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Molecular-Level Insights into the Interactions of Nicotine and Cotinine with DPPC Phospholipid Bilayers.

Small alkaloids such as nicotine and its major metabolite, cotinine, are widely present in biological and environmental systems, yet their membrane interaction mechanisms and related cytotoxic effects remain poorly quantified. Here, molecular dynamics simulations combined with umbrella sampling were used to investigate the adsorption, distribution, orientation, and transmembrane behavior of nicotine and cotinine in DPPC bilayers. Both molecules rapidly migrated from bulk water to the water-lipid interface within 8 ns and showed strong interfacial enrichment, with residence probabilities of 85%

Sorafenib-loaded porphyrin-phospholipid liposomes for enhanced chemophototherapy in hepatocellular carcinoma.

Sorafenib (SF) remains a frontline chemotherapeutic agent for treating hepatocellular carcinoma (HCC). However, its clinical utility is severely hampered by systemic toxicity and the rapid emergence of drug resistance. To overcome these challenges, we developed a liposomal nanoplatform co-encapsulating SF and a porphyrin-phospholipid conjugate (2HPoP) for combined chemo-photodynamic therapy. The synthesized SF-loaded 2HPoP liposomes (2HPoP lip@SF) exhibited favorable physicochemical characteristics, including high encapsulation efficiency, colloidal stability, and prolonged storage stability.

Loss of STARD7 Impairs Mitochondrial Phospholipid Homeostasis and Contributes to Mitochondrial Myopathy.

Mitochondria are composed of phospholipid bilayers rich in phosphatidylcholine (PC). StAR-related lipid transfer domain-containing protein 7 (STARD7) functions as a lipid transfer protein that plays a crucial role in maintaining mitochondrial PC homeostasis. In this study, we investigated the physiological role of STARD7 in skeletal muscle using muscle-specific knockout (mKO) mice. STARD7 expression was markedly higher in the soleus, a mitochondria-dense slow-twitch muscle, compared with fast-twitch fibers. Although muscle fibers from mKO mice exhibited no apparent structural abnormalities, th

Bacterial phospholipid selective quaternary phosphonium polymers with potent antibacterial activity.

Cationic polymers hold strong promise for treating bacterial infections. Most reported cationic antibacterial polymers incorporate nitrogen- … ocholine (DOPC) in mammalian membranes, CP-3 can selectively bind to the anionic bacterial-specific phospholipids phosphatidylglycerol (POPG) through electrostatic interactions, thereby effectively disrupt bacterial membrane integrity. Due to the unique bacterial phospholipids targeting ability and membrane damaging mechanism, CP-3 demonstrates rapid bactericid …

Phospholipid-modified glycogen nanoparticles for synergistic chemo-photothermal treatment of glioblastoma.

Glioblastoma multiforme (GBM) remains one of the most aggressive central nervous system malignancies, with therapeutic efficacy severely constrained by the blood-brain barrier (BBB), which limits drug delivery to the tumor site, and by the lack of tumor-specific targeting, leading to off-target effects and inadequate intratumoral accumulation. To address these interconnected challenges, we designed a dual-targeted biomimetic nanoplatform (GIM@Lip-Bio/FA) using glycogen as a biodegradable core for co-loading methotrexate (MTX) and IR780, followed by coating with a lipid layer sequentially modif

Phosphatidic acid phosphatase LPIN1 in phospholipid metabolism and stemness in hematopoiesis and AML.

Targeting metabolism represents a promising approach to eradicate leukemic stem cells (LSCs) that are considered critical drivers of relapse in acute myeloid leukemia (AML). In this study, we demonstrate that the phosphatidic acid phosphatase LPIN1, which regulates the synthesis of diacylglycerol, the key substrate for triacylglycerol, and phospholipid production, is crucial for the function of healthy and leukemic hematopoietic stem and progenitor cells (HSPC and LSC). LPIN1 mRNA was highly expressed in the CD34+ compartment of primary human AML samples. LPIN1 suppression inhibited the prolif

Diet-induced phospholipid remodeling dictates ferroptosis sensitivity and tumorigenesis in the pancreas.

High-fat diet (HFD) intake has been linked to an increased risk of pancreatic ductal adenocarcinoma (PDAC), a lethal and therapy-resistant cancer. However, whether and how specific dietary fats drive cancer development remains unresolved. Leveraging an oncogenic Kras -driven mouse model that closely mimics human PDAC progression, we screened a dozen isocaloric HFDs differing solely in fat source and representing the diversity of human fat consumption. Unexpectedly, diets rich in oleic acid - a monounsaturated fatty acid (MUFA) typically associated with good health - markedly enhanced tumorigen

Structure and interfacial properties of phospholipid-containing sponge nanoparticles and their interaction with myoglobin.

HYPOTHESIS: Sponge phase (L3) lipid nanoparticles (L3-NPs) have been shown to have large potential for the encapsulation of biomolecules, such as enzymes, with applications in food and pharmaceutical science. In this study, we introduce new formulations of L3-NPs including the phospholipids dioleoylphosphatidylcholine (DOPC) and dioleoyltrimethylammonium propane (DOTAP). The interaction of these new L3-NPs with myoglobin is of interest for the development of iron supplements which can be incorporated during food processing. EXPERIMENTS: We characterized the sample structure by small-angle X-r…

Phospholipid Complex-based Topical Gel for Codelivery of Erlotinib and Methotrexate in Psoriasis.

Topical drug delivery systems offer a targeted and patient-compliant approach for managing psoriasis, enabling noninvasive, localized, and sustained therapy, with reduced systemic side effects and improved therapeutic outcomes. In this study, we prepared phospholipid complex (PLC) based gel of methotrexate (MTX) and erlotinib (ERL) as a potential dual treatment for psoriasis. The phospholipids used in this study were biocompatible and exhibited enhanced skin permeation. The physical interactions between drugs and phospholipids in the MTX-loaded phospholipid complex (MPLC) and ERL-loaded phosph…

Vesicular phospholipid gels: A new strategy to improve topical antimicrobial dermatotherapy.

Therapeutically effective and biocompatible dermal formulations that can ensure localization of a high level of antimicrobial drug at the site of action for an appropriate duration, while at the same time providing intrinsic reepithelization properties, are of particular importance for the treatment of infected and injured skin. The current research aimed to explore the potentials of using vesicular phospholipid gels (VPGs), semisolid formulations consisting of tightly packed liposomes (100-200 nm), as innovative local depot drug vehicles for advanced topical dermatotherapy. Ciprofloxacin hydr

The "gut" corona at the surface of nanoparticles is dependent on exposure to bile salts and phospholipids.

HYPOTHESIS: The formation of a biomolecular corona on nanoparticle surfaces significantly influences their biological behaviour, particularly in drug delivery applications. Despite the prevalence of ingestion of particles (e.g, during oral drug delivery), our understanding of corona formation within the gastrointestinal (GI) tract remains limited, especially for non-protein components. The hypothesis of this work is that the exposure of nanoparticles to bile components will form a "corona" structure and protein corona will represent proteomes different from the original bile fluid. Two major a

Influence of phospholipid structures on volatile organic compounds generation in model systems.

To investigate the regularities and differences in oxidation products of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) by gas chromatography-mass spectrometry (GC-MS), and examine the influence of variations in fatty acid compositions and head groups on the kinds and contents of volatile organic compounds (VOCs) generated. A total of 42 VOCs were identified from PE (16:0-18:2), PC (16:0-18:2), and PC (16:0-18:1), with aldehydes and ketones being the main VOCs in three phospholipids (PLs). The content of most VOCs produced by PE (16:0-18:2), PC (16:0-18:2), and PC (16:0-18:1) incre…

Острая лихорадка Q, выявленная синдромом антифосфолипида: отчет о деле.

ВВЕДЕНИЕ: Q лихорадка - это зооноз, вызванный коксиеллой печени. Острая инфекция носит в основном асимптомический характер. В других случаях он вызывает в основном болезнь, похожую на грипп, пневмонию или гепатит. Мы представляем нетипичный случай острой Q лихорадки, обнаруженной массивным плевральным эфлуцией. Мы сообщаем о случае, когда 43-летний мужчина поступил в больницу из-за острого дыхательного расстройства. Дальнейшие анализы показали, что эосинофильное плефилирование, связанное с легочным эмболизмом и глубоким феморальным тромбозом вены. Этиологические исследования выявили острую Q л

Совпадение в аннотации оригинала
INTRODUCTION: Q fever is a zoonosis caused by Coxiella burnetii. Acute infection is mainly asymptomatic. In other cases it mainly causes a f … revealed an acute Q fever (IgM and IgG against C. burnetii phase II antigens) associated with anti-phospholipids. The outcome was favorable with vitamin K antagonists, doxycycline, and hydroxychloroquine, till the negativation of the anti-phospholipid antibodies. DISCUSSION AND CONCLUSION: During acute C. burnetii infections, anti-phospholipid antibodies are …

Localization of phospholipid-related signal molecules in salivary glands of rodents: A review.

BACKGROUND: In the 1950s, Hokin conducted initial studies on phosphoinositide turnover/cycle in salivary glandular cells. From these studies, the idea emerged that receptor-mediated changes in intramembranous levels of phosphoinositides represent an early step in the stimulus-response pathway. Based on this idea and the general view that knowledge of the exact localization of a given endogenous molecule in cells in situ is important for understanding its functional significance, we have reviewed available information about the localization of several representative phosphoinositide-signaling m

Phosphatidylglycerol Is the Lipid Donor for Synthesis of Phospholipid-Linked Enterobacterial Common Antigen.

The Gram-negative outer membrane (OM) is an asymmetric bilayer with phospholipids in its inner leaflet and mainly lipopolysaccharide (LPS) in its outer leaflet and is largely impermeable to many antibiotics. In Enterobacterales (e.g., Escherichia, Salmonella, Klebsiella, and Yersinia), the outer leaflet of the OM also contains phosphoglyceride-linked enterobacterial common antigen (ECAPG). This molecule consists of the conserved ECA carbohydrate linked to diacylglycerol-phosphate (DAG-P) through a phosphodiester bond. ECAPG contributes to the OM permeability barrier and modeling suggests that …

In Silico Drug Design of Benzothiadiazine Derivatives Interacting with Phospholipid Cell Membranes.

The use of drugs derived from benzothiadiazine, a bicyclic heterocyclic benzene derivative, has become a widespread treatment for diseases such as hypertension, low blood sugar or the human immunodeficiency virus, among others. In this work we have investigated the interactions of benzothiadiazine and four of its derivatives designed in silico with model zwitterionic cell membranes formed by dioleoylphosphatidylcholine, 1,2-dioleoyl-sn-glycero-3-phosphoserine and cholesterol at the liquid-crystal phase inside aqueous potassium chloride solution. We have elucidated the local structure of benzot

Progesterone Phospholipid Gel for Intramuscular Administration Prepared by In Situ-Phase Separation.

Long-term daily injection of progesterone for the treatment of threatened abortion can be a source of considerable pain to patients. To reduce the frequency of injections and improve patient compliance, a novel injectable phospholipid-based phase separation gel (PPSG) was prepared using small molecular materials such as phospholipids, medium-chain triglycerides (MCTs), and ethanol. Progesterone was loaded into PPSGs to promote rapid gel formation in situ via a sol-gel transformation mechanism, thereby achieving a sustained controlled release. Furthermore, progesterone was distributed in the oi…

PI4-kinase and PfCDPK7 signaling regulate phospholipid biosynthesis in Plasmodium falciparum.

PfCDPK7 is an atypical member of the calcium-dependent protein kinase (CDPK) family and is crucial for the development of Plasmodium falciparum. However, the mechanisms whereby PfCDPK7 regulates parasite development remain unknown. Here, we perform quantitative phosphoproteomics and phospholipid analysis and find that PfCDPK7 promotes phosphatidylcholine (PC) synthesis by regulating two key enzymes involved in PC synthesis, phosphoethanolamine-N-methyltransferase (PMT) and ethanolamine kinase (EK). In the absence of PfCDPK7, both enzymes are hypophosphorylated and PMT is degraded. We further f

Myocardial involvement in anti-phospholipid syndrome: Beyond acute myocardial infarction.

Anti-phospholipid antibodies (aPL) are the serological biomarkers of anti-phospholipid syndrome (APS), an autoimmune disorder characterized by vascular events and/or pregnancy morbidity. APS is a unique condition as thrombosis might occur in arterial, venous or capillary circulations. The heart provides a frequent target for circulating aPL, leading to a wide variety of clinical manifestations. The most common cardiac presentation in APS, valvular involvement, acknowledges a dual etiology comprising both microthrombotic and inflammatory mechanisms. We describe the cases of 4 patients with prim

Effect of Eye Spray Phospholipid Concentration on the Tear Film and Ocular Comfort.

OBJECTIVES: To evaluate the effect of eye spray phospholipid concentration on symptoms and tear film stability. METHODS: High-concentration … oncentration phospholipid spray. CONCLUSIONS: The liposomal eye spray with higher concentration of phospholipids significantly improved ocular comfort and tear film stability in contrast to the eye spray with lower concentration of phospholipids, hence practitioners need to choose an appropriate eye spray to maximize the patient benefit.