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The role of cholesterol metabolism in leukemia.

Leukemia is a common hematological malignancy with overall poor prognosis. Novel therapies are needed to improve the outcome of leukemia patients. Cholesterol metabolism reprogramming is a featured alteration in leukemia. Many metabolic-related genes and metabolites are essential to the progress and drug resistance of leukemia. Exploring potential therapeutical targets related to cholesterol homeostasis is a promising area. This review summarized the functions of cholesterol and its derived intermediate metabolites, and also discussed potential agents targeting this metabolic vulnerability in

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… .; LDs lipid droplets. … Lipid droplet-organelle interactions: emerging roles in lipid metabolism . Curr Opin Cell Biol 2015 ; 35 : 91 – 97 . 25988547 10.1016/j.ceb.2015.04.017 [14] Martin S Parton RG . Lipid droplets: a unified view of a dynamic organelle . …

Navigating the Landscape of Exosomal microRNAs: Charting Their Pivotal Role as Biomarkers in Hematological Malignancies.

Under physiological and pathological conditions, all cells release extracellular vesicles named exosomes, which act as transporters of lipidic, protein, and genetic material from parent to recipient cells. Neoplastic cells can secrete higher number of exosomes to exert pro-tumoral effects such as microenvironmental changes, disease progression, immunosuppression and drug-resistance. This holds true for both organ-specific cancers and hematologic malignancies. One of the most important components of exosomal cargo are microRNAs which can mediate all the abovementioned effects. More specifically

Oroxylin A: A Promising Flavonoid for Prevention and Treatment of Chronic Diseases.

There have been magnificent advancements in the understanding of molecular mechanisms of chronic diseases over the past several years, but these diseases continue to be a considerable cause of death worldwide. Most of the approved medications available for the prevention and treatment of these diseases target only a single gene/protein/pathway and are known to cause severe side effects and are less effective than they are anticipated. Consequently, the development of finer therapeutics that outshine the existing ones is far-reaching. Natural compounds have enormous applications in curbing seve

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… droplet content, retinol, cholesterol, triglyceride ↓ATGL, α-SMA, α1collagen, fibronectin, desmin, ROS | [ 79 ] | In vivo | 20 mg/kg | C57BL/6 | ↑Antioxidant activity, ↓liver fibrosis, collagen deposition lipid droplet content, retinol, cholesterol, triglyceride, α-SMA, collagen I | [ 79 ] | In vitro … Loss of lipid droplets (LDs) is an important feature of liver fibrosis [ 164 ]. Therefore, the effect of OA on the disappearance of lipid droplets was examined in a study. …

The Hypoxia-Retinoid Axis in Idiopathic Pulmonary Fibrosis: Multifaceted Etiology and Therapeutic Potential.

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease with limited therapeutic options. This review focuses on the role of retinoids, particularly all-trans retinoic acid (atRA), and hypoxia in the pathogenesis of IPF. Despite an established understanding of genetic and environmental factors in IPF, the interplay between retinoid signaling and the response to hypoxia remains poorly explored due to its complexity. Preclinical evidence suggests that atRA could help reduce pulmonary fibrosis by modulating TGF-β signaling pathways and epithelial-to-mesenchymal transition (EM

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… The REs can be hydrolyzed to produce atROL and transferred by an unclear mechanism to the hepatic stellate cells (HSCs), where atROL is esterified again by LRAT and stored inside cytoplasmic lipid droplets [ 80 ]. … The identity of the RE hydrolases responsible for releasing atROL from REs stored in lipid droplets remains uncertain; however, it is suggested that four enzymes are involved at least in vitro: esterase-10 (ES-10), LPL, PLRP2, and hormone sensitive lipase (HSL). …

Okay, so I need to translate this medical text into Russian. Let me first read through the original sentence carefully. The sentence is: "N-Azacytidine Inhibits Myeloma Cell Growth While Preserving Multiple Myeloma Patient Derived-Bone Marrow Mesenchymal Stromal Cells Differentiation." Hmm, the key here is to translate it accurately using proper clinical and anatomical terms. Let me break it down. First, "N-Azacytidine" is a drug name. In Russian, drug names are often transliterated or use the original name with some adaptation. I think in Russian medical literature, they might use the international nonproprietary name, which is "N-азацидидин" or maybe "N-азацидид"? Wait, no, let me check. Wait, the international nonproprietary name for N-Azacytidine is "азацидидин" (azacitidine) in Russian. Wait, but the chemical name is N-Azacytidine, which is a nucleoside analog. In Russian, the term for azacitidine is "азацидидин" (azacitidine). Wait, but the original says "N-Azacytidine", so maybe it's "N-азацидидин" but I think in Russian medical terms, they might just use "азацидидин" without the

Множественная миелома (ММ) — неизлечимая гематологическая порча, вызванная аномальным распространением неизлечимо дифференцированных плазменных клеток в костном мозге. Текущие исследования показывают, что N-azacytidine как эпигенетическое лекарство и нуклеозный метаболический ингибитор могут быть эффективными при лечении MM. Вместе с тем данные о мезенхимальных стромальных клетках костного мозга (МСЦВ) в качестве критической клеточной популяции в процессах гематопоизи и реконструирования костей ограничены.МЕТОДЫ: Воздействие N-azacytidine на клеточную линию миэломы AMO-1, мезенхимальные строма

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… Namely, based on the number of cells in which lipid droplets were formed, no significant differences were found in the presence of N-azacytidine compared to untreated cells. … Also, no changes in presence of N-azacytidine were noticed, although its stimulatory influence on lipid droplets formation at 1 uM and 10 uM was published [ 77 , 80 ]. …

Диметилфумарат уменьшает травму от печени ишемии и реперуляции путем подавления сигнала CGAS-STING.

Повреждение печени во время периоперационной фазы операции на печени часто происходит в результате печени. Неправильная активация сигнала СТИНГ может вызвать чрезмерную воспламенение реакции на усугубление печени. Диметилфумарат (DMF) — разрешенный УЛХ иммунодулятор, используемый для лечения множественного склероза и псориаза в силу его заметных свойств против воспаления. Однако механизм и целевые показатели ДМФ в области иммуномодуляции остаются неясными. Здесь мы обнаружили, что DMF подавляет активацию CGAS-STING, индуцируемую HSV-1, ДНК яичек и митохондриальная ДНК в различных клетках. DMF

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… Hyperbaric oxygen promotes cGAS‐STING activation, aiding liver cancer immunotherapy. 11 We demonstrated that TRIM14 influences the selective autophagic degradation of cGAS by modulating its ubiquitination. 26 Our study indicates that HNF1A targets TBK1 to inhibit the lipid droplet‐activated … cGAS‐STING pathway, while STING regulates mTORC1 activation, influencing the autophagic degradation of lipid droplets. 9 , 10 , 12 Furthermore, low doses of sorafenib can inhibit cGAS‐STING activation, suggesting its potential as a treatment for STING overactivation. 35 This research …

Advanced Diagnostic Techniques

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Специальный выпуск "Роль липидов в здравоохранении и болезнях".

Липиды представляют собой гидрофобные биомолекулы, которые, как правило, характеризуются как восковые или масляные и нерастворимые в воде, включающие в себя структурно разнообразную группу, включающую триглицериды, фосфолипиды, воски и стероиды [...].

Close interactions between lncRNAs, lipid metabolism and ferroptosis in cancer.

Abnormal lipid metabolism including synthesis, uptake, modification, degradation and transport has been considered a hallmark of malignant tumors and contributes to the supply of substances and energy for rapid cell growth. Meanwhile, abnormal lipid metabolism is also associated with lipid peroxidation, which plays an important role in a newly discovered type of regulated cell death termed ferroptosis. Long noncoding RNAs (lncRNAs) have been proven to be associated with the occurrence and progression of cancer. Growing evidence indicates that lncRNAs are key regulators of abnormal lipid metabo

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… When the cholesterol in the cell exceeds what the cell needs, cholesterol is either converted to cholesterol ester (CE) by the action of cholesterol acyltransferase (ACAT) 50 , which is stored in lipid droplets or secreted in lipoproteins, or is excreted from the cell via an ATP binding cassette (ABC … When there is too much FA, most of the FA can be connected to the glycerol backbone to form TG, which is then stored in cytoplasmic lipid droplets (LDs) 145 . This storage itself is not disease-causing, but TG, as a substance for storing FA, can release FA at any time. …

A Super-Enhancer-Driven Transcriptional Regulatory Circuit Underlying Abiraterone Resistance in Castration-Resistant Prostate Cancer.

Castration-resistant prostate cancer (CRPC) remains the leading cause of mortality among prostate cancer patients. While second-generation androgen receptor (AR) pathway-targeted therapies, such as Abiraterone, have significantly improved survival outcomes, resistance to these treatments ultimately emerges, posing a critical challenge. Understanding the mechanisms underlying Abiraterone resistance is essential for developing strategies to enhance patient outcomes. In this study, a super-enhancer (SE)-driven transcriptional regulatory circuit is identified involving BCL6, NFIB, and SMAD3 that f

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… To validate this, we examined the lipid droplet abundance within cells following the knockdown of BCL6, SMAD3 and NFIB individually, revealing a significant decrease in lipid droplets (Figure S5A,B , Supporting Information). … The accumulation of lipid droplets, that consist of a central core of triglycerides and cholesteryl esters, is caused by aberrant lipid metabolism. …

Количественная оценка холестерина в мозговой и спинной кордах во время развития, обезвоживания и ремиелинации.

Хлестерин в центральной нервной системе (КНС) в значительной степени неэстерифицирован (>99%) и присутствует главным образом в миелинской оболочке (~70% от общего количества холестерина CNS). Однако во время неврологических заболеваний наблюдалось накопление холестерина. В этом поперечном исследовании мы измерили уровень свободного холестерина и холестерина эстера в мозгу и спинные мозги модели мыши Plp1-iCKO-Myrf во время послеродовой миелиации, демиелинации и ремиелиции с использованием газовой хроматографии-массы спектрометрии с одним ионным мониторингом (GC-MS-SIM) и жидкой хроматографии-м

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… Lending support to a role for ACAT1 in cholesterol ester formation in the Plp1 -iCKO- Myrf model, lipid droplet accumulation was observed in microglia during peak demyelination. LCAT is an extracellular enzyme that is secreted by astrocytes and acts on cholesterol in lipoprotein particles [ 22 ]. … Excess cholesterol in the brain is esterified (1%) and stored as lipid droplets inside cells [ 8 ], or converted to oxysterols that can cross the blood–brain barrier [ 42 ]. …

Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer.

Uncontrolled proliferation is a feature defining cancer and it is linked to the ability of cancer cells to effectively adapt their metabolic needs in response to a harsh tumor environment. Metabolic reprogramming is considered a hallmark of cancer and includes increased glucose uptake and processing, and increased glutamine utilization, but also the deregulation of lipid and cholesterol-associated signal transduction, as highlighted in recent years. In the first part of the review, we will i) provide an overview of the major types of lipids found in eukaryotic cells and their importance as med

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… It remains to be determined whether excessive accumulation of lipids is a consequence of the genetic alterations occurring in ccRCC or whether changes in lipid metabolism which result in lipid droplets accumulation, promotes an escalating malignancy of the cells. … Lipid droplets in inflammation and cancer. Prostaglandins Leukot Essent Fatty Acids. 2010;82:243–250. doi: 10.1016/j.plefa.2010.02.005. 94. Du W., Zhang L., Brett-Morris A., Aguila B., Kerner J., Hoppel C.L., Puchowicz M., Serra D., Herrero L., Rini B.I., et al. …

Advances in the application of Raman spectroscopy in haematological tumours.

Hematologic malignancies are a diverse collection of cancers that affect the blood, bone marrow, and organs. They have a very unpredictable prognosis and recur after treatment. Leukemia, lymphoma, and myeloma are the most prevalent symptoms. Despite advancements in chemotherapy and supportive care, the incidence rate and mortality of patients with hematological malignancies remain high. Additionally, there are issues with the clinical diagnosis because several hematological malignancies lack defined, systematic diagnostic criteria. This work provided an overview of the fundamentals, benefits,

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic

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… The IM expands into an autophagosome (AP) with a double-layer membrane, which can engulf any cellular component, including proteins, damaged organelles and lipid droplets. … S: SC nucleus; L: lysosome; M: mitochondria; LD: lipid droplet. AVs include autophagosomes and autolysosomes. * p < 0.05. This was reprinted from Reference [ 3 ]. 2.1. …

Митохондриальная ДНК (mtDNA) в качестве жидкого биомаркера в нейродегенеративных расстройствах: систематический обзор.

ИСТОРИЯ ВОПРОСА: В ряде исследований была проведена оценка периферийных и цереброспинных жидкостей (CSF) mtDNA как предполагаемого биомаркера нейродегенеративных заболеваний, что зачастую приводит к непоследовательным выводам. Мы систематически анализировали текущие данные, позволяющие оценить уровни крови и CSF mtDNA и возможное бремя в болезни Паркинсона (PD), болезни Альцгеймера (ALS) и амиотропическом боковом склерозе (ALS). Множественный склероз (MS) был также включен в качестве парадигмы хронического нейроинфламмации под воздействием нейродегенерации. МЕТОДЫ: Медлин, Эмбаза, Скопус и веб

Non-Hematologic Toxicity of Bortezomib in Multiple Myeloma: The Neuromuscular and Cardiovascular Adverse Effects.

The overall approach to the treatment of multiple myeloma (MM) has undergone several changes during the past decade. and proteasome inhibitors (PIs) including bortezomib, carfilzomib, and ixazomib have considerably improved the outcomes in affected patients. The first-in-class selective PI bortezomib has been initially approved for the refractory forms of the disease but has now become, in combination with other drugs, the backbone of the frontline therapy for newly diagnosed MM patients, as well as in the maintenance therapy and relapsed/refractory setting. Despite being among the most widely

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… These pathological findings were reproduced in an in vitro model, indeed, primary human myoblasts exposed to bortezomib within the dose range found in the plasma of treated patients presented excessive storage of lipid droplets together with structural and functional mitochondrial abnormalities, and … Neither storage of lipid droplets nor morphological evidence of apoptosis or necrosis was observed in any muscle samples. …

Functions and Therapeutic Potentials of Long Noncoding RNA in Skeletal Muscle Atrophy and Dystrophy.

Skeletal muscle is the most abundant tissue in the human body and is responsible for movement, metabolism, energy production and longevity. Muscle atrophy is a frequent complication of several diseases and occurs when protein degradation exceeds protein synthesis. Genetics, ageing, nerve injury, weightlessness, cancer, chronic diseases, the accumulation of metabolic byproducts and other stimuli can lead to muscle atrophy. Muscular dystrophy is a neuromuscular disorder, part of which is caused by the deficiency of dystrophin protein and is mostly related to genetics. Muscle atrophy and muscular

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… For example, LINC00473 can crosslink with mitochondria and lipid droplet proteins, thereby influencing lipolysis and mitochondrial oxidative metabolism [ 20 ]. … It functions by encapsulating damaged organelles, protein aggregates or lipid droplets within autophagosomes, which subsequently fuse with lysosomes to degrade these contents [ 26 ]. …

Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis.

Osteocytes are the main cells in mineralized bone tissue. Elevated osteocyte apoptosis has been observed in lytic bone lesions of patients with multiple myeloma. However, their precise contribution to bone metastasis remains unclear. Here, we investigated the pathogenic mechanisms driving melanoma-induced osteocyte death. Both in vivo models and in vitro assays were combined with untargeted RNA sequencing approaches to explore the pathways governing melanoma-induced osteocyte death. We could show that ferroptosis is the primary mechanism behind osteocyte death in the context of melanoma bone m

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… Notably, there was a greater accumulation of lipid droplets in the cytoplasm of melanoma CM-treated MLO-Y4 cells compared to the untreated group (Fig. 3i ). … We thus conducted transmission electron microscopy (TEM) analysis and observed a greater accumulation of lipid droplets in the cytoplasm of MLO-Y4 cells treated with melanoma (Fig. 4d ). Znpp treatment, however, significantly decreased the formation of these lipid droplets (Fig. 4d ). …

Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients.

The molecular explanation about why some pancreatic cancer (PaCa) patients die early and others die later is poorly understood. This study aimed to discover potential novel markers and drug targets that could be useful to stratify and extend expected survival in prospective early-death patients. We deployed a deep learning algorithm and analyzed the gene copy number, gene expression, and protein expression data of death versus alive PaCa patients from the GDC cohort. The genes with higher relative amplification (copy number >4 times in the dead compared with the alive group) were EWSR1, FLT3,

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… None of the nine genes reported in [ 3 ] associated with survival in lipid droplets (LDs) were found to be significantly up- or down-regulated in our analysis. This may be due to differences in the type of analyzed sample, as explained in the discussion section. … Identification of prognostic lipid droplet-associated genes in pancreatic cancer patients via bioinformatics analysis Lipids Health Dis. 2021 20 58 10.1186/s12944-021-01476-y 34078402 PMC8171034 4. Cabasag C.J. Arnold M. Rutherford M. Bardot A. Ferlay J. Morgan E. Little A. De P. Dixon E. …

Silencing SFRP1 in bone mesenchymal stem cells alleviates pediatric B-ALL-driven bone loss by activating Wnt/β-catenin signaling.

BackgroundBone loss is the most common skeletal complication of childhood acute lymphoblastic leukemia (ALL) and seriously affects the long-term survival quality of children. However, the mechanisms behind bone loss are complicated and need to be elucidated. This study seeks to examine the principal parameters influencing the osteogenic development of bone marrow mesenchymal stem cells (BMSCs) in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) experiencing bone loss, and to identify viable ways for alleviating bone loss.MethodsFirstly, bone mass of adolescent B-ALL patients