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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).)

Presents forthcoming papers for the "European Journal of Biochemistry". "A guanyloribonuclease mouse liver cytosol," by A. Pantazaki and colleagues; "Revised nonmenclature for eukaryotic DNA polymerases," by P.M.J. Burgers and colleagues; "The folding and solution conformation of penicillin G acylase," by C.D. Lindsay and colleagues.

Lists papers due for publication in the "European Journal of Biochemistry" after the January 16, 1984 issue. "Labelling and cross-linking of Escherichia coli penicillin-binding proteins with bis-Beta-lactam antibiotics"; "Sorbitol dehydrogenase. The primary structure of the sheep-liver enzyme"; "Extensive variations and basic features in the alcohol dehydrogenase-sorbitol dehydrogenase family".

The article presents information on various papers to be published in the "European Journal of Biochemistry." Some of them are, "Lipid Domains in Plasma Membranes From Rat Liver," by F. Schroeder, "Calcium Modulates Fatty Acid Dynamics in Rat Liver Plasma Membranes," by F. Schroeder, and C.S. Argilaga, and others.

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]

Numerous complementary feeds to support liver function are commercially available for small animals. Aiming to furnish a scientific support for clinicians/nutritionists that necessitate a complementary feed to support liver function in dogs and cats, with the present paper, we analyzed scientific evidences supporting the use, for this purpose, of ingredients/additives such as artichoke (Cynara scolymus), curcumin, dandelion (Taraxacum officinale), milk thistle (Silybum marianum), phosphatidylcholine, and S-adenosylmethionine. Although sustained by significant results, our review found only few scientific papers, and albeit we believe that they represent a significant aid in handling hepatopathies, in the authors' opinion, this topic probably deserves, and would benefit of, further studies. [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]

Glycyrrhizae Radix et Rhizoma (GRER) has been used as a medicinal plant and dietary supplements for its beneficial effect in immunomodulatory effects. Sulfur fumigation (SF) processing was widely used in the storage and maintenance of Chinese medicine because of its convenience and cheapness. However, the disadvantage of SF has been reported, but the systematic study of SF on GRER was deficient. In this paper, the active ingredients, sulfur-fumigated products, immunomodulatory effect, and liver injury of SF-GRER were studied. After SF, the liquiritin decreased from 4.49 ± 0.03 mg/g to 3.94 ± 0.08 mg/g (P < 0.01). Compared with the NSF-GRER group, the SF-GRER group showed a decreased immunoregulation in the thymus index, spleen index, and serum IL-6 and SOD levels (P < 0.05). After 2 weeks of continuous intragastric administration of SF-GRER in healthy mice, the level of serum aspartate aminotransferase (AST) significantly increased (P < 0.05) and the area of liver lesion significantly increased compared with the NSF-GRER (P < 0.05) group. The sulfonated products (m/z, 631.13) corresponding to liquiritin apioside (m/z, 551.17) and isoliquiritin apioside (m/z, 551.17) were screened out in SF-GRER by using UPLC-Orbitrap-MS. The sulfonated products provided in this paper were discovered for the first time and could be powerfully applied for the identification of SF-GRER. SF destroyed the chemical composition of GRER, inhibited immunoregulation, and induced liver injury. The feasibility of this processing method needs to be reconsidered. [ABSTRACT FROM AUTHOR]

Background: Several options have been proposed for the treatment of congenital extrahepatic portosystemic shunts (cEHPSS) in dogs, but formal comparisons among different treatment options are currently unavailable. A previous evidence‐based review (2012) found low quality of evidence for papers assessing the treatment of cEHPSS in dogs. Objectives: To assess the quality of evidence available in the treatment of cEHPSS, summarize the current state of knowledge with respect to outcome after cEHPSS management, and compare different treatment techniques. Animals: Not used. Methods: A bibliographic search was performed without date or language restrictions. Studies were assessed for quality of evidence (study design, study group sizes, subject enrollment quality, and overall risk of bias) and outcome measures reported (perioperative outcome, clinical outcome, and surgical or interventional outcome), all reported with 95% confidence intervals. A network meta‐analysis was performed. Results: Forty‐eight studies were included. Six retrospective studies (grade 4b) compared 2 techniques and 7 were abstracts (grade 5). The quality of evidence was low and risk of bias high. Regarding surgical outcome, statistically significant superiority of ameroid constrictor over thin film band was observed (P =.003). No other comparisons were statistically significant. Conclusions and Clinical Importance: The evidence base of choice of treatment of cEHPSS in dogs remains weak despite recent publications on the subject. Ameroid is superior to thin film band in causing EHPSS closure. Blinded randomized studies comparing different treatment modalities, which routinely include postoperative imaging to assess cEHPSS closure and acquired portosystemic shunt development are essential. [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]

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]

Nonalcoholic fatty liver disease, a type of metabolic syndrome, continues to rise globally. Currently, there is no approved drug for its treatment. Improving lifestyle and exercise can alleviate symptoms, but patients' compliance is poor. More and more studies have shown the potential of Polygoni Multiflori Radix (PMR) in the treatment of NAFLD and metabolic syndrome. Therefore, this paper reviews the pharmacological effects of PMR and its main chemical components (tetrahydroxystilbene glucoside, emodin, and resveratrol) on NAFLD. PMR can inhibit the production of fatty acids and promote the decomposition of triglycerides, reduce inflammation, and inhibit the occurrence of liver fibrosis. At the same time, it maintains an oxidation equilibrium status in the body, to achieve the therapeutic purpose of NAFLD and metabolic syndrome. Although more standardized studies and clinical trials are needed to confirm its efficacy, PMR may be a potential drug for the treatment of NAFLD and its complications. However, the occurrence of adverse reactions of PMR has affected its extensive clinical application. Therefore, it is necessary to further study its toxicity mechanism, enhance efficacy and control toxicity, and even reduce toxicity, which will contribute to the safe clinical use of PMR. [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]

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 Thiele et al papers. To view these articles, visit https://doi.org/10.1111/apt.16567 and https://doi.org/10.1111/apt.16633 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Thiele et al papers. To view these articles, visit https://doi.org/10.1111/apt.16567 and https://doi.org/10.1111/apt.16672 [ABSTRACT FROM AUTHOR]

Purpose: Liver is one of the organs with a high incidence of tumors in the human body. Malignant liver tumors seriously threaten human life and health. The difficulties of liver tumor segmentation from computed tomography (CT) image are: (a) The contrast between the liver tumors and healthy tissues in CT images is low and the boundary is blurred; (b) The image of liver tumor is complex and diversified in size, shape, and location. Methods: To solve the above problems, this paper focused on the human liver and liver tumor segmentation algorithm based on convolutional neural network (CNN), and specially designed a three‐dimensional dual path multiscale convolutional neural network (TDP‐CNN). To balance the performance of segmentation and requirement of computational resources, the dual path was used in the network, then the feature maps from both paths were fused at the end of the paths. To refine the segmentation results, we used conditional random fields (CRF) to eliminate the false segmentation points in the segmentation results to improve the accuracy. Results: In the experiment, we used the public dataset liver tumor segmentation (LiTS) to analyze the segmentation results qualitatively and quantitatively. Ground truth segmentation of liver and liver tumor was manually labeled by an experienced radiologist. Quantitative metrics were Dice, Hausdorff distance, and average distance. For the segmentation results of liver tumor, Dice was 0.689, Hausdorff distance was 7.69, and the average distance was 1.07; for the segmentation results of the liver, Dice was 0.965, Hausdorff distance was 29.162, and the average distance was 0.197. Compared with other liver and liver tumor segmentation algorithms in Medical Image Computing and Intervention (MICCAI) 2017 competition, our method of liver segmentation ranked first, and liver tumor segmentation ranked second. Conclusions: The experimental results showed that the proposed algorithm had good performance in both liver and liver tumor segmentation. [ABSTRACT FROM AUTHOR]

Aim. The aim of this paper is to investigate the effects of ethyl pyruvate (EP) on experimental liver fibrosis induced by bile duct ligation (BDL) and explore the underlying molecular mechanisms. Material and Method. Rats were randomly divided into three groups: the sham group, the BDL group, and the BDL+EP group. Liver fibrosis was induced by common bile duct ligation and was evaluated by serum biochemical parameter levels, Masson's trichrome staining, α-SMA expression, and collagen I deposition. The levels of Nrf2 signaling pathway-related antioxidant genes (Nrf2, SOD2, NQO1, and GSH-Px) in liver tissues were also measured. Meanwhile, the mRNA expression levels of HMGB1, IL-1β, TNF-α, and HSP27 were analyzed. In BDL-induced liver fibrosis rats, the successfully established model was confirmed by the significant increase of serum ALT and AST levels, the high liver fibrosis score, α-SMA expression, and collagen deposition. Results. Compared with the BDL group, EP administration could diminish fibrosis level and substantially increase the expression of Nrf2 signaling pathway-related antioxidant genes. Furthermore, EP significantly suppressed the mRNA expression levels of HMGB1, IL-1β, TNF-α, and HSP27. Conclusions. The results suggested that EP administration could effectively inhibit the liver fibrosis induced by BDL in rat, which may be associated with the enhanced activity of Nrf2 to mediate antioxidant enzyme system and downregulate the inflammatory genes. [ABSTRACT FROM AUTHOR]

For several years, research has been carried out on the effectiveness of solutions for perfusion and preservation of organs, including the liver. There is a search for an optimal pharmacological composition of these solutions, allowing to preserve or improve vital functions of the organ for as long as possible until it is transplanted into a recipient. Hormones due to their properties, often resulting from their pleiotropic effects, may be a valuable component for optimizing the composition of liver perfusion and preservation solutions. The paper presents the current state of knowledge on liver perfusion and preservation solutions modified with hormones. It also shows the characteristics of the hormones evaluated, taking into account their physiological functions in the body. [ABSTRACT FROM AUTHOR]

Summary: Background: Direct‐acting anti‐viral therapy (DAA) has transformed hepatitis C virus (HCV) care, particularly in patients with decompensated cirrhosis. However, their impact on hepatocellular carcinoma (HCC) remains unclear. Aim: To use a national registry of patients with advanced liver disease to explore the relationship between DAA therapy and HCC. Methods: All patients with de novo HCC post DAA therapy were frequency matched with patients who did not develop HCC. Demographic, clinical and laboratory data were obtained. Cross‐sectional imaging and multidisciplinary team reports were reviewed for dates of HCC diagnosis and HCC progression. Patients were categorised by treatment outcome and time of HCC development. Data were examined by multivariable analysis and Kaplan‐Meier estimation. Results: Eighty patients with HCC were compared with 165 patients without HCC, treated between June 2014 and September 2015. Mean follow‐up from start of DAA therapy was 32.4 months. Twenty‐eight patients were diagnosed with early HCC (within 6 months of therapy) and 52 presented late. Baseline nonmalignant lesions (HR: 1.99), thrombocytopaenia (HR: 1.59) and diabetes (HR: 1.68) increased likelihood of HCC. Response to therapy was reduced in patients who developed liver cancer (SVR in patients with HCC = 54/80 (68%), SVR in patients without HCC = 143/165 (87%), P < 0.001, OR: 3.13, 95% CI: 1.64‐5.99). We found no difference between tumour size, progression or survival between viraemic and nonviraemic patients. Conclusion: There is no alteration in prognosis or cancer progression following HCC development after HCV treatment. However, baseline nonmalignant liver lesions, diabetes and thrombocytopaenia increase the risk of HCC, and HCC is associated with a decreased SVR rate. Linked Content This article is linked to Hollande and Pol paper. To view this article, visit https://doi.org/10.1111/apt.15328. [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]

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]

Linked Content This article is linked to Wong and Coenen et al and Hooymans papers. To view these articles visit https://doi.org/10.1111/apt.13879 and https://doi.org/10.1111/apt.13955. [ABSTRACT FROM AUTHOR]

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]

This paper describes the fragments obtained by digestion with RNAase T1 from rat liver serine-tRNA1 as well as from a mixture of very lipophilic serine-tRNAs. From the data obtained by these digest as well as from the digestion with pancreatic RNAase the nucleotide sequence of the anticodon of serine-tRNA1 can be constructed. Evidence from different nucleotide sequences in other serine-tRNAs is presented [ABSTRACT FROM AUTHOR]

1. Tryptic digest, s of the [14C]carboxymethylated derivatives of the t, hree isoenzymes EE, ES and SS of horse liver alcohol dehydrogenase have been compared in "fingerprint" experiments. 2. Eight peptide spots present in the digest of the carboxymethylated EE enzyme were not detected in the digest of the carboxymethylated SS enzyme; and seven spots found in the latter were not discovered in the former. No other differences were noticed. The ES derivative yielded both types of spots but in reduced amounts, It is concluded that the E- and S-types of subunits are very similar and that the ES isoenzyme is a hybrid molecule. 3. From the carboxymethylated SS and ES isoenzymes the S-chain peptides that, differ from their counterparts in the E-chain were prepared and their structures analysed. They were compared to the known structures [ 1 — 3] of the corresponding E-chain peptides. It is concluded that all the differences between the two sets of peptides are accounted for by amino acid changes at only six positions along the protein chains of the E- and S-types of subunits, and an ancestral geneduplication is suggested. The differences at five positions (17, 94, 101, 110 and 366) are amino acid exchanges compatible with one-base mutations, while the nature of the sixth difference (position 115) is not fully established. 4. The six differences make the S-chain more hydrophobic and three units of charge more positive than the E-chain. These properties fit the solubilities and electrophoretic mobilities of the three isoenzymes. The difference in substrate specificity between the E- and S-chains might be explained by a direct participation in the substrate binding site of some of the residues exchanged, but, other explanations cannot be excluded. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Tsung et al paper. To view this article, visit https://doi.org/10.1111/apt.15413. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Shen et al and Kim and Kim papers. To view these articles, visit https://doi.org/10.1111/apt.15298 and https://doi.org/10.1111/apt.15364. [ABSTRACT FROM AUTHOR]

There is long-standing evidence that male and female rat livers differ in enzyme activity. More recently, differences in gene expression profiling have also been found to exist; however, it is still unclear whether there is morphological expression of male/female differences in the normal liver. Such differences could help to explain features seen at the pathological level, such as the greater regenerative potential generally attributed to the female liver. In this paper, hepatocytes ( HEP), Kupffer cells ( KC) and hepatic stellate cells ( HSC) of male and female rats were examined to investigate hypothesised differences in number, volume and spatial co-localisation of these cell types. Immunohistochemistry and design-based stereology were used to estimate total numbers, numbers per gram and mean cell volumes. The position of HSC within lobules (periportal vs. centrilobular) and their spatial proximity to KC was also assessed. In addition, flow cytometry was used to investigate the liver ploidy. In the case of HEP and KC, differences in the measured cell parameters were observed between male and female specimens; however, no such differences were detected for HSC. Female samples contained a higher number of HEP per gram, with more binucleate cells. The HEP nuclei were smaller in females, which was coincident with more abundant diploid particles in these animals. The female liver also had a greater number of KC per gram, with a lower percentage of KC in the vicinity of HSC compared with males. In this study, we document hitherto unknown morphological sexual dimorphism in the rat liver, namely in HEP and KC. These differences may account for the higher regenerative potential of the female liver and lend weight to the argument for considering the rat liver as a sexually dimorphic organ. [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]

Titanium dioxide nanoparticles (TiO2) were used in various fields such as food industry, cosmetics, medicine, and agriculture. Despite the many advantages of nanotechnology, the adverse effects of nanoparticles are inevitable. The present study was conducted to evaluate the protective effect of bee bread on titanium dioxide (TiO2) nanoparticle toxicity. Male rats were randomly divided into four groups: Group 1 received daily by gavage (10 mL/kg bw) of distilled water, Group 2 received bee bread ethanolic extract (100 mg/kg bw), Group 3 received TiO2 (100 mg/kg bw) and distilled water (10 mL/kg bw), and Group 4 received TiO2 (100 mg/kg bw) and bee bread ethanolic extract (100 mg/kg bw). All treatments were given daily by gavage during 30 days. At the end of the experiment period, blood samples were collected to analyze fasting blood glucose, lipid profile (TC, TG, LDL-C, HDL-C, and VLDL-C), liver enzymes (AST, ALT, and LDH), total protein, urea, albumin, creatinine, sodium, potassium, and chloride ions. In addition, histological examinations of the kidneys, liver, and brain were investigated. The results showed that the subacute administration of TiO2 alone (100 mg/kg bw) had induced hyperglycemia (309 ± 5 mg/dL) and elevation of hepatic enzyme levels, accompanied by a change in both lipid profile and renal biomarkers as well as induced congestion and dilatation in the hepatic central vein and congestion in kidney and brain tissues. However, the cotreatment with bee bread extract restored these biochemical parameters and attenuated the deleterious effects of titanium nanoparticles on brain, liver, and kidney functions which could be due to its rich content on functional molecules. The findings of this paper could make an important contribution to the field of using bee bread as a detoxifying agent against titanium dioxide nanoparticles and other xenobiotics. [ABSTRACT FROM AUTHOR]