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17 pages, 859 KB  
Article
The Use of Piperidinium Surfactants in Nematicide Formulations
by Rushana Kushnazarova, Alla Mirgorodskaya, Eugeny Nikitin, Anastasia Egorova, Alsu Gatiyatullina, Tatiana Kalinnikova and Lucia Zakharova
Molecules 2026, 31(9), 1470; https://doi.org/10.3390/molecules31091470 (registering DOI) - 29 Apr 2026
Abstract
A series of hexadecylpiperidinium surfactants containing alkyl (PMe-16, PEt-16, PBu-16), benzyl (Benz-16, 1-Benz-3-HP-16, 1-Benz-4-HP-16), and hydroxyl (3-HPMe-16, 4-HPMe-16) substituents in the ring were tested with the nematode Caenorhabditis elegans to investigate the relationship between nematocidal activity and the structural features of surfactants. It [...] Read more.
A series of hexadecylpiperidinium surfactants containing alkyl (PMe-16, PEt-16, PBu-16), benzyl (Benz-16, 1-Benz-3-HP-16, 1-Benz-4-HP-16), and hydroxyl (3-HPMe-16, 4-HPMe-16) substituents in the ring were tested with the nematode Caenorhabditis elegans to investigate the relationship between nematocidal activity and the structural features of surfactants. It was found that increasing the hydrophobicity of the substituent in the surfactant head group reduced the nematocidal activity in the order PMe-16 > PEt-16 > PBu-16 > Benz-16. The lead compound, PMe-16, showed significantly higher activity than the commercial insecticide carbofuran, and was able to induce nearly complete nematode mortality within 24 h at a concentration of 50 μg·mL−1, as well as suppress culture development at concentrations of 25–100 μg·mL−1. All tested piperidinium surfactants inhibited nematode population development at 100 μg·mL−1, while PMe-16 remained effective at concentrations as low as 25 μg·mL−1. The membranotropic properties of the surfactants were evaluated using a turbidimetric method with dipalmitoylphosphatidylcholine (DPPC)-based liposomes as a model of biomembranes. Dynamic light scattering measurements were performed in parallel to assess changes in liposome size and zeta potential as a function of surfactant content, as well as to determine the critical concentration required to induce lipid bilayer destabilization. These results provide indirect evidence of surfactant–membrane interactions. The combinations of piperidinium surfactants and carbofuran showed pronounced synergistic effects, reducing the insecticide dose while maintaining efficacy. Synergy was evaluated using the Bliss independence model and the Highest Single Agent model. The addition of the most active surfactants (PMe-16 and 4-HPMe-16) at 6.25 μg·mL−1 enabled an approximately twofold reduction in the carbofuran dose while maintaining full nematocidal activity. Full article
(This article belongs to the Special Issue Synthesis and Derivatization of Heterocyclic Compounds)
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14 pages, 8492 KB  
Article
The Antioxidant and Neuroregenerative Effects of Thymoquinone in a Rat Intracerebral Hemorrhage Model
by Khamim Thohari, Asra Al Fauzi and Djoko Agus Purwanto
Biomedicines 2026, 14(5), 1009; https://doi.org/10.3390/biomedicines14051009 (registering DOI) - 29 Apr 2026
Abstract
Background/Objectives: Intracerebral hemorrhage (ICH) is a severe subtype of stroke characterized by extensive secondary brain injury driven by oxidative stress, inflammation, and progressive neuronal loss, leading to poor neurological outcomes. Thymoquinone, a bioactive compound derived from Nigella sativa, has demonstrated potent antioxidant and [...] Read more.
Background/Objectives: Intracerebral hemorrhage (ICH) is a severe subtype of stroke characterized by extensive secondary brain injury driven by oxidative stress, inflammation, and progressive neuronal loss, leading to poor neurological outcomes. Thymoquinone, a bioactive compound derived from Nigella sativa, has demonstrated potent antioxidant and neuroprotective properties, but its integrated effects in hemorrhagic stroke remain insufficiently explored. This study aimed to evaluate the antioxidant and neuroregenerative effects of thymoquinone in a rat model of ICH. Methods: Male Wistar rats with experimentally induced ICH were randomized into untreated controls and two treatment groups receiving thymoquinone (150 mg/kg and 250 mg/kg) for three consecutive days. Oxidative injury and antioxidant responses were assessed using membrane blebbing, malondialdehyde (MDA), superoxide dismutase (SOD) activity, and nuclear factor erythroid 2-related factor 2 (NRF2) expression, while neuroprotection was evaluated by neuronal counts in perihematomal tissue. Results: Thymoquinone treatment significantly reduced membrane blebbing and MDA levels, while markedly increasing SOD activity and NRF2 expression in a dose-dependent manner. These biochemical improvements were accompanied by significant preservation of neuronal morphology and increased neuronal survival, with the 250 mg/kg dose showing the strongest effects. Conclusions: In conclusion, thymoquinone confers robust antioxidant and neuroprotective benefits in experimental ICH and represents a promising candidate for mitigating secondary brain injury following intracerebral hemorrhage. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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22 pages, 963 KB  
Article
Bacterial Cellulose Membranes Functionalized with In Situ Green-Synthesized Silver Nanoparticles for Antibacterial Applications
by Gul Naz Ashraf, Marta Palau Gauthier, Qiutian She, Pilar Rivera-Gil and Javier Macia
Int. J. Mol. Sci. 2026, 27(9), 3943; https://doi.org/10.3390/ijms27093943 - 28 Apr 2026
Abstract
This study demonstrates how synthesis conditions and bacterial cellulose (BC) functionalization influence the physicochemical properties and antibacterial performance of BC membranes containing green-synthesized silver nanoparticles (AgNPs). Mint and avocado-seed extracts enabled AgNP formation in aqueous media but differed in composition. UV–Vis screening across [...] Read more.
This study demonstrates how synthesis conditions and bacterial cellulose (BC) functionalization influence the physicochemical properties and antibacterial performance of BC membranes containing green-synthesized silver nanoparticles (AgNPs). Mint and avocado-seed extracts enabled AgNP formation in aqueous media but differed in composition. UV–Vis screening across pH and temperature revealed inefficient synthesis at acidic pH, whereas higher temperatures produced broader localized surface plasmon resonance (LSPR) bands. Neutral conditions generated the most intense and narrow LSPR signals. Under optimized conditions (pH 7, 23 °C), AgNPs were confirmed by TEM, and their colloidal properties differed between extracts: mint-derived particles exhibited smaller hydrodynamic diameters and lower polydispersity than avocado-derived AgNPs. Two BC functionalization strategies were evaluated: immersion in pre-formed AgNP dispersions and in situ synthesis within the BC matrix. In situ membranes displayed stronger and better-defined LSPR peaks. Agitation released nanoparticles from all BC-AgNP membranes, with smaller species released from in situ systems. Antibacterial assays against E. coli showed greater bactericidal activity for in situ membranes. Avocado-derived in situ BC-AgNPs produced larger inhibition halos and prevented bacterial regrowth in liquid culture. Overall, in situ green synthesis within BC provides an effective route to robust and sustainable antibacterial BC membranes. Full article
(This article belongs to the Section Molecular Nanoscience)
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23 pages, 1712 KB  
Article
Surface Engineering of NK Cells with Poly-L-Glutamic Acid Enhances Tumor-Selective Immunotherapy Against Ovarian Cancer
by Yoonbum Park, Ashok Kumar Jangid, Kyung Mu Noh, Eunha Kim, Chae Eun Lee and Kyobum Kim
Cells 2026, 15(9), 800; https://doi.org/10.3390/cells15090800 (registering DOI) - 28 Apr 2026
Abstract
Natural killer (NK) cells are promising effectors for cancer immunotherapy, as they can recognize and eliminate tumor cells without prior antigen sensitization. However, insufficient tumor recognition remains a critical limitation that reduces the anticancer efficacy of NK cells against solid tumors. To address [...] Read more.
Natural killer (NK) cells are promising effectors for cancer immunotherapy, as they can recognize and eliminate tumor cells without prior antigen sensitization. However, insufficient tumor recognition remains a critical limitation that reduces the anticancer efficacy of NK cells against solid tumors. To address this limitation, we developed a lipid-mediated cell membrane engineering strategy to enhance the targeting and cytotoxic efficacy of NK cells toward solid tumors, particularly ovarian cancer cells. In this strategy, poly-L-glutamic acid (PLE) was employed as an ovarian cancer-targeting module due to the specific affinity of PLE for cholesterol-rich membrane domains. To display PLE on NK cells, a lipid moiety is incorporated to anchor PLE onto the NK cell membrane via hydrophobic insertion, enabling rapid and non-genetic surface modification. As a result, the surface-engineered NK cells with PLE-Lipid (i.e., PLE-NK) displayed PLE on the NK cell surface, allowing direct recognition of ovarian cancer cells without compromising the intrinsic properties of NK cells. This enhanced recognition subsequently increased NK–cancer cluster formation by promoting interactions between membrane-presented PLE on NK cells and cholesterol on ovarian cancer cells. Consequently, PLE-NK cells exhibited enhanced cytotoxicity against ovarian cancer cells (i.e., OVCAR-3 cells) and effectively disrupted 3D tumoroids, while PLE-NK cells showed no off-target effects on normal fibroblasts. Collectively, these findings demonstrate that PLE-Lipid-mediated NK surface engineering provides a simple and effective strategy to improve the tumor targeting ability of NK cells and offers a promising platform for NK cell-based immunotherapy against ovarian cancer. Full article
(This article belongs to the Special Issue Cellular and Molecular Insights into Gynecologic Tumors)
26 pages, 2840 KB  
Article
Development of a Hybrid Gas Hydrate–Membrane Process for Natural Gas Upgrading: Modeling and Experimental Validation
by Kirill A. Smorodin, Artem A. Atlaskin, Sergey S. Kryuchkov, Maria E. Atlaskina, Yaroslav L. Shirokov, Nikita S. Tsivkovsky, Alexander A. Sysoev, Vyacheslav V. Zhmakin, Dmitry M. Zarubin, Anton N. Petukhov, Sergey S. Suvorov, Andrey V. Vorotyntsev and Ilya V. Vorotyntsev
Energies 2026, 19(9), 2124; https://doi.org/10.3390/en19092124 - 28 Apr 2026
Abstract
Hybrid gas separation technologies combining different physicochemical mechanisms represent a promising approach for the efficient treatment of complex natural gas mixtures. In this work, a hybrid process integrating gas hydrate crystallization and membrane gas separation was investigated for the upgrading of multicomponent natural [...] Read more.
Hybrid gas separation technologies combining different physicochemical mechanisms represent a promising approach for the efficient treatment of complex natural gas mixtures. In this work, a hybrid process integrating gas hydrate crystallization and membrane gas separation was investigated for the upgrading of multicomponent natural gas-containing hydrocarbons (C1–C4), acid gases (CO2 and H2S), and inert components. Polysulfone hollow-fiber membranes were fabricated, and their gas transport properties were experimentally determined using an eight-component quasi-real natural gas mixture under elevated pressure conditions. The obtained mixed-gas permeance values were used as input parameters for the development of a detailed mathematical model of a hollow-fiber membrane module implemented in the Aspen Custom Modeler. The model was applied to simulate membrane separation of both gas- and hydrate-derived streams produced by the gas hydrate crystallizer. Simulation results were analyzed in terms of hydrocarbon composition, acid gas removal efficiency, and hydrocarbon recovery as a function of the stage-cut. The modeling predictions were validated experimentally using a laboratory membrane module integrated with the gas hydrate crystallization unit. Good agreement between the experimental data and simulation results was observed for all major components. The deviation between modeled and experimental concentrations remained small, while the discrepancy in hydrocarbon recovery was higher and reached approximately 10–20%, which is attributed to the cumulative uncertainty of flow rate and composition measurements. These results confirm the adequacy of the developed model. The hybrid process demonstrates strong complementarity between the thermodynamic selectivity of hydrate formation and the transport selectivity of membrane separation, enabling efficient removal of acid gases while maintaining acceptable hydrocarbon recovery. The results indicate that the proposed gas hydrate–membrane hybrid process is a promising strategy for advanced natural gas purification and upgrading. Full article
31 pages, 2438 KB  
Review
Integrative Peptide Drug Development: Chemical Engineering, AI-Driven Design, and Cell-Penetrating Peptides
by Yong Eun Jang, Minjun Kwon, Chan Woo Kwon, Seok Gi Kim, Ji Su Hwang, Nimisha Pradeep George, Seung Ryong Paik, Sampa Misra, Shaherin Basith, Seung Soo Sheen and Gwang Lee
Pharmaceutics 2026, 18(5), 537; https://doi.org/10.3390/pharmaceutics18050537 (registering DOI) - 28 Apr 2026
Abstract
Peptide therapeutics occupy a unique chemical space between small molecules and biologics, combining high target specificity with structural programmability and favorable safety profiles. Recent regulatory approvals and expanding clinical pipelines underscore the growing therapeutic and commercial relevance of peptide-based drugs. This review outlines [...] Read more.
Peptide therapeutics occupy a unique chemical space between small molecules and biologics, combining high target specificity with structural programmability and favorable safety profiles. Recent regulatory approvals and expanding clinical pipelines underscore the growing therapeutic and commercial relevance of peptide-based drugs. This review outlines chemical modification approaches and contemporary design strategies, and evaluates their impact on proteolytic stability, pharmacokinetics, membrane permeability, and target engagement. We then highlight recent advances in artificial intelligence (AI)-guided peptide drug design, including machine learning models, protein language models, and generative architectures that enable high-throughput activity prediction, property optimization, and de novo sequence generation. These approaches collectively accelerate the traditional discovery–design–validation cycle while reducing experimental attrition through data-driven, structure-informed modeling frameworks. Among these applications, AI also enables the rational design of cell-penetrating peptides (CPPs) to enhance intracellular delivery and biological activity. Building on these methodological advances, we further examine their application to peptide therapeutics, with particular emphasis on AI-based predictive models for CPPs as well as on therapeutic applications within the central nervous and pulmonary systems. We conclude by outlining future perspectives and emphasize that the systematic integration of AI-enabled sequence design with rational chemical engineering and advanced delivery technologies, supported by rigorous experimental validation, will be critical for developing robust and clinically durable peptide-based medicines. Full article
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17 pages, 10549 KB  
Article
Parametric Reconstruction and Pore-Scale Transport Analysis of Microporous Layers in PEM Fuel Cells
by Shengbo Sun, Lingquan Li, Hao Wang and Guogang Yang
Nanomaterials 2026, 16(9), 529; https://doi.org/10.3390/nano16090529 (registering DOI) - 27 Apr 2026
Abstract
The microporous layer (MPL) is a key functional component in proton exchange membrane fuel cells (PEMFCs), and clarifying the quantitative relationship between its microstructure and mass transport properties is essential for improving cell performance. In this study, a three-dimensional MPL model was developed [...] Read more.
The microporous layer (MPL) is a key functional component in proton exchange membrane fuel cells (PEMFCs), and clarifying the quantitative relationship between its microstructure and mass transport properties is essential for improving cell performance. In this study, a three-dimensional MPL model was developed using a stochastic reconstruction method, and, together with a random walk algorithm, was employed to systematically investigate the effects of porosity, carbon sphere radius, maximum overlap ratio, seed ratio, and polytetrafluoroethylene (PTFE) content on permeability, effective diffusivity, and tortuosity. The results reveal that increasing porosity reduces tortuosity from 1.7 to 1.3, while permeability and effective diffusivity increase by factors of approximately 6.5 and 1.8, respectively. As the carbon sphere radius increases, tortuosity decreases from 1.55 to 1.35, accompanied by an increase in permeability from 2 × 10−16 m2 to 20 × 10−16 m2. Moreover, increasing the PTFE content raises permeability from 5 × 10−16 m2 to 22.5 × 10−16 m2, corresponding to an enhancement by a factor of approximately 4.5. The high-accuracy fitting equations obtained from the simulation results provide theoretical guidance for the microstructural design and optimization of MPLs, which can enhance oxygen transport and water management, reduce mass transport losses, and thereby benefit high-power-density operation and the overall efficiency of PEM fuel cells. Full article
(This article belongs to the Section Energy and Catalysis)
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17 pages, 3251 KB  
Article
The Influence of Hop Prenylated Chalcones on Mitochondrial Membrane Potential Depolarization and a Response to Oxidative Stress in MCC13 Merkel Cells
by Marcelina Chmiel, Aleksandra Włoch, Daniel Broda, Agata Bajek-Bil and Monika Stompor-Gorący
Pharmaceuticals 2026, 19(5), 687; https://doi.org/10.3390/ph19050687 (registering DOI) - 27 Apr 2026
Abstract
Background: Prenylated chalcones are recognized for their beneficial nutritional properties and have attracted increasing interest due to their anticancer activities, which involve various mechanisms and pathways. In the current study, we investigated the influence of prenylated chalcone xanthohumol (XH) and its two [...] Read more.
Background: Prenylated chalcones are recognized for their beneficial nutritional properties and have attracted increasing interest due to their anticancer activities, which involve various mechanisms and pathways. In the current study, we investigated the influence of prenylated chalcone xanthohumol (XH) and its two minor derivatives xanthohumol C (XHC) and 1″,2″-dihydroxantohumol C (DHXHC) on the formation of reactive oxygen species (ROS), causing oxidative stress. Concomitantly, we studied the effect of mitochondrial transmembrane potential changes on human skin cancer, namely Merkel cell carcinoma (MCC13). Methods: The cancer cells were treated with the mentioned compounds for 24 and 48 h at various concentrations. Results: Our findings showed that ROS generation was dose-dependent at 24 h for xanthohumol, whereas for xanthohumol C and 1″2″-dihydroxanthohumol C, a significant increase in ROS occurred only at the highest concentration (100 μM) after 48 h. Mitochondrial membrane potential was significantly diminished by all the compounds. Conclusions: Taken together, our results indicate that the aforementioned chalcones exhibit cytotoxic activity against the MCC13 cell line and may be promising candidates for further investigation as anticancer agents. Full article
(This article belongs to the Section Medicinal Chemistry)
17 pages, 3218 KB  
Article
Nano-Delivery System for the Prevention and Control of the Disease
by Jianxin Zhou, Yalan Mo, Mingfeng Feng, Wenchang Zhang, Chaonan Li, Zhuqing Li, Binghong Jia, Xiaogang Li and Yiping Liu
Molecules 2026, 31(9), 1448; https://doi.org/10.3390/molecules31091448 - 27 Apr 2026
Abstract
Kiwifruit soft rot is a major cause of postharvest loss owing to rapid fruit decay during storage. This study focused on kiwifruit soft rot during the postharvest storage stage, when fungal development may be promoted by room temperature and high humidity. Soft rot [...] Read more.
Kiwifruit soft rot is a major cause of postharvest loss owing to rapid fruit decay during storage. This study focused on kiwifruit soft rot during the postharvest storage stage, when fungal development may be promoted by room temperature and high humidity. Soft rot symptoms were observed in the pericarp and fruit flesh. In this study, carvacrol-loaded nanoliposomes (CAR@NL) were prepared by an O/W emulsification–solvent evaporation method to control kiwifruit soft rot. The physicochemical properties of CAR@NL were characterized by laser particle size analysis, Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM). Their antifungal activity and preservation efficacy were evaluated by in vitro antifungal assays and fruit storage experiments. The prepared CAR@NL showed an average particle size of approximately 280 nm, an encapsulation efficiency of 85.75%, and a drug loading capacity of 20.14%, along with favorable sustained-release properties. CAR@NL exhibited strong antifungal activity, with an EC50 value of 41.76 mg/L. DAPI staining indicated no obvious effect on fungal DNA, whereas propidium iodide (PI) staining revealed increased fluorescence intensity with increasing concentration and treatment time, indicating disruption of hyphal membrane integrity and severe structural damage. Flow cytometric analysis further showed that, at 50 mg/L, the total apoptosis rate was 2.96% in the untreated control group, 5.22% in the CAR@NL-treated group, and 33.6% in the carbendazim-treated group, demonstrating the lower cytotoxicity of CAR@NL toward mammalian cells. In addition, CAR@NL showed good stability and preservation performance during fruit storage. Overall, CAR@NL may serve as a safe and effective postharvest agent for the control of kiwifruit soft rot. Full article
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62 pages, 3341 KB  
Review
Membrane Technology for N-Nitrosamine Compounds Removal from Water: A Critical Review of Experimental and Simulation Practices and Enhancement Opportunities
by Mudhar A. Al-Obaidi and Iqbal M. Mujtaba
Processes 2026, 14(9), 1397; https://doi.org/10.3390/pr14091397 - 27 Apr 2026
Abstract
N-nitrosamine compounds, a disinfection byproduct of chlorination and chloramination in water and wastewater treatment processes, are classified as a probable human carcinogen. The current review focuses on analysing the feasibility of membrane technology while examining the challenges and opportunities in the elimination [...] Read more.
N-nitrosamine compounds, a disinfection byproduct of chlorination and chloramination in water and wastewater treatment processes, are classified as a probable human carcinogen. The current review focuses on analysing the feasibility of membrane technology while examining the challenges and opportunities in the elimination of N-nitrosamine compounds, particularly NDMA, from wastewater. To systematically attain this goal, this paper uses a systematic literature review that screens and critically assesses peer-reviewed experimental and numerical published papers on N-nitrosamine removal, occasioning in 37 high-quality papers for synthesis. In this regard, a detailed analysis of experimental and numerical studies elaborates that conventional RO membranes often introduce a specific low removal of NDMA from wastewater due to their low molecular weight and neutral charge, which addresses a critical issue. The critical analysis of the experimental and numerical studies depicts that the membrane type, structural properties, and chemical interaction have a key role in the removal of NDMA. To systematically improve the NDMA removal, a wide set of investigations have explored innovative treatment methods, including Nano pore plugging and hydrophilic coatings. This demonstrates potential for improving NDMA removal, albeit at the penalty of reduced water permeability. Additionally, the heat treatment of membranes has attained a notable improvement, ensuing in NDMA rejection of up to 92%. A multi-stage RO configuration model has depicted a maximum NDMA rejection of 93.1%. The future research should focus on investigating possible improvement of NDMA removal from wastewater such as Nano pore plugging and hydrophilic coatings, besides optimising RO configurations and membrane designs with a deeper understanding of membrane fouling. Full article
24 pages, 49240 KB  
Article
Novel Selective Anticancer Effect of Epididymis-Derived Extracellular Vesicles Against HCC38 and MCF-7 Breast Cancer Cell Lines
by Razi Zoabi, Zenab Ali Saleh, Elias Issaq, Etedal Morad, Reem Miari, Hanan Taha, Ahmad Kadriya, Abraham O. Samson and Mizied Falah
Int. J. Mol. Sci. 2026, 27(9), 3870; https://doi.org/10.3390/ijms27093870 - 27 Apr 2026
Abstract
Prevalent cancers primarily include breast, lung and bronchus, prostate, and colorectal cancers. In contrast, cancer of the epididymis is very rare, and we propose that this tissue could carry inherent anticancer components, in particular, small extracellular vesicles (EVs) with antineoplastic properties. All cell [...] Read more.
Prevalent cancers primarily include breast, lung and bronchus, prostate, and colorectal cancers. In contrast, cancer of the epididymis is very rare, and we propose that this tissue could carry inherent anticancer components, in particular, small extracellular vesicles (EVs) with antineoplastic properties. All cell types release extracellular vesicles (EVs) into their intercellular space, which act in the crosstalk required to achieve homeostasis. Among these, small EVs, which are membrane-bound vesicles with an average diameter of 30–200 nm, can transfer cell-specific cargo, such as lipids, proteins, DNA and RNA, which can be selectively received by neighboring or distant cells, and trigger specific cell processes, such as growth, division, or apoptosis. Here, we isolated small EVs from epididymis tissue, and examined their effect on morphology, viability, apoptosis, cell cycle phases, and certain gene and protein expression levels, particularly of the pro-apoptotic p53 protein, in HCC38 and MCF-7 breast cancer cell lines, as well as in a normal fibroblast cell line. The various analyses demonstrated effects on breast cancer cells but not on normal cells. Specifically, epididymis-derived EVs (Ep-EVs) selectively induced apoptosis and cell cycle arrest in cancer cells, while normal cells were unaffected. Moreover, the relative uptake of Ep-EVs in HCC38 and MCF-7 breast cancer cells was significant, indicating a direct association between vesicle internalization and the biological response. Taken together, these findings demonstrate a solid experimental foundation supporting the therapeutic potential of Ep-EVs in breast cancer, with promising implications for their development as a broader anticancer platform. Full article
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18 pages, 2641 KB  
Article
Novel NSAID Analogs Exhibit Anti-Leukemic Activity Through Modulation of Apoptotic and Survival Pathways
by Hind A. Alkhatabi, Mohammed Basabrain, Alaa G. Alahmadi, Shiekhah M. Alzahrani, Yosra A. Muhammad, Maha Almuhaiyawi, Maha M. Alreemi, Reem M. Alotibi, Roaa M. Alreemi, Heba A. Alkhattabi, Reem N. Hassan, Wedad M. Albeshri, Mohammed El-Mezgueldi and Abdelsattar M. Omar
Int. J. Mol. Sci. 2026, 27(9), 3850; https://doi.org/10.3390/ijms27093850 - 26 Apr 2026
Abstract
Acute myeloid leukemia (AML) is a complex blood cancer that primarily affects relapsing or refractory patients receiving conventional chemotherapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) have anticancer properties with restricted clinical efficacy attributable to cyclooxygenase (COX)-induced toxicities. To address this issue, a group of benzylamide [...] Read more.
Acute myeloid leukemia (AML) is a complex blood cancer that primarily affects relapsing or refractory patients receiving conventional chemotherapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) have anticancer properties with restricted clinical efficacy attributable to cyclooxygenase (COX)-induced toxicities. To address this issue, a group of benzylamide analogs of the classical NSAIDs (NSI-1–NSI-9) were developed and synthesized to mask the carboxylic acid moiety and minimize COX-induced adverse effects while maintaining anticancer activity. The cytotoxic effect of such substances has been demonstrated in some leukemia cell lines (HL-60, MV4-11, KG1a, and K562). NSI-5 exerted the highest anti-leukemic activity among these sulindac analogs, as determined at a sub-micromolar level in all cell lines studied, by IC50. This mechanistic data also demonstrated that NSI-5 induced apoptosis that was dose-dependent, especially in HL-60 cell lines, and increased the sub-G1 cell fraction. This apoptotic process was also accompanied by a significant decrease in mitochondrial membrane potential, which is characteristic of the induction of the intrinsic apoptotic process. Interestingly, NSI-5 decreased the intracellular reactive oxygen species (ROS) and the expression of most antioxidants (catalase and glutathione synthetase), as well as the redox balance. Gene characterization in vitro also suggested activation of apoptotic pathways, where expression of Bax, Bak1, and Caspase-3 increased, suggesting a potential p53-independent apoptotic pathway, in contrast to control for Bcl-2 expression. Collectively, these findings indicate that NSI-5 is a promising in vitro anti-leukemic lead compound, with activity associated with mitochondrial dysfunction and altered redox regulation. The observed effects are consistent with previously reported COX-independent activity of structurally related NSAID derivatives, and support further investigation of NSI-5 in preclinical models. Full article
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19 pages, 1828 KB  
Review
Metabolic Control of Membrane Lipid Asymmetry in Cancer
by Kyung-Hee Kim and Byong Chul Yoo
Int. J. Mol. Sci. 2026, 27(9), 3846; https://doi.org/10.3390/ijms27093846 - 26 Apr 2026
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Abstract
The plasma membrane plays essential roles in cellular transport and signaling. One of its fundamental structural features is the asymmetric distribution of lipids between the inner and outer leaflets. This asymmetry is actively maintained by lipid transport systems, including flippases, floppases, and scramblases, [...] Read more.
The plasma membrane plays essential roles in cellular transport and signaling. One of its fundamental structural features is the asymmetric distribution of lipids between the inner and outer leaflets. This asymmetry is actively maintained by lipid transport systems, including flippases, floppases, and scramblases, and is critical for membrane integrity and signaling regulation. Accumulating evidence indicates that membrane lipid asymmetry is frequently altered in cancer cells, leading to the externalization of normally inner-leaflet phospholipids such as phosphatidylserine and phosphatidylethanolamine. These alterations can influence tumor signaling, immune interactions, and membrane-associated biological processes. Recent studies further suggest that metabolic reprogramming in cancer may play an important role in regulating membrane lipid asymmetry. Changes in cellular energy status, oxidative stress, calcium signaling, and lipid metabolism can modulate lipid transport systems and membrane organization. In addition, tumor metabolism generates diverse circulating metabolites, including lactate, lysophospholipids, and acylcarnitines, which may influence membrane properties and lipid redistribution. These observations raise the possibility that membrane lipid asymmetry functions as a metabolically responsive interface linking intracellular metabolic state to cell surface signaling and tumor–microenvironment interactions. In this review, we propose a conceptual framework in which cancer-associated metabolic reprogramming influences lipid transport systems and membrane organization, thereby reshaping phospholipid distribution across the plasma membrane. We discuss how metabolic perturbations—including changes in energy metabolism, redox balance, calcium signaling, and lipid remodeling—may regulate membrane lipid asymmetry and explore the implications of these processes for tumor signaling, immune interactions, and emerging membrane-targeted therapeutic strategies. Full article
(This article belongs to the Special Issue Tumor Markers and Tumor Microenvironment)
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18 pages, 5295 KB  
Article
Overexpression of the Large-Conductance Mechanosensitive Channel Gene in Oenococcus oeni Enhances Its Ethanol Stress Tolerance
by Longxiang Liu, Yang Zhao, Lemeng Zhang, Yujuan Zheng, Shuai Peng, Hongyu Zhao, Xinyu Zhao, Yumiao Zhang, Jingjing Fang and Weiyu Song
Microorganisms 2026, 14(5), 973; https://doi.org/10.3390/microorganisms14050973 (registering DOI) - 26 Apr 2026
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Abstract
Oenococcus oeni (O. oeni) can initiate and complete the malolactic fermentation (MLF) process, which significantly improves wine quality. However, stress factors commonly encountered in wine, such as acid stress and ethanol stress, can hinder this process. Overexpression of certain key functional [...] Read more.
Oenococcus oeni (O. oeni) can initiate and complete the malolactic fermentation (MLF) process, which significantly improves wine quality. However, stress factors commonly encountered in wine, such as acid stress and ethanol stress, can hinder this process. Overexpression of certain key functional genes using genetic recombination technology can enhance the stress tolerance of O. oeni. In this study, the large-conductance mechanosensitive channel (mscl) gene was overexpressed in O. oeni SD-2a using genetic recombination technology. The results showed that overexpression of this gene enhanced the growth rate of O. oeni under 10% ethanol stress conditions. Physiological index measurements indicated that overexpression of this gene enhanced the control of cell membrane permeability in the recombinant strain at different time points under ethanol stress and altered cell membrane fluidity at these time points. Proteomic analysis after 12 h of treatment under 10% ethanol stress revealed that mscl overexpression significantly altered the protein expression pattern of O. oeni. The most significantly affected proteins included some cell membrane transporters (for sugars, lipids, amino acids, and nucleotides) and proteins involved in cell wall synthesis. These results suggest that mscl overexpression enhances the ethanol stress tolerance of O. oeni by altering its cell membrane properties and affecting the expression levels of proteins related to cell membrane transport and cell wall synthesis. This study provides a theoretical reference for obtaining O. oeni recombinant strains with enhanced stress tolerance through genetic recombination technology. Full article
(This article belongs to the Section Food Microbiology)
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18 pages, 921 KB  
Article
Colloidal Hydroxyapatite Nanoparticles as a Carrier for Cannabinol: The Effect on Model Langmuir Monolayers and Bilayer Lipid Membranes
by Emilia Świątek, Jan Taudul, Daria Kępińska, Dorota Nieciecka and Paweł Krysiński
Colloids Interfaces 2026, 10(3), 33; https://doi.org/10.3390/colloids10030033 - 24 Apr 2026
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Abstract
Cannabinol (CBN) is a highly lipophilic phytocannabinoid whose biomedical application is limited by poor water solubility. In this study, colloidal hydroxyapatite nanoparticles (nHAp) were evaluated as a carrier for CBN, and their effect on model lipid membranes was investigated. Interactions between CBN and [...] Read more.
Cannabinol (CBN) is a highly lipophilic phytocannabinoid whose biomedical application is limited by poor water solubility. In this study, colloidal hydroxyapatite nanoparticles (nHAp) were evaluated as a carrier for CBN, and their effect on model lipid membranes was investigated. Interactions between CBN and lipids were examined using Langmuir monolayers and lipid bilayers (black lipid membranes, BLMs). Langmuir monolayer studies revealed strong interactions between CBN and lipids, resulting in changes in isotherms, compressibility, and monolayer stability. BLM measurements indicated that delivery of CBN via nHAp modifies the electrical properties and stability of the lipid bilayer, suggesting alterations in membrane organization and permeability. These results demonstrate that hydroxyapatite nanoparticles can effectively serve as a carrier for cannabinol while modulating its interactions with lipid membranes. Full article
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