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Regulation of postnatal forebrain amoeboid microglial cell proliferation and development by the transcription factor Runx1.

Microglia are the immune cells of the nervous system, where they act as resident macrophages during inflammatory events underlying many neuropathological conditions. Microglia derive from primitive myeloid precursors that colonize the nervous system during embryonic development. In the postnatal brain, microglia are initially mitotic, rounded in shape (amoeboid), and phagocytically active. As brain development proceeds, they gradually undergo a transition to a surveillant nonphagocytic state characterized by a highly branched (ramified) morphology. This ramification process is almost recapitul

Molecular cloning and characterization of LCRG1 a novel gene localized to the tumor suppressor locus D17S800-D17S930.

Laryngeal carcinoma (LC) is the most commonly diagnosed malignancy and recently the incidence of this disease has increased. By means of the mRNA differential display method we identified a cDNA, Laryngeal carcinoma related gene 1 (LCRG1) which has significantly reduced expression in 40% (12/30) of primary LCs and in 6 of 10 various cancer cell lines. Northern Blot analysis showed that LCRG1 was expressed more abundantly in human heart, pancreas, skeletal muscle, and in murine testis, liver, brain and heart than in other tissues. The cDNA sequence of this gene is identical to part of the seque

Bridging the gap: ferroptosis of immune cells in the tumor microenvironment.

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly recognized as a pivotal immunomodulatory mechanism within the tumor microenvironment (TME). Beyond its well-established role in tumor cell elimination, emerging evidence reveals that immune cell subsets exhibit distinct susceptibility to ferroptosis, with profound consequences for antitumor immunity. This review systematically delineates the dual and cell-type-specific roles of ferroptosis across innate and adaptive immune populations: while ferroptosis-mediated depletion of immunosuppress

Role of autophagy in cholangiocarcinoma: An autophagy-based treatment strategy.

Cholangiocarcinomas (CCAs) are diverse biliary epithelial tumours involving the intrahepatic, perihilar and distal parts of the biliary tree. The three entirely variable entities have distinct epidemiology, molecular characteristics, prognosis and strategy for clinical management. However, many cholangiocarcinoma tumor-cells appear to be resistant to current chemotherapeutic agents. The role of autophagy and the therapeutic value of autophagy-based therapy are largely unknown in CCA. The multistep nature of autophagy offers a plethora of regulation points, which are prone to be deregulated and

Pharmacological treatment options for mast cell activation disease.

Mast cell activation disease (MCAD) is a term referring to a heterogeneous group of disorders characterized by aberrant release of variable subsets of mast cell (MC) mediators together with accumulation of either morphologically altered and immunohistochemically identifiable mutated MCs due to MC proliferation (systemic mastocytosis [SM] and MC leukemia [MCL]) or morphologically ordinary MCs due to decreased apoptosis (MC activation syndrome [MCAS] and well-differentiated SM). Clinical signs and symptoms in MCAD vary depending on disease subtype and result from excessive mediator release by MC

Ferroptosis: a new dawn in the treatment of acute lymphoblastic leukemia.

Acute lymphoblastic leukemia poses substantial challenges in therapeutic management. As a novel form of programmed cell death, ferroptosis has emerged as a promising research direction in cancer therapy. Studies have emphasized the pivotal role of ferroptosis in ALL, indicating that targeting this pathway could provide a novel therapeutic strategy. This article systematically reviews the molecular regulatory mechanisms of ferroptosis in ALL and explores its potential clinical applications in the treatment and prognostic evaluation of the disease.

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… During this process, polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA) and adrenic acid (AdA) are esterified to phosphatidylethanolamine (PE) by acyl-CoA synthetase long-chain family member 4 (ACSL4) and lysophosphatidylcholine acyltransferase 3 (LPCAT3), forming AA-PE and AdA-PE conjugates … Subsequently, these phosphatidylethanolamines are oxidized by 15-lipoxygenase (ALOX15) to form phospholipid hydroperoxides (PLOOH) ( 23 ). …

Потенциальные цели микроглии в лечении нейродегенеративных заболеваний: механизм и терапевтические последствия.

В случае различных нейродегенеративных расстройств активируются микроглиальные клетки. Кроме того, дисфункциональная и гиперактивированная микроглия инициирует митохондриальную автофагию, окислительный стресс и патологическое накопление белка, заканчивающееся нейроинфламмацией, которая усугубляет повреждения допаминергических нейронов и вносит значительный вклад в патологию нейродегенеративного расстройства. Микроглиальная чрезмерная активация тесно связана с секрецией провоспалительных цитокинов, фагоцитозом травмированных нейронов и модуляцией нейротоксичной среды. В этом обзоре резюмируется

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… Subsequently, lysophosphatidylcholine acyltransferase 3 esterifies PUFA-coenzyme A into phosphatidylethanolamines. Lipoxygenases ultimately oxidize this phosphatidylethanolamine into lipid peroxides, initiating ferroptosis (Dixon et al., 2012). … synthetase family member 4; ARE: antioxidant response elements; DMT1: divalent metal transporter 1; GLUT: glucose transporters; GPX4: glutathione peroxidase 4; GSH: glutathione; LIP: labile iron pool; L-OH: lipid alcohols; L-OOH: lipid hydroperoxides; Nrf2: nuclear factor erythroid 2-related factor 2; PEs: phosphatidylethanolamines …

Food-derived compounds targeting ferroptosis for cancer therapy: from effects to mechanisms.

Ferroptosis is distinctive type programmed cell death. Tumor cells, with their higher iron levels, render them more susceptible to ferroptosis Inducing ferroptosis can activate immune cells, regulate immune evasion, and inhibit the biology activity of cancer cells. Therefore, ferroptosis-induced cancer cell death could become a promising approach for cancer treatment. Dietary compounds are an important source for drug discovery, and there has been an increasing amount of literature on food-derived ferroptosis inducers and their applications in cancer treatment. This review provides an overview

Оптимизация доставки каннабидиол: повышение растворимости и проницаемости воды посредством фосфолипидной комплексации.

Каннабидиол (КБР) продемонстрировал терапевтический потенциал в лечении эпилепсии, множественного склероза, болезни Альцгеймера, Паркинсона и Крона. Несмотря на ее многообещающие последствия и анальгетические, антивоспалительные и аксиолитические свойства, полный потенциал КБР сдерживается низкой растворимостью воды (0,7-10 мкг/мл), низкой проницаемостью и химической нестабильностью. Цель этого исследования состояла в том, чтобы повысить проницаемость кишечника (GI) в результате распада, стабильности и проницаемости кишечника КБР путем создания комплекса КБР-фосфолипид (CBD-PLC). Мы предположи

Repurposing Drugs in Oncology (ReDO)-mebendazole as an anti-cancer agent.

Mebendazole, a well-known anti-helminthic drug in wide clinical use, has anti-cancer properties that have been elucidated in a broad range of pre-clinical studies across a number of different cancer types. Significantly, there are also two case reports of anti-cancer activity in humans. The data are summarised and discussed in relation to suggested mechanisms of action. Based on the evidence presented, it is proposed that mebendazole would synergise with a range of other drugs, including existing chemotherapeutics, and that further exploration of the potential of mebendazole as an anti-cancer

Canine Cancer: Strategies in Experimental Therapeutics.

Cancer is the most common cause of death in adult dogs. Many features of spontaneously developing tumors in pet dogs contribute to their potential utility as a human disease model. These include similar environmental exposures, similar clonal evolution as it applies to important factors such as immune avoidance, a favorable body size for imaging and serial biopsy, and a relatively contracted time course of disease progression, which makes evaluation of temporal endpoints such as progression free or overall survival feasible in a comparatively short time frame. These criteria have been leverage

Микроглиа регулирует расчистку миелин и метаболизм холестерина после демиелинации с помощью интерферона регулирующего коэффициента 5.

Регулирующий фактор интерферона 5 (IRF5) — это фактор транскрипции, который играет определенную роль в организации врожденной иммунной реакции, особенно в ответ на вирусные инфекции. В частности, IRF5 был определен как ген микроглийного риска, связанный с множественным склерозом (MS), однако его конкретная роль в патогенезе MS остается неясной. С помощью ирф5-/- мышей наше исследование обнаруживает неканоническую функцию IRF5 в восстановлении MS. Ирф5-/- мыши продемонстрировали повышенный ущерб в экспериментальной модели аутоиммунной энцефаломиелита (EAE) и продемонстрировали неисправный набор

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… Additionally, we observed differences in the accumulation of phosphatidylcholines and phosphatidylethanolamines (data not shown), which are major components of cellular membranes. … This increase in phosphatidylcholines and phosphatidylethanolamines could correlate with inflammatory processes [ 56 ]. …

Don't eat me/eat me signals as a novel strategy in cancer immunotherapy.

Cancer stands as one of the prominent global causes of death, with its incidence burden continuously increasing, leading to a substantial rise in mortality rates. Cancer treatment has seen the development of various strategies, each carrying its drawbacks that can negatively impact the quality of life for cancer patients. The challenge remains significant within the medical field to establish a definitive cancer treatment that minimizes complications and limitations. In the forthcoming years, exploring new strategies to surmount the failures in cancer treatment appears to be an unavoidable pur

Nanoparticles for Effective Combination Therapy of Cancer.

Cancer continues to remains a major healthcare problem across the world despite strong translational research efforts towards tackling the disease. Surgery, when possible, along with radiation and chemotherapy continue to remain the mainstay of cancer treatment. Novel targeted therapies or biologics and immunotherapies have recently been approved to improve treatment efficacies while reducing collateral damage to normal, non-cancerous tissues. Combination therapies have shown better results than individual monotherapies in the clinic but often the improvements in therapeutic indices remain mar

Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma.

Pathways that govern cellular bioenergetics are deregulated in tumor cells and represent a hallmark of cancer. Tumor cells have the capacity to reprogram pathways that control nutrient acquisition, anabolism and catabolism to enhance their growth and survival. Tumorigenesis requires the autonomous reprogramming of key metabolic pathways that obtain, generate and produce metabolites from a nutrient-deprived tumor microenvironment to meet the increased bioenergetic demands of cancer cells. Intra- and extracellular factors also have a profound effect on gene expression to drive metabolic pathway

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… A second lipidomics study revealed upregulation of ceramides and phosphatidylethanolamines (PEs) and downregulation of phosphatidylcholines, sphingomyelin and one species of PE in MM patients ( 97 ). … domain-containing histone methyltransferase NADPH | Nicotinamide adenine dinucleotide phosphate NDMM | Newly diagnosed MM NEK2 | NIMA-related kinase 2 NIMA | Never in mitosis gene A NHL | Non-Hodgkin’s lymphoma NK | Natural killer NF-κB | Nuclear factor kappa B OXPHOS | Oxidative phosphorylation PE | Phosphatidylethanolamine …

Combinational Antitumor Strategies Based on the Active Ingredients of Toad Skin and Toad Venom.

A multidrug combination strategy is an important mean to improve the treatment of cancer and is the mainstream scheme of clinical cancer treatment. The active ingredients of traditional Chinese medicine, represented by toad skin and toad venom, have the advantages of high efficiency, low toxicity, wide action and multiple targets and have become ideal targets in combined treatment strategies for tumors in recent years. Toad skin and toad venom are traditional Chinese animal medicines derived from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider that have shown excellent therapeutic

Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues.

Compared with conventional optical microscopy techniques, mass spectrometry imaging (MSI) or imaging mass spectrometry (IMS) is a powerful, label-free analytical technique, which can sensitively and simultaneously detect, quantify, and map hundreds of biomolecules, such as peptides, proteins, lipid, and other organic compounds in cells and tissues. So far, although several soft ionization techniques, such as desorption electrospray ionization (DESI) and secondary ion mass spectrometry (SIMS) have been used for imaging biomolecules, matrix-assisted laser desorption/ionization (MALDI) is still t

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… Recently, a study ( Duenas et al., 2017a ) applied high-spatial resolution MALDI-MSI to map and visualize the 3D chemical imaging of a single cell for spatial distribution of phospholipid classes, phosphatidylcholine (PC), phosphatidylethanolamines (PE), and so on, in newly fertilized individual zebrafish … To investigate the possible role of epididymis in the complex maturation of sperm, MALDI-MSI investigated the precise location of lipid metabolites in the rat epididymis, mainly detecting phosphatidylcholines, sphingolipids, glycerophosphates, triacylglycerols, plasmalogens, phosphatidylethanolamines …

Pro-inflammatory Cytokines, Ferroptosis, and Cancer.

Ferroptosis, iron-dependent regulated cell death, is induced by the polyunsaturated fatty acid peroxidation of membrane phospholipids and is controlled by glutathione peroxidase 4. In recent years, convincing evidence has emerged, demonstrating a close relationship between chemo-, radio-, immuno-, and targeted therapy resistance and ferroptosis resistance. In this review, we discuss the basic principles of ferroptosis in cancer. Considerable attention is paid to the formation of an immunosuppressive tumor microenvironment. The main focus is centered on the involvement of the excessive, chronic

Transferrin-conjugated SNALPs encapsulating 2'-O-methylated miR-34a for the treatment of multiple myeloma.

Stable nucleic acid lipid vesicles (SNALPs) encapsulating miR-34a to treat multiple myeloma (MM) were developed. Wild type or completely 2'-O-methylated (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with transferrin (Tf) in order to target MM cells overexpressing transferrin receptors (TfRs). The type of miR-34a chemical backbone did not significantly affect the characteristics of SNALPs in terms of mean size, polydispersity index, and zeta potential, while the encapsulation of an OMet miR-34a resulted in a significant increase of miRNA encapsulation into the SNALPs.

Nebulised surfactant for the treatment of severe COVID-19 in adults (COV-Surf): A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: SARS-Cov-2 virus preferentially binds to the Angiotensin Converting Enzyme 2 (ACE2) on alveolar epithelial type II cells, initiating an inflammatory response and tissue damage which may impair surfactant synthesis contributing to alveolar collapse, worsening hypoxia and leading to respiratory failure. The objective of this study is to evaluate the feasibility, safety and efficacy of nebulised surfactant in COVID-19 adult patients requiring mechanical ventilation for respiratory failure. TRIAL DESIGN: This study is a dose-escalating randomized open-label clinical trial of 20 COVID-