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Lipopolysaccharide-induced cytokine and receptor expression and neutrophil infiltration in the liver of osteopetrosis (op/op) mutant mice.

BACKGROUND/AIMS: Mice homozygous for the osteopetrosis (op) mutation are genetically deficient in macrophage colony-stimulating factor (M-CSF/CSF-1) and are characterized by defective differentiation and function of macrophages. The aim of this study is to assess the contribution of M-CSF to lipopolysaccharide (LPS)-induced cytokine expression and neutrophil infiltration in the liver. METHODS: We investigated the effects of LPS administration in M-CSF-deficient op/op mutant mice. The expression of cytokines and receptors in the liver was studied by immunohistochemistry and RT-PCR. Neutrophil

Diagnostic value of T2 relaxation time for hepatic iron grading in rat model of fatty and fibrotic liver.

The objective of this study was to assess the quantitative diagnostic value of T2 relaxation time for determining liver iron grades in the presence of fat and fibrosis. Sixty Sprague-Dawley (SD) male rats were randomly divided into control (10 rats) and model (50 rats) groups. The model group of coexisting iron, steatosis, and liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4) dissolved in edible vegetable oil (40% v/v). The control group received an intraperitoneal injection of 0.9% saline. All rats underwent multi-echo gradient and spin echo (M-GRASE) magn

NTP Toxicology and Carcinogenesis Studies of o-Nitroanisole (CAS No. 91-23-6) in F344 Rats and B6C3F1 Mice (Feed Studies).

o-Nitroanisole is used as an intermediate for the preparation of o-anisidine and in the manufacture of azo dyes. Toxicology and carcinogenesis studies were conducted by administering o-nitroanisole (>99% pure) in the diet to groups of male and female F344 rats and B6C3F1 mice for 14 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Chinese hamster ovary cells, and mouse lymphoma cells. 14-DAY STUDIES: Groups of five male and five female F344 rats received diets containing 0, 583, 1,166, 2,332, 4,665, or 9,330 ppm o-nitroanisole. Mean body weight

Differential expression of stress-inducible proteins in chronic hepatic iron overload.

INTRODUCTION: Oxidative stress can trigger a cellular stress response characterized by induction of antioxidants, acute phase reactants (APRs) and heat shock proteins (HSPs), which are presumed to play a role in limiting tissue damage. In rodents, hepatic iron overload causes oxidative stress that results in upregulation of antioxidant defenses with minimal progressive liver injury. The aim of this study was to determine whether iron overload modulates expression of other stress-responsive proteins such as APRs and HSPs that may confer protection against iron-induced damage in rodent liver. M

THE CORRELATION BETWEEN THE HISTOLOGICAL CHANGES AND THE FATE OF LIVING TUBERCLE BACILLI IN THE ORGANS OF TUBERCULOUS RABBITS.

It has been found that although there is some parallelism between the quantity of tubercle bacilli demonstrable histologically and the numbe … es has been discussed. It has been seen that from the beginning this accumulation is greater in the Kupffer cells of the liver, in the macrophages of the spleen and in the reticular cells of the bone marrow than within the mononuclears of the lung, the organ where the bacilli grow with the greatest rapidity and are destroyed with the greatest difficulty. Acid-f …

Autophagy induced by AXL receptor tyrosine kinase alleviates acute liver injury via inhibition of NLRP3 inflammasome activation in mice.

Severe hepatic inflammation is a common cause of acute or chronic liver disease. Macrophages are one of the key mediators which regulate the progress of hepatic inflammation. Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop. However, the functional contribution of each TAM family member to the progression of hepatic inflammation remains elusive. In this study, we explore the role of individual TAM family proteins during autophagy inducti

NTP Comparative Toxicity and Carcinogenicity Studies of o-Nitrotoluene and o-Toluidine Hydrochloride (CAS Nos. 88-72-2 and 636-21-5) Administered in Feed to Male F344/N Rats.

o-Nitrotoluene and o-toluidine hydrochloride are structurally related chemicals that are suspected and demonstrated animal carcinogens, resp … cts in rats administered o-toluidine hydrochloride consisted of minimal hemosiderin accumulation in Kupffer cells; the incidence of this lesion in the stop-exposure group decreased during the recovery period. o-Toluidine hydrochloride caused fewer and much smaller PGST-positive foci than those caused by o-nitrotoluene. o-Nitrotoluene caused an accumulation of h …

[The experimental studies on Capillaria hepatica].

Capillaria hepatica is an extremely common parasite of rats. Several human cases have also been reported from various parts of the world and recently these aroused the clinical interests. The present study was undertaken to investigate the biological observations of C. hepatica and the changes occurring in blood picture and serum protein in the experimentally infected hosts. The source of C. hepatica obtained from the deposit of non-embryonated eggs encapsulated in the liver of house rats(Rattus norvegicus) in Seoul. The eggs isolated from the infected liver tissues by the freshly prepared art

Navigating hepatotoxicity of antibody-drug conjugates: from mechanistic insights to clinical and postmarketing evidence.

Antibody-drug conjugates (ADCs) are rapidly developing targeted cancer therapeutic agents that combine specific monoclonal antibodies with cytotoxic agents. Currently, 17 ADCs are approved for the global market for treating hematological and solid tumors with more than 100 ADCs are in phase III clinical trials. ADC-induced hepatotoxicity is a significant concern with unclear mechanisms, and the incidence of hepatic adverse events (AEs) varies across different ADCs. Most hepatic AEs are moderate; however, some ADCs can cause life threatening or fatal AEs. The management of hepatic AEs is limite

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… Both hepatocytes and Kupffer cells contribute to ADC disposition in the liver. … Figure 2c illustrates off-target hepatotoxicity by showing how hepatocytes, Kupffer cells and LSECs internalize ADCs or free payloads through non-specific or receptor-mediated mechanisms. …

Anti-PEG Antibodies and Their Biological Impact on PEGylated Drugs: Challenges and Strategies for Optimization.

Polyethylene glycol (PEG) has been widely utilized in optimizing therapeutics due to its excellent biocompatibility and chemical stability. However, multiple dosing of PEGylated drugs may result in toxicity due to PEG accumulation in tissues, leading to the formation of anti-PEG antibodies (APAs), which can accelerate drug clearance, reduce efficacy, and alongside enhanced side effects, such as allergic reactions. Notably, pre-existing APAs have also been detected in individuals with no prior exposure to PEGylated drugs, raising additional clinical concerns. This review summarizes the mechanis

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… If the encapsulated drug is cytotoxic, aggregation of liposomes with hepatic Kupffer cells may lead to apoptosis and necrosis of these cells. Recovery of Kupffer cell function takes about two weeks, during which the presence of bacteremia could be fatal for cancer patients [ 37 ]. … Effect of Kupffer cells depletion on ABC phenomenon induced by Kupffer cells-targeted liposomes Asian J. Pharm. Sci. 2019 14 455 464 10.1016/j.ajps.2018.07.004 32104474 PMC7032111 38. Zhao Y.X. Wang C.L. Wang L. Yang Q. Tang W.Y. She Z.N. Deng Y.H. …

The role of the innate immune system in the development and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Most patients present with advanced or metastatic HCC at diagnosis and face a dismal prognosis. Tyrosine kinases are the gold standard treatment for this disease but yield limited survival benefits. Immune checkpoint inhibitors that augment adaptive immunity have been tested in HCC. Complex interactions between tumor cells, lymphocytes and the tumor environment determine the efficacy of such immunotherapies. Innate immune mechanisms - known drivers of liver disease progression in pre-HCC conditions such as fibrosis or cirr

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… DC: Dendritic cell; HCC: Hepatocellular carcinoma; HSC: Hepatic stellate cell; KC: Kupffer cell; NASH: Nonalcoholic steatosis hepatis; NK: Natural killer; NKT: Natural killer T cell. … On the other hand, a prolonged activation of both Kupffer cells (KCs) and inflammatory monocytes represents a characteristic (pathological) feature observed in the context of chronic liver inflammation [ 51 ], potentially leading to HCC. …

Heterogeneous tissue-specific macrophages orchestrate metastatic organotropism of breast cancer: implications for promising therapeutics.

Compelling evidences have manifested that breast cancer cells prefer to metastasize to certain distant organs, including brain, lung, bone and liver. According to the canonical "seed and soil" theory, this prominent biological behavior, termed as metastatic organotropism, involves intricate interactions between breast cancer cells (the "seeds") and specific residents in the tumor microenvironment (the "soil"), initiating from pre-metastatic niche formation to metastatic outgrowth. Recently, multifaceted heterogeneity of tissue-specific macrophages (TSMs) and their roles played in organotropic

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… cells (KCs) in liver. … TSMs inside metastatic organs of an MBC patient are represented by alveolar and intestinal macrophages in lung, Kupffer cells, liver capsular macrophages, central vein macrophages and lipid-associated macrophages in liver, microglia and CNS-associated macrophages in the CNS, osteoclasts, osteomacs and …

NTP Toxicology and Carcinogenesis Studies of para-Chloroaniline Hydrochloride (CAS No. 20265-96-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

p-Chloroaniline has a large production volume and is used as a dye intermediate. Toxicology and carcinogenesis studies of p-chloroaniline (g … mg/kg in male and female rats. Compound-related lesions in mice included hemosiderosis of the liver Kupffer cells and congestion of the spleen. In the 13-week studies, 10 rats of each sex were administered doses of 0, 5, 10, 20, 40, or 80 mg/kg. All male rats lived to the end of the 13-week studies. One of 10 female rats that received 80 mg/kg died from unknown …

Liver failure due to relapsed myeloma and hepatic iron overload.

Multiple myeloma is a hematologic malignancy that classically manifests with hypercalcaemia, renal insufficiency, anaemia and lytic bone lesions. Liver dysfunction in multiple myeloma is a lesser known complication that occurs through biliary obstruction, liver infiltration by plasma cells, amyloid/light chain deposition or due to liver injury from medications. Although transfusion-related hepatic iron overload-leading to significant liver disease-is a recognised complication in certain hematologic malignancies, little is known about transfusional iron overload in patients with multiple myelom

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… In addition, increased deposits of iron in the hepatocytes and Kupffer Cells were noted, consistent with secondary iron overload ( Figures 2B ). Figure 1. Liver biopsy (A and B). A: H&E 20×, periductular clusters of malignant plasma cells with features of plasmablasts. … B: Iron Stain 10×: increased intracytoplasmic iron deposits in hepatocytes and Kupffer Cells. The observed liver failure was primarily attributed to malignant infiltration by relapsed myeloma and secondarily contributed by transfusional iron overload. …

Critical considerations for targeting colorectal liver metastases with nanotechnology.

Colorectal cancer remains a significant cause of morbidity and mortality worldwide. Half of all patients develop liver metastases, presenting unique challenges for their treatment. The shortcomings of conventional chemotherapy has encouraged the use of nanomedicines; the application of nanotechnology in the diagnosis and treatment of disease. In spite of technological improvements in nanotechnology, the complexity of biological systems hinders the prospect of nanomedicines being applied in cancer therapy at the present time. This review highlights current biological barriers and discusses aspe

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… ABBREVIATIONS asialoglycoprotein receptor colorectal cancer dendritic cell extracellular matrix enhanced permeability and retention hepatic stellate cell Kupffer cell liver sinusoidal endothelial cell lymphatic vessel endothelial hyaluronan receptor metastatic colorectal cancer mononuclear … Kupffer cells, the specialized macrophages of the liver, are located in the lumen of the sinusoids and their primary function involves the removal of particulates from the portal blood. …

Злоумышленная малярия: результаты вскрытия и морфологические характеристики.

ВАЖНЯЯ малярия, обусловленная инфекцией плазмодия фальципарума, передающейся москитами < < Анофелес > > , представляет собой чрезвычайную ситуацию, угрожающую жизни людей и приводящую к высокому уровню смертности в странах Африки к югу от Сахары. P. falciparum инфицирует красные кровяные клетки, вызывая их агрегацию и сцепление с эндотелиальной облицовкой малых сосудов. Этот микроваскулированный секвестр может препятствовать кровотоку, что приводит к ишемии и кровоизлиянию в организм, вызванному разрывом небольших судов. В случае внезапной смерти диагноз возможен только после вскры

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… Microscopic analysis of liver tissue highlighted hyperplastic Kupffer cells and macrophages in the sinusoids and within the portal tracts, both rich in malarial pigment (Fig. 3 d); PRBCs were also noted in hepatic sinusoids. The spleen showed haemorrhagic suffusion. … cells of the liver rich in hemozoin ( d H&E stain original magnification × 200, arrow highlights hemozoin in Kupffer cells) Fig. 4 Disarray of myocardial fibers ( a H&E stain, original magnification × 100); haemorrhagic necrotic area involving the anteroseptal wall ( b H&E stain, original magnification …

Hepatic amyloidosis in a patient with chronic liver failure: A case report.

BackgroundAmyloidosis is a rare disorder that can be classified into various types, and the most common type is the systemic light chain type. The prognosis of this disease is extremely poor. In general, amyloidosis mainly affects the kidneys and heart and manifests as abnormal proliferation of clonal plasma cells. Cases in which the liver is the primary organ affected by amyloidosis, as in this report, are less common in clinical practice.Case summaryA 62-year-old man was admitted with persistent liver dysfunction of unknown cause and poor treatment outcomes. His condition persisted, and he d

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… C68 staining revealed a small number of activated Kupffer cells. α-SMA staining revealed a large number of activated hepatic stellate cells. Positive staining for MUM1 was observed in a few plasma cells. IgG staining was positive (light pink staining), while IgG4 staining was negative. … Prussian blue staining showed the deposition of iron particles in liver cells and Kupffer cells. Copper staining was negative. Polarized light microscopy revealed positive Congo red and oxidized Congo red staining. …

Regulatory T cells and immune escape in HCC: understanding the tumor microenvironment and advancing CAR-T cell therapy.

Liver cancer, which most commonly manifests as hepatocellular carcinoma (HCC), is the sixth most common cancer in the world. In HCC, the immune system plays a crucial role in the growth and proliferation of tumor cells. HCC achieve immune escape through the tumor microenvironment, which significantly promotes the development of this cancer. Here, this article introduces and summarizes the functions and effects of regulatory T cells (Tregs) in the tumor microenvironment, highlighting how Tregs inhibit and regulate the functions of immune and tumor cells, cytokines, ligands and receptors, etc, t

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… Kupffer cells, a type of macrophage, exhibit both M1 and M2 phenotypes. As liver cancer progresses, Kupffer cells transition from an intermediate phenotype to the M1 phenotype, characterized by an anti-inflammatory profile. When exposed to factors like IL-3 and IL-4, M1 cells secrete TGF-β. … With the increasing levels of TGF-β in the TME, Kupffer cells gradually transition from an anti-inflammatory to an immune-suppressive phenotype, promoting immune evasion ( 17 , 41 ). …

Targeting fibrosis, mechanisms and cilinical trials.

Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response. Multiple organs can develop fibrosis, including the liver, kidney, heart, and lung. Fibrosis such as liver cirrhosis, idiopathic pulmonary fibrosis, and cystic fibrosis caused substantial disease burden. Persistent abnormal activation of myofibroblasts mediated by various signals, such as transforming growth factor, platelet-derived growth factor, and fibroblast growh factor, has been recongized as a major event in the occurrence and progression of fibrosi

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… Extracellular events from Kupffer cells (liver-resident macrophages), hepatocytes, B lymphocytes, and T lymphocytes further modulate the activation of HSCs 87 , 88 . … PPARβ/δ is mainly expressed in hepatocytes, Kupffer cells, and HSCs in liver 231 , 232 . PPARβ/δ-null mice exhibited aggravated hepatoxicity in carbon tetrachloride (CCl 4 )-treated mice 233 . …

Ассоциация базового липополисачарида и протеина с расширенным уровнем инвалидности, динамика развития у пациентов с повторным множественным склерозом: экспериментальное исследование.

Прогнозирование развития этой болезни на ранней стадии возбудителя наиболее часто встречающегося вида множественного склероза (MS), известного как релапсирующий множественный склероз (RRMS), имеет важное значение для быстрого изменения методов лечения, нацеленного на сокращение рецидивов и инвалидности в клинических условиях. В этом исследовании приняли участие в общей сложности 58 пациентов с системой RRMS, число которых в рамках расширенной шкалы взносов для инвалидов (EDSS) составляет менее 4. Проведена базовая магнитно-резонансная съемка (MRI) и проведена оценка повреждений мозга и спинног

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… After binding with LPS, the complex of LBP and LPS is eliminated from circulation by the CD14 receptor on Kupffer cells [ 19 ]. Therefore, sCD14 is also an indirect marker of endotoxemia. … Role of Kupffer Cells in Driving Hepatic Inflammation and Fibrosis in HIV Infection. Front. Immunol. 2020;11:1086. doi: 10.3389/fimmu.2020.01086. 20. Lublin F.D., Reingold S.C., Cohen J.A., Cutter G.R., Sørensen P.S., Thompson A.J., Wolinsky J.S., Balcer L.J., Banwell B., Barkhof F., et al. …