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A ketogenesis-ferroptosis axis maintains leukemic stem cell survival and leukemia progression.

Hepatic ketogenesis generates ketone bodies as an alternative energy source during carbohydrate restriction or ketogenic diets, yet its role in non-hepatic cell types remains poorly defined. Here, we show that leukemic stem cells (LSCs) in acute myeloid leukemia (AML) exhibit elevated ketogenesis, driven by fatty acid oxidation (FAO), to produce β-hydroxybutyrate (BHB). LSCs express high levels of 3-hydroxy-3-methylglutaryl-coenzyme A (CoA) synthase 2 (HMGCS2), the rate-limiting enzyme in ketogenesis, compared with blast cells and normal hematopoietic stem cells (HSCs). Deletion of Hmgcs2 in A

Cationic amphiphilic scandenone derivatives as membrane-active anti-MRSA agents.

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major challenge in anti-infective therapy, highlighting the need for antibacterial agents with novel structures and mechanisms of action. Herein, a gram-scale preparation of the natural antibacterial isoflavone scandenone was established, enabling systematic structural optimization of this prenylated isoflavonoid scaffold. Guided by a cationic amphiphilic design strategy, a series of scandenone-derived quaternary ammonium derivatives were synthesized to enhance antibacterial activity and membrane targeting. Among them, compound 16c d

Bioorthogonal Surface Modification of Measles and Vaccinia Viruses Using Metabolic Azide Reporters.

Enveloped viruses, such as measles virus (MV) and vaccinia virus (VACV), acquire their lipid bilayer envelopes from host cell membranes during viral assembly. These membranes can be chemically modified to enable selective labeling and visualization. This chapter details a metabolic labeling strategy in which Vero cells, a prototypical host cell line, are supplemented with peracetylated azido sugars (Ac4GalNAz, Ac4ManNAz) and azido-choline analogs (AECho). These bioorthogonal metabolic reporters are incorporated into glycan and phospholipid via biosynthetic pathways, resulting in azide-function

Nobiletin as a Geroprotective Flavonoid: Mechanisms of Action, Therapeutic Potential, and Challenges of Bioavailability.

Flavonoids are a diverse group of naturally occurring polyphenolic compounds found in plant-based foods and are known for their broad-spectrum biological activities. Among them, nobiletin, a polymethoxylated flavone derived from citrus peels, has gained attention for its multifaceted role in promoting healthy ageing and mitigating age-related diseases. This review explores the chemical properties, mechanisms of action, therapeutic potential, and challenges related to nobiletin. The focus is placed on its antioxidant, anti-inflammatory, neuroprotective, cardioprotective, and metabolic regulator

A copper uptake ABC transport system is essential for Mycobacterium tuberculosis virulence.

Mycobacterium tuberculosis (Mtb) is a facultative intracellular pathogen that thrives primarily inside the phagosome of macrophages. A key Mtb survival strategy is to exploit and manipulate metal cation trafficking inside macrophages. Copper plays dual roles in host-pathogen interactions, i.e. as a bactericidal toxin for the host, as well as micronutrients for the bacteria. In contrast to the well-studied copper resistance pathways, the copper uptake machinery of Mtb remains poorly characterized. We here show that Rv1273c and Rv1272c form a heterodimeric copper influx ABC transporter in Mtb, a

Agxt2l-mediated glycerophospholipid metabolism in trophocytes explains Apis mellifera queen's higher oviposition over A. cerana.

Apis mellifera and Apis cerana are two important honey bee species widely kept and studied. But their queens differ greatly in egg-laying capacity. To determine the mechanisms of this difference, we compare gene expression, chromatin accessibility and spatial localization of differential genes in the ovaries of the two species in virgin queens and laying queens using ATAC-seq, RNA-Seq, homologous gene alignment and spatial transcriptome. The results reconfirm that the egg-laying capability of A. mellifera queens is significantly higher than that of A. cerana queens. The chromatin accessibility

The Effects of Several Natural Protoberberine Alkaloids and Cinnamic Acid Derivatives Used for Traditional Medicine on the Membrane Boundary Potential and Lipid Packing Stress.

Here we elucidated the effects of natural protoberberine alkaloids (rotundine, berberine, and nitidine) and cinnamic acid derivatives (ethyl-4-methoxycinnamate and osthole) found in Vietnamese medicinal plants, on the boundary potential of lipid bilayers and phase behavior of membrane lipids. Lipid bilayers were composed of neutral phosphatidylcholines (PC) and negatively charged phosphatidylserines (PS). Tested compounds did not produce any noticeable changes in the boundary potential with the exception of osthole, which caused a potential drop by about 30 mV independently of the membrane pho

Metal-based complexes with antiplatelet properties: antagonists of the platelet-activating factor receptor (PAFR) and other aggregating agents.

Metal complexes displaying anti-inflammatory and antithrombotic properties are a promising research area. Development of new and effective anti-inflammatory and antithrombotic agents is necessary to prevent inflammatory-assisted diseases, thromboembolic disease and oxidative stress. In this frontier article, we report on coordination and organometallic compounds displaying anti-inflammatory and/or antithrombotic potencies, particularly through the inhibition of platelet aggregation. Non -classic targets, such as the platelet-activating factor (PAF), a phospholipid signaling molecule of the imm

Neuronal polyunsaturated fatty acids are protective in ALS/FTD.

Here we report a conserved transcriptomic signature of reduced fatty acid and lipid metabolism gene expression in a Drosophila model of C9orf72 repeat expansion, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), and in human postmortem ALS spinal cord. We performed lipidomics on C9 ALS/FTD Drosophila, induced pluripotent stem (iPS) cell neurons and postmortem FTD brain tissue. This revealed a common and specific reduction in phospholipid species containing polyunsaturated fatty acids (PUFAs). Feeding C9 ALS/FTD flies PUFAs yielded a modest in

The Multifaceted Role of Annexin A1 in Colorectal Cancer: From Molecular Mechanisms to Predictive and Prognostic Implications.

Annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein, is considered a key modulator of cancer biology. Numerous pieces of evidence support its multifaceted involvement in tumor progression, metastatic dissemination, immune escape, and resistance to therapy in various malignancies, such as melanoma, along with liver, lung, and digestive tract tumors, including stomach and colorectal cancer (CRC). Although colon and rectal cancer (RC) exhibit overlapping characteristics, they are classified as separate clinical entities due to differences in tumor biology and therapy approaches.

Совпадение в полном тексте источника
… This core region includes several calcium-binding sites that facilitate an ANXA1 calcium-dependent attachment to the cellular phospholipid membranes. … ANXA1 domains 2 and 3 play a key role in the mediation of the interaction with membrane phospholipids by a calcium-dependent binding mechanism [ 38 , 42 , 45 ]. …

Not-So-Rare Defects of RBC Lipidic Composition: Four New Cases of Flippase Deficiency Due to ATP11C Mutations.

Adenosine Triphosphatase (ATPase) Phospholipid Transporting 11C gene (ATP11C), located on the X chromosome, encodes the major phosphatidylserine flippase in human erythroid cells. Only five patients have so far been reported with defective ATP11C, displaying mild hemolytic anemia and reduced flippase activity. In this study, we report four Italian male patients in three unrelated families with novel private mutations in the ATP11C gene, resulting in impaired flippase activity associated with mild/compensated hemolytic anemia. The decreased flippase activity was measured as % of phosphatidylser

Rapid 64Cu radiolabeling and in vivo evaluation of DSPE-NODAGA liposomes in a murine mammary tumor model.

Understanding the in vivo behavior of nanomedicines is critical for optimizing their therapeutic efficacy and facilitating personalized treatment strategies. In the quest to develop positron emission tomography (PET) methodology for liposome biodistribution studies, we systematically compared three liposome radiolabeling strategies - remote loading of 64Cu into liposomes containing the hydrophilic chelator NOTA, membrane labeling using ATSM, and surface labeling with DSPE-NODAGA (phospholipid DSPE conjugated with chelator NODAGA) - to identify an effective method for liposome radiolabeling wit

LPLAT11/MBOAT7-driven phosphatidylinositol remodeling ensures radial glial cell integrity in developing neocortex.

Phosphatidylinositol (PI) is highly enriched in arachidonic acid, an essential polyunsaturated fatty acid for brain development. This enrichment is mediated by the phospholipid remodeling enzyme lysophospholipid acyltransferase 11 (LPLAT11), also known as membrane-bound O-acyltransferase 7 (MBOAT7), whose deficiency causes microcephaly in both humans and mice. Here, we show that Mboat7 deficiency impairs indirect neurogenesis in the developing neocortex by compromising radial glial cell (RGC) integrity, resulting in fewer layer II-V neurons. Mboat7-deficient RGCs exhibited decreased proliferat

Gαi2 Signaling Regulates Neonatal Respiratory Adaptation.

Heterotrimeric Gi proteins are crucial modulators of G protein-coupled receptor signaling, with Gαi2 ubiquitously expressed and implicated in diverse physiological processes. Previous reports described partial lethality in Gnai2-deficient mice, but the timing and mechanism of death remained unclear. Here, we demonstrate that impaired neonatal respiratory adaptation contributes to mortality in Gnai2-deficient neonates. Despite normal Mendelian distribution at birth and no overt malformations, at least 20% of the expected Gnai2-deficient neonates died within minutes after birth, displaying abnor

ANXA2 promotes chondrocyte differentiation and fracture healing by regulating the phosphorylation of STAT3 and PI3K/AKT signaling pathways.

Fractures are common and serious skeletal injuries, and accelerating their healing while alleviating patient suffering remains a clinical challenge. Annexin A2 (ANXA2) is a widely distributed, calcium-dependent, phospholipid-binding protein involved in bone remodeling. However, its role in chondrocyte differentiation and endochondral ossification remains unclear. In this study, we found that ANXA2 is expressed in chondrocytes during growth plate development and fracture healing, as well as during chondrocyte differentiation and maturation in vitro, with its highest expression occurring in the

Effects of dietary soybean phosphatidylethanolamine on intestinal metabolism and microbiota in mice fed low-fat and high-fat diets.

Phosphatidylethanolamine (PE) is the second most abundant phospholipid in soybeans, which are widely used in the food industry as emulsifiers, thickeners, preservatives, and other additives. High-fat diets are known to disrupt intestinal metabolism and cause microbial disorders, leading to metabolic and intestinal health issues. To elucidate the effects of PE on these high-fat diet-induced disorders, we innovatively explored the interaction between regional intestinal bile acids and microbiota, revealing that PE supplementation can mitigate high-fat diet-induced metabolic disorders. PE downreg

Development and Optimization of a Bromothymol Blue-Based PLA2 Assay Involving POPC-Based Self-Assemblies.

Phospholipase A2 (PLA2) is a superfamily of phospholipase enzymes that dock at the water/oil interface of phospholipid assemblies, hydrolyzing the ester bond at the sn-2 position. The enzymatic activity of these enzymes differs based on the nature of the substrate, its supramolecular assemblies (micelle, liposomes), and their composition, reflecting the interfacial nature of the PLA2s and requiring assays able to directly quantify this interaction of the enzyme(s) with these supramolecular assemblies. We developed and optimized a simple, universal assay method employing the pH-sensitive indica

Impact of formulation parameters and circulation time on PEGylated liposomal doxorubicin related hand-foot syndrome.

PEGylated liposomal doxorubicin (PLD) has effectively reduced the cardiac toxicity of free doxorubicin (DOX) due to its unique nanoscale properties. However, an unexpected accumulation of PLD in the skin has led to hand-foot syndrome (HFS), negatively impacting quality of life and psychological well-being. In this study, self-limiting HFS rat models were created to mimic human symptoms through varying dosing schedules and intensities of PLD. The effects of PLD formulation parameters on HFS were also investigated. The results demonstrated that replacing ammonium sulfate with citric buffer, incr

The DNA demethylase TET1 modifies the impact of maternal folic acid status on embryonic brain development.

Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1-/- embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/- offspr

Investigation of the Aggregation of Aβ Peptide (1-40) in the Presence of κ-Carrageenan-Stabilised Liposomes Loaded with Homotaurine.

The kinetics of amyloid aggregation was studied indirectly by monitoring the changes in the polydispersity of mixed dispersion of amyloid β peptide (1-40) and composite liposomes. The liposomes were prepared from the 1,2-dioleoyl-sn-glicero-3-phoshocholine (DOPC) phospholipid and stabilised by the electrostatic adsorption of κ-carrageenan. The produced homotaurine-loaded and unloaded liposomes had a highly negative electrokinetic potential and remarkable stability in phosphate buffer (pH 4 and 7.4). For the first time, the appearance and evolution of the aggregation of Aβ were presented throug