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The halogenated solvent trichloroethylene (TCE) has had many uses in medicine, construction, consumer products, and the military. Many of these uses have been discontinued or restricted due to its toxicity, which affects multiple target organs and includes both acute, high-dose toxicity and chronic, low-dose toxicity that also encompass several cancers. US and international agencies have conducted risk and hazard assessments for TCE, with comprehensive publications coming out in the last 10–15 years. Accordingly, the focus of this article is to review recently published data since that time (i.e., 2014) that clarify unsettled questions or provide additional insights into the metabolism and mechanisms of toxicity of TCE in several target organs. Besides metabolism, the review focuses on the kidneys, liver, immune system, nervous system, cardiovascular and pulmonary systems, the search for biomarkers, and recent analyses of human cancer risk and incidence from TCE exposure. [ABSTRACT FROM AUTHOR]

Folic acid, also known as vitamin B9, is a water-soluble vitamin from the B group that plays a pivotal role (as the carrier of one-carbon units) in the regulation of early development and nutrient metabolism in animals. Traditional animal nutrition posits that rumen microorganisms can synthesize folate, thereby meeting the growth, development, and production needs of ruminants. However, the quantity of synthesized folate is subject to variations in dietary composition, genetic enhancements, increased production performance, and changes in feeding systems. These factors may result in the folate synthesized by rumen microorganisms not reaching the optimal production potential of the animals. Despite a significant proportion of dietary folic acid/folate being degraded in the rumen, studies have shown that supplementing folic acid (or combined with vitamin B12, methionine, etc.) in the diet can enhance rumen fermentation, increase the folate level in ruminant tissues (such as the liver and blood), regulate nutrient metabolism, and improve milk yield and quality to a certain extent. Further research is required to assess the impact of dietary folic acid levels on rumen microbial metabolism, folate distribution among different tissues and organs, and the demand for folate at various developmental stages, as well as the interaction between folic acid and other nutrients which are involved in one-carbon metabolism process. This will help to optimize the nutritional supply for ruminants and fully exploit their production performance potential. Ruminants are animals like cattle, sheep and goats with a specialized stomach for fermenting food. Although microorganisms in this stomach can synthesize folate, there is a risk of insufficient supply when these animals are farmed as livestock. Addingfolic acid to feed can help regulate ruminants' metabolism and production performance, especially during pregnancy and lactation. More attention needs to be paid to folic acid requirements and metabolic characteristics of ruminants to help healthy and efficient production management. [ABSTRACT FROM AUTHOR]

The configuration of the hepatic arteries is known to vary substantially between individuals. Here, we report a rare retroperitoneal configuration of an accessory hepatic artery existing alongside a left and right hepatic artery branching from the proper hepatic artery. During routine dissection, we discovered an anomalous configuration of the hepatic arteries that does not fit the commonly used categorizations for abnormal hepatic vasculature. We briefly discuss potential implications of this finding. Case Report: The left and right hepatic arteries branch directly from the common hepatic artery and supply the liver. The accessory hepatic artery arises directly from the superior mesenteric artery, travels posterior to the portal triad, and enters the porta hepatis. It was found to travel posterior to the neck of the pancreas, duodenum, and portal triad at the same depth as the inferior vena cava, suggesting that the accessory right hepatic artery was traveling retroperitoneally, posterior to the opening of the lesser sac. The accessory hepatic artery exclusively supplies the cystic arteries. Considering existing classification schemes, our case most closely resembles Michels's type 6 and Hiatt's type 3, but most specifically López-Andújar's type 6. To the best of our knowledge, this is one of the first reported cases of a retroperitoneal accessory right hepatic artery. Conclusions: Knowledge of the possible variations of the hepatic arteries is important to reduce the risk of iatrogenic injury and improve patient outcomes in surgery, especially in laparoscopic cases or pancreatoduodectomies where more unique variants may be especially difficult to identify or easier to injure. Future research should explore the frequency of retroperitoneal accessory right hepatic arteries, as their unique course may be easily missed. [ABSTRACT FROM AUTHOR]

Objective. We previously developed a FLASH planning framework for streamlined pin-ridge-filter (pin-RF) design, demonstrating its feasibility for single-energy proton FLASH planning. In this study, we refined the pin-RF design for easy assembly using reusable modules, focusing on its application in liver stereotactic ablative body radiotherapy (SABR). Approach. This framework generates an intermediate intensity-modulated proton therapy (IMPT) plan and translates it into step widths and thicknesses of pin-RFs for a single-energy FLASH plan. Parameters like energy spacing, monitor unit limit, and spot quantity were adjusted during IMPT planning, resulting in pin-RFs assembled using predefined modules with widths from 1 to 6 mm, each with a water-equivalent-thickness of 5 mm. This approach was validated on three liver SABR cases. FLASH doses, quantified using the FLASH effectiveness model at 1–5 Gy thresholds, were compared to conventional IMPT (IMPT-CONV) doses to assess clinical benefits. Main results. The highest demand for 6 mm width modules, moderate for 2–4 mm, and minimal for 1- and 5-mm modules were shown across all cases. At lower dose thresholds, the two-beam case reduced indicators including liver V 21Gy and skin D max by >19.4%, while the three-beam cases showed reductions ⩽ 11.4%, indicating the need for higher fractional beam doses for an enhanced FLASH effect. Positive clinical benefits were seen only in the two-beam case at the 5 Gy threshold. At the 1 Gy threshold, the two-beam FLASH plan outperformed the IMPT-CONV plan, reducing dose indicators for all relevant normal tissues by up to 31.2%. In contrast, the three-beam cases showed negative clinical benefits, with skin D max and liver V 21Gy increasing by up to 17.4% due to lower fractional beam doses and closer beam arrangements. Significance. This study evaluated the feasibility of modularizing streamlined pin-RFs in single-energy proton FLASH planning for liver SABR, offering guidance on optimal module composition and strategies to enhance FLASH planning. [ABSTRACT FROM AUTHOR]

Simple Summary: In this work, we developed three neural networks based on the U-net architecture to automatically segment the healthy liver area, the metastatic liver area, and liver metastases in micro-CT images of mice with pancreatic ductal adenocarcinoma and liver metastases. The best network for each task was then identified by cross-validation. The results demonstrated the ability of the selected networks to segment the above areas in a manner comparable to manual segmentation, at the same time saving time and ensuring reproducibility. Therefore, despite the limited number of animals involved, our pilot study represents a first step toward the development of automated tools to support liver metastasis research in the preclinical setting. Background: The liver is one of the most common sites for the spread of pancreatic ductal adenocarcinoma (PDAC) cells, with metastases present in about 80% of patients. Clinical and preclinical studies of PDAC require quantification of the liver's metastatic burden from several acquired images, which can benefit from automatic image segmentation tools. Methods: We developed three neural networks based on U-net architecture to automatically segment the healthy liver area (HL), the metastatic liver area (MLA), and liver metastases (LM) in micro-CT images of a mouse model of PDAC with liver metastasis. Three alternative U-nets were trained for each structure to be segmented following appropriate image preprocessing and the one with the highest performance was then chosen and applied for each case. Results: Good performance was achieved, with accuracy of 92.6%, 88.6%, and 91.5%, specificity of 95.5%, 93.8%, and 99.9%, Dice of 71.6%, 74.4%, and 29.9%, and negative predicted value (NPV) of 97.9%, 91.5%, and 91.5% on the pilot validation set for the chosen HL, MLA, and LM networks, respectively. Conclusions: The networks provided good performance and advantages in terms of saving time and ensuring reproducibility. [ABSTRACT FROM AUTHOR]

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The present study was aimed to investigate the impact of malathion on the biochemical and histological parameters of African freshwater catfish, Clarias gariepinus. Ethical permission was taken from the IAEC, and the experiment was conducted according to the CPCSEA guidelines for animal handling. During this study, fish were divided into three groups. The first group served as a control, the second group was treated with a low dose (400µg/L) of malathion, and the third group was treated with a high dose (800µg/L) of malathion for 10 days. The results of the study exhibited alterations in the biochemical parameters and histopathology of the liver. Biochemical constituents such as protein and carbohydrate concentration in the liver of fish treated with 400µg/L and 800µg/L of malathion decreased as compared to the control. The histopathological structure of the liver exposed to 400µg/L malathion for 10 days indicated toxic lesions such as enucleated hepatocytes, degeneration of the central vein, infiltration of erythrocytes, and pycnotic nuclei, whereas the liver exposed to 800µg/L malathion for 10 days showed irregular-shaped hepatocytes, binucleated hepatocytes, melanomacrophage necrosis, reduced central vein, and sinusoidal dilation. Thus, it may be concluded that malathion significantly altered the biochemical constituents of the liver and deteriorated the histological structure, which in turn altered the metabolic functions of the liver. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the leading causes of death in which the molecular tumorigenesis and cellular heterogeneity are poorly understood. The genetic principle that specific driver mutations in oncogenes, DNA repair genes, and tumor-suppressor genes can independently drive cancer development has been widely explored. Additionally, a repertory of harmful epigenetic modifications in DNA and chromatin—impacting the expression of genes involved in cellular proliferation, differentiation, genome stability, cell-cycle control, and DNA repair—are now acknowledged across various biological contexts that contribute to cancer etiology. Notably, the dynamic hypermethylation and hypomethylation in enhancer and promoter regions that promote activation or silencing of the master regulatory genes of the epigenetic programs is often altered in tumor cells due to mutation. Genome instability is one of the cancer hallmarks that contribute to transdifferentiation and intratumoral heterogeneity. Thus, it is broadly accepted that tumor tissue is dominated by genetically and epigenetically distinct sub-clones which display a set of genetic and epigenetic mutations. Here we summarize some functions of key genetic and epigenetic players and biochemical pathways leading to liver cell transformation. We discuss the role of the potential epigenetic marks in target genes thought to be involved in sequential events following liver lipid metabolism dysregulation, inflammation, fibrosis, cirrhosis, and finally hepatocellular carcinoma. We also briefly describe new findings showing how epigenetic drugs together with chemotherapy and immunotherapy can improve overall responses in patients with hepatic tumors. [ABSTRACT FROM AUTHOR]

Background: Creating a model for acute liver failure in animal models is essential for research on liver regeneration and cancer. Current surgical techniques allow for a maximum of 80% partial hepatectomy in rats, with low survival rates due to poor inflow control. The common resection technique involves ligation at the liver lobe neck, causing peri-operative blood loss and postoperative blood loss. Methods: A 90% partial hepatectomy was performed on 5 rats using a bile duct-saving portal ligation technique, involving two hilum dissections for bile duct preservation. The first dissection controlled the blood supply to the median and left lateral lobes, and the second to the right inferior and superior lobes. Before closing, all rats were given 5 mL of 10% dextrose intraperitoneally and had access to ClearH2O DietGel Recovery and 20% dextrose. Weight and behavior were closely monitored for seven days post-operatively. Results: This method resulted in 100% survival, with a 3.1% increase in liver mass and 12.3% increase in liver-to-body mass ratio. Conclusions: This technique is the first bile duct-saving portal ligation for rodent models of acute liver failure, with long-term survival and complete hepatic regeneration. Our procedure offers a viable 90% hepatectomy model for research with improved survival and regeneration outcomes. [ABSTRACT FROM AUTHOR]

In vivo genome editing holds great therapeutic potential for treating monogenic diseases by enabling precise gene correction or addition. However, improving the efficiency of delivery systems remains a key challenge. In this study, we investigated the use of lipid nanoparticles (LNPs) for in vivo knock-in of ectopic DNA. Our in vitro experiments demonstrated that the homology-independent targeted integration (HITI)-mediated genome-editing method achieved significantly higher knock-in efficiency at the Alb locus in hepatic cells compared to the traditional homology-directed repair (HDR)-mediated approach. By optimizing LNP composition and administration routes, we successfully achieved HITI-mediated GFP knock-in (2.1–2.7%) in the livers of mice through intravenous delivery of LNP-loaded genome editing components. Notably, repeated intravenous dosing led to a twofold increase in liver GFP knock-in efficiency (4.3–7.0%) compared to a single dose, highlighting the potential for cumulative genome editing effects. These findings provide a solid foundation for the use of LNPs in in vivo knock-in strategies, paving the way for future genome-editing therapies. [ABSTRACT FROM AUTHOR]

Perfluorooctane sulfonate (PFOS) is one of the most widely used perfluorinated compounds, and as an environmental endocrine disruptor and environmental persistent pollutant, the threat of PFOS to human health is of increasing concern. Exposure to PFOS has been shown to be closely associated with liver disease, but the intrinsic molecular targets and mechanisms of PFOS-induced liver damage are not well understood. This study was conducted to explore whether the Wnt/β-Catenin signaling pathway and the endoplasmic reticulum stress signaling pathway are involved in damage of PFOS to the liver. In this study, we used the CCK-8 method to detect cell viability, a microscope and DAPI staining to observe cell morphology, flow cytometry to detect cell ROS and apoptosis levels; and Western blot to detect the expressions of proteins in the WNT/β-Catenin, endoplasmic reticulum stress and apoptosis-related pathways. We found that PFOS activated WNT/β-Catenin and endoplasmic reticulum stress-related pathways in L-02 cells and could lead to the development of oxidative stress and apoptosis. Our findings showed that PFOS could cause damage to L-02 cells, and the WNT/β-Catenin signaling and endoplasmic reticulum stress pathways were involved in the changes caused by PFOS to L-02 cells, which provided a new theoretical basis for studying the hepatotoxicity and mechanism of PFOS. PFOS can lead to increased intracellular ROS levels, causing oxidative stress, endoplasmic reticulum stress and activation of the WNT/β-catenin signaling pathway. Our experimental results showed that PFOS can cause damage to L-02 cells, and the WNT/β-Catenin signaling pathway and endoplasmic reticulum stress pathway are involved in the process of damage caused by PFOS to L-02 cells. [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]

Background: A PBPK model allows the prediction of the concentration of drug amounts in different tissues and organs over time and can be used to simulate and optimize different therapeutic protocols in healthy and sick individuals. The objective of this work was to create a PBPK model to predict propofol doses for healthy canines and canines with hepatic impairment. Methods: The study methodology was divided into two major phases, in which the first phase consisted of creating the PBPK model for healthy canines, and in the second phase, this model was adjusted for canines with hepatic impairment. The model for healthy canines presented good predictive performance, evidenced by the value of the performance measure of the geometric mean fold error that ranged from 0.8 to 1.25, meeting the double error criterion. The simulated regimen for healthy canines, i.e., of 5 mg/kg (administered as a bolus) followed by a continuous infusion at a rate of 0.13 mg/kg/min, was sufficient and ensured that all simulated subjects achieved the target plasma concentration. Canines with 60% and 40% liver function had infusion rate adjustments to ensure that individuals did not exceed the therapeutic window for maintenance of anesthesia. Results: The results presented in this manuscript are suggestive of the effectiveness and practicality of a PBPK model for propofol in canines, with a particular focus on hepatic impairment. [ABSTRACT FROM AUTHOR]

Background and Purpose: We investigated the effectiveness of Vaccinium arctostaphylos L. fruit extract (VAFE) in protecting hepatocytes against N -diethylnitrosamine (DEN)-related hepatocellular carcinoma (HCC) by exploring its impact on biochemical, molecular, and antioxidant pathways, as well as its role in regulating the HOTAIR/miR-124/Notch1 axis pathway. Materials and Methods: In the present study, 50 Wistar rats in 5 groups (n = 10/group) of normal, HCC (80 mg/kg DEN), HCC rats receiving 200 and 400 mg/kg DEN + VAFE, and normal rats receiving 400 mg/kg VAFE were divided. The serum concentrations of liver function indices (bilirubin, total protein, albumin, alanine aminotransferase, aspartate aminotransferase, C-reactive protein, and alkaline phosphatase), inflammatory cytokines (interleukin (IL)-1β, IL-10, tumor necrosis factor-α, and IL-6) and oxidants parameters (catalase, superoxide dismutase, and glutathione peroxidase enzyme activity and nitric oxide levels) were measured. Liver tissue HOTAIR, miR-124, Notch1, and Jagged1 genes and proteins were measured. p53-positive cells of liver hepatocytes were evaluated by immunohistochemical technique. Results: DEN induced significant changes in body and liver weight, serum liver enzymes, antioxidant levels, inflammatory markers, and HOTAIR/miR-124/Notch1 axis genes/proteins expression related to liver pathways. VAFE demonstrated dose-dependent effects in countering these changes, significantly improving weight, liver health, antioxidant capacity, and inflammatory responses, especially at 400 mg/kg. The histopathological evaluation showed improvements in liver tissue structure with VAFE treatment. Conclusion: Overall, our study demonstrates the administration of VAFE can anticancer effects of DEN-induced HCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Contrary to the traditional theory of streamline flow in the portal vein, our meta-analysis showed that regardless of the primary location of the tumor, metastases preferentially migrate to the right lobe of the liver. This can be attributed, according to recent breakthroughs in blood hydrodynamics, to the blood flow being physiologically turbulent, the Taylor's dispersion phenomenon, or to the complicated role of circulating tumor cells, as well as the more well-established difference in the volume and mass ratios among the two lobes, the difference of blood flow per minute between them, and various anatomical reasons. Background: The "streamline flow" of the portal vein (PV) is a controversial yet well-known theory presented almost 125 years ago. It states that blood from the superior mesenteric vein (SMV) goes preferentially to the right liver lobe, while splenic and inferior mesenteric veins divert blood predominantly to the left lobe, affecting this way the metastatic distribution of colorectal cancer (CRC). The aim of this systematic review is to assess its validity by examining and combining all the relevant literature with a critical eye. Materials and methods: This study constitutes a systematic review of the literature and adheres to all PRISMA system criteria. Three search engines (PubMed, Google Scholar, and the Cochrane Library) were used, and 11 out of 435 studies between 1984 and 2024 were finally included in this meta-analysis. All statistical analysis was conducted using RevMan Web, Version: 7.12.0, and Jamovi v 2.3.260 software. Results: The meta-analysis revealed that regardless of the primary location of the tumor, the metastases preferentially migrate to the right lobe due to various possible reasons. The prevalence of metastases from right colon cancer to the right liver lobe was 75%, while the prevalence of left colon cancer metastases to the right lobe was 68%. This difference was not found statistically significant. Conclusions: The theory has been proven inaccurate, at least from the perspective of the origin-associated distribution of CRC metastases in the liver lobes, and therefore bears no clear predictive value. Further research under different perspectives is essential for determining more definite conclusions. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is defined as a clinical syndrome characterized by excessive fat accumulation in liver, predominantly influenced by dietary choices. This study provides an extensive quantitative literature analysis on dietary influences on NAFLD. Bibliometric data were collected through the search string TOPIC = ("NAFLD*" OR "nonalcoholic fatty liver*" OR "non-alcoholic fatty liver*") AND TOPIC = ("diet*" OR "nutrition*" OR "food*" OR "feed*"), which yielded 12,445 publications indexed within the Web of Science Core Collection. Utilizing VOSviewer software, term maps were generated to visually illustrate recurring phrases alongside citation data. The literature, which has seen exponential growth since the 2010s, predominantly consists of original articles, with a ratio of 4.7:1 compared to reviews. Notably, the significant contributors to this field were China and the United States. The majority of publications were found journals specialized in Gastroenterology & Hepatology, Nutrition & Dietetics, Biochemistry & Molecular Biology, Endocrinology & Metabolism, and Pharmacology & Pharmacy. Key dietary compounds/compounds classes such as resveratrol, polyphenols, curcumin, berberine, quercetin, flavonoids, omega-3 fatty acids, docosahexaenoic acid (DHA), genistein, and palmitic acid were frequently mentioned and cited. Many of them were demonstrated to have some potential benefits on NAFLD, both in human and animal studies. [ABSTRACT FROM AUTHOR]

Carcinoid heart disease (CaHD) is an important complication among patients with metastatic neuroendocrine tumors and carcinoid syndrome (CS). CS patients (25%-65%) eventually develop CaHD; these patients face a significantly increased risk of morbidity and mortality. Guidance papers (eg, clinical practice guidelines, consensus guidelines, and expert statements) have been established by major organizations across the disciplines of cardiology and oncology; however, these recommendations are not routinely implemented. The aim of this article is to encourage the integration of current recommendations from national societies into clinical practice. Early screening upon recognition of CS and prior to the development of CaHD symptoms is paramount, as no existing therapies are approved to reverse the fibrotic damage to the heart once it occurs. Valvular replacement is the only definitive treatment for CaHD once it has developed. When patients are noted to have urinary 5-hydroxyindoleacetic acid (5-HIAA) levels ≥300 µmol/24 h and/or serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels >260 pg/mL, echocardiography is recommended. Systemic approaches to control tumor growth and hormonal secretion include somatostatin analogs (SSAs), followed by options including peptide receptor radiotherapy (PRRT), everolimus and liver embolization. Telotristat is the primary choice for control of diarrhea refractory to SSA. Diuretics are the mainstay of heart failure symptom management for patients who develop CaHD. Considerations for future research are discussed, including the ongoing TELEHEART (TELotristat Ethyl in a HEART biomarker study) trial involving telotristat and not yet activated CHARRT (Carcinoid Heart disease And peptide Receptor Radiotargetted Therapy) study involving PRRT with lutetium 177 (177Lu) dotatate. [ABSTRACT FROM AUTHOR]

The Deadly Liver Mob (DLM) is a peer-delivered incentivised health promotion program by and for Aboriginal and Torres Strait Islander Australians, and was introduced in response to the disproportionate number of Aboriginal and Torres Strait Islander Australians who are impacted by blood borne viruses (BBVs) and sexually transmitted infections (STIs). The goal of the program is to increase access to BBV and STI education, screening, treatment, and vaccination in recognition and response to the systemic barriers that Aboriginal and Torres Strait Islander peoples face in accessing health care. This commentary introduces a series of papers that report on various aspects of the evaluation of the Deadly Liver Mob (DLM) program. In this paper, we explain what DLM is and how we constructed an evaluation framework for this complex health promotion intervention. [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]

Background: Liver diseases are constantly increasing throughout the world and are often associated with other diseases, but above all they are caused by improper diet. Adherence to a diet with abundant vegetables has now been widely demonstrated to be important in combating this pathological condition. The aim of this study was to explore the protective role of lycopene (LYC) extracts from cooked and fresh tomato. Methods: The study cohort included 969 participants assessed in the NUTRIHEP cohort (2005–2006) and the associated follow-up (2014–2016), divided into two groups, based on liver condition: NAFLD, or AFLD and FLD. Results: The results indicated a statistical significance of LYC consumption, showing a protective role against liver disease, the best concentration being 9.50 mg/die, with an RR value of 0.59, p = 0.01, 0.39 to 0.90 at 95% C.I., and RRR = 0.40, p = 0.002, 0.22 to 0.71 at 95% C.I. Conclusions: The protective role of LYC extracts from tomato has not been amply demonstrated in humans. We conclude that this is one of the few papers in the literature to evaluate the protective effect of LYC against liver disease, as well as how this molecule could be used in future possible treatments. Utilizing lycopene as a supplement alone or in combination with other foods could be useful for developing treatments with reduced contraindications. [ABSTRACT FROM AUTHOR]

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

Transplantation is currently the only effective treatment for patients with end-stage liver failure. In recent years, many advanced studies have been conducted to improve the efficiency of organ preservation techniques. Modifying the composition of the preservation fluids currently used may improve graft function and increase the likelihood of transplantation success. The modified fluid is expected to extend the period of safe liver storage in the peri-transplantation period and to increase the pool of organs for transplantation with livers from marginal donors. This paper provides a literature review of the effects of antioxidants on the efficacy of liver preservation fluids. Medline (PubMed), Scopus, and Cochrane Library databases were searched using a combination of MeSH terms: "liver preservation", "transplantation", "preservation solution", "antioxidant", "cold storage", "mechanical perfusion", "oxidative stress", "ischemia-reperfusion injury". Studies published up to December 2023 were included in the analysis, with a focus on publications from the last 30 years. A total of 45 studies met the inclusion criteria. The chemical compounds analyzed showed mostly bioprotective effects on hepatocytes, including but not limited to multifactorial antioxidant and free radical protective effects. It should be noted that most of the information cited is from reports of studies conducted in animal models, most of them in rodents. [ABSTRACT FROM AUTHOR]

Multiple recurrent genetic and epigenetic aberrations have been associated with worse prognosis in multiple studies of neuroendocrine tumours (NETs), but these have been mainly small cohorts and univariate analysis. This review and meta‐analysis will focus upon the literature available on NETs of the gastrointestinal (GI) tract, liver, biliary tract and pancreas. PubMed and Embase were searched for publications that investigated the prognostic value of (epi)genetic changes of neuroendocrine tumours. A meta‐analysis was performed assessing the association of the (epi)genetic alterations with overall survival (OS), disease‐free survival (DFS) or locoregional control (LRC). In the pancreas DAXX/ATRX [hazard ratio (HR) = 3.29; 95% confidence interval (CI) = 2.28–4.74] and alternative lengthening telomeres (ALT) activation (HR = 8.20; 95% CI = 1.40–48.07) showed a pooled worse survival. In the small bowel NETs gains on chromosome 14 were associated with worse survival (HR 2.85; 95% CI = 1.40–5.81). NETs from different anatomical locations must be regarded as different biological entities with diverging molecular prognosticators, and epigenetic changes being important to the pathogenesis of these tumours. This review underpins the prognostic drivers of pancreatic NET which lie in mutations of DAXX/ATRX and ALT pathways. However, there is reaffirmation that prognostic molecular biomarkers of small bowel NETs should be sought in copy number variations (CNVs) rather than in single nucleotide variations (SNVs). This review also reveals how little is known about the prognostic significance of epigenetics in NETs. [ABSTRACT FROM AUTHOR]

The present study was conducted on a fertile eggs of total number 200 of broiler Ross 308 from 31weeks laying flock, their weight ranged from (49.2-58.9gm). The eggs were inserted to an automatic incubator according to standard procedures (37.5 of temperature and 60% of RH). Eggs were candled and un fertilized eggs were removed at day 6 of incubation. At the same day of injection, the remaining were randomly subdivided into 3 groups at incubator each set contain 60 egg. Solutions for injection were freshly prepared at the same day of injection; ascorbic acid was dissolved at physiological saline 0.9 % then fertilized with 0.22Mm filter paper and subsequently placed in incubator 2 hours before injection. The three groups were: non-injected control group (negative control), saline group injected with 0.6 ml of physiologic al isotonic saline (0.9%), and Ascorbic acid injected group (3 mg of pure ascorbic acid with 0.6ml of physiological saline). Histological examination of Ascorbic acid group showed highlighting typical structure of hepatic tissue with intact central vein endothelial lining, highlighting obvious regular organization of muscle fibers with multinucleated light vesicular & elongated peripheral nuclei, highlighting obvious improvement along intestinal tissue structure with increasing in intestinal villi length with significant difference than control negative group as well as control positive group. Hatchability percentage noted better in ascorbic group than other groups. Also, platelet count, White blood cells count, monocyte level was better in ascorbic group. [ABSTRACT FROM AUTHOR]

Living Donor Liver Transplantation (LDLT) is a promising approach to treating end-stage liver diseases, however, some post-operatory complications such as pneumonia, bacteremia, urinary tract infections, and hepatic dysfunction have been reported. In murine models using partial hepatectomy (PHx), a model that emulates LDLT, it has been determined that the synthesis of hepatic cell proliferation factors that are associated with noradrenaline synthesis are produced in locus coeruleus (LC). In addition, studies have shown that PHx decreases GABA and 5-HT2A receptors, promotes loss of dendritic spines, and favors microgliosis in rat hippocampus. The GABA and serotonin-altered circuits suggest that catecholaminergic neurons such as dopamine and noradrenaline neurons, which are highly susceptible to cellular stress, can also be damaged. To understand post-transplant affections and to perform well-controlled studies it is necessary to know the potential causes that explain as a liver surgical procedure can produce brain damage. In this paper, we review several cellular processes that could induce gliosis in LC after rat PHx. [ABSTRACT FROM AUTHOR]

Malignant focal liver lesions (FLLs) represent various kinds of epithelial and mesenchymal tumors. In pediatric patients, the understanding of pediatric liver diseases and associated imaging manifestations is essential for making accurate diagnosis and differential diagnosis. This paper will discuss the latest knowledge of the common pediatric malignant FLLs, including undifferentiated embryonal sarcoma, rhabdomyosarcoma, epithelioid hemangioendothelioma, angiosarcoma, and malignant rhabdoid tumor. Medical imaging features are not only helpful for clinical diagnosis, but can also be useful in the evaluation and follow-up of pre- and post-treatment. The future perspectives of contrast-enhanced ultrasound (CEUS) enhancement patterns of FLLs in pediatric patients are also mentioned. [ABSTRACT FROM AUTHOR]

Malignant focal liver lesions (FLLs) are commonly reported in adults but rarely seen in the pediatric population. Due to the rarity, the understanding of these diseases is still very limited. In children, most malignant FLLs are congenital. It is very important to choose appropriate imaging examination concerning various factors. This paper will outline common pediatric malignant FLLs, including hepatoblastoma, hepatocellular carcinoma, and cholangiocarcinoma and discuss them against the background of the latest knowledge on comparable/similar tumors in adults. Medical imaging features are of vital importance for the non-invasive diagnosis and follow-up of treatment of FLLs in pediatric patients. The use of CEUS in pediatric patients for characterizing those FLLs that remain indeterminate on conventional B mode ultrasounds may be an effective option in the future and has great potential to be integrated into imaging algorithms without the risk of exposure to ionizing radiation. [ABSTRACT FROM AUTHOR]

This technical paper introduces a novel organ preservation system based on isochoric (constant volume) supercooling. The system is designed to enhance the stability of the metastable supercooling state, offering potential long-term preservation of large biological organs at subfreezing temperatures without the need for cryoprotectant additives. Detailed technical designs and usage protocols are provided for researchers interested in exploring this field. The paper also presents a control system based on the thermodynamics of isochoric freezing, utilizing pressure monitoring for process control. Sham experiments were performed using whole pig liver sourced from a local food supplier to evaluate the system's ability to sustain supercooling without ice nucleation for extended periods. The results demonstrated sustained supercooling without ice nucleation in pig liver tissue for 24 and 48 h. These findings suggest the potential of this technology for large-volume, cryoprotectant-free organ preservation with real-time control over the preservation process. The simplicity of the isochoric supercooling device and the design details provided in the paper are expected to serve as encouragement for other researchers in the field to pursue further research on isochoric supercooling. However, final evidence that these preserved organs can be successfully transplanted is still lacking. [ABSTRACT FROM AUTHOR]

Celery juice use is a trend all over the world, acclaimed with healing effects from acne, to autoimmune diseases. The paper aims to show the effect of celery juice for weight loss and liver cleansing, starting from the healing effect of acne and autoimmune diseases. The best way to detox was 3-6-9 which is segmented into 1-3 days, 4-6 days, and 7-9 days, where each part strictly follows the diet regime, and the 9th day is all liquids. The goal of detoxification is to cleanse the liver and increase the body's energy levels. This review examines whether detox diets are necessary, their content and effectiveness. This paper was based on a 9-day clinical trial with healthy adult volunteers to evaluate the effects of celery juice, including 28 volunteers, 17 men and 11 women aged 29 - 61 years. Participants answered a questionnaire, which was used to assess their usual daily nutrient intake and body toxicity. The questionnaire also contained questions about their: gender, age, height and weight, pulse, arm circumference of the respondents. Inclusion criteria were gender, age over 20 years. For 9 days, subjects were served intermittent meals. Blood samples were taken from participants before the first meal and after the detox cleansing. Body weight and arm circumference, blood pressure and pulse of the participants were measured. The meals and celery juice were all prepared and served according to guidelines recommended by Celery Juice Medicine, which uses a fat-free, gluten-free, eggfree celery seed detox formula, according to Medical Medium platform. The whole detox was divided into 3-6-9 days for 9 days. Blood samples were analyzed for bilirubin level with (bilirubin blood test-method), alanine-transaminase (ALT) level with serum-glutamic-pyruvic-transaminasemethod, and aspartate-aminotransferase (AST) level with serum-glutamic-oxaloacetic-transaminase - SGOT test method. In this study, after detoxing celery, 89% of participants had lower levels of bilirubin, ALT and AST in their blood, and 81% had weight loss. After the detox, blood analyses showed a significant improvement of health, especially in the liver/hepatic profile, the detoxification diet has an influence on weight loss, and it has been proven effective in removing toxins from the body and improving health in general. The tendency toward improvement in liver detoxification measures is consistent with the hypothesis that improved liver detoxification capacity may contribute to well-being. It is important that the next studies concentrate on other therapeutic and industrial attributes of celery. [ABSTRACT FROM AUTHOR]

Simple Summary: Most of the existing data on the resection of liver metastases with inferior vena cava infiltration come from case reports or small case series. This systematic review on the subject found postoperative morbidity and mortality rates and overall survival to be acceptable, offering a surgical alternative to these patients previously considered unresectable. Combined hepatic and inferior vena cava (IVC) resection is the only potentially curative treatment for patients with colorectal liver metastases (CRLM) involving the IVC. Most of the existing data come from case reports or small case series. In this paper, a systematic review based on the PICO strategy was performed in accordance with the PRISMA statement. Papers from January 1980 to December 2022 were searched in Embase, PubMed, and the Cochrane Library databases. Articles considered for inclusion had to present data on simultaneous liver and IVC resection for CRLM and report surgical and/or oncological outcomes. From a total of 1175 articles retrieved, 29, including a total of 188 patients, met the inclusion criteria. The mean age was 58.3 ± 10.8 years. The most frequent techniques used were right hepatectomy ± caudate lobe for hepatic resections (37.8%), lateral clamping (44.8%) for vascular control, and primary closure (56.8%) for IVC repair. The thirty-day mortality reached 4.6%. Tumour relapse was reported in 65.8% of the cases. The median overall survival (OS) was 34 months (with a confidence interval of 30–40 months), and the 1-year, 3-year, and 5-year OS were 71.4%, 19.8%, and 7.1%, respectively. In the absence of prospective randomized studies, which are difficult to perform, IVC resection seems to be safe and feasible. [ABSTRACT FROM AUTHOR]

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]

Human liver organoids (HLOs) hold significant potential for recapitulating the architecture and function of liver tissues in vivo. However, conventional culture methods of HLOs, forming Matrigel domes in 6-/24-well plates, have technical limitations such as high cost and low throughput in organoid-based assays for predictive assessment of compounds in clinical and pharmacological lab settings. To address these issues, we have developed a unique microarray 3D bioprinting protocol of progenitor cells in biomimetic hydrogels on a pillar plate with sidewalls and slits, coupled with a clear bottom, 384-deep well plate for scale-up production of HLOs. Microarray 3D bioprinting, a droplet-based printing technology, was used to generate a large number of small organoids on the pillar plate for predictive hepatotoxicity assays. Foregut cells, differentiated from human iPSCs, were mixed with Matrigel and then printed on the pillar plate rapidly and uniformly, resulting in coefficient of variation (CV) values in the range of 15–18%, without any detrimental effect on cell viability. Despite utilizing 10–50-fold smaller cell culture volume compared to their counterparts in Matrigel domes in 6-/24-well plates, HLOs differentiated on the pillar plate exhibited similar morphology and superior function, potentially due to rapid diffusion of nutrients and oxygen at the small scale. Day 25 HLOs were robust and functional on the pillar plate in terms of their viability, albumin secretion, CYP3A4 activity, and drug toxicity testing, all with low CV values. From three independent trials of in situ assessment, the IC50 values calculated for sorafenib and tamoxifen were 6.2 ± 1.6 μM and 25.4 ± 8.3 μM, respectively. Therefore, our unique 3D bioprinting and miniature organoid culture on the pillar plate could be used for scale-up, reproducible generation of HLOs with minimal manual intervention for high-throughput assessment of compound hepatotoxicity. [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]

An abdominal Computed Tomography (CT) scan gives more information about diseases of the liver, gallbladder, and biliary tract. In the image processing approach, liver segmentation is an essential step to be done before liver lesion detection. Liver segmentation removes the unwanted regions from the CT image and makes the task of lesion detection easier. In this paper, a novel Morph-Rec model based on morphological reconstruction operation is proposed for liver segmentation from CT images. The proposed work is focused on segmenting the liver region from the CT slices irrespective of the size and shape of the liver region. The proposed model is validated on 2650 CT slices of 120 and 20 CT scans from the LITS and 3DIRCADb datasets, respectively. The proposed Morph-Rec method is evaluated using metrics such as dice score, accuracy, F1 score, Jaccard index and Matthew's correlation coefficient. To justify the adaptability and efficiency of the proposed model, it is also validated on 50 CT slices of nine CT scans provided by a local scan centre. The proposed method has produced excellent results on all metrics and the obtained results are better than the state-of-the-art conventional methods for liver segmentation. Hence, the proposed technique is an automatic and dataset-generic model that can perform liver segmentation precisely on any CT acquisition of the liver. [ABSTRACT FROM AUTHOR]

Schisandra chinensis (S. chinensis) has a long history as a traditional Chinese medicine that is astringent, beneficial to vital energy, tonifies the kidney, tranquilizes the heart, etc. Significantly, Schisandrol A (SA) is extracted from S. chinensis and shows surprising and satisfactory biological activity, including anti-inflammatory, hepatoprotective, cardiovascular protection, and antitumor properties, among others. SA has a more pronounced protective effect on central damaged nerves among its numerous pharmacological effects, improving neurodegenerative diseases such as Alzheimer's and Parkinson's through the protection of damaged nerve cells and the enhancement of anti-oxidant capacity. Pharmacokinetic studies have shown that SA has a pharmacokinetic profile with a rapid absorption, wide distribution, maximal concentration in the liver, and primarily renal excretion. However, hepatic and intestinal first-pass metabolism can affect SA's bioavailability. In addition, the content of SA, as an index component of S. chinensis Pharmacopoeia, should not be less than 0.40%, and the content of SA in S. chinensis compound formula was determined with the help of high-performance liquid chromatography (HPLC), which is a stable and reliable method, and it can lay a foundation for the subsequent quality control. Therefore, this paper systematically reviews the preparation, pharmacological effects, pharmacokinetic properties, and content determination of SA with the goal of updating and deepening the understanding of SA, as well as providing a theoretical basis for the study of SA at a later stage. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyse papers describing the use of Electrochemotherapy (ECT) in local treatment of primary and secondary liver tumours located at different sites and with different histologies. Other Local Ablative Therapies (LAT) are also discussed. Analyses of these papers demonstrate that ECT use is safe and effective in lesions of large size, independently of the histology of the treated lesions. ECT performed better than other thermal ablation techniques in lesions > 6 cm in size and can be safely used to treat lesions distant, close, or adjacent to vital structures. ECT spares vessel and bile ducts, is repeatable, and can be performed between chemotherapeutic cycles. ECT can fill the gap in local ablative therapies due to being lesions too large or localized in highly challenging anatomical sites. [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]

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: This study investigated the potential link between serum klotho levels and cognitive function in patients with non-alcoholic fatty liver disease (NAFLD). Materials and Methods: Utilizing NHANES data from 2011 to 2014, the research included 356 eligible participants. NAFLD was identified with the United States Fatty Liver Index (US-FLI), and cognition was measured by various tests including the Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST), Immediate Recall Test (IRT), and Delayed Recall Test (DRT). Weighted logistic regression and restricted cubic splines were employed to analyze the relationship between klotho levels and cognitive scores. Results: A significant nonlinear association was observed between klotho levels and the performance in DSST and Delayed Recall Test (DRT). After controlling for confounding factors, the study found a positive association between higher serum klotho levels and improved cognitive performance in both AFT and DSST. However, there was no significant relationship between klotho levels and the IRT or DRT, regardless of whether the natural logarithm or quartile was considered. Discussion: The findings suggest that a higher serum klotho level may be positively correlated with better cognitive performance in NAFLD patients. [ABSTRACT FROM AUTHOR]

The effect of dark deprivation on the morphofunctional state and rhythmostasis of the liver under CCl4 toxic exposure has been studied. The relevance of this study is due to the fact that the hepatotoxic effect of carbon tetrachloride on the liver is well studied, but there are very few data on the relationship between CCl4 intoxication and circadian biorhythms, and most of the studies consider the susceptibility of the organism in general and of the liver in particular to the influence of CCl4 in some separate periods of the rhythm, but not the influence of this chemical agent on the structure of the whole rhythm. In addition, earlier studies indicate that light disturbance causes certain changes in the morphofunctional state of the liver and the structure of the circadian rhythm of a number of parameters. As a result of this study, we found that the effect of CCl4 in conditions of prolonged dark deprivation causes more significant structural and functional changes in hepatocytes, as well as leading to significant changes in the circadian rhythms of a number of parameters, which was not observed in the action of CCl4 as a monofactor. We assume that the severity of structural and functional changes is due to the light-induced deficiency of melatonin, which has hepatoprotective properties. Thus, the mechanisms of CCl4 action on CRs under conditions of light regime violations leave a large number of questions requiring further study, including the role of melatonin in these processes. [ABSTRACT FROM AUTHOR]

Δ9-Tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis which is being increasingly consumed by pregnant people. In humans, THC is sequentially metabolized in the liver to its circulating metabolites 11-hydroxy-THC (11-OH-THC, psychoactive) and 11-nor-9-carboxy-THC (THC-COOH, non-psychoactive). Human and macaque data show that fetal exposure to THC is considerably lower than the corresponding maternal exposure. Through perfused human placenta studies, we showed that this is due to the active efflux of THC (fetal-to-maternal) by a placental transporter(s) other than P-glycoprotein or breast cancer resistance protein. The identity of this placental transporter(s) as well as whether THC or its metabolites are substrates or inhibitors of hepatic solute carrier transporters is unknown. Therefore, we investigated whether 5 μM THC, 0.3 μM 11-OH-THC, and 2.5 μM THC-COOH are substrates and/or inhibitors of placental or hepatic solute carrier transporters at their pharmacologically relevant concentrations. Using HEK cells overexpressing human OATP1B1, OATP1B3, OATP2B1, OCT1, OCT3, OAT2, OAT4, or NTCP, and prototypic substrates/inhibitors of these transporters, we found that THC and THC-COOH were substrates but not inhibitors of OCT1. THC-COOH was a weak substrate of OCT3 and a weak inhibitor of OAT4. THC, 11-OH-THC, and THC-COOH were found not to be substrates/inhibitors of the remaining transporters investigated. [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]

Non-alcoholic fatty liver disease (NAFLD) is the fastest-growing cause of liver-associated death globally. Whole-body knockout (KO) of Na+/H+ exchanger 1 (NHE1, SLC9A1) was previously proposed to protect against high-fat diet-induced liver damage; however, mechanistic insight was lacking. The aim of the present work was to address this question in vitro to determine how NHE1, specifically in hepatocytes, impacts lipid overload-induced inflammation, fibrosis, and hepatocyte--hepatic stellate cell (HSC) crosstalk. We induced palmitate (PA)-based steatosis in AML12 and HepG2 hepatocytes; manipulated NHE1 activity pharmacologically and by CRISPR/Cas9-mediated KO and overexpression; and measured intracellular pH (pHi), steatosis-associated inflammatory and fibrotic mediators, and cell death. PA treatment increased NHE1 mRNA levels but modestly reduced NHE1 protein expression and hepatocyte pHi. NHE1 KO in hepatocytes did not alter lipid droplet accumulation but reduced inflammatory signaling (p38 MAPK activity), lipotoxicity (4-HNE accumulation), and apoptosis (poly-ADP-ribose-polymerase-1 (PARP) cleavage). Conditioned medium from PA-treated hepatocytes increased the expression of NHE1 and of the fibrosis regulator tissue inhibitor of matrix metalloproteinases-2 in LX-2 HSCs, in a manner abolished by NHE1 KO in hepatocytes. We conclude that NHE1 is regulated in NAFLD in vitro and contributes to the ensuing damage by aggravating hepatocyte injury and stimulating hepatocyte--HSC crosstalk. [ABSTRACT FROM AUTHOR]

Background: Primary hepatic Neuroendocrine carcinoma (PHNEC) is exceptionally rare, and when it cannot be surgically removed locally, systemic combination therapy is the preferred treatment. However, current treatments have shown limited effectiveness, and more effective approach remains a matter of debate. Case Presentation: We present a case involving a female patient diagnosed with non-surgically suitable PHNEC, confirmed through pathology. Following four cycles of standard first-line systemic chemotherapy, this intervention was prompted by imaging indicating suboptimal local lesion control, the patient underwent localized interventional and microwave ablation therapy. Subsequently, an evaluation based on mRECIST criteria revealed complete remission post-procedure. The disease sustained this remission status throughout the 14-month follow-up, with the administration of 14 cycles of immunocheckpoint inhibitor maintenance therapy, showing no signs of local recurrence or distant metastasis and devoid of any associated complications. Conclusion: This case introduces a novel therapeutic avenue for individuals who are ineligible for surgery and have not responded to systemic chemotherapy. The diagnosis and management of PHNEC are deliberated within the framework of this particular case. [ABSTRACT FROM AUTHOR]

Objective(s): Gestational diabetes mellitus (GDM), one of the most common metabolic disorders in pregnancy, impacts maternal and fetal health. This study was designed to assess the effects of mild GDM on the histology, ultrastructure, and morphometry of fetal liver tissue. Materials and Methods: In this experimental study, twenty pregnant rats were randomly allocated into control and streptozotocin (STZ)-induced diabetic groups. Mild hyperglycemia was induced by intraperitoneal injection of STZ (40 mg/kg/bw) on the 5th day of gestation. At day 19 of gestation, fetal livers were separated and subjected to histological, transmission electron microscopic, and quantitative morphometric examinations. Results: In the GDM group, PAS staining was positive, revealing scattered eosinophilic inclusions in some hepatocytes. Masson trichrome staining was also positive and showed some fibrous tissue as fine fibers in the portal spaces that extended to the central vein. Reticulin staining in the GDM group was focally positive in the areas of fibrosis and the portal spaces. Ultrastructural examination showed pyknotic nuclei, karyolysis, degranulation and vesiculation of the rough endoplasmic reticulum, and degeneration of mitochondria in the GDM group. The morphometric examination demonstrated that the mean area of hepatocytes was significantly lower in the GDM group than in the control group (P<0.05). Moreover, the mean diameter of the central vein and the density of megakaryocytes were significantly higher in the GDM group than in the control group (P<0.05). Conclusion: Uncontrolled mild GDM induced the histological, ultrastructural and morphometric alterations in the fetal liver. [ABSTRACT FROM AUTHOR]

Context. The genotype of laying hens is one of the most important factors influencing their carcass composition and anatomical features. Aims. The aim of the present study was to compare two genotypes of laying hens, Lohmann Brown and Lohmann White, after the laying period. Methods. The experimental material consisted of 26 carcasses obtained after slaughtering spent laying hens at the age of 83 weeks. Key results. The genotype of the birds had a significant (P < 0.05) effect on carcass weight, and the proportion (%) of the breast muscle, leg muscle and gizzard weight. Significant correlations were also found between bodyweight and the weight of the stomach, proventriculus, liver and spleen. The origin of the laying hens also had a significant impact on the length of the sections on intestinal segments, namely, jejunum, ileum and colon. Significant differences in the correlations between bodyweight and length of duodenum, jejunum and rectum were also found. The compared hybrids of laying hens differed significantly in the dimensions of the femur and tibia. Lohmann Brown (LB) hens were characterized by higher greatest length, medial length, smallest breadth of the corpus, and greatest breadth of the distal end of the femur compared with Lohmann White (LW) hens. Dimensions of the tibia greatest length, axial length, smallest breadth of the corpus, greatest breadth of the distal end and greatest depth of the distal end in LB hens were also significantly (P < 0.05) higher than those in LW hens. Conclusions. The results showed that the genotype of laying hens tested after the laying period influenced carcass weight and muscle percentage, as well as differentiated the birds in terms of dimensions of individual segments of the digestive tract, femur, and tibia bones. Implications. The results of this research may be useful for consumers of laying hen carcasses and people interested in poultry anatomy. [ABSTRACT FROM AUTHOR]

Aim: To meta-analyze the utility of transarterial radioembolization (TARE) in patients with liver metastatic breast cancer (BC), based on the objective response rate (ORR) and disease control rate (DCR). Methods: A literature search was performed retrieving studies with (1) at least 10 patients with liver metastatic BC treated with TARE and (2) adequate information to derive ORR and DCR. The ORR is the ratio between patients with liver lesions showing complete response (CR) or partial response (PR) over the total number of patients treated with TARE; the DCR is the ratio between patients with CR, PR, or stable disease (SD) over the total number of patients treated with TARE. Results: Eighteen studies (650 patients) were eligible; the ORR of TARE resulted 50.71% (95% C.I.: 40.04–61.36) and the DCR resulted 88.37% (95% C.I.: 81.89–93.57). Taking into account resin spheres (395 patients), the ORR was 60.35% (95% C.I.: 46.55–73.36) and the DCR was 92.73% (95% C.I.: 87.17–96.80%). Considering glass spheres (144 patients), the ORR was 32.38% (95% C.I.: 18.43–48.16) and the DCR was 82.69% (95% C.I.: 59.29–97.26). Conclusions: This meta-analysis favors the use of TARE in patients with liver metastatic BC either with resin or glass spheres. [ABSTRACT FROM AUTHOR]

Ivermectin is a widely used antiparasitic in livestock, but its use can result in residues in bovine products and excretions. The objective of the present study was to determine the presence of ivermectin residues in cattle meat, liver, milk, faeces, and urine and assess consumer risk from chronic exposure through contaminated bovine products using a deterministic approach. To determine the presence of ivermectin residues, 124 samples were analysed by liquid chromatography. Residues were found in 68% of faeces samples and small percentages (3%) in liver, milk, and urine, with no residues detected in meat. The mean ivermectin residue in the liver (16.46 µg/kg) remained below the maximum residue limit (MRL); however, in milk (12.46 µg/kg), the residues exceeded the permitted MRL. The results obtained from chronic dietary exposure show that the consumption of ivermectin residues was low, and the risk was assessed as being rare to very rare. Additionally, this study reveals concerning levels of ivermectin residues in milk that may far exceed established safety limits. This situation emphasises the urgent need for stricter regulations and monitoring in milk production, particularly from small farms, to protect vulnerable populations. However, from a one health perspective, the presence of residues in faeces poses potential environmental hazards, warranting further research. Moreover, the detection of residues in milk, despite the ban on ivermectin use in dairy cattle, underscores the importance of compliance with food safety regulations and the need for continued vigilance in this area. [ABSTRACT FROM AUTHOR]

Transportation, an unavoidable process in livestock farming, causes metabolic disorders in the body, which then lead to endocrine disruption, being immunocompromised, and growth suppression. Lipid metabolism dysregulation is a critical phenotype induced by transportation. The liver is a vital organ in lipid metabolism, with a role in both lipid synthesis and lipolysis. However, the specific mechanisms by which transportation affects hepatic lipid metabolism remain unclear. This study employed rats as a model to investigate the effects of transportation on hepatic lipid metabolism. Rats subjected to transportation showed altered serum lipid profiles, including decreased serum triglyceride (TG), low-density lipoprotein cholesterol (VLDL-C), and non-esterified fatty acid (NEFA) immediately after transportation (IAT) and serum total cholesterol (TC) on day 3, and increasing serum TG, TC, and low-density lipoprotein cholesterol (LDL-C) on day 10. Meanwhile, fatty droplets in the liver were also reduced at IAT and increased on days 3 and 10. Notably, transportation also affected hepatic-lipid-metabolism-related enzyme activities and signaling pathways, such as increased AMP-activated protein kinase alpha (AMPKα) phosphorylation and modulations in key proteins and genes related to lipid metabolism, decreased hepatic acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) activities at IAT, and increased carnitine palmitoyl transferase 1 alpha (CPT-1α) at IAT and ACC and CPT-1α activities on days 3 and 10. Supplementation with alkaline mineral complex water (AMC) before and after transportation mitigated the adverse effects on hepatic lipid metabolism by modulating the AMPKα-SREBP-1c/PPARα pathway, enhancing lipid synthesis, and reducing the oxidative catabolism of fatty acids. AMC inhibited the transportation-induced activation of AMPKα and restored the balance of lipid-metabolism-related enzymes and pathways. These findings highlight AMC's potential as a therapeutic intervention to alleviate transportation-induced lipid metabolism disorders, offering significant implications for improving animal welfare and reducing economic losses in livestock farming. [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]