedInnovation GmbH, Wissenschaftsstandort Berlin-Adlershof (WISTA), Groß-Berliner Damm 151, 12487 Berlin, Germany
| | - Sebastian P Schwaminger
- Medical University of Graz, Otto Loewi Research Center, Division of Medicinal Chemistry, Neue Stiftingtalstrasse 6, 8010, Graz, Austria; BioTechMed-Graz, Mozartgasse 12, 8010 Graz, Austria
| | - Rudolf E Stauber
- Medical University of Graz, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Auenbruggerplatz 15, 8036 Graz, Austria
| | - Karl Oettl
- Medical University of Graz, Otto Loewi Research Center, Division of Medicinal Chemistry, Neue Stiftingtalstrasse 6, 8010, Graz, Austria.
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Tiwari A, Aziz RA, Gattani R, Kumar Prajapati S, Tripathi R. Liver decompensation: the yard stick that measures indications and adverse effects of human albumin infusion. Hepatol Int 2023; 17:770-772. [PMID: 36753027 DOI: 10.1007/s12072-023-10483-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 01/06/2023] [Indexed: 02/09/2023]
Affiliation(s)
- Avinash Tiwari
- Department of Gastroenterology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, 190011, India.
| | - Riffat Abdul Aziz
- Department of Gastroenterology, Father Muller Medical College, Mangalore, Karnataka, 575002, India
| | - Ramkishor Gattani
- Department of Gastroenterology, Institute of Medical Sciences-Banaras Hindu University (BHU), Varanasi, Uttar Pradesh, 221005, India
| | - Sandeep Kumar Prajapati
- Department of Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Dhanvantari Nagar, Puducherry, India
| | - Riddhima Tripathi
- Sharda University School of Medical Sciences and Research, Greater Noida, Uttar Pradesh, India
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Rahali MA, Lakis R, Sauvage FL, Pinault E, Marquet P, Saint-Marcoux F, El Balkhi S. Posttranslational-modifications of human-serum-albumin analysis by a top-down approach validated by a comprehensive bottom-up analysis. J Chromatogr B Analyt Technol Biomed Life Sci 2023; 1224:123740. [PMID: 37182409 DOI: 10.1016/j.jchromb.2023.123740] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Revised: 05/03/2023] [Accepted: 05/05/2023] [Indexed: 05/16/2023]
Abstract
The posttranslational modifications (PTM) of human serum albumin (HSA) can result in the development of isoforms that have been identified as potential biomarkers for advanced hepatic diseases. However, previous approaches using top-down (TD) analysis to identify isoforms based on molecular weight may have resulted in misidentifications. The nature of the identified isoforms has never been confirmed in previous works. Here, we aimed to critically evaluate TD for the characterization and determination of HSA isoforms in patients and make an inventory of HSA-PTM. Serum samples from control subjects and patients with liver dysfunctions were analyzed using both top-down (TD) and bottom-up (BU) approaches. TD analysis involved using a LC-TOF-MS system to obtain a multicharged spectrum of HSA, which was deconvoluted to identify isoforms. Spectra were then used for relative quantitation analysis of albumin isoform abundances based on trapezoidal integration. For BU analysis, serums were reduced +/- alkylated, digested with trypsin and analyzed in the Q-TOF, data-dependent acquisition (DDA) mode to generate a SWATH-MS high-resolution mass spectral library of all HSA peptides. Tryptic digests of another set of serum samples were then analyzed using data-independent acquisition (DIA) mode to confirm the presence of HSA isoforms and their modification sites. TD detected 15 isoforms corresponding to various modifications, including glycation, cysteinylation, nitrosylation, and oxidation (di- and tri-). In BU, the spectral library containing 127 peptides allowed for the characterization of the important isoforms with their modified sites, including some modifications that were only characterized in BU (carbamylation, deamidation, and amino-acid substitution). The method used for determining isoforms offered acceptable reproducibility (intra-/inter-assay CVs < 15%) for all isoforms present at relative abundances higher than 2%. Overall, the study found that several isoforms could be missed or misidentified by TD. However, all HSA isoforms identified by TD and reported to be relevant in liver dysfunctions were confirmed by BU. This critical evaluation of TD approach helped design an adequate and reliable method for the characterization of HSA isoforms in patients and offers the possibility to estimate isoform abundances within 3 min. These findings have significant implications for the diagnosis and treatment of liver dysfunctions.
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Affiliation(s)
- Mohamad-Ali Rahali
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France
| | - Roy Lakis
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France
| | - François-Ludovic Sauvage
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France
| | - Emilie Pinault
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France
| | - Pierre Marquet
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France; Department of pharmacology, toxicology and pharmacovigilance, CHU Limoges, Limoges, France
| | - Franck Saint-Marcoux
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France; Department of pharmacology, toxicology and pharmacovigilance, CHU Limoges, Limoges, France
| | - Souleiman El Balkhi
- P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France; Department of pharmacology, toxicology and pharmacovigilance, CHU Limoges, Limoges, France.
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Smith JW, O'Meally RN, Burke SM, Ng DK, Chen JG, Kensler TW, Groopman JD, Cole RN. Global Discovery and Temporal Changes of Human Albumin Modifications by Pan-Protein Adductomics: Initial Application to Air Pollution Exposure. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 2023; 34:595-607. [PMID: 36939690 DOI: 10.1021/jasms.2c00314] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Assessing personal exposure to environmental toxicants is a critical challenge for predicting disease risk. Previously, using human serum albumin (HSA)-based biomonitoring, we reported dosimetric relationships between adducts at HSA Cys34 and ambient air pollutant levels (Smith et al., Chem. Res. Toxicol. 2021, 34, 1183). These results provided the foundation to explore modifications at other sites in HSA to reveal novel adducts of complex exposures. Thus, the Pan-Protein Adductomics (PPA) technology reported here is the next step toward an unbiased, comprehensive characterization of the HSA adductome. The PPA workflow requires <2 μL serum/plasma and uses nanoflow-liquid chromatography, gas-phase fractionation, and overlapping-window data-independent acquisition high-resolution tandem mass spectrometry. PPA analysis of albumin from nonsmoking women exposed to high levels of air pollution uncovered 68 unique location-specific modifications (LSMs) across 21 HSA residues. While nearly half were located at Cys34 (33 LSMs), 35 were detected on other residues, including Lys, His, Tyr, Ser, Met, and Arg. HSA adduct relative abundances spanned a ∼400 000-fold range and included putative products of exogenous (SO2, benzene, phycoerythrobilin) and endogenous (oxidation, lipid peroxidation, glycation, carbamylation) origin, as well as 24 modifications without annotations. PPA quantification revealed statistically significant changes in LSM levels across the 84 days of monitoring (∼3 HSA lifetimes) in the following putative adducts: Cys34 trioxidation, β-methylthiolation, benzaldehyde, and benzene diol epoxide; Met329 oxidation; Arg145 dioxidation; and unannotated Cys34 and His146 adducts. Notably, the PPA workflow can be extended to any protein. Pan-Protein Adductomics is a novel and powerful strategy for untargeted global exploration of protein modifications.
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Affiliation(s)
- Joshua W Smith
- Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, United States
| | - Robert N O'Meally
- Department of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, United States
| | - Sean M Burke
- Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, United States
| | - Derek K Ng
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, United States
| | - Jian-Guo Chen
- Qidong Liver Cancer Institute, Qidong People's Hospital, Affiliated Qidong Hospital of Nantong University, Qidong, Jiangsu 226200, P. R. China
| | - Thomas W Kensler
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, United States
| | - John D Groopman
- Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, United States
| | - Robert N Cole
- Department of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, United States
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Wang YL, Liu YH, Zhu CW. Application of effective albumin concentration in treatment of chronic liver disease. Shijie Huaren Xiaohua Zazhi 2023; 31:214-220. [DOI: 10.11569/wcjd.v31.i6.214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/28/2023] Open
Abstract
Albumin is a non-glycosylated plasma protein. Besides the role of increasing blood volume and maintaining plasma colloid osmotic pressure, albumin also has multiple biological functions such as transport, antioxidant and anti-inflammatory effects, immune regulation, etc. In-depth studies on the structure and function of albumin have revealed that the post-transcriptional modification of albumin reduces the effective albumin concentration in patients with chronic liver disease, so the clinically effective albumin concentration rather than total albumin concentration can more accurately reflect the disease progression and prognosis, and more effectively guide exogenous albumin treatment in such patients. This article summarizes the clinical correlation between post-transcriptional modification of albumin and the liver and its related diseases, as well as the studies on effective albumin, in order to provide evidence-based information on effective albumin concentration and to better guide the clinical treatment of chronic liver disease.
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Effective albumin – A novel paradigm in the management of decompensated liver cirrhosis. J Transl Int Med 2023; 11:11-14. [DOI: 10.2478/jtim-2022-0070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2023] Open
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Jeng LB, Chan WL, Teng CF. Prognostic Significance of Serum Albumin Level and Albumin-Based Mono- and Combination Biomarkers in Patients with Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:cancers15041005. [PMID: 36831351 PMCID: PMC9953807 DOI: 10.3390/cancers15041005] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 01/31/2023] [Accepted: 02/03/2023] [Indexed: 02/08/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer. Although many surgical and nonsurgical therapeutic options have been established for treating HCC, the overall prognosis for HCC patients receiving different treatment modalities remains inadequate, which causes HCC to remain among the most life-threatening human cancers worldwide. Therefore, it is vitally important and urgently needed to develop valuable and independent prognostic biomarkers for the early prediction of poor prognosis in HCC patients, allowing more time for more timely and appropriate treatment to improve the survival of patients. As the most abundant protein in plasma, human serum albumin (ALB) is predominantly expressed by the liver and exhibits a wide variety of essential biological functions. It has been well recognized that serum ALB level is a significant independent biomarker for a broad spectrum of human diseases including cancer. Moreover, ALB has been commonly used as a potent biomaterial and therapeutic agent in clinical settings for the treatment of various human diseases. This review provides a comprehensive summary of the evidence from the up-to-date published literature to underscore the prognostic significance of serum ALB level and various ALB-based mono- and combination biomarkers in the prediction of the prognosis of HCC patients after treatment with different surgical, locoregional, and systemic therapies.
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Affiliation(s)
- Long-Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan
- Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan
- Cell Therapy Center, China Medical University Hospital, Taichung 404, Taiwan
| | - Wen-Ling Chan
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung 413, Taiwan
- Epigenome Research Center, China Medical University Hospital, Taichung 404, Taiwan
| | - Chiao-Fang Teng
- Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan
- Program for Cancer Biology and Drug Development, China Medical University, Taichung 404, Taiwan
- Research Center for Cancer Biology, China Medical University, Taichung 404, Taiwan
- Correspondence: ; Tel.: +886-4-2205-2121; Fax: +886-4-2202-9083
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Paar M, Seifried K, Cvirn G, Buchmann A, Khalil M, Oettl K. Redox State of Human Serum Albumin in Multiple Sclerosis: A Pilot Study. Int J Mol Sci 2022; 23:ijms232415806. [PMID: 36555448 PMCID: PMC9779316 DOI: 10.3390/ijms232415806] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/07/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
Like in many other pathologies, oxidative stress is involved in the development of neurodegenerative disorders. Human serum albumin (HSA) is the main protein in different body fluids including cerebrospinal fluid (CSF). By its redox state in terms of cysteine-34, albumin serves as marker for oxidative burden. We aimed to evaluate the redox state of HSA in patients with multiple sclerosis in serum and CSF in comparison to controls to identify possible correlations with disease activity and severity. Samples were stored at -70 °C until analysis by HPLC for the determination of albumin redox state in terms of the fractions of human mercaptalbumin (HMA), human nonmercaptalbumin1 (HNA1), and human nonmercaptalbumin2 (HNA2). Albumin in CSF showed significantly higher fractions of the reduced form HMA and decreased HNA1 and HNA2. There was no difference between albumin redox states in serum of patients and controls. In CSF of patients HNA2 showed a trend to higher fractions compared to controls. Albumin redox state in serum was associated with physical disability in remission while albumin redox state in CSF was related to disease activity. Thus, albumin redox state in serum and CSF of patients in relation to disease condition merits further investigation.
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Affiliation(s)
- Margret Paar
- Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria
| | - Katharina Seifried
- Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria
| | - Gerhard Cvirn
- Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria
| | - Arabella Buchmann
- Department of Neurology, Medical University of Graz, 8036 Graz, Austria
| | - Michael Khalil
- Department of Neurology, Medical University of Graz, 8036 Graz, Austria
- Correspondence: (M.K.); (K.O.); Tel.: +43-(0)316-385-30313 (M.K.); +43-(0)316-385-72121 (K.O.)
| | - Karl Oettl
- Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria
- Correspondence: (M.K.); (K.O.); Tel.: +43-(0)316-385-30313 (M.K.); +43-(0)316-385-72121 (K.O.)
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Hu S, Guo Q, Wang S, Zhang W, Ye J, Su L, Zou S, Zhang D, Zhang Y, Yu D, Xu J, Wei Y. Supplementation of serum albumin is associated with improved pulmonary function: NHANES 2013–2014. Front Physiol 2022; 13:948370. [PMID: 36262258 PMCID: PMC9574070 DOI: 10.3389/fphys.2022.948370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 09/14/2022] [Indexed: 11/13/2022] Open
Abstract
Background: The serum albumin level is reflective of the function of multiple organs, such as the liver and kidneys. However, the association between serum albumin and pulmonary function is unclear; therefore, this study aimed to determine the relationship between pulmonary function and serum albumin, including the threshold of serum albumin at the changes of the pulmonary function in the total population and in different strata of population. Methods: In this cross-sectional study, We examined the relationship between serum albumin and two independent indicators of pulmonary function: forced vital capacity (FVC) and forced expiratory volume in one second (FEV 1), using data from National Health and Nutrition Examination Survey (NHANES 2013–2014) (n = 3286). We used univariate analysis, stratified analysis, and multiple regression equation analysis to examine the correlation between serum albumin levels and FVC and FEV 1, and performed smoothed curve fitting, threshold effect, and saturation effect analysis (for stratification) to determine the threshold serum albumin level at which FVC and FEV 1 begin to change. Results: The adjusted smoothed curve fit plot showed a linear relationship between serum albu-min levels and FVC: for every 1 g/dl increase in the serum albumin level, FVC increased by 80.40 ml (11.18, 149.61). Serum albumin and FEV 1 showed a non-linear relationship. When serum al-bumin reached the inflection point (3.8 g/dl), FEV 1 increased with increasing serum albumin and the correlation coefficient β was 205.55 (140.15, 270.95). Conclusion: Serum albumin is a core indicator of liver function, and abnormal liver function has a direct impact on pulmonary function. In the total population, serum albumin levels were linearly and positively correlated with FVC. Above 3.6 g/dl, serum albumin was positively correlated with FEV 1. Based on the total population and different population strata, this study revealed a positive association between the serum albumin level and pulmonary function, and identified the threshold of serum albumin when Indicators of pulmonary function tests starts to rise, providing a new early warning indicator for people at high risk of pulmonary insufficiency and has positive implications for the prevention of combined respiratory failure in patients with liver insufficiency.
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Study of Albumin Oxidation in COVID-19 Pneumonia Patients: Possible Mechanisms and Consequences. Int J Mol Sci 2022; 23:ijms231710103. [PMID: 36077496 PMCID: PMC9456270 DOI: 10.3390/ijms231710103] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 08/25/2022] [Accepted: 09/02/2022] [Indexed: 11/23/2022] Open
Abstract
Oxidative stress induced by neutrophils and hypoxia in COVID-19 pneumonia leads to albumin modification. This may result in elevated levels of advanced oxidation protein products (AOPPs) and advanced lipoxidation end-products (ALEs) that trigger oxidative bursts of neutrophils and thus participate in cytokine storms, accelerating endothelial lung cell injury, leading to respiratory distress. In this study, sixty-six hospitalized COVID-19 patients with respiratory symptoms were studied. AOPPs-HSA was produced in vitro by treating human serum albumin (HSA) with chloramine T. The interaction of malondialdehyde with HSA was studied using time-resolved fluorescence spectroscopy. The findings revealed a significantly elevated level of AOPPs in COVID-19 pneumonia patients on admission to the hospital and one week later as long as they were in the acute phase of infection when compared with values recorded for the same patients 6- and 12-months post-infection. Significant negative correlations of albumin and positive correlations of AOPPs with, e.g., procalcitonin, D-dimers, lactate dehydrogenase, aspartate transaminase, and radiological scores of computed tomography (HRCT), were observed. The AOPPs/albumin ratio was found to be strongly correlated with D-dimers. We suggest that oxidized albumin could be involved in COVID-19 pathophysiology. Some possible clinical consequences of the modification of albumin are also discussed.
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Pande G, Hatti M, Rai MK, Rai P, Kumar K, VP K, Nehra A, Kumar S, Ranjan Rout S, Mishra SK, Kumar D, Kumar U, Mishra P, Majeed A, Saraswat VA, Singh K, Singh H, Misra DP, Agarwal V. Response Guided Slow Infusion of Albumin, Vasoconstrictors and Furosemide Improves Ascites Mobilization and Survival in Acute on Chronic Liver Failure: A Proof-of-Concept Study. J Inflamm Res 2022; 15:5027-5039. [PMID: 36072778 PMCID: PMC9444030 DOI: 10.2147/jir.s377494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 08/13/2022] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND AND AIMS Acute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcomes. Severely deranged systemic hemodynamics and decreased effective arterial blood volume contribute to tissue damage and organ failure. Response-guided therapy with albumin, vasoconstrictors, and furosemide may help overcome effective hypovolemia, improve diuresis and impact survival. METHODS In the observation cohort, 230 patients with ACLF (CANONIC criteria) with ascites (≥Grade II) and ACLF ≥Grade I were enrolled. A total of 136 patients (GROUP I) received response-guided (urine sodium >80mmol/day) slow albumin-furosemide infusion ± terlipressin (SAFI ± T), while 94 patients (GROUP II) received standard medical therapy. Twenty-eight-day survival, ascites mobilization (nil or grade 1), and adverse events were noted. In another mechanistic cohort (n = 40), laboratory evidences for improvement in various pathophysiological alterations; gut permeability, endotoxemia, cytokine storm, neutrophil dysfunction, and hemodynamic alterations following SAFI ± T/Noradrenaline (NAdr) were evaluated. RESULTS Age, gender, CLIF-C-ACLF, SOFA and MELD scores, ACLF grades and urine sodium were not different between the two groups in the observation cohort. Ascites was mobilized in 102/136 in GROUP I (SAFI ± T) and 23/94 in GROUP II (p < 0.05). Twenty-eight-day survival was significantly higher in GROUP I = 103/136 (75.7%) vs GROUP II = 50/94 (53.2%), (P = <0.001). All those who were unable to reach urine sodium >80 mmol/day died. Four patients in GROUP I developed scrotal gangrene. In the mechanistic cohort, 72% of patients survived with significant improvement in gut permeability, endotoxemia, serum cytokines, neutrophil dysfunction, and hemodynamic alterations. CONCLUSION Ascitic fluid mobilization by response-guided SAFI ± T/NAdr therapy improves survival by improving splanchnic and systemic hemodynamics, decreasing gut congestion, gut permeability, and endotoxemia, improving neutrophil functions, and reducing pro-inflammatory cytokines in circulation.
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Affiliation(s)
- Gaurav Pande
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Manjunath Hatti
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Mohit Kumar Rai
- Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Praveer Rai
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Kamlesh Kumar
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Krishna VP
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Abhimanyu Nehra
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Sudeep Kumar
- Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Smarak Ranjan Rout
- Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Sourav Kumar Mishra
- Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Dinesh Kumar
- Department of Advanced Spectroscopy and Imaging, Center of Biomedical Research, Lucknow, India
| | - Umesh Kumar
- Department of Advanced Spectroscopy and Imaging, Center of Biomedical Research, Lucknow, India
| | - Prabhaker Mishra
- Biostatistics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Abdul Majeed
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Vivek Anand Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Kritika Singh
- Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Harshit Singh
- Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Durga Prasanna Misra
- Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Vikas Agarwal
- Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Kulkarni AV, Premkumar M, Arab JP, Kumar K, Sharma M, Reddy ND, Padaki NR, Reddy RK. Early Diagnosis and Prevention of Infections in Cirrhosis. Semin Liver Dis 2022; 42:293-312. [PMID: 35672014 DOI: 10.1055/a-1869-7607] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Strategies to prevent infection and improve outcomes in patients with cirrhosis. HAV, hepatitis A virus; HBV, hepatitis B virus; COVID-19, novel coronavirus disease 2019; NSBB, nonselective β-blocker; PPI, proton pump inhibitors.Cirrhosis is a risk factor for infections. Majority of hospital admissions in patients with cirrhosis are due to infections. Sepsis is an immunological response to an infectious process that leads to end-organ dysfunction and death. Preventing infections may avoid the downstream complications, and early diagnosis of infections may improve the outcomes. In this review, we discuss the pathogenesis, diagnosis, and biomarkers of infection; the incremental preventive strategies for infections and sepsi; and the consequent organ failures in cirrhosis. Strategies for primary prevention include reducing gut translocation by selective intestinal decontamination, avoiding unnecessary proton pump inhibitors' use, appropriate use of β-blockers, and vaccinations for viral diseases including novel coronavirus disease 2019. Secondary prevention includes early diagnosis and a timely and judicious use of antibiotics to prevent organ dysfunction. Organ failure support constitutes tertiary intervention in cirrhosis. In conclusion, infections in cirrhosis are potentially preventable with appropriate care strategies to then enable improved outcomes.
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Affiliation(s)
- Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Juan P Arab
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Karan Kumar
- Department of Hepatology, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India
| | - Mithun Sharma
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Nageshwar D Reddy
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Nagaraja R Padaki
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Rajender K Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
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Boss K, Stettner M, Szepanowski F, Mausberg AK, Paar M, Pul R, Kleinschnitz C, Oettl K, Kribben A. Severe and long-lasting alteration of albumin redox state by plasmapheresis. Sci Rep 2022; 12:12165. [PMID: 35842435 PMCID: PMC9288533 DOI: 10.1038/s41598-022-16452-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 07/11/2022] [Indexed: 11/22/2022] Open
Abstract
Plasmapheresis (PE) is an established form of therapeutic apheresis (TA). Purpose of this longitudinal prospective single center study was to investigate the effect of PE on albumin redox state (ARS), as infusion of commercial albumin during PE may alter albumin oxidation which has an impact on its functional properties and oxidative stress level. 43 subjects with autoimmune-mediated neurological disorders were included. 20 subjects in the experimental group received five treatments of PE. 13 subjects received five treatments of immunoadsorption and 10 subjects received no TA as controls. ARS was determined before and after TA and 12 days after the last TA by fractionating it into human mercaptalbumin (HMA), human non-mercaptalbumin 1 (HNA-1), and human non-mercaptalbumin 2 (HNA-2) by high-performance liquid chromatography. Irreversibly oxidised HNA-2 increased over the course of five PE treatments from 2.8% (IQR 1.3–3.7%) to 13.6% (IQR 10.9–15.9) (P < 0.01) and remained elevated 12 days after the last PE procedure (7.7% IQR 7.1–10.5, P < 0.05). The study showed for the first time that PE exerts a severe and long-lasting alteration on ARS indicating a new adverse effect of PE, that may influence oxidative stress level.
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Affiliation(s)
- Kristina Boss
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, 45147, Essen, Germany.
| | - Mark Stettner
- Department of Neurology and Center for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Fabian Szepanowski
- Department of Neurology and Center for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Anne K Mausberg
- Department of Neurology and Center for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Margret Paar
- Division of Physiological Chemistry, Otto Loewi Research Center, Medical University of Graz, Graz, Austria
| | - Refik Pul
- Department of Neurology and Center for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Christoph Kleinschnitz
- Department of Neurology and Center for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Karl Oettl
- Division of Physiological Chemistry, Otto Loewi Research Center, Medical University of Graz, Graz, Austria
| | - Andreas Kribben
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, 45147, Essen, Germany
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Liu YT, Hu YQ, Wang YL, Huang K, Chen GF, Zhou H, Liu CH, Yang T. Antibiotic pretreatment promotes orally-administered triptolide absorption and aggravates hepatotoxicity and intestinal injury in mice. JOURNAL OF ETHNOPHARMACOLOGY 2022; 292:115224. [PMID: 35351577 DOI: 10.1016/j.jep.2022.115224] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 01/27/2022] [Accepted: 03/22/2022] [Indexed: 06/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Triptolide (TP) exhibits extensive pharmacological activity, but its hepatotoxicity and intestinal injury are significant and limit its clinical use. AIM OF THE STUDY To investigate the effect of gut microbiota disturbance after antibiotic pretreatment on TP-induced hepatotoxicity, intestinal injury and their mechanism. MATERIALS AND METHODS We compared the characteristics of TP-induced hepatotoxicity and intestinal injury in mice with or without antibiotic pretreatment. The levels of cytokines in the serum, immunohistochemistry, and the pharmacokinetics of TP were determined. RESULT Antibiotic pretreatment aggravates TP-induced hepatotoxicity and ileum/colon injury. TP induces hepatotoxicity in a dose-dependent manner after antibiotic pretreatment. Serum IL-1β and IL-6 levels were increased in mice given oral TP after antibiotic pretreatment. TP can increase the expression of NLRP3 inflammasome in hepatocytes, and Oral TP after antibiotic pretreatment can significantly enhance its expression, but NLRP3 inflammasome no significant change in colon and ileum. The pharmacokinetic characteristics of TP are altered significantly by antibiotic pretreatment, as shown by a 145.87% increase in Cmax, a 155.11% increase in AUC0-t, a 155.1% increase in relative bioavailability, and a 15.44% delay in MRT. Moreover, TP causes hepatotoxicity in a time-dependent manner. CONCLUSIONS Antibiotic pretreatment aggravates triptolide-induced hepatotoxicity and intestinal injury through elevated inflammatory response and promoted triptolide absorption.
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Affiliation(s)
- Yu-Ting Liu
- Institute of Cardiovascular Disease, Institute of Cardiovascular Disease of Integrated Traditional Chinese Medicine and Western Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Ye-Qing Hu
- Institute of Cardiovascular Disease, Institute of Cardiovascular Disease of Integrated Traditional Chinese Medicine and Western Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yu-Lin Wang
- Institute of Cardiovascular Disease, Institute of Cardiovascular Disease of Integrated Traditional Chinese Medicine and Western Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Kai Huang
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, 201203, China
| | - Gao-Feng Chen
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, 201203, China
| | - Hua Zhou
- Institute of Cardiovascular Disease, Institute of Cardiovascular Disease of Integrated Traditional Chinese Medicine and Western Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Cheng-Hai Liu
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, 201203, China
| | - Tao Yang
- Institute of Cardiovascular Disease, Institute of Cardiovascular Disease of Integrated Traditional Chinese Medicine and Western Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, 201203, China.
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Simicic D, Cudalbu C, Pierzchala K. Overview of oxidative stress findings in hepatic encephalopathy: From cellular and ammonium-based animal models to human data. Anal Biochem 2022; 654:114795. [PMID: 35753389 DOI: 10.1016/j.ab.2022.114795] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 05/26/2022] [Accepted: 06/15/2022] [Indexed: 11/30/2022]
Abstract
Oxidative stress is a natural phenomenon in the body. Under physiological conditions intracellular reactive oxygen species (ROS) are normal components of signal transduction cascades, and their levels are maintained by a complex antioxidants systems participating in the in-vivo redox homeostasis. Increased oxidative stress is present in several chronic diseases and interferes with phagocytic and nervous cell functions, causing an up-regulation of cytokines and inflammation. Hepatic encephalopathy (HE) occurs in both acute liver failure (ALF) and chronic liver disease. Increased blood and brain ammonium has been considered as an important factor in pathogenesis of HE and has been associated with inflammation, neurotoxicity, and oxidative stress. The relationship between ROS and the pathophysiology of HE is still poorly understood. Therefore, sensing ROS production for a better understanding of the relationship between oxidative stress and functional outcome in HE pathophysiology is critical for determining the disease mechanisms, as well as to improve the management of patients. This review is emphasizing the important role of oxidative stress in HE development and documents the changes occurring as a consequence of oxidative stress augmentation based on cellular and ammonium-based animal models to human data.
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Affiliation(s)
- D Simicic
- CIBM Center for Biomedical Imaging, Switzerland; Animal Imaging and Technology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Laboratory of Functional and Metabolic Imaging, EPFL, Lausanne, Switzerland
| | - C Cudalbu
- CIBM Center for Biomedical Imaging, Switzerland; Animal Imaging and Technology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | - K Pierzchala
- CIBM Center for Biomedical Imaging, Switzerland; Animal Imaging and Technology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Laboratory of Functional and Metabolic Imaging, EPFL, Lausanne, Switzerland.
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Bera C, Wong F. Management of hepatorenal syndrome in liver cirrhosis: a recent update. Therap Adv Gastroenterol 2022; 15:17562848221102679. [PMID: 35721838 PMCID: PMC9201357 DOI: 10.1177/17562848221102679] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 05/07/2022] [Indexed: 02/04/2023] Open
Abstract
Hepatorenal syndrome (HRS) is a serious form of renal dysfunction in patients with cirrhosis and ascites. It is an important component of the acute-on-chronic liver failure (ACLF) syndrome. Significant recent changes in the understanding of the pathophysiology of renal dysfunction in cirrhosis include the role of inflammation in addition to hemodynamic changes. The term acute kidney injury (AKI) is now adopted to include all functional and structural forms of acute renal dysfunction in cirrhosis, with various stages describing the severity of the condition. Type 1 hepatorenal syndrome (HRS1) is renamed HRS-AKI, which is stage 2 AKI [doubling of baseline serum creatinine (sCr)] while fulfilling all other criteria of HRS1. Albumin is used for its volume expanding and anti-inflammatory properties to confirm the diagnosis of HRS-AKI. Vasoconstrictors are added to albumin as pharmacotherapy to improve the hemodynamics. Terlipressin, although not yet available in North America, is the most common vasoconstrictor used worldwide. Patients with high grade of ACLF treated with terlipressin are at risk for respiratory failure if there is pretreatment respiratory compromise. Norepinephrine is equally effective as terlipressin in reversing HRS1. Recent data show that norepinephrine may be administered outside the intensive care setting, but close monitoring is still required. There has been no improvement in overall or transplant-free survival shown with vasoconstrictor use, but response to vasoconstrictors with reduction in sCr is associated with improvement in survival. Non-responders to vasoconstrictor plus albumin will need liver transplantation as definite treatment with renal replacement therapy as a bridge therapy. Combined liver and kidney transplantation is recommended for patients with prolonged history of AKI, underlying chronic kidney disease or with hereditary renal conditions. Future developments, such as the use of biomarkers and metabolomics, may help to identify at risk patients with earlier diagnosis to allow for earlier treatment with improved outcomes.
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Affiliation(s)
- Chinmay Bera
- Division of Gastroenterology and Hepatology,
Department of Medicine, Toronto General Hospital, University Health Network,
University of Toronto, Toronto, ON, Canada
| | - Florence Wong
- Division of Gastroenterology and Hepatology,
Department of Medicine, Toronto General Hospital, University Health Network,
University of Toronto, 9EN/222 Toronto General Hospital, 200 Elizabeth
Street, 9EN222, Toronto, ON M5G2C4, Canada
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A simple colorimetric assay to determine the concentration and proportion of human mercaptalbumin. Pract Lab Med 2022; 31:e00281. [PMID: 35711386 PMCID: PMC9192801 DOI: 10.1016/j.plabm.2022.e00281] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/26/2022] [Accepted: 05/16/2022] [Indexed: 12/13/2022] Open
Abstract
Objectives Design and methods Results Conclusions
Concentrations of the reduced form of human serum albumin (human mercaptalbumin) were measured by a colorimetric assay using Michler's Hydrol. The assay uses the total thiol concentration to approximate the human mercaptalbumin concentration. Accuracy was improved by alkylating part of the samples and canceling the contribution of the non-thiol component to the colorimetric changes. Combining Michler's Hydrol assay with bromocresol purple assay enabled us to obtain the proportions of mercaptalbumin and non-mercaptalbumin, which correlated with HPLC as a reference method.
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China L, Becares N, Rhead C, Tittanegro T, Freemantle N, O'Brien A. Targeted Albumin Infusions Do Not Improve Systemic Inflammation or Cardiovascular Function in Decompensated Cirrhosis. Clin Transl Gastroenterol 2022; 13:e00476. [PMID: 35333783 PMCID: PMC9132514 DOI: 10.14309/ctg.0000000000000476] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 02/09/2022] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Albumin is recommended in decompensated cirrhosis, and studies have shown potential immunomodulatory effects. However, 2 large trials of repeated albumin infusions demonstrated contrasting results between outpatients and hospitalized patients. We investigated markers of systemic inflammation, immune function, albumin binding, and cardiovascular function using samples from Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) taken at baseline, day 5, and day 10 of the trial to identify why targeted albumin infusions had no effect in hospitalized patients. METHODS Plasma samples were analyzed from 143 patients (n = 71 targeted albumin; n = 72 standard care at baseline) for cytokines, cardiovascular markers, prostaglandin E2, the effect of plasma on macrophage function, and albumin radioligand binding and oxidation status. The sample size was based on our feasibility study, and samples were selected by a trial statistician stratified by the serum albumin level and the presence of infection at randomization and analyses performed blinded to the study arm. Data were linked to 3-month mortality and treatment groups compared. RESULTS Increased baseline model for end-stage liver disease score, white cell count, calprotectin, CD163, tumor necrosis factor, renin, atrial natriuretic peptide, and syndecan-1 were associated with 3-month mortality. Despite infusing substantially differing volumes of albumin, there were no significant differences in inflammatory markers, albumin-prostaglandin E2 binding, or cardiovascular markers between treatment arms. DISCUSSION Contrary to many preclinical studies, targeted intravenous albumin therapy in hospitalized decompensated cirrhosis had no effect across a broad range of systemic inflammation, albumin function, and cardiovascular mediators and biomarkers compared with standard care, consistent with the null clinical findings.
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Affiliation(s)
- Louise China
- UCL Institute for Liver and Digestive Health, London, UK
| | | | - Camilla Rhead
- UCL Institute for Liver and Digestive Health, London, UK
| | | | - Nick Freemantle
- Comprehensive Clinical Trials Unit, University College London, London, UK
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A novel TICT-based near-infrared fluorescent probe for light-up sensing and imaging of human serum albumin in real samples. CHINESE CHEM LETT 2022. [DOI: 10.1016/j.cclet.2022.05.071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Artru F, McPhail MJW, Triantafyllou E, Trovato FM. Lipids in Liver Failure Syndromes: A Focus on Eicosanoids, Specialized Pro-Resolving Lipid Mediators and Lysophospholipids. Front Immunol 2022; 13:867261. [PMID: 35432367 PMCID: PMC9008479 DOI: 10.3389/fimmu.2022.867261] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 03/08/2022] [Indexed: 12/30/2022] Open
Abstract
Lipids are organic compounds insoluble in water with a variety of metabolic and non-metabolic functions. They not only represent an efficient energy substrate but can also act as key inflammatory and anti-inflammatory molecules as part of a network of soluble mediators at the interface of metabolism and the immune system. The role of endogenous bioactive lipid mediators has been demonstrated in several inflammatory diseases (rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, cancer). The liver is unique in providing balanced immunotolerance to the exposure of bacterial components from the gut transiting through the portal vein and the lymphatic system. This balance is abruptly deranged in liver failure syndromes such as acute liver failure and acute-on-chronic liver failure. In these syndromes, researchers have recently focused on bioactive lipid mediators by global metabonomic profiling and uncovered the pivotal role of these mediators in the immune dysfunction observed in liver failure syndromes explaining the high occurrence of sepsis and subsequent organ failure. Among endogenous bioactive lipids, the mechanistic actions of three classes (eicosanoids, pro-resolving lipid mediators and lysophospholipids) in the pathophysiological modulation of liver failure syndromes will be the topic of this narrative review. Furthermore, the therapeutic potential of lipid-immune pathways will be described.
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Affiliation(s)
- Florent Artru
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Mark J W McPhail
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Evangelos Triantafyllou
- Section of Hepatology and Gastroenterology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
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Albumin Binds COVID-19 Spike 1 Subunit and Predicts In-Hospital Survival of Infected Patients—Possible Alteration by Glucose. J Clin Med 2022; 11:jcm11030587. [PMID: 35160039 PMCID: PMC8836760 DOI: 10.3390/jcm11030587] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/17/2022] [Accepted: 01/20/2022] [Indexed: 01/27/2023] Open
Abstract
(1) Background: This study aimed to analyze if the serum albumin levels of hospitalized SARS-CoV-2 (COVID-19) patients on admission could predict <30 days in-hospital all-cause mortality, and if glucose levels on admission affected this predictive ability. (2) Methods: A multicenter retrospective cohort of 1555 COVID-19-infected adult patients from public hospitals of the Madrid community were analyzed. (3) Results: Logistic regression analysis showed increased mortality for ages higher than 49 y. After adjusting for age, comorbidities and on-admission glucose levels, it was found that on-admission serum albumin ≥3.5 g/dL was significantly associated with reduced mortality (OR 0.48; 95%CI:0.36–0.62). There was an inverse concentration-dependent association between on-admission albumin levels and <30 days in-hospital all-cause mortality. However, when on-admission glucose levels were above 125 mg/dL, higher levels of serum albumin were needed to reach an association with survival. In vitro experiments showed that the spike protein S1 subunit of SARS-CoV-2 binds to native albumin. The binding ability of native albumin to the spike protein S1 subunit was decreased in the presence of an increasing concentration of glycated albumin. (4) Conclusions: On-admission serum albumin levels were inversely associated with <30 days in-hospital all-cause mortality. Native albumin binds the spike protein S1 subunit, suggesting that native albumin may act as a scavenger of the SARS-CoV-2 virus.
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