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42 pages, 1302 KB  
Review
Genome Editing Approaches in Flax (Linum usitatissimum L.): From Tools to Trait Improvement
by Marta Podralska, Aleksandra Górska and Mariusz Kaczmarek
Int. J. Mol. Sci. 2026, 27(13), 6012; https://doi.org/10.3390/ijms27136012 (registering DOI) - 4 Jul 2026
Abstract
Genome editing, particularly CRISPR/Cas-based systems, has emerged as a key tool for functional genomics and trait improvement in flax (Linum usitatissimum L.), an important fiber and oilseed crop. This review focuses specifically on flax as an emerging target species and distinguishes experimentally [...] Read more.
Genome editing, particularly CRISPR/Cas-based systems, has emerged as a key tool for functional genomics and trait improvement in flax (Linum usitatissimum L.), an important fiber and oilseed crop. This review focuses specifically on flax as an emerging target species and distinguishes experimentally validated applications from approaches adapted from model plants. Recent progress includes the characterization of endogenous U6 promoters, which improved guide RNA expression and contributed to enhanced genome editing performance under optimized conditions. Reported studies demonstrate efficient targeted mutagenesis in flax; however, editing outcomes remain strongly dependent on genotype, construct design, and regeneration capacity, and stable homozygous edited lines are still limited. Target genes include pathways involved in lignin and cellulose biosynthesis, fatty acid metabolism, and stress responses, influencing fiber quality, oil composition, and stress adaptation. Despite current bottlenecks such as low homologous recombination efficiency and regeneration constraints, base editing, prime editing, and multiplex CRISPR systems provide promising avenues for precision breeding in flax. Full article
(This article belongs to the Section Molecular Plant Sciences)
19 pages, 22527 KB  
Article
Iron-Reversible Bactericidal Activity of Marine-Derived Aspergillus ostianus Hydroxamate Pyrazinones Against Replicating and Hypoxia-Induced Non-Replicating Mycobacterium smegmatis
by Muhammad Azhari, Shinnosuke Isshiki, Riku Horinouchi, Marlia Singgih, Masayoshi Arai, Afrillia Nuryanti Garmana, Rika Hartati, Yuni Elsa Hadisaputri, Nunung Yuniarti and Elin Julianti
Mar. Drugs 2026, 24(7), 236; https://doi.org/10.3390/md24070236 - 3 Jul 2026
Viewed by 189
Abstract
Tuberculosis therapy is prolonged partly because dormant subpopulations of Mycobacterium tuberculosis show reduced susceptibility to first-line drugs. Therefore, agents active against both replicating and non-replicating mycobacteria remain important to explore. Here, we investigated secondary metabolites from the Indonesian marine-derived fungus Aspergillus ostianus for [...] Read more.
Tuberculosis therapy is prolonged partly because dormant subpopulations of Mycobacterium tuberculosis show reduced susceptibility to first-line drugs. Therefore, agents active against both replicating and non-replicating mycobacteria remain important to explore. Here, we investigated secondary metabolites from the Indonesian marine-derived fungus Aspergillus ostianus for activity against Mycobacterium smegmatis, a BSL-1 mycobacterial model, under aerobic and hypoxia-induced non-replicating conditions, and examined the underlying mechanism. Bioassay-guided fractionation and spectroscopic analysis identified three hydroxamate pyrazinones: neohydroxyaspergillic acid (NHAA), hydroxyaspergillic acid (HAA), and neoaspergillic acid (NAA). The MIC values were 1.56 µg/mL for NHAA and 3.13 µg/mL for HAA and NAA under both aerobic and hypoxic atmospheres. Time-kill kinetics showed ≥3-log10 CFU reductions within 24–72 h at 4–8× MIC under aerobic conditions and within 48–96 h at 4–8× MIC under hypoxia, with no regrowth at the final sampling point. Scanning electron microscopy and release of UV-absorbing intracellular material at OD260/OD280 were consistent with envelope disruption in both atmospheres. Antimycobacterial activity was attenuated in a concentration-dependent manner by exogenous Fe3+ and was reversed at 100 µM FeCl3, whereas isoniazid activity was unaffected, supporting iron-reversible and pyrazinone-specific killing. Together with the established Fe3+-binding hydroxamate pharmacophore shared by this compound class, these findings support iron sequestration as a plausible mechanism and identify fungal hydroxamate pyrazinones as scaffolds that retain bactericidal activity against hypoxia-adapted non-replicating mycobacteria, warranting further evaluation in M. tuberculosis models. Full article
(This article belongs to the Special Issue Marine Natural Products with Antibacterial and Antibiofilm Activity)
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27 pages, 1939 KB  
Article
Subcritical Water Extraction Enables the Production of Cichoric and Caftaric Acid-Standardized Echinacea purpurea Root Extracts with Defined Composition and Favorable Biological Properties
by Petko Denev, Desislava Teneva, Manol Ognyanov, Mariya Pimpilova, Ani Petrova, Georgi Dimitrov, Bela Vasileva, Kamelia Hristova-Panusheva, Natalia Krasteva, George Miloshev and Milena Georgieva
Molecules 2026, 31(13), 2351; https://doi.org/10.3390/molecules31132351 - 3 Jul 2026
Viewed by 170
Abstract
This study investigates subcritical water extraction (SWE) as an alternative to hydroalcoholic extraction for the production of Echinacea purpurea root extracts standardized to hydroxycinnamic acids (cichoric and caftaric acids). Extractions were performed at 100 °C, 125 °C, 150 °C, and 170 °C for [...] Read more.
This study investigates subcritical water extraction (SWE) as an alternative to hydroalcoholic extraction for the production of Echinacea purpurea root extracts standardized to hydroxycinnamic acids (cichoric and caftaric acids). Extractions were performed at 100 °C, 125 °C, 150 °C, and 170 °C for 10–30 min. The recovery of cichoric and caftaric acids was significantly (p < 0.05) influenced by extraction temperature, with the highest values obtained within the range of 100–125 °C. Further experiments identified 110 °C for 10 min as the optimal condition, yielding the highest cumulative recovery of cichoric and caftaric acids (1.87 ± 0.10% of dry material). In the resulting dry extracts, SWE at 100–125 °C produced hydroxycinnamic acid contents of 5.5–7.1%, whereas the total dry extract yield in-creased from 24–28% at 100 °C to 40–41% at 150–170 °C (p < 0.05). Higher temperatures, however, reduced cichoric and caftaric acid cumulative content to 0.6–1.7% (p < 0.05), indicating a degradation of the target compounds. In contrast, total polyphenol recovery in-creased continuously with temperature, reaching 4.86% at 170 °C for 30 min. This was accompanied by marked increases in rutin, gallic and caffeic acid, reaching 458.5 mg/100 g dry weight (DW), 175.5 mg/100 g DW and 945.7 mg/100 g DW (p < 0.05), respectively, suggesting the release of bound phenolics following partial disruption of plant cell wall structures. SWE also enhanced the extraction of carbohydrates, uronic acids, fructans, proteins and organic acids, demonstrating an extensive temperature-dependent modification of the root matrix. 5-HMF was not detected in extracts obtained below 125 °C, but increased progressively at higher temperatures, reaching 200 mg/100 g (p < 0.05) at 170 °C. Biological evaluation in the human colorectal adenocarcinoma cell line (HT29) showed favorable cytocompatibility of SWE extracts, confirmed by cell viability, morphological assessment and low DNA damage in the Comet Assay. Overall, SWE enables the production of cichoric and caftaric acid-standardized E. purpurea extracts without organic solvents, supporting its application in pharmaceutical, nutraceutical, food and cosmeceutical products. Full article
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22 pages, 6150 KB  
Article
Cetyl All-Trans-Retinoate as a Lipidic ATRA Prodrug with Enhanced Anticancer and Chemosensitizing Activity
by Paweł Moroz, Klaudia Muciek, Marta Świtalska, Joanna Wietrzyk, Zbigniew Lazar and Anna Gliszczyńska
Int. J. Mol. Sci. 2026, 27(13), 5982; https://doi.org/10.3390/ijms27135982 - 3 Jul 2026
Viewed by 55
Abstract
Tretinoin (all-trans-retinoic acid, ATRA) is an established therapy for acute promyelocytic leukemia (APL) and neuroblastoma (NB); however, its broader oncological application is limited by poor bioavailability and rapid resistance development. In this study, we developed lipidic ester derivatives of ATRA as [...] Read more.
Tretinoin (all-trans-retinoic acid, ATRA) is an established therapy for acute promyelocytic leukemia (APL) and neuroblastoma (NB); however, its broader oncological application is limited by poor bioavailability and rapid resistance development. In this study, we developed lipidic ester derivatives of ATRA as a potential prodrug approach aimed at modulating its physicochemical and biological properties. Three ATRA derivatives were evaluated in vitro in six human cancer cell lines: leukemia (MV4-11), gastric (AGS), colon (HT-29), lung (A549), and breast cancer cells (MCF-7, MDA-MB-468). Cytotoxicity toward normal human breast epithelial cells (MCF-10A) was also assessed. Among the synthesized derivatives, cetyl all-trans-retinoate (ATRA-CA) exhibited the strongest anticancer activity, showing up to threefold greater potency than ATRA, with inhibitory concentrations ranging from 1.34 to 23.1 µM and minimal toxicity toward normal cells. Moreover, ATRA-CA enhanced the efficacy of conventional chemotherapeutics. In A549 cells, treatment with 5 and 10 µM ATRA-CA reduced the cisplatin IC50 from 25.7 ± 3.2 µM to 9.1 ± 3.0 and 5.9 ± 1.5 µM, corresponding to synergistic (CI = 0.63) and additive (CI = 0.88) effects, respectively. Similar effects were observed in MCF-7 cells and in combination with doxorubicin and paclitaxel. Full article
(This article belongs to the Section Molecular Biology)
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21 pages, 26731 KB  
Article
Network Pharmacology and Molecular Docking of Syzygium nervosum Extracts on Antiproliferative Effect in Prostate Cancer
by Napatsorn Saiyasit, Tanakamol Mahawan, Nitchakan Darai, Pilaiporn Thippraphan, Yawitthaphorn Soihin, Sunee Chansakaow, Aya Naiki-Ito, Satoru Takahashi and Weerakit Taychaworaditsakul
Int. J. Mol. Sci. 2026, 27(13), 5977; https://doi.org/10.3390/ijms27135977 - 3 Jul 2026
Viewed by 182
Abstract
Prostate cancer (PCa) is one of the most common causes of cancer-related mortality in men globally. Although current therapies can control early-stage disease, advanced PCa remains difficult to treat because of therapeutic resistance and adverse side effects, highlighting the need for new treatment [...] Read more.
Prostate cancer (PCa) is one of the most common causes of cancer-related mortality in men globally. Although current therapies can control early-stage disease, advanced PCa remains difficult to treat because of therapeutic resistance and adverse side effects, highlighting the need for new treatment strategies. Syzygium nervosum (SN), a medicinal plant rich in bioactive compounds such as gallic acid and ellagic acid, has demonstrated anticancer properties in several malignancies; however, its effects on PCa remain unclear. This study investigated the anticancer potential of SN using integrated computational and in vitro approaches. DU145 and PC-3 prostate cancer cells were treated with SN extract at concentrations of 25–400 µg/mL for 24 and 48 h. Cell viability, colony formation, and cell-cycle progression were evaluated to determine antiproliferative activity. In parallel, computational analyses were performed to predict molecular targets of SN-derived compounds. Our results displayed that SN extract reduced cell viability, suppressed clonogenic growth, and disrupted cell-cycle progression in both cell lines. Computational findings suggested that gallic and ellagic acids may interact with key regulatory proteins related to cell proliferation and survival, including AKT and CDK2. Overall, SN demonstrates promising anticancer activity and may represent a potential therapeutic source for prostate cancer treatment. Full article
(This article belongs to the Special Issue Molecular Study on Biofunctional Properties of Plant Bioactives)
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20 pages, 1733 KB  
Article
Oral Food Supplement with Bio-Activated Silicium and Vitamins D3 and K2 in the Conservative Management of Osteoporotic Vertebral Compression Fractures
by Roberto Gazzeri, Marcelo Galarza, Felice Occhigrossi, Christian Carulli, Stefano Telera, Jacopo Mosca and Matteo Luigi Giuseppe Leoni
J. Clin. Med. 2026, 15(13), 5206; https://doi.org/10.3390/jcm15135206 - 3 Jul 2026
Viewed by 159
Abstract
Background: Osteoporotic vertebral compression fractures (OVCFs) are the most prevalent manifestation of osteoporotic skeletal disease, associated with severe pain, functional decline, and elevated risk of subsequent fractures. Conservative management remains the first-line approach for stable fractures, yet pain control is often suboptimal, [...] Read more.
Background: Osteoporotic vertebral compression fractures (OVCFs) are the most prevalent manifestation of osteoporotic skeletal disease, associated with severe pain, functional decline, and elevated risk of subsequent fractures. Conservative management remains the first-line approach for stable fractures, yet pain control is often suboptimal, and vertebral collapse progresses in up to 37% of patients. Bio-activated orthosilicic acid combined with vitamins D3 and K2 (BioSi-DK) may support fracture healing through complementary mechanisms acting on osteoblast differentiation, collagen synthesis, osteocalcin carboxylation, and mineralization, but its clinical efficacy in OVCFs has not previously been investigated. Methods: A retrospective, multi-center comparative cohort study was conducted in patients aged >50 years with DXA-confirmed osteoporosis and acute thoracolumbar OVCFs (AO Spine OF1-OF2) managed conservatively. Patients receiving BioSi-DK supplementation (two capsules daily for two months, then one capsule daily for four months) in addition to standard conservative treatment were compared with controls receiving conservative treatment alone. Propensity score matching (1:1, sex-exact constraint, caliper 0.3 SD) was applied across twelve pre-specified baseline covariates. The primary outcome was pain intensity at six months, assessed by numerical rating scale (NRS). Secondary outcomes included NRS change, analgesic use, Patient Global Impression of Change (PGIC), requirement for vertebral augmentation (kyphoplasty), MRI marrow edema score (MES), and Genant grade change. Results: After propensity score matching, 38 patients (19 per group) with balanced baseline characteristics were analyzed (mean age 71.2 ± 6.5 years; 89.5% female; mean T-score −2.61 ± 0.32; mean baseline NRS 8.26 ± 0.95). The BioSi-DK group achieved a significantly lower post-treatment NRS score compared with controls (2.05 ± 2.17 vs. 3.84 ± 2.83; p = 0.015; Cohen’s d = −0.71) and a significantly greater mean NRS reduction (−6.21 ± 1.90 vs. −4.42 ± 2.12 points; p = 0.005; d = −0.89). Analgesic discontinuation was more frequent in the BioSi-DK group (68.4% vs. 36.8%; p = 0.068). Kyphoplasty was required in 5.3% of BioSi-DK patients versus 21.1% of controls (p = 0.340; OR = 0.21), and vertebral compression grade remained stable in 100% of supplemented patients versus 84% of controls. At two months, MES improvement by at least one category was more frequently observed in the BioSi-DK group than in controls, suggesting an earlier edema resolution effect; at six months, MES distribution was comparable between groups (p = 0.620). Conclusions: BioSi-DK supplementation as an adjunct to conservative management was associated with a statistically significant and clinically large reduction in pain at six months, with favorable trends in analgesic burden, kyphoplasty requirement, and edema resolution. The safety profile was excellent. These findings support the conduct of prospective, randomized, placebo-controlled trials to confirm BioSi-DK as an effective adjunct therapy for OVCFs. Full article
(This article belongs to the Special Issue Clinical Progress of Spine Surgery)
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22 pages, 2535 KB  
Article
Asymmetrically Disubstituted Pyrenebutyrate Complexes of Pt(IV) as Cisplatin Prodrugs with Improved Anticancer Activity
by Rositsa Mihaylova, Veronika Mihaylova, Nikola Burdzhiev, Ivo D. Ivanov, Zhanina Petkova, Georgi Momekov, Denitsa Momekova and Anife Ahmedova
Molecules 2026, 31(13), 2336; https://doi.org/10.3390/molecules31132336 - 3 Jul 2026
Viewed by 152
Abstract
Among the non-classical platinum complexes, Pt(IV) prodrugs are most promising as versatile scaffolds for structural modification and fine tuning of their activation-by-reduction mechanism of action and the resulting anticancer activity. Herein, four new asymmetrically disubstituted pyrenebutyrate complexes of Pt(IV) (25 [...] Read more.
Among the non-classical platinum complexes, Pt(IV) prodrugs are most promising as versatile scaffolds for structural modification and fine tuning of their activation-by-reduction mechanism of action and the resulting anticancer activity. Herein, four new asymmetrically disubstituted pyrenebutyrate complexes of Pt(IV) (25) were synthesized and thoroughly studied. In this series, the second axial ligand was derived from dicarboxylic acids of different length—4 and 5 C-atoms, or replacement of the C-atom in the middle with either O- or S-atom. The structural effects on reduction kinetics, lipophilicity and cellular internalization of the complexes were monitored by NMR, HPLC, fluorescence and ICP-MS measurements. Their cytotoxicity was tested on a panel of cancer cell lines and mechanistic insights were obtained from proteome analysis and microscope imaging. The data indicate that all complexes, especially complex 3, represent a promising class of Pt(IV) prodrugs, exhibiting significantly higher cytotoxic activity than cisplatin in all tested models, including a cisplatin-resistant line. This was explained with a stronger and more integrated apoptotic response than cisplatin: pronounced Bax upregulation (3.6-fold), maximal cleaved caspase-3 (4-fold), activation of both intrinsic and extrinsic pathways, and effective p53 Ser15/Ser46 phosphorylation. The consistent rank order of potency (3 > 4 > 52 ≫ cisplatin) suggests that subtle ligand modifications can substantially enhance efficacy, possibly by improving cellular uptake or altering DNA binding. Full article
(This article belongs to the Special Issue Design and Biological Applications of Platinum-Based Complexes)
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22 pages, 27570 KB  
Article
Glutamate Ionotropic Kainate Receptors as Therapeutic Targets in Enzalutamide-Resistant and Neuroendocrine Prostate Cancer
by Huan Qu, Pengfei Xu, Joy C. Yang, Fan Wei, Junwei Zhao, Leyi Wang, Eva Corey, Nicholas Mitsiades, Kit Lam, Kenneth A. Iczkowski, Yuanpei Li, Allen C. Gao, Marc Dall’Era and Chengfei Liu
Int. J. Mol. Sci. 2026, 27(13), 5945; https://doi.org/10.3390/ijms27135945 - 2 Jul 2026
Viewed by 173
Abstract
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is the major form of resistance to androgen receptor signaling inhibitors (ARSI) in advanced prostate cancer, characterized by pronounced invasiveness and lineage plasticity. Through in-depth analysis of prostate cancer cohorts, we found that glutamate ionotropic receptor kainate (GRIK) [...] Read more.
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is the major form of resistance to androgen receptor signaling inhibitors (ARSI) in advanced prostate cancer, characterized by pronounced invasiveness and lineage plasticity. Through in-depth analysis of prostate cancer cohorts, we found that glutamate ionotropic receptor kainate (GRIK) family members, specifically GRIK2 and GRIK5, are highly expressed in neural lineage plastic prostate cancer cells, NEPC patient-derived xenografts (PDX), and NEPC patient samples. Their expression positively correlates with neuroendocrine markers and inversely correlates with androgen receptor (AR) activity. Additionally, functional analyses indicated that AR has a direct transcriptional inhibitory effect on GRIK2 and GRIK5, and the absence of AR signaling leads to the upregulation of GRIK2 and GRIK5. Further RNA sequencing analysis revealed that GRIK5 silencing reprograms the cellular transcriptome, resulting in significant downregulation of AR signaling and fatty acid metabolism, while simultaneously activating immune and inflammatory responses in enzalutamide-resistant prostate cancer cells. In both cell line and NEPC PDX organoid models, loss of GRIK5 impaired proliferation and clonogenic growth. Notably, GRIK5 also contributes to enzalutamide resistance. Pharmacological evaluation revealed that Pan-GRIK antagonists exhibit anti-tumor activity, although the required relatively high concentrations suggest that more potent therapeutic strategies should be developed. Collectively, this study establishes that GRIK family members play critical roles in enzalutamide resistance and NEPC progression, highlighting GRIK signaling as a potential therapeutic target for overcoming lineage plasticity in prostate cancer. Full article
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16 pages, 3701 KB  
Article
Stabilizing Nanoemulsions with Blended Biosurfactants: Role of Sophorolipids and Lecithin in Emulsion Performance
by Yew Seng Leow, Dayang Radiah Awang Biak, Nur Syakina Jamali, Huey Fang Teh and Norhafizah Abdullah
BioTech 2026, 15(3), 51; https://doi.org/10.3390/biotech15030051 - 2 Jul 2026
Viewed by 97
Abstract
Sophorolipids (SLs) produced from Starmerella bombicola using four different secondary substrates such as refined, bleached, and deodorized palm olein (RBD PO), RBD palm kernel olein (RBD PKO), RBD coconut olein (RBD CO) and fatty acid methyl ester (FAME) waste are reported. Their interfacial [...] Read more.
Sophorolipids (SLs) produced from Starmerella bombicola using four different secondary substrates such as refined, bleached, and deodorized palm olein (RBD PO), RBD palm kernel olein (RBD PKO), RBD coconut olein (RBD CO) and fatty acid methyl ester (FAME) waste are reported. Their interfacial characteristics at medium-chain triglyceride (MCT) oil-water interface and ability to form nano/submicron emulsions were studied. The effects of SLs from different sources, SL concentrations and blend ratios of SLs and soybean lecithin on characteristics of emulsions produced by ultrasonication were examined. Initially, emulsion formed using SLs coded (from F2 to F5) showed large droplets (d32 > 1000 nm) and poor stability. They were then blended with soybean lecithin at a ratio of 3:1 to produce emulsions coded F6 to F9 with smaller droplets (d32 < 400 nm) and great stability over a range of temperatures (from 40 °C to 90 °C) and pH values (from 3 to 9). However, highly acidic (pH 2) and low ionic strength (1 mM NaCl) processing caused the separation of the emulsions. These emulsions also displayed potential antimicrobial activities towards Bacillus cereus and Pseudomonas aeruginosa, as well as cytotoxic effects against the human epithelial colorectal adenocarcinoma cell line (Caco-2). These results illustrated that stable emulsions required a mixture of SLs and soybean lecithin. Full article
(This article belongs to the Section Industry, Agriculture and Food Biotechnology)
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23 pages, 5428 KB  
Article
The Effect of Citrate Plasticisers TBC and ATBC on Biobased and Sustainable PHB-Based Polymer Blends
by Lorenzo Novembre, Luca Sconosciuto, Vito Emanuele Carofiglio, Domenico Centrone, Alessandro Sannino and Antonio Greco
Polymers 2026, 18(13), 1641; https://doi.org/10.3390/polym18131641 - 1 Jul 2026
Viewed by 241
Abstract
The development of fully biodegradable poly(3-hydroxybutyrate) (PHB)-based materials with improved mechanical performance remains a major challenge due to the limited ductility and processability of this highly crystalline polymer. Blending and plasticisation are viable strategies to enhance PHB toughness; however, the interactions governing polymer–plasticiser [...] Read more.
The development of fully biodegradable poly(3-hydroxybutyrate) (PHB)-based materials with improved mechanical performance remains a major challenge due to the limited ductility and processability of this highly crystalline polymer. Blending and plasticisation are viable strategies to enhance PHB toughness; however, the interactions governing polymer–plasticiser compatibility and their impact on structure–property relationships remain not fully understood. In this work, the compatibility and plasticisation mechanisms of two citrate-based plasticisers, tributyl citrate (TBC) and acetyl tributyl citrate (ATBC), were systematically investigated in biodegradable blends based on PHB, polylactic acid (PLA), and poly(butylene adipate-co-terephthalate) (PBAT). Polymer–plasticiser affinity was evaluated through Hansen Solubility Parameters and interaction radius, which indicated good compatibility of PHB with both plasticisers and a stronger affinity for ATBC. Differential scanning calorimetry showed that citrate plasticisers reduced the glass transition temperature, modified crystallisation kinetics, and altered the crystalline morphology of the blends. Dynamic mechanical analysis confirmed the reduction in the glass transition temperature of PHB–PLA systems, which is in agreement with the DSC results. Migration experiments showed equilibrium after approximately 72 h, with PHB–PLA blends exhibiting better plasticiser retention than PHB–PBAT systems. TBC consistently showed higher migration than ATBC, in line with its lower molecular weight and higher volatility. Mechanical testing demonstrated that plasticisation efficiency strongly depended on blend composition: TBC was more effective in enhancing ductility in PHB–PLA blends, whereas ATBC performed better in PHB–PBAT systems. It was also highlighted that the plasticisers had a remarkable ability to substantially increase the ductility of the blends compared with their unplasticised counterparts, as reflected by the pronounced decrease in stiffness and the marked increase in elongation at break. SEM analysis of tensile fracture surfaces evidenced a brittle failure mode for PHB–PLA blends, whereas PHB–PBAT systems exhibited a ductile fracture mode with fibrillar features and clear signs of phase separation. Finally, thermogravimetric analysis showed no appreciable thermal degradation within the processing temperature window used for mixing and hot pressing, confirming the thermal stability of the materials under the selected conditions. These findings establish clear correlations between thermodynamic compatibility, migration behaviour, thermal properties, fracture mechanisms, and mechanical performance, providing useful guidelines for the design of citrate-plasticised PHB-based biodegradable materials. Full article
(This article belongs to the Section Circular and Green Sustainable Polymer Science)
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19 pages, 9927 KB  
Article
Ethylene-Responsive Transcription Factor 013 Regulates Physiological and Molecular Responses to Salt Stress in Arabidopsis thaliana
by Rahmatullah Jan, Shahzad Iqbal, Sajad Ali, Muhammad A. Almalki, Mohammad Alfredan, Sajjad Asaf and Kyung-Min Kim
Antioxidants 2026, 15(7), 834; https://doi.org/10.3390/antiox15070834 - 1 Jul 2026
Viewed by 170
Abstract
Soil salinity severely limits plant growth by disrupting cellular homeostasis and inducing oxidative damage. Although ethylene-responsive transcription factors (ERFs) are central regulators of stress responses, the function of ERF013 in salt stress responses remains poorly understood. In this study, we investigated the role [...] Read more.
Soil salinity severely limits plant growth by disrupting cellular homeostasis and inducing oxidative damage. Although ethylene-responsive transcription factors (ERFs) are central regulators of stress responses, the function of ERF013 in salt stress responses remains poorly understood. In this study, we investigated the role of ERF013 in Arabidopsis thaliana using ERF013 overexpression lines (OE-ERF013) and genome-edited (ge-erf013) under 250 mM NaCl stress, in comparison with wild-type control (CK) and salt-treated wild-type (WT) plants. Under salinity stress, OE-ERF013 plants maintained vigorous shoot and root growth, exhibiting a 17% increase in shoot fresh weight and a 100% in root fresh weight relative to WT-T plants, whereas ge-erf013 mutants displayed severe growth inhibition. Salt stress markedly elevated superoxide (O2) and hydrogen peroxide (H2O2) levels in WT-T (62% and 134%) and ge-erf013 plants (122% and 193%) compared with CK, while OE-ERF013 plants showed a significant reduction in O2·and H2O2 levels, which decreased by 34% and 64%, respectively, relative to WT-T. Improved redox homeostasis in OE-ERF013 plants was associated with enhanced catalase (CAT) and superoxide dismutase (SOD) activities (55% and 44%), increased DPPH radical-scavenging activity (62%), maintained total antioxidant capacity (ABTS), and reduced lipid peroxidation, whereas ge-erf013 plants exhibited a 47% increase in malondialdehyde (MDA) content relative to WT-T. Furthermore, OE-ERF013 plants displayed reduced electrolyte leakage and sustained higher relative water content (RWC), with only a 15% decline under salt stress. Transcript analysis revealed strong upregulation of key ion homeostasis genes (SOS1, SOS2, NHX1, and HKT1) in OE-ERF013 plants, while their expression was suppressed in ge-erf013 mutants relative to WT-T. Additionally, OE-ERF013 plants accumulated higher abscisic acid (ABA) levels and showed increased expression of ABA biosynthesis-related genes (ATAO3 and ATABA3), accompanied by enhanced osmotic adjustment through elevated proline, soluble sugars, and sucrose accumulation, as well as improved chlorophyll stability. Collectively, these results demonstrate that ERF013 acts as a positive regulator of responses to salinity by coordinating ABA signaling, antioxidant defense, ion homeostasis, and osmotic regulation in Arabidopsis thaliana. Full article
(This article belongs to the Section ROS, RNS and RSS)
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15 pages, 660 KB  
Article
Phenolic Profile, Antioxidant and Antiproliferative Activity, and Acute Toxicity of Bursera hindsiana Engl
by Julio César López-Romero, Heriberto Torres-Moreno, José Luis Montijo-Montijo, Maribel Plascencia-Jatomea, Mónica Alejandra Villegas-Ochoa, Norma Julieta Salazar-López and Gustavo Adolfo González Aguilar
Compounds 2026, 6(3), 40; https://doi.org/10.3390/compounds6030040 - 1 Jul 2026
Viewed by 91
Abstract
The aim of this study was to determine the phenolic compound profile, antioxidant activity, antiproliferative activity, and toxicity of B. hindsiana. Ethanolic extractions of B. hindsiana leaves and stems were performed. The content of phenolic compounds was determined by the Folin–Ciocalteu method, [...] Read more.
The aim of this study was to determine the phenolic compound profile, antioxidant activity, antiproliferative activity, and toxicity of B. hindsiana. Ethanolic extractions of B. hindsiana leaves and stems were performed. The content of phenolic compounds was determined by the Folin–Ciocalteu method, while the phenolic compound profile was determined by UPLC-DAD. The antioxidant activity was evaluated using the DPPH, ABTS, ORAC, and FRAP methods. Antiproliferative activity was determined by the MTT method against HeLa, A549, and ARPE-19 cell lines. Acute toxicity was determined in Artemia salina. The results showed that the B. hindsiana leaf extract had the highest concentration of phenolic compounds, with quercetin-3-β-glucoside, rutin, and chlorogenic acid being the major compounds. Regarding antioxidant activity, the leaf extract showed a greater capacity (p < 0.05) to stabilize free radicals and reduce metals. For antiproliferative activity, the leaf extract also showed a greater capacity (p < 0.05) to inhibit the proliferation cancer cell lines. Finally, the B. hindsiana extracts presented an LC50 value greater than 100 µg/mL in A. salina. Overall, the B. hindsiana extracts show promising biological potential, which may be associated with the phenolic compounds present, with low toxicity. This research is the first study reporting the phenolic compound profile and the leaf and stem biological activities from B. hindsiana. Full article
(This article belongs to the Special Issue Phenolic Compounds: Extraction, Chemical Profiles, and Bioactivity)
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21 pages, 28037 KB  
Article
Quercetin and Rosmarinic Acid Functionalized Hybrid Electrospun Nanofibers with Strong Antioxidant and Anticancer Activities
by Nikoleta Stoyanova, Nasko Nachev, Ani Georgieva, Reneta Toshkova and Mariya Spasova
Biomimetics 2026, 11(7), 453; https://doi.org/10.3390/biomimetics11070453 - 1 Jul 2026
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Abstract
In this study, novel electrospun polymer mats based on biocompatible poly(lactic acid) (PLA) and hydrophilic poly(ethylene glycol) (PEG) were successfully fabricated for the co-delivery of two natural polyphenols, quercetin (QUE) and rosmarinic acid (RA). Scanning electron microscopy (SEM) revealed the formation of defect-free, [...] Read more.
In this study, novel electrospun polymer mats based on biocompatible poly(lactic acid) (PLA) and hydrophilic poly(ethylene glycol) (PEG) were successfully fabricated for the co-delivery of two natural polyphenols, quercetin (QUE) and rosmarinic acid (RA). Scanning electron microscopy (SEM) revealed the formation of defect-free, continuous nanofibers with high interconnected porosity. By mimicking the structural features of the native extracellular matrix, these nanofibrous platforms facilitate pronounced combined antioxidant and anticancer action. X-ray diffraction (XRD) analysis confirmed that the rapid solvent evaporation during electrospinning induced a physical state transformation, converting both QUE and RA from their native crystalline structures into an amorphous dispersion within the polymer fibrous materials, thereby optimizing their potential bioavailability. The obtained hybrid fibrous materials possessed good mechanical properties. Moreover, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay demonstrated that the incorporation of PEG enhanced matrix hydrophilicity, allowing the four-component PLA/PEG/QUE/RA mats to achieve the highest antioxidant efficiency (98.1%), suggesting an enhanced, complementary radical-neutralization pathway. Furthermore, in vitro biological assessments against human cervical carcinoma cell line (HeLa) and normal murine embryo fibroblasts BALB/3T3 demonstrated prominent anticancer activity, while noncancerous cells were significantly less affected. The dual-loaded PLA/PEG/QUE/RA fibrous mats induced significant cell shrinkage, chromatin condensation, and apoptotic cell death in HeLa cells, while normal BALB/3T3 fibroblasts retained cell membrane integrity and displayed higher resistance. Modeled after the native extracellular matrix, these bioinspired materials demonstrate significant antioxidant and anticancer activity, highlighting their potential for applications in localized cancer therapy, wound management, and tissue engineering. Full article
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14 pages, 1767 KB  
Article
Individual Amino Acid Supplementation Does Not Enhance Short-Term Proliferation of Selected Cancer Cell Lines In Vitro: Potential Implications for Nutritional Support in Cancer Cachexia
by Walburga Dieterich, Rashmita Pradhan, Abdulhadi Suwandi, Rabia Ülkü Korkmaz, Markus F. Neurath and Yurdagül Zopf
Nutrients 2026, 18(13), 2125; https://doi.org/10.3390/nu18132125 - 1 Jul 2026
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Abstract
Background: Cancer-related cachexia is primarily characterized by systemic inflammation and progressive muscle wasting, which is why a high-protein diet (from 1.2 to 1.5 g/kg/day) is commonly recommended. However, concerns remain that an excessive supply of amino acids could promote tumor growth due [...] Read more.
Background: Cancer-related cachexia is primarily characterized by systemic inflammation and progressive muscle wasting, which is why a high-protein diet (from 1.2 to 1.5 g/kg/day) is commonly recommended. However, concerns remain that an excessive supply of amino acids could promote tumor growth due to the metabolic flexibility of cancer cells, thereby favoring proliferation and survival. Systematic evidence addressing these concerns under controlled conditions for various types of cancer cells remains limited and inconclusive. Methods: We investigated the short-term effects of all 20 amino acids at both moderate (2×) and high (10×) concentrations to evaluate three key oncological endpoints in four human cancer cell lines: MDA-MB-231 (breast), HT29 (colorectal), PC3 (prostate), and PANC-1 (pancreatic). Cell proliferation was assessed by BrdU incorporation, metabolic activity by WST-1 assay, and apoptosis signaling by caspase-3/7 activity measurement. Results: Amino acid supplementation was not associated with a significant change in proliferation at either concentration across all four cell lines studied. Metabolic activity showed only minor variations throughout, with PC3 cells exhibiting slightly greater variability, although this did not reach statistical significance. Caspase-3/7 activity remained largely unchanged under all conditions; however, high-concentration lysine induced an approximately 2.5-fold increase in PANC1 cells, which was not statistically significant. Conclusions: These findings suggest that short-term exposure to individual amino acids, even at supraphysiological conditions, does not acutely enhance proliferative activity in the cancer cell lines studied, supporting the rationale for adequate protein and amino acid intake in patients with cancer cachexia. Full article
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15 pages, 8535 KB  
Article
The Non-Specific Lipid Transfer Protein Gene OsLTP10 Regulates Fatty Acid Metabolism and Grain Quality in Rice
by Taoli Liu, Hao Zhou, Qin Xie, Yunhua Zhu, Penghui Shen, Fanzi Chen, Zhoufei Luo, Haiou Li, Yanning Tan, Zhigang Huang, Ruozhong Wang, Yi Su, Qing Liu and Langtao Xiao
Agronomy 2026, 16(13), 1269; https://doi.org/10.3390/agronomy16131269 - 30 Jun 2026
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Abstract
The non-specific lipid transfer proteins (nsLTPs) are able to bind various hydrophobic compounds and facilitate the transport of fatty acids between intracellular membranes, and nsLTPs are found in rice endosperm and embryo during seed development. However, whether nsLTPs function as lipid carriers and [...] Read more.
The non-specific lipid transfer proteins (nsLTPs) are able to bind various hydrophobic compounds and facilitate the transport of fatty acids between intracellular membranes, and nsLTPs are found in rice endosperm and embryo during seed development. However, whether nsLTPs function as lipid carriers and thereby affect lipid metabolism in rice grains remains unclear. To elucidate whether nsLTPs influence fatty acid distribution in rice, we generated OsLTP10-OE (OsLTP10 overexpression) and OsLTP10-CR (OsLTP10 CRISPR/Cas9) lines. Phenotypic and metabolic analyses indicated that OsLTP10 expression is closely associated with fatty acid (FA) profiles and grain appearance. In general, total fatty acid content in the brown rice of OsLTP10-OE was higher than that in wildtype, but OsLTP10-CR was lower than wildtype. While FA accumulation was altered in both tissues, the endosperm (milled grain) was more severely affected than the bran, with individual FAs in the milled grains of OsLTP10-OE expanding by 31.87–52.00%. Additionally, key grain quality traits were substantially altered; OsLTP10-CR lines displayed a significantly enlarged white-belly chalkiness area alongside a 19.50% reduction in amylose content, whereas OsLTP10-OE lines showed decreased chalkiness and a 7.80% increase in amylose. Overall, the fatty acid content and composition, chalkiness, brown rice size, and amylose were influenced by OsLTP10. Full article
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