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Background and Aims: This study prospectively compared the diagnostic accuracies of the improved Attenuation Measurement (iATT) algorithm and the Controlled Attenuation Parameter (CAP) and assessed the interchangeability of iATT with magnetic resonance imaging-derived proton density fat fraction (MRI-derived PDFF)., Methods: Patients with chronic liver disease were prospectively enrolled and underwent iATT, CAP and MRI-derived PDFF measurements for hepatic steatosis evaluation. According to MRI-derived PDFF values, steatosis grades were categorised as steatosis (S)0 (< 5.2%), S1 (≥ 5.2%, < 11.3%), S2 (≥ 11.3%, < 17.1%) and S3 (≥ 17.1%). Correlation coefficients (CCs) were determined, diagnostic performances were compared by the area under the receiver operating characteristic curve (AUROC) and agreement was evaluated using the calculated percentage error (PE) and expected limit of agreement (LOA)., Results: A total of 414 patients (median age 64 years, 203 females) were evaluated. The CC between iATT and MRI-derived PDFF was 0.727 (95% confidence interval [CI] 0.678-0.770), which was higher than that between CAP and MRI-derived PDFF at 0.615 (95% CI 0.551-0.672) (p < 0.001). The AUROCs of iATT for ≥ S1, ≥ S2 and ≥ S3 were 0.901 (95% CI 0.870-0.931), 0.878 (95% CI 0.846-0.910) and 0.839 (95% CI 0.794-0.883), respectively. The diagnostic performances of iATT for ≥ S1 and ≥ S2 showed significantly higher AUROCs than those of CAP (p < 0.001, p = 0.036, respectively). The calculated PE and the expected LOA for CAP and iATT were 38.94% and 22.66% and 32.94% and 30.03%, respectively., Conclusions: iATT was superior to CAP and comparable to MRI-derived PDFF in assessing hepatic steatosis., Trial Registration: This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000047411)., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: There is an unmet need for a reliable and reproducible non-invasive measure of fatty liver content (FLC) for monitoring steatotic liver disease in clinical practice. Sonographic FLC assessment is qualitative and operator-dependent, and the dynamic quantification range of algorithms based on a single ultrasound (US) parameter is unsatisfactory. This study aims to develop and validate a new multiparametric algorithm based on B-mode images to quantify FLC using Magnetic Resonance (MR) values as standard reference., Methods: Patients with elevated liver enzymes and/or bright liver at US (N = 195) underwent FLC evaluation by MR and by US. Five US-derived quantitative features [attenuation rate(AR), hepatic renal-ratio(HR), diaphragm visualization(DV), hepatic-portal-vein-ratio(HPV), portal-vein-wall(PVW)] were combined by mixed linear/exponential regression in a multiparametric model (Steatoscore2.0). One hundred and thirty-four subjects were used for training and 61 for independent validations; score-computation underwent an inter-operator reproducibility analysis., Results: The model is based on a mixed linear/exponential combination of 3 US parameters (AR, HR, DV), modelled by 2 equations according to AR values. The computation of FLC by Steatoscore2.0 (mean ± std, 7.91% ± 8.69) and MR (mean ± std, 8.10% ± 10.31) is highly correlated with a low root mean square error in both training/validation cohorts, respectively (R = 0.92/0.86 and RMSE = 5.15/4.62, p < .001). Steatoscore2.0 identified patients with MR-FLC≥5%/≥10% with sensitivity = 93.2%/89.4%, specificity = 86.1%/95.8%, AUROC = 0.958/0.975, respectively and correlated with MR (R = 0.92) significantly (p < .001) better than CAP (R = 0.73)., Conclusions: Multiparametric Steatoscore2.0 measures FLC providing values highly comparable with MR. It is reliable, inexpensive, easy to use with any US equipment and qualifies to be tested in larger, prospective studies as new tool for the non-invasive screening and monitoring of FLC., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Obesity has increased dramatically worldwide. Being overweight or obese can lead to various conditions, including dyslipidaemia, hypertension, glucose intolerance and metabolic syndrome (MetS), which may further lead to type 2 diabetes mellitus (T2DM). Previous studies have identified a link between β-cell dysfunction and the severity of MetS, with multiple organs and tissues affected. Identifying the associations between pancreatic β-cell dysfunction and organs is critical. Research has focused on the interaction between the liver, gut and pancreatic β-cells. However, the mechanisms and related core targets are still not perfectly elucidated. The aims of this review were to summarize the mechanisms of β-cell dysfunction and to explore the potential pathogenic pathways and targets that connect the liver, gut, adipose tissue, muscle, and brain to pancreatic β-cell dysfunction., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: Porto-sinusoidal vascular disease (PSVD) is an under-recognized and under-diagnosed disease. The purpose of this study was to investigate the clinical features and prognosis of PSVD., Methods: The patients who underwent liver biopsies were analyzed retrospectively. The clinical and pathological data were reviewed and screened according to the latest diagnostic criteria of PSVD., Results: A total of 234 patients were diagnosed as PSVD, including 103 patients presented with portal hypertension (PH) and 131 patients without PH. At baseline, the alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT) levels were higher in the no-PH group. The liver stiffness increased in the PH group. In histological review, obliterative portal venopathy, sinusoidal dilatation and architectural disturbance were more common in the PH group, while portal tract abnormalities were more widely distributed in the no-PH group. After a median follow-up of 43.6 months, the survival rate of patients with baseline liver decompensation was 76.0%, and that of patients at a liver compensated stage in the PH group was 98.7%. First variceal bleeding occurred in 13.8% of patients with gastric-oesophageal varices. None of the patients in the no-PH group developed portal hypertension during follow-up., Conclusions: PSVD can manifest as PH or mild liver enzyme abnormalities. There are significant differences in pathological features among patients with different clinical manifestations. Recurrent ascites are the main cause of death in PSVD patients. However, patients without PH have a slow disease progression, with recurrent elevated GGT levels being their main clinical feature., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Lentiviral vectors (LV) are efficient vehicles for in vivo gene delivery to the liver. LV integration into the chromatin of target cells ensures their transmission upon proliferation, thus allowing potentially life-long gene therapy following a single administration, even to young individuals. The glycoprotein of the vesicular stomatitis virus (VSV.G) is widely used to pseudotype LV, as it confers broad tropism and high stability. The baculovirus-derived GP64 envelope protein has been proposed as an alternative for in vivo liver-directed gene therapy. Here, we perform a detailed comparison of VSV.G- and GP64-pseudotyped LV in vitro and in vivo. We report that VSV.G-LV transduced hepatocytes better than GP64-LV, however the latter showed improved transduction of liver sinusoidal endothelial cells (LSEC). Combining GP64-pseudotyping with the high surface content of the phagocytosis inhibitor CD47 further enhanced LSEC transduction. Coagulation factor VIII (FVIII), the gene mutated in hemophilia A, is naturally expressed by LSEC, thus we exploited GP64-LV to deliver a FVIII transgene under the control of the endogenous FVIII promoter and achieved therapeutic amounts of FVIII and correction of hemophilia A mice., (© 2024. The Author(s).)

Few instances of neoplastic formations in the liver of chinchillas have been found, even though the species is widely used in different scientific experiments. In the present article we investigate the anatomical features of the chinchilla's liver using CT and three dimension (3D) imaging. For the trials we used 12 (six males and six females) clinically healthy chinchillas all at 18 months of age. The animals were positioned in dorsal recumbency. We used Th8 to L2 vertebrae and the sternum as bone markers for the transverse CT study. The investigated anatomical landmarks for the CT coronal study were the vertebrae, costal arch, soft abdominal wall, diaphragm, stomach and the right kidney. 3D reconstructions were accomplished with a specific imaging software. On transverse and coronal CT images, the chinchilla's liver was composed of lobus hepatis sinister lateralis, 'middle lobe'-without proper Latin term in NAV 2017, lobus hepatis dexter and lobus caudatus. The 'middle lobe' was separated into the 'left middle lobe' and the 'right middle lobe'. Lobus hepatis dexter consisted of lobus hepatis dexter medialis and lobus hepatis dexter lateralis. There was an anatomical relation between the liver, fundus ventriculi and corpus ventriculi. Proc. caudatus was in close contact with the right kidney. Vesica fellea was elongated and ellipsoid. 3D reformatted images confirmed the results obtained by transverse and coronal CT studies. The CT density of the liver in HU was 195.6 ± 73.1. The CT and 3D reconstructed images were visualized at high resolution. This data could be used as a basis for further morphological and imaging studies., (© 2024 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: Abdominal normothermic regional perfusion (A-NRP) allows in-situ reperfusion and recovery of abdominal organs metabolism in donors after circulatory death (DCD). Besides improving liver transplantation outcomes, liver injury and function can be assessed during A-NRP., Methods: To refine liver viability assessment during A-NRP, prospectively collected data of controlled DCD donors managed at our Institution between October 2019 and May 2022 were retrospectively analyzed. Baseline characteristics, procedural variables and A-NRP parameters of donors whose liver was successfully transplanted were compared to those of donors whose liver was discarded., Results: Twenty-seven donors were included and in 20 (74%) the liver was accepted (positive outcome). No differences between study groups were observed concerning baseline characteristics and warm ischemia times (WIT). Initial lactate levels were positively correlated with functional WIT (r 2  = 0.4, p = 0.04), whereas transaminase levels were not. Blood flow during A-NRP was comparable, whereas oxygen consumption (VO 2 ) was significantly higher in the positive outcome group after 1 h. Time courses of lactate, AST and ALT were significantly different between study groups (p < 0.001). Donors whose liver was accepted showed faster lactate clearance, a difference which was amplified by normalizing lactate clearance to oxygen delivery (DO 2 ) and VO 2 . Lactate clearance was correlated to transaminase levels and DO 2 -normalized lactate clearance was the parameter best discriminating between study groups., Conclusions: DO 2 -normalized lactate clearance may represent an element of liver viability assessment during A-NRP., (© 2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Cell junctions, including anchoring, occluding and communicating junctions, play an indispensable role in the structural and functional organization of multicellular tissues, including in liver. Specifically, hepatic cell junctions mediate intercellular adhesion and communication between liver cells. The establishment of the hepatic cell junction network is a prerequisite for normal liver functioning. Hepatic cell junctions indeed support liver-specific features and control essential aspects of the hepatic life cycle. This review paper summarizes the role of cell junctions and their components in relation to liver physiology, thereby also discussing their involvement in hepatic dysfunctionality, including liver disease and toxicity., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Liver cancer presents a growing global health concern, necessitating advanced approaches for intervention. This review investigates the use and effectiveness of software navigation in interventional radiology for liver tumour procedures. Methods: In accordance with Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐ScR) guidelines, a scoping review was conducted of the literature published between 2013 and 2023 sourcing articles through MEDLINE, Scopus, CINAHL and Embase. Eligible studies focused on liver cancer, utilised cone‐beam computed tomography (CBCT), and employed software for intervention. Twenty‐one articles were deemed eligible for data extraction and analysis. Results: Categorised by type, software applications yielded diverse benefits. Feeder detection software significantly enhanced vessel identification, reducing non‐target embolisation by up to 43%. Motion correction software demonstrated a 20% enhancement in image quality, effectively mitigating breathing‐induced motion artefacts. Liver perfusion software facilitated efficient tumour targeting while simultaneously reducing the occurrence of side effects. Needle guide software enabled precise radiofrequency ablation needle placement. Additionally, these software applications provided detailed anatomical simulations. Overall, software integration resulted in shorter procedures, reduced radiation exposure and decreased contrast media usage. Conclusion: This scoping review highlights the innovative yet relatively underexplored role of software navigation for liver tumour procedures. The integration of software applications not only enhances procedural efficiency but also bolsters operator confidence, and contributes to improved patient outcomes. Despite the current lack of uniformity and standardisation, these software‐driven advancements hold significant promise for transforming liver tumour interventions. To realise these benefits, further research is needed to explore the clinical impact and optimal utilisation of software navigation tools in interventional radiology. [ABSTRACT FROM AUTHOR]

Liver, an important regulator of metabolic homeostasis, is critical for healthy brain function. In particular, age‐related neurodegenerative diseases seriously reduce the quality of life for the elderly. As population aging progresses rapidly, unraveling the mechanisms that effectively delay aging has become critical. Appropriate exercise is reported to improve aging‐related cognitive impairment. Whereas current studies focused on exploring the effect of exercise on the aging brain itself, ignoring the persistent effects of peripheral organs on the brain through the blood circulation. The aim of this paper is to summarize the communication and aging processes of the liver and brain and to emphasize the metabolic mechanisms of the liver–brain axis about exercise ameliorating aging‐related neurodegenerative diseases. A comprehensive understanding of the potential mechanisms about exercise ameliorating aging is critical for improving adaptation to age‐related brain changes and formulating effective interventions against age‐related cognitive decline. [ABSTRACT FROM AUTHOR]

Hepatic ischemia/reperfusion injury (IRI) remains a severe threat during liver surgery and transplantation, accounting for unfavorable clinical outcomes. Modafinil (MOD), a wakefulness‐inducing compound, is increasingly disclosed to protect against IRI. However, the specific literatures covering the association between MOD and hepatic IRI are few. Here, this paper is committed to unraveling the role and response mechanism of MOD in hepatic IRI. After the establishment of hepatic IRI mice model and cell model, relevant assay kits measured the concentrations of biochemical indicators of hepatotoxicity and hematoxylin and eosin staining estimated liver morphology. Enzyme‐linked immunosorbent assay, reverse‐transcription quantitative polymerase chain reaction, and western blot evaluated inflammatory levels. Terminal‐deoxynucleoitidyl transferase‐mediated nick end labeling assay and western blot appraised apoptosis. Western blot also analyzed the expression of Toll‐like receptor 9 (TLR9)/myeloid differentiation primary response gene 88 (MyD88)/p38 signaling‐associated proteins. Cell counting kit‐8 method judged cell viability. MOD was discovered to mitigate liver dysfunction and morphological damage, inflammatory response, apoptosis in vivo and improve cell viability, suppress inflammatory response and apoptosis in vitro. In addition, MOD inactivated TLR9/Myd88/p38 signaling both in vitro and in vivo. Further, TLR9 elevation reversed the inhibitory role of MOD in inflammatory response and cell apoptosis in vitro. Anyway, MOD blocked TLR9/Myd88/p38 signaling to exhibit anti‐inflammatory and anti‐apoptotic properties in hepatic IRI. [ABSTRACT FROM AUTHOR]

Summary: The SIMulation supported LIVer Assessment for donor organs (SimLivA) project aims to develop a mathematical model to accurately simulate the influence of mechanical alterations in marginal liver grafts (specifically steatotic ones) and cold ischemia on early ischemia‐reperfusion injury (IRI) during liver transplantation. Our project tackles significant research challenges, including the co‐development of computational methodologies, experimental studies, clinical processes, and technical workflows. We aim to refine a continuum‐biomechanical model for enhanced IRI prediction, collect pivotal experimental and clinical data, and assess the clinical applicability of our model. Our efforts involve augmenting and tailoring a coupled continuum‐biomechanical, multiphase, and multi‐scale partial differential equation‐ordinary differential equation (PDE‐ODE) model of the liver lobule, allowing us to numerically simulate IRI depending on the degree of steatosis and the duration of ischemia. The envisaged model will intertwine the structure, perfusion, and function of the liver, serving as a crucial aid in clinical decision‐making processes. We view this as the initial step towards an in‐silico clinical decision support tool aimed at enhancing the outcomes of liver transplantation. In this paper, we provide an overview of the SimLivA project and our preliminary findings, which include: a cellular model that delineates critical processes in the context of IRI during transplantation; and the integration of this model into a multi‐scale PDE‐ODE model using a homogenized, multi‐scale, multi‐component approach within the Theory of Porous Media (TPM) framework. The model has successfully simulated the interconnected relationship between structure, perfusion, and function—all of which are integral to IRI. Initial results show simulations at the cellular scale that describe critical processes related to IRI during transplantation. After integrating this model into a multiscale PDE‐ODE model, first simulations were performed on the spatial distribution of key functions during warm and cold ischaemia. In addition, we were able to study the effect of tissue perfusion and temperature, two critical parameters in the context of liver transplantation and IRI. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Kuo et al papers. To view these articles, visit https://doi.org/10.1111/apt.17637 and https://doi.org/10.1111/apt.17677 [ABSTRACT FROM AUTHOR]

Liver cultures may be used for disease modeling, testing therapies, and predicting drug‐induced injury. The complexity of the liver cultures has evolved from hepatocyte monocultures to co‐cultures with non‐parenchymal cells and finally to precision‐cut liver slices. The latter culture format retains liver's native biomolecular and cellular complexity and therefore holds considerable promise for in vitro testing. However, liver slices remain functional for ≈72 h in vitro and display limited utility for some disease modeling and therapy testing applications that require longer culture times. This paper describes a microfluidic device for longer‐term maintenance of functional organotypic liver cultures. This microfluidic culture system is designed to enable direct injection of liver tissue into a culture chamber through a valve‐enabled side port. Liver tissue is embedded in collagen and remained functional for up to 31 days, highlighted by continued production of albumin and urea. These organotypic cultures also express several enzymes involved in xenobiotic metabolism. Conversely, matched liver tissue embedded in collagen in a 96‐well plate loses its phenotype and function within 3–5 days. The microfluidic organotypic liver cultures described here represent a significant advance in liver cultivation and may be used for future modeling of liver diseases or for individualized liver‐directed therapies. [ABSTRACT FROM AUTHOR]

Microgravity as experienced during spaceflight affects a number of physiological processes in various organs. However, effects on the liver have yet been poorly documented. Nevertheless, the liver is a metabolically highly active organ involved in carbohydrate metabolism, lipid metabolism and xenobiotic biotransformation. The present paper provides an overview of the effects of microgravity on the liver observed in experimental animals during actual spaceflight and upon simulation of microgravity on Earth. These include (i) induction of liver injury and inflammation associated with apoptosis and oxidative stress, (ii) changes in liver carbohydrate metabolism resulting in the onset of a diabetogenic phenotype, (iii) modifications in hepatic lipid metabolism leading to early non‐alcoholic fatty liver disease and (iv) alterations of the hepatic xenobiotic biotransformation machinery. Although most of these observations remain to be fully validated in humans, appropriate measures to counteract liver pathogenesis should be considered, especially in view of long‐term space missions. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) typically presents with hepatic fibrosis in advanced disease, resulting in increased liver stiffness. A subset of patients further develops liver cirrhosis and hepatocellular carcinoma. Cardiovascular disease is a common comorbidity in patients with MASLD and its prevalence is increasing in parallel. Recent evidence suggests that especially liver stiffness, whether or not existing against a background of MASLD, is associated with heart diseases. We conducted a narrative review on the role of liver stiffness in the prediction of highly prevalent heart diseases including heart failure, cardiac arrhythmias (in particular atrial fibrillation), coronary heart disease, and aortic valve sclerosis. Research papers were retrieved from major scientific databases (PubMed, Web of Science) until September 2023 using 'liver stiffness' and 'liver fibrosis' as keywords along with the latter cardiac conditions. Increased liver stiffness, determined by vibration-controlled transient elastography or hepatic fibrosis as predicted by biomarker panels, are associated with a variety of cardiovascular diseases, including heart failure, atrial fibrillation, and coronary heart disease. Elevated liver stiffness in patients with metabolic liver disease should lead to considerations of cardiac workup including N-terminal pro-- B-type natriuretic peptide/B-type natriuretic peptide determination, electrocardiography, and coronary computed tomography angiography. In addition, patients with MASLD would benefit from heart disease case-finding strategies in which liver stiffness measurements can play a key role. In conclusion, increased liver stiffness should be a trigger to consider a cardiac workup in metabolically compromised patients. [ABSTRACT FROM AUTHOR]

Purpose: Quantitative T1ρ imaging is an emerging technique to assess the biochemical properties of tissues. In this paper, we report our observation that liver iron content (LIC) affects T1ρ quantification of the liver at 3.0T field strength and develop a method to correct the effect of LIC. Theory and Methods: On‐resonance R1ρ (1/T1ρ) is mainly affected by the intrinsic R2 (1/T2), which is influenced by LIC. As on‐resonance R1ρ is closely related to the Carr–Purcell–Meiboom–Gill (CPMG) R2, and because the calibration between CPMG R2 and LIC has been reported at 1.5T, a correction method was proposed to correct the R2 contribution to the R1ρ. The correction coefficient was obtained from the calibration results and related transformed factors. To compensate for the difference between CPMG R2 and R1ρ, a scaling factor was determined using the values of CPMG R2 and R1ρ, obtained simultaneously from a single breath‐hold from volunteers. The livers of 110 subjects were scanned to validate the correction method. Results: LIC was significantly correlated with R1ρ in the liver. However, when the proposed correction method was applied to R1ρ, LIC and the iron‐corrected R1ρ were not significantly correlated. Conclusion: LIC can affect T1ρ in the liver. We developed an iron‐correction method for the quantification of T1ρ in the liver at 3.0T. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Kaur et al papers. To view these articles, visit https://doi.org/10.1111/apt.18202 and https://doi.org/10.1111/apt.18238 [ABSTRACT FROM AUTHOR]

The article titled "Correction to 'Attenuative role of mangiferin in oxidative stress mediated liver dysfunction in arsenic intoxicated murines'" discusses an editing error in Figure 5A of the original paper. The error involved the duplication of the "Normal" liver subpanel, which slightly overlapped. The authors confirm that this error does not affect the experimental results or conclusions mentioned in the paper. The corrected Figure 5A shows the normal hepatic architecture and the effects of mangiferin treatment on liver dysfunction caused by arsenic intoxication. The authors apologize for the error. [Extracted from the article]

LINKED CONTENT: This article is linked to Kuo et al papers. To view these articles, visit https://doi.org/10.1111/apt.17637 and https://doi.org/10.1111/apt.17742 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Idalsoaga et al papers. To view these articles, visit https://doi.org/10.1111/apt.18193 and https://doi.org/10.1111/apt.18220 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Eunice et al papers. To view these articles, visit https://doi.org/10.1111/apt.17914 and https://doi.org/10.1111/apt.17951 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Dominik et al paper. To view this article, visit https://doi.org/10.1111/apt.17945 [ABSTRACT FROM AUTHOR]

Summary: Non‐alcoholic fatty liver disease (NAFLD) is a global health problem. Iron is the leading cause of liver damage in patients with transfusion‐dependent thalassaemia (TDT), and data on the contribution of NAFLD to liver damage in TDT is lacking. Forty‐five heavily transfused TDT patients who did not have biochemical or ultrasonic evidence of liver cirrhosis were evaluated for effects of iron overload, including the presence of diabetes mellitus, hypogonadism, serum ferritin, R2‐MRI‐liver, and liver enzymes alanine aminotransferase and aspartate aminotransferase. Liver fibrosis and steatosis were estimated using transient elastography (TE). Nine (20%) patients had significant steatosis (S1), and their body mass index (BMI) and liver fibrosis scores were higher than in patients without significant steatosis (S0) (p = 0.03 and p = 0.004, respectively). On regression analysis, the controlled attenuation parameter (CAP) score (i.e., degree of liver steatosis) was associated only with increasing BMI. The TE score (i.e., degree of liver fibrosis) was associated with increasing age, CAP score, male gender, and presence of diabetes. Neither liver steatosis nor fibrosis showed significant association with the liver iron concentration or iron‐related organ damage (hypogonadism). In this cohort of TDT patients, steatosis of the liver, which is associated with increasing BMI, appeared to increase the risk of liver fibrosis. [ABSTRACT FROM AUTHOR]

Background: After pediatric split liver transplantation, intra‐abdominal loss of domain due to large‐for‐size left lateral grafts is a frequent problem for fascial closure and potentially leads to reduced liver perfusion and abdominal compartment syndrome. Therefore, delayed fascial closure with the use of temporary silastic meshes and reoperation or alternative fascial bridging procedures are necessary. Methods: Between March 2019 and October 2021, biologic meshes were used for abdominal wall expansion in 6 cases of pediatric split liver transplantation. These cases were analyzed retrospectively. Results: One male and 5 female children with median age of 6 months (range: 0–57 months) and weight of 6 kg (range: 3.5–22 kg) received a large‐for‐size left lateral graft. Graft‐to‐recipient weight ratio (GRWR) was 4.8% (range: 1.5%–8.5%) in median. Biologic mesh implantation for abdominal wall expansion was done in median 7 days (range: 3–11 days) after transplantation when signs of abdominal compartment syndrome with portal vein thrombosis in 3 and of the liver artery in 1 case occurred. In 2 cases, bovine acellular collagen matrix and 4 cases ovine reinforced tissue matrix was used. Median follow‐up was 12.5 months (range: 4–28 months) and showed good liver perfusion by sonography and normal corporal development without signs of ventral hernia. One patient died because of fulminant graft rejection and emergency re‐transplantation 11 months after the initial transplantation. Conclusions: Biologic meshes can be used as safe method for abdominal wall expansion to achieve fascial closure in large‐for‐size liver transplant recipients. Usage for primary fascial closure can be considered in selected patients. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Higuchi et al papers. To view these articles, visit https://doi.org/10.1111/apt.16745 and https://doi.org/10.1111/apt.16792 [ABSTRACT FROM AUTHOR]

Lead, a heavy metal, has emerged as one of the most significant pollutants, bearing irreversible consequences on human and animal health in conjunction with industrial development. Presently, the use of medicinal plants to alleviate the adverse effects of heavy metal toxicity has captured the attention of researchers. Hence, the objective of this study was to assess the impact of levamisole and broccoli extract on the electrophoretic pattern of serum proteins, hematological parameters, and histopathological alterations in the liver, kidney, and spleen tissues within a lead poisoning model of rats. This experimental investigation spanned 28 days, involving 42 male Wistar rats categorized into seven groups: a control group, a lead acetate (AL) group administered at 1000 ppm in drinking water, a broccoli (B) group at 300 mg/kg/day, a levamisole (LE) group at 2.5 mg/kg/day, and combination groups of lead and broccoli (AL + B), lead and levamisole (AL + LE), and lead, broccoli, and levamisole (AL + LE + B). Upon completion of the study, hematological and biochemical parameters were assessed, and serum protein concentrations were analyzed using electrophoresis. Liver, kidney, and spleen tissues were fixed and subjected to histopathological examination with H&E staining. The findings indicated a significant decrease in white blood cells (WBC), red blood cells (RBC), and hemoglobin (Hb) levels in the AL group compared to other groups (p < 0.01). Conversely, the B group exhibited a notable increase in RBC and WBC compared to the AL group (p < 0.05). The most pronounced lead‐induced damage was observed in the liver, resulting in elevated levels of specific enzymes such as AST and ALT in the AL group, accompanied by a decline in albumin and total protein (p < 0.001). A reduction in globulin levels, including Beta‐2 globulin, was noted in the AL + B and AL + LE groups compared to the AL group (p < 0.001, p < 0.05). Histopathological findings also unveiled increased infiltration of inflammatory cells and hemorrhage in the liver tissue, followed by the spleen, significantly higher in the AL group compared to other experimental groups (p < 0.05). Additionally, congestion and inflammation were evident in the spleen tissue compared to other groups. These tissue damages were mitigated in other combination treatment groups. Based on the aforementioned results, the combination of broccoli and levamisole is deemed effective in ameliorating liver and spleen injuries caused by lead and enhancing biochemical parameters and serum proteins. [ABSTRACT FROM AUTHOR]

The protective effect of Fe against Cd‐induced toxicity in the liver and kidney of rats during concurrent administration of both metals was investigated in this study. Fifty female rats (130–150 g) were distributed into five groups of 10 rats each (n = 10): Group I (control), received normal saline solution; Group II (1.2 mg CdCl2/kg b.w.); Group III (1.2 mg CdCl2 + 0.25 mg FeCl2/kg b.w.); Group IV (1.2 mg CdCl2 + 0.75 mg FeCl2/kg b.w.); and Group V (1.2 mg CdCl2 + 1.5 mg FeCl2/kg b.w.). Administration of both tested substances lasted for 47 days. Cd was injected intraperitoneally once a week, while Fe was administered to the Cd‐exposed animals by oral gavage thrice weekly. The animals were killed at the end of the study, their blood was collected, and their liver and kidneys were harvested for biochemical and histological analysis. Following Cd administration, the kidney and liver showed a significant increase in Cd concentration, while Fe concentration in the kidney decreased. However, cotreatment with Fe decreased Cd concentration in the kidney and liver and increased Fe concentration in the kidney but not the liver, and the effect was more pronounced in the higher than lower doses. In the kidney, cotreatment with Fe especially at higher doses inhibited Cd‐induced lipid peroxidation and plasma uric acid concentration. In the liver, lipid peroxidation which Cd did not alter was found to be elevated after cotreatment with the highest dose Fe. Inflammatory cell infiltrations of the central vein and renal tubular and glomeruli injury induced by Cd were not obviated by Fe cotreatment. It seems that both tissues respond differently to the concurrent administration of these metals and that Fe protected the kidney against oxidative injury‐induced by Cd but not histopathological changes in both tissues. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tan et al paper. To view this article, visit https://doi.org/10.1111/apt.17914 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Hey et al paper. To view this article, visit https://doi.org/10.1111/apt.17917 [ABSTRACT FROM AUTHOR]

There are nearly 150 living donors in the United States who donated more than one solid organ. Using our divisional database, we found 20 individuals who donated a liver and a kidney at different times. We performed a retrospective chart review of these donors, studying their motivating factors, complications and outcomes. The donors included 11 (55%) males and nine females. Thirteen (65%) donated the kidney before the liver. Fourteen (70%) were nondirected donors at the first donation, and four of the six directed donors in the first donation became nondirected in the second donation. Seventeen (85%) were nondirected at the second donation. Common reasons for donating the second time were a good experience with the first donation and knowing that one can donate again. Outcomes and the incidence of early complications were not significantly different after the 2nd versus the 1st donation. All donors recovered and currently are doing well. Our results show a significant number of dual organ donors are nondirected and motivated by their strong desire to help. A positive experience with the 1st donation often was the driving factor for the 2nd. A history of previous organ donation did not negatively impact the 2nd donation. [ABSTRACT FROM AUTHOR]

In sepsis, limited food intake and increased energy expenditure induce a starvation response, which is compromised by a quick decline in the expression of hepatic PPARα, a transcription factor essential in intracellular catabolism of free fatty acids. The mechanism upstream of this PPARα downregulation is unknown. We found that sepsis causes a progressive hepatic loss-of-function of HNF4α, which has a strong impact on the expression of several important nuclear receptors, including PPARα. HNF4α depletion in hepatocytes dramatically increases sepsis lethality, steatosis, and organ damage and prevents an adequate response to IL6, which is critical for liver regeneration and survival. An HNF4α agonist protects against sepsis at all levels, irrespectively of bacterial loads, suggesting HNF4α is crucial in tolerance to sepsis. In conclusion, hepatic HNF4α activity is decreased during sepsis, causing PPARα downregulation, metabolic problems, and a disturbed IL6-mediated acute phase response. The findings provide new insights and therapeutic options in sepsis. Synopsis: Besides inflammation, metabolic dysregulation also contributes to sepsis lethality, offering therapeutic potential. This study shows that loss of hepatic HNF4α activity in sepsis disrupts PPARα-regulated lipid metabolism and the acute phase response, both of which can be restored by the agonist NCT. Hepatic HNF4α loses its function during sepsis due to alterations in its chromatin binding. These changes in HNF4α chromatin binding during sepsis mainly affect H3K27 acetylation, thereby modulating enhancer activity, with little effect on chromatin accessibility. Hepatocyte-specific HNF4α knockout mice show reduced PPARα expression and activity, decreased IL6-induced acute phase response, and increased lipid accumulation during sepsis, all of these contributing to sepsis lethality. The HNF4α agonist NCT protects against sepsis by preventing lipid metabolic dysregulation caused by HNF4α and PPARα loss-of-function and enhancing the hepatic acute phase response. The HNF4α loss-of-function in sepsis could be translated to pigs and a humanized liver mouse model, emphasizing the relevance of the findings. Besides inflammation, metabolic dysregulation also contributes to sepsis lethality, offering therapeutic potential. This study shows that loss of hepatic HNF4α activity in sepsis disrupts PPARα-regulated lipid metabolism and the acute phase response, both of which can be restored by the agonist NCT. [ABSTRACT FROM AUTHOR]

Eimeria stiedae is one of the few eukaryotic pathogens that exclusively infect the liver and serves as a good model to study the host–pathogen interactions in this vital organ. In this study, we show that rabbits infected with E. stiedae develop severe but self‐healing cholangitis. RNA‐seq analysis of the liver gene expression landscapes over the long course of E. stiedae infection identified 912 differentially expressed genes (DEGs) in the prepatent period (794 up‐ and 118 downregulated genes), 2889 DEGs in the early oocyst shedding period (1870 up‐ and 1019 downregulated genes), 2859 DEGs in the peak oocyst shedding period (1923 up‐ and 936 downregulated genes), and 327 DEGs in the recovery period (164 up‐ and 163 downregulated genes). Combined with pathological observations, we identified dynamic changes in host–parasite interactions involving multiple pathways. They showed that E. stiedae infection induced full‐blown inflammatory, Th1 and Th17 immune responses at all time points. This was associated with the strong innate immune responses during the prepatent period, including increased Toll‐like and NOD‐like receptor signaling. Despite mounting several damage control and repair responses, such as PI3K‐Akt signaling, Ras signaling, and extracellular matrix‐receptor interactions, the liver underwent severe metabolic dysfunction, oxidative damage, and coagulopathy after patency and at peak infection, possibly as a result of suppressed peroxisome activities and downregulated PPAR signaling. These responses largely disappeared during late infection, suggesting that the liver self‐heals after severe cholangitis. These data provide new insights into host–pathogen interactions during Eimeria infection and improve our understanding of the pathogenesis of parasitic cholangitis. [ABSTRACT FROM AUTHOR]

The current treatment approach to patients with liver cirrhosis relies on the individual management of complications. Consequently, there is an unmet need for an overall therapeutic strategy for primary and secondary prevention of complications. The clinical potential of long‐term albumin infusions supported by recent clinical trials has expanded its indications and holds promise to transform the management and secondary prevention of cirrhosis‐related complications. This renewed interest in albumin comes with inherent controversies, compounding challenges and pressing need for rigorous evaluation of its clinical potential to capitalize on its therapeutic breakthroughs. Australia is among a few countries worldwide to adopt outpatient human albumin infusion. Here, we summarize currently available evidence of the potential benefits of human albumin for the management of multiple liver cirrhosis‐related complications and discuss key challenges for wide application of long‐term albumin administration strategy in Australian clinical practice. Australian Gastroenterological week (AGW), organised by the Gastroenterological Society of Australia (GESA), was held between 9‐11 September 2022. A panel of hepatologists, advanced liver nurses and one haematologist, were invited to a roundtable meeting to discuss the use of long‐term albumin infusions for liver cirrhosis. management in Australia. In this review, we summarise the proceedings of this meeting in context of the current literature. [ABSTRACT FROM AUTHOR]

ATP citrate lyase (ACLY) inhibitors have the potential of modulating central processes in protein, carbohydrate, and lipid metabolism, which can have relevant physiological consequences in aging and age‐related diseases. Here, we show that hepatic phospho‐active ACLY correlates with overweight and Model for End‐stage Liver Disease score in humans. Wild‐type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB‐204990, and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy‐fed mice treated with potassium hydroxycitrate. Analysis of soleus tissue indicated that potassium hydroxycitrate produced the modulation of wound healing processes. In vivo, potassium hydroxycitrate modulated locomotor function toward increased wire hang performance and reduced rotarod performance in healthy‐fed mice, and improved locomotion in mice exposed to cardiotoxin‐induced muscle atrophy. Our findings implicate ACLY and ACLY inhibitors in different aspects of aging and muscle regeneration. [ABSTRACT FROM AUTHOR]

Background: In this study, we comprehensively profiled the T‐cell receptor (TCR) repertoire of the tumor and adjacent normal tissue in patients with HBV‐associated hepatocellular carcinoma (HCC) and determined the baseline characteristics and clinical significance of TCR. Methods: High‐throughput sequencing was used to determine the profile of complementarity‐determining region 3 (CDR3) of the TCR‐β chain variable (TRBV) in the tumor and normal tissue samples of 14 HCC patients. At the same time, TRBV diversity and differences in expression between tumor and normal tissues were investigated. The cumulative frequency of top 100 CDR3 (CF100), clonality, and Shannon entropy as indices to evaluate diversity, Results: The diversity of TRBV CDR3 showed no significant difference between tumor and normal tissues. Of the 58 V gene segments in TRBV, TRBV16 and TRBV7‐6 had a significantly higher frequency in the tumor group than in the normal group (p < 0.05). The frequency of 14 J gene segments showed no significant difference between tumor and normal tissues. In contrast, the frequency of 22 TRBVx/BJx combinations was significantly higher in the tumor than in the normal tissue. In addition, the length and type of TRBV CDR3 were similar in tumor and normal tissues, and a Gaussian distribution was observed in both groups. Conclusion: This study provided a large amount of information about the TCR lineage in HBV‐associated HCC, laying the foundation for further research. In addition, the fact that the immune repertoire (TRBV CDR3) hardly differs between tumor and adjacent normal tissue provides a new clue for exploring the mechanism of the liver as an organ with immune privileges. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tong et al papers. To view these articles, visit https://doi.org/10.1111/apt.17263 and https://doi.org/10.1111/apt.17320 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tong et al papers. To view these articles, visit https://doi.org/10.1111/apt.17263 and https://doi.org/10.1111/apt.17319 [ABSTRACT FROM AUTHOR]

This article discusses the development and advancements of magnetic resonance imaging (MRI) in the field of medicine. It highlights the contributions of Paul C. Lauterbur and Raymond Damadian in the invention of MRI and their impact on the field. The article also mentions various MRI techniques and contrast mechanisms that have been introduced over the years, including T1ρ MRI. The focus of the paper by Qian and colleagues is on using dynamic glucose-enhanced T1ρ imaging to study glucose metabolism in the liver of patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The study demonstrates the potential of this technique in detecting and quantifying changes in liver metabolism. The article concludes by discussing the advantages of this novel application, including real-time functional and metabolic information, non-invasiveness, and improved image quality. However, it acknowledges the limitations of the study and suggests further research in this area. [Extracted from the article]

Imaging demonstrated an American Association for the Surgery of Trauma (AAST) grade 4 liver laceration, predominantly of the left lobe of liver, with moderate volume hemoperitoneum without contrast extravasation (Fig. The AAST Grade IV liver injury sustained in this case was considered avoidable. [Extracted from the article]

Background. Patients with β‐thalassemia major depend on lifelong transfusion, resulting in tissue iron overload. This longitudinal retrospective observational study aims to assess myocardial and liver iron overload using magnetic resonance imaging (MRI) and investigate the lag between myocardial and liver iron unloading in β‐thalassemia patients undergoing chelation therapy. Methods. Beta‐thalassemia major patients with at least two MRI studies between 2016 and 2020 were enrolled. Myocardial and liver iron overload were defined as T2∗ less than 20 and 2.1, respectively. Outcomes included mortality, myocardial and liver T2∗ changes, and systolic dysfunction assessed by cardiac MRI. Results. Fifty‐five patients with a mean age of 24.62 ± 7.94 years, a mean follow‐up duration of 24.3 ± 12.9 months, and a mean ferritin level of 1475.75 ± 771.12 ng/mL were enrolled. All of the abovementioned patients only took deferoxamine as the iron‐chelating medication. Mortality occurred in three patients (5.5%) during follow‐up. Liver T2∗ significantly increased (p value <0.05), while myocardial T2∗ showed a nonsignificant increase. Iron unloading of the myocardium was not significantly different from that of the liver and did not result in a significant lag (56% vs. 44%; p value = 0.419). Baseline myocardial T2∗ correlated with extramedullary hematopoiesis, weekly number of deferoxamine injections (p value <0.01), timing between the transfusions, and serum ferritin (p value <0.05). Conclusion. Liver T2∗ reduced during deferoxamine chelation therapy, while myocardial T2∗ remained unchanged. No significant lag was observed between myocardial and liver iron unloading. Further studies are required to elucidate these findings. [ABSTRACT FROM AUTHOR]

The circadian clock coordinates the daily rhythmicity of biological processes, and its dysregulation is associated with various human diseases. Despite the direct targeting of rhythmic genes by many prevalent and World Health Organization (WHO) essential drugs, traditional approaches can't satisfy the need of explore multi‐timepoint drug administration strategies across a wide range of drugs. Here, droplet‐engineered primary liver organoids (DPLOs) are generated with rhythmic characteristics in 4 days, and developed Chronotoxici‐plate as an in vitro high‐throughput automated rhythmic tool for chronotherapy assessment within 7 days. Cryptochrome 1 (Cry1) is identified as a rhythmic marker in DPLOs, providing insights for rapid assessment of organoid rhythmicity. Using oxaliplatin as a representative drug, time‐dependent variations are demonstrated in toxicity on the Chronotoxici‐plate, highlighting the importance of considering time‐dependent effects. Additionally, the role of chronobiology is underscored in primary organoid modeling. This study may provide tools for both precision chronotherapy and chronotoxicity in drug development by optimizing administration timing. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are major contributors to immunological responses following solid organ transplantation. Donor derived EVs are best known for their role in transplant rejection through transferring donor major histocompatibility complex proteins to recipient antigen presenting cells, a phenomenon known as ‛cross‐decoration'. In contrast, donor liver‐derived EVs are associated with organ tolerance in small animal models. Therefore, the cellular source of EVs and their cargo could influence their downstream immunological effects. To investigate the immunological effects of EVs released by the liver in a physiological and transplant‐relevant model, we isolated EVs being produced during normothermic ex vivo liver perfusion (NEVLP), a novel method of liver storage prior to transplantation. We found EVs were produced by the liver during NEVLP, and these EVs contained multiple anti‐inflammatory miRNA species. In terms of function, liver‐derived EVs were able to cross‐decorate allogeneic cells and suppress the immune response in allogeneic mixed lymphocyte reactions in a concentration‐dependent fashion. In terms of cytokine response, the addition of 1 × 109 EVs to the mixed lymphocyte reactions significantly decreased the production of the inflammatory cytokines TNF‐α, IL‐10 and IFN‐γ. In conclusion, we determined physiologically produced liver‐derived EVs are immunologically regulatory, which has implications for their role and potential modification in solid organ transplantation. [ABSTRACT FROM AUTHOR]

Background and Aims: Acute liver injury (ALI) often follows biliary acute pancreatitis (BAP), but the exact cause and effective treatment are unknown. The aim of this study was to investigate the role of the gut microflora–bile acids–liver axis in BAP‐ALI in mice and to assess the potential therapeutic effects of Yinchenhao decoction (YCHD), a traditional Chinese herbal medicine formula, on BAP‐ALI. Methods: Male C57BL/6 mice were allocated into three groups: negative control (NC), BAP model, and YCHD treatment groups. The severity of BAP‐ALI, intrahepatic bile acid levels, and the gut microbiota were assessed 24 h after BAP‐ALI induction in mice. Results: Our findings demonstrated that treatment with YCHD significantly ameliorated the severity of BAP‐ALI, as evidenced by the mitigation of hepatic histopathological changes and a reduction in liver serum enzyme levels. Moreover, YCHD alleviated intrahepatic cholestasis and modified the composition of bile acids, as indicated by a notable increase in conjugated bile acids. Additionally, 16S rDNA sequencing analysis of the gut microbiome revealed distinct alterations in the richness and composition of the microbiome in BAP‐ALI mice compared to those in control mice. YCHD treatment effectively improved the intestinal flora disorders induced by BAP‐ALI. Spearman's correlation analysis revealed a significant association between the distinct compositional characteristics of the intestinal microbiota and the intrahepatic bile acid concentration. Conclusions: These findings imply a potential link between gut microbiota dysbiosis and intrahepatic cholestasis in BAP‐ALI mice and suggest that YCHD treatment may confer protection against BAP‐ALI via the gut microflora–bile acids–liver axis. [ABSTRACT FROM AUTHOR]

Statins are used to reduce liver cholesterol levels but also carry a dose‐related risk of skeletal muscle toxicity. Concentrations of statins in plasma are often used to assess efficacy and safety, but because statins are substrates of membrane transporters that are present in diverse tissues, local differences in intracellular tissue concentrations cannot be ruled out. Thus, plasma concentration may not be an adequate indicator of efficacy and toxicity. To bridge this gap, we used physiologically based pharmacokinetic (PBPK) modeling to predict intracellular concentrations of statins. Quantitative data on transporter clearance were scaled from in vitro to in vivo conditions by integrating targeted proteomics and transporter kinetics data. The developed PBPK models, informed by proteomics, suggested that organic anion–transporting polypeptide 2B1 (OATP2B1) and multidrug resistance–associated protein 1 (MRP1) play a pivotal role in the distribution of statins in muscle. Using these PBPK models, we were able to predict the impact of alterations in transporter function due to genotype or drug–drug interactions on statin systemic concentrations and exposure in liver and muscle. These results underscore the potential of proteomics‐guided PBPK modeling to scale transporter clearance from in vitro data to real‐world implications. It is important to evaluate the role of drug transporters when predicting tissue exposure associated with on‐ and off‐target effects. [ABSTRACT FROM AUTHOR]

Globally, large quantity of animal byproducts is generated from the slaughter of food animals, but there is lack of research articles related to drying of these byproducts and its use as pet food. Therefore, this study was conducted with the aim of utilization of intact whole buffalo liver by drying for pet treat, evaluating its shelf life and palatability. The intact liver surface was superficially sliced, and the surface was pierced. Thereafter, the livers were pretreated in 3% sugar and 4% salt solution (1 : 3 w / v) for 3 h followed by microwaving for 4 min and hot air drying at 60°C for 40 h (designated as T2L). The livers which were dried the same as T2L except surface piercing were referred as T1L, whereas the livers dried only using hot air oven were referred as control (CL). The moisture and protein contents of the dried CL and T2L were found to be 28.46% and 14.29% and 43.85% and 52.76%, respectively. Sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE) image of T2L revealed the presence of few low as well as high molecular weight protein bands which were absent in CL and T1L indicating a comparatively lower level of protein degradation in T2L. The shelf life of T1L and T2L samples based on microbiological and lipid oxidation analyses was found to be more than 60 days at 25 and 4°C. Palatability studies using dogs showed that all dried samples were highly palatable. Thus, it could be concluded that intact buffalo liver could be dried using surface slicing, with/without piercing followed by salt and sugar pretreatment, 4 min microwaving, and hot air drying at 60°C for 40 h. Future study should focus on the sensory properties such as aroma, texture, and flavor and sensory analysis of the dried liver by human. [ABSTRACT FROM AUTHOR]

Permeability transition pore (PTP) opening dissipates ion and electron gradients across the internal mitochondrial membrane (IMM), including excess Ca2+ in the mitochondrial matrix. After opening, immediate PTP closure must follow to prevent outer membrane disruption, loss of cytochrome c, and eventual apoptosis. Flickering, defined as the rapid alternative opening/closing of PTP, has been reported in heart, which undergoes frequent, large variations in Ca2+. In contrast, in tissues that undergo depolarization events less often, such as the liver, PTP would not need to be as dynamic and thus these tissues would not be as resistant to stress. To evaluate this idea, it was decided to follow the reversibility of the permeability transition (PT) in isolated murine mitochondria from two different tissues: the very dynamic heart, and the liver, which suffers depolarizations less frequently. It was observed that in heart mitochondria PT remained reversible for longer periods and at higher Ca2+ loads than in liver mitochondria. In all cases, Ca2+ uptake was inhibited by ruthenium red and PT was delayed by Cyclosporine A. Characterization of this phenomenon included measuring the rate of oxygen consumption, organelle swelling and Ca2+ uptake and retention. Results strongly suggest that there are tissue‐specific differences in PTP physiology, as it resists many more Ca2+ additions before opening in a highly active organ such as the heart than in an organ that seldom suffers Ca2+ loading, such as the liver. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Higuchi et al papers. To view these articles, visit https://doi.org/10.1111/apt.16745 and https://doi.org/10.1111/apt.16774 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Lazarus et al papers. To view these articles, visit https://doi.org/10.1111/apt.16720 and https://doi.org/10.1111/apt.16750 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Lazarus et al papers. To view these articles, visit https://doi.org/10.1111/apt.16720 and https://doi.org/10.1111/apt.16768 [ABSTRACT FROM AUTHOR]