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Molecules, Volume 30, Issue 10 (May-2 2025) – 4 articles

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22 pages, 6497 KiB  
Article
Discovery of Hydrazineyl Amide Derivative of Pseudolaric Acid B for Reprogramming Tumor-Associated Macrophages Against Tumor Growth
by Xia Peng, Siqi Yu, Lin Xu, Qinghua Wang, Lin Yang, Yi Su, Zhirou Xiong, Mengjie Shao, Meiyu Geng, Ao Zhang, Lei Zhang, Jing Ai and Chunyong Ding
Molecules 2025, 30(10), 2088; https://doi.org/10.3390/molecules30102088 (registering DOI) - 8 May 2025
Abstract
Tumor-associated macrophages (TAMs) are pivotal for tumor development and progression. Reprogramming the M2-like pro-tumoral behavior of TAMs towards the M1-like anti-tumor phenotype to unleash their potential against tumors has become one of the most promising anti-tumor immunotherapy strategies. In this work, the natural [...] Read more.
Tumor-associated macrophages (TAMs) are pivotal for tumor development and progression. Reprogramming the M2-like pro-tumoral behavior of TAMs towards the M1-like anti-tumor phenotype to unleash their potential against tumors has become one of the most promising anti-tumor immunotherapy strategies. In this work, the natural product pseudolaric acid B (PAB, 1) was found to markedly decrease ARG1 mRNA expression and significantly increase NOS2 expression in the IL-4/IL-13-pre-stimulated RAW 264.7 cells through cellular phenotype screening of a series of pseudolaric acid-related natural products, suggesting its potential to reprogram the pro-tumoral TAMs towards the M1-like phenotype against tumors. Further chemical modification of the carboxylic acid moiety of 1 led to a series of amide or pyranoside derivatives with ARG1- and NOS2-modulating activity. Among them, hydrazineyl amide 12 stands out as the most potent, without significant diminution in cell viability. It inhibited the M2-like polarized tumor-promoting phenotype of macrophages, as evidenced by a decrease in CD206 expression and an increase in CD86 expression in flow cytometry, as well as a decrease in ARG1 protein level in Western blot assays. In addition, 12 could reverse the suppression of Ki67+, IFN γ+, and granzyme B+ CD8+ T cell proliferation and activation induced by pro-tumoral macrophages. More importantly, it could reshape the tumor immune microenvironment and inhibit tumor growth in immunocompetent murine tumor models. Hsp90 was predicted to be a potential target of 12 by a target fishing software, which was further demonstrated by molecular docking. Collectively, the amide derivative 12 of PAB demonstrated promising anti-tumor TAM-reprogramming activity, which is worthy of further investigation. Full article
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13 pages, 5005 KiB  
Article
Formicarium-Inspired Hierarchical Conductive Architecture for CoSe2@MoSe2 Catalysts Towards Advanced Anion Exchange Membrane Electrolyzers
by Zhongmin Wan, Zhongkai Huang, Changjie Ou, Lihua Wang, Xiangzhong Kong, Zizhang Zhan, Tian Tian, Haolin Tang, Shu Xie and Yongguang Luo
Molecules 2025, 30(10), 2087; https://doi.org/10.3390/molecules30102087 (registering DOI) - 8 May 2025
Abstract
The exploration of high-performance, low-cost, and dual-function electrodes is crucial for anion exchange membrane water electrolysis (AEMWE) to meet the relentless demand for green H2 production. In this study, a heteroatom-doped carbon-cage-supported CoSe2@MoSe2@NC catalyst with a formicarium structure [...] Read more.
The exploration of high-performance, low-cost, and dual-function electrodes is crucial for anion exchange membrane water electrolysis (AEMWE) to meet the relentless demand for green H2 production. In this study, a heteroatom-doped carbon-cage-supported CoSe2@MoSe2@NC catalyst with a formicarium structure has been fabricated using a scalable one-step selenization strategy. The component-refined bifunctional catalyst exhibited minimal overpotential values of 116 mV and 283 mV at 10 mA cm−2 in 1 M KOH for the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), respectively. Specifically, rationally designed heterostructures and flexible carbonaceous sponges facilitate interfacial reaction equalization, modulate local electronic distributions, and establish efficient electron transport pathways, thereby enhancing catalytic activity and durability. Furthermore, the assembled AEMWE based on the CoSe2@MoSe2@NC bifunctional catalysts can achieve a current density of 106 mA cm−2 at 1.9 V and maintain a favorable durability after running for 100 h (a retention of 95%). This work highlights a new insight into the development of advanced bifunctional catalysts with enhanced activity and durability for AEMWE. Full article
(This article belongs to the Special Issue Water Electrolysis)
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28 pages, 12614 KiB  
Article
Nanoparticles as New Antifungals in the Prevention of Bovine Mycotic Mastitis Caused by Candida spp. and Diutina spp.—In Vitro Studies
by Magdalena Kot, Agata Lange, Weronika Jabłońska, Aleksandra Kalińska, Barbara Nasiłowska, Wojciech Skrzeczanowski and Marcin Gołębiewski
Molecules 2025, 30(10), 2086; https://doi.org/10.3390/molecules30102086 (registering DOI) - 8 May 2025
Abstract
Bacterial infections are the primary cause of mastitis in dairy cattle. Fungal mastitis occurs in 1–12% of cases. Antibiotic therapy, the standard treatment for mastitis, has led to antibiotic-resistant bacteria, reducing treatment efficacy and increasing fungal mastitis occurrence. Antibiotics lack biocidal effects [...] Read more.
Bacterial infections are the primary cause of mastitis in dairy cattle. Fungal mastitis occurs in 1–12% of cases. Antibiotic therapy, the standard treatment for mastitis, has led to antibiotic-resistant bacteria, reducing treatment efficacy and increasing fungal mastitis occurrence. Antibiotics lack biocidal effects on fungi, which often exhibit resistance to antifungal agents. This study evaluated the antifungal properties of nanoparticles (NPs) against Candida albicans, Candida glabrata, Candida parapsilosis, Diutina rugosa var. rugosa, Diutina catenulata, and Diutina rugosa. Tested NPs included gold (AuNPs), silver (AgNPs), copper (CuNPs), iron with hydrophilic carbon coating (FeCNPs) (1.56–25 mg/L), and platinum (PtNPs) (0.625–10 mg/L), along with their complexes. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) at 0.75–25 mg/L for AuNPs, AgNPs, CuNPs, and FeCNPs and 0.313–10 mg/L for PtNPs, as well as fungal sensitivity to standard antifungals, were determined. Each strain showed different sensitivities depending on the NPs used and their concentrations. C. glabrata was the most resistant to nanoparticles, while D. catenulata was the most susceptible. PtNPs and FeCNPs showed no or weak biocidal properties. Some mycotic-resistant strains were sensitive to nanoparticles. This study indicates a high in vitro antifungal potential for the application of nanoparticles, especially AgCuNPs, as a new effective non-antibiotic agent for the prevention and control of mycotic mastitis in dairy cattle. Full article
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30 pages, 7649 KiB  
Article
Comparison of Cytotoxicity and Antioxidant, Antibacterial, and Anti-Inflammatory Activity of Aqueous and Ethanolic Extracts from Malus domestica, Prunus armeniaca, and Prunus cerasus Leaves
by Martyna Zagórska-Dziok, Aleksandra Ziemlewska, Magdalena Wójciak, Ireneusz Sowa, Ewa Wąsik-Szczepanek and Zofia Nizioł-Łukaszewska
Molecules 2025, 30(10), 2085; https://doi.org/10.3390/molecules30102085 - 8 May 2025
Abstract
This study presents a comprehensive evaluation of the biological properties of aqueous and aqueous–ethanolic leaf extracts from Malus domestica, Prunus armeniaca, and Prunus cerasus, which are plant waste materials. Phytochemical profiles were analyzed using HPLC, and antioxidant potential was assessed [...] Read more.
This study presents a comprehensive evaluation of the biological properties of aqueous and aqueous–ethanolic leaf extracts from Malus domestica, Prunus armeniaca, and Prunus cerasus, which are plant waste materials. Phytochemical profiles were analyzed using HPLC, and antioxidant potential was assessed via DPPH, ABTS, FRAP, and superoxide dismutase (SOD) activity assays. Extracts showed concentration-, plant-, and extract type-dependent radical scavenging effects exceeding 80%, significant Fe3+ ion reduction, and up to 40% enhancement of SOD activity. In vitro studies on HDF and HaCaT cells revealed reduced intracellular ROS levels, indicating antioxidant potential. Cytotoxicity assays (Alamar Blue, Neutral Red) demonstrated increased skin cell viability by up to 35% at ≤50 or 125 µg/mL, while higher doses reduced viability by up to 70%, depending on the extract. Antibacterial activity varied among plant species and was effective against seven bacterial strains. ELISA assays showed anti-inflammatory effects, with IL-1β and IL-6 levels reduced by 48% and 40%, respectively, and IL-10 increased by up to 27%. These findings suggest that the tested leaf extracts support both enzymatic and non-enzymatic antioxidant defense mechanisms and may be valuable as functional ingredients in dermatological or cosmetic applications. Full article
(This article belongs to the Special Issue Research Progress of New Antimicrobial Drugs)
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