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19 pages, 1961 KB  
Article
Prognostic Impact of Baseline Albumin–Bilirubin Score on Mortality After Transcatheter Edge-to-Edge Mitral Repair
by Ümeyir Savur, Berhan Keskin, Aysel Akhundova, Aykun Hakgor, Haci Murat Güneş and Bilal Boztosun
Medicina 2026, 62(5), 944; https://doi.org/10.3390/medicina62050944 (registering DOI) - 12 May 2026
Viewed by 215
Abstract
Background and Objectives: Transcatheter edge-to-edge repair (TEER) has emerged as an effective treatment option for patients with severe mitral regurgitation who are at high surgical risk. However, clinical outcomes after TEER remain heterogeneous and are influenced not only by cardiac parameters but [...] Read more.
Background and Objectives: Transcatheter edge-to-edge repair (TEER) has emerged as an effective treatment option for patients with severe mitral regurgitation who are at high surgical risk. However, clinical outcomes after TEER remain heterogeneous and are influenced not only by cardiac parameters but also by systemic comorbidities and multiorgan dysfunction. The albumin–bilirubin (ALBI) score, derived from serum albumin and bilirubin levels, has recently been proposed as a simple marker of hepatic dysfunction and cardio-hepatic interaction. This study aimed to evaluate the prognostic value of baseline ALBI score in predicting long-term mortality after TEER. Materials and Methods: In this single-center retrospective cohort study, 106 consecutive patients with symptomatic moderate-to-severe or severe mitral regurgitation who underwent TEER between January 2019 and December 2025 were included. Baseline ALBI score was calculated using pre-procedural serum albumin and bilirubin levels. Cox proportional hazards regression analysis was used to identify predictors of long-term mortality. Variable selection was performed using least absolute shrinkage and selection operator (LASSO) regression, followed by ridge-penalized multivariable Cox modeling to minimize overfitting. The incremental prognostic value of ALBI was assessed using concordance index (C-index) comparison between predictive models. Receiver operating characteristic (ROC) analysis and Kaplan–Meier survival analysis were also performed. Results: During a median follow-up of 17.9 months, 30 patients (28.3%) died. Higher baseline ALBI scores were significantly associated with increased mortality risk. In multivariable analysis, ALBI score (HR 3.35, 95% CI 1.46–7.71; p = 0.004), left atrial volume index (LAVI) (HR 1.02, 95% CI 1.01–1.03; p = 0.005), and log-transformed B-type natriuretic peptide (BNP) (HR 1.37, 95% CI 1.02–1.86; p = 0.039) remained independent predictors of mortality. Addition of the ALBI score improved model discrimination, increasing the C-index from 0.845 to 0.886. ROC analysis demonstrated good predictive performance of the ALBI score (area under the curve [AUC] = 0.877), with an optimal cut-off value of −1.67. Conclusions: Baseline ALBI score is independently associated with long-term mortality after TEER and may provide potential incremental prognostic information. However, the observed improvement is modest and should be interpreted cautiously. These findings support a potential role of ALBI as a complementary marker, which requires validation in larger prospective studies. Full article
(This article belongs to the Section Cardiology)
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19 pages, 1091 KB  
Article
Distinct Inflammatory and Dissemination Signatures Defined by Macrophage Migration Inhibitory Factor (MIF), Interleukin-8 (IL-8/CXCL8), and Stem Cell Factor (SCF) in Pancreatic Adenocarcinoma
by Augustin Catalin Dima, Daniel Vasile Balaban, Iulia-Ioana Stanescu-Spinu, Ana Teodorescu, George Manucu, Laura Ioana Coman, Alina Dima, Cezar Betianu, Mihai Tanase, Daniela Miricescu, Mariana Jinga and Catalin Carstoiu
Diagnostics 2026, 16(9), 1373; https://doi.org/10.3390/diagnostics16091373 - 30 Apr 2026
Viewed by 401
Abstract
Background/Objectives: Pancreatic adenocarcinoma remains one of the most lethal malignancies, largely due to aggressive biological behavior and limited available insight into biomarker-based prognostic stratification. The aim of our research was to investigate the role of macrophage migration inhibitory factors (MIFs), interleukin-8 (IL-8/CXCL8), and [...] Read more.
Background/Objectives: Pancreatic adenocarcinoma remains one of the most lethal malignancies, largely due to aggressive biological behavior and limited available insight into biomarker-based prognostic stratification. The aim of our research was to investigate the role of macrophage migration inhibitory factors (MIFs), interleukin-8 (IL-8/CXCL8), and stem cell factors (SCFs) in pancreatic adenocarcinoma. Methods: In this single-center study, sixty hospitalized patients diagnosed with pancreatic adenocarcinoma were prospectively enrolled, and a cross-sectional analysis of baseline cytokine levels was performed. Serum MIF, IL-8/CXCL8, and SCF were assessed in a single analytical run using Luminex xMAP technology. Results: Elevated MIF and IL-8/CXCL8 levels characterized an inflammatory phenotype, associated with leukocytosis, neutrophilia, increased fibrinogen levels, and unequal prevalence of new-onset diabetes. Higher MIF levels were further associated with larger tumor dimension, while IL-8/CXCL8 was associated with increased bilirubin level and recent weight loss (p < 0.05). In contrast, increased SCF predicted a dissemination phenotype as defined by metastasis occurrence (65.4% vs. 28.6%, p = 0.012). SCF demonstrated significant discriminatory ability for metastasis (AUC 0.712, p = 0.013) and remained significantly associated in multivariable analysis. Conclusions: MIF and IL-8/CXCL8 primarily reflect inflammation-driven processes, whereas SCF identifies a dissemination-dominant phenotype, suggesting distinct biological pathways underlying disease progression in pancreatic cancer. Full article
(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, Third Edition)
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16 pages, 295 KB  
Article
Serum HMGB1 and Alcohol-Related Liver Disease
by Iwona Popiolek, Piotr Hydzik, Krzysztof Ciszowski, Barbara Balicka-Slusarczyk, Ewa Gomolka, Beata Szkolnicka, Lubomir Skladany, Juan Pablo Arab, Ivica Grgurevic and Michal Kukla
J. Clin. Med. 2026, 15(9), 3397; https://doi.org/10.3390/jcm15093397 - 29 Apr 2026
Viewed by 238
Abstract
Background/Objectives: Alcohol-related liver disease (ALD) lacks widely adopted biomarkers that reflect disease activity and severity. High-mobility group box 1 (HMGB1), a damage-associated molecular pattern, has been implicated in ALD pathogenesis. We evaluated the detectability of circulating HMGB1 in patients with ALD during active [...] Read more.
Background/Objectives: Alcohol-related liver disease (ALD) lacks widely adopted biomarkers that reflect disease activity and severity. High-mobility group box 1 (HMGB1), a damage-associated molecular pattern, has been implicated in ALD pathogenesis. We evaluated the detectability of circulating HMGB1 in patients with ALD during active alcohol use and examined clinical associations. Methods: In this observational study, we enrolled hospitalized adults with ongoing ethanol use between 1 November 2023, and 31 December 2024. Controls had no history of excessive alcohol consumption and normal liver biochemistry. Clinical features, laboratory tests, and severity scores (including MELD, MELD-Na, and CLIF-C AD) were recorded. Serum HMGB1 was measured by ELISA; values ≥ 0.08 ng/mL were considered detectable. Results: The cohort included 68 participants (58 with ALD and 10 controls); 29 patients had cirrhosis. HMGB1 was detectable in 32 measurements (42%), with a median concentration of 4.6 ng/mL (IQR, 0.78–10.6; range, 0.08–140.6). Detectable HMGB1 was more frequent in ALD than in controls (47% vs. 11%). Compared with HMGB1-negative patients, HMGB1-positive patients had higher total bilirubin and creatinine levels, prolonged activated partial thromboplastin time, higher white cell counts, and lower serum sodium. Liver enzyme activities and INR did not differ meaningfully by HMGB1 status. MELD, MELD-Na, and CLIF-C AD scores were higher in HMGB1-positive patients. Admission ethanol levels were higher in HMGB1-negative patients. Mortality and readmission did not differ by HMGB1 status. Conclusions: Detectable circulating HMGB1 is present in a subset of patients with ALD and is associated with greater liver disease severity. Full article
11 pages, 571 KB  
Article
Postmortem Aqueous Humor Analysis in Pigs as an Index of Antemortem Serum Biochemistry Profile and Diagnostic Aid in Animal Welfare
by Željko Mihaljević, Ksenija Šandor, Šimun Naletilić, Zdravka Vidić, Iva Kilvain and Marica Lolić
Animals 2026, 16(9), 1358; https://doi.org/10.3390/ani16091358 - 29 Apr 2026
Viewed by 325
Abstract
The present study aimed to assess whether postmortem analysis of aqueous humor in pigs can be used to estimate antemortem serum biochemical values. The experimental design used a control group to establish regression equations linking postmortem aqueous humor to antemortem serum biochemical values. [...] Read more.
The present study aimed to assess whether postmortem analysis of aqueous humor in pigs can be used to estimate antemortem serum biochemical values. The experimental design used a control group to establish regression equations linking postmortem aqueous humor to antemortem serum biochemical values. These models enabled reconstruction of the physiological status in decomposed forensic cases associated with heatstroke and hypoxia in pigs that died following a ventilation system failure on a commercial farm, and assessment of physiological distress, cause of death, and potential intentional animal abuse. Concentrations of albumin (ALB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), amylase (AMY), total bilirubin (TBIL), urea nitrogen (UN), creatinine (CRE), calcium (Ca), phosphate (PHOS), sodium (Na), potassium (K), glucose (GLU) and total protein (TP) were measured in aqueous humor and compared with serum samples obtained after slaughter of 30 pigs. Biochemical analyses were performed using a chemistry analyzer with commercial reagent rotors designed. Strong correlations were observed for Na, K and CRE concentrations and for ALT and UN activities between aqueous humor and serum, while TP, ALB, AMY, TBIL and Ca showed weaker associations. Notably, CRE and UN showed strong postmortem correlations with serum values in pigs, consistent with findings in cats and other species, highlighting their reliability as indicators of renal function. Electrolyte concentrations, particularly K and Na, followed consistent and well-recognized patterns described in both human and veterinary forensic studies, with K levels in pigs comparable to those observed in other domestic animals. The results indicate that postmortem aqueous humor analysis of CRE, Na, K, AST, and UN provides a reliable estimation of corresponding serum values in pigs, representing a useful diagnostic and forensic tool in the case of animal welfare. Full article
(This article belongs to the Special Issue Animal Health and Welfare Assessment of Pigs)
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26 pages, 6075 KB  
Article
Exposure to Polystyrene Microplastics Disrupts Blood Cell Homeostasis and Metabolic Profiles in Pregnant Mice and Offspring: The Role of Oxidative Stress and Inflammation
by Lin Lin, Ti-Zhen Yan, Hai-Wen Zhuo, Rong-Hua Zhang, Hong-Yi Liu, Xing-He Wang, Qing-Wo Lu, Rui Guo, Jian-Feng Qiu, Bo Zhang and Qing-Ming Luo
Toxics 2026, 14(5), 354; https://doi.org/10.3390/toxics14050354 - 23 Apr 2026
Viewed by 787
Abstract
Micro/nanoplastics (MNPs) are emerging contaminants of concern for maternal and fetal health, yet their effects on the maternal–fetal circulation and serum metabolic homeostasis remain unclear. Here, we investigated the maternal and offspring toxicity of polystyrene microplastics (PS-MPs) and serum metabolomic alterations in dams [...] Read more.
Micro/nanoplastics (MNPs) are emerging contaminants of concern for maternal and fetal health, yet their effects on the maternal–fetal circulation and serum metabolic homeostasis remain unclear. Here, we investigated the maternal and offspring toxicity of polystyrene microplastics (PS-MPs) and serum metabolomic alterations in dams and offspring. PS-MPs accumulated in multiple tissues, including blood, indicating maternal-to-offspring transfer. Continuous exposure reduced litter size, induced hepatic oxidative stress, and increased IL-6 and TNF-α levels in a dose-dependent manner in both dams and offspring. In dams, PS-MPs also decreased red blood cell and platelet counts and altered leukocyte composition, with increased lymphocyte and decreased neutrophil percentages at the high dose. Untargeted serum metabolomics revealed distinct exposure-related metabolic profiles, including 18 putatively annotated signature metabolites and 26 differentially abundant metabolites. Bilirubin and presqualene diphosphate were exclusively detected in exposed animals, whereas metabolites associated with lipid oxidation and mitochondrial fatty acid β-oxidation were elevated after exposure. RT-qPCR further supported altered expression of genes involved in these pathways. Overall, PS-MPs disrupted hematological homeostasis and metabolic regulation, likely through hepatic lipid peroxidation and systemic inflammation, and serum bilirubin and presqualene diphosphate may serve as candidate biomarkers of exposure. Full article
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29 pages, 9213 KB  
Article
Hepato-Protective Effect of Pomegranate and Persimmon Juices Against Oxidative Stress and Inflammation in Cyclosporine-Induced Cholestasis in Rats
by Rasha S. Mohamed and Karem Fouda
Foods 2026, 15(9), 1473; https://doi.org/10.3390/foods15091473 - 23 Apr 2026
Viewed by 449
Abstract
Background: Oxidative liver damage, fibrosis, cirrhosis and liver failure are caused by reactive oxygen species and inflammatory responses triggered by bile retention during prolonged cholestasis. Pomegranate and persimmon fruits, which are loaded with bioactive compounds that have anti-inflammatory and antioxidant properties, were evaluated [...] Read more.
Background: Oxidative liver damage, fibrosis, cirrhosis and liver failure are caused by reactive oxygen species and inflammatory responses triggered by bile retention during prolonged cholestasis. Pomegranate and persimmon fruits, which are loaded with bioactive compounds that have anti-inflammatory and antioxidant properties, were evaluated separately for their efficacy in preventing oxidative stress and inflammation in cholestasis. Methods: Pomegranate and persimmon juices were analyzed for their vitamin C, carotenoids and organic acid levels, phenolic profile, and antioxidant activity. Liver protection against oxidative stress and inflammation brought on by cyclosporine-induced cholestasis in rats was verified by biochemical measurements, metabolite identification, and histopathologic examination. To forecast the mechanism of pomegranate and persimmon anti-inflammatory action, an in silico assessment was also carried out. Results: Vitamin C levels in pomegranate and persimmon juices were 99.55 and 51.75 µg/g, respectively. In both pomegranate and persimmon juices, gallic acid was the most prevalent phenolic compound (123.20 and 50.69 µg/g, respectively). Pomegranate and persimmon juices significantly (p < 0.05) reduced the rise in liver values of MDA, NO, TNF-α, IL-6, IL-1β, and TLR4, as well as serum values of total and direct bilirubin caused by cyclosporine. Additionally, the alteration of metabolites, particularly amino acids, demonstrated the inhibitory effect of pomegranate and persimmon juices on liver damage. Gallic acid’s and catechin’s substantial binding affinities with target inflammatory cytokines (TNF-α and TLR4) were further validated by molecular docking. Conclusions: These results showed that pomegranate and persimmon juices mainly modulated inflammation and oxidative stress to provide hepato-protective benefits against cyclosporine-induced cholestatic liver injury. Full article
(This article belongs to the Section Food Nutrition)
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13 pages, 910 KB  
Article
Evaluation of Serum Homocysteine and High-Sensitivity Cardiac Troponins in Cats with Hepatic Lipidosis: An Observational Clinical Study
by Ahmet Cihat Tunç, Cemalettin Ayvazoğlu, Şemistan Kızıltepe, Sercan Hüseyin Bayendur and Abuzer Acar
Vet. Sci. 2026, 13(5), 413; https://doi.org/10.3390/vetsci13050413 - 23 Apr 2026
Viewed by 474
Abstract
Feline hepatic lipidosis (FHL) is a life-threatening, common hepatobiliary disease characterized by massive triglyceride accumulation in the liver, often triggered by anorexia and negative energy balance in cats. This condition causes severe metabolic stress that may secondarily impact myocardial integrity. This observational clinical [...] Read more.
Feline hepatic lipidosis (FHL) is a life-threatening, common hepatobiliary disease characterized by massive triglyceride accumulation in the liver, often triggered by anorexia and negative energy balance in cats. This condition causes severe metabolic stress that may secondarily impact myocardial integrity. This observational clinical study evaluated serum homocysteine (Hcy) and high-sensitivity cardiac troponins (hs-cTnI, hs-cTnT) to assess secondary myocardial injury and their prognostic value in FHL. Fifty cats, comprising 30 with naturally occurring FHL and 20 healthy controls, were included. Serum Hcy, hs-cTnI, and hs-cTnT concentrations were measured using feline-specific ELISA kits, and routine biochemical parameters, alongside hospitalization times, were recorded. Results indicated that Hcy, total bilirubin, and liver enzymes were significantly elevated in the FHL group compared to controls (p < 0.001). However, hs-cTnI and hs-cTnT levels did not differ significantly between the groups. Notably, Hcy exhibited a strong positive correlation with hospitalization time (r = 0.89, p < 0.001). The absence of significant hs-cTn elevations suggests the feline myocardium remains largely resistant to acute necrosis during FHL. Nevertheless, relative hyperhomocysteinemia is a powerful prognostic biomarker for prolonged hospitalization in affected cats. Full article
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13 pages, 557 KB  
Article
Investigation of Changes in Irisin and Nesfatin-1 Levels in Chronic Viral Hepatitis
by Feray Ferda Senol, Ilkay Bahcecı, Sermin Algül, Ozlem Aytac, Arzu Şenol and Yusuf Çelik
J. Clin. Med. 2026, 15(9), 3209; https://doi.org/10.3390/jcm15093209 - 23 Apr 2026
Viewed by 379
Abstract
Background: Chronic viral hepatitis is a major global health problem associated with progressive liver injury and an increased risk of cirrhosis and hepatocellular carcinoma. The identification of novel biomarkers may improve disease monitoring and diagnostic accuracy. Methods: In this prospective case–control [...] Read more.
Background: Chronic viral hepatitis is a major global health problem associated with progressive liver injury and an increased risk of cirrhosis and hepatocellular carcinoma. The identification of novel biomarkers may improve disease monitoring and diagnostic accuracy. Methods: In this prospective case–control study, a total of 90 participants were included: 20 patients with chronic hepatitis B (CHB); 20 with chronic hepatitis C (CHC); 20 with HBeAg-negative chronic infection (HCI); and 30 age-, sex-, and body mass index-matched healthy controls. Serum irisin and nesfatin-1 levels were measured using enzyme-linked immunosorbent assays (ELISAs). Group comparisons were performed using multivariate analysis of variance (MANOVA) followed by Scheffé post hoc tests. Receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic performance. Results: Significant differences were observed among groups in terms of irisin, nesfatin-1, total bilirubin, and platelet counts (p ≤ 0.05). Nesfatin-1 levels were significantly higher in all patient groups compared with healthy controls (p < 0.001). Irisin levels were only significantly lower in the HCI group (p < 0.001). ROC analysis indicated that nesfatin-1 may have the potential to discriminate between infected patients and healthy individuals; however, the generalizability of this finding is limited by the study design and sample size. Conclusions: Nesfatin-1 may represent a potential biomarker for chronic viral hepatitis, whereas alterations in irisin levels may be more specific to the inactive carrier phase. Full article
(This article belongs to the Topic Biomarker Development and Application, 2nd Edition)
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25 pages, 3765 KB  
Article
Oxidative Stress and Antioxidant Defense During Liver Regeneration After Acetaminophen Toxicity: The Preventive Potential of the Microalga Desmodesmus armatus
by Halyna P. Kopylchuk, Ivanna M. Nykolaichuk, Mariia S. Ursatyi, Larysa M. Cheban, Oleksii Skorokhod and Oksana M. Voloshchuk
Antioxidants 2026, 15(4), 492; https://doi.org/10.3390/antiox15040492 - 15 Apr 2026
Cited by 1 | Viewed by 711
Abstract
Liver regeneration after partial hepatectomy (PH) is critically influenced by redox balance, which may be severely disrupted under drug-induced liver injury. This study evaluated oxidative stress parameters and inflammatory markers in rats subjected to 70% PH following acetaminophen (APAP)-induced toxicity and assessed the [...] Read more.
Liver regeneration after partial hepatectomy (PH) is critically influenced by redox balance, which may be severely disrupted under drug-induced liver injury. This study evaluated oxidative stress parameters and inflammatory markers in rats subjected to 70% PH following acetaminophen (APAP)-induced toxicity and assessed the preventive effect of the microalga Desmodesmus armatus. Reactive oxygen species (superoxide anion, hydroxyl radical, and hydrogen peroxide), antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase), serum aminotransferases, bilirubin, and C-reactive protein were analyzed 0–168 h post-hepatectomy. APAP intoxication markedly increased mitochondrial ROS production, suppressed mitochondrial antioxidant enzyme activity, and prolonged elevations of ALT, AST, bilirubin, and CRP, accompanied by severe histological damage. Preventive administration of D. armatus suspension (10 mL/kg body weight at 1.5 × 106 and 1.5 × 107 cells/mL) attenuated oxidative stress in a dose-dependent manner. It significantly reduced ROS levels, restored mitochondrial antioxidant defenses, decreased cytolytic and cholestatic markers, and mitigated systemic inflammation. Overall, D. armatus exhibited hepatoprotective and redox-modulating properties, which may contribute to a more favorable microenvironment for liver recovery under toxic conditions. These findings highlight the potential of microalgae-based interventions as supportive strategies for reducing liver injury and improving recovery following acute liver injury. Full article
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13 pages, 467 KB  
Article
Predictors of Cirrhosis and Cholangiocarcinoma in Patients with Primary Sclerosing Cholangitis: An Academic Center Experience
by Ahmad Hassan Ali, Alhareth Al-Juboori, Deepthi S. Rao, Jamal A. Ibdah, Nanda Deepa Thimmappa, Ayman H. Gaballah and Ghassan M. Hammoud
Livers 2026, 6(2), 30; https://doi.org/10.3390/livers6020030 - 15 Apr 2026
Viewed by 492
Abstract
Background and goals: The outcomes of patients with primary sclerosing cholangitis (PSC) in central Missouri are unknown. The University of Missouri–Columbia services 600,000 individuals in central Missouri. Our aims were (a) to examine the outcomes of PSC patients receiving care at our academic [...] Read more.
Background and goals: The outcomes of patients with primary sclerosing cholangitis (PSC) in central Missouri are unknown. The University of Missouri–Columbia services 600,000 individuals in central Missouri. Our aims were (a) to examine the outcomes of PSC patients receiving care at our academic institution, and (b) to identify the predictors of PSC-related serious adverse events. Methods: A retrospective study of patients with PSC in a non-transplant center. The primary outcome was the development of ≥1 of PSC-related serious adverse event for (1) progression to cirrhosis, or (2) development of cholangiocarcinoma. Results: From 2000 to 2018, 42 patients fulfilled the criteria for the diagnosis of PSC. A total of 55% of the patients were male, and 79% had associated inflammatory bowel disease (IBD). The median follow-up from time of diagnosis of PSC until the last follow-up or death was 5.5 years. A total of 57% of the patients developed ≥ 1 PSC-related adverse event; 36% (8/22) of those who progressed to decompensation underwent liver transplantation. The median time from diagnosis of PSC until progression to decompensation was 6.3 years; the median time from decompensation to transplantation was 10.8 years. A total of 12% of the patients developed ≥ 1 cancer (cholangiocarcinoma = 2; gallbladder cancer = 2; colon cancer = 1; and hepatocellular carcinoma = 1). The overall mortality was 9.5%. The median time from PSC diagnosis until death was 10.2 years. A Cox hazards regression analysis showed only age (HR = 1.16; p = 0.032; 95% CI, 1.01–1.13) and serum bilirubin (HR = 1.42; p = 0.036; 95% CI, 1.03–2.69) at the time of PSC diagnosis were independently associated with PSC-related serious events. Conclusions: Age and bilirubin are important predictors of PSC-related outcomes. Full article
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26 pages, 6269 KB  
Article
Iron Overload-Associated Oxidative Stress and Immune Cell Dysfunction in Thalassemia: Integrative Analysis of Hematological, Biochemical, and Flow Cytometric Biomarkers
by Sirichai Srichairatanakool, Narisara Paradee, Bishant Pokharel, Yanping Zhong, Onsaya Kerdto, Wuttipat Kiratipaisarl, Adisak Tantiworawit, Chatree Chai-Adisaksopha and Somdet Srichairatanakool
Antioxidants 2026, 15(4), 482; https://doi.org/10.3390/antiox15040482 - 14 Apr 2026
Viewed by 677
Abstract
Thalassemia is a hereditary hemoglobinopathy characterized by ineffective erythropoiesis, chronic hemolysis, and transfusion-related iron overload, which collectively contribute to oxidative stress and organ dysfunction. The present study aimed to investigate the relationships between iron metabolism, oxidative stress biomarkers, and immune cell function across [...] Read more.
Thalassemia is a hereditary hemoglobinopathy characterized by ineffective erythropoiesis, chronic hemolysis, and transfusion-related iron overload, which collectively contribute to oxidative stress and organ dysfunction. The present study aimed to investigate the relationships between iron metabolism, oxidative stress biomarkers, and immune cell function across different clinical conditions. Peripheral blood samples were obtained from healthy individuals and patients with iron deficiency anemia, obesity, thalassemia trait (TT), β-thalassemia HbE (BTE), and β-thalassemia major (BTM). Hematological parameters were measured using automated hematology analyzers, while biochemical indicators, including liver enzymes and bilirubin, were determined using clinical chemistry assays. Iron overload was evaluated using serum iron parameters and T2*-weighted magnetic resonance imaging. Oxidative stress biomarkers, including reduced glutathione, thiobarbituric acid-reactive substances, and total antioxidant capacity, were assessed spectrophotometrically. Flow cytometric analysis was used to measure reactive oxygen species, redox-active iron, and lipid peroxide levels in granulocytes and lymphocytes. Thalassemia patients exhibited severe anemia, elevated liver enzymes, increased bilirubin levels, and significant alterations in iron metabolism compared with healthy controls. Hepatic iron accumulation was more common than cardiac iron deposition, particularly in BTE patients. Granulocyte oxidative burst activity was significantly reduced in thalassemia patients, whereas lymphocyte responses remained relatively preserved. Increased variability in glutathione levels suggested activation of intracellular antioxidant defense mechanisms in response to chronic oxidative stress. These findings highlight the complex interplay between iron overload, oxidative stress, and the immune cell dysfunction associated with thalassemia, thereby providing insights into improved monitoring and therapeutic strategies. Full article
(This article belongs to the Special Issue Oxidative Stress in Hematologic Disease)
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30 pages, 9530 KB  
Article
Liposomal Myricetin Nanoantioxidants Attenuate Methotrexate-Induced Hepatotoxicity by Modulating Oxidative Stress, Inflammation, and Apoptosis in Rats
by Fahad Alshammari, Ekramy M. Elmorsy, Abdulrahman S. Aldaghmi, Fahd Alaajam, Eida M. Alshammari, Mona M. Elghareeb, Manal S. Fawzy and Noha M. Abd El-Fadeal
Antioxidants 2026, 15(4), 452; https://doi.org/10.3390/antiox15040452 - 4 Apr 2026
Viewed by 676
Abstract
Methotrexate (MTX) is widely used for its chemotherapeutic and immunosuppressive properties, but is limited by oxidative stress-mediated hepatotoxicity. Nanoantioxidant delivery systems can enhance the stability, solubility, and in vivo efficacy of natural antioxidants. This study investigated the hepatoprotective effects of myricetin (MYR), a [...] Read more.
Methotrexate (MTX) is widely used for its chemotherapeutic and immunosuppressive properties, but is limited by oxidative stress-mediated hepatotoxicity. Nanoantioxidant delivery systems can enhance the stability, solubility, and in vivo efficacy of natural antioxidants. This study investigated the hepatoprotective effects of myricetin (MYR), a flavonoid with potent antioxidant activity, and its liposomal nanoantioxidant formulation (MYR-loaded liposomal nanoparticles, MYR-LNPs) against MTX-induced liver injury in male albino Sprague Dawley rats. Sixty rats were randomly allocated to six groups: control, MTX, MYR, MYR-LNPs, and combinations of MTX with MYR-LNPs. MYR-LNPs were successfully formulated and physicochemically characterized, exhibiting a mean particle size of 95.6 nm, a zeta potential of −32 mV, and a narrow polydispersity index, collectively confirming their colloidal stability and suitability for hepatic delivery. MTX markedly disrupted liver function, increasing serum AST, ALT, ALP, and bilirubin and decreasing total protein, albumin, and globulin, whereas co-treatment with MYR-LNPs substantially restored these parameters and outperformed free MYR. MTX-induced oxidative stress, reflected by depleted hepatic GSH and antioxidant enzymes (GPx, SOD, CAT, GST), elevated reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyls and downregulated NRF2/HO-1, was significantly counteracted by MYR-LNPs. In addition, MYR-LNPs mitigated MTX-evoked inflammation and nitrosative stress by reducing NF-κB, TNF-α, IL-1β, nitric oxide, and iNOS expression. They corrected apoptotic imbalance by lowering Bax and caspase 3 while increasing Bcl-2. Histopathological and ultrastructural assessments confirmed that MYR-LNPs preserved hepatic architecture and mitochondrial integrity. These findings indicate that MYR-loaded liposomal nanoantioxidants provide superior protection against MTX-induced hepatotoxicity by modulating oxidative stress, inflammation, and apoptosis, supporting their potential as an advanced nanodrug delivery strategy for antioxidant therapy. Full article
(This article belongs to the Special Issue Recent Trends in Nanoantioxidants—2nd Edition)
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18 pages, 626 KB  
Article
Renal Impairment as an Independent Predictor of Sepsis in Cirrhosis: A Retrospective Cohort Study
by Mariana Boulos, Lana Majdoub, Maamoun Basheer and Nimer Assy
Microorganisms 2026, 14(4), 785; https://doi.org/10.3390/microorganisms14040785 - 30 Mar 2026
Cited by 1 | Viewed by 533
Abstract
Sepsis is a life-threatening complication among patients with liver cirrhosis and is associated with high morbidity and mortality. Early diagnosis is challenging due to immune dysfunction, chronic systemic inflammation, and overlap between clinical and laboratory findings during infection and hepatic decompensation. Therefore, there [...] Read more.
Sepsis is a life-threatening complication among patients with liver cirrhosis and is associated with high morbidity and mortality. Early diagnosis is challenging due to immune dysfunction, chronic systemic inflammation, and overlap between clinical and laboratory findings during infection and hepatic decompensation. Therefore, there is a need to identify routinely available predictors that may enable the stratifying of patients at risk of developing sepsis in this population and facilitate intensive monitoring, antibiotic treatment, and potentially reduce mortality. The aim of this study is to evaluate the association between routine laboratory parameters and the development of sepsis among cirrhotic patients. A total of 171 cirrhotic patients met the inclusion criteria and were followed at a tertiary liver clinic between February 2015 and February 2022. Sepsis was defined according to Sepsis-3 criteria. Univariate analyses were performed to compare sepsis patients versus non-sepsis patients. Multivariable logistic regression was conducted to identify independent predictors of sepsis. Among 171 patients, 41 (24%) developed sepsis and 130 (76%) did not. Baseline characteristics were similar between groups: patients with sepsis were slightly older (67.5 ± 10.9 vs. 64.5 ± 12.3 years, p = 0.172), with no significant differences in sex (53.7% vs. 56.2%, p = 0.78) or ethnicity (Arab ethnicity 56.1% vs. 39.1%, p = 0.055). Ascites was more frequent in the sepsis group (53.7% vs. 26.2%, p = 0.001), whereas esophageal varices were less common (12.2% vs. 35.4%, p = 0.006). Rates of hepatic encephalopathy and acute kidney injury did not differ significantly. Higher creatinine (1.35 (0.80–3.35) vs. 0.80 (0.70–1.49) mg/dL, p < 0.001), INR (1.50 (1.20–1.80) vs. 1.30 (1.10–1.50), p = 0.011), and total bilirubin (1.90 (0.61–2.85) vs. 0.90 (0.59–1.70) mg/dL, p = 0.049) was observed in the sepsis group. In the multivariable model including age, sex, ethnicity, ascites, esophageal varices, INR, creatinine, neutrophil-to-lymphocyte ratio, and CRP, baseline serum creatinine was the only independent predictor of sepsis (adjusted OR 1.58 per 1 mg/dL increase, 95% CI 1.08–2.33, p = 0.01). Receiver operating characteristic (ROC) analysis demonstrated that the multivariable model had acceptable discriminative ability for prediction of sepsis, with an area under the curve (AUC) of 0.741 (95% CI 0.647–0.835). Among ambulatory patients with liver cirrhosis, baseline serum creatinine was independently associated with the development of sepsis. These findings highlight the need for dedicated risk-stratification tools in the outpatient setting. Further external validation in independent cohorts is required. Full article
(This article belongs to the Section Medical Microbiology)
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22 pages, 1565 KB  
Article
Protective Effects of Vitamin D Against Doxorubicin Chemotherapy–Induced Hepatotoxicity in Wistar Albino Rats: Evidence from 99mTc-Pyrophosphate Scintigraphy and Oxidative–Inflammatory Pathways
by Murat Kalın, Haluk Kerim Karakullukcu, Mina Karakullukcu, Aylin Arslan, Serdar Savaş Gül, Reyhan Toyran, Ömer Faruk Özkan, Gülçin Ercan and Hatice Aygun
Nutrients 2026, 18(7), 1097; https://doi.org/10.3390/nu18071097 - 29 Mar 2026
Viewed by 718
Abstract
Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and [...] Read more.
Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and Methods: Adult male Wistar albino rats were randomly assigned to six groups (n = 7): Control, Vitamin D (5000 IU/kg), Vitamin D (60,000 IU/kg), Doxorubicin, DOX + Vitamin D (5000 IU/kg), and DOX + Vitamin D (60,000 IU/kg). Vitamin D3 (cholecalciferol) was administered orally either as a daily dose (5000 IU/kg for 12 days) or as a single bolus dose (60,000 IU/kg). Doxorubicin (6 mg/kg/day, cumulative dose 18 mg/kg) was administered intraperitoneally on days 10–12. Hepatic injury was evaluated using 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, serum liver enzymes (AST, ALT, LDH, total bilirubin), renal markers (BUN, creatinine), calcium and 25-hydroxyvitamin D [25(OH)D], oxidative stress parameters (MDA, TOS, TAS, GSH, SOD, Nrf2), and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10). Results: Doxorubicin markedly increased hepatic 99mTc-PYP uptake and significantly elevated AST, ALT, LDH, bilirubin, MDA, TOS, TNF-α, IL-6, and IL-1β levels while reducing Nrf2, GSH, SOD, TAS, and IL-10 (all p < 0.001). Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D [25(OH)D] levels compared with controls (32.3 ± 2.7 vs. 74.1 ± 3.8 and 69.3 ± 3.2 ng/mL for the 5000 and 60,000 IU/kg groups, respectively; p < 0.001) and attenuated DOX-induced hepatic injury, as indicated by reduced radiotracer uptake and improved oxidative and inflammatory markers. Vitamin D also mitigated DOX-associated increases in renal injury markers (BUN and creatinine) without inducing hypercalcemia. No significant differences were observed between the two vitamin D dosing regimens in most outcome measures. Conclusion: Vitamin D supplementation exerted protective effects against doxorubicin-induced liver injury, likely through modulation of oxidative stress and inflammatory pathways. Additionally, 99mTc-PYP scintigraphy may serve as a useful imaging tool for detecting acute hepatocellular injury and evaluating therapeutic responses. Full article
(This article belongs to the Section Micronutrients and Human Health)
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16 pages, 789 KB  
Article
Performance of Serum-Based Non-Invasive Fibrosis Scores Compared with Liver Biopsy in Patients with Chronic Hepatitis B
by Umut Devrim Binay, Faruk Karakeçili, Orçun Barkay and Betül Kuru
Medicina 2026, 62(4), 646; https://doi.org/10.3390/medicina62040646 - 28 Mar 2026
Viewed by 466
Abstract
Background and Objectives: Accurate assessment of liver fibrosis is essential for treatment decisions in patients with chronic hepatitis B (CHB). Although liver biopsy is considered the reference standard, its invasive nature limits routine use. Serum-based non-invasive fibrosis scores have been proposed as [...] Read more.
Background and Objectives: Accurate assessment of liver fibrosis is essential for treatment decisions in patients with chronic hepatitis B (CHB). Although liver biopsy is considered the reference standard, its invasive nature limits routine use. Serum-based non-invasive fibrosis scores have been proposed as alternatives; however, their diagnostic performance in CHB remains variable. This study aimed to compare multiple serum-based non-invasive fibrosis scores with liver biopsy findings and to evaluate their association with histological activity. Materials and Methods: This retrospective cross-sectional study included 219 adult patients with CHB who underwent liver biopsy with simultaneous laboratory evaluation. Patients with viral co-infections (HIV, HCV, or HDV), metabolic syndrome, diabetes mellitus, hepatic steatosis, or incomplete data were excluded. Non-invasive fibrosis scores—including APRI, FIB-4, AST/ALT ratio (AAR), age–platelet index (API), GGT-to-platelet ratio (GPR), Lok index, modified Forns index, Albumin–Bilirubin (ALBI) score, and red cell distribution width (RDW)-based indices—were calculated using routine laboratory parameters. Histopathological fibrosis staging served as the reference standard. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis, and areas under the curve (AUC) were compared using the DeLong test. Associations with histological activity index (HAI) were assessed using Spearman correlation. Results: For the prediction of significant fibrosis (≥F2), FIB-4 demonstrated the highest AUC, followed by ALBI and APRI. For advanced fibrosis (≥F3), FIB-4 again showed the highest AUC, followed by APRI and GPR. For significant fibrosis (≥F2), DeLong analysis revealed no statistically significant differences between FIB-4 and the other serum-based scores (p > 0.05). APRI (r = 0.556, p < 0.001) and FIB-4 (r = 0.463, p < 0.001) showed the strongest correlations with HAI. In ROC analysis for moderate-to-severe histological activity (HAI ≥ 4), APRI demonstrated the highest diagnostic accuracy (AUC = 0.677). Conclusions: Serum-based non-invasive fibrosis scores demonstrate comparable but overall modest diagnostic performance for biopsy-confirmed fibrosis in patients with chronic hepatitis B. Indices such as FIB-4 and APRI demonstrated relatively better discrimination and may be considered as screening or rule-out tools in selected clinical contexts. APRI and FIB-4 also show associations with histological activity; however, their clinical application should be interpreted with caution, given their moderate discriminatory capacity. Full article
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