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Iron in the Tumor Microenvironment-Connecting the Dots.

Iron metabolism and tumor biology are intimately linked. Iron facilitates the production of oxygen radicals, which may either result in iron-induced cell death, ferroptosis, or contribute to mutagenicity and malignant transformation. Once transformed, malignant cells require high amounts of iron for proliferation. In addition, iron has multiple regulatory effects on the immune system, thus affecting tumor surveillance by immune cells. For these reasons, inconsiderate iron supplementation in cancer patients has the potential of worsening disease course and outcome. On the other hand, chronic im

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… FPN1 is highly expressed in iron-recycling macrophage populations, such as red-pulp macrophages (RPMs) in the spleen and Kupffer cells (KCs) in the liver, at the basolateral surface of absorptive intestinal epithelial cells (IECs) in the duodenum and proximal jejunum and in the synzytiotrophoblast ( …

Mesoporous Silica Nanoparticles as Drug Delivery Vehicles in Cancer.

Even though cancer treatment has improved over the recent decades, still more specific and effective treatment concepts are mandatory. Surgical removal is not always possible, metastases are challenging and chemo- and radiotherapy can not only have severe side-effects but also resistances may occur. To cope with these challenges more efficient therapies with fewer side-effects are required. One promising approach is the use of drug delivery vehicles. Here, mesoporous silica nanoparticles (MSN) are discussed as biodegradable drug carrier to improve efficacy and reduce side-effects. MSN excellen

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… Moreover, histopathological analysis indicated no significant toxicity compared to controls, even though apparently macrophages in the liver (Kupffer cells) were swollen one day after MSN injection. The authors assumed that MSN were degraded and then excreted via the kidneys [ 85 ]. …

Семья " Interleukin-17 " в области здравоохранения и иммунных заболеваний: от происхождения до клинических последствий.

Семья интерлейкин-17 является ключевой группой цитокинов и демонстрирует широкий спектр биологических функций, включая регулирование подстрекательского каскада в различных аутоиммунных и подстрекательских болезнях, таких, как множественный склероз, оптический спектр нейромилита, миастения гравис, синдром Гильен-Барре, острый распределенный энцфаломиэлит, диабет, воспалительные кожные заболевания, суставное воспаление и рак. Хотя функция семьи интерлейкин-17 привлекает все большее внимание к исследованиям на протяжении многих лет, выражение, функции и механизмы регулирования различных членов се

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… Extracellular vesicles derived from the culture medium of Thy1 + cells triggered the expression of IL-17B and IL-25 in sinusoidal endothelial cells and Kupffer cells. … IL-17B stimulation promoted the growth of SHPCs in culture, suggesting that Thy1 + EVs, by targeting sinusoidal endothelial cells, Kupffer cells, and SHPCs, coordinate the IL-17RB signaling pathway to facilitate liver regeneration (Ichinohe et al., 2017). …

Tissue-Resident Myeloid and Histiocytic Cells in Health and Disease: Novel Emerging Concepts.

Although all myeloid cells are considered to derive from hematopoietic stem cells, the cells in each myeloid lineage are heterogeneous populations, and their distribution and functions vary, depending on underlying physiologic and pathologic processes, age, sex, and genetic and epigenetic signatures. In general, myeloid cells can be separated into circulating and tissue-resident cells. Tissue-resident myeloid cells can further be divided into cells derived from circulating monocytes, circulating stem cells, or local tissue-restricted stem or progenitor cells. Depending on underlying diseases a

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… Specialized macrophages (e.g., Kupffer cells, microglia, and Langerhans cells) are influenced by local factors such as TGF‐β, Interleukin‐10 (IL‐10), or colony‐stimulating factors (CSF). …

Каннабидиол как иммунный модулятор: всеобъемлющий обзор.

Каннабидиол (КБР), непсихоактивный фитоканнабиноид, полученный из сативы Каннабиса, стал многообещающим терапевтическим агентом в силу его разнообразных фармакологических свойств, включая сильные антивоспалительные, нейрозащитные и иммунодуляторные эффекты. КБР модифицирует иммунную реакцию, включая регулирование активности клеток Т, введение апоптоза макрофага, подавление провоспалительных цитокинов и модуляцию сигнальных путей воспаления и иммунной гомеостазии. Был проведен всеобъемлющий поиск литературы с использованием баз данных PubMed, Scopus и Web of Science в целях выявления соответств

Cancer Neoaxonogenesis: Mechanisms and Factors Involved in the Recruitment of Peripheral Nerves by Cancer Tissue.

Peripheral nerves provide a direct connection between the brain and the tumor microenvironment. This connection allows the nervous system to influence processes associated with the development, progression, and metastasis of different tumor types. Therefore, tumor innervation by peripheral nerve fibers is currently emerging as a characteristic that contributes to multiple hallmarks of cancer. Several experimental studies have shown that cancer progression involves actively inducing the ingrowth of autonomic and sensory nerve fibers into tumor tissue. In this process, known as neoaxonogenesis,

Posttransplant complications: molecular mechanisms and therapeutic interventions.

Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation.

Potential Immunotherapy Targets for Liver-Directed Therapies, and the Current Scope of Immunotherapeutics for Liver-Related Malignancies.

Liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is increasing in incidence and mortality across the globe. An improved understanding of the complex tumor microenvironment has opened many therapeutic doors and led to the development of novel pharmaceuticals targeting cellular signaling pathways or immune checkpoints. These interventions have significantly improved tumor control rates and patient outcomes, both in clinical trials and in real-world practice. Interventional radiologists play an important role in the multidisciplinary team given their expertise

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… The hepatic sinusoidal architecture consists of several unique cell types that participate in antigen presentation: hepatic stellate cells (HSC), liver sinusoidal endothelial cells (LSC), Kupffer cells (KC), and dendritic cells (DC) [ 3 , 4 , 5 ]. …

Enhancing the Safety of Nanoparticles in Medicine: Highlights of Progress and Critical Objectives.

Nanoparticles have transformed drug delivery, imaging, vaccination, and precision therapeutics, but their clinical translation remains constrained by safety profiles that are inseparable from material design, biological identity, host factors, and manufacturing. This review critically evaluates recent progress, persistent limitations, and priority objectives for safer nanomedicine. Unlike reviews organized primarily by material class or isolated toxicology endpoints, we integrate physicochemical determinants, protein corona formation, immune recognition, organ disposition, preclinical models,

Targeting super enhancers for liver disease: a review.

BackgroundSuper enhancers (SEs) refer to the ultralong regions of a gene accompanied by multiple transcription factors and cofactors and strongly drive the expression of cell-type-related genes. Recent studies have demonstrated that SEs play crucial roles in regulating gene expression related to cell cycle progression and transcription. Aberrant activation of SEs is closely related to the occurrence and development of liver disease. Liver disease, especially liver failure and hepatocellular carcinoma (HCC), constitutes a major class of diseases that seriously endanger human health. Currently,

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… CXCL6-EGFR-induced Kupffer cells secrete TGF-beta1 promoting hepatic stellate cell activation via the SMAD2/BRD4/C-MYC/EZH2 pathway in liver fibrosis. Journal of Cellular and Molecular Medicine. 2018;22(10):5050–5061. doi: 10.1111/jcmm.13787. …

EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.

Fibrosis is a condition characterized by the excessive accumulation of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have identified EP300, a histone acetyltransferase, as a crucial regulator of the epigenetic changes that contribute to fibrosis. In fact, EP300-mediated acetylation of histones alters global chromatin structure and gene expression, promoting the development and progression of fibrosis. Here, we review the role of EP300-mediated epigenetic regulation in multi-organ fibrosis and its potential as a therapeutic target. We discuss

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… Moreover, these authors determined two potential ligands for the epidermal growth factor receptor (EGFR) during HSC activation: amphiregulin (AREG) and progranulin (GRN), which are relevant mechanisms in immune cells such as Kupffer cells and monocyte-derived macrophages since they secrete high amounts …

Микробиота человека в области здравоохранения и отдельные раковые заболевания.

Большинство эпителиальных поверхностей нашего тела, пищеварительный тракт, дыхательные и врожденные системы, колонизируются большим количеством бактерий, археи, грибов, протозоанов и вирусов. Эти микробиота, особенно кишки, играют важную и полезную роль в пищеварении, метаболизме и синтезе витаминов. Их метаболиты стимулируют производство цитокина человеком, которое используется против потенциальных патогенов. На состав микробиоты влияет ряд внутренних и внешних факторов, включая питание, возраст, болезни и образ жизни. Такие изменения, называемые дисбиозом, могут быть связаны с развитием разл

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… Animal studies have found that lipopolysaccharide influences hepatic Kupffer cells, which produce the inflammatory cytokines TNF-α and IL-6. Cytokines activated by the LPS-TLR4-NF-кB signaling pathway can induce HCC by stimulating precancerous hepatocellular proliferation [ 302 ]. …

Delivery of Drugs into Cancer Cells Using Antibody-Drug Conjugates Based on Receptor-Mediated Endocytosis and the Enhanced Permeability and Retention Effect.

Innumerable people worldwide die of cancer every year, although pharmaceutical therapy has actualized many benefits in human health. For background, anti-cancer drug development is difficult due to the multifactorial pathogenesis and complicated pathology of cancers. Cancer cells excrete hydrophobic low-molecular anti-cancer drugs by overexpressed efflux transporters such as multiple drug resistance 1 (MDR1) at the apical membrane. Mutation-driven drug resistance is also developed in cancer. Moreover, the poor distribution of drug to cancer cells is a serious problem, because patients suffer f

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… Macrophages, Kupffer cells in the liver, and microglial cells in the brain play such an ingestive role. Phagocytosis, a type of endocytosis, by phagocytes such as macrophages forms phagosomes (1–3 μm in diameter) [ 88 , 89 ]. …

The Role of Platelet Dysfunctions in the Pathogenesis of the Hemostatic-Coagulant System Imbalances.

Platelet dysfunction plays a critical role in the pathogenesis of various disorders affecting the hemostatic-coagulant system. This review aims to explore the mechanisms by which platelet dysfunctions contribute to the disruption of hemostasis, leading to an increased risk of both thrombosis and bleeding. Platelets, traditionally known for their role in clot formation, can exhibit altered functionality under pathological conditions such as cardiovascular diseases, metabolic disorders, and autoimmune diseases, impacting their interaction with coagulation factors and vascular endothelium. The re

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… Additionally, the interaction between platelets and Kupffer cells in the liver appears to be involved in the clearance of both bacterial cells and platelets during infection. …

Potential Molecular Targeted Therapy for Unresectable Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers, representing a serious worldwide health concern. The recurrence incidence of hepatocellular carcinoma (HCC) following surgery or ablation is as high as 70%. Thus, the clinical applicability of standard surgery and other locoregional therapy to improve the outcomes of advanced HCC is restricted and far from ideal. The registered trials did not identify a treatment that prolonged recurrence-free survival, the primary outcome of the majority of research. Several investigator-initiated trials have demonstrated that var

Causes, clinical findings and therapeutic options in chylomicronemia syndrome, a special form of hypertriglyceridemia.

The prevalence of hypertriglyceridemia has been increasing worldwide. Attention is drawn to the fact that the frequency of a special hypertriglyceridemia entity, named chylomicronemia syndrome, is variable among its different forms. The monogenic form, termed familial chylomicronemia syndrome, is rare, occuring in 1 in every 1 million persons. On the other hand, the prevalence of the polygenic form of chylomicronemia syndrome is around 1:600. On the basis of the genetical alterations, other factors, such as obesity, alcohol consumption, uncontrolled diabetes mellitus and certain drugs may sign

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… On the other hand, infiltrating macrophages and Kupffer cells take up large amounts of chylomicrons in the liver, leading to hepatomegaly. A similar phenomenon can also be observed in the spleen, as well. …

Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets.

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third in cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, and genetic factors. No specific genetic alterations are unequivocally linked to HCC tumorigenesis. Current standard therapies include surgical options, systemic chemotherapy, and kinase inhibitors, like sorafenib and regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint inhibitors, such as atezolizumab and pembrolizumab, s

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… In the liver, TLR4 is normally expressed on the cell surface of hepatocytes, Kupffer cells, and hepatic stellate cells but at relatively low levels. However, in the presence of liver damage, TLR4 expression is upregulated [ 225 ]. …

The Black Hole: CAR T Cell Therapy in AML.

Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed/refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen-targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything. One must consider the fact that only around 30% of

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… Target Antigen | Function | Expression on Normal Cells | Expression on HSCs | Expression on LSCs CLL-1 | Glycoprotein, Transmembrane receptor | Myeloid, lung, epithelial cells | - | + CD 33 | SIGLEC family protein, Transmembrane receptor | Progenitor, myeloid, Kupffer cells | + | + CD 7 | Ig superfamily …

Single-cell sequencing in molecular diagnostics: Transformative yet untapped potential.

Single-cell sequencing (SCS) techniques have the potential to offer precise insights into cellular diversity by revealing unique genetic and transcriptomic profiles at the single-cell level. This advanced technology has been used extensively in research, but it has still not translated to clinical diagnostics, despite its potential. SCS provides more accurate granular information about heterogeneous cell populations and the creation of personalized treatment strategies. However, the integration of SCS into clinical practice is challenging. This review discusses the potential of SCS technologie

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… Previously unidentified subtypes of hepatocytes, Kupffer cells, and endothelial cells with distinct gene expression profiles were identified, together with a rare subset of bile duct cells with the ability to develop into organoids. …

Tailoring cells for clinical needs: Meeting report from the Advanced Therapy in Healthcare symposium (October 28-29 2017, Doha, Qatar).

New technologies and therapies designed to facilitate development of personalized treatments are rapidly emerging in the field of biomedicine. Strikingly, the goal of personalized medicine refined the concept of therapy by developing cell-based therapies, the so-called "living drugs". Breakthrough advancements were achieved in this regard in the fields of gene therapy, cell therapy, tissue-engineered products and advanced therapeutic techniques. The Advanced Therapies in Healthcare symposium, organized by the Clinical Research Center Department of Sidra Medicine, in Doha, Qatar (October 2017),

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… Liver endothelial sinusoidal cells and Kupffer cells are the main FVIII producers in the liver. By using cell-specific promoters, optimized with miRNA, a tolerizing pattern towards the transgene was shown in mice, mediated by T-regs intervention. …