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Keywords = membrane formation mechanism

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20 pages, 2559 KiB  
Article
Anticancer Activity of Vitex agnus-castus Seed Extract on Gastric Cancer Cells
by Özlem Türksoy-Terzioğlu, Feyza Tosya, Ayşe Büşranur Çelik, Sibel Bölek, Levent Gülüm, Gökhan Terzioğlu and Yusuf Tutar
Nutrients 2025, 17(15), 2564; https://doi.org/10.3390/nu17152564 - 6 Aug 2025
Abstract
Background/Objectives: Vitex agnus-castus has been traditionally used to treat hormonal disorders, and recent evidence suggests its potential anticancer properties. However, its effects on gastric cancer remain unclear. Methods: This study examined the cytotoxic, apoptotic, and anti-metastatic effects of hydroalcoholic Vitex agnus-castus [...] Read more.
Background/Objectives: Vitex agnus-castus has been traditionally used to treat hormonal disorders, and recent evidence suggests its potential anticancer properties. However, its effects on gastric cancer remain unclear. Methods: This study examined the cytotoxic, apoptotic, and anti-metastatic effects of hydroalcoholic Vitex agnus-castus seed extract in gastric cancer cells. Antioxidant capacity (DPPH, ABTS) and total phenolic and flavonoid contents were analyzed. Cytotoxicity was assessed using the MTT assay in HGC27, MKN45, and AGS gastric cancer cell lines and CCD-1072Sk fibroblasts. Apoptosis, mitochondrial membrane potential (MMP), and cell cycle changes were evaluated via Annexin V-FITC/PI, Rhodamine 123, and PI staining, respectively. RT-qPCR and gene enrichment analyses were conducted to investigate the molecular mechanisms. Apoptosis-related protein expression was analyzed through enzyme-linked immunosorbent assay (ELISA). Results: The extract exhibited high antioxidant activity and a significant phenolic content. It reduced cell viability in a dose-dependent manner in gastric cancer cells, while exerting low toxicity in fibroblasts. It significantly increased apoptosis, induced G0/G1-phase cell cycle arrest, upregulated pro-apoptotic genes (CASP3, CASP7, TP53, BCL2L11), and downregulated anti-apoptotic genes (XIAP, NOL3). Gene enrichment analysis highlighted pathways like apoptosis, necrosis, and cysteine endopeptidase activity. The extract also disrupted MMP, inhibited migration and spheroid formation, suppressed EMT markers (SNAIL, SLUG, TWIST1, N-CADHERIN), and upregulated E-CADHERIN. The expression of Caspase 3 and Bax proteins increased and Bcl2 protein decreased. Conclusions: These findings suggest that Vitex agnus-castus seed extract exerts strong anticancer effects in gastric cancer cells by promoting apoptosis, reducing proliferation, and inhibiting migration. Further studies are warranted to explore its clinical relevance. Full article
(This article belongs to the Section Phytochemicals and Human Health)
22 pages, 1000 KiB  
Review
Is the Activation of the Postsynaptic Ligand Gated Glycine- or GABAA Receptors Essential for the Receptor Clustering at Inhibitory Synapses?
by Eva Kiss, Joachim Kirsch, Jochen Kuhse and Stefan Kins
Biomedicines 2025, 13(8), 1905; https://doi.org/10.3390/biomedicines13081905 - 5 Aug 2025
Abstract
One major challenge in cellular neuroscience is to elucidate how the accurate alignment of presynaptic release sites with postsynaptic densely clustered ligand-gated ion channels at chemical synapses is achieved upon synapse assembly. The clustering of neurotransmitter receptors at postsynaptic sites is a key [...] Read more.
One major challenge in cellular neuroscience is to elucidate how the accurate alignment of presynaptic release sites with postsynaptic densely clustered ligand-gated ion channels at chemical synapses is achieved upon synapse assembly. The clustering of neurotransmitter receptors at postsynaptic sites is a key moment of synaptogenesis and determinant for effective synaptic transmission. The number of the ionotropic neurotransmitter receptors at these postsynaptic sites of both excitatory and inhibitory synapses is variable and is regulated by different mechanisms, thus allowing the modulation of synaptic strength, which is essential to tune neuronal network activity. Several well-regulated processes seem to be involved, including lateral diffusion within the plasma membrane and local anchoring as well as receptor endocytosis and recycling. The molecular mechanisms implicated are numerous and were reviewed recently in great detail. The role of pre-synaptically released neurotransmitters within the complex regulatory apparatus organizing the postsynaptic site underneath presynaptic terminals is not completely understood, even less for inhibitory synapses. In this mini review article, we focus on this aspect of synapse formation, summarizing and contrasting findings on the functional role of the neurotransmitters glycine and γ-aminobutyric acid (GABA) for initiation of postsynaptic receptor clustering and regulation of Cl channel receptor numbers at inhibitory synapses gathered over the last two decades. Full article
(This article belongs to the Special Issue Synaptic Function and Modulation in Health and Disease)
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9 pages, 1938 KiB  
Brief Report
Single-Component Silicon-Containing Polyurethane for High-Performance Waterproof and Breathable Nanofiber Membranes
by Dongxu Lu, Yanbing Li, Yake Chai, Ximei Wen, Liming Chen and Sanming Sun
Fibers 2025, 13(8), 105; https://doi.org/10.3390/fib13080105 - 5 Aug 2025
Abstract
High-performance waterproof and breathable nanofiber membranes (WBNMs) are in great demand for various advanced applications. However, the fabrication of such membranes often relies on fluorinated materials or involves complex preparation processes, limiting their practical use. In this study, we present an innovative approach [...] Read more.
High-performance waterproof and breathable nanofiber membranes (WBNMs) are in great demand for various advanced applications. However, the fabrication of such membranes often relies on fluorinated materials or involves complex preparation processes, limiting their practical use. In this study, we present an innovative approach by utilizing silicon-containing polyurethane (SiPU) as a single-component, fluorine-free raw material to prepare high-performance WBNMs via a simple one-step electrospinning process. The electrospinning technique enables the formation of SiPU nanofibrous membranes with a small maximum pore size (dmax) and high porosity, while the intrinsic hydrophobicity of SiPU imparts excellent water-repellent characteristics to the membranes. As a result, the single-component SiPU WBNM exhibits superior waterproofness and breathability, with a hydrostatic pressure of 52 kPa and a water vapor transmission rate (WVTR) of 5798 g m−2 d−1. Moreover, the optimized SiPU-14 WBNM demonstrates outstanding mechanical properties, including a tensile strength of 6.15 MPa and an elongation at break of 98.80%. These findings indicate that the single-component SiPU-14 WBNMs not only achieve excellent waterproof and breathable performance but also possess robust mechanical strength, thereby enhancing the comfort and expanding the potential applications of protective textiles, such as outdoor apparel and car seats. Full article
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16 pages, 7605 KiB  
Article
From Cap to Collar: Ontogeny of the Endocytic Collar in Neurospora crassa
by Marisela Garduño-Rosales, Caleb Oliver Bedsole, Brian D. Shaw and Rosa R. Mouriño-Pérez
J. Fungi 2025, 11(8), 577; https://doi.org/10.3390/jof11080577 - 3 Aug 2025
Viewed by 141
Abstract
Endocytosis in filamentous fungi is spatially restricted to a subapical zone known as the endocytic collar, which plays essential roles in membrane recycling and the maintenance of polarized growth. In this study, we investigated the ontogeny of the endocytic collar in Neurospora crassa [...] Read more.
Endocytosis in filamentous fungi is spatially restricted to a subapical zone known as the endocytic collar, which plays essential roles in membrane recycling and the maintenance of polarized growth. In this study, we investigated the ontogeny of the endocytic collar in Neurospora crassa by tracking fimbrin-labeled endocytic patches using confocal microscopy during conidial germination, hyphal branching, and regeneration following mechanical injury. We consistently observed an initial accumulation of endocytic patches at the hyphal tip, forming an apical cap, which later reorganized into a subapical collar. This transition was correlated with a significant increase in elongation rate and the appearance of a Spitzenkörper, indicating a link between exocytosis and collar positioning. Although this correlation is robust, our data do not establish causality; rather, collar formation appears to occur after surpassing a critical elongation. Our findings suggest that exocytosis displaces endocytosis from the apex, resulting in the formation of the collar, which is not required for the establishment of polarized growth but is essential for its maintenance. These results support the development of a unified model of collar formation in filamentous fungi and provide new insight into the spatial coordination between endocytic and exocytic processes during hyphal development. Full article
(This article belongs to the Section Fungal Cell Biology, Metabolism and Physiology)
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16 pages, 1652 KiB  
Review
Lipid−lncRNA Crossroads: An Overview of Interactions Between Lipids and lncRNA
by Andrea Bayona-Hernandez, Ana Miladinović, Ludovica Antiga, Pavel Hozak, Martin Sztacho and Enrique Castano
Cells 2025, 14(15), 1193; https://doi.org/10.3390/cells14151193 - 2 Aug 2025
Viewed by 165
Abstract
Long non-coding RNAs (lncRNAs) interact with a variety of biomolecules, including DNA, mRNAs, microRNA, and proteins, to regulate various cellular processes. Recently, their interactions with lipids have gained increasing attention as an emerging research area. Both lipids and lncRNAs play central roles in [...] Read more.
Long non-coding RNAs (lncRNAs) interact with a variety of biomolecules, including DNA, mRNAs, microRNA, and proteins, to regulate various cellular processes. Recently, their interactions with lipids have gained increasing attention as an emerging research area. Both lipids and lncRNAs play central roles in cellular regulation, and growing evidence reveals a complex interplay between these molecules. These interactions contribute to key biological functions, such as cancer progression, lipid droplet transport, autophagy, liquid−liquid phase separation, and the formation of organelles without membranes. Understanding the lipid−lncRNA interface opens new avenues for unraveling cellular regulation and disease mechanisms, holding great potential not only for elucidating the fundamental aspects of cellular biology but also for identifying innovative therapeutic targets for metabolic disorders and cancer. This review highlights the biological relevance of lipid–lncRNA interactions by exploring their roles in cellular organization, regulation, and diseases, including metabolic and cancer-related disorders. Full article
(This article belongs to the Section Cell Microenvironment)
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13 pages, 2939 KiB  
Review
A Review of Maricultural Wastewater Treatment Using an MBR: Insights into the Mechanism of Membrane Fouling Mitigation Through a Microalgal–Bacterial Symbiotic and Microbial Ecological Network
by Yijun You, Shuyu Zhao, Binghan Xie, Zhipeng Li, Weijia Gong, Guoyu Zhang, Qinghao Li, Xiangqian Zhao, Zhaofeng Xin, Jinkang Wu, Yuanyuan Gao and Han Xiang
Membranes 2025, 15(8), 234; https://doi.org/10.3390/membranes15080234 - 1 Aug 2025
Viewed by 208
Abstract
Membrane bioreactors (MBRs) have been utilized for maricultural wastewater treatment, where high-salinity stress results in dramatic membrane fouling in the actual process. A microalgal–bacterial symbiotic system (MBSS) offers advantages for photosynthetic oxygen production, dynamically regulating the structure of extracellular polymeric substances (EPSs) and [...] Read more.
Membrane bioreactors (MBRs) have been utilized for maricultural wastewater treatment, where high-salinity stress results in dramatic membrane fouling in the actual process. A microalgal–bacterial symbiotic system (MBSS) offers advantages for photosynthetic oxygen production, dynamically regulating the structure of extracellular polymeric substances (EPSs) and improving the salinity tolerance of bacteria and algae. This study centered on the mechanisms of membrane fouling mitigation via the microalgal–bacterial interactions in the MBSS, including improving the pollutant removal, optimizing the system parameters, and controlling the gel layer formation. Moreover, the contribution of electrochemistry to decreasing the inhibitory effects of high-salinity stress was investigated in the MBSS. Furthermore, patterns of shifts in microbial communities and the impacts have been explored using metagenomic technology. Finally, this review aims to offer new insights for membrane fouling mitigation in actual maricultural wastewater treatment. Full article
(This article belongs to the Special Issue Emerging Superwetting Membranes: New Advances in Water Treatment)
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8 pages, 3048 KiB  
Communication
Layer-by-Layer Nanoassembly of Cu(OH)2 Multilayer Membranes for Nanofiltration
by Wenbo Sun, Yanpeng Xue and Guozhi Liu
Coatings 2025, 15(8), 895; https://doi.org/10.3390/coatings15080895 (registering DOI) - 1 Aug 2025
Viewed by 158
Abstract
A facile way to prepare Cu(OH)2 inorganic nanofiltration membranes with neatly arranged multilayers has been developed based on the reaction of a sodium hydroxide solution and a copper ammonia solution at the liquid–liquid interfaces. The effects of the concentration, temperature, and time [...] Read more.
A facile way to prepare Cu(OH)2 inorganic nanofiltration membranes with neatly arranged multilayers has been developed based on the reaction of a sodium hydroxide solution and a copper ammonia solution at the liquid–liquid interfaces. The effects of the concentration, temperature, and time of the liquid–liquid reaction on membrane structure and pore sizes were studied by SEM, TEM, and X-ray diffraction. The growth mechanism of the membrane was discussed and the formation process model was proposed. It was found that the reaction temperature was a key factor in obtaining a Cu(OH)2 monolayer, and this could be used to adjust the thickness and pore size of the monolayer. The as-prepared Cu(OH)2 membranes exhibited excellent filtration performance with the pure water fluxes of 156.2 L·m−2 h−1 bar−1 and retention rates of 100% for methylene blue (50 ppm) at a pressure of 0.1 MPa. This successfully opens up a new method of synthesizing multilayer nanoarrays’ Cu(OH)2 structure for nanofiltration. Full article
(This article belongs to the Special Issue Deposition-Based Coating Solutions for Enhanced Surface Properties)
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17 pages, 3389 KiB  
Article
Enhanced OH Transport Properties of Bio-Based Anion-Exchange Membranes for Different Applications
by Suer Kurklu-Kocaoglu, Daniela Ramírez-Espinosa and Clara Casado-Coterillo
Membranes 2025, 15(8), 229; https://doi.org/10.3390/membranes15080229 - 31 Jul 2025
Viewed by 371
Abstract
The demand for anion exchange membranes (AEMs) is growing due to their applications in water electrolysis, CO2 reduction conversion and fuel cells, as well as water treatment, driven by the increasing energy demand and the need for a sustainable future. However, current [...] Read more.
The demand for anion exchange membranes (AEMs) is growing due to their applications in water electrolysis, CO2 reduction conversion and fuel cells, as well as water treatment, driven by the increasing energy demand and the need for a sustainable future. However, current AEMs still face challenges, such as insufficient permeability and stability in strongly acidic or alkaline media, which limit their durability and the sustainability of membrane fabrication. In this study, polyvinyl alcohol (PVA) and chitosan (CS) biopolymers are selected for membrane preparation. Zinc oxide (ZnO) and porous organic polymer (POP) nanoparticles are also introduced within the PVA-CS polymer blends to make mixed-matrix membranes (MMMs) with increased OH transport sites. The membranes are characterized based on typical properties for AEM applications, such as thickness, water uptake, KOH uptake, Cl and OH permeability and ion exchange capacity (IEC). The OH transport of the PVA-CS blend is increased by at least 94.2% compared with commercial membranes. The incorporation of non-porous ZnO and porous POP nanoparticles into the polymer blend does not compromise the OH transport properties. On the contrary, ZnO nanoparticles enhance the membrane’s water retention capacity, provide basic surface sites that facilitate hydroxide ion conduction and reinforce the mechanical and thermal stability. In parallel, POPs introduce a highly porous architecture that increases the internal surface area and promotes the formation of continuous hydrated pathways, essential to efficient OH mobility. Furthermore, the presence of POPs also contributes to reinforcing the mechanical integrity of the membrane. Thus, PVA-CS bio-based membranes are a promising alternative to conventional ion exchange membranes for various applications. Full article
(This article belongs to the Special Issue Membrane Technologies for Water Purification)
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36 pages, 1730 KiB  
Review
Pharmacological Potential of Cinnamic Acid and Derivatives: A Comprehensive Review
by Yu Tian, Xinya Jiang, Jiageng Guo, Hongyu Lu, Jinling Xie, Fan Zhang, Chun Yao and Erwei Hao
Pharmaceuticals 2025, 18(8), 1141; https://doi.org/10.3390/ph18081141 - 31 Jul 2025
Viewed by 377
Abstract
Cinnamic acid, an organic acid naturally occurring in plants of the Cinnamomum genus, has been highly valued for its medicinal properties in numerous ancient Chinese texts. This article reviews the chemical composition, pharmacological effects, and various applications of cinnamic acid and its derivatives [...] Read more.
Cinnamic acid, an organic acid naturally occurring in plants of the Cinnamomum genus, has been highly valued for its medicinal properties in numerous ancient Chinese texts. This article reviews the chemical composition, pharmacological effects, and various applications of cinnamic acid and its derivatives reported in publications from 2016 to 2025, and anticipates their potential in medical and industrial fields. This review evaluates studies in major scientific databases, including Web of Science, PubMed, and ScienceDirect, to ensure a comprehensive analysis of the therapeutic potential of cinnamic acid. Through systematic integration of existing knowledge, it has been revealed that cinnamic acid has a wide range of pharmacological activities, including anti-tumor, antibacterial, anti-inflammatory, antidepressant and hypoglycemic effects. Additionally, it has been shown to be effective against a variety of pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, and foodborne Pseudomonas. Cinnamic acid acts by disrupting cell membranes, inhibiting ATPase activity, and preventing biofilm formation, thereby demonstrating its ability to act as a natural antimicrobial agent. Its anti-inflammatory properties are demonstrated by improving oxidative stress and reducing inflammatory cell infiltration. Furthermore, cinnamic acid enhances metabolic health by improving glucose uptake and insulin sensitivity, showing promising results in improving metabolic health in patients with diabetes and its complications. This systematic approach highlights the need for further investigation of the mechanisms and safety of cinnamic acid to substantiate its use as a basis for new drug development. Particularly in the context of increasing antibiotic resistance and the search for sustainable, effective medical treatments, the study of cinnamic acid is notably significant and innovative. Full article
(This article belongs to the Section Pharmacology)
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41 pages, 2975 KiB  
Review
Algal Metabolites as Novel Therapeutics Against Methicillin-Resistant Staphylococcus aureus (MRSA): A Review
by Ibraheem Borie M. Ibraheem, Reem Mohammed Alharbi, Neveen Abdel-Raouf, Nouf Mohammad Al-Enazi, Khawla Ibrahim Alsamhary and Hager Mohammed Ali
Pharmaceutics 2025, 17(8), 989; https://doi.org/10.3390/pharmaceutics17080989 (registering DOI) - 30 Jul 2025
Viewed by 267
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as a “superbug”, and its resistance mechanisms, including target modification, drug inactivation, efflux pumps, biofilm formation, and quorum sensing. The limitations of conventional antibiotics (e.g., β-lactams, vancomycin, macrolides) are discussed, alongside the promise of algal-derived compounds such as fatty acids, pigments, polysaccharides, terpenoids, and phenolic compounds. These metabolites exhibit potent anti-MRSA activity by disrupting cell division (via FtsZ inhibition), destabilizing membranes, and inhibiting protein synthesis and metabolic pathways, effectively countering multiple resistance mechanisms. Leveraging advances in algal biotechnology, this review highlights the untapped potential of marine algae to drive innovative, sustainable therapeutic strategies against antibiotic resistance. Full article
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19 pages, 4058 KiB  
Article
Antitumor Activity of Ruditapes philippinarum Polysaccharides Through Mitochondrial Apoptosis in Cellular and Zebrafish Models
by Mengyue Liu, Weixia Wang, Haoran Wang, Shuang Zhao, Dongli Yin, Haijun Zhang, Chunze Zou, Shengcan Zou, Jia Yu and Yuxi Wei
Mar. Drugs 2025, 23(8), 304; https://doi.org/10.3390/md23080304 - 29 Jul 2025
Viewed by 196
Abstract
Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this [...] Read more.
Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this study, we enzymatically extracted a polysaccharide, named ERPP, from Ruditapes philippinarum and comprehensively evaluated its anti-colorectal cancer activity. We conducted in vitro assays, including CCK-8 proliferation, clonogenic survival, scratch wound healing, and Annexin V-FITC/PI apoptosis staining, and the results demonstrated that ERPP significantly inhibited HT-29 cell proliferation, suppressed colony formation, impaired migratory capacity, and induced apoptosis. JC-1 fluorescence assays provided further evidence of mitochondrial membrane potential (MMP) depolarization, as manifested by a substantial reduction in the red/green fluorescence ratio (from 10.87 to 0.35). These antitumor effects were further validated in vivo using a zebrafish HT-29 xenograft model. Furthermore, ERPP treatment significantly attenuated tumor angiogenesis and downregulated the expression of the vascular endothelial growth factor A (Vegfaa) gene in the zebrafish xenograft model. Mechanistic investigations revealed that ERPP primarily activated the mitochondrial apoptosis pathway. RT-qPCR analysis showed an upregulation of the pro-apoptotic gene Bax and a downregulation of the anti-apoptotic gene Bcl-2, leading to cytochrome c (CYCS) release and caspase-3 (CASP-3) activation. Additionally, ERPP exhibited potent antioxidant capacity, achieving an 80.2% hydroxyl radical scavenging rate at 4 mg/mL. ERPP also decreased reactive oxygen species (ROS) levels within the tumor cells, thereby augmenting anticancer efficacy through its antioxidant activity. Collectively, these findings provide mechanistic insights into the properties of ERPP, underscoring its potential as a functional food component or adjuvant therapy for colorectal cancer management. Full article
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17 pages, 2524 KiB  
Article
A Model-Driven Approach to Assessing the Fouling Mechanism in the Crossflow Filtration of Laccase Extract from Pleurotus ostreatus 202
by María Augusta Páez, Mary Casa-Villegas, Vanesa Naranjo-Moreno, Neyda Espín Félix, Katty Cabezas-Terán and Alfonsina Andreatta
Membranes 2025, 15(8), 226; https://doi.org/10.3390/membranes15080226 - 29 Jul 2025
Viewed by 353
Abstract
Membrane technology is primarily used for the separation and purification of biotechnological products, which contain proteins and enzymes. Membrane fouling during crossflow filtration remains a significant challenge. This study aims to initially validate crossflow filtration models, particularly related to pore-blocking mechanisms, through a [...] Read more.
Membrane technology is primarily used for the separation and purification of biotechnological products, which contain proteins and enzymes. Membrane fouling during crossflow filtration remains a significant challenge. This study aims to initially validate crossflow filtration models, particularly related to pore-blocking mechanisms, through a comparative analysis with dead-end filtration models. One crossflow microfiltration (MF) and six consecutive ultrafiltration (UF) stages were implemented to concentrate laccase extracts from Pleurotus ostreatus 202 fungi. The complete pore-blocking mechanism significantly impacts the MF, UF 1000, UF 100 and UF 10 stages, with the highest related filtration constant (KbF) estimated at 12.60 × 10−4 (m−1). Although the intermediate pore-blocking mechanism appears across all filtration stages, UF 100 is the most affected, with an associated filtration constant (KiF) of 16.70 (m−1). This trend is supported by the highest purification factor (6.95) and the presence of 65, 62 and 56 kDa laccases in the retentate. Standard pore blocking occurs at the end of filtration, only in the MF and UF 1000 stages, with filtration constants (KsF) of 29.83 (s−0.5m−0.5) and 31.17 (s−0.5m−0.5), respectively. The absence of cake formation and the volume of permeate recovered indicate that neither membrane was exposed to exhaustive fouling that could not be reversed by backwashing. Full article
(This article belongs to the Section Membrane Applications for Other Areas)
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18 pages, 652 KiB  
Review
The Role of Advanced Glycation End-Products in the Pathophysiology and Pharmacotherapy of Cardiovascular Disease
by Karina O. Mota, Carla M. L. de Vasconcelos, Lorrie A. Kirshenbaum and Naranjan S. Dhalla
Int. J. Mol. Sci. 2025, 26(15), 7311; https://doi.org/10.3390/ijms26157311 - 29 Jul 2025
Viewed by 291
Abstract
Advanced glycation end-products (AGEs) are formed by the non-enzymatic glycation of proteins, lipids, and nucleic acids due to the consumption of high-carbohydrate diets; their production is also promoted by a sedentary lifestyle as well as cigarette smoking. Elevated levels of AGEs in the [...] Read more.
Advanced glycation end-products (AGEs) are formed by the non-enzymatic glycation of proteins, lipids, and nucleic acids due to the consumption of high-carbohydrate diets; their production is also promoted by a sedentary lifestyle as well as cigarette smoking. Elevated levels of AGEs in the circulatory system and internal organs of the body are commonly observed in a number of cardiovascular diseases such as hypertension, diabetes, atherosclerosis, coronary artery disease, aortic aneurysm, atrial fibrillation, myocardial infarction, and heart failure, which are associated with the development of oxidative stress and myocardial inflammation. The adverse effects of AGEs on the cardiovascular system are elicited by both non-receptor mechanisms involving the cross-linking of extracellular and intracellular proteins, and by receptor-mediated mechanisms involving the binding of AGEs with advanced glycation end-product receptors (RAGEs) on the cell membrane. AGE–RAGE interactions along with the cross-linking of proteins promote the generation of oxidative stress, the production of inflammation, the occurrence of intracellular Ca2+-overload, and alterations in the extracellular matrix leading to the development of cardiovascular dysfunction. AGEs also bind with two other protein receptors in the circulatory system: soluble RAGEs (sRAGEs) are released upon the proteolysis of RAGEs due to the activation of matrix metalloproteinase, and endogenous secretory RAGEs (esRAGEs) are secreted as a spliced variant of endogenous RAGEs. While the AGE–RAGE signal transduction axis serves as a pathogenic mechanism, both sRAGEs and esRAGEs serve as cytoprotective interventions. The serum levels of sRAGEs are decreased in ischemic heart disease, vascular disease, and heart failure, as well as in other cardiovascular diseases, but are increased in chronic diabetes and renal disease. Several interventions which can reduce the formation of AGEs, block the AGE–RAGE axis, or increase the levels of circulating sRAGEs have been shown to exert beneficial effects in diverse cardiovascular diseases. These observations support the view that the AGE–RAGE axis not only plays a critical role in pathogenesis, but is also an excellent target for the treatment of cardiovascular disease. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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17 pages, 3410 KiB  
Article
Squama Manitis Extract Exhibits Broad-Spectrum Antibacterial Activity Through Energy and DNA Disruption Mechanisms
by Li Chen, Kunping Song, Mengwei Cheng, Aloysius Wong, Xuechen Tian, Yixin Yang, Mia Yang Ang, Geok Yuan Annie Tan and Siew Woh Choo
Biology 2025, 14(8), 949; https://doi.org/10.3390/biology14080949 - 28 Jul 2025
Viewed by 315
Abstract
The global antimicrobial resistance crisis demands innovative strategies to combat bacterial infections, including those caused by drug-sensitive pathogens that evade treatment through biofilm formation or metabolic adaptations. Here, we demonstrate that Squama Manitis extract (SME)—a traditional Chinese medicine component—exhibits broad-spectrum bactericidal activity against [...] Read more.
The global antimicrobial resistance crisis demands innovative strategies to combat bacterial infections, including those caused by drug-sensitive pathogens that evade treatment through biofilm formation or metabolic adaptations. Here, we demonstrate that Squama Manitis extract (SME)—a traditional Chinese medicine component—exhibits broad-spectrum bactericidal activity against clinically significant pathogens, including both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) species (MIC = 31.25 mg/mL), achieving significant reduction in bacterial viability within 24 h. Through integrated multi-omics analysis combining scanning electron microscopy and RNA sequencing, we reveal SME’s unprecedented tripartite mechanism of action: (1) direct membrane disruption causing cell envelope collapse, (2) metabolic paralysis through coordinated suppression of TCA cycle and fatty acid degradation pathways, and (3) inhibition of DNA repair systems (SOS response and recombination downregulation). Despite its potent activity, SME shows low cytotoxicity toward mammalian cells (>90% viability) and can penetrate Gram-negative outer membranes. These features highlight SME’s potential to address drug-resistant infections through synthetic lethality across stress response, energy metabolism, and DNA integrity pathways. While advocating for synthetic alternatives to endangered animal products, this study establishes SME as a polypharmacological template for resistance-resilient antimicrobial design, demonstrating how traditional knowledge and modern systems biology can converge to guide sustainable anti-infective development. Full article
(This article belongs to the Section Microbiology)
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31 pages, 7303 KiB  
Review
Membrane-Targeting Antivirals
by Maxim S. Krasilnikov, Vladislav S. Denisov, Vladimir A. Korshun, Alexey V. Ustinov and Vera A. Alferova
Int. J. Mol. Sci. 2025, 26(15), 7276; https://doi.org/10.3390/ijms26157276 - 28 Jul 2025
Viewed by 271
Abstract
The vast majority of viruses causing human and animal diseases are enveloped—their virions contain an outer lipid bilayer originating from a host cell. Small molecule antivirals targeting the lipid bilayer cover the broadest spectrum of viruses. In this context, we consider the chemical [...] Read more.
The vast majority of viruses causing human and animal diseases are enveloped—their virions contain an outer lipid bilayer originating from a host cell. Small molecule antivirals targeting the lipid bilayer cover the broadest spectrum of viruses. In this context, we consider the chemical nature and mechanisms of action of membrane-targeting antivirals. They can affect virions by (1) physically modulating membrane properties to inhibit fusion of the viral envelope with the cell membrane, (2) physically affecting envelope lipids and proteins leading to membrane damage, pore formation and lysis, (3) causing photochemical damage of unsaturated membrane lipids resulting in integrity loss and fusion arrest. Other membrane-active compounds can target host cell membranes involved in virion’s maturation, coating, and egress (endoplasmic reticulum, Golgi apparatus, and outer membrane) affecting these last stages of viral reproduction. Both virion- and host-targeting membrane-active molecules are promising concepts for broad-spectrum antivirals. A panel of approved antivirals would be a superior weapon to respond to and control emerging disease outbreaks caused by new viral strains and variants. Full article
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