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The histopathological changes in the liver and kidney of Rasbora daniconius have been investigated after exposed to sublethal concentration of paper mill effluent. The result of acute toxicity shows that the paper mill effluent was highly toxic. The fish, Rasbora daniconius were exposed two sub-lethal concentrations of paper mill effluent [1.9% (1/5) and 0.95 % (1/10) LC50 of 96hr] for 30 days to study the impacts on the histology of liver and kidney. Histopathological examination reveled, swollen hepatocytes, nuclear hypertrophy, rupture sinusoids, hemorrhages, vacuolation in hepatic cells and broken central vein in liver. Kidney showed hypertrophy of hematopoietic tissues, cell necrosis, blocked glomerules with full of blood stain, dilated renal tubules with pyknotic nuclei and tubular necrosis. Histopathological changes were dose dependent. The results of histopathological changes in liver and kidney of Rasbora daniconius shows that, fish were under high stress during exposure to sublethal concentration of paper mill effluent. [ABSTRACT FROM AUTHOR]

Distance-based microfluidic paper-based analytical devices (μ PADs) are simple and user-friendly detection platforms for disease screening, environment monitoring and food safety. However, the current distance-based μ PADs still face major challenges of relatively low sensitivity and accuracy. In this work, we propose a novel chromogenic reaction-free distance-based (CRFD) μ PAD strategy for sensitive and accurate quantitation of microRNAs (miRNAs) via viscosity amplification and surface hydrophobicity modulations. The CRFD μ PAD with sampling, indicator (with red ink), and detection zones is scaled with reference patterns. Target miRNA in sample is pre-amplified with rolling circle amplification (RCA) reaction to specifically enhance its viscosity. The difference of flow between target and control is further enlarged on CRFD μ PADs whose surface hydrophobicity is rationally modulated by in situ metal-organic frameworks (MOFs) modification. Meanwhile, the repeatability and flow shape are significantly improved. For a proof-of-concept demonstration, the miR-221 and miR-222 in liver cells lysis were sensitively detected by naked-eye with limits of detection of 0.33 and 0.37 pM, respectively. A smartphone-based auto-reading system (SAS) was developed to further improve the accuracy and convenience, showing greatly reduced relative standard deviation (RSD) of assay from 12.2% to 1.0%. This facile and extensible strategy is promising for rapid detection in complex biosystem. [Display omitted] • Distance-based μ PADs without chromogenic reaction are used for microRNA detection. • Viscosity is specifically amplified by RCA to generate the flow distance difference. • Sensitivity is improved by in situ MOF modification that modulate the surface. • A smartphone-based system is developed to improve the accuracy and convenience. [ABSTRACT FROM AUTHOR]

To develop an effective hybrid bioartificial liver (BAL) device, the material of the scaffold is very important to support hepatocytes that have both growth ability and hepatic differentiated functions. In this study we used paper (Kimwipe, Kimberly-Clark Corp., Roswell, GA, U.S.A.) as a scaffold. Primary hepatocytes isolated from a normal adult rat liver could proliferate on the paper. The secretion of albumin into culture medium by the cells on the paper increased with time in culture and, compared to the cells on dishes, the amount of 48 h albumin secretion at Day 10 was two times larger. Perpendicular sections of hepatocytes on the paper revealed that the cells fell into cavities made by intersecting fibers, piled up, and formed three to four layers. The piled-up cells changed their shape from flat to cuboidal and enlarged their cytoplasm, which was rich in organelles such as mitochondria and peroxisomes with a nucleoid. In addition, they formed bile canalicular structures between the cells. Their morphological appearance was similar to in vivo hepatocytes. Paper (Kimwipe) may be a good candidate as a scaffold to make a BAL device. [ABSTRACT FROM AUTHOR]

Hepatic enzyme induction is generally an adaptive response associated with increases in liver weight, induction of gene expression, and morphological changes in hepatocytes. The additive growth and functional demands that initiated the response to hepatic enzyme induction cover a wide range of stimuli including pregnancy and lactation, hormonal fluctuations, dietary constituents, infections associated with acute-phase proteins, as well as responses to exposure to xenobiotics. Common xenobiotic enzyme inducers trigger pathways involving the constitutive androstane receptor (CAR), the peroxisome proliferator-activated receptor (PPAR), the aryl hydrocarbon receptor (AhR), and the pregnane-X-receptor (PXR). Liver enlargement in response to hepatic enzyme induction is typically associated with hepatocellular hypertrophy and often, transient hepatocyte hyperplasia. The hypertrophy may show a lobular distribution, with the pattern of lobular zonation and severity reflecting species, strain, and sex differences in addition to effects from specific xenobiotics. Toxicity and hepatocarcinogenicity may occur when liver responses exceed adaptive changes or induced enzymes generate toxic metabolites. These undesirable consequences are influenced by the type and dose of xenobiotic and show considerable species differences in susceptibility and severity that need to be understood for assessing the potential effects on human health from similar exposures to specific xenobiotics. [ABSTRACT FROM PUBLISHER]

This article presents a list of several research papers to be published in the European Journal of Biochemistry. Some of listed papers are "Changes in the Insulin-Sensitive Glycosyl-Phosphatidyl-Inositol Signalling System With Aging in Rat Hepatocytes," "Localization of the Tightly Bound Divalent-Cation-Dependcnt and Nucleotidc-Dependent Conformation Changes m G-Actin Using Limited Proteolytic Digestion" and "Structure of the Promoter Region of the Gene Encoding Cytochrome c Oxidase Subunit V in Dictyostelium."

Background: Quercetin, a widespread polyphenolic flavonoid, is known for its extensive health benefits and is commonly found in the plant kingdom. The natural occurrence and extraction methods of quercetin are crucial due to its bioactive potential. Purpose: This review aims to comprehensively cover the natural sources of quercetin, its extraction methods, bioavailability, pharmacokinetics, and its role in various cell death pathways and liver fibrosis. Methods: A comprehensive literature search was performed across several electronic databases, including PubMed, Embase, CNKI, Wanfang database, and ClinicalTrials.gov, up to 10 February 2024. The search terms employedwere "quercetin", "natural sources of quercetin", "quercetin extraction methods", "bioavailability of quercetin", "pharmacokinetics of quercetin", "cell death pathways", "apoptosis", "autophagy", "pyroptosis", "necroptosis", "ferroptosis", "cuproptosis", "liver fibrosis", and "hepatic stellate cells". These keywords were interconnected using AND/OR as necessary. The search focused on studies that detailed the bioavailability and pharmacokinetics of quercetin, its role in different cell death pathways, and its effects on liver fibrosis. Results: This review details quercetin's involvement in various cell death pathways, including apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis, with particular attention to its regulatory influence on apoptosis and autophagy. It dissects the mechanisms through which quercetin affects these pathways across different cell types and dosages. Moreover, the paper delves into quercetin's effectson liver fibrosis, its interactions with hepatic stellate cells, and its modulation of pertinent signaling cascades. Additionally, it articulates from a physical organic chemistry standpoint the uniqueness of quercetin's structure and its potential for specific actions in the liver. Conclusion: The paper provides a detailed analysis of quercetin, suggesting its significant role in modulating cell death mechanisms and mitigating liver fibrosis, underscoring its therapeutic potential. [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]

Liver disease is a global health problem that affects the well-being of tens of thousands of people. Dihydroquercetin (DHQ) is a flavonoid compound derived from various plants. Furthermore, DHQ has shown excellent activity in the prevention and treatment of liver injury, such as the inhibition of hepatocellular carcinoma cell proliferation after administration, the normalization of oxidative indices (like SOD, GSH) in this tissue, and the down-regulation of pro-inflammatory molecules (such as IL-6 and TNF-α). DHQ also exerts its therapeutic effects by affecting molecular pathways such as NF-κB and Nrf2. This paper discusses the latest research progress of DHQ in the treatment of various liver diseases (including viral liver injury, drug liver injury, alcoholic liver injury, non-alcoholic liver injury, fatty liver injury, and immune liver injury). It explores how to optimize the application of DHQ to improve its effectiveness in treating liver diseases, which is valuable for preparing potential therapeutic drugs for human liver diseases in conjunction with DHQ. [ABSTRACT FROM AUTHOR]

Acute-on-chronic liver failure (ACLF) is a group of clinical syndromes related to severe acute liver function damage and multiple organ failure caused by various acute inducing factors on the basis of chronic liver disease. Due to its serious condition, rapid progression and high mortality, it has attracted more and more attention. Recent studies have shown that the pathogenesis of ACLF mainly includes direct injury and immune injury. As the main immune cells in the liver, the immunoregulatory role of liver macrophages in ACLF has been increasingly recognized. Liver macrophages have excellent phenotype conversion function and plasticity characteristics under the influence of epigenetic reprogramming or local microenvironment. This adaptive expression ability can use key mediators to promote the early conversion of anti-inflammatory phenotype to alleviate liver injury. A large number of studies have shown that liver macrophages have a certain potential in reversing the process of ACLF. Therefore, from the perspective of the plasticity characteristics of liver macrophages, this paper expounds the role of liver macrophages in ACLF and the research on the intervention of ACLF disease process, and summarizes its potential significance in the treatment of ACLF. [ABSTRACT FROM AUTHOR]

A novel cholic acid-conjugated carboplatin (CP-CA) is developed as a liver-targeting prodrug of carboplatin (CP) for liver cancer. Instead of using CP as a raw material, CP-CA was synthesized simultaneously. This paper is focused on the comparison of CP-CA and CP with respect to their pharmacokinetic (PK) and tissue distribution profiles in rats after their intravenous administration. Additionally, their uptake by human liver tumor cell Huh7 and normal human liver cell HL7702 are investigated. The inductively coupled plasma mass spectrometry (ICP-MS) method is applied for the determination of platinum in plasma, tissues, and cells. The PK results show that both the AUC0–t and AUC0–∞ data on Pt for CP-CA are significantly higher than those for CP (p < 0.01), indicating that the plasma exposure of CP-CA is significantly higher than that of CP. The CL1, Vd1, and Vd2 data on Pt for CP-CA are significantly lower than those for CP (p < 0.01), while the MRT0–t is significantly higher (p < 0.01), which is possibly related to a higher PPBR, and can strongly support the higher AUC0–t and AUC0–∞ of Pt for CP-CA compared to for CP. The tissue distribution results show that CP-CA is mainly distributed and accumulated in the liver after its intravenous administration to rats, revealing its liver-targeting profile. Compared to CP, CP-CA is more easily taken up by human liver cancer cells and normal human liver cells. The results suggest that CP-CA has a potential for further development as a new prodrug specific to liver cancer. [ABSTRACT FROM AUTHOR]

In this paper, a structured illumination microscopy (SIM) image reconstruction algorithm combined with notch function (N-SIM) is proposed. This method suppresses the defocus signal in the imaging process by processing the low-frequency signal of the image. The existing super-resolution image reconstruction algorithm produces streak artifacts caused by defocus signal. The experimental results show that the algorithm proposed in our study can well suppress the streak artifacts caused by defocused signals during the imaging process without losing the effective information of the image. The image reconstruction algorithm is used to analyze the mouse hepatocytes, and the image processing tool developed by MATLAB is applied to identify, detect and count the reconstructed images of mitochondria and lipid droplets, respectively. It is found that the mitochondrial activity in oxidative stress induced growth inhibitor 1 (OSGIN1) overexpressed mouse hepatocytes is higher than that in normal cells, and the interaction with lipid droplets is more obvious. This paper provides a reliable subcellular observation platform, which is very meaningful for biomedical work. [ABSTRACT FROM AUTHOR]

Grapefruit essential oil has been proven to have wide range of bioactivities. However, bioactivity of its molecular distillate has not been well studied. In this study, a light phase oil was obtained by molecular distillation from cold-pressed grapefruit essential oil and GC-MS was used to identify its chemical composition. The antimicrobial activity of the light phase oil was tested by filter paper diffusion method, and the anticancer activity was determined by the Cell Counting Kit-8 (CCK-8) assay. Twenty-four components were detected with a total relative content of 99.74%, including 97.48% of terpenes and 1.66% of oxygenated terpenes. The light phase oil had the best antimicrobial effect on Bacillus subtilis, followed by Escherichia coli, Staphylococcus aureus and Salmonellaty phimurium. DPPH and ABTS assays demonstrated that the light phase oil had good antioxidant activity. The CCK-8 assay of cell proliferation showed that the light phase oil had a good inhibitory effect on the proliferation of HepG2 liver cancer cells and HCT116 colon cancer cells. [ABSTRACT FROM AUTHOR]

Leukocyte cell-derived chemotaxin-2 (LECT2) is an important cytokine synthesized by liver. Significant research interest is stimulated by its crucial involvement in inflammatory response, immune regulation, disease occurrence and development. However, bibliometric study on LECT2 is lacking. In order to comprehend the function and operation of LECT2 in human illnesses, we examined pertinent studies on LECT2 investigation in the Web of Science database, followed by utilizing CiteSpace, VOSview, and Scimago Graphica for assessing the yearly quantity of papers, countries/regions involved, establishments, authors, publications, citations, and key terms. Then we summarized the current research hotspots in this field. Our study found that the literature related to LECT2 has a fluctuating upward trend. "Angiogenesis", "ALECT2", "diagnosis", and "biliary atresia" are the current investigative frontiers. Our findings indicated that liver diseases (e.g. liver fibrosis and hepatic cell carcinoma), systemic inflammatory disease, and amyloidosis are the current research focus of LECT2. The current LECT2 research outcomes are not exceptional. We hope to promote the scientific research of LECT2 and exploit its potential for clinical diagnosis and treatment of related diseases through a comprehensive bibliometric review. [ABSTRACT FROM AUTHOR]

Background: Patrinia villosa (Thunb.) Juss is one of the plant resources of the famous traditional Chinese medicine "Bai jiang cao (herba patriniae)," and it is considered to function at the liver meridian, thereby treating diseases of the liver as demonstrated by the traditional theory of TCM. Unfortunately, the therapeutic mechanism of the whole plant of PV is so far unknown. Method: UPLC QTOF-MS/MS was used to analyze the profile of PV. Male Sprague-Dawley rats were categorized into five groups, and PV groups (125 and 375mg/kg) were administered by oral gavage for seven consecutive days. The model of liver injury was induced by intraperitoneal injection of 40% CCl4 oil solution. H&E staining was performed for histological evaluation. The ELISA method was used to assess the serumlevel of ALT, AST, and T-BIL. Serum and liver bile acid (BA) profiling was analyzed by LC-MS/MS. TUNEL-stained liver sections were used to monitor apoptosis caused by CCl4. HepG2 cells were used to detect autophagy caused by CCl4. Results: A total of 16 compounds were identified from the 70% methanol extract of PV. PV (125 and 375 mg/kg) could reverse the ectopic overexpression of AST, ALT, and T-BIL caused by CCl4 administration. H&E staining indicated that PV (125 and 375 mg/kg) could reduce the infiltration of inflammatory cells and restore liver tissue and hepatocyte structures. Six bile acids, including DCA, HDCA, GCA, TCA, TCDCA, and TUDCA, were significantly altered both in the serum and liver tissue after CCl4 administration, and the level of all these six bile acids was restored by PV treatment. Moreover, PV inhibited apoptosis caused by CCl4 stimulation in liver tissue and suppressed autophagy in HepG2 cells treated with CCl4. Conclusion: The results in this paper for the first time reveal the alteration of the bile acid profile in CCl4-induced liver injury and demonstrate that inhibiting apoptosis and autophagy was involved in P. villosa-elicited liver protection, providing a scientific basis for the clinical utilization of P. villosa as a natural hepatic protective agent. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally and the sixth most common cancer worldwide. Evidence shows that growth differentiation factor 15 (GDF15) contributes to hepatocarcinogenesis through various mechanisms. This paper reviews the latest insights into the role of GDF15 in the development of HCC, its role in the immune microenvironment of HCC, and its molecular mechanisms in metabolic dysfunction associated steatohepatitis (MASH) and metabolic associated fatty liver disease (MAFLD)-related HCC. Additionally, as a serum biomarker for HCC, diagnostic and prognostic value of GDF15 for HCC is summarized. The article elaborates on the immunological effects of GDF15, elucidating its effects on hepatic stellate cells (HSCs), liver fibrosis, as well as its role in HCC metastasis and tumor angiogenesis, and its interactions with anticancer drugs. Based on the impact of GDF15 on the immune response in HCC, future research should identify its signaling pathways, affected immune cells, and tumor microenvironment interactions. Clinical studies correlating GDF15 levels with patient outcomes can aid personalized treatment. Additionally, exploring GDF15-targeted therapies with immunotherapies could improve anti-tumor responses and patient outcomes. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is the most common primary malignancy of the liver, with hepatocellular differentiation. It is ranked sixth among the most common cancers worldwide and is the third leading cause of cancer-related deaths. The most important etiological factors discussed here are viral infection (HBV, HCV), exposure to aflatoxin B1, metabolic syndrome, and obesity (as an independent factor). Directly or indirectly, they induce chromosomal aberrations, mutations, and epigenetic changes in specific genes involved in intracellular signaling pathways, responsible for synthesis of growth factors, cell proliferation, differentiation, survival, the metastasis process (including the epithelial–mesenchymal transition and the expression of adhesion molecules), and angiogenesis. All these disrupted molecular mechanisms contribute to hepatocarcinogenesis. Furthermore, equally important is the interaction between tumor cells and the components of the tumor microenvironment: inflammatory cells and macrophages—predominantly with a pro-tumoral role—hepatic stellate cells, tumor-associated fibroblasts, cancer stem cells, extracellular vesicles, and the extracellular matrix. In this paper, we reviewed the molecular biology of hepatocellular carcinoma and the intricate mechanisms involved in hepatocarcinogenesis, and we highlighted how certain signaling pathways can be pharmacologically influenced at various levels with specific molecules. Additionally, we mentioned several examples of recent clinical trials and briefly described the current treatment protocol according to the NCCN guidelines. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examines how statins, which are drugs commonly used to lower cholesterol, affect the growth of liver cancer cells. Statins can be either lipophilic (lipid-soluble) or hydrophilic (water-soluble), and this characteristic influences how they enter cells. In our research, we compared the effects of lipophilic simvastatin and hydrophilic pravastatin. We found that simvastatin significantly reduces cancer cell growth and increases cell death depending on the dosage and duration of treatment. In contrast, pravastatin, due to its limited uptake, has a minimal impact on cancer cells. These findings suggest that the type of statin used could be crucial in cancer treatment, potentially offering better outcomes for patients with liver cancer. The HMG-CoA reductase inhibitors, statins, are drugs used globally for lowering the level of cholesterol in the blood. Different clinical studies of statins in cancer patients have indicated a decrease in cancer mortality, particularly in patients using lipophilic statins compared to those on hydrophilic statins. In this paper, we selected two structurally different statins (simvastatin and pravastatin) with different lipophilicities and investigated their effects on the proliferation and apoptosis of hepatocellular carcinoma cells. Lipophilic simvastatin highly influences cancer cell growth and survival in a time- and concentration-dependent manner, while pravastatin, due to its hydrophilic structure and limited cellular uptake, showed minimal cytotoxic effects. [ABSTRACT FROM AUTHOR]

Simple Summary: The microenvironment of hepatocellular carcinoma is a really complex milieu, containing a wide variety of cells with specific tasks, belonging to both the mesenchimal and immunitary systems, the extracellular matrix, growth factors, proinflammatory cytokines, and translocated bacterial products. This intricate environment represents a source of potential targets in order to establish a wide and multitask therapeutic strategy for hepatocellular carcinoma. Hepatocellular carcinoma is a malignant tumor that originates from hepatocytes in an inflammatory substrate due to different degrees of liver fibrosis up to cirrhosis. In recent years, there has been growing interest in the role played by the complex interrelationship between hepatocellular carcinoma and its microenvironment, capable of influencing tumourigenesis, neoplastic growth, and its progression or even inhibition. The microenvironment is made up of an intricate network of mesenchymal cells, immune system cells, extracellular matrix, and growth factors, as well as proinflammatory cytokines and translocated bacterial products coming from the intestinal microenvironment via the enterohepatic circulation. The aim of this paper is to review the role of the HCC microenvironment and describe the possible implications in the choice of the most appropriate therapeutic scheme in the prediction of tumor response or resistance to currently applied treatments and in the possible development of future therapeutic perspectives, in order to circumvent resistance and break down the tumor's defensive fort. [ABSTRACT FROM AUTHOR]

(1) Background: Madelung's disease—known also as Benign Symmetric Adenolipomatosis (BSA) or Multiple Symmetric Lipomatosis (MSL), is a rare subcutaneous tissue disease characterized by the proliferation of non-encapsulated fat tissue with mature adipocytes. Patients develop symmetrical fatty deposits of varying sizes, (located particularly around the neck, shoulders, upper and middle back, arms, abdomen, and thighs), having clinical, esthetic, and psychiatric repercussions. (2) Methods: We report a case diagnosed with BSA upon admission to the Neurological and Internal Medicine Departments of the Emergency Clinical Hospital of Galati. (3) Results: This patient developed compressive phenomena and liposarcoma with liver metastasis, followed by death shortly after hospital presentation. The histopathology examination confirmed right latero-cervical liposarcoma and round cell hepatic metastasis. The specific metabolic ethiopathogenic mechanism has not been elucidated, but the adipocytes of BSA are different from normal cells in proliferation, hormonal regulation, and mitochondrial activity; a rare mitochondrial gene mutation, together with other interacting genetic or non-genetic factors, have been considered in recent studies. A thorough literature search identified only three cases reporting malignant tumors in BSA patients. (4) Conclusions: The goal of our paper is to present this rare case in the oncogenic synergism of two tumors. In the management of this BSA disorder, possible malignant transformation should be considered, although only scarce evidence was found supporting this. [ABSTRACT FROM AUTHOR]

Oncolytic Newcastle disease virus is a new type of cancer immunotherapy drug. This paper proposes a scheme for delivering oncolytic viruses using hydrogel microneedles. Gelatin methacryloyl (GelMA) was synthesized by chemical grafting, and GelMA microneedles encapsulating oncolytic Newcastle disease virus (NDV) were prepared by micro-molding and photocrosslinking. The release and expression of NDV were tested by immunofluorescence and hemagglutination experiments. The experiments proved that GelMA was successfully synthesized and had hydrogel characteristics. NDV was evenly dispersed in the allantoic fluid without agglomeration, showing a characteristic virus morphology. NDV particle size was 257.4 ± 1.4 nm, zeta potential was −13.8 ± 0.5 mV, virus titer TCID50 was 107.5/mL, and PFU was 2 × 107/mL, which had a selective killing effect on human liver cancer cells in a dose and time-dependent manner. The NDV@GelMA microneedles were arranged in an orderly cone array, with uniform height and complete needle shape. The distribution of virus-like particles was observed on the surface. GelMA microneedles could successfully penetrate 5% agarose gel and nude mouse skin. Optimal preparation conditions were freeze-drying. We successfully prepared GelMA hydrogel microneedles containing NDV, which could effectively encapsulate NDV but did not detect the release of NDV. [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]

Background: Mesenchymal stem cells (MSCs) have important research value and broad application prospects in liver diseases. This study aims to comprehensively review the cooperation and influence of countries, institutions, authors, and journals in the field of MSCs in liver diseases from the perspective of bibliometrics, evaluate the clustering evolution of knowledge structure, and discover hot trends and emerging topics. Methods: The articles and reviews related to MSCs in liver diseases were retrieved from the Web of Science Core Collection using Topic Search. A bibliometric study was performed using CiteSpace and VOSviewer. Results: A total of 3404 articles and reviews were included over the period 2001-2021. The number of articles regarding MSCs in liver diseases showed an increasing trend. These publications mainly come from 3251 institutions in 113 countries led by China and the USA. Li L published the most papers among the publications, while Pittenger MF had the most co-citations. Analysis of the most productive journals shows that most are specialized in medical research, experimental medicine and cell biology, and cell & tissue engineering. The macroscopical sketch and micro-representation of the whole knowledge field are realized through co-citation analysis. Liver scaffold, MSC therapy, extracellular vesicle, and others are current and developing areas of the study. The keywords "machine perfusion", "liver transplantation", and "microRNAs" also may be the focus of new trends and future research. Conclusions: In this study, bibliometrics and visual methods were used to review the research of MSCs in liver diseases comprehensively. This paper will help scholars better understand the dynamic evolution of the application of MSCs in liver diseases and point out the direction for future research. [ABSTRACT FROM AUTHOR]

In the current paper, we have successfully synthesized three new mercury coordination polymers with fascinating structures and properties via a flexible sulfur donor ligand, namely, {[Hg(μ2-Cl)(μ2-Ls)]} n [BF4] n (1), {[Hg(μ2-Cl)(μ2-Ls)]} n [ClO4] n (2), and [Hg(SCN)2(μ2-Ls)] n (3) [Ls = 1,1-bis(3-methyl-4-imidazoline-2-thione)methane]. These complexes have been characterized by means of different techniques such as single crystal X-ray crystallography, FT-IR, elemental analysis (CHNS), UV-Vis, PXRD, BET, and TGA. Suitable single crystals of all complexes were obtained using the branch tube method with a very high yield and good stability due to the high affinity of mercury to bind to the thione groups. The cationic moieties of polymers 1 and 2 were isostructural, with a HgCl2S2 coordination core structure. The voids of the quasi-hexagonal packing of the columnar chains were occupied by unbonded tetrahedral BF4− ions in 1 and perchlorate anions in polymer 2. Polymer 3 has a less distorted tetrahedral geometry than 1 and 2, with a HgS4 core structure. By considering the thiophilicity of mercury, a thioamide-based Ls ligand was used to detoxify Hg(II) into insoluble polymers 1–3. The results of an MTT assay for (HepG2) liver cells confirmed the excellent cytoprotective effect of this ligand against mercury. Based on IC50 calculations, their toxicity was in order of polymer 1 > polymer 2 > polymer 3. These polymers were also considered as adsorbents for the reversible removal of iodine from solution and the kinetics of the process has been studied in detail. Interestingly, all of them showed an excellent stability and high capacity, in order of 763.53 mg g−1, 877.10 mg g−1, and 905.31 mg g−1 for polymers 1–3, respectively. [ABSTRACT FROM AUTHOR]

This paper provides a comprehensive review of the current understanding of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH), focusing on key factors influencing its pathogenesis and emerging therapeutic strategies. This review highlights the growing prevalence of NAFLD and NASH, emphasizing their multifactorial nature. The manuscript identifies various contributors to NAFLD development, including genetic, dietary, and environmental factors, while examining the intricate interplay between these factors and their impact on hepatic lipid metabolism, inflammation, and insulin resistance. Genetic predisposition, dietary fat intake, and excessive fructose consumption are discussed as significant contributors to NAFLD progression. The article emphasizes the lack of a single therapeutic approach and underscores the need for combination strategies. Lifestyle interventions, particularly weight loss through diet and exercise, remain crucial, while pharmacological options like GLP-1 receptor agonists, obeticholic acid, lanifibranor, and resmetirom show promise but require further validation. Bariatric surgery and emerging endoscopic procedures offer potential in eligible patients. In sum, this article underscores the complexity of NAFLD and NASH, addresses key factors influencing pathogenesis, and discusses emerging therapies advocating for a multifaceted approach to this increasingly prevalent and clinically relevant condition. [ABSTRACT FROM AUTHOR]

Introduction: For a large variety of liver pathologies, the plasma unconjugated (UB) and conjugated (CB) bilirubin concentrations appear to be coupled. For example, in alcoholic cirrhosis, UB and CB are roughly the same over a large range of total bilirubin, requiring an initial massive increase (about 40-fold) in plasma CB to reach the level of UB and then similar increases in UB and CB as the disease progresses. This coupling has been either unrecognized or ignored and this paper is the first attempt to try to explain it quantitatively in terms of known hepatic cell metabolic and membrane transport properties.Methods: A simplified pharmacokinetic model is developed and applied to a variety of hyperbilirubinemic pathologies. A central feature of the model is based on the recent observation that double knockout of the rat OATP1A and OATP1B hepatic transporters produces a roughly 400-fold increase in plasma CB, indicating that there is a normal rapid recycling of CB from the cell to the plasma with reuptake via OATP. We use the experimental rat Km of OATP CB transport to show that OATP uptake becomes saturated at relatively low plasma CB concentrations, decreasing uptake, and producing massive (up to 1000-fold) increases in CB in some pathologies. It is assumed that UB and CB are competing for the OATP transporter, producing the increased plasma UB that is observed in "pure" CB pathologies.Results: The model accurately describes the clinically observed UB and CB for pure UB (Gilbert's, hemolytic anemia) and CB (Dubin-Johnson, Rotor syndrome, biliary atresia) pathologies as well as in cirrhosis.Conclusion: This model is a preliminary, first attempt to quantitatively describe UB and CB pharmacokinetics. It is hoped that it will stimulate more detailed measurements and analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: To date, essential oil fractions are emerging as functional compounds of interest for the food and perfume industries. The aim of this study is to evaluate the ability of citral-enriched fractions obtained from lemon essential oil (Cfr-LEO) to counteract, in healthy human hepatocytes, the activity of lipopolysaccharide (LPS), a trigger of inflammation, oxidative stress, and epithelial–mesenchymal transition. In our paper, we report that the pretreatment of hepatocytes with Cfr-LEO counteracts the effects induced by LPS. The data obtained lay the basis for the development of commercial products such as food and drink aimed at preventing or alleviating chronic conditions associated with liver dysfunction. Lemon essential oil (LEO) is known for its aromatic and healthy properties; however, less consideration is given to the biological properties of the fractions obtained from LEO. This study aims to evaluate the ability of a citral-enriched fraction obtained from LEO (Cfr-LEO) to counteract lipopolysaccharide (LPS)-mediated inflammation, oxidative stress, and epithelial–mesenchymal transition (EMT) in healthy human hepatocytes. Human immortalized hepatocytes (THLE-2 cell line) were pretreated with Cfr-LEO and subsequently exposed to LPS at various time points. We report that the pretreatment with Cfr-LEO counteracts LPS-mediated effects by inhibiting inflammation, oxidative stress, and epithelial–mesenchymal transition in THLE-2. In particular, we found that pretreatment with Cfr-LEO reduced NF-κB activation and the subsequent proinflammatory cytokines release, ROS production, and NRF2 and p53 expression. Furthermore, the pretreatment with Cfr-LEO showed its beneficial effect in counteracting LPS-induced EMT. Taken together, these results support Cfr-LEO application in the nutraceutical research field not only for its organoleptic properties, conferred by citral enrichment, but also for its biological activity. Our study could lay the basis for the development of foods/drinks enriched with Cfr-LEO, aimed at preventing or alleviating chronic conditions associated with liver dysfunction. [ABSTRACT FROM AUTHOR]

Primary chicken embryo liver (CEL) cells are derived from the liver tissue of chicken embryonated eggs (CEE) using an aseptic isolation technique and growth under a controlled atmosphere in an artificial environment for cell attachment and proliferation. Although this primary cultured cell has been established for more than six decades, utilization of primary cells is still the preferable medium nowadays as the “gold standard” due to several advantages over other diagnostic techniques. Cells provide better adaptability of the viruses and easily mimic the natural host environment with high virus titration. The volume of virus suspension could be increased by applying an immortal chicken embryo liver-derived cell line. The current review aimed to highlight the importance and challenges of using primary chicken embryo liver cells in poultry virus studies. Primary CEL cells are widely used as an alternative host for diagnosis of infectious poultry viruses, cultivation and passaging of virus isolates, and vaccine production. Yet, there are some challenges and limitations in handling this primary cell, which requires appropriate facilities and environment to sustain the rapid growth of confluent monolayer cells, as highlighted in this paper. The availability of specific pathogen-free CEE is a major concern due to limited resources globally, thus creating a challenge for vaccine manufacturers to upscale the cultured cells. Future improvement of primary cell culture preparation necessitates new technology by applying cellular microcarrier in the bioreactor machine for efficient cell growth and subsequent routine virus cultivation. This study can help the researchers understand the advantages of primary CEL cells and their applications due to their significant impact on poultry viruses. [ABSTRACT FROM AUTHOR]

As one of the malignant tumors with high mortality, the initial symptoms of liver cancer are not obvious. In addition, the liver is the largest internal organ of the human body, and its structure and distribution are relatively complex. Therefore, in order to help doctors judge liver cancer more accurately, this paper proposes a variant model based on Unet network. Before segmentation, the image is preprocessed, and Pulse Coupled Neural Network (PCNN) algorithm is used to filter the image adaptively to make the image clearer. For the segmentation model, the SE module is used as the input of the residual network, and then its output is connected to the Unet model through bilinear interpolation to perform the down-sampling and up-sampling operations. The dataset is a combination of Hainan Provincial People's Hospital and some public datasets Lits. The results show that this method has better segmentation performance and accuracy than the original Unet method, and the dice coefficient, mIou and other evaluation indicators have increased by at least 2.1%, which is a method that can be applied to cancer segmentation. [ABSTRACT FROM AUTHOR]

This paper involved the synthesis of a new compound by condensing OPhenylenediamine (OPD) and 4-Methyl-o-phenylenediamine with pyrrole-2-carboxaldehyde through a condensation reaction. Following that, transition metal complexes of Mn (II) and Co (II) were prepared by reacting the respective metal chlorides with the ligand in a 1:1 molar ratio. To characterize the ligand and its metal complexes, a comprehensive range of spectroscopic and analytical techniques was employed, confirming their tetrahedral geometry. Additionally, the researchers investigated the potential cytotoxic effects of hepatic cells cancer (SK-GT-4) cancer cells treated with the Schiff bases and its metal compounds. [ABSTRACT FROM AUTHOR]

This paper studies the preparation of a carbohydrate derivative of lipotripeptide (N-lactitol-Gly)2-LysC16 of an irregular structure with two terminal residues of D-galactose, a branching link based on aliphatic L-lysine and its carbohydrate-free analog with 1-pyrenbutanol as a fluorescent label in a hydrophobic fragment. The developed synthesis scheme includes universal approaches of peptide chemistry and the stages of the formation of an acyclic carbohydrate based on lactose in the hydrophilic domain of amphiphile. The compounds are designed to create compositions of the vector BAS delivery systems with the ability to visualize the process of interaction with the target cells. [ABSTRACT FROM AUTHOR]

Liver cancer is the main source of death in the globe. Manual cancer tissue diagnosis is monotonous and troublesome. Hence, the paper fosters a high-exactness automatic diagnosis strategy for liver cancer growth. The image processing approach can utilize Computer Aided Diagnosis (CAD) for the arrangement of liver malignant growth to help the specialist. The CAD system is used to give a robotized approach to deal with successful arrangement of liver malignancy using feasible arrangements. Early affirmation and finding of liver growth are crucial for the space of liver cancers. Medical image processing is utilized to isolate tumors in a non-prominent way. Different strategies for recognizing liver tumors dependent upon abnormal lesion size and shape have been made. In like manner, automatic procedures for dividing the liver and liver tumors are pursued in clinical practice. This paper examines out a combination of liver malignant growth determination algorithms and philosophies. [ABSTRACT FROM AUTHOR]

Copper complexes are considered as potential candidates for anticancer therapy and medical applications. In this paper, three new Cu(II) complexes, [Cu(IPY)2](ClO4)2·H2O (CuI1), [Cu(IPY)(L -Phe)H2O]ClO4·0.5H2O (CuI2) and [Cu(IPY)(L -Val)H2O]ClO4 (CuI3) (where IPY = 2-(1H-imidazol-2-yl)pyridine, L -Phe = L -phenylalanine, and L -Val = L -valine), with good amphipathic properties were synthesized and characterized. Their single crystal X-ray diffraction results revealed that CuI1 was four-coordinated, while CuI2 and CuI3 both adopted a five-coordinated tetragonal pyramidal configuration. Multi-spectral methods, viscosity experiment and molecular docking technique showed that the three complexes interacted with DNA through insertion. The results of the gel electrophoresis experiments indicated that DNA was oxidatively cleaved by all the complexes in a concentration-dependent manner. Moreover, singlet oxygen (1O2), hydrogen peroxide (H2O2) and superoxide anion radicals (˙O2−) were associated with the oxidative cleavage of DNA. All the complexes also had good binding affinity with human serum albumin (HSA). The MB degradation assay revealed that all complexes could react with H2O2 to form ˙OH through Fenton-like processes. The complexes displayed good antiproliferative activity against the tested human cancer cells in vitro, including cervical carcinoma cells (HeLa), liver cancer cells (HepG2 and BEL-7402) and gastric adenocarcinoma cells (SGC-7901), but showed lower toxicity to normal liver cells (LO2). The anticancer mechanism research revealed that CuI1, CuI2 and CuI3 arrested the cell cycle at the S phase, elevated intracellular reactive oxygen species (ROS) levels and induced loss of mitochondrial membrane potential (MMP). The results indicated that these Cu(II) complexes could induce DNA damage and ROS-mediated mitochondrial dysfunction, leading to cancer cell apoptosis. Our work provides a theoretical basis for the design of new low-toxicity and highly efficient anticancer Cu(II) complexes by incorporating biological metabolites and aromatic heterocyclic ligands. [ABSTRACT FROM AUTHOR]

Accurate descriptions of the variability in single-cell oxygen consumption and its size-dependency are key to establishing more robust tissue models. By combining microfabricated devices with multiparameter identification algorithms, we demonstrate that single human hepatocytes exhibit an oxygen level-dependent consumption rate and that their maximal oxygen consumption rate is significantly lower than that of typical hepatic cell cultures. Moreover, we found that clusters of two or more cells competing for a limited oxygen supply reduced their maximal consumption rate, highlighting their ability to adapt to local resource availability and the presence of nearby cells. We used our approach to characterize the covariance of size and oxygen consumption rate within a cell population, showing that size matters, since oxygen metabolism covaries lognormally with cell size. Our study paves the way for linking the metabolic activity of single human hepatocytes to their tissue- or organ-level metabolism and describing its size-related variability through scaling laws. [ABSTRACT FROM AUTHOR]

mRNA-based gene editing platforms have tremendous promise in the treatment of genetic diseases. However, for this potential to be realized in vivo, these nucleic acid cargos must be delivered safely and effectively to cells of interest. Ionizable lipid nanoparticles (LNPs), the most clinically advanced non-viral RNA delivery system, have been well-studied for the delivery of mRNA but have not been systematically optimized for the delivery of mRNA-based CRISPR-Cas9 platforms. In this study, we investigated the effect of microfluidic and lipid excipient parameters on LNP gene editing efficacy. Through in vitro screening in liver cells, we discovered distinct trends in delivery based on phospholipid, cholesterol, and lipid-PEG structure in LNP formulations. Combination of top-performing lipid excipients produced an LNP formulation that resulted in 3-fold greater gene editing in vitro and facilitated 3-fold greater reduction of a therapeutically-relevant protein in vivo relative to the unoptimized LNP formulation. Thus, systematic optimization of LNP formulation parameters revealed a novel LNP formulation that has strong potential for delivery of gene editors to the liver to treat metabolic disease. [ABSTRACT FROM AUTHOR]

Cell junctions, including anchoring, occluding and communicating junctions, play an indispensable role in the structural and functional organization of multicellular tissues, including in liver. Specifically, hepatic cell junctions mediate intercellular adhesion and communication between liver cells. The establishment of the hepatic cell junction network is a prerequisite for normal liver functioning. Hepatic cell junctions indeed support liver‐specific features and control essential aspects of the hepatic life cycle. This review paper summarizes the role of cell junctions and their components in relation to liver physiology, thereby also discussing their involvement in hepatic dysfunctionality, including liver disease and toxicity. [ABSTRACT FROM AUTHOR]

Liver cancer represents a significant global burden in terms of cancer-related mortality, with resistance to anti-angiogenic drugs such as Sorafenib and Lenvatinib presenting a formidable challenge. Tumor angiogenesis, characterized by the formation of new blood vessels within tumors, plays a pivotal role in cancer progression and metastasis. Tumor endothelial cells, specialized endothelial cells lining tumor blood vessels, exhibit unique phenotypic and functional traits that drive aberrant vessel formation and contribute to therapy resistance. CD105, a cell-surface glycoprotein that is highly expressed on endothelial cells during angiogenesis, including tumor endothelial cells, regulates endothelial cell proliferation, migration, and vessel formation by modulating transforming growth factor-beta (TGF-β) signaling pathways. Elevated CD105 expression on tumor endothelial cells correlates with increased angiogenic activity and poor prognosis in cancer patients. Targeting CD105 with antibodies presents a promising strategy to inhibit tumor angiogenesis and disrupt tumor vasculature, offering potential therapeutic benefits by interfering with the tumor microenvironment and inhibiting its progression. This study investigates tumor angiogenesis through a three-dimensional (3D) microfluidic co-culture system incorporating endothelial cells and hepatocellular carcinoma (HCC) cells. The primary focus is on the role of CD105 expression within the liver tumor microenvironment and its contribution to increased chemoresistance. Additionally, this research examines the influence of CD105 expression on the efficacy of tyrosine kinase inhibitors (TKIs) and its pivotal function in facilitating angiogenesis in liver tumors. The proposed microfluidic chip model investigates liver cancer cell interactions within a microfluidic chip model designed to simulate aspects of liver tumor angiogenesis. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the effect of microvesicles(MVs) from quiescent and TGF-β1 stimulated hepatic stellate cells (HSC-MVs, TGF-β1HSC-MVs) on H2O2-induced human umbilical vein endothelial cells (HUVECs) injury and CCl4-induced rat hepatic vascular injury. Methods: HUVECs were exposed to hydrogen peroxide (H2O2) to establish a model for vascular endothelial cell injury. HSC-MVs or TGF-β1HSC-MVs were co-cultured with H2O2-treated HUVECs, respectively. Indicators including cell survival rate, apoptosis rate, oxidative stress, migration, invasion, and angiogenesis were measured. Simultaneously, the expression of proteins such as PI3K, AKT, MEK1+MEK2, ERK1+ERK2, VEGF, eNOS, and CXCR4 was assessed, along with activated caspase-3. SD rats were intraperitoneally injected with CCl4 twice a week for 10 weeks to induce liver injury models. HSC-MVs or TGF-β1HSC-MVs were injected into the tail vein of rats. Liver and hepatic vascular damage were also detected. Results: In H2O2-treated HUVECs, HSC-MVs increased cell viability, reduced cytotoxicity and apoptosis, improved oxidative stress, migration, and angiogenesis, and upregulated protein expression of PI3K, AKT, MEK1/2, ERK1/2, VEGF, eNOS, and CXCR4. Conversely, TGF-β1HSC-MVs exhibited opposite effects. CCl4- induced rat hepatic injury model, HSC-MVs reduced the release of ALT and AST, hepatic inflammation, fatty deformation, and liver fibrosis. HSC-MVs also downregulated the protein expression of CD31 and CD34. Conversely, TGF-β1HSC-MVs demonstrated opposite effects. Conclusion: HSC-MVs demonstrated a protective effect on H2O2-treated HUVECs and CCl4-induced rat hepatic injury, while TGF-β1HSC-MVs had an aggravating effect. The effects of MVs involve PI3K/AKT/VEGF, CXCR4, and MEK/ERK/eNOS pathways. [ABSTRACT FROM AUTHOR]

Primary hepatic angiosarcoma (PHA) is a rare liver malignancy with few studies describing its radiological characteristics. This article aims to assess the imaging features of each of the multiple delayed contrast-enhanced magnetic resonance imaging (MRI) scans, in addition to the conventional MRI protocol, in a patient with PHA. Standard MRI sequences and a liver protocol were used in the examination of a 71 year-old male with pathologically proven PHA after current imaging evaluation. In addition, the patient underwent transversal and coronal MRI T1-weighted scans at 10 min, 20 min and 90 min after intravenous (IV) administration of gadobenatedimeglumine (Gd-BOPTA). The PHA revealed a variable appearance on MRI, with classic imaging being insufficient in making a reliable diagnosis. Lesions have increased vascularity, which translates into increased IV contrast uptake in the MRI arterial phase, showing progressive and globular enhancement in the portal and parenchymatous phases. On delayed scans, at 10 min after IV administration, the lesions maintained no washout, but slightly began to washout at 20 min post-contrast. However, in the hepatobiliary phase (90 min post-contrast injection), on an MRI T1-weighted sequence, PHA lesions were hypointense, suggesting the absence of hepatocytes, thus indicating high-grade malignancy. This approach proved the conclusion that in a patient with PHA, an extra MRI T1-weighted scan at 90 min post-gadobenatedimeglumine injection can provide helpful information in differential diagnosis. [ABSTRACT FROM AUTHOR]

Presents articles to be published in the "European Journal of Biochemistry." "Characterization of a cDNA Clone Encoding Mollusc Insulin-Related Peptide II of Lymnaea Stagnalis," by A. B. Smith, W. P. M. Geraerts, I. Meester, H. van Heerikhuizen and J. Joosse; "Effects of Dexamethasone and cAMP on Tyrosine Aminotransferase Expression in Cultured Fetal Rat Hepatocytes," by L. L. Shelly and G. C. T. Yeoh; "Transient Kinetics of Flavin-Photosensitized Oxidation of Reduced Redox Proteins--Comparison of c-type Cytochromosomes and Plastocyanins," by J. A. Navarro, M. A. De la Rosa and G. Tollin; "Membrane-Bound Cytochromes in Chloroflexus Aurantiacus Studied by EPR," by P. van Vliet, D. Zannoni, W. Nitschke and A. W. Rutherford; Others.

The effect of methylene blue on the disposition of ethanol was studied in rats and humans. Methylene blue increased the metabolism of [14C]ethanol to 14CO2 in isolated hepatocytes and in intact rats by 75% and 30%, respectively. In healthy volunteers, methylene blue did not affect the pharmacokinetics of ethanol and did not alleviate the ethanol-induced NAD redox changes as reflected by the increase in the [lactate]/[pyruvate] ratio. [ABSTRACT FROM PUBLISHER]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]