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Advances in various imaging modalities for breast lesions have improved diagnostic capabilities not only for tumors but also for non-tumorous lesions. Contrast-enhanced ultrasound (CEUS) plays a crucial role not only in the differential diagnosis of breast lesions, identification of sentinel lymph nodes, and diagnosis of lymph node metastasis but also in assessing the therapeutic effects of neoadjuvant chemotherapy (NAC). In CEUS, two image interpretation approaches, i.e., qualitative analysis and quantitative analysis, are employed and applied in various clinical settings. In this paper, we review CEUS for breast lesions, including its various applications. [ABSTRACT FROM AUTHOR]

Liver ultrasound is widely used in clinical practice due to its advantages of non-invasiveness, non-radiation, and real-time imaging. Accurate segmentation of the liver region in ultrasound images is essential for accelerating the auxiliary diagnosis of liver-related diseases. This paper proposes BACANet, a deep learning algorithm designed for real-time liver ultrasound segmentation. Our approach utilizes a lightweight network backbone for liver feature extraction and incorporates a convolutional attention mechanism to enhance the network's ability to capture global contextual information. To improve early localization of liver boundaries, we developed a selective large kernel convolution module for boundary feature extraction and introduced explicit liver boundary supervision. Additionally, we designed an enhanced attention gate to efficiently convey liver body and boundary features to the decoder to enhance the feature representation capability. Experimental results across multiple datasets demonstrate that BACANet effectively completes the task of liver ultrasound segmentation, achieving a balance between inference speed and segmentation accuracy. On a public dataset, BACANet achieved a DSC of 0.921 and an IOU of 0.854. On a private test dataset, BACANet achieved a DSC of 0.950 and an IOU of 0.907, with an inference time of approximately 0.32 s per image on a CPU processor. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer that could potentially be surrounded by healthy arteries or veins that a surgeon would have to avoid during treatment. A realistic 3D liver model is an unmet need for HCC preoperative planning. Methods: This paper presents a method to create a soft phantom model of the human liver with the help of a 3D-printed mold, silicone, ballistic gel, and a blender. Results: For silicone, the elastic modulus of seven different ratios of base silicone and silicone hardener are tested; while for ballistic gel, a model using 20% gelatin and 10% gelatin is created for the tumor and the rest of the liver, respectively. It is found that the silicone modulus of elasticity matches with the real liver modulus of elasticity. It is also found that the 10% gelatin part of the ballistic gel model is an excellent emulation of a healthy human liver. Conclusion: The 3D flexible liver phantom made from a 10% gelatin-to-water mixture demonstrates decent fidelity to real liver tissue in terms of texture and elasticity. It holds significant potential for improving medical training, preoperative planning, and surgical research. We believe that continued development and validation of such models could further enhance their utility and impact in the field of hepatobiliary treatment planning and education. [ABSTRACT FROM AUTHOR]

Automatic segmentation of the liver in abdominal CT images is critical for guiding liver cancer biopsies and treatment planning. Yet, automatic segmentation of CT liver images remains challenging due to the poor contrast between the liver and surrounding organs in abdominal CT images. In this paper, we propose a novel network for liver segmentation, and the network is essentially a U-shaped network with an encoder–decoder structure. Firstly, the complementary feature enhancement unit is designed in the network to mitigate the semantic gap between encoder and decoder. The complementary feature enhancement unit is based on subtraction, which enhances the complementary features between encoder and decoder. Secondly, this paper proposes a new cross attention model that no longer generates value by convolution, which reduces redundant information and enhances the contextual information of single sparse attention by encoding contextual information by 3 × 3 convolution. The dice score, accuracy, and precision of our network on the LiTS dataset were 95.85 % , 97.19 % , and 97.11 % , and the dice score, accuracy, and precision on the dataset consisted of 3Dircadb and CHAOS were 93.65 % , 94.38 % , and 97.53 % . [ABSTRACT FROM AUTHOR]

Using liver phantoms for mimicking human tissue in clinical training, disease diagnosis, and treatment planning is a common practice. The fabrication material of the liver phantom should exhibit mechanical properties similar to those of the real liver organ in the human body. This tissue-equivalent material is essential for qualitative and quantitative investigation of the liver mechanisms in producing nutrients, excretion of waste metabolites, and tissue deformity at mechanical stimulus. This paper reviews the mechanical properties of human hepatic tissues to develop liver-mimicking phantoms. These properties include viscosity, elasticity, acoustic impedance, sound speed, and attenuation. The advantages and disadvantages of the most common fabrication materials for developing liver tissue-mimicking phantoms are also highlighted. Such phantoms will give a better insight into the real tissue damage during the disease progression and preservation for transplantation. The liver tissue-mimicking phantom will raise the quality assurance of patient diagnostic and treatment precision and offer a definitive clinical trial data collection. [ABSTRACT FROM AUTHOR]

The liver is a major metabolic organ of the human body and has a high incidence of diseases. In recent years, the annual incidence of liver disease has increased, seriously endangering human life and health. The study of the occurrence and development mechanism of liver diseases, discovery of new therapeutic targets, and establishment of new methods of medical treatment are major issues related to the national economy and people's livelihood. The development of stable and effective research models is expected to provide new insights into the pathogenesis of liver diseases and the search for more effective treatment options. Organoid technology is a new in vitro culture system, and organoids constructed by human cells can simulate the morphological structure, gene expression, and glucose and lipid metabolism of organs in vivo, providing a new model for related research on liver diseases. This paper reviews the latest research progress on liver organoids from the establishment of cell sources and application of liver organoids and discusses their application potential in the field of liver disease research. [ABSTRACT FROM AUTHOR]

The liver plays a crucial role in the immune response during endotoxemia and is one of the critical targets for sepsis-related injuries. As a secretory factor involved in inflammation, pentraxin-3 (PTX3) has been demonstrated to regulate hepatic homeostasis; however, the relationship between PTX3 and cell crosstalk between immune cells and hepatocytes in the liver remains incompletely understood. In this study, we revealed that, compared with WT mice, Ptx3−/− mice with lipopolysaccharide (LPS)-induced endotoxemia exhibited alleviated liver damage, with reduced serum alanine transaminase and aspartate transaminase levels and an improved survival rate. Mechanistically, RNA-Seq and western blot results revealed that Ptx3 knockdown in hepatocytes increased the expression of Tfrc and Ccl20; consequently, Ptx3 deficiency regulated LPS-induced hepatocyte ferroptosis via increased mitochondrial reactive oxygen species and Fe2+ and recruited more macrophages by CCL20/CCR6 axis to be involved in inflammation and the clearance of harmful substances. Moreover, western blot and immunofluorescence staining confirmed that the NF-κB signaling pathway was upregulated upon LPS treatment in Ptx3-knockdown macrophages, promoting phagocytosis and polarization toward M1 macrophages. Collectively, our findings show that the absence of Ptx3 can ameliorate sepsis-induced liver injury by regulating hepatocyte ferroptosis and promote the recruitment and polarization of M1 macrophages. These findings offer a key basis for the development of effective treatments for acute infections. [ABSTRACT FROM AUTHOR]

The document is a correction notice for an article titled "Near-infrared molecular sensor for visualizing and tracking ONOO- during the process of anti-tuberculosis drug-induced liver damage" published in Analytical & Bioanalytical Chemistry. The correction addresses an error in Fig. 3A due to personal negligence, providing a new corrected version of the figure. The authors assure that this correction does not affect the discussion and conclusions of the original paper, and apologize for any inconvenience caused. The correction was reported by multiple authors. [Extracted from the article]

Nanotechnology has grown extensively in past few years and has offered several benefits in healthcare and many associated fields. Nanoparticles have shown great therapeutic potential in drug delivery, combating life-threatening diseases, tissue engineering, wound healing, and vaccine development. However, with these potential benefits, various concerns have been raised due to their toxic effects on living organisms. Cerium oxide nanoparticles (CeO2 NPs), also known as nano ceria, have manifested as a promising remedial agent in liver and kidney associated problems due to their distinctive physical, chemical, and unique biochemical activities. However, it raises concerns associated with their toxicity in these organs. In this review, we have discussed the therapeutic role of CeO2 NPs in treatment of various hepatorenal disorders such as inflammation, fibrosis, liver sepsis, and nephrotoxicity as an anti-inflammatory agent and potentially encountering oxidative stress due to its antioxidant properties. Besides the therapeutic effects, we have comprehensively reviewed the hepatotoxicity and nephrotoxicity mechanisms with relative nano-toxicity of other nanoparticles. Furthermore, this review also highlights the future research directions of CeO2 NPs to understand their dual role in liver and kidney to maximize their therapeutic effects while reducing toxicity. [ABSTRACT FROM AUTHOR]

We perform an analytical study on the propagation properties of Laguerre higher-order cosh-Gaussian beam (LhchGB) passing through liver tissue, utilizing the power spectrum refractive index and the extended Huygens-Fresnel integral. Our investigation includes numerical simulations based on the derived formula, illustrating how varying beam parameter configurations within liver tissue impact the properties of the beam. Additionally, we thoroughly discuss the influence of both optical parameters and biological tissue characteristics on the received intensity. Our observations indicate that the LhchGB undergoes changes in its shape as it traverses a considerable distance through this medium. The results presented in this paper hold significant importance for their potential applications in determining the deterioration or disruption of biological tissue, as well as in the fields of medical imaging and medical diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: Total tumor volume (TTV) is associated with overall and recurrence-free survival in patients with colorectal cancer liver metastases (CRLM). However, the labor-intensive nature of such manual assessments has hampered the clinical adoption of TTV as an imaging biomarker. This study aimed to develop and externally evaluate a CRLM auto-segmentation model on CT scans, to facilitate the clinical adoption of TTV. Methods: We developed an auto-segmentation model to segment CRLM using 783 contrast-enhanced portal venous phase CTs (CT-PVP) of 373 patients. We used a self-learning setup whereby we first trained a teacher model on 99 manually segmented CT-PVPs from three radiologists. The teacher model was then used to segment CRLM in the remaining 663 CT-PVPs for training the student model. We used the DICE score and the intraclass correlation coefficient (ICC) to compare the student model's segmentations and the TTV obtained from these segmentations to those obtained from the merged segmentations. We evaluated the student model in an external test set of 50 CT-PVPs from 35 patients from the Oslo University Hospital and an internal test set of 21 CT-PVPs from 10 patients from the Amsterdam University Medical Centers. Results: The model reached a mean DICE score of 0.85 (IQR: 0.05) and 0.83 (IQR: 0.10) on the internal and external test sets, respectively. The ICC between the segmented volumes from the student model and from the merged segmentations was 0.97 on both test sets. Conclusion: The developed colorectal cancer liver metastases auto-segmentation model achieved a high DICE score and near-perfect agreement for assessing TTV. Critical relevance statement: AI model segments colorectal liver metastases on CT with high performance on two test sets. Accurate segmentation of colorectal liver metastases could facilitate the clinical adoption of total tumor volume as an imaging biomarker for prognosis and treatment response monitoring. Key Points: Developed colorectal liver metastases segmentation model to facilitate total tumor volume assessment. Model achieved high performance on internal and external test sets. Model can improve prognostic stratification and treatment planning for colorectal liver metastases. [ABSTRACT FROM AUTHOR]

Introduction: The use of anti-retroviral therapy (ART) has made HIV a manageable condition, but there are risks associated with medications like reverse transcriptase inhibitors (RTIs) and integrase strand transfer inhibitors (INSTIs), such as liver and renal toxicity. It is essential to understand these risks for effective treatment and case management. Investigating liver toxicity related to RTIs and INSTIs in Nigeria is crucial for optimizing HIV treatment. This study aimed to assess the impact of tenofovir lamivudine dolutegravir (TLD) on the liver function of HIV patients at Nigerian Navy Hospital (NNH)-Warri. Methods: The liver function of 170 participants was assessed, with 120 on ART and the remainder being HIV-negative attendees at NNH-Warri. The study used a cross-sectional design and selected participants through random sampling. We collected data using a semi-structured questionnaire. Blood samples were taken through venipuncture and stored at – 20 °C before analysis. Ethical approval was obtained, and data analysis was conducted using SPSS Statistical Software Version 23, with significance set at p < 0.05. Results: The study found significant differences in AST, TP, Alb, and GST levels between HIV-positive subjects receiving TLD and HIV-negative individuals. HIV-positive subjects had lower AST and Alb levels but higher TP and GST levels. Further analysis revealed correlations between age, gender, and liver enzymes, highlighting the complex relationship between HIV, liver function, and treatment outcomes. Conclusion: The study suggests that decreased AST levels may have a protective effect, while ALT activity had minimal impact. Changes in TP, Alb, and GSTs emphasize the importance of monitoring hepatic synthetic function and detoxification pathways in HIV patients taking TLD. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) causes a systemic illness that can result in various manifestations. In addition to severe acute respiratory syndrome, patients often exhibit complications unrelated to the respiratory system. Potential liver damage can occur in 14.8 to 53.0% of the affected patients. Liver impairment in COVID-19 can also occur because of the use of polypharmacy during disease management. It is essential to be aware of drug-induced liver injury (DILI) in patients diagnosed with COVID-19, especially when considering the off-label usage of medications in both preventative and therapeutic regimens used on a wide scale. This review aims to give pertinent information regarding drugs utilized thus far in COVID-19 patients and their potential toxicity to the liver. We also present a suggested management approach to DILI in COVID-19 patients and lessons learned from the pharmacological management of this pandemic. [ABSTRACT FROM AUTHOR]

Background: Among various growth parameters, liver and spleen size is an important parameter used for the evaluation of patients with certain disorders and abnormalities in these organs. Aim: To determine the normal dimensions for the liver, spleen, and kidney in Egyptian infants, children, and adolescents from birth to 18 years. Methods: This cross-sectional randomized study was conducted on 1861 Egyptian infants, children, and adolescents from birth to 18 years for the establishment of Z score reference of liver, spleen, and kidney parameters. Results: Egyptian children of both sexes (51.5% boys and 48.5% girls) from birth to 18 years old were studied. Then Z scores reference for liver, spleen, and kidney parameters for both sexes were represented in detailed tables and graphs. There was no statistically significant difference between both sexes, so we used unisex tables and graphs (P > 0.05). Conclusions: Determination of pathologic changes in the size of the liver, spleen, and kidney necessitates knowing the normal range of dimensions for these organs. So, our study established a Z score chart for normal values of liver, spleen, and kidney size for children and adolescents from birth to 18 years. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound-guided fine needle biopsy is an effective method for obtaining tissue samples from various organs; however, challenges such as inadequate specimens persist. This study compared a newly designed Tricore needle with a Franseen needle for endoscopic ultrasound-guided fine needle biopsy of porcine liver. Both needles were tested on four male Yorkshire pigs. Specimens were obtained with an 100% (36/36) success rate with no procedure-related adverse effects. The Tricore needle experienced significantly less resistance during puncture than Franseen needle (3.83 vs. 5.97 N, P < 0.001) and better ultrasound visibility (168.97 vs. 125.04, P = 0.004). The Tricore needle also achieved faster specimen acquisition time (48.94 vs. 59.90 s, P = 0.038), larger total specimen area (6.67 vs. 4.68 mm2, P = 0.049), fewer fragments (23.94 vs. 31.94, P = 0.190), lager fragment area (0.28 vs. 0.15 mm2, P < 0.001), and more the number of complete portal tracts (15.44 vs. 9.33, P = 0.017) compared to the Franseen needle. The newly designed Tricore needle showed enhanced procedural performance and specimen quantity and quality compared to commercially available Franseen needle. Although further clinical studies are required, the Tricore needle may represent a favorable option for endoscopic ultrasound-guided fine-needle biopsy procedures. [ABSTRACT FROM AUTHOR]

This study aimed to estimate the hepatic and immune ameliorating potential of extracted bovine lactoferrin (LF), Selenium nanoparticles (SeNPs) or their combination (LF/SeNPs) against bleomycin (BLM) induced hepatic injury. Fifty adult male rats (160–200 g) were equally divided into five groups: (1) the saline control group, (2) BLM-injected (15 mg/kg twice a week, ip), and (3–5) groups treated orally with LF (200 mg/kg/day), SeNPs (0.0486 mg/kg/day) or LF/SeNPs combination (200.0486 mg/kg/day) for 6 weeks post BLM-intoxication. Blood and liver samples were subjected to biochemical, histopathological, and immunohistochemical analyses. The results revealed that BLM caused a significant increase in hepatic lipid peroxidation and nitric oxide, as well as serum markers of liver functions (AST, ALT and GGT activities), and levels of GM-CSF, CD4, TNF-α, IL-1β, TGF-β1, fibronectin, triglycerides, cholesterol and LDL-C. Additionally, hepatic glutathione, Na+/K+-ATPase, and glutathione peroxidase, as well as serum HDL-C, total protein and albumin levels were significantly reduced. Moreover, BLM injection resulted in marked histopathological alterations and severe expression of caspase 3. Post-treatment of BLM-intoxicated rats with LF, SeNPs or LF/SeNPs combination obviously improved the BLM-induced hepatic damages; this was achieved from the marked modulations in the mentioned parameters, besides improving the histopathological hepatic architecture. It is worth mentioning that LF/SeNPs exerted the greatest potency. In conclusion, the obtained results demonstrated that LF, SeNPs and LF/SeNPs succeeded in attenuating the BLM-induced hepatic dysfunction. Therefore, these supplements might be used to protect against drug-associated side effects. [ABSTRACT FROM AUTHOR]

Image segmentation of the liver is an important step in treatment planning for liver cancer. However, manual segmentation at a large scale is not practical, leading to increasing reliance on deep learning models to automatically segment the liver. This manuscript develops a generalizable deep learning model to segment the liver on T1-weighted MR images. In particular, three distinct deep learning architectures (nnUNet, PocketNet, Swin UNETR) were considered using data gathered from six geographically different institutions. A total of 819 T1-weighted MR images were gathered from both public and internal sources. Our experiments compared each architecture's testing performance when trained both intra-institutionally and inter-institutionally. Models trained using nnUNet and its PocketNet variant achieved mean Dice-Sorensen similarity coefficients>0.9 on both intra- and inter-institutional test set data. The performance of these models suggests that nnUNet and PocketNet liver segmentation models trained on a large and diverse collection of T1-weighted MR images would on average achieve good intra-institutional segmentation performance. [ABSTRACT FROM AUTHOR]

Summary: Background: The incidence of colorectal carcinoma is increasing, and it is now the third most common type of cancer worldwide. Liver resection for colorectal liver metastasis is the only potentially curative method of treatment. Surgical removal of carcinomas arising in most of the other organs, without the concomitant performance of a lymphadenectomy, is not accepted as an appropriate treatment for cure and staging. However, there has been no clear conclusion on whether or not to perform lymphatic node dissection in conjunction with a hepatectomy. Methods: We performed systematic review of all relevant articles published until December 2022. The reference lists of relevant studies were screened to retrieve any further potential articles. All original papers on lymphatic node dissection with a hepatectomy for colorectal liver metastasis were retrieved and included in the systematic review. Results: The initial search strategy retrieved 1213 publications, 1044 were excluded in the primary selection and 122 were excluded in the secondary selection after reading the full text of the potentially relevant studies. Finally, 47 studies were identified and included in the systematic review, with a total 17,798 patients being evaluated. There were no randomized controlled trials comparing liver resection alone with liver resection in conjunction with a routine regional lymphadenectomy. Conclusion: This systematic review deals with all aspects of lymphatic node dissection concurrent with liver resection. We found no evidence that systemic lymphadenectomy during liver resection would improve the survival of the patients. However, this pattern of extrahepatic disease can provide an important piece of prognostic information. [ABSTRACT FROM AUTHOR]

Wastewater treatment plants (WWTPs) continuously release a complex mixture of municipal, hospital, industrial, and runoff chemicals into the aquatic environment. These contaminants are both legacy contaminants and emerging-concern contaminants, affecting all tissues in a fish body, particularly the liver. The fish liver is the principal detoxifying organ and effects of consistent pollutant exposure can be evident on its cellular and tissue level. The objective of this paper is thus to provide an in-depth analysis of the WWTP contaminants' impact on the fish liver structure, physiology, and metabolism. The paper also gives an overview of the fish liver biotransformation enzymes, antioxidant enzymes, and non-enzymatic antioxidants, their role in metabolizing xenobiotic compounds and coping with oxidative damage. Emphasis has been placed on highlighting the vulnerability of fish to xenobiotic compounds, and on biomonitoring of exposed fish, generally involving observation of biomarkers in caged or native fish. Furthermore, the paper systematically assesses the most common contaminants with the potential to affect fish liver tissue. [ABSTRACT FROM AUTHOR]

Medical image analysis plays a pivotal role in the evaluation of diseases, including screening, surveillance, diagnosis, and prognosis. Liver is one of the major organs responsible for key functions of metabolism, protein and hormone synthesis, detoxification, and waste excretion. Patients with advanced liver disease and Hepatocellular Carcinoma (HCC) are often asymptomatic in the early stages; however delays in diagnosis and treatment can lead to increased rates of decompensated liver diseases, late-stage HCC, morbidity and mortality. Ultrasound (US) is commonly used imaging modality for diagnosis of chronic liver diseases that includes fibrosis, cirrhosis and portal hypertension. In this paper, we first provide an overview of various diagnostic methods for stages of liver diseases and discuss the role of Computer-Aided Diagnosis (CAD) systems in diagnosing liver diseases. Second, we review the utility of machine learning and deep learning approaches as diagnostic tools. Finally, we present the limitations of existing studies and outline future directions to further improve diagnostic accuracy, as well as reduce cost and subjectivity, while also improving workflow for the clinicians. [ABSTRACT FROM AUTHOR]

Replacing cereals with food leftovers could reduce feed-food competition and keep nutrients and energy in the food chain. Former food products (FFPs) are industrial food leftovers no more intended for human but still suitable as alternative and sustainable feedstuffs for monogastric. In this study, omics approaches were applied to evaluate the impact of dietary FFPs on pig liver proteome and plasma peptidome. Thirty-six Swiss Large White male castrated pigs were randomly assigned to three dietary treatments [control (CTR), 30% CTR replaced with salty FFP (SA), 30% CTR replaced with sugary FFP (SU)] from the start of the growing phase (22.4 ± 1.7 kg) until slaughtering (110 ± 3 kg). The low number of differentially regulated proteins in each comparison matrix (SA/SU vs. CTR) and the lack of metabolic interaction indicated a marginal impact on hepatic lipid metabolism. The plasma peptidomics investigation showed low variability between the peptidome of the three dietary groups and identified three possible bioactive peptides in the SA group associated with anti-hypertension and vascular homeostasis regulation. To conclude, the limited modulation of liver proteome and plasma peptidome by the SA and SU diets strenghtened the idea of reusing FFPs as feed ingredients to make pig production more sustainable. [ABSTRACT FROM AUTHOR]

Diagnosing liver lesions is crucial for treatment choices and patient outcomes. This study develops an automatic diagnosis system for liver lesions using multiphase enhanced computed tomography (CT). A total of 4039 patients from six data centers are enrolled to develop Liver Lesion Network (LiLNet). LiLNet identifies focal liver lesions, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), metastatic tumors (MET), focal nodular hyperplasia (FNH), hemangioma (HEM), and cysts (CYST). Validated in four external centers and clinically verified in two hospitals, LiLNet achieves an accuracy (ACC) of 94.7% and an area under the curve (AUC) of 97.2% for benign and malignant tumors. For HCC, ICC, and MET, the ACC is 88.7% with an AUC of 95.6%. For FNH, HEM, and CYST, the ACC is 88.6% with an AUC of 95.9%. LiLNet can aid in clinical diagnosis, especially in regions with a shortage of radiologists. The distinction of liver lesions is critical for the accurate diagnosis and treatment of liver cancer. Here, the authors develop LiLNet, a deep learning-based system to identify focal liver lesions as well as benign and malignant liver tumours from CT images with high accuracy across multiple patient cohorts. [ABSTRACT FROM AUTHOR]

Clostridium butyricum (CB) has received much attention as a probiotic; however, few studies have focused on its effects on liver health. Here, we studied the influence of CB on the liver health of spotted sea bass through transcriptomics and metabolomics studies and preliminarily explored its molecular mechanisms. This study showed that CB significantly reduced hepatic aspartate aminotransferase (AST) activity and increased alkaline phosphatase (AKP) and acid phosphatase (ACP) activity (P < 0.05). CB has demonstrated significant effects in strengthening liver immunity and can increase hepatic amylase and trypsin activities and promote hepatic catabolism of carbohydrates and amino acids. Integration of the liver transcriptomics and metabolomics showed altered transcript levels of mainly gluconeogenic, lipogenic, and amino acid metabolic pathways. It regulated the abundance of metabolic biomarkers such as arachidonate, crotonyl-CoA, and D-glucose 1-phosphate. Our findings support that CB can reduce liver damage in spotted sea bass, enhance liver immunity, and improve liver metabolism. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) causes significant oxidative stress, which can lead to major clinical complications and tissue destruction. In this study, the antioxidant and anti-inflammatory effects of a mixture of Iranian probiotic strains were evaluated in Cd-exposed rats. Twenty-one adult male Wistar rats were randomized into three groups of seven rats: the control group, Cd-treated (3 mg/kg, a single dose) animals, and the rats treated with Cd + probiotic (Cd + Pro) for 30 days. Histological changes were assessed using hematoxylin and eosin staining, as well as Masson's trachoma staining. The qRT-PCR method was used for evaluating pro-inflammatory genes' expression. Liver biomarkers (ALT, ALP, and AST), biochemical enzymes, and blood parameters were measured using commercial kits, and hematological parameters were determined in both Cd- and the Cd + Pro–treated groups. Histopathologically, results revealed that the native probiotic mixture improved the function of Cd-treated liver cells, compared with Cd-treated rats. Also, positive changes of blood parameters and liver biomarker were observed in the treated group compared with the Cd-treated group. There was a down-regulation of TNF-α and IL-6 genes' expression in Cd + Pro–treated compared with the Cd-treated group. In addition, Cd + Pro–treated rats displayed lower production of lipid peroxides, lower levels of hepatic toxicity biomarkers, and increased levels of CAT and SOD antioxidant biomarkers compared to Cd-treated animals. Iranian native probiotics showed antioxidant and anti-inflammatory properties, and it is suggested to investigate their health benefits in animal studies in the future. [ABSTRACT FROM AUTHOR]

Chemotherapy with Vincristine (Vcr) is often compromised by undesirable gastrointestinal, myeloid and hepatic effects. In this study, we evaluated and compared the efficacy of taurine (Tau) and/or protocatechuic acid (Pca) in alleviating Vcr-induced hepatotoxicity, enterotoxicity and myelotoxicity in rats. In two cycles of five daily injections each, rats were exposed to Vcr (0.1 mg/kg, i.p.) alone or in combination with orally administered Tau (50 mg/kg) and/or Pca (50 mg/kg). Blood was collected for haematology and measurement of liver enzymes and inflammatory cytokines. Genotoxicity assay was performed on bone marrow, while the liver and intestines were subjected to biochemical assays, histopathology and immunohistochemical staining. Administration of Vcr triggered bone marrow suppression (anaemia, leucopenia, thrombocytopenia and increased frequency of micronucleated polychromatic erythrocytes, MnPCEs), increased serum transaminases (ALT, AST) and alkaline phosphatase (ALP) and altered hepatic and intestinal morphology. However, supplementation with Tau and/or Pca alleviated most of the toxic effects of Vcr by reducing tissue levels of malondialdehyde (MDA), hydrogen peroxide (H2O2) and advanced oxidation protein products (AOPP), but stimulating glutathione S-transferase (GST) and glutathione peroxidase (GPx) activities. In addition, Tau and/or Pca enhanced anti-inflammatory (reduced serum TNFα) and anti-apoptotic mechanisms (reduced cytochrome c/Bax expression and increased Bcl-2 expression) in the ileum and liver. Overall, Tau or Pca protected the liver, ileum and bone marrow against Vcr-induced toxicities via antioxidant, anti-inflammatory and anti-apoptotic mechanisms. The data supports their individual use, rather than their combination, as adjuvant therapy in patients undergoing chemotherapeutic intervention. [ABSTRACT FROM AUTHOR]

3D spheroids of primary human hepatocytes (3D PHH) retain a differentiated phenotype with largely conserved metabolic function and proteomic fingerprint over weeks in culture. As a result, 3D PHH are gaining importance as a model for mechanistic liver homeostasis studies and in vitro to in vivo extrapolation (IVIVE) in drug discovery. However, the kinetics and regulation of drug transporters have not yet been assessed in 3D PHH. Here, we used organic cation transporter 1 (OCT1/SLC22A1) as a model to study both transport kinetics and the long-term regulation of transporter activity via relevant signalling pathways. The kinetics of the OCT1 transporter was studied using the fluorescent model substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) and known OCT1 inhibitors in individual 3D PHH. For long-term studies, 3D PHH were treated with xenobiotics for seven days, after which protein expression and OCT1 function were assessed. Global proteomic analysis was used to track hepatic phenotypes as well as prototypical changes in other regulated proteins, such as P-glycoprotein and Cytochrome P450 3A4. ASP+ kinetics indicated a fully functional OCT1 transporter with a Km value of 14 ± 4.0µM as the mean from three donors. Co-incubation with known OCT1 inhibitors decreased the uptake of ASP+ in the 3D PHH spheroids by 35–52%. The long-term exposure studies showed that OCT1 is relatively stable upon activation of nuclear receptor signalling or exposure to compounds that could induce inflammation, steatosis or liver injury. Our results demonstrate that 3D PHH spheroids express physiologically relevant levels of fully active OCT1 and that its transporter kinetics can be accurately studied in the 3D PHH configuration. We also confirm that OCT1 remains stable and functional during the activation of key metabolic pathways that alter the expression and function of other drug transporters and drug-metabolizing enzymes. These results will expand the range of studies that can be performed using 3D PHH. [ABSTRACT FROM AUTHOR]

Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we have developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are highest in liver tissue, which is also a hub for lipid production. While the loss of GSH does not cause liver failure, it decreases lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we find that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production. Glutathione has pleiotropic functions in different organs. Here the authors specifically examine deletion of a glutathione synthetic enzyme in the liver of adult mice and show that lack of glutathione affects lipid abundance through repressing NRF2. [ABSTRACT FROM AUTHOR]

Metastatic spread of tumour cells to tissues and organs around the body is the most frequent cause of death from breast cancer. This has been modelled mainly using mouse models such as syngeneic mammary cancer or human in mouse xenograft models. These have limitations for modelling human disease progression and cannot easily be used for investigation of drug resistance and novel therapy screening. To complement these approaches, advances are being made in ex vivo and 3D in vitro models, which are becoming progressively better at reliably replicating the tumour microenvironment and will in the future facilitate drug development and screening. These approaches include microfluidics, organ-on-a-chip and use of advanced biomaterials. The relevant tissues to be modelled include those that are frequent and clinically important sites of metastasis such as bone, lung, brain, liver for invasive ductal carcinomas and a distinct set of common metastatic sites for lobular breast cancer. These sites all have challenges to model due to their unique cellular compositions, structure and complexity. The models, particularly in vivo, provide key information on the intricate interactions between cancer cells and the native tissue, and will guide us in producing specific therapies that are helpful in different context of metastasis. [ABSTRACT FROM AUTHOR]

Objectives: We proposed a strategy for the creation of a 6-mm transjugular intrahepatic portosystemic shunt (TIPS) and to assess its effectiveness compared to a conventional 8-mm shunt for TIPS-induced hepatic encephalopathy (HE). Methods: Patients were reviewed retrospectively using propensity score matching (1:1) and divided into 6-mm and 8-mm shunt groups based on shunt diameter. The stent patency, HE incidence, and rebleeding rate between the two groups were then compared. Results: From January 2018 to June 2021, both 6-mm shunt group and 8-mm shunt group included 58 patients. The 6-mm shunt group had significantly smaller liver volumes (879.3 ± 237.1 vs. 1008.8 ± 293.0; p = 0.010), and the median stent patency times were 30.7 and 33.8 months in the 6-mm and 8-mm groups, respectively (p = 0.124). No statistically significant difference was found between the two groups in the 1-year (8.6% vs. 3.4%; p = 0.242) and 2-year (17.2% vs. 12.1%; p = 0.242) rebleeding rates. The 1-year cumulative incidences of overt HE were 12.1% and 27.6% in the 6-mm and 8-mm groups, respectively (p = 0.040), and the 2-year cumulative overt HE incidences in these groups were 19.0% and 36.2%, respectively (p = 0.038). Notably, patients with a 6-mm shunt also experienced less hepatic impairment. Conclusions: For patients with variceal bleeding and a small liver volume, the 6-mm shunt significantly reduced the incidence of overt HE, protected perioperative liver function, and did not affect stent patency or rebleeding rate. Clinical relevance statement: For patients with variceal bleeding with small liver volume, the 6-mm transjugular intrahepatic portosystemic shunt (TIPS) significantly reduced the incidence of overt hepatic encephalopathy after TIPS, protected perioperative liver function, and did not affect stent patency and rebleeding rate. Key Points.: • A strategy for the creation of a 6-mm transjugular intrahepatic portosystemic shunt for patients with variceal bleeding and a small liver volume was proposed. • The 6-mm transjugular intrahepatic portosystemic shunt significantly reduced the incidence of overt hepatic encephalopathy. • The 6-mm transjugular intrahepatic portosystemic shunt did not affect stent patency or rebleeding rate. [ABSTRACT FROM AUTHOR]

Circadian gene expression is fundamental to the establishment and functions of the circadian clock, a cell-autonomous and evolutionary-conserved timing system. Yet, how it is affected by environmental-circadian disruption (ECD) such as shiftwork and jetlag are ill-defined. Here, we provided a comprehensive and comparative description of male liver circadian gene expression, encompassing transcriptomes, whole-cell proteomes and nuclear proteomes, under normal and after ECD conditions. Under both conditions, post-translation, rather than transcription, is the dominant contributor to circadian functional outputs. After ECD, post-transcriptional and post-translational processes are the major contributors to whole-cell or nuclear circadian proteome, respectively. Furthermore, ECD re-writes the rhythmicity of 64% transcriptome, 98% whole-cell proteome and 95% nuclear proteome. The re-writing, which is associated with changes of circadian regulatory cis-elements, RNA-processing and protein localization, diminishes circadian regulation of fat and carbohydrate metabolism and persists after one week of ECD-recovery. Circadian gene expression is fundamental to the circadian clock. Here the author showed post-translational processing is the dominant contributor to circadian nuclear proteome and Environmental Circadian Disruption re-writes the entire gene expression process from transcription to post-translation. [ABSTRACT FROM AUTHOR]

Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older livers exhibit increased ferroptosis during HIRI. Inhibiting ferroptosis significantly attenuates older HIRI phenotypes. Mass spectrometry reveals that fat mass and obesity-associated gene (FTO) expression is downregulated in older livers, especially during HIRI. Overexpressing FTO improves older HIRI phenotypes by inhibiting ferroptosis. Mechanistically, acyl-CoA synthetase long chain family 4 (ACSL4) and transferrin receptor protein 1 (TFRC), two key positive contributors to ferroptosis, are FTO targets. For ameliorative effect, FTO requires the inhibition of Acsl4 and Tfrc mRNA stability in a m6A-dependent manner. Furthermore, we demonstrate nicotinamide mononucleotide can upregulate FTO demethylase activity, suppressing ferroptosis and decreasing older HIRI. Collectively, these findings reveal an FTO-ACSL4/TFRC regulatory pathway that contributes to the pathogenesis of older HIRI, providing insight into the clinical translation of strategies related to the demethylase activity of FTO to improve graft function after older donor liver transplantation. Transplanted older livers are prone to injury through unclear mechanisms, precluding effective treatment development. Here, the authors show that decreased FTO expression in older livers inhibits Acsl4 and Tfrc mRNA stability in an m6A-dependent manner, increasing cell death in older donor livers. [ABSTRACT FROM AUTHOR]

Histopathological changes are widely used as biomarkers of the health status of fish exposed to chemical compounds. Individuals of the common kilka Clupeonella caspia Svetovidov, 1941 caught from the Middle Caspian Sea exhibited significant changes in the cellular structure of the liver. The more common were signs of hyperemia: an edema of the liver parenchyma, vascular congestion, lympho-macrophage infiltration, small hemorrhages, and a narrowing of the bile duct lumen. [ABSTRACT FROM AUTHOR]

In this paper, we report on the detection and measurement of refractive properties of healthy and cancerous human liver samples taken from real data using a prism pair technique that covers the near-visible and infrared spectral range. Then, according to real samples, an all-optical refractive index biosensor is designed and simulated. Newly used data on the wavelength-dependent refractive index of human liver tissues are presented and detected under different conditions. Remarkably, the real index contrast is mentioned as an index of the difference between normal liver tissue and liver metastases. According to real data from the human body, a special account can be made on the detection of the healthy and cancerous liver in this article. Numerous photon crystal-based biosensors are proposed for various diseases, but no serious research has been done on unhealthy livers, and this article tries to cover this type of disease as well. The obtained sensitivity values are reported as 1000 nm/RIU for the given bio samples. [ABSTRACT FROM AUTHOR]

Background: No previous research papers have reported a comparative survey of local radiologic diagnoses and central review in children with hepatoblastoma. Objective: To evaluate the utility of central review of children with hepatoblastoma enrolled in a clinical trial. Materials and methods: The study included 91 children enrolled in a clinical trial conducted by the Japanese Study Group for Pediatric Liver Tumor. We compared the results of the initial pre-treatment extent of tumor (PRETEXT) disease staging performed at local sites with the results obtained on central review to determine the concurrence rates for tumor staging and additional criteria. Results: The concurrence rate for PRETEXT staging was 70%. As the stage increased, the concurrence rate decreased. Using additional criteria, central review identified 143 lesions (157.1%), about 1.8 times higher than the number identified for the local site diagnoses. The additional criterion found most often on central review was "multifocal lesion" (n=19). The concurrence rate for lung metastases was high. However, our central review found many false-positive assertions of hepatic vein lesions, portal vein invasion and extrahepatic lesions among the local site diagnoses. Conclusion: In a clinical trial of hepatoblastoma, central review provided a more precise diagnosis than local site diagnoses with respect to severe PRETEXT stages III and IV cases and other cases including hepatic and portal vein invasion. The central review process appears to be effective and essential for improving the quality of clinical trials. [ABSTRACT FROM AUTHOR]

A study was conducted to determine the influence of decontamination on winter flounder living downstream from a pulp and paper mill. The fish and controls were held 8–26 weeks under contaminant-free conditions in aquaria supplied with ambient sea water. Groups of flounder, for comparison, were also sampled near the paper mill at the time of or following autopsy. No differences were apparent in length/organ-weight relationships between depurated and control groups after 26 weeks at 0–6°C, but condition factor, gonadal and hepatosomatic indices, coincident with elevated levels of detoxifying enzymes, differed from field-derived samples. Pathological changes, including hemosiderin deposits in the liver and spleen, decreased, whereas pericholangitis and clear cell foci were apparent in the depurated fish and in the field samples. In two additional groups decontaminated for 8–16 weeks at 6–16°C, there was no evidence of pericholangitis, but hemosiderin deposits persisted and an increase of fibrosis and clear cell foci occurred in contrast to the field group. These results suggest that some tissue repair in the liver transpired primarily during summer while other lesions, such as preneoplastic clear cell foci, which were probably induced prior to depuration, increased, but hemosiderin concentration remained unchanged. The latter observation is consistent with previous studies that suggest that hemosiderin concentration is not seasonally but age influenced. [ABSTRACT FROM AUTHOR]

In this paper, we describe an algorithm for accurately segmenting multiple nudfclei from clumps of non-overlapping immuno-histochemically stained histological hepatic (liver) images. This problem is notoriously difficult because of the degree of presence of stains among the multi-nucleated cells, the poor contrast of cell cytoplasm, and the presence of mucus, blood, and inflammatory cells in the images. Hepatocellular carcinoma, characterized by cellular and nuclear enlargement, nuclear pleomorphism, and multi-nucleation, poses a prominent threat. Our proposed method addresses the aforementioned issues for an automated diagnosis system by judging the presence of multiple nuclei in a two-step process: the Quickhull algorithm defines the convex hull of each cell in the image and candidate nuclei regions are located with morphological operations. A combination of features containing local minima and shape-dependent features is extracted for the detection of single or multiple nuclei in each cell with a significant reduction in the number of false positives and false negatives providing an accuracy of 89.76%. [ABSTRACT FROM AUTHOR]

The purpose of this study was to elucidate the mechanism underlying toxicity in the livers of male and female rats after treatment with 1-tetradecyl-3-methylimidazolium tetrafluoroborate ([C14mim]BF4, 0 [control], 12.5, 25, or 50 mg/kg) for 90 days. The results showed that [C14mim]BF4 exposure led to a high level of ROS and MDA in rat livers and the lower expression of Nrf2 and its downstream related antioxidant proteins. In addition, the expression of NF-κB p65 and the levels of inflammatory cytokines were upregulated in exposure groups rats' liver. After 30 days of cessation of exposure, the liver injury of rats in the 50 mg/kg exposure group was alleviated, and the above indicators were improved to varying degrees. The paper shows that [C14mim]BF4 could damage rat liver through oxidative stress and inflammatory pathway. [ABSTRACT FROM AUTHOR]

The Liver Imaging and Reporting Data System (LI-RADS) is a comprehensive system for standardizing the terminology, technique, interpretation, reporting, and data collection of liver imaging with the overarching goal of improving communication, clinical care, education, and research relating to patients at risk for or diagnosed with hepatocellular carcinoma (HCC). In 2018, the American Association for the Study of Liver Diseases (AASLD) integrated LI-RADS into its clinical practice guidance for the imaging-based diagnosis of HCC. The harmonization between the AASLD and LI-RADS diagnostic imaging criteria required minor modifications to the recently released LI-RADS v2017 guidelines, necessitating a LI-RADS v2018 update. This article provides an overview of the key changes included in LI-RADS v2018 as well as a look at the LI-RADS v2018 diagnostic algorithm and criteria, technical recommendations, and management suggestions. Substantive changes in LI-RADS v2018 are the removal of the requirement for visibility on antecedent surveillance ultrasound for LI-RADS 5 (LR-5) categorization of 10-19 mm observations with nonrim arterial phase hyper-enhancement and nonperipheral “washout”, and adoption of the Organ Procurement and Transplantation Network definition of threshold growth (≥ 50% size increase of a mass in ≤ 6 months). Nomenclatural changes in LI-RADS v2018 are the removal of -us and -g as LR-5 qualifiers. [ABSTRACT FROM AUTHOR]

The liver represents the most frequent location of metastatic disease in colorectal cancer (CRC). In oligometastatic disease, while surgery remains the mainstay of treatment, loco-regional therapies allow to locally control tumor progression and prolong survival. There is consensus in the use of transhepatic arterial radioembolization (TARE) in metastatic CRC chemorefractory patients, with liver-only or liver-dominant disease. Beyond this indication, TARE may be considered in other clinical scenarios, such as in the second-line combined with chemotherapy, as a bridge in between different lines of systemic therapies, and as ablative technique under specific circumstances. This paper outlines the current evidence for TARE in mCRC and presents possible future indications and directions [ABSTRACT FROM AUTHOR]

Surgical process modelling is an innovative approach that aims to simplify the challenges involved in improving surgeries through quantitative analysis of a well-established model of surgical activities. In this paper, surgical process model strategies are applied for the analysis of different Minimally Invasive Liver Treatments (MILTs), including ablation and surgical resection of the liver lesions. Moreover, a generic surgical process model for these differences in MILTs is introduced. The generic surgical process model was established at three different granularity levels. The generic process model, encompassing thirteen phases, was verified against videos of MILT procedures and interviews with surgeons. The established model covers all the surgical and interventional activities and the connections between them and provides a foundation for extensive quantitative analysis and simulations of MILT procedures for improving computer-assisted surgery systems, surgeon training and evaluation, surgeon guidance and planning systems and evaluation of new technologies. [ABSTRACT FROM AUTHOR]

Nuclear factor erythroid 2-related factor-2 (Nrf2) antioxidant signaling is involved in liver protection, but this generalization overlooks conflicting studies indicating that Nrf2 effects are not necessarily hepatoprotective. The role of Nrf2/heme oxygenase-1 (HO-1) in cholestatic liver injury (CLI) remains poorly defined. Here, we report that Nrf2/HO-1 activation exacerbates liver injury rather than exerting a protective effect in CLI. Inhibiting HO-1 or ameliorating bilirubin transport alleviates liver injury in CLI models. Nrf2 knockout confers hepatoprotection in CLI mice, whereas in non-CLI mice, Nrf2 knockout aggravates liver damage. In the CLI setting, oxidative stress activates Nrf2/HO-1, leads to bilirubin accumulation, and impairs mitochondrial function. High levels of bilirubin reciprocally upregulate the activation of Nrf2 and HO-1, while antioxidant and mitochondrial-targeted SOD2 overexpression attenuate bilirubin toxicity. The expression of Nrf2 and HO-1 is elevated in serum of patients with CLI. These results reveal an unrecognized function of Nrf2 signaling in exacerbating liver injury in cholestatic disease. Activation of the Nrf2/HO-1 antioxidant signaling pathway exacerbates cholestatic liver injury due to excessive accumulation of bilirubin, rather than exerting a protective effect as in non-cholestatic liver injury. [ABSTRACT FROM AUTHOR]

Background: Copper oxide nanoparticles (CuO-NPs) have gained interest due to their availability, efficiency, and their cost-effectiveness. Betaine is an essential methyl donor and takes part in various physiological activities inside the body; it is found to have protective and curative effects against various liver diseases. The present study aimed to evaluate the hepatotoxic effect of CuO-NPs on adult male albino rats and the ability of betaine to alleviate such hepatotoxicity. Methods: Forty adult male albino Wister rats were grouped into 4 groups (10 rats/group): group I a negative control, group II (CuO-NPs) injected with CuO-NPs intra peritoneal by insulin needle (0.5 mg/kg/day), group III (betaine + CuO-NPs) administered betaine orally by gavage needle (250 mg/kg/day 1 h before CuO-NPs) and CuO-NPs (0.5 mg/kg/day) finally, group IV (betaine) administered betaine orally by gavage needle (250 mg/kg/day) for consecutive 28 days. Blood and liver samples were gathered and processed for biochemical, molecular, histopathological, and immunohistochemical investigations. Results: Group II displayed a marked rise in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) levels. Furthermore, there is an excessive upregulation of the inflammatory biomarkers interleukin1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). On the other hand, substantial reduction in glutathione (GSH) levels and significant downregulation at glutathione peroxidase (GPx) mRNA gene expression. Regarding the histopathological deviations, there were severe congestion, dilatation and hyalinization of blood vessels, steatosis, hydropic degeneration, hepatocytic necrosis, increased binucleation, degenerated bile ducts, hyperplasia of ducts epithelial lining, and inflammatory cells infiltration. Immunohistochemically, there was a pronounced immunoreactivity toward IL-1β. Luckily, the pre-administration of betaine was able to mitigate these changes. MDA was dramatically reduced, resulting in the downregulation of IL-1β and TNF-α. Additionally, there was a considerable rise in GSH levels and an upregulation of GPx. Histopathological deviations were substantially improved as diminished dilatation, hyalinization and congestion of blood vessels, hepatocytes, and bile ducts are normal to some extent. In addition, IL-1β immunohistochemical analysis revealed marked decreased intensity. Conclusion: Betaine can effectively reduce the hepatotoxicity caused by CuO-NPs via its antioxidant properties and its ability to stimulate the cell redox system. [ABSTRACT FROM AUTHOR]

The liver gene expression of the peroxisomal β-oxidation enzyme acyl-coenzyme A oxidase 1 (ACOX1), which catabolizes very long chain fatty acids (VLCFA), increases in the context of obesity, but how this pathway impacts systemic energy metabolism remains unknown. Here, we show that hepatic ACOX1-mediated β-oxidation regulates inter-organ communication involved in metabolic homeostasis. Liver-specific knockout of Acox1 (Acox1-LKO) protects mice from diet-induced obesity, adipose tissue inflammation, and systemic insulin resistance. Serum from Acox1-LKO mice promotes browning in cultured white adipocytes. Global serum lipidomics show increased circulating levels of several species of ω−3 VLCFAs (C24-C28) with previously uncharacterized physiological role that promote browning, mitochondrial biogenesis and Glut4 translocation through activation of the lipid sensor GPR120 in adipocytes. This work identifies hepatic peroxisomal β-oxidation as an important regulator of metabolic homeostasis and suggests that manipulation of ACOX1 or its substrates may treat obesity-associated metabolic disorders. The peroxisomal β-oxidation enzyme ACOX1 increases in liver with obesity, but the physiological significance is unclear. Here, the authors show that liver-specific knockout of Acox1 leads to accumulation of omega-3 VLCFAs that promote metabolic health through activation of GPR120 in adipose tissue. [ABSTRACT FROM AUTHOR]

The liver has multiple regeneration modes, including hepatocellular hypertrophy and self-renewal of hepatocytes. When hepatocyte proliferation is impaired, hepatic progenitor cells may proliferate through ductular reaction (DR), differentiate into hepatocytes, and contribute to fibrosis. However, the three-dimensional spatial relationship between DR and regenerating hepatocytes and dynamic changes in DR associated with fibrosis remain poorly understood. Here, we performed three-dimensional (3D) imaging of cleared 42 liver explants with chronic and acute liver diseases and 4 normal livers to visualize DR. In chronic hepatic liver diseases, such as viral hepatitis, steatohepatitis, autoimmune hepatitis, and cryptogenic cirrhosis, the total length and number of branches of DR showed a significant positive correlation. We studied the spatial relationship between DR and GS-expressing cells using glutamine synthetase (GS) and cytokeratin 19 (CK19) as markers of liver regeneration and DR, respectively. The percentage of CK19-positive cells that co-expressed GS was less than 10% in chronic liver diseases. In contrast, nearly one-third of CK19-positive cells co-expressed GS in acute liver diseases, and chronic cholestatic liver diseases, including primary biliary cholangitis and primary sclerosing cholangitis, showed no co-expression. We also found that DR was longer and had more branching in livers with progressive fibrosis compared to those with regressive fibrosis. Our results suggest that DR displays varying degrees of spatial complexity and contribution to liver regeneration. DR may serve as hepatobiliary junctions that maintain continuity between hepatocytes and bile ducts rather than hepatocyte regeneration in chronic liver diseases. [ABSTRACT FROM AUTHOR]

Globally liver diseases are the most life-threatening diseases, and according to global cancer statistics, liver cancer is the most common. Early detection of liver cancer can prevent millions of patients' mortality every year. Automatic liver cancer detection will help radiologists to determine the tumour identification and its severity, and it is also helpful to reduce the occurrence of errors which results in a reduction in the number of deaths from liver cancer. It gives more accurate results in less time, saving the radiologist's effort and time. The proposed model focused on improving the segmenting of liver images and then classifying the liver tumours from the CT images. The present study suggests the hyper tangent Fuzzy C-Means (HTFCM) to segment the liver images. It used Hyper tangent distance to calculate the data point distance from the cluster centres and obtained segmentation results almost closer to the ground truth liver images. Due to the fuzziness in the liver images, all state-of-the-art models except the proposed model cannot precisely locate the tumours. This study solved the issue of linear mapping using fuzzy logic, improved the classification accuracy, and reduced the processing time of early diagnosis of liver diseases. The proposed model improves the classification accuracy to 99.58% and reduces the processing time by 2-25 s to classify the liver tumours. [ABSTRACT FROM AUTHOR]

Conventional transarterial chemoembolization (cTACE) utilizing ethiodized oil as a chemotherapy carrier has become a standard treatment for intermediate-stage hepatocellular carcinoma (HCC) and has been adopted as a bridging and downstaging therapy for liver transplantation. Water-in-oil emulsion made up of ethiodized oil and chemotherapy solution is retained in tumor vasculature resulting in high tissue drug concentration and low systemic chemotherapy doses. The density and distribution pattern of ethiodized oil within the tumor on post-treatment imaging are predictive of the extent of tumor necrosis and duration of response to treatment. This review describes the multiple roles of ethiodized oil, particularly in its role as a biomarker of tumor response to cTACE. Clinical relevance: With the increasing complexity of locoregional therapy options, including the use of combination therapies, treatment response assessment has become challenging; Ethiodized oil deposition patterns can serve as an imaging biomarker for the prediction of treatment response, and perhaps predict post-treatment prognosis. Key Points: • Treatment response assessment after locoregional therapy to hepatocellular carcinoma is fraught with multiple challenges given the varied post-treatment imaging appearance. • Ethiodized oil is unique in that its' radiopacity can serve as an imaging biomarker to help predict treatment response. • The pattern of deposition of ethiodozed oil has served as a mechanism to detect portions of tumor that are undertreated and can serve as an adjunct to enhancement in order to improve management in patients treated with intraarterial embolization with ethiodized oil. [ABSTRACT FROM AUTHOR]

Deep convolutional neural networks have made significant strides in the field of medical image segmentation. Although existing convolutional structures enhance performance by leveraging local image information, they often lose the interdependence information between contexts. Therefore, the article utilizes the multi-attention mechanism of the Transformer structure to more comprehensively express relationships between contexts and introduced the Transformer network architecture into the field of medical image segmentation. Most models based on this Transformer structure typically require large datasets for training. However, in the medical field, the limited size of datasets makes training models with the Transformer structure challenging. To address this, the article propose a Weighted Medical Transformer (WMT) model that imposes low requirements on dataset quantity. The weighting mechanism in the WMT model aims to improve the issue of inaccurate relative positional coding when dealing with small medical datasets. Additionally, a coarse-grained and fine-grained segmentation mechanism is introduced, focusing on both the detailed aspects within image blocks and the boundary information connecting blocks. Experimental results on a liver dataset demonstrate that the model achieves F1 and IoU scores of 88.48% and 79.41%, respectively. Results on the MoNuSeg dataset show comparable high F1 and IoU scores of 79.58% and 66.19%, respectively. The model's accuracy surpasses that of U-Net++ and U-Net models. Compared to other models, this approach is applicable to scenarios with limited datasets, exhibiting high execution efficiency and accuracy. [ABSTRACT FROM AUTHOR]

Background: Liver uptake in [68Ga]Ga-PSMA-11 PET is used as an internal reference in addition to clinical parameters to select patients for [177Lu]Lu-PSMA-617 radioligand therapy (RLT). Due to increased demand, [68Ga]Ga-PSMA-11 was replaced by [18F]F-PSMA-1007, a more lipophilic tracer with different biodistribution and splenic uptake was suggested as a new internal reference. We compared the intra-patient tracer distribution between [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007. Methods: Fifty patients who underwent PET examinations in two centers with both [18F]F-PSMA-1007 and [68Ga]Ga-PSMA-11 within one year were included. Mean standardized uptake values (SUVmean) were obtained for liver, spleen, salivary glands, blood pool, and bone. Primary tumor, local recurrence, lymph node, bone or visceral metastasis were also assessed for intra- and inter-individual comparison. Results: Liver SUVmean was significantly higher with [18F]F-PSMA-1007 (11.7 ± 3.9) compared to [68Ga]Ga-PSMA-11 (5.4 ± 1.7, p <.05) as well as splenic SUVmean (11.2 ± 3.5 vs.8.1 ± 3.5, p <.05). The blood pool was comparable between the two scans. Malignant lesions did not show higher SUVmean on [18F]F-PSMA-1007. Intra-individual comparison of liver uptake between the two scans showed a linear association for liver uptake with SUVmean [68Ga]Ga-PSMA-11 = 0.33 x SUVmean [18F]F-PSMA-1007 + 1.52 (r =.78, p <.001). Conclusion: Comparing biodistribution of [68Ga]Ga and [18F]F tracers, liver uptake on [68Ga]Ga-PSMA-11 PET is the most robust internal reference value. Liver uptake of [18F]F-PSMA-1007 was significantly higher, but so was the splenic uptake. The strong intra-individual association of hepatic accumulation between the two scans may allow using of a conversion factor for [18F]F-PSMA-1007 as a basis for RLT selection. [ABSTRACT FROM AUTHOR]

Cytochrome P450 2E1 (CYP2E1) plays an important role in liver damage. However, it is still unclear how CYP2E1 transcriptional regulation works. Naringin is a flavonoid enriched in grapefruit, orange, and tomatoes with antioxidant and anti-inflammatory properties. This study aims to study the potential antioxidants and the anti-inflammatory effects of naringin in mice-induced liver damage by D-galactosamine (D-gal) administration. Mice were divided into four groups: group 1, the normal control group; group 2, the D-gal group was injected (200 mg /kg; s.c.) daily for 8 weeks; and groups 3 and 4, naringin groups received naringin (150 mg/kg and 300 mg/kg; p.o.) daily concurrent with D-gal for 8 weeks. Serum was prepared to measure aspartate transaminase (AST) and alanine transaminases (ALT). Liver tissue homogenate was prepared to measure nitric oxide (NO), catalase, cytochrome P450 2E1 (CYP2E1), tumor necrotic factor (TNF-α), C-X-C motif chemokine ligand 1 (CXCL1), and CD44. Finally, histological and immunohistochemical studies were performed. Supplementation with naringin for 8 weeks significantly decreased the levels of AST, ALT, CYP2E1, TNF-α, CXCL1, and CD44, and pathology of the liver showed improvement of treated groups with increased dose as hepatic cells showed signs of regeneration with binucleated hepatic cells with normal hepatic architecture and suppressed P53 hyperactivity as an apoptotic marker. Naringin exhibited hepatoprotective effects in mice by inhibiting reactive oxygen species (ROS), down-regulating of CYP2E1 liver content, and producing a significant decline in different inflammatory markers as well as suppressing apoptosis. [ABSTRACT FROM AUTHOR]