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Targeting of mitochondrial fission through natural flavanones elicits anti-myeloma activity.

BackgroundMitochondrial alterations, often dependent on unbalanced mitochondrial dynamics, feature in the pathobiology of human cancers, including multiple myeloma (MM). Flavanones are natural flavonoids endowed with mitochondrial targeting activities. Herein, we investigated the capability of Hesperetin (Hes) and Naringenin (Nar), two aglycones of Hesperidin and Naringin flavanone glycosides, to selectively target Drp1, a pivotal regulator of mitochondrial dynamics, prompting anti-MM activity.MethodsMolecular docking analyses were performed on the crystallographic structure of Dynamin-1-like

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… Immunofluorescence staining of lipid droplets Lipid droplets were determined using LipidTOX (Thermo Fisher Scientific) or BODIPY 493/503 (Thermo Fisher Scientific) probe staining, according to standard protocols. … S9D) and lipid droplet content (Fig. 5 H; Additional file 1 : Fig. S9E). …

Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review.

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo, following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms

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… droplet accumulation, ↑CD23 expression, Lipid peroxidation-independent mechanisms | [ 26 ] Raji, Ramos, U937-GTB, U937-1 and Mono Mac-6 | Highly sensitive | * | * | 30, 60 and 120 μM | 24 h and 72 h | ↑ Apoptosis and necrosis (EPA) ↓ Cell multiplication ↑TAG-rich lipid droplets (EPA) ↑Lipid peroxidation … In addition, some EPA-resistant cells such as U-698 have a limited ability to uptake PUFAs leading to reduced accumulation of cytosolic lipid droplets, a characteristic of responsive cells [ 26 , 71 ]. …

Терапевтический потенциал диметилФумарата для обработки высококалорийной/высокосортной диетологической ожиренией.

Ожирение характеризуется несбалансированностью между потреблением энергии и расходами, которая вызывает ненормальный рост жировых тканей. Диметилфумарат (ДМП) и его первичный активный метаболит монометилфумарат (ММФ) являются активаторами Nrf2 и признаны в качестве стратегических антиоксидантов. Цель этого исследования состояла в том, чтобы оценить потенциал MMF и DMF в плане воздействия на адипогенез и ожирение, а также выявить соответствующие молекулярные механизмы. Предадипоциты 3T3-L1 были инкубированы с дифференциальной среды (MIX) и одновременно обработаны различными концентрациями MMF.

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… Formation of lipid droplets could clearly be observed in the MIX groups in the absence and presence of the lowest concentration of MMF. … Histological analysis of the liver indicated accumulated lipid droplets in tissue from HFHSD animals, which is characteristic of hepatic steatosis ( h ). Further analysis confirmed that DMF prevented HFHSD-induced steatosis ( i ). …

Мукоадгезивные наноэмульсии для доставки нозы в мозг диметилфумарат: разработка, характеристика и доказательство согласия

Фон. Диметилфумарат (ДМП) является утвержденным терапевтическим агентом для лечения множественного склероза, известным своими противовоспалительными и нейрозащитными свойствами. Однако его пероральное управление часто сопровождается побочными эффектами желудочно-кишечного кишечника, что ограничивает его терапевтический потенциал. В настоящем исследовании была разработана новая формула наноэмульсии (NE), которая была охарактеризована с целью усиления воздействия ДМП в цереброспинарной жидкости (CSF) после внутринационального администрирования. Методы: Состав был подготовлен методом самоэмульсиф

Biomolecular condensates as dynamic regulators of musculoskeletal homeostasis, disease, and therapeutic challenges.

Biomolecular condensates are membraneless assemblies that concentrate proteins, nucleic acids, and other biomolecules into dynamic cellular compartments. Liquid-liquid phase separation (LLPS) is one important route by which such condensates form, particularly when multivalent interactions generate liquid-like, reversible assemblies. However, not every condensate or disease-associated assembly should be explained solely by LLPS. In the musculoskeletal system, condensates have been linked to transcription, signal transduction, RNA metabolism, stress responses, tissue development, homeostasis, an

Exosomes liquid biopsy in Lymphoma precision medicine: applications and challenges.

Liquid biopsy is an emerging non-invasive detection technology that diagnoses tumors and provides prognostic value by analyzing samples such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. Exosomes are nanoscale extracellular vesicles (EVs) secreted by cells, encapsulating a diverse array of biomolecules, including proteins, nucleic acids (e.g., mRNA and miRNA), and lipids. Lymphoma cells secrete various exosomes, whose contents carry abundant tumor-associated information and serve as messengers in the tumor microenvironment (TME). Consequently, tumor-derived ex

PEX11B Palmitoilation пары пероксисомальная дисфункция с клетками Шванна не работают в диабетической нейропатии.

Диабетическая нейропатия (ДН) является распространенным и болезненным осложнением диабета; однако механизмы, лежащие в основе ее патогенеза, остаются неясными, а эффективные клинические методы лечения отсутствуют. Цель этого исследования заключается в изучении роли пероксисома в клетках Шванна в DN. МЕТОДЫ: Изобилие пероксисома в акустических нервах мышей или клеток Шванна анализировалось с помощью лазерной суперразрешительной съемки и западного пятна. Пробоотборник RPF-GPF-SKL (Ser-Lys-Leu) использовался для оценки уровней пексафагии (пероксисомы-автофагика). Для оценки пальмитоилирования PEX

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… Additionally, using the lipid droplet marker protein PLIN2 staining, we observed that oleic acid (OA) treatment significantly increased the number and size of lipid droplets, while 0.4 mM PA treatment resulted in a decrease in the area and a slight decrease in the number of lipid droplets (Fig.  2 C–E … D Quantification of lipid droplets (LDs) area. Data is shown as means ± SD with One-way ANOVA Dunnett’s test (n = 31 cells). * p  < 0.05, *** p  < 0.001. E Quantification of lipid droplets (LDs) number. …

Иммунометаболизм в старении мозга и нейродегенерации: преодоление метаболических путей и иммунные ответные меры.

Сложный набор взаимодействий между иммунной системой и метаболизмом, известный как иммунометаболизм, стал критическим регулятором последствий заболеваний в центральной нервной системе. В ходе многочисленных исследований метаболические расстройства увязывались с ослабленной иммунной реакцией при старении мозга, нейродегенеративных расстройствах и травме мозга. В этом обзоре мы обсудим вопрос о том, как нарушения баланса иммунометаболизма мозга способствуют патофизиологии дисфункции мозга. В первой части обзора резюмируется вклад таких критических групп иммунной клетки, как микроглии, астроциты,

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… The accumulation of lipid droplets can enhance pro-inflammatory responses in microglia [ 49 ]. Aged microglia show significant lipid droplet accumulation under steady-state conditions, which is linked to exacerbated type I interferon responses and altered immunometabolism following ischemia. … Microglial depletion and repopulation using colony-stimulating factor 1 receptor (CSF1R) antagonists in aged mice decreased lipid droplet accumulation, attenuated innate immune responses, and improved motor function after stroke. …

Последствия злоупотребления наркотиками для путей ферроптоза: потенциальные терапевтические цели для расстройств, связанных с потреблением психоактивных веществ.

Серьезными проблемами в области здравоохранения во всем мире, особенно в развитых странах, по-прежнему являются расстройства, связанные с потреблением психоактивных веществ. Для ОСВ характерна устойчивая нейроинфламмация и синаптическая дисфункция мозга. Несмотря на десятилетия интенсивного расследования, детальные механизмы, лежащие в основе ВСГ, по-прежнему остаются иллюзорными. Ферроптоз — это высокорегулируемый процесс смерти клеток, на который сильно влияют метаболизм железа, пероксидация липидов, производство реактивных видов кислорода (РОС) и антиоксидантные системы. Он был связан с мно

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… Inside cells, lipids can be stored as neutral lipids in lipid droplets or mobilized through lipolysis and β-oxidation to meet cellular energy demands. … Recent evidence further demonstrates that cocaine induces substantial lipid droplet accumulation in microglia both in vitro and in vivo . …

LncRNA Gas5, a Target of the Nonsense-Mediated Decay Pathway in the Brain, Regulates Neuroinflammation and Neurodegenerative Disease Pathways in a Tauopathy Mouse Model.

Dysregulation of target genes of nonsense-mediated decay (NMD) in the brain remains sparsely known in tauopathies. PS19 transgenic mice expressing human mutant P301S tau were evaluated for levels of lncRNA Gas5, a target of NMD. The results show Gas5 decreased in the brains of PS19 mice as they aged. We evaluated the consequences of blocking the NMD-mediated turnover of Gas5 using a small molecule administered intranasally to PS19 mice. The results show NPC86 disassociated Upf1 and Gas5, thereby hindering NMD. NPC86 treatment increased Gas5 levels in the cortex of male PS19 mice concurrent wit

Assessing Heterogeneity of Osteolytic Lesions in Multiple Myeloma by ¹H HR-MAS NMR Metabolomics.

Multiple myeloma (MM) is a malignancy of plasma cells characterized by multifocal osteolytic bone lesions. Macroscopic and genetic heterogeneity has been documented within MM lesions. Understanding the bases of such heterogeneity may unveil relevant features of MM pathobiology. To this aim, we deployed unbiased ¹H high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) metabolomics to analyze multiple biopsy specimens of osteolytic lesions from one case of pathological fracture caused by MM. Multivariate analyses on normalized metabolite peak integrals allowed clusteriza

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… In contrast, tumor samples had higher content of glycerolipids at 2.00 and 2.23 ppm ( p < 0.05, Supplementary Figure S2 and Table S1 ) likely originating either from membrane phospholipids, due to high cancer cellularity, or from triacylglycerides and fatty acid chains composing lipid droplets. 2.2. … droplets. …

Lipid metabolism in multiple myeloma: pathogenesis, therapeutic opportunities, and future directions.

BackgroundMultiple myeloma (MM) is a complex hematological malignancy characterized by the clonal expansion of plasma cells in the bone marrow. Emerging studies have emphasized the importance of lipid metabolism, which is closely associated with the survival, proliferation, and drug resistance of tumor cells. The hypoxic environment in the bone marrow (BM) contributes to metabolic reprogramming in MM cells, including alterations in metabolite levels, changes in metabolic enzyme activity, and metabolic shifts. Cancer cells possess the ability to adapt their metabolism in order to fulfill their

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… This includes a significant upregulation of de novo lipogenesis, enhanced lipid uptake, abnormal formation of lipid droplets, and disrupted lipid trafficking processes ( 19 ). … In this process, MM cells utilize the fatty acids taken up from BMAs to synthesize lipid droplets and extracellular vesicles. …

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio.

To meet the anabolic demands of the proliferative potential of tumor cells, malignant cells tend to rewire their metabolic pathways. Although different types of malignant cells share this phenomenon, there is a large intracellular variability how these metabolic patterns are altered. Fortunately, differences in metabolic patterns between normal tissue and malignant cells can be exploited to increase the therapeutic ratio. Modulation of cellular metabolism to improve treatment outcome is an emerging field proposing a variety of promising strategies in primary tumor and metastatic lesion treatme

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… Lipid droplets are closely related to the fatty acids as they serve as storage depots of fatty acids. Lipid droplets can influence the metabolic regulation of tumor cells and tumor-associated immune cells. … In hypoxic tumor regions specifically, accumulation of lipid droplets has been observed, which is potentially related to an increased Fatty Acid Oxidation (FAO). The role of lipid droplets has been extensively reviewed before ( 128 , 129 ). …

ATGL sensitizes hepatocellular carcinoma cells to genotoxic drugs by modulating p53 acetylation/phosphorylation status.

Hepatocellular carcinoma (HCC) accounts for approximately 90% of liver cancer cases. Few therapeutic options are available for HCC patients due to intrinsic drug resistance or the low efficacy of conventional chemotherapeutic drugs, including genotoxic agents. We previously demonstrated that adipose triglyceride lipase (ATGL) is downregulated in HCC and shows anti-neoplastic activity by affecting sensitivity to different therapeutic approaches. On the basis of this evidence, we assessed the contribution of ATGL activity to the modulation of the DNA damage response induced by genotoxic drugs. W

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… Metabolically, ATGL leads to a reduction in the size and number of lipid droplets, consequently enhancing mitochondrial β-oxidation. … Lipid droplets in cancer: from composition and role to imaging and therapeutics. Molecules. 2022;27:991. 35164256 10.3390/molecules27030991 PMC8840564 22. …

Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia.

Cancer cachexia is a complex metabolic syndrome characterized by unintentional loss of skeletal muscle and body fat. This syndrome is frequently associated with different types of cancer and negatively affects the prognosis and outcome of these patients. It involves a dynamic interplay between tumor cells and adipose tissue, where tumor-derived extracellular vesicles (EVs) play a crucial role in mediating intercellular communication. Tumor cells release EVs containing bioactive molecules such as hormones (adrenomedullin, PTHrP), pro-inflammatory cytokines (IL-6), and miRNAs (miR-1304-3p, miR-2

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… FA are esterified with glycerol, giving rise to triglycerides, which are then stored in the lipid droplets of white adipocytes. … Furthermore, breast cancer-derived EVs carrying miR-155 induced a decrease in the lipid droplet content and an upregulation of UCP1 protein and HSL and ATGL enzymes in white adipocytes [ 134 ] . …

Advanced Diagnostic Techniques

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Высоко избирательная и верзольная платформа для визуализации липаса Моноацилглицерол.

Monoacylglycerol Lipase (MAGL) — ключевой фермент для прекращения сигнала в эндоканнабиноидной системе (ECS). Ингибиция MAGL приводит к косвенной активации каннабиноидных рецепторов, что дает уникальные преимущества для лечения, например, множественных склерозов, эпилепсии и других неврологических расстройств. Технологии молекулярной съемки являются ценными инструментами, позволяющими преодолеть нынешнее плохое понимание распределения и роли MAGL в пато- и физиологических процессах в рамках сигнала ECS. В этой связи мы представляем информацию о проектировании, синтезе и подтверждении высокосел

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… Besides the ER staining, dense MAGL localization was observed in small, spherical structures reminiscent of lipid droplets. … This observation is in agreement with the reported role of lipid droplets and MAGL in cancer metabolism.[ 64 , 65 ] MAGL plays a vital role in neuronal inflammation[ 24 , 66 , 67 ] and the integrity of the blood–brain barrier.[ 68 , 69 ] Therefore, we investigated the …

Insights into the role of RNA m6A modification in the metabolic process and related diseases.

According to the latest consensus, many traditional diseases are considered metabolic diseases, such as cancer, type 2 diabetes, obesity, and cardiovascular disease. Currently, metabolic diseases are increasingly prevalent because of the ever-improving living standards and have become the leading threat to human health. Multiple therapy methods have been applied to treat these diseases, which improves the quality of life of many patients, but the overall effect is still unsatisfactory. Therefore, intensive research on the metabolic process and the pathogenesis of metabolic diseases is imperati

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… They found that FTO or YTHDF1 can suppress or increase MTCH2 expression, respectively. 77 YTHDF1 knockout enhances the expression of the HSD17B11 gene, which regulates the formation of lipid droplets in esophageal cancer cells. 76 YTHDF2 was found to target m 6 A-modified JAK2 transcripts and promote … Fat tissue can be divided into white adipose tissue and brown adipose tissue, which convert excess energy into lipid droplets or generate heat, respecti-vely. 148 , 149 Generally, obesity is the result of dysregulation of energy metabolism, characterized as excess energy being converted into lipid droplets …

Case report and comprehensive literature review: A rare instance of lipoid pneumonia.

RATIONALE: This case report elucidates the diagnostic challenges and natural progression of lipoid pneumonia (LP), a rare pulmonary condition, highlighting the critical importance of long-term monitoring. PATIENT CONCERNS: An 82-year-old female presented with a 2-year history of chronic cough and an acute exacerbation. DIAGNOSES: Initial diagnosis was severe pneumonia. Definitive diagnosis of LP was confirmed by computed tomography -guided lung biopsy, which revealed lipid-laden macrophages. INTERVENTIONS: Suspected lipid exposure was discontinued, and supportive conservative care was provi

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… These macrophages are filled with lipid droplets, and the nucleus is often pushed to 1 side, giving a foamy or “wheel-like” appearance. This can be highlighted by Oil Red O or Sudan staining, which shows the lipid components as red or orange, respectively, providing diagnostic confirmation. … In exogenous LP, BALF typically shows macrophages that phagocytize exogenous lipid droplets (exhibiting birefringence under polarized light), whereas endogenous LP is primarily characterized by cholesterol crystals (appearing as needle-shaped clefts). …

Obesity, the Adipose Organ and Cancer in Humans: Association or Causation?

Epidemiological observations, experimental studies and clinical data show that obesity is associated with a higher risk of developing different types of cancer; however, proof of a cause-effect relationship that meets the causality criteria is still lacking. Several data suggest that the adipose organ could be the protagonist in this crosstalk. In particular, the adipose tissue (AT) alterations occurring in obesity parallel some tumour behaviours, such as their theoretically unlimited expandability, infiltration capacity, angiogenesis regulation, local and systemic inflammation and changes to

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… TNF-α and IL-6 are induced by leptin, which stimulated the formation of lipid droplets and increased cell proliferation in intestinal epithelial cells in an in vitro study [ 117 ]. … These conditions parallel a status of muscle mass dysfunction and atrophy, with a concomitant infiltration of lipid droplets derived from AT lipolysis, that further impairs muscle tissue structure and strength [ 162 ]. …