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Search Results (2,670)

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55 pages, 2196 KB  
Review
The Inflammaging-Redox-InflammamiR Axis in Metabolic Aging: From Diagnostic Clusters to Integrated Risk Phenotypes
by Nurzhanyat Ablaikhanova, Ingkar Okhas, Aidos Bolatov, Beibarys Mukhitdin, Zhazira Zhunusbayeva, Gulmira Assan, Marzhan Kulbayeva, Anar Tolebaeva, Arailym Yessenbekova and Iryna Rusanova
Biomolecules 2026, 16(7), 1008; https://doi.org/10.3390/biom16071008 - 10 Jul 2026
Abstract
Age-associated metabolic dysfunction is commonly defined by abnormalities in adiposity, glucose regulation, lipid metabolism, and blood pressure. Although clinically useful, these criteria do not fully capture the biological heterogeneity that explains why older adults with similar metabolic profiles may follow divergent trajectories toward [...] Read more.
Age-associated metabolic dysfunction is commonly defined by abnormalities in adiposity, glucose regulation, lipid metabolism, and blood pressure. Although clinically useful, these criteria do not fully capture the biological heterogeneity that explains why older adults with similar metabolic profiles may follow divergent trajectories toward type 2 diabetes, cardiovascular disease, metabolic dysfunction-associated steatotic liver disease, frailty or multimorbidity. This narrative Review summarizes clinical, translational, and mechanistic evidence on the biological processes that shape metabolic aging, with particular emphasis on inflammaging, immunosenescence, cellular senescence, oxidative stress, mitochondrial dysfunction, adipose tissue dysfunction, endothelial injury, and inflammation-related microRNAs. We first discuss how chronic low-grade inflammation and immune remodeling alter the interpretation of conventional metabolic syndrome components in older adults. We then review redox imbalance and mitochondrial stress as amplifiers of insulin resistance, lipid injury, vascular dysfunction, and tissue remodeling. The review also examines inflammation-related microRNAs, including circulating and extracellular-vesicle-associated miRNAs, as post-transcriptional regulators that may connect inflammatory, metabolic, and redox pathways. Finally, we discuss how conventional metabolic markers may be integrated with inflammatory mediators, oxidative-stress indicators, adipokines, endothelial and senescence-related markers, and miRNA profiles to improve biological interpretation of metabolic risk. Within this context, we present the Inflammaging–Redox–InflammamiR Axis as a conceptual framework for organizing these overlapping mechanisms rather than as an established diagnostic or causal model. The proposed biomarker tiers and candidate risk phenotypes are author-derived, hypothesis-generating constructs intended to guide future longitudinal and interventional research. Clinical translation will require standardized assays, longitudinal validation, external replication, and intervention studies. Full article
(This article belongs to the Section Molecular Biomarkers)
22 pages, 9475 KB  
Review
Molecular Pathways of Cardiometabolic Residual Risk in Type 2 Diabetes: Insulin Resistance, Metaflammation, and Liver–Kidney–Vascular Crosstalk
by Antonio Maria Labate, Elena Cimino, Laura Giacomelli, Stefano Ettori, Oladayo Adigun Oladeji and Barbara Agosti
Int. J. Mol. Sci. 2026, 27(14), 6170; https://doi.org/10.3390/ijms27146170 - 10 Jul 2026
Abstract
Cardiometabolic residual risk in type 2 diabetes mellitus (T2D) persists despite major advances in glucose-lowering therapy, lipid management, blood pressure control, weight reduction, and organ-protective strategies. This residual burden should not be interpreted solely as the consequence of incomplete achievement of conventional therapeutic [...] Read more.
Cardiometabolic residual risk in type 2 diabetes mellitus (T2D) persists despite major advances in glucose-lowering therapy, lipid management, blood pressure control, weight reduction, and organ-protective strategies. This residual burden should not be interpreted solely as the consequence of incomplete achievement of conventional therapeutic targets, but rather as the clinical expression of persistent molecular activity involving multiple interconnected organs and pathways. Insulin resistance, metaflammation, oxidative stress, mitochondrial dysfunction, lipotoxicity, endothelial impairment, hepatic metabolic dysregulation, renal inflammation, fibrotic remodeling, and metabolic memory interact within a dynamic network linking adipose tissue, liver, kidney, immune cells, and vasculature. In this review, we discuss the biochemical and molecular drivers of cardiometabolic residual risk in T2D, with particular emphasis on impaired insulin receptor substrate/PI3K/Akt signaling, stress-kinase activation, NLRP3 inflammasome priming and assembly, MASLD-related lipotoxicity and fibrogenesis, podocyte and tubular injury, endothelial nitric oxide synthase uncoupling, AGE-RAGE signaling, and thrombo-inflammatory vascular injury. These pathways explain why biological vulnerability may persist even when conventional clinical parameters appear adequately controlled. We also examine the role of translational biomarkers and simple clinical indices, including TyG-derived indices, adiposity markers, hepatic steatosis and fibrosis scores, albuminuria, eGFR, and lipid-related markers, as accessible windows into active biological pathways. Finally, we review how contemporary therapeutic strategies may modulate selected components of this residual-risk network. A pathway-centered interpretation of T2D may support more precise residual-risk phenotyping and help move cardiometabolic care beyond isolated target control toward mechanism-based prevention. This review further links these mechanisms to the contemporary cardiovascular–kidney–metabolic (CKM) framework, as defined by the 2026 AHA/ACC/ADA/ASN CKM Guideline, and disaggregates the underlying molecular network into organ-specific pathway cascades that make the causal relationships between metabolic, inflammatory, hepatic, renal, and vascular injury more explicit. Full article
(This article belongs to the Special Issue Biochemical Perspectives on Diabetes)
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25 pages, 14558 KB  
Article
An Interpretable Machine Learning Model for the Differentiation of Liver Cysts and Liver Tumors Based on Computed Tomography (CT) Imaging
by Mamoun Qjidaa, Anass Benfares, Mohammed Amine El Azami El Hassani, Amine Benkabbou, Amine Souadka, Anass Majbar, Zakaria El Moatassim, Maroua Oumlaz, Oumayma Lahnaoui, Raouf Mouhcine, Ahmed Lakhssassi, Maaaroufi Mustapha, Alami Badreddine, Hassan Qjidaa, Massou Siham, Ouazzani Jamil Mohammed and Abdeljabbar Cherkaoui
Livers 2026, 6(4), 66; https://doi.org/10.3390/livers6040066 - 9 Jul 2026
Abstract
Background: Metastatic liver tumors (MLT) and parasitic liver cysts (PLC) are common liver conditions that often exhibit similar imaging characteristics, making accurate diagnosis challenging using imaging alone. This overlap can result in diagnostic errors and delayed treatment, particularly in resource-limited settings or when [...] Read more.
Background: Metastatic liver tumors (MLT) and parasitic liver cysts (PLC) are common liver conditions that often exhibit similar imaging characteristics, making accurate diagnosis challenging using imaging alone. This overlap can result in diagnostic errors and delayed treatment, particularly in resource-limited settings or when invasive procedures such as biopsies are not feasible due to risk or unavailability. This study aimed to develop a reliable and transparent machine learning approach to distinguish MLT from PLC using radiomic features derived from computed tomography (CT). Methods: We propose an explainable radiomics-based machine learning framework for the non-invasive, accurate, and interpretable discrimination of MLT and PLC, designed to assist radiologists in reducing diagnostic ambiguity and expediting patient management. This retrospective study included 30 adult patients, comprising 15 with liver metastases and 15 with pathologic hepatic cysts. Radiomic features were extracted from pre-treatment CT scans using PyRadiomics. Feature selection was performed using three complementary methods: Mutual Information, Lasso regression, and LightGBM importance ranking. HistGradientBoosting classifiers were then trained on each selected feature set. Results: Model performance was evaluated using 5-fold cross-validation and assessed with ROC AUC, accuracy, precision, recall, and F1-score. SHAP analysis was applied to interpret the models and identify key radiomic biomarkers. Statistical comparisons were performed using DeLong’s test for AUCs, McNemar’s test for classification agreement, and paired t-tests for metrics such as accuracy and F1-score. The Mutual Information-based model achieved the highest mean AUC (0.9717 ± 0.0267), significantly outperforming the other models (p < 0.035). Key features contributing to classification included texture entropy, interquartile range, and gray level non-uniformity. Conclusion: We developed a robust and interpretable machine learning framework for differentiating metastatic liver tumors from parasitic liver cysts using CT-derived radiomic features. The integration of Mutual Information feature selection, ensemble learning, and SHAP explainability ensured high diagnostic accuracy, strong calibration, and transparency. The proposed framework demonstrates substantial clinical relevance and holds promise for real-world implementation. Full article
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14 pages, 460 KB  
Review
Evidence-Based Bedside Management of Overt Hepatic Encephalopathy: From Guidelines to Clinical Practice
by Eugenio Franceschini, Andrea De Sinno, Matteo Cappelli Aimone Chiorat and Dante Pio Pallotta
Livers 2026, 6(4), 65; https://doi.org/10.3390/livers6040065 - 9 Jul 2026
Abstract
Overt hepatic encephalopathy (OHE) is a defining decompensation event in liver cirrhosis, associated with substantial morbidity, mortality, and high readmission rates. For the bedside clinician, managing OHE presents a complex diagnostic and investigative challenge that extends well beyond the simple administration of laxatives. [...] Read more.
Overt hepatic encephalopathy (OHE) is a defining decompensation event in liver cirrhosis, associated with substantial morbidity, mortality, and high readmission rates. For the bedside clinician, managing OHE presents a complex diagnostic and investigative challenge that extends well beyond the simple administration of laxatives. This review synthesizes core recommendations from the 2022 EASL and the recent 2026 ACG guidelines to provide a structured, evidence-based framework for acute inpatient management. We emphasize that OHE diagnosis remains a clinical endeavor, where serum ammonia is valuable primarily for its high negative predictive value rather than as a confirmatory biomarker. Successful resolution hinges on a proactive ‘detective approach’ to identify and correct precipitating factors—such as infections, gastrointestinal bleeding, and iatrogenic dehydration—which drive clinical deterioration. Furthermore, we highlight the critical role of the ‘four pillars’ of management, including structured discharge planning, caregiver education, and nutritional support to ensure effective secondary prophylaxis. By bridging the gap between the latest international clinical consensus and bedside practice, this review provides essential strategies to optimize OHE management, minimize recurrence, and ultimately reduce the healthcare burden of this pleomorphic syndrome. Full article
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14 pages, 1172 KB  
Article
Analytical and Clinical Validation of a Serum microRNA RT-qPCR Assay for Detection of Acute Cellular Rejection in Liver Transplant Recipients
by Yipeng Wang, Robert Huff, Haleigh Parker, Chang Han, Byung-In Lee, Shuguang Huang, Mackenzie Burke, Bao-Li Loza, Brendan J. Keating, Kim Olthoff and Abraham Shaked
Diagnostics 2026, 16(14), 2152; https://doi.org/10.3390/diagnostics16142152 - 9 Jul 2026
Abstract
Background: Acute cellular rejection (ACR) remains a significant cause of graft dysfunction after liver transplantation and requires timely detection. Liver biopsy, the diagnostic gold standard for ACR, is invasive and unsuitable for frequent monitoring, while liver enzyme tests lack specificity for detecting ACR. [...] Read more.
Background: Acute cellular rejection (ACR) remains a significant cause of graft dysfunction after liver transplantation and requires timely detection. Liver biopsy, the diagnostic gold standard for ACR, is invasive and unsuitable for frequent monitoring, while liver enzyme tests lack specificity for detecting ACR. Circulating microRNAs (miRNAs), including miR-122 and miR-885, have been previously identified as predictive biomarkers of ACR in liver transplant recipients. HepatoTrack™ is a serum-based miRNA RT-qPCR assay designed for noninvasive assessment of ACR using these biomarkers. This study evaluated the analytical performance and clinical validity of HepatoTrack™ for diagnosing ACR in liver transplant recipients. Methods: HepatoTrack™ uses 100 μL of serum and a one-step RT-qPCR workflow. It quantifies miR-122 and miR-885 normalized to miR-23a, with synthetic cel-miR-39 included as an exogenous control. Analytical validation assessed performance characteristics. Clinical performance was evaluated in a cohort of liver transplant recipients undergoing for-cause liver biopsy and used for model development and validation. Results: Analytical validation demonstrated robust assay performance. The HepatoTrack™ Prediction Score (HPS) algorithm was trained using 47 subjects from the training cohort based on a linear regression model incorporating longitudinal miRNA changes. In the independent testing cohort (n = 37), HPS achieved a sensitivity of 92.9%, specificity of 73.9%, positive predictive value (PPV) of 68.4%, and negative predictive value (NPV) of 94.4% for biopsy-confirmed ACR. HPS achieved an area under the curve (AUC) of 0.831 compared with 0.731 for ALT and 0.660 for AST. Conclusions: HepatoTrack™ support the analytical and clinical validity for detection of biopsy-confirmed acute cellular rejection in liver transplant recipients. The assay provides a noninvasive molecular test to aid in the diagnosis of acute cellular rejection and may complement existing post-transplant diagnostic evaluation. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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23 pages, 818 KB  
Systematic Review
Therapeutic Effects of Dihydromyricetin on Wholly Alcohol-Attributed Conditions: A Systematic Review
by Samantha G. Skinner, Saikumar Matcha and Daryl L. Davies
Nutrients 2026, 18(14), 2221; https://doi.org/10.3390/nu18142221 - 8 Jul 2026
Abstract
Background: Alcohol use is a major global health burden and is causally linked to several wholly alcohol-attributed conditions, including alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). Current therapeutic options remain limited. Dihydromyricetin (DHM), a plant-derived flavonoid with antioxidant and anti-inflammatory [...] Read more.
Background: Alcohol use is a major global health burden and is causally linked to several wholly alcohol-attributed conditions, including alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). Current therapeutic options remain limited. Dihydromyricetin (DHM), a plant-derived flavonoid with antioxidant and anti-inflammatory properties, has emerged as a potential candidate for mitigating alcohol-induced toxicity. This systematic review aimed to comprehensively evaluate the therapeutic effects of DHM across alcohol-related conditions. Methods: A systematic literature search was conducted in PubMed from inception through December 2025 for studies investigating the effects of DHM or DHM-containing extracts on alcohol-related outcomes. Both preclinical (in vitro and in vivo) and clinical studies were considered. Study quality was assessed qualitatively due to heterogeneity precluding use of a standardized risk-of-bias tool. Results were synthesized narratively by outcome category; meta-analysis was not performed. This review was unregistered with no prior protocol. Results: A total of 22 studies were included, comprising 8 in vitro, 17 in vivo, and 2 clinical studies, with some studies contributing data to more than one category. Across models, DHM consistently attenuated ethanol-induced cytotoxicity, oxidative stress, inflammation, and hepatic steatosis. DHM improved liver injury biomarkers (e.g., AST and ALT), enhanced antioxidant defenses, and modulated key signaling pathways including Nrf2 and AMPK. Additionally, DHM supported mitochondrial function and intestinal barrier integrity. However, findings related to ethanol metabolism and neurobehavioral outcomes were inconsistent. Clinical evidence was limited to two small trials using Hovenia dulcis extracts, which demonstrated reductions in hangover severity and selected inflammatory markers but did not directly evaluate isolated DHM. Conclusions: DHM demonstrates robust preclinical efficacy in mitigating alcohol-induced injury, particularly in hepatic outcomes. Despite promising mechanistic and experimental evidence, clinical data remain limited. The certainty of evidence is constrained by preclinical study heterogeneity, the absence of formal risk-of-bias assessment, and the lack of clinical trials using isolated DHM. Well-designed clinical trials using standardized DHM formulations are needed to establish its complete therapeutic potential in alcohol-related disorders. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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16 pages, 592 KB  
Article
Longitudinal Changes in Serum Procalcitonin After Bariatric Surgery and Their Associations with Anthropometric, Metabolic, and Inflammatory Parameters
by Gurbet Ünal Özen, Çağrı Büyükkasap, Beyza Dursun and Aslı Akyol
J. Clin. Med. 2026, 15(13), 5293; https://doi.org/10.3390/jcm15135293 - 7 Jul 2026
Viewed by 154
Abstract
Objective: Obesity is a systemic disease characterized by low-grade chronic inflammation and increased metabolic risk. Although bariatric surgery is known to improve metabolic and inflammatory status, the longitudinal behavior of emerging inflammatory biomarkers such as procalcitonin (PCT) remains insufficiently characterized. This study [...] Read more.
Objective: Obesity is a systemic disease characterized by low-grade chronic inflammation and increased metabolic risk. Although bariatric surgery is known to improve metabolic and inflammatory status, the longitudinal behavior of emerging inflammatory biomarkers such as procalcitonin (PCT) remains insufficiently characterized. This study aimed to evaluate postoperative changes in serum procalcitonin (PCT) levels in patients undergoing bariatric surgery and to investigate their associations with anthropometric measurements, liver enzymes, and novel inflammatory indices. Methods: In this retrospective longitudinal cohort study, 38 patients who underwent sleeve gastrectomy and had complete preoperative and postoperative follow-up data at months 1, 3, and 6 were included. Anthropometric and biochemical parameters were analyzed, and systemic inflammation was assessed using PCT, Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI). Repeated-measures analyses were performed according to data distribution, and correlations were evaluated using Spearman analysis. Results: PCT levels showed a significant reduction at postoperative month 1 compared with the preoperative period. However, despite continued reductions in body weight, BMI, and fat mass at postoperative months 3 and 6, PCT levels plateaued without further significant change. In the preoperative period, PCT demonstrated strong positive correlations with liver enzymes (p < 0.01). At postoperative month 1, PCT was significantly associated with glucose and HbA1c levels. Although SII and SIRI decreased after surgery, no significant correlation with PCT was observed. Conclusions: PCT decreased in the early postoperative period after sleeve gastrectomy and may reflect early metabolic and inflammatory changes associated with rapid weight loss. However, its sensitivity for monitoring long-term inflammatory changes appears limited. The observed preoperative associations with liver enzymes may suggest a potential relationship between PCT levels, liver enzyme alterations, and metabolic alterations in obesity. Full article
(This article belongs to the Special Issue Bariatric Surgery: Current Status and Emerging Clinical Trends)
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29 pages, 11699 KB  
Article
Plasma Exosomes Associated with Growth Divergence in High-Density Cultured Grass Carp (Ctenopharyngodon idella): miRNA-Protein Profiling Reveals Cross-Tissue Communication Networks
by Tengfei Zhu, Zhipeng Zheng, Hao Chen, Yingying Yu, Huayang Guo, Baosuo Liu, Kecheng Zhu, Nan Zhang, Lin Xian, Shuhui Zheng, Yang Liu, Songlin Chen and Dianchang Zhang
Int. J. Mol. Sci. 2026, 27(13), 6059; https://doi.org/10.3390/ijms27136059 - 6 Jul 2026
Viewed by 125
Abstract
Grass carp (Ctenopharyngodon idella) is a major freshwater aquaculture species in China, but its growth is limited under intensive high-density farming. This study aimed to investigate the characteristics of plasma exosomes associated with distinct growth performance by isolating and characterizing exosomes [...] Read more.
Grass carp (Ctenopharyngodon idella) is a major freshwater aquaculture species in China, but its growth is limited under intensive high-density farming. This study aimed to investigate the characteristics of plasma exosomes associated with distinct growth performance by isolating and characterizing exosomes from fast- and slow-growing grass carp after nine months of culture. Exosomes showed typical morphology and expressed characteristic markers (CD63, CD81, TSG101). Small RNA sequencing identified 3325 miRNAs, with 177 highly abundant miRNAs differentially expressed: immune-related miRNAs were upregulated, while development-inhibitory miRNAs were downregulated in fast-growing fish. Target gene enrichment highlighted pathways in neural and skeletal development and amino acid metabolism. Integrative analysis across tissues revealed 26 miRNAs with coordinated expression patterns between plasma exosomes and brain, liver, or muscle, validated by qPCR. DIA proteomics quantified 4203 proteins, identifying 843 differentially enriched proteins linked to immune response, energy metabolism, and endoplasmic reticulum stress. Notably, TYMP was upregulated in muscle and exosomes, while several proteins (e.g., GYG2, BHMT) showed coordinated downregulation across tissues and exosomes in large fish. These results provide comprehensive evidence of exosome-mediated cross-tissue communication in teleosts and suggest a potential role for plasma exosomal miRNAs and proteins as non-invasive biomarkers correlated with growth status in aquaculture. Full article
(This article belongs to the Section Molecular Biology)
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17 pages, 11110 KB  
Article
Integrated Plasma and Tissue Lipid Profiling Demonstrates a Distinctive Metabolic Profile in MAFLD-Associated Non-Cirrhotic Hepatocellular Carcinoma
by Fatema Safri, Russell Pickford, Yikun Xu, William Yang, Romario Nguyen, Lawrence Yuen, Vincent Lam, Christopher Nahm, Tony Pang, Jacob George and Liang Qiao
Int. J. Mol. Sci. 2026, 27(13), 6060; https://doi.org/10.3390/ijms27136060 - 6 Jul 2026
Viewed by 173
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is now the leading cause of hepatocellular carcinoma (HCC) globally. HCC surveillance is currently restricted to patients with cirrhosis, leaving those without cirrhosis, who present with more advanced disease and poorer outcomes without adequate risk stratification tools. [...] Read more.
Metabolic dysfunction-associated fatty liver disease (MAFLD) is now the leading cause of hepatocellular carcinoma (HCC) globally. HCC surveillance is currently restricted to patients with cirrhosis, leaving those without cirrhosis, who present with more advanced disease and poorer outcomes without adequate risk stratification tools. This study compared lipid profiles across MAFLD and MAFLD-related HCC (MAFLD-HCC) patients, with and without cirrhosis, to characterise metabolic dysregulation underlying non-cirrhotic MAFLD-HCC (ncMAFLD-HCC). Plasma and liver lipidomic profiles were obtained from 221 patients (140 MAFLD, 66 cirrhotic MAFLD-HCC (cMAFLD-HCC), and 15 ncMAFLD-HCC) using untargeted liquid chromatography mass spectrometry. Univariate, multivariable and enrichment analyses were performed for statistically determining the lipid profile difference between the groups. Seventy percent of lipid classes were more abundant in MAFLD than in ncMAFLD-HCC and cMAFLD-HCC. Multivariate analysis revealed distinct lipid profiles across the three groups in both plasma and liver. Over 100 lipid species including diglyceride (DAG), sphingomyelin (SM), triglyceride (TG), dihydroceramide (DHCer), and linoleic acid derivatives were differentially expressed in ncMAFLD-HCC versus MAFLD, with enrichment in pathways such as glycerolipid metabolism, G-protein signalling, MAPK signalling, EGFR-TKI resistance pathway, implicated in HCC development. ncMAFLD-HCC exhibits a distinct lipid signature, offering preliminary mechanistic insight and a foundation for non-invasive biomarker development. Full article
(This article belongs to the Section Molecular Oncology)
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16 pages, 7810 KB  
Article
Synergy of Extremely Low-Frequency Electromagnetic Fields (ELFEFs) and Sex Hormones Against Oxidative Stress in Multiple Sclerosis
by Begoña M. Escribano, Manuel E. Valdelvira, Ana Muñoz-Jurado, Montse Feijóo, Eduardo Agüera-Morales, Javier Caballero-Villarraso, Abel Santamaría and Isaac Túnez
Antioxidants 2026, 15(7), 851; https://doi.org/10.3390/antiox15070851 - 6 Jul 2026
Viewed by 105
Abstract
Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method with neuromodulatory capacity in neurodegenerative diseases such as multiple sclerosis (MS). Its therapeutic value is linked to its activity against oxidative stress by activation of antioxidant defenses. The sex hormones, estrogens (E), progesterone [...] Read more.
Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method with neuromodulatory capacity in neurodegenerative diseases such as multiple sclerosis (MS). Its therapeutic value is linked to its activity against oxidative stress by activation of antioxidant defenses. The sex hormones, estrogens (E), progesterone (P) and testosterone (T), have demonstrated their power as adjuvants to TMS, improving cortical excitability. The aim of this study was to evaluate the effect of these hormones as adjuvants to extremely low-frequency electromagnetic fields (ELFEFs) in the treatment of experimental autoimmune encephalomyelitis (EAE), the experimental model of MS. The effect of these hormones as replacement therapy was also evaluated in ovariectomized rats treated with ELFEFs. Sixty-five female Dark Agouti rats were divided into 13 groups (5 rats/group), in which biomarkers of oxidative stress and the glutathione redox cycle in non-nervous organs (kidney, liver, heart, intestines and blood) were analyzed. The results show that ELFEFs alone are more effective against oxidative stress. However, P and E were more effective than ELFEFs, both as adjuvants and in hormone replacement therapy, in activating the glutathione system. Therefore, it could be concluded that sex hormones play an important role against MS, enhancing the antioxidant effect of ELFEFs. Full article
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21 pages, 3429 KB  
Article
Liver–Metabolic Phenotypes and Renal Vulnerability in Community-Acquired Sepsis: Insights from the SepsisFAT Cohort
by Lara Šamadan Marković, Hana Panić, Juraj Krznarić, Branimir Gjurašin and Neven Papić
Metabolites 2026, 16(7), 468; https://doi.org/10.3390/metabo16070468 - 4 Jul 2026
Viewed by 149
Abstract
Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is associated with adverse outcomes in sepsis, but risk stratification within MASLD remains insufficiently defined. We investigated whether an admission liver–metabolic phenotype framework combining cardiometabolic burden with liver injury/fibroinflammatory risk markers identifies clinically relevant organ-support vulnerability in [...] Read more.
Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is associated with adverse outcomes in sepsis, but risk stratification within MASLD remains insufficiently defined. We investigated whether an admission liver–metabolic phenotype framework combining cardiometabolic burden with liver injury/fibroinflammatory risk markers identifies clinically relevant organ-support vulnerability in community-acquired sepsis. Methods: This secondary analysis of the prospective SepsisFAT cohort (378 adults with community-acquired sepsis) classified patients into four phenotypes by cardiometabolic burden (≥2 of: diabetes, hypertension, dyslipidemia, BMI ≥ 30 kg/m2) and liver-risk positivity (FIB-4 ≥ 2.67, APRI ≥ 1.0, liver stiffness ≥ 10 kPa, or FAST ≥ 0.55). The primary outcome was acute kidney injury (AKI), while continuous renal replacement therapy (CRRT), other organ-support outcomes and in-hospital mortality were secondary endpoints. Results: Phenotype distribution was Low-risk 137 (36.2%), Cardiometabolic-only 84 (22.2%), Liver-dominant 88 (23.3%), and Mixed liver–cardiometabolic 69 (18.3%). AKI and CRRT increased across phenotypes (13.9% to 40.6% and 5.1% to 26.1%, respectively), and in-hospital mortality was highest in the Mixed phenotype (26.1%). After Firth-penalized adjustment for age, sex, and admission SOFA, the Mixed phenotype remained independently associated with AKI (aOR 2.82, 95% CI 1.37–5.90) and CRRT (aOR 3.87, 1.50–10.80), confirmed in non-renal SOFA and admission eGFR-adjusted sensitivity analyses. Cardiometabolic burden alone did not confer excess organ-support risk. The same gradient persisted within the MASLD subgroup. Conclusions: Admission liver–metabolic phenotyping identified a renal-vulnerable sepsis subgroup not captured by binary MASLD classification alone. These findings support prospective, multicenter external validation of liver–metabolic phenotyping as a pragmatic approach to renal risk stratification in community-acquired sepsis. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
15 pages, 1310 KB  
Article
Exploratory Analysis of Liver Tissue and Preservation Fluid Biomarkers (β-Hydroxybutyrate and Arginase) in Relation to Graft Steatosis
by Kawthar Safi, Angelika Joanna Pawlicka, Grażyna Kubiak-Tomaszewska, Marta Struga, Andriy Zhylko, Maciej Krasnodębski, Michał Grąt and Alicja Chrzanowska
J. Clin. Med. 2026, 15(13), 5239; https://doi.org/10.3390/jcm15135239 - 4 Jul 2026
Viewed by 161
Abstract
Background: Reliable intraoperative tools for donor liver assessment are needed, particularly in the context of steatotic and extended-criteria grafts. While histology remains the reference standard, it is limited by sampling variability and logistical constraints. Preservation fluid may provide a complementary, whole-organ source of [...] Read more.
Background: Reliable intraoperative tools for donor liver assessment are needed, particularly in the context of steatotic and extended-criteria grafts. While histology remains the reference standard, it is limited by sampling variability and logistical constraints. Preservation fluid may provide a complementary, whole-organ source of biochemical information. Methods: In this single-center prospective exploratory pilot study, liver tissue and preservation fluid were collected from 30 donation-after-brain-death grafts during the back-table procedure. Biochemical parameters, including arginase activity, β-hydroxybutyrate (βHB), acetoacetate, and total protein, were measured using standard assays. Associations with histological steatosis on wedge biopsy were assessed using nonparametric correlation analyses, and paired preservation fluid samples were compared. Results: Most grafts demonstrated absent or mild steatosis; only two exhibited moderate steatosis, and none were severely steatotic. No preservation fluid biomarker showed a statistically significant association with histological steatosis. Weak, non-significant positive correlations were observed for βHB and arginase activity (Spearman r ≈ 0.33–0.35). Protein concentration and arginase activity decreased between start and end samples, whereas ketone body levels remained relatively stable. Conclusions: Preservation fluid biomarker measurement during routine graft preparation is feasible. Although no significant associations with histological steatosis were identified, the observed weak correlations suggest possible associations requiring validation in larger studies. Larger, adequately powered studies, including a broader spectrum of steatosis and clinically relevant outcomes, are required to determine potential clinical applicability. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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23 pages, 3671 KB  
Article
From Invaders to Resources: Evaluating Freshwater Invasive Species as Sustainable Sources for Aquaculture Feed
by Giorgia Zicarelli, Sara Glorio Patrucco, Barbara Caldaroni, Christian Caimi, Rebecca Gentile, Alessandra Maganza, Sara Bellezza Oddon, Annalisa Cotugno, Giuseppe Esposito, Ilaria Biasato, Stefania Bergagna, Daniela Marchis, Marzia Pezzolato, Caterina Faggio, Elena Bozzetta, Marino Prearo, Antonia Concetta Elia, Laura Gasco and Paolo Pastorino
Sustainability 2026, 18(13), 6808; https://doi.org/10.3390/su18136808 - 4 Jul 2026
Viewed by 247
Abstract
The increasing spread of invasive alien species (IAS) represents one of the major causes of biodiversity loss, making containment practices necessary. In this regard, the circular economy framework proposes to reuse the biomass from IAS in growing sectors such as aquaculture, in which [...] Read more.
The increasing spread of invasive alien species (IAS) represents one of the major causes of biodiversity loss, making containment practices necessary. In this regard, the circular economy framework proposes to reuse the biomass from IAS in growing sectors such as aquaculture, in which more sustainable practices are required. This study evaluated the possibility of using biomass derived from two widespread freshwater IAS, Procambarus clarkii and Silurus glanis, as dietary ingredients for Oncorhynchus mykiss. Experimental diets were formulated by incorporating 20% of IAS-derived muscle powder into a commercial feed, and their effects were assessed through a 35-day feeding trial. Chemical analyses confirmed the nutritional suitability of the formulated diets and the absence of antibiotic residues. No mortality or significant differences in growth performance were observed among treatments. Blood biochemical parameters showed limited variations, remaining within physiological ranges, while oxidative stress biomarkers indicated only minor, diet-specific responses without evidence of oxidative damage. An increase in Hsp70 expression suggested adaptive physiological responses rather than pathological stress. Histological analyses of liver and gut tissues revealed no structural alterations across experimental groups. Overall, the results demonstrate that the inclusion of IAS-derived biomass at 20% is well tolerated by O. mykiss and does not impair fish health. These findings support the potential of invasive species valorization as a sustainable strategy for aquaculture feed production, contributing to both resource efficiency and ecosystem management. Full article
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16 pages, 2544 KB  
Communication
Sequential [11C]Acetate and [18F]FDG PET/CT Assessment of Systemic Chronic Active Epstein–Barr Virus Disease: An Exploratory Retrospective Study
by Momo Wakui, Shuichi Yanai, Junichi Tsuchiya, Masahide Yamamoto, Hirofumi Yamada, Kota Yokoyama, Shinichi Taura, Tatsuhiko Anzai, Ayako Arai and Ukihide Tateishi
Diagnostics 2026, 16(13), 2071; https://doi.org/10.3390/diagnostics16132071 - 2 Jul 2026
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Abstract
Systemic chronic active Epstein–Barr virus disease (sCAEBV) is a rare and potentially fatal disorder characterized by inflammatory manifestations and organ infiltration by EBV-infected T- or NK-cells. Although [18F]FDG PET/CT has limited utility for assessing the disease activity of sCAEBV, [11 [...] Read more.
Systemic chronic active Epstein–Barr virus disease (sCAEBV) is a rare and potentially fatal disorder characterized by inflammatory manifestations and organ infiltration by EBV-infected T- or NK-cells. Although [18F]FDG PET/CT has limited utility for assessing the disease activity of sCAEBV, [11C]acetate PET/CT has not previously been evaluated in this setting. We therefore conducted this exploratory retrospective study to assess the utility of sequentially performed [11C]acetate and [18F]FDG PET/CT in sCAEBV. Five patients diagnosed with sCAEBV according to the criteria of the Research Group on Measures against Intractable Diseases, Ministry of Health, Labour and Welfare of Japan (consistent with the 2017 WHO classification) and assessed between July 2017 and December 2018 were included; patients younger than 20 years were excluded. Each patient underwent both [11C]acetate and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) on the same day. The maximum and mean standardized uptake values (SUVmax and SUVmean) of the liver and spleen and the liver-to-spleen ratio (LSR) were correlated with laboratory parameters, including alanine aminotransferase (ALT) and lactate dehydrogenase (LDH), using Spearman’s rank correlation coefficient. The LSR was compared between active and inactive cases using the Mann–Whitney U test. Twenty-one lymph node regions were assessed in each patient, and the SUVmax of detected lesions was measured. The detection rate of lymph node lesions between the two tracers was compared using McNemar’s test, and the SUVmax of lymph node lesions was compared between the two tracers and between active and inactive cases using the Mann–Whitney U test. All statistical analyses were performed using R version 4.5.3 (R Foundation for Statistical Computing, Vienna, Austria), and a p-value < 0.05 was considered statistically significant. Five patients (three men and two women; mean age 31.8 years, range 21–39 years) were included. [11C]acetate PET/CT showed significant negative correlations between spleen SUV and liver enzymes (AST, ALT, and LDH), and significant positive correlations between the LSR and all five liver enzymes tested (AST, ALT, LDH, γGTP, and ALP) (Spearman’s rank correlation coefficient; p < 0.05 for all). No significant correlations were observed with [18F]FDG PET/CT. The LSR on [11C]acetate PET/CT was numerically higher in active cases than in inactive cases, though this difference was not statistically significant (0.88 ± 0.02 vs. 0.61 ± 0.02; p = 0.20, Mann–Whitney U test). Lymph node lesion detectability did not differ significantly between the two tracers (16 vs. 12 regions; p = 0.13, McNemar’s test). In this pilot study, [11C]acetate PET/CT spleen SUV showed significant negative correlations with liver enzymes (AST, ALT, and LDH), and the LSR showed significant positive correlations with all measured liver enzymes, suggesting that [11C]acetate PET/CT reflects both hepatic and splenic involvement in sCAEBV. [11C]acetate PET/CT may therefore serve as a novel imaging biomarker for assessing disease activity in sCAEBV, warranting further investigation in larger cohorts. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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Article
Diagnostic Performance of Microvascular Imaging for Detecting Histologically Confirmed Liver Fibrosis in Autoimmune Hepatitis: Comparison with Transient Elastography and Serum Biomarkers
by Nazugum Ashimova, Aigul Raissova, Evgeniy Yenin, Rabiga Khozhamkul, Zhamilya Zholdybay, Maigul Shamshidinova, Takhmina Usenova, Andreas Teufel, Aigerim Mustapayeva and Alexander Nersesov
Diagnostics 2026, 16(13), 2072; https://doi.org/10.3390/diagnostics16132072 - 2 Jul 2026
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Abstract
Background/Objectives: Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease that may progress to cirrhosis and liver failure if not diagnosed early. Although liver biopsy remains the reference standard for fibrosis assessment, its invasive nature limits routine use. This study aimed to [...] Read more.
Background/Objectives: Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease that may progress to cirrhosis and liver failure if not diagnosed early. Although liver biopsy remains the reference standard for fibrosis assessment, its invasive nature limits routine use. This study aimed to compare the diagnostic performance of ultrasound-based microvascular imaging (MVI), transient elastography (TE), and serum fibrosis indices (APRI and FIB-4) in patients with biopsy-confirmed AIH. Methods: Fifty-five patients with probable or definite AIH according to IAIHG criteria were included in the study. All patients underwent liver biopsy, and fibrosis stage was assessed using the METAVIR system. TE and MVI examinations were performed, and APRI and FIB-4 scores were calculated. Diagnostic performance was evaluated using AUROC, sensitivity, and specificity. Spearman correlation and logistic regression analyses were additionally performed. Results: The mean age of the patients was 49.2 years, and most patients were women. Cirrhosis was present in 58.2% of the cohort. TE demonstrated high diagnostic accuracy, whereas FIB-4 showed moderate performance and APRI demonstrated limited utility. MVI achieved the highest diagnostic performance, with AUROC values of 0.99 for significant fibrosis and 0.97 for cirrhosis. MVI showed the strongest correlation with histological fibrosis stage (r = 0.916, p < 0.001), followed by TE (r = 0.907, p < 0.001). MVI was strongly associated with histologically confirmed cirrhosis (OR 16.7, 95% CI 2.36–118.2, p = 0.004). Conclusions: MVI demonstrates diagnostic performance comparable to TE and may represent a promising adjunctive non-invasive imaging biomarker for fibrosis assessment in AIH. Larger multicenter studies are required for external validation before routine clinical implementation. Full article
(This article belongs to the Special Issue Diagnostic Imaging in Gastrointestinal and Liver Diseases)
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