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15 pages, 453 KB  
Article
Protective Effects of Ginseng Extract Against Oxidative Stress in Chilled Rooster Semen: Implications for Sperm Quality and Fertility
by Ruthaiporn Ratchamak, Khanitta Pengmeesri and Eakapol Wangkahart
Animals 2026, 16(13), 1960; https://doi.org/10.3390/ani16131960 (registering DOI) - 25 Jun 2026
Abstract
Oxidative stress is a primary driver of sperm deterioration during chilled storage of poultry semen, and identifying effective natural antioxidant supplements for semen extenders is an important practical goal for poultry reproductive management. This study evaluated the protective effects of ginseng extract (Panax [...] Read more.
Oxidative stress is a primary driver of sperm deterioration during chilled storage of poultry semen, and identifying effective natural antioxidant supplements for semen extenders is an important practical goal for poultry reproductive management. This study evaluated the protective effects of ginseng extract (Panax ginseng) supplementation on sperm viability, motility, oxidative stress biomarkers, antioxidant defense, and fertility in chilled Leung Hang Kao rooster semen. Pooled semen was diluted in IGGKPh extender supplemented with ginseng extract at 0, 1, 2, 3, or 4 mg/mL and stored at 5 °C for 0, 24, and 48 h. Sperm viability, total motility, progressive motility, malondialdehyde (MDA) concentration, total antioxidant capacity (T-AOC), glutathione peroxidase (GPx) activity, catalase (CAT) activity, and fertility following artificial insemination were evaluated at each time point. All ginseng-supplemented groups showed significantly lower MDA concentrations and higher GPx activity than the unsupplemented control throughout storage. At 48 h, total motility and progressive motility were highest in the 2 and 3 mg/mL groups, while T-AOC was best maintained in the 1 and 2 mg/mL groups. CAT activity did not differ significantly among groups at 48 h (p = 0.2498). Fertility was significantly higher in the 1 and 2 mg/mL groups than in the control after 24 and 48 h of storage, and the alignment between T-AOC and fertility across storage time points indicated that overall antioxidant buffering capacity was a stronger determinant of fertilizing competence than individual enzyme activities or MDA concentration alone. Concentrations of 3–4 mg/mL, despite producing lower MDA at 48 h, did not confer superior fertility outcomes, suggesting a hormetic dose–response relationship. Based on integrated evidence from sperm quality, antioxidant status, and in vivo fertility, ginseng extract supplementation at 1–2 mg/mL is recommended as the most suitable range for preserving chilled Leung Hang Kao rooster semen and may represent a practical natural antioxidant strategy for Thai native poultry breeding programs. Full article
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28 pages, 4446 KB  
Review
Chitosan-Based Hydrogels in Vascular Tissue Engineering Applications
by Lauren Taylor and Shih-Feng Chou
Materials 2026, 19(13), 2715; https://doi.org/10.3390/ma19132715 (registering DOI) - 24 Jun 2026
Abstract
The development of biocompatible materials has gained traction due to the increasing clinical demands for customizable and functional medical devices. Chitosan, a deacetylated derivative of chitin, is a naturally occurring biopolymer with strong antimicrobial properties, immunocompatibility, and structural adaptability, making it a promising [...] Read more.
The development of biocompatible materials has gained traction due to the increasing clinical demands for customizable and functional medical devices. Chitosan, a deacetylated derivative of chitin, is a naturally occurring biopolymer with strong antimicrobial properties, immunocompatibility, and structural adaptability, making it a promising candidate for biomedical applications. Through mechanisms such as crosslinking, ionic bonding, gas formation, and UV radiation, the mechanical properties and stimulus responses of chitosan-based hydrogels can be tailored for drug delivery at specific sites or under specific pH, light, or electrical conditions. Beyond drug delivery, chitosan hydrogels have shown considerable potential for vascular tissue repair. The porous structure of chitosan allows patient specific vascular scaffolding to be created that promotes the recovery rate veins and stenting procedures. Thermally sensitive hydrogels can deliver drugs to target regions to further assist in vascular healing. Furthermore, recent developments with composite polymers and coatings engineered to self-assemble within veins provide scaffolds for vascular tissue growth. This manuscript reviews chitosan hydrogel fabrication methods and their corresponding materials properties, with particular emphasis on drug delivery to vascular tissues. Furthermore, relevant findings from clinical trials are summarized to support the potential of chitosan hydrogels for future clinical use. Challenges of chitosan hydrogels, such as insufficient mechanical strength, high degradation rates, and complex manufacturing, remain as areas for research break-through. Full article
22 pages, 3736 KB  
Article
Diversity and Community Structure of Bacteria in High-Altitude Proglacial Lakes in Southern Qinghai-Xizang Plateau
by Yanyan Zheng and Dorji Phurbu
Microorganisms 2026, 14(7), 1398; https://doi.org/10.3390/microorganisms14071398 (registering DOI) - 24 Jun 2026
Abstract
The proglacial lakes of the Qinghai-Xizang Plateau serve as natural laboratories for studying microbial adaptation to extreme environments. However, research on the composition and functional characteristics of microorganisms in these settings remains limited. In this study, three typical high-altitude proglacial lakes in southern [...] Read more.
The proglacial lakes of the Qinghai-Xizang Plateau serve as natural laboratories for studying microbial adaptation to extreme environments. However, research on the composition and functional characteristics of microorganisms in these settings remains limited. In this study, three typical high-altitude proglacial lakes in southern Xizang (Qudengnima proglacial lake, Gangbugou proglacial lake, and Qiangyong proglacial lake) were selected as research subjects. Bacterial community structure, diversity in the water and sediment of these lakes were analyzed using 16S rRNA sequencing. The results showed that Pseudomonadota, Actinomycetota, and Bacteroidota were highly abundant across all samples. The relative abundances of Cyanobacteriota and Acidobacteriota, however, exhibited distinct habitat preferences: Cyanobacteriota was enriched in the water, whereas Acidobacteriota was predominantly found in sediment. Alpha diversity analysis showed that both species diversity and richness in Qiangyong proglacial lake were significantly higher than those in the other proglacial lakes, and within the same lake, both diversity and richness in sediment were higher than in the water. Beta diversity analysis indicated that the bacterial community structures in sediment were similar across different proglacial lakes, whereas those in water varied considerably among the lakes. LEfSe analysis identified 94 biomarkers that exhibited significant differences among the different proglacial lake environments at an LDA score threshold of 4. Redundancy analysis revealed that pH, total phosphorus, and ammonium nitrogen were the physicochemical factors significantly influencing the bacterial community structure in the water, while total carbon was the key driver for the community in sediments. This study preliminarily characterized the bacterial community structure and diversity in high-altitude proglacial lakes on the southern Qinghai-Xizang Plateau, which lays a theoretical foundation for exploiting microbial resources and understanding their ecological functions in such extreme environments. Full article
(This article belongs to the Section Environmental Microbiology)
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20 pages, 1029 KB  
Article
Multilevel Characterization of Eggs from Laying Hens Fed Dried Haematococcus pluvialis Biomass: Natural Biofortification, Lipid Modulation, and Instrumental Sensory Assessment
by Francesca Accetta, Giovanni Pace, Ambrogina Albergamo, Luciano Falqui, Vincenzo Lo Turco, Luigi Liotta and Ambra Rita Di Rosa
Poultry 2026, 5(4), 46; https://doi.org/10.3390/poultry5040046 (registering DOI) - 24 Jun 2026
Abstract
This study evaluated the effects of dietary supplementation with dried Haematococcus pluvialis biomass on egg quality in laying hens using a multilevel analytical approach. A total of 100 ISA Brown hens were divided into two groups: a control group (CTRL) fed a basal [...] Read more.
This study evaluated the effects of dietary supplementation with dried Haematococcus pluvialis biomass on egg quality in laying hens using a multilevel analytical approach. A total of 100 ISA Brown hens were divided into two groups: a control group (CTRL) fed a basal diet and an experimental group (HP) receiving the same diet supplemented with 0.075% H. pluvialis. Supplementation did not significantly affect most physical egg parameters, although yolk index and yolk height were improved in the HP group. A marked increase in yolk pigmentation was observed, with values reaching 15 on the DSM color fan compared to 8.4 in CTRL (p < 0.0001). Significant enhancements in yolk nutritional quality were detected, including increased total carotenoids and the presence of astaxanthin exclusively in the HP group. Mineral composition was also markedly affected, with significant increases in essential elements such as Fe, Mg, Zn, I, and P in both albumen and yolk. The fatty acid profile was favorably modulated, showing a reduction in saturated fatty acids and an increase in monounsaturated fatty acids, along with improved nutritional indices (AI, TI, HH). Instrumental sensory analysis revealed clear discrimination between groups based on color (E-eye), while differences in volatile profiles (E-nose) were less pronounced. However, a reduction in oviposition rate and egg mass was observed in the supplemented group. Overall, the inclusion of H. pluvialis biomass represents an effective strategy for the natural biofortification of eggs, improving their nutritional and functional value. Full article
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35 pages, 4094 KB  
Review
Renaissance of Traditional Mineral Drugs in Cancer: Advanced Delivery Strategies and Bioengineering Approaches
by Aolin Chen, Ping Luo, Jing Cao, Taohong Su, Xinxin Ding, Xinzhi Guo, Wenhao Zhou, Yang Chen and Fang Wang
Pharmaceutics 2026, 18(7), 768; https://doi.org/10.3390/pharmaceutics18070768 (registering DOI) - 23 Jun 2026
Abstract
Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based [...] Read more.
Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based oncology therapeutics. We highlight how mineral drugs exert potent anticancer effects through interconnected pathways, including regulated cell death (e.g., apoptosis, ferroptosis), cell-cycle arrest, and immunomodulation. Crucially, we evaluate recent advances in drug delivery systems, such as liposomes, polymeric nanoparticles, inorganic frameworks, and stimuli-responsive (e.g., pH, redox, enzyme) release systems that successfully overcome traditional pharmacological barriers. These bioengineering strategies not only improve solubility and tumor targeting but also significantly widen the therapeutic window, as evidenced by enhanced tumor suppression and reduced systemic toxicity in preclinical models. Despite this progress, challenges regarding in vivo chemical transformations and tumor heterogeneity remain. Ultimately, we propose a closed-loop “Composition–Mechanism–Delivery” design paradigm to guide future research, facilitating the translation of ethnopharmacological heritage into precision mineral-based therapeutics. Full article
(This article belongs to the Special Issue Advanced Drug Delivery Systems for Natural Products)
22 pages, 2799 KB  
Article
Therapeutic Potential of Rosmarinus officinalis Extract on Endometriosis: Evidence from In Vitro Models
by Sofía del Valle, Ignacio Edgardo Ruiz Arias, Gustavo Leirós, Mariela Bilotas, Nancy Adriana Espinoza-Sánchez, Burkhard Greve, Martin Götte, Analía Ricci and Gabriela Meresman
Int. J. Mol. Sci. 2026, 27(13), 5654; https://doi.org/10.3390/ijms27135654 (registering DOI) - 23 Jun 2026
Abstract
Natural therapeutic alternatives are increasingly explored in endometriosis, a highly prevalent gynecological disorder with limited therapeutic options. Rosmarinus officinalis (rosemary) has attracted increasing scientific interest due to its biological activity. This study aimed to characterize a hydroethanolic rosemary extract (RE) and evaluate its [...] Read more.
Natural therapeutic alternatives are increasingly explored in endometriosis, a highly prevalent gynecological disorder with limited therapeutic options. Rosmarinus officinalis (rosemary) has attracted increasing scientific interest due to its biological activity. This study aimed to characterize a hydroethanolic rosemary extract (RE) and evaluate its effects on key cellular processes involved in endometriosis pathophysiology. Major phenolic compounds in RE were quantified by RP-HPLC, and antioxidant activity was assessed using DPPH, ABTS, and FRAP assays. After RE treatment, cell viability (WST-1), migration (wound healing assay), cell cycle distribution (DAPI staining), apoptosis (Annexin V/PI), p21 and cyclin A expression (Western blot), and intracellular ROS levels (DCFH-DA) were evaluated in endometrial stromal (t-HESC, St-T1b) and endometriotic epithelial (12-Z) cells. Phytochemical analysis revealed rosmarinic acid (RA) at 4.2%, while carnosic acid (CA) and carnosol (CS) together accounted for 23.7% of the extract. RE reduced cell viability and cell migration in 12-Z and t-HESC cells (p < 0.05). S-phase accumulation with a concomitant reduction in the G1 phase was observed across all evaluated cell lines (p < 0.05), along with increased p21 and cyclin A expression in stromal cells (p < 0.05). RE induced cell death in both 12-Z (p < 0.05) and St-T1b cells (p < 0.0001). In t-HESC cells, RE reduced both basal and H2O2-induced ROS levels (p < 0.01). These findings indicate that RE modulates key mechanisms involved in endometriosis pathophysiology, supporting its multi-target therapeutic potential as a nutraceutical approach for endometriosis management. Full article
(This article belongs to the Special Issue Natural Compounds: Impact on Health and Disease)
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30 pages, 21538 KB  
Article
Alginate-Based Solid Foam Incorporating Rügen Chalk: A Novel Platform for Modern Application of Peloids
by Mantas Jurkonis, Modestas Žilius, Karolis Banionis, Elena Jasiūnienė and Jurga Bernatoniene
Pharmaceuticals 2026, 19(7), 973; https://doi.org/10.3390/ph19070973 (registering DOI) - 23 Jun 2026
Abstract
Background/Objectives: Natural calcium carbonate materials such as Rügen chalk have a long history of use in balneology and rehabilitation, particularly for musculoskeletal disorders, yet their application remains largely confined to traditional, labour-intensive forms such as powders, suspensions, and packs, which limit usability and [...] Read more.
Background/Objectives: Natural calcium carbonate materials such as Rügen chalk have a long history of use in balneology and rehabilitation, particularly for musculoskeletal disorders, yet their application remains largely confined to traditional, labour-intensive forms such as powders, suspensions, and packs, which limit usability and broader clinical translation. This study aimed to develop an alginate-based solid foam incorporating Rügen chalk and to evaluate how key formulation components influence its structural, mechanical, and thermal properties relevant for therapeutic use. Methods: Alginate–chalk foams were prepared by mechanical mixing of a sodium alginate–Rügen chalk paste with an amino acid-based surfactant, while in situ CO2 generation from D–glucono–δ–lactone (GDL) induced calcium-mediated alginate gelation and foam stabilization. A central composite design with response surface methodology was used to assess the effects of alginate, chalk, and Perlastan®–GDL content on foam pH, overrun, firmness, springiness, pore volume, sphericity, pore density, specific internal surface area, and heat-loss time. Foam microstructure was characterized by optical microscopy and microcomputed tomography (µCT), and the thermal conductivity and cooling behaviour of the selected formulation were compared with therapeutic peat. Results: Stable, elastic solid foams with a three-dimensional porous architecture were obtained across the investigated composition range. Foam overrun (30.8–57.1%) was primarily governed by sodium alginate and Rügen chalk concentrations, while firmness (7.4–15.2 N) increased predominantly with alginate content, and springiness remained high (70–78%), indicating good elastic recovery. Response surface modelling and ANOVA confirmed sodium alginate as the dominant factor influencing both mechanical and structural properties, with statistically significant effects on overrun, firmness, springiness, heat loss, porosity, and specific internal surface. µCT analysis revealed that all foam formulations were predominantly composed of fine, closed-cell pores, with over 96% of pores having volumes below 0.5 mm3 and a consistent median pore volume of 0.02 mm3. Structural differences between formulations were governed primarily by pore number and spatial distribution rather than pore size. Strong correlations were identified between µCT-derived parameters, particularly between specific internal surface, porosity, and pore density, confirming that internal architecture is controlled by pore population rather than individual pore dimensions. Thermal analysis demonstrated that the optimized formulation exhibited thermal conductivity comparable to therapeutic peat and maintained clinically relevant temperatures (35–45 °C) for more than one hour. Based on predefined performance criteria (overrun ≥ 50%, firmness ≤ 10 N, heat loss ≥ 120 s), formulation 7 was identified as optimal, combining favourable mechanical properties, structural uniformity and thermal retention. Conclusions: Alginate-based solid foams incorporating Rügen chalk constitute a feasible and tunable platform that combines efficient mineral loading, elastic porosity, and effective heat retention, offering a practical and modern alternative to conventional mineral-based therapeutic applications in balneology and rehabilitation. Full article
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13 pages, 664 KB  
Article
Baseline Characterization of the Gut Microbiota of Field and Colony Populations of Phlebotomus tobbi and Preliminary Assessment of the Anti-Leishmanial Activity of Cultivable Bacteria
by Mehmet Karakuş, Ayda Yılmaz, Mert Okbay, Metin Pekağırbaş and Ozge Erisoz Kasap
Pathogens 2026, 15(7), 658; https://doi.org/10.3390/pathogens15070658 (registering DOI) - 23 Jun 2026
Viewed by 43
Abstract
Sand fly midgut microbiota plays a critical role in shaping Leishmania development and vector competence, yet functional evidence from natural vector populations remains limited. In this study, sand flies were collected between 2020 and 2022 in Cukurova region, Türkiye to characterize the gut [...] Read more.
Sand fly midgut microbiota plays a critical role in shaping Leishmania development and vector competence, yet functional evidence from natural vector populations remains limited. In this study, sand flies were collected between 2020 and 2022 in Cukurova region, Türkiye to characterize the gut bacterial composition of Phlebotomus tobbi and evaluate the anti-leishmanial potential of cultivable isolates. A total of 1739 sand flies were captured (878 females, 861 males), of which Ph. tobbi was the predominant species (n = 1312). 16S rRNA amplicon sequencing (V4–V6) showed that the gut microbiota was dominated by Proteobacteria, with Erwinia aphidicola/persicina representing the most abundant species across all analyzed groups. Fourteen cultivable bacterial species were identified by MALDI-TOF MS, including Serratia liquefaciens, Pantoea agglomerans, and Micrococcus luteus. Functional XTT assays against Leishmania infantum promastigotes demonstrated variable inhibitory activity among isolates. The strongest leishmanicidal effects were observed with S. liquefaciens (32.3%) and M. luteus (28.8%). Morphological examination confirmed promastigote rounding and cell death in isolates showing >25% activity. These findings define the gut bacterial landscape of Ph. tobbi in an endemic region and identify bacterial taxa with in vitro anti-leishmanial activity, highlighting their potential for future microbiota-based or paratransgenic control strategies. Full article
(This article belongs to the Special Issue One Health Surveillance of Sand-Fly and Leishmania Transmission)
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25 pages, 1386 KB  
Review
Intermolecular-Interaction-Driven Adaptive Remodeling: A Network Perspective on Plant Abiotic Stress Responses
by Leidi Liu, Xiangfei Cheng, Yihua Xu, Lu Liu, Shuai Zhong, Xiaohua Chao, Yumin Chen, Chengde Yu, Chengming Fan and Changsong Zou
Plants 2026, 15(12), 1920; https://doi.org/10.3390/plants15121920 (registering DOI) - 22 Jun 2026
Viewed by 200
Abstract
Abiotic stresses, including drought, salinity, alkalinity, temperature extremes, flooding, heavy metals, and emerging pollutants, challenge plant growth and productivity by disturbing water relations, ion balance, redox homeostasis, membrane stability, energy metabolism, and developmental progression. Although substantial progress has been made in the identification [...] Read more.
Abiotic stresses, including drought, salinity, alkalinity, temperature extremes, flooding, heavy metals, and emerging pollutants, challenge plant growth and productivity by disturbing water relations, ion balance, redox homeostasis, membrane stability, energy metabolism, and developmental progression. Although substantial progress has been made in the identification of stress-responsive hormones, second messengers, kinases, transcription factors, transporters, and metabolic regulators, plant stress adaptation cannot be fully explained by linear signaling cascades or single tolerance genes. A major unresolved question is how early molecular events are reorganized into coordinated physiological and developmental outputs that support survival, recovery, and productivity. In this review, we propose an intermolecular interaction-driven adaptive remodeling framework for plant abiotic stress responses. This framework emphasizes that stress tolerance emerges from dynamic changes in receptor–ligand recognition, protein–protein interactions, calcium decoding, redox-sensitive modification, phosphorylation networks, transcriptional regulation, chromatin-associated control, and metabolite-mediated feedback. We further emphasize ROS as integrative redox switches that connect stress sensing, defense activation, senescence-related transitions, and recovery, and chromatin-associated mechanisms as regulators that may stabilize primed or memory-like adaptive states. We discuss how these interaction networks converge on core signaling hubs, including abscisic acid, reactive oxygen species, Ca2+, and kinase/phosphatase systems, and how they remodel stomatal behavior, root architecture, ion and pH homeostasis, redox buffering, metabolism, development, and reproductive resilience. We further highlight how natural variation, multi-omics, genome editing, high-throughput phenotyping, and field validation can translate interaction-centered stress biology into crop resilience. This perspective provides a conceptual bridge between molecular stress perception, network behavior, physiological adaptation, and climate-resilient agriculture. Full article
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18 pages, 4890 KB  
Article
Biosurfactants as Stabilizers of Silver Nanoparticles: A Sustainable Approach for Antimicrobial Applications
by Renata R. Silva, Hugo M. Meira, Marcos Antonio B. Lima, Jaciana dos S. Aguiar, Leonie A. Sarubbo and Juliana M. Luna
Microorganisms 2026, 14(6), 1379; https://doi.org/10.3390/microorganisms14061379 (registering DOI) - 22 Jun 2026
Viewed by 157
Abstract
Microbial resistance to conventional antimicrobials is a growing public health challenge, driving the search for effective and sustainable alternatives. Among emerging strategies, the combination of silver nanoparticles (AgNPs), recognized for their potent antimicrobial action, with biosurfactants, natural, biodegradable compounds capable of interacting with [...] Read more.
Microbial resistance to conventional antimicrobials is a growing public health challenge, driving the search for effective and sustainable alternatives. Among emerging strategies, the combination of silver nanoparticles (AgNPs), recognized for their potent antimicrobial action, with biosurfactants, natural, biodegradable compounds capable of interacting with microbial cell membranes and promoting their stabilization stands out. In this context, the aim of this study was to produce a biosurfactant by Candida glabrata UCP 1002 from agroindustrial residues, reducing costs and environmental impacts. The compound exhibited a surface tension of 29 mN/m, a critical micellar concentration of 0.3%, and a yield of 9 g/L; furthermore, it demonstrated stability across wide ranges of temperature, pH, and salinity. The AgNPs were synthesized using the biosurfactant as a stabilizing agent and ascorbic acid as a reducing agent, resulting in stable particles. In antimicrobial assays, the formulation inhibited Gram-positive microorganisms, Gram-negative microorganisms, and fungi. The best results were obtained against Pseudomonas aeruginosa (26.63%) and Candida albicans (28.11%), followed by Staphylococcus aureus (17.58%), Enterobacter sp. (14.42%), and Escherichia coli (13.68%). Although less effective than commercial antibiotics such as streptomycin and moxifloxacin, it showed potential as a complementary alternative in combating multidrug-resistant pathogens. Cytotoxicity assays revealed low toxicity toward normal cells (28.42% inhibition in Vero CCL-81) and minimal activity against tumor cells. The results demonstrate that the BS-AgNPs association combines relevant antimicrobial activity with environmental safety and biocompatibility, establishing itself as a promising and sustainable approach for application in health, industry, and the environment, with potential for scale-up production from low-cost raw materials. Full article
(This article belongs to the Special Issue Antimicrobial Ability of Natural Products)
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19 pages, 6981 KB  
Article
Gastroprotective Effects of Tordylium trachycarpum Extract Against Ethanol-Induced Gastric Injury: Involvement of Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms
by Venos Saeed Abdullah, Kamaran Younis M. Amin and Hawraz Ibrahim M. Amin
Gastrointest. Disord. 2026, 8(2), 29; https://doi.org/10.3390/gidisord8020029 (registering DOI) - 20 Jun 2026
Viewed by 159
Abstract
Background/Objectives: Tordylium trachycarpum Boiss. (Apiaceae) is traditionally used in Kurdish ethnomedicine for the management of gastrointestinal disorders; however, its pharmacological efficacy and safety profile remain insufficiently investigated. This study evaluated, for the first time, the gastroprotective activity and associated antioxidant, inflammatory, and apoptotic [...] Read more.
Background/Objectives: Tordylium trachycarpum Boiss. (Apiaceae) is traditionally used in Kurdish ethnomedicine for the management of gastrointestinal disorders; however, its pharmacological efficacy and safety profile remain insufficiently investigated. This study evaluated, for the first time, the gastroprotective activity and associated antioxidant, inflammatory, and apoptotic responses of the methanolic extract of T. trachycarpum using an ethanol-induced gastric ulcer model in Sprague–Dawley rats. Methods: Preliminary phytochemical screening revealed the presence of phenolics, flavonoids, terpenoids, tannins, coumarins, and glycosides. Acute oral toxicity testing demonstrated no signs of toxicity at doses up to 5 g/kg. Gastric ulceration was induced by absolute ethanol, and animals were pretreated with the extract (250 and 500 mg/kg) or omeprazole (20 mg/kg). Results: The extract significantly decreased the gastric lesion area from 258.50 ± 6.38 mm2 in the ulcer control group to 143.70 ± 0.76 mm2 and 115.50 ± 0.76 mm2, corresponding to ulcer inhibition rates of 44.41% and 55.31%. Additionally, the extract increased mucus production, maintained mucosal structure, and raised stomach pH. Biochemical analysis showed a significant increase in antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)] and a reduction in malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. In addition, the extract modulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10). Blood-based ELISA analysis demonstrated increased expression of heat shock protein 70 (HSP70) and reduced Bax levels, suggesting anti-apoptotic activity. Conclusions: These findings indicate that T. trachycarpum exerts significant gastroprotective activity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, supporting its traditional use and highlighting its potential as a natural therapeutic candidate for the management of gastric ulcers. Full article
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22 pages, 25871 KB  
Article
Identification of β-Lapachone as a Potent USP22 Inhibitor That Suppresses Cancer Stemness and Enhances Chemosensitivity in Lung Adenocarcinoma
by Yuanyuan Gao, Keqiang Zhang, Wendong Li, John Liu, David Kwon, Lilian Gu, Aimin Li, Hongwei Holly Yin, Claudia Kowolik, Mahima Raul, David A. Horne and Dan J. Raz
Int. J. Mol. Sci. 2026, 27(12), 5561; https://doi.org/10.3390/ijms27125561 (registering DOI) - 19 Jun 2026
Viewed by 200
Abstract
Ubiquitin-specific protease 22 (USP22) regulates epigenetic gene expression by deubiquitinating histone H2B (H2Bub1) and upregulating oncogenic proteins and pathways, while antagonizing p53-mediated tumor suppression. USP22 is frequently overexpressed in cancers and associated with therapy resistance and poor prognosis yet remains largely untargeted pharmacologically. [...] Read more.
Ubiquitin-specific protease 22 (USP22) regulates epigenetic gene expression by deubiquitinating histone H2B (H2Bub1) and upregulating oncogenic proteins and pathways, while antagonizing p53-mediated tumor suppression. USP22 is frequently overexpressed in cancers and associated with therapy resistance and poor prognosis yet remains largely untargeted pharmacologically. Here, using a fluorescence-based USP22 deubiquitinase assay to screen the LOPAC®1280 library, we identified β-Lapachone, a natural ortho-naphthoquinone with strong anticancer activities, as a potent USP22 inhibitor. β-Lapachone potently inhibited USP22 enzymatic activity, with a half-maximal inhibitory concentration (IC50) of ~0.75 μM, and molecular docking revealed its occupation of the catalytic pocket adjacent to the USP22 active-site triad, supporting a potential binding mode. Functionally, β-Lapachone suppressed proliferation and induced apoptosis in A549 and H1299 RAS-mutant lung adenocarcinoma (LUAD) cells, while USP22 knockout conferred marked resistance, indicating partial USP22 dependence. In patient-derived LUAD models, β-Lapachone inhibited sphere formation and reduced CD133+ cancer stem cell populations. Notably, it synergized with cisplatin to enhance DNA damage and apoptosis. In vivo, β-Lapachone significantly suppressed tumor growth in a syngeneic KRAS-mutant/p53-Null mouse lung cancer model and further potentiated cisplatin-induced antitumor effects. Collectively, these findings identify β-Lapachone as a potent inhibitor of USP22 and validate USP22 inhibition as a key mechanism underlying its anticancer activity in LUAD cells, both in vitro and in vivo. Full article
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25 pages, 1032 KB  
Article
Mucoadhesive Nanostructured Lipid Carriers of Ketoconazole for Enhanced Dermal Delivery and Antifungal Activity: Formulation Optimization and In Vivo Evaluation
by Mashan Almutairi, Ahmed Adel Ali Youssef, Yazed S. Alsowaida, Ahmed Alobaida and Samir A. Ross
Pharmaceutics 2026, 18(6), 753; https://doi.org/10.3390/pharmaceutics18060753 (registering DOI) - 19 Jun 2026
Viewed by 319
Abstract
Background/Objective: Topical therapy remains a cornerstone in managing fungal infections due to the deep-seated nature of the pathogens and the persistence of the disease. Ketoconazole (KTZ) is a broad-spectrum antifungal agent, but its highly lipophilic nature presents considerable challenges in developing effective topical [...] Read more.
Background/Objective: Topical therapy remains a cornerstone in managing fungal infections due to the deep-seated nature of the pathogens and the persistence of the disease. Ketoconazole (KTZ) is a broad-spectrum antifungal agent, but its highly lipophilic nature presents considerable challenges in developing effective topical formulations. Additionally, oral KTZ has been subject to labeling restrictions and market withdrawal due to its association with severe hepatic adverse effects. This study was conducted to design, optimize, and evaluate KTZ-loaded nanolipid carriers (NLCs; KTZ-NLCs) as a delivery platform that could improve cutaneous bioavailability and enhance antifungal activity. Methods: The optimized KTZ-NLCs were further incorporated into a mucoadhesive system (KTZ-NLCs-C) through the inclusion of Carbopol® 940 NF, aiming to improve the retention of the formulation on the skin surface. NLCs were characterized in terms of their physical appearance, particle size, polydispersity index, zeta potential, pH, viscosity, drug content, and entrapment efficiency. The optimized KTZ-NLC and KTZ-NLCs-C formulations were subsequently assessed for in vitro drug release, ex vivo skin permeation and deposition, as well as in vivo skin irritation. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KTZ over 24 h. The ex vivo transdermal flux and permeability coefficient of KTZ from the lead KTZ-NLCs-C formulation were approximately 2.8-fold greater than those achieved with the marketed cream formulation. The in vivo skin irritation studies indicate that NLC-based formulations are suitable for topical applications. The lead formulation was stable for 90 days (the final time point evaluated) under refrigerated and room-temperature storage conditions. Conclusions: These findings suggest that the NLC-based system is a promising platform for the topical delivery of KTZ and has the potential to enhance the therapeutic outcomes for patients with superficial fungal infections. Full article
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17 pages, 5984 KB  
Article
Removal of Congo Red Dye from Aqueous Solution via Natural Seeds Integrated with Zinc Oxide-Doped Manganese Ferrite
by Elham A. Alzahrani, Ghaida H. Munshi, Abeer Mohammed AL-Balawi, Salwa D. Al-Malwi, Naha Meslet Alsebaii, Khloud Saeed Al-Thubaiti, Sumbul Hafeez and Seungdae Oh
Nanomaterials 2026, 16(12), 775; https://doi.org/10.3390/nano16120775 (registering DOI) - 19 Jun 2026
Viewed by 267
Abstract
This study reports the preparation of a nanocomposite using a black cumin surface as a carbon framework on which zinc oxide-doped manganese ferrite nanoparticles were deposited and grown. A simple precipitation method was used to prepare the nanocomposite. The resulting composite was characterized [...] Read more.
This study reports the preparation of a nanocomposite using a black cumin surface as a carbon framework on which zinc oxide-doped manganese ferrite nanoparticles were deposited and grown. A simple precipitation method was used to prepare the nanocomposite. The resulting composite was characterized using various characterization analyses such as FTIR, XRD, EDX, SEM, TEM, and TGA. The composite surface was highly conformed with functional groups, and the nanocomposite was formed due to electrostatic and non-electrostatic interactions between the carbon framework and the nanoparticles. X-ray analysis revealed a crystalline structure with crystal sizes up to 45 nm. Microscopic images revealed the surface morphology, confirming the irregular distribution of particles within the composite. The resulting composite material was used for adsorption application. The composite material was tested for the removal of Congo red dye from water. It was found that under optimal conditions, a dose of 2 g per liter of absorbent removed nearly 100% of dye from a 10 mL volume of 10 mg per liter Congo red solution within 90 min and 7 pH. A monolayer adsorption was confirmed by the isotherm analysis. The monolayer adsorption capacity for the present study was ~13.0 mg per gram. The adsorption kinetics suggested the fitting of pseudo-second order. Based on the findings, it was concluded that the chemical mechanism was responsible for the present adsorption process. The regeneration study demonstrates the stability of current adsorbent up to two cycles only. This nanocomposite is the first of its kind which promotes the creation of nanocomposites in the future by using natural materials and reduces the dependency on activated carbon. Full article
(This article belongs to the Section Environmental Nanoscience and Nanotechnology)
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16 pages, 14998 KB  
Article
Gradient Anisotropic Natural Rubber-PNIPAM Composite Hydrogels for Programmable NIR-Responsive Actuation
by Qing Zhang, Xueliang Feng, Yuxin Yan, Lin Chen, Honghua Fan, Wenjing Zhou, Kaipeng Li, Xiaohong Yang, Xueyu Du and Chunxin Ma
Gels 2026, 12(6), 550; https://doi.org/10.3390/gels12060550 (registering DOI) - 19 Jun 2026
Viewed by 157
Abstract
Heterogeneous hydrogels capable of complex, programmable deformation are highly desirable for soft actuators, yet general strategies that simultaneously impart structural anisotropy, rapid responsiveness, and mechanical robustness remain limited. Here, a gradient anisotropic natural rubber-poly(N-isopropylacrylamide) (NR-PNIPAM) composite hydrogel is developed through a simple one-pot [...] Read more.
Heterogeneous hydrogels capable of complex, programmable deformation are highly desirable for soft actuators, yet general strategies that simultaneously impart structural anisotropy, rapid responsiveness, and mechanical robustness remain limited. Here, a gradient anisotropic natural rubber-poly(N-isopropylacrylamide) (NR-PNIPAM) composite hydrogel is developed through a simple one-pot polymerization strategy by coupling pH-regulated colloidal stability with gravity-directed redistribution of natural rubber latex particles. Under an optimized pH window, NR nanoparticles gradually migrate during gelation and are fixed as a continuous gradient within the PNIPAM network, generating built-in structural asymmetry for nonuniform deformation. Meanwhile, NR nanoparticles act as soft reinforcing domains to improve mechanical strength, while water-soluble graphene nanosheets provide efficient photothermal conversion for remotely-controlled near-infrared (NIR)-responsive actuation. Benefiting from this synergistic design, the hydrogel exhibits programmable bending and localized folding with high actuation rates of 129° s−1 and 46° s−1, respectively, along with a tensile strength of 0.32 MPa and an active lifting capability exceeding 70 times its own weight. The material further enables biomimetic gripping and lifting under NIR stimulation. This work establishes a general route to robust gradient hydrogels by integrating colloidal regulation, structural anisotropy, and photothermal actuation, offering a versatile platform for high-performance soft intelligent systems. Full article
(This article belongs to the Special Issue Advances in Functional Gel (3rd Edition))
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