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17 pages, 7385 KiB  
Article
Microbial Alliance of Paenibacillus sp. SPR11 and Bradyrhizobium yuanmingense PR3 Enhances Nitrogen Fixation, Yield, and Salinity Tolerance in Black Gram Under Saline, Nutrient-Depleted Soils
by Praveen Kumar Tiwari, Anchal Kumar Srivastava, Rachana Singh and Alok Kumar Srivastava
Nitrogen 2025, 6(3), 66; https://doi.org/10.3390/nitrogen6030066 (registering DOI) - 7 Aug 2025
Abstract
Salinity is a major abiotic stress limiting black gram (Vigna mungo) productivity, particularly in arid and semi-arid regions. Saline soils negatively impact plant growth, nodulation, nitrogen fixation, and yield. This study evaluated the efficacy of co-inoculating salt-tolerant plant growth-promoting bacteria Paenibacillus [...] Read more.
Salinity is a major abiotic stress limiting black gram (Vigna mungo) productivity, particularly in arid and semi-arid regions. Saline soils negatively impact plant growth, nodulation, nitrogen fixation, and yield. This study evaluated the efficacy of co-inoculating salt-tolerant plant growth-promoting bacteria Paenibacillus sp. SPR11 and Bradyrhizobium yuanmingense PR3 on black gram performance under saline field conditions (EC: 8.87 dS m−1; pH: 8.37) with low organic carbon (0.6%) and nutrient deficiencies. In vitro assays demonstrated the biocontrol potential of SPR11, inhibiting Fusarium oxysporum and Macrophomina phaseolina by 76% and 62%, respectively. Germination assays and net house experiments under 300 mM NaCl stress showed that co-inoculation significantly improved physiological traits, including germination rate, root length (61.39%), shoot biomass (59.95%), and nitrogen fixation (52.4%) in nitrogen-free media. Field trials further revealed enhanced stress tolerance markers: chlorophyll content increased by 54.74%, proline by 50.89%, and antioxidant enzyme activities (SOD, CAT, PAL) were significantly upregulated. Electrolyte leakage was reduced by 55.77%, indicating improved membrane stability. Agronomic performance also improved, with co-inoculated plants showing increased root length (7.19%), grain yield (15.55 q ha−1; 77.04% over control), total biomass (26.73 q ha−1; 57.06%), and straw yield (8.18 q ha−1). Pod number, seed count, and seed weight were also enhanced. Nutrient analysis showed elevated uptake of nitrogen, phosphorus, potassium, and key micronutrients (Zn, Fe) in both grain and straw. To the best of our knowledge, this is the very first field-based report demonstrating the synergistic benefits of co-inoculating Paenibacillus sp. SPR11 and Bradyrhizobium yuanmingense PR3 in black gram under saline, nutrient-poor conditions without external nitrogen inputs. The results highlight a sustainable strategy to enhance legume productivity and resilience in salt-affected soils. Full article
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27 pages, 3377 KiB  
Article
Effect of Thuja occidentalis L. Essential Oil Combined with Diatomite Against Selected Pests
by Janina Gospodarek, Elżbieta Boligłowa, Krzysztof Gondek, Krzysztof Smoroń and Iwona B. Paśmionka
Molecules 2025, 30(15), 3300; https://doi.org/10.3390/molecules30153300 - 6 Aug 2025
Abstract
Combining products of natural origin with different mechanisms of action on insect herbivores may provide an alternative among methods of plant protection against pests that are less risky for the environment. The aim of the study was to evaluate the effectiveness of mixtures [...] Read more.
Combining products of natural origin with different mechanisms of action on insect herbivores may provide an alternative among methods of plant protection against pests that are less risky for the environment. The aim of the study was to evaluate the effectiveness of mixtures of Thuja occidentalis L. essential oil and diatomite (EO + DE) compared to each substance separately in reducing economically important pests such as black bean aphid (BBA) Aphis fabae Scop., Colorado potato beetle (CPB) Leptinotarsa decemlineata Say., and pea leaf weevil (PLW) Sitona lineatus L. The effects on mortality (all pests) and foraging intensity (CPB and PLW) were tested. The improvement in effectiveness using a mixture of EO + DE versus single components against BBA was dose- and the developmental stage-dependent. The effect of enhancing CPB foraging inhibition through DE addition was obtained at a concentration of 0.2% EO (both females and males of CPB) and 0.5% EO (males) in no-choice experiments. In choice experiments, mixtures EO + DE with both 0.2% and 0.5% EO concentrations resulted in a significant reduction in CPB foraging. A significant strengthening effect of EO 0.5% through the addition of DE at a dose of 10% against PLW males was observed in the no-choice experiment, while, when the beetles had a choice, the synergistic effect of a mixture of EO 0.5% and DE 10% was also apparent in females. In conclusion, the use of DE mixtures with EO from T. occidentalis appears to be a promising strategy. The results support the idea of not using doses of EO higher than 0.5%. Full article
24 pages, 2024 KiB  
Article
New Insights into the Synergistic Bioactivities of Zingiber officinale (Rosc.) and Humulus lupulus (L.) Essential Oils: Targeting Tyrosinase Inhibition and Antioxidant Mechanisms
by Hubert Sytykiewicz, Sylwia Goławska and Iwona Łukasik
Molecules 2025, 30(15), 3294; https://doi.org/10.3390/molecules30153294 - 6 Aug 2025
Abstract
Essential oils (EOs) constitute intricate mixtures of volatile phytochemicals that have garnered significant attention due to their multifaceted biological effects. Notably, the presence of bioactive constituents capable of inhibiting tyrosinase enzyme activity and scavenging reactive oxygen species (ROS) underpins their potential utility in [...] Read more.
Essential oils (EOs) constitute intricate mixtures of volatile phytochemicals that have garnered significant attention due to their multifaceted biological effects. Notably, the presence of bioactive constituents capable of inhibiting tyrosinase enzyme activity and scavenging reactive oxygen species (ROS) underpins their potential utility in skin-related applications, particularly through the modulation of melanin biosynthesis and protection of skin-relevant cells from oxidative damage—a primary contributor to hyperpigmentation disorders. Zingiber officinale Rosc. (ginger) and Humulus lupulus L. (hop) are medicinal plants widely recognized for their diverse pharmacological properties. To the best of our knowledge, this study provides the first report on the synergistic interactions between essential oils derived from these species (referred to as EOZ and EOH) offering novel insights into their combined bioactivity. The purpose of this study was to evaluate essential oils extracted from ginger rhizomes and hop strobiles with respect to the following: (1) chemical composition, determined by gas chromatography–mass spectrometry (GC-MS); (2) tyrosinase inhibitory activity; (3) capacity to inhibit linoleic acid peroxidation; (4) ABTS•+ radical scavenging potential. Furthermore, the study utilizes both the combination index (CI) and dose reduction index (DRI) as quantitative parameters to evaluate the nature of interactions and the dose-sparing efficacy of essential oil (EO) combinations. GC–MS analysis identified EOZ as a zingiberene-rich chemotype, containing abundant sesquiterpene hydrocarbons such as α-zingiberene, β-bisabolene, and α-curcumene, while EOH exhibited a caryophyllene diol/cubenol-type profile, dominated by oxygenated sesquiterpenes including β-caryophyllene-9,10-diol and 1-epi-cubenol. In vitro tests demonstrated that both oils, individually and in combination, showed notable anti-tyrosinase, radical scavenging, and lipid peroxidation inhibitory effects. These results support their multifunctional bioactivity profiles with possible relevance to skin care formulations, warranting further investigation. Full article
(This article belongs to the Special Issue Essential Oils—Third Edition)
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21 pages, 2202 KiB  
Article
Galactose Inhibits the Translation of Erg1 that Enhances the Antifungal Activities of Azoles Against Candida albicans
by Sijin Hang, Li Wang, Zhe Ji, Xuqing Shen, Xinyu Fang, Wanqian Li, Yuanying Jiang and Hui Lu
Antibiotics 2025, 14(8), 799; https://doi.org/10.3390/antibiotics14080799 - 5 Aug 2025
Abstract
Background/Objectives: The diminished efficacy of azoles in treating fungal infections is attributed to the emergence of resistance among pathogenic fungi. Employing a synergistic approach with other compounds to enhance the antifungal activity of azoles has shown promise, yet the availability of clinically valuable [...] Read more.
Background/Objectives: The diminished efficacy of azoles in treating fungal infections is attributed to the emergence of resistance among pathogenic fungi. Employing a synergistic approach with other compounds to enhance the antifungal activity of azoles has shown promise, yet the availability of clinically valuable adjuvants for azoles and allylamines remains limited. Studies have demonstrated that the human host environment provides multiple carbon sources, which can influence the susceptibility of C. albicans to antifungal agents. Therefore, a comprehensive investigation into the mechanisms by which carbon sources modulate the susceptibility of C. albicans to azoles may uncover a novel pathway for enhancing the antifungal efficacy of azoles. Methods: This study explored the impact of various carbon sources on the antifungal efficacy of azoles through methodologies including minimum inhibitory concentration (MIC) assessments, super-MIC growth (SMG) assays, disk diffusion tests, and spot assays. Additionally, the mechanism by which galactose augments the antifungal activity of azoles was investigated using a range of experimental approaches, such as gene knockout and overexpression techniques, quantitative real-time PCR (qRT-PCR), Western blot analysis, and cycloheximide (CHX) chase experiments. Results: This study observed that galactose enhances the efficacy of azoles against C. albicans by inhibiting the translation of Erg1. This results in the suppression of Erg1 protein levels and subsequent inhibition of ergosterol biosynthesis in C. albicans. Conclusions: In C. albicans, the translation of Erg1 is inhibited when galactose is utilized as a carbon source instead of glucose. This novel discovery of galactose’s inhibitory effect on Erg1 translation is expected to enhance the antifungal efficacy of azoles. Full article
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23 pages, 1970 KiB  
Review
Resveratrol as a Therapeutic Agent in Alzheimer’s Disease: Evidence from Clinical Studies
by Nidhi Puranik, Meenakshi Kumari, Shraddha Tiwari, Thakur Dhakal and Minseok Song
Nutrients 2025, 17(15), 2557; https://doi.org/10.3390/nu17152557 - 5 Aug 2025
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal dysfunction. It is driven by the accumulation of amyloid-beta (Aβ) plaques, Tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Resveratrol (RSV) is a natural polyphenolic compound found in [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal dysfunction. It is driven by the accumulation of amyloid-beta (Aβ) plaques, Tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Resveratrol (RSV) is a natural polyphenolic compound found in grapes, berries, and red wine that has garnered attention for its potential neuroprotective properties in combating AD. The neuroprotective effects of RSV are mediated through the activation of sirtuins (SIRT1), inhibition of Aβ aggregation, modulation of Tau protein phosphorylation, and the attenuation of oxidative stress and inflammatory responses. RSV also enhances mitochondrial function and promotes autophagy, which are important processes for maintaining neuronal health. Preclinical studies have demonstrated its efficacy in reducing Aβ burden, improving cognitive performance, and mitigating synaptic damage; however, challenges such as poor bioavailability, rapid metabolism, and limited blood–brain barrier penetration restrict its clinical applicability. Recent technological advances and selected modifications are being explored to overcome these limitations and enhance its therapeutic efficacy. This review summarizes the multifaceted neuroprotective mechanisms of RSV, the synergistic potential of natural compounds in enhancing neuroprotection, and the advancements in formulation strategies aimed at mitigating AD pathology. Leveraging the therapeutic potential of natural compounds represents a compelling paradigm shift for AD management, paving the way for future clinical applications. Full article
(This article belongs to the Special Issue The Neuroprotective Activity of Natural Dietary Compounds)
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25 pages, 3642 KiB  
Article
A Novel Steroidogenic Action of Anti-Müllerian Hormone in Teleosts: Evidence from the European Sea Bass Male (Dicentrarchus labrax)
by Alessia Mascoli, Cinta Zapater, Soledad Ibañez, Mateus Contar Adolfi, Manfred Schartl and Ana Gómez
Int. J. Mol. Sci. 2025, 26(15), 7554; https://doi.org/10.3390/ijms26157554 - 5 Aug 2025
Abstract
The Anti-Müllerian hormone (AMH) is widely recognized for promoting Müllerian duct regression in higher vertebrates and regulating key reproductive functions like steroidogenesis, folliculogenesis, and Leydig cell development. In teleost fish, which lack Müllerian ducts, Amh primarily influences male reproductive functions, including sex determination, [...] Read more.
The Anti-Müllerian hormone (AMH) is widely recognized for promoting Müllerian duct regression in higher vertebrates and regulating key reproductive functions like steroidogenesis, folliculogenesis, and Leydig cell development. In teleost fish, which lack Müllerian ducts, Amh primarily influences male reproductive functions, including sex determination, testis differentiation, and germ cell proliferation. In adult fish, Amh supports gonad development and spermatogenesis, but its role in teleost gonadal physiology remains largely underexplored. This study reveals a novel steroidogenic function in the European sea bass (Dicentrarchus labrax) using in vitro testis culture, in vivo plasmid injection, and cell-based transactivation assays. The Amh-induced significant increase in androgen levels was also confirmed in Japanese medaka (Oryzias latipes) treated with recombinant sea bass Amh. Beyond activating the canonical Smad pathway, Amh also triggered the cAMP/PKA signalling pathway via its cognate type II receptor, Amhr2. Inhibitors of these pathways independently and synergistically counteracted Amh-induced CRE-Luc activity, indicating pathway crosstalk. Moreover, inhibition of the cAMP pathway suppressed Amh-induced androgen production in testis cultures, emphasizing the crucial role of protein kinase A in mediating Amh steroidogenic action. These findings uncover a novel steroidogenic function of Amh in teleosts and highlight its broader role in male reproductive physiology. Full article
(This article belongs to the Special Issue Molecular Research in Animal Reproduction)
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14 pages, 3099 KiB  
Article
Moxifloxacin and BH3 Mimetic-MIM1 Demonstrate a Potential Synergistic Anti-Melanoma Mode of Action by Cytotoxic and Proapoptotic Activity Enhancement in A375 and G361 Melanoma Cells
by Artur Beberok, Zuzanna Rzepka, Marta Karkoszka-Stanowska and Dorota Wrześniok
Molecules 2025, 30(15), 3272; https://doi.org/10.3390/molecules30153272 - 5 Aug 2025
Abstract
The MIM1-BH3 mimetic, which inhibits the Mcl-1 antiapoptotic protein, may be an efficacious molecule able to induce apoptosis. Previously, we found that moxifloxacin (MXFL) is able to modulate Mcl-1 protein expression. Therefore, in the current study, we assessed the impact of the MXFL, [...] Read more.
The MIM1-BH3 mimetic, which inhibits the Mcl-1 antiapoptotic protein, may be an efficacious molecule able to induce apoptosis. Previously, we found that moxifloxacin (MXFL) is able to modulate Mcl-1 protein expression. Therefore, in the current study, we assessed the impact of the MXFL, MIM1, and MXFL/MIM1 mixtures on viability and apoptosis in amelanotic A375 and melanotic G361 melanoma cells. The obtained results showed that MXFL and MIM1 exerted high cytotoxic and proapoptotic potential. In the case of two-component models, we have demonstrated that the use of the MIM1 and MXFL mixtures resulted in a significant intensification of both cytotoxic and proapoptotic activity, shown as a modulatory effect on the early and late phases of apoptosis toward the analyzed melanoma cells when compared with MIM1 or MXFL alone. We report, for the first time, the high proapoptotic activity of MIM1 and MXFL applied in a two-component model toward melanoma cells, pointing to the Mcl-1 protein as an important molecular target. The observed potential synergistic mode of action—expressed as cytotoxic and proapoptotic activity enhancement, detected for MIM1 and MXFL—may represent a new direction for further in vitro and in vivo experiments concerning the role of the Mcl-1 protein in the treatment of melanoma. Moreover, the presented results certainly contribute to expanding the knowledge of the pharmacology of both fluoroquinolones and BH3 mimetics, and also enable a better understanding of melanoma cell biology. Full article
(This article belongs to the Section Chemical Biology)
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23 pages, 3221 KiB  
Article
Drought Modulates Root–Microbe Interactions and Functional Gene Expression in Plateau Wetland Herbaceous Plants
by Yuanyuan Chen, Shishi Feng, Qianmin Liu, Di Kang and Shuzhen Zou
Plants 2025, 14(15), 2413; https://doi.org/10.3390/plants14152413 - 4 Aug 2025
Viewed by 20
Abstract
In plateau wetlands, the interactions of herbaceous roots with ectorhizosphere soil microorganisms represent an important way to realize their ecological functions. Global change-induced aridification of plateau wetlands has altered long-established functional synergistic relationships between plant roots and ectorhizosphere soil microbes, but we still [...] Read more.
In plateau wetlands, the interactions of herbaceous roots with ectorhizosphere soil microorganisms represent an important way to realize their ecological functions. Global change-induced aridification of plateau wetlands has altered long-established functional synergistic relationships between plant roots and ectorhizosphere soil microbes, but we still know little about this phenomenon. In this context, nine typical wetlands with three different moisture statuses were selected from the eastern Tibetan Plateau in this study to analyze the relationships among herbaceous plant root traits and microbial communities and functions. The results revealed that drought significantly inhibited the accumulation of root biomass and surface area as well as the development of root volumes and diameters. Similarly, drought significantly reduced the diversity of ectorhizosphere soil microbial communities and the relative abundances of key phyla of archaea and bacteria. Redundancy analysis revealed that plant root traits and ectorhizosphere soil microbes were equally regulated by soil physicochemical properties. Functional genes related to carbohydrate metabolism were significantly associated with functional traits related to plant root elongation and nutrient uptake. Functional genes related to carbon and energy metabolism were significantly associated with traits related to plant root support and storage. Key genes such as CS,gltA, and G6PD,zwf help to improve the drought resistance and barrenness resistance of plant roots. This study helps to elucidate the synergistic mechanism of plant and soil microbial functions in plateau wetlands under drought stress, and provides a basis for evolutionary research and conservation of wetland ecosystems in the context of global change. Full article
(This article belongs to the Special Issue Soil-Beneficial Microorganisms and Plant Growth: 2nd Edition)
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24 pages, 10561 KiB  
Article
Investigating the Potential of Propranolol as an Anti-Tumor Agent in Colorectal Cancer Cell Lines
by Shiekhah Mohammad Alzahrani, Huda Abdulaziz Al Doghaither, Hind Ali Alkhatabi, Mohammad Abdullah Basabrain and Peter Natesan Pushparaj
Int. J. Mol. Sci. 2025, 26(15), 7513; https://doi.org/10.3390/ijms26157513 - 4 Aug 2025
Viewed by 41
Abstract
The incidence and mortality of colorectal cancer (CRC) have increased globally. Several therapeutic approaches have been suggested to address this health issue, in addition to classical methods. Propranolol (PRO) is a beta-blocker that was repurposed to treat infantile hemangiomas, and its anti-tumor activity [...] Read more.
The incidence and mortality of colorectal cancer (CRC) have increased globally. Several therapeutic approaches have been suggested to address this health issue, in addition to classical methods. Propranolol (PRO) is a beta-blocker that was repurposed to treat infantile hemangiomas, and its anti-tumor activity has been reported. This study aimed to investigate the effects of PRO in a panel of CRC cell lines and its potential impact when combined with chemotherapy. The effects of PRO on cell cytotoxicity, cell morphology, colony formation, cell death induction, cell cycle, mitochondrial and intracellular reactive oxygen species (ROS), and migration were measured in all cells. CompuSyn software was utilized to assess the possible synergistic or additive interaction in the combined treatment. The results showed that PRO suppressed cell proliferation, altered cell morphology, inhibited colony formation, induced apoptosis, altered cell cycle and ROS generation, and inhibited the migration of treated cells in a cell-type-specific, time-dependent, and dose-dependent manner compared with the control. HT-29 was the most sensitive cell line to PRO in terms of cytotoxicity, apoptosis, cell cycle arrest, and ROS generation, while SW-480 was the most sensitive in terms of migration inhibition. Moreover, the PRO and capecitabine combination exhibited a synergistic effect and induced mitochondrial apoptosis in metastatic CRC cells. The data suggest that PRO could be a promising adjuvant therapy for primary and advanced CRC. This study identified variations between CRC cell lines in response to PRO, which may be related to their genetic and epigenetic differences. In addition, the findings highlight the potential of combination strategies to improve therapeutic outcomes in metastatic CRC. Full article
(This article belongs to the Special Issue Programmed Cell Death and Oxidative Stress: 3rd Edition)
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14 pages, 3666 KiB  
Review
Electrochemical (Bio) Sensors Based on Metal–Organic Framework Composites
by Ping Li, Ziyu Cui, Mengshuang Wang, Junxian Yang, Mingli Hu, Qiqing Cheng and Shi Wang
Electrochem 2025, 6(3), 28; https://doi.org/10.3390/electrochem6030028 - 4 Aug 2025
Viewed by 45
Abstract
Metal–organic frameworks (MOFs) have characteristics such as a large specific surface area, distinct functional sites, and an adjustable pore size. However, the inherent low conductivity of MOFs significantly affects the charge transfer efficiency when they are used for electrocatalytic sensing. Combining MOFs with [...] Read more.
Metal–organic frameworks (MOFs) have characteristics such as a large specific surface area, distinct functional sites, and an adjustable pore size. However, the inherent low conductivity of MOFs significantly affects the charge transfer efficiency when they are used for electrocatalytic sensing. Combining MOFs with conductive materials can compensate for these deficiencies. For MOF/metal nanoparticle composites (e.g., composites with gold, silver, platinum, and bimetallic nanoparticles), the high electrical conductivity and catalytic activity of metal nanoparticles are utilized, and MOFs can inhibit the agglomeration of nanoparticles. MOF/carbon-based material composites integrate the high electrical conductivity and large specific surface area of carbon-based materials. MOF/conductive polymer composites offer good flexibility and tunability. MOF/multiple conductive material composites exhibit synergistic effects. Although MOF composites provide an ideal platform for electrocatalytic reactions, current research still suffers from several issues, including a lack of comparative studies, insufficient research on structure–property correlations, limited practical applications, and high synthesis costs. In the future, it is necessary to explore new synthetic pathways and seek; inexpensive alternative raw materials. Full article
(This article belongs to the Special Issue Feature Papers in Electrochemistry)
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26 pages, 1165 KiB  
Review
Maillard Reaction in Flour Product Processing: Mechanism, Impact on Quality, and Mitigation Strategies of Harmful Products
by Yajing Qi, Wenjun Wang, Tianxiang Yang, Wangmin Ding and Bin Xu
Foods 2025, 14(15), 2721; https://doi.org/10.3390/foods14152721 - 3 Aug 2025
Viewed by 271
Abstract
The Maillard reaction refers to the reaction between carbonyl compounds with reducing properties and amino-containing compounds that undergo condensation and polymerization to produce melanoidins. In flour product processing, the Maillard reaction is a critical chemical reaction influencing color, flavor, nutrition, and safety. A [...] Read more.
The Maillard reaction refers to the reaction between carbonyl compounds with reducing properties and amino-containing compounds that undergo condensation and polymerization to produce melanoidins. In flour product processing, the Maillard reaction is a critical chemical reaction influencing color, flavor, nutrition, and safety. A moderate Maillard reaction contributes to desirable color and flavor profiles in flour products, whereas an excessive reaction leads to amino acid loss and the formation of harmful substances, posing potential health risks. This review summarizes the substrate sources, reaction stages, influencing factors, impact on quality, and mitigation strategies of harmful products, aiming to provide a reference for regulating the Maillard reaction in flour product processing. Currently, most existing mitigation strategies focus on inhibiting harmful products, while research on the synergistic optimization of color and flavor remains insufficient. Future research should focus on elucidating the molecular mechanisms of reaction pathways, understanding multi-factor synergistic effects, and developing composite regulation technologies to balance the sensory quality and safety of flour products. Full article
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17 pages, 1747 KiB  
Article
Rasagiline Inhibits Human Melanoma Cell Viability and Interacts Synergistically with Mitoxantrone and Antagonistically with Cisplatin—In Vitro Isobolographic Studies
by Danuta Krasowska, Paula Wróblewska-Łuczka, Michał Chojnacki, Katarzyna Załuska-Ogryzek, Jacek Kurzepa and Jarogniew J. Łuszczki
Cancers 2025, 17(15), 2563; https://doi.org/10.3390/cancers17152563 - 3 Aug 2025
Viewed by 271
Abstract
Background: The increased incidence of malignant melanoma is observed in patients with Parkinson’s disease. Methods: The anti-proliferative effects of carbidopa and rasagiline on four human malignant melanoma cell lines (A375, SK-MEL28, FM55P and FM55M2) were determined in MTT assay. The interaction profiles of [...] Read more.
Background: The increased incidence of malignant melanoma is observed in patients with Parkinson’s disease. Methods: The anti-proliferative effects of carbidopa and rasagiline on four human malignant melanoma cell lines (A375, SK-MEL28, FM55P and FM55M2) were determined in MTT assay. The interaction profiles of rasagiline in combinations with cisplatin (CDDP) and mitoxantrone (MTX) in four human melanoma cell lines (A375, SK-MEL28, FM55P and FM55M2) were assessed by means of the isobolographic analysis in the MTT test; Results: Rasagiline, but not carbidopa, produced clear-cut anti-proliferative effects on various melanoma cell lines. The median inhibitory concentrations (IC50 values) of rasagiline in the MTT were 280.69 µM for A375, 402.89 µM for SK-MEL28, 349.44 µM for FM55P, and 117.45 µM for FM55M2, respectively. The experimentally-derived selectivity index for rasagiline ranged from 8.22 to 28.18. Flow cytometry assay revealed, in two melanoma cell lines (FM55P and A375), a significant increase in the number of cells in the G0/G1 (up to 76.48% and 75.46% for cell lines, respectively), accompanied by a decrease in the percentage of cells in the S phase (decrease to 9.91% and 10.83% for cell lines, respectively), which may indicate potential cytostatic properties of rasagiline. The combinations of rasagiline with CDDP (at the fixed-ratio of 1:1) exerted either antagonistic interactions (p < 0.05) in the A375 and SK-MEL28, or additive interactions, with a tendency toward antagonism in the FM55P and FM55M2 cell lines in the MTT test. In contrast, the combinations of rasagiline with MTX (ratio of 1:1) produced either synergistic interaction (p < 0.05) in the FM55P cell line or additive interactions with a tendency toward synergy in the FM55M2, SK-MEL28, and A375 cell lines in the MTT test. Conclusions: Rasagiline combined with MTX exerted the most desirable synergistic interactions in relation to the anti-proliferative effects in four malignant melanoma cell lines, as assessed isobolographically. In contrast, rasagiline should not be combined with CDDP during the treatment of malignant melanoma due to the antagonistic interactions in the MTT assay. Full article
(This article belongs to the Special Issue Research on New Drugs and Drug Targets in Melanoma)
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13 pages, 1608 KiB  
Article
Enhanced Antioxidant and Anti-Inflammatory Activities of Diospyros lotus Leaf Extract via Enzymatic Conversion of Rutin to Isoquercitrin
by Yeong-Su Kim, Chae Sun Na and Kyung-Chul Shin
Antioxidants 2025, 14(8), 950; https://doi.org/10.3390/antiox14080950 (registering DOI) - 2 Aug 2025
Viewed by 131
Abstract
Isoquercitrin, a monoglucoside form of quercetin, exhibits superior antioxidant, anti-inflammatory, and cardiovascular protective effects in comparison to its precursor, rutin. However, its natural abundance is limited. This study aimed to increase the functional value of Diospyros lotus leaf extract through enzymatic conversion of [...] Read more.
Isoquercitrin, a monoglucoside form of quercetin, exhibits superior antioxidant, anti-inflammatory, and cardiovascular protective effects in comparison to its precursor, rutin. However, its natural abundance is limited. This study aimed to increase the functional value of Diospyros lotus leaf extract through enzymatic conversion of rutin to isoquercitrin using α-l-rhamnosidase and to evaluate the changes in biological activities after conversion. A sugar-free D. lotus leaf extract was prepared and subjected to enzymatic hydrolysis with α-l-rhamnosidase under optimized conditions (pH 5.5, 55 °C, and 0.6 U/mL). Isoquercitrin production was monitored via high-performance liquid chromatography. Antioxidant and anti-inflammatory activities were assessed using the 2,2-diphenyl-1-picrylhydrazyl radical scavenging and lipoxygenase (LOX) inhibition assays, respectively. The enzymatic reaction resulted in complete conversion of 30 mM rutin into isoquercitrin within 180 min, increasing isoquercitrin content from 9.8 to 39.8 mM. The enzyme-converted extract exhibited significantly enhanced antioxidant activity, with a 48% improvement in IC50 value compared with the untreated extract. Similarly, LOX inhibition increased from 39.2% to 48.3% after enzymatic conversion. Both extracts showed higher inhibition than isoquercitrin alone, indicating synergistic effects of other phytochemicals present in the extract. This study is the first to demonstrate that α-l-rhamnosidase-mediated conversion of rutin to isoquercitrin in D. lotus leaf extract significantly improves its antioxidant and anti-inflammatory activities. The enzymatically enhanced extract shows potential as a functional food or therapeutic ingredient. Full article
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14 pages, 879 KiB  
Article
Axially Disubstituted Silicon(IV) Phthalocyanine as a Potent Sensitizer for Antimicrobial and Anticancer Photo and Sonodynamic Therapy
by Marcin Wysocki, Daniel Ziental, Zekeriya Biyiklioglu, Malgorzata Jozkowiak, Jolanta Dlugaszewska, Hanna Piotrowska-Kempisty, Emre Güzel and Lukasz Sobotta
Int. J. Mol. Sci. 2025, 26(15), 7447; https://doi.org/10.3390/ijms26157447 - 1 Aug 2025
Viewed by 174
Abstract
The unique properties of phthalocyanines (Pcs), such as strong absorption, high photostability, effective singlet oxygen generation, low toxicity and biocompatibility, versatile chemical modifications, broad spectrum of antimicrobial activity, and synergistic effects with other treatment modalities, make them a preferred superior sensitizer in the [...] Read more.
The unique properties of phthalocyanines (Pcs), such as strong absorption, high photostability, effective singlet oxygen generation, low toxicity and biocompatibility, versatile chemical modifications, broad spectrum of antimicrobial activity, and synergistic effects with other treatment modalities, make them a preferred superior sensitizer in the field of antimicrobial photodynamic therapy. The photodynamic and sonodynamic activity of 3-(3-(diethylamino)phenoxy)propanoxy substituted silicon(IV) Pc were evaluated against bacteria and cancer cells. Stability and singlet oxygen generation upon light irradiation and ultrasound (1 MHz, 3 W) were assessed with 1,3-diphenylisobenzofuran. The phthalocyanine revealed high photostability in DMF and DMSO, although the singlet oxygen yields under light irradiation were low. On the other hand, the phthalocyanine revealed excellent sonostability and caused a high rate of DPBF degradation upon excitation by ultrasounds at 1 MHz. The silicon phthalocyanine presented significant bacterial reduction growth, up to 5 log against MRSA and S. epidermidis upon light excitation, whereas the sonodynamic effect was negligible. The phthalocyanine revealed high activity in both photodynamic and sonodynamic manner toward hypopharyngeal tumor (FaDu, 95% and 42% reduction, respectively) and squamous cell carcinoma (SCC-25, 96% and 62% reduction, respectively). The sensitizer showed ca. 30% aldehyde dehydrogenase inhibition in various concentrations and up to 85% platelet-activating factor acetylhydrolase for 0.25 μM, while protease-activated protein C was stimulated up to 66% for 0.75 μM. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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16 pages, 4215 KiB  
Article
Ag/TA@CNC Reinforced Hydrogel Dressing with Enhanced Adhesion and Antibacterial Activity
by Jiahao Yu, Junhao Liu, Yicheng Liu, Siqi Liu, Zichuan Su and Daxin Liang
Gels 2025, 11(8), 591; https://doi.org/10.3390/gels11080591 - 31 Jul 2025
Viewed by 245
Abstract
Developing multifunctional wound dressings with excellent mechanical properties, strong tissue adhesion, and efficient antibacterial activity is crucial for promoting wound healing. This study prepared a novel nanocomposite hydrogel dressing based on sodium alginate-polyacrylic acid dual crosslinking networks, incorporating tannic acid-coated cellulose nanocrystals (TA@CNC) [...] Read more.
Developing multifunctional wound dressings with excellent mechanical properties, strong tissue adhesion, and efficient antibacterial activity is crucial for promoting wound healing. This study prepared a novel nanocomposite hydrogel dressing based on sodium alginate-polyacrylic acid dual crosslinking networks, incorporating tannic acid-coated cellulose nanocrystals (TA@CNC) and in-situ reduced silver nanoparticles for multifunctional enhancement. The rigid CNC framework significantly improved mechanical properties (elastic modulus of 146 kPa at 1 wt%), while TA catechol groups provided excellent adhesion (36.4 kPa to pigskin, 122% improvement over pure system) through dynamic hydrogen bonding and coordination interactions. TA served as a green reducing agent for uniform AgNPs loading, with CNC negative charges preventing particle aggregation. Antibacterial studies revealed synergistic effects between TA-induced membrane disruption and Ag+-triggered reactive oxygen species generation, achieving >99.5% inhibition against Staphylococcus aureus and Escherichia coli. The TA@CNC-regulated porous structure balanced swelling performance and water vapor transmission, facilitating wound exudate management and moist healing. This composite hydrogel successfully integrates mechanical toughness, tissue adhesion, antibacterial activity, and biocompatibility, providing a novel strategy for advanced wound dressing development. Full article
(This article belongs to the Special Issue Recent Research on Medical Hydrogels)
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