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24 pages, 6550 KiB  
Article
DNA Fingerprint Profile of Zizania spp. Plant, Monitoring Its Leaves with Screening of Their Biological Activity: Antimicrobial, Antioxidant and Cytotoxicity
by Latifah A. Al Shammari
Life 2025, 15(8), 1240; https://doi.org/10.3390/life15081240 - 5 Aug 2025
Abstract
This study presents an integrated approach combining molecular, phytochemical, and biological analyses to characterize a newly discovered Zizania specimen from the northern Nile Delta, Egypt. Genetic fingerprinting using RAPD and ISSR markers revealed 85% band-sharing similarity with Zizania texana (Z. texana), [...] Read more.
This study presents an integrated approach combining molecular, phytochemical, and biological analyses to characterize a newly discovered Zizania specimen from the northern Nile Delta, Egypt. Genetic fingerprinting using RAPD and ISSR markers revealed 85% band-sharing similarity with Zizania texana (Z. texana), though distinct morphological and genetic traits suggested potential intraspecific variation. Phytochemical profiling identified high concentrations of bioactive compounds, including quercetin (42.1 µg/mL), β-caryophyllene (11.21%), and gallic acid (23.4 µg/mL), which are pertinent and correlated with robust biological activities. The ethanolic leaf extract exhibited significant antioxidant capacity (IC50 = 38.6 µg/mL in DPPH assay), potent antimicrobial effects against Candida albicans (C. albicans) (IC50 = 4.9 ± 0.6 µg/mL), and dose-dependent cytotoxicity against cancer cell lines. MCF-7 has the lowest IC50 (28.3 ± 1.5 µg/mL), indicating the highest potency among the tested cell lines. In contrast, HepG2 demonstrates moderate sensitivity (IC50 = 31.4 ± 1.8 µg/mL), while A549 shows the highest IC50 value (36.9 ± 2.0 µg/mL), indicating greater resistance. These findings underscore the taxonomic novelty of the specimen and its potential as a source of natural antioxidants, antimicrobials, and anticancer agents. The study highlights the importance of interdisciplinary approaches in resolving taxonomic uncertainties and unlocking the medicinal value of understudied aquatic plants. Full article
(This article belongs to the Special Issue Therapeutic Innovations from Plants and Their Bioactive Extracts)
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21 pages, 2189 KiB  
Article
Effects of Salicylic Acid Application Method and Concentration on the Growth and Ornamental Quality of Poinsettia (Euphorbia pulcherrima Willd.)
by Alessandro Esposito, Alessandro Miceli, Filippo Vetrano, Samantha Campo and Alessandra Moncada
Horticulturae 2025, 11(8), 904; https://doi.org/10.3390/horticulturae11080904 (registering DOI) - 4 Aug 2025
Abstract
In the context of increasing demand for sustainable floriculture, this study evaluated the effects of salicylic acid (SA) on phenotypic traits of poinsettia (Euphorbia pulcherrima Willd.). A factorial experiment was conducted in a commercial glasshouse using rooted poinsettia cuttings treated with three [...] Read more.
In the context of increasing demand for sustainable floriculture, this study evaluated the effects of salicylic acid (SA) on phenotypic traits of poinsettia (Euphorbia pulcherrima Willd.). A factorial experiment was conducted in a commercial glasshouse using rooted poinsettia cuttings treated with three SA concentrations (10−3, 10−4, 10−5 M) applied via foliar or root application. Morphological parameters, colorimetric traits (CIELAB), canopy development, and biomass accumulation were assessed throughout the cultivation cycle. SA had no significant influence on the plant height, leaf number, or biomass of stems, leaves, and roots. However, notable phenotypic changes were observed. Foliar applications, particularly at 10−5 M, induced visible changes in leaf and bract color, including reduced brightness, saturation, and red pigmentation, especially in newly developed tissues. Conversely, root applications had milder effects and were generally associated with a more stable bract color. The 10−4 M root treatment promoted greater bract surface and color saturation. Canopy expansion and dry matter accumulation were also influenced by SA in a dose- and method-dependent manner, with high-dose foliar treatments (10−3 M) exerting suppressive effects. These findings suggest that the application mode and concentration of SA are critical in modulating ornamental quality traits, with low-to-moderate doses—particularly via root application—offering promising strategies to enhance plant performance in sustainable poinsettia cultivation. Full article
(This article belongs to the Section Protected Culture)
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18 pages, 1812 KiB  
Review
Nanocarriers for Medical Ozone Delivery: A New Therapeutic Strategy
by Manuela Malatesta and Flavia Carton
Nanomaterials 2025, 15(15), 1188; https://doi.org/10.3390/nano15151188 - 3 Aug 2025
Viewed by 59
Abstract
Ozone (O3) occurs in nature as a chemical compound made of three oxygen atoms. It is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O3 dates back to the beginning of the 20th century [...] Read more.
Ozone (O3) occurs in nature as a chemical compound made of three oxygen atoms. It is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O3 dates back to the beginning of the 20th century and is currently based on the application of low doses, inducing a moderate oxidative stress that stimulates the antioxidant cellular defenses without causing cell damage. Low O3 doses also induce anti-inflammatory and regenerative effects, and their anticancer potential is under investigation. In addition, the oxidative properties of O3 make it an excellent antibacterial, antimycotic, and antiviral agent. Thanks to these properties, O3 is currently widely used in several medical fields. However, its chemical instability represents an application limit, and ozonated oil is the only stabilized form of medical O3. In recent years, novel O3 formulations have been proposed for their sustained and more efficient administration, based on nanotechnology. This review offers an overview of the nanocarriers designed for the delivery of medical O3, and of their therapeutic applications. The reviewed articles demonstrate that research is active and productive, though it is a rather new entry in the nanotechnological field. Liposomes, nanobubbles, nanoconstructed hydrogels, polymeric nanoparticles, and niosomes were designed to deliver O3 and have been proven to exert antiseptic, anticancer, and pro-regenerative effects when administered in vitro and in vivo. Improving the therapeutic administration of O3 through nanocarriers is a just-started challenge, and multiple prospects may be foreseen. Full article
(This article belongs to the Section Biology and Medicines)
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16 pages, 3511 KiB  
Article
Phlogacanthus pulcherrimus Leaf Extract as a Functional Feed Additive: Influences on Growth Indices, Bacterial Challenge Survival, and Expression of Immune-, Growth-, and Antioxidant-Related Genes in Labeo chrysophekadion (Bleeker, 1849)
by Sontaya Sookying, Panitnart Auputinan, Dutrudi Panprommin and Paiboon Panase
Life 2025, 15(8), 1220; https://doi.org/10.3390/life15081220 - 1 Aug 2025
Viewed by 198
Abstract
This research examined the impact of dietary supplementation with Phlogacanthus pulcherrimus extract (PPE) on the growth, disease resistance, and expression of immune-, growth-, and antioxidant-related genes in Labeo chrysophekadion. Over 150 days, 90 fish from each group were fed diets with 0 [...] Read more.
This research examined the impact of dietary supplementation with Phlogacanthus pulcherrimus extract (PPE) on the growth, disease resistance, and expression of immune-, growth-, and antioxidant-related genes in Labeo chrysophekadion. Over 150 days, 90 fish from each group were fed diets with 0 (control), 0.25, 0.50, or 0.75 g/kg of PPE. Phytochemical analysis revealed phenolics (96.00 mg GAE/g), flavonoids (17.55 mg QE/g), anthraquinones, and triterpenoids, along with moderate antioxidant activity (IC50 = 1314.08 μg/mL). One-way ANOVA of growth indices, including weight gain, specific growth rate, feed conversion ratio, and survival rate, revealed no significant differences (p > 0.05); however, PPE supplementation significantly enhanced immune and antioxidant gene expression. IL-1β was significantly (p < 0.05) upregulated at all doses, with the highest expression observed at 0.50 g/kg, showing a fivefold increase compared to the control. In addition, the highest relative expressions of IGF-1 and CAT were found at 0.75 g/kg, with 4.5-fold and 3.5-fold increases compared to the control, respectively. PPE at 0.75 g/kg decreased the cumulative mortality rate (CMR) by 20% compared to the control group, which had a CMR of 50% following exposure to Aeromonas hydrophila. PPE acted as an effective immunostimulant and antioxidant, supporting reduced antibiotic reliance in aquaculture. Full article
(This article belongs to the Special Issue Nutrition–Physiology Interactions in Aquatic Species)
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20 pages, 1876 KiB  
Article
Evaluation of Clean-Label Additives to Inhibit Molds and Extend the Shelf Life of Preservative-Free Bread
by Ricardo H. Hernández-Figueroa, Aurelio López-Malo, Beatriz Mejía-Garibay, Nelly Ramírez-Corona and Emma Mani-López
Microbiol. Res. 2025, 16(8), 179; https://doi.org/10.3390/microbiolres16080179 - 1 Aug 2025
Viewed by 84
Abstract
This study evaluates the efficacy of commercial clean-label additives, specifically fermentates, in inhibiting mold growth in vitro and extending the shelf life of preservative-free bread. The mold growth on selected bread was modeled using the time-to-growth approach. The pH, aw, and [...] Read more.
This study evaluates the efficacy of commercial clean-label additives, specifically fermentates, in inhibiting mold growth in vitro and extending the shelf life of preservative-free bread. The mold growth on selected bread was modeled using the time-to-growth approach. The pH, aw, and moisture content of fresh bread were determined. In addition, selected fermentates were characterized physicochemically. Fermentates, defined as liquid or powdered preparations containing microorganisms, their metabolites, and culture supernatants, were tested at varying concentrations (1% to 12%) to assess their antimicrobial performance and impact on bread quality parameters, including moisture content, water activity, and pH. The results showed significant differences in fermentate efficacy, with Product A as the best mold growth inhibitor in vitro and a clear dose-dependent response. For Penicillium corylophilum, inhibition increased from 51.90% at 1% to 62.60% at 4%, while P. chrysogenum had an inhibition ranging from 32.26% to 34.49%. Product F exhibited moderate activity on both molds at 4%, inhibiting between 28.48% and 46.27%. The two molds exhibited differing sensitivities to the fermentates, with P. corylophilum consistently more susceptible to inhibition. Product A displayed a low pH (2.61) and high levels of lactic acid (1053.6 mmol/L) and acetic acid (1061.3 mmol/L). Product F presented a similar pH but lower levels of lactic and acetic acid. A time-to-growth model, validated by significant coefficients (p < 0.05) and high predictive accuracy (R2 > 0.95), was employed to predict the appearance of mold on bread loaves. The model revealed that higher concentrations of fermentates A and F delayed mold growth, with fermentate A demonstrating superior efficacy. At 2% concentration, fermentate A delayed mold growth for 8 days, compared to 6 days for fermentate F. At 8% concentration, fermentate A prevented mold growth for over 25 days, significantly outperforming the control (4 days). Additionally, fermentates influenced bread quality parameters, with fermentate A improving crust moisture retention and reducing water activity at higher concentrations. These findings highlight the potential of fermentates as sustainable, consumer-friendly alternatives to synthetic preservatives, offering a viable solution to the challenge of bread spoilage while maintaining product quality. Full article
(This article belongs to the Collection Microbiology and Technology of Fermented Foods)
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16 pages, 1131 KiB  
Article
Clinical and Cognitive Improvement Following Treatment with a Hemp-Derived, Full-Spectrum, High-Cannabidiol Product in Patients with Anxiety: An Open-Label Pilot Study
by Rosemary T. Smith, Mary Kathryn Dahlgren, Kelly A. Sagar, Deniz Kosereisoglu and Staci A. Gruber
Biomedicines 2025, 13(8), 1874; https://doi.org/10.3390/biomedicines13081874 - 1 Aug 2025
Viewed by 299
Abstract
Background/Objectives: Cannabidiol (CBD) is a non-intoxicating cannabinoid touted for a variety of medical benefits, including alleviation of anxiety. While legalization of hemp-derived products in the United States (containing ≤0.3% delta-9-tetrahydrocannabinol [d9-THC] by weight) has led to a rapid increase in the commercialization [...] Read more.
Background/Objectives: Cannabidiol (CBD) is a non-intoxicating cannabinoid touted for a variety of medical benefits, including alleviation of anxiety. While legalization of hemp-derived products in the United States (containing ≤0.3% delta-9-tetrahydrocannabinol [d9-THC] by weight) has led to a rapid increase in the commercialization of hemp-derived CBD products, most therapeutic claims have not been substantiated using clinical trials. This trial aimed to assess the impact of 6 weeks of treatment with a proprietary hemp-derived, full-spectrum, high-CBD sublingual solution similar to those available in the marketplace in patients with anxiety. Methods: An open-label pilot clinical trial (NCT04286594) was conducted in 12 patients with at least moderate levels of anxiety. Patients self-administered a hemp-derived, high-CBD sublingual solution twice daily during the 6-week trial (target daily dose: 30 mg/day CBD). Clinical change over time relative to baseline was assessed for anxiety, mood, sleep, and quality of life, as well as changes in cognitive performance on measures of executive function and memory. Safety and tolerability of the study product were also evaluated. Results: Patients reported significant reductions in anxiety symptoms over time. Concurrent improvements in mood, sleep, and relevant quality of life domains were also observed, along with stable or improved performance on all neurocognitive measures. Few side effects were reported, and no serious adverse events occurred. Conclusions: These pilot findings provide initial support for the efficacy and tolerability of the hemp-derived, high-CBD product in patients with moderate-to-severe levels of anxiety. Double-blind, placebo-controlled studies are indicated to obtain robust data regarding efficacy and tolerability of these types of products for anxiety. Full article
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18 pages, 1404 KiB  
Article
Comparative Analysis of the Long-Term Real-World Efficacy of Interleukin-17 Inhibitors in a Cohort of Patients with Moderate-to-Severe Psoriasis Treated in Poland
by Wiktor Kruczek, Aleksandra Frątczak, Iga Litwińska-Inglot, Karina Polak, Zuzanna Pawlus, Paulina Rutecka, Beata Bergler-Czop and Bartosz Miziołek
J. Clin. Med. 2025, 14(15), 5421; https://doi.org/10.3390/jcm14155421 - 1 Aug 2025
Viewed by 126
Abstract
Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, [...] Read more.
Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article
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19 pages, 3489 KiB  
Article
Impact of Nitrogen Fertilisation and Inoculation on Soybean Nodulation, Nitrogen Status, and Yield in a Central European Climate
by Waldemar Helios, Magdalena Serafin-Andrzejewska, Marcin Kozak and Sylwia Lewandowska
Agriculture 2025, 15(15), 1654; https://doi.org/10.3390/agriculture15151654 - 1 Aug 2025
Viewed by 178
Abstract
Soybean (Glycine max [L.] Merr.) cultivation is expanding in Central Europe due to the development of early-maturing cultivars and growing demand for plant-based protein produced without the use of genetically modified organisms. However, nitrogen (N) management remains a major challenge in temperate [...] Read more.
Soybean (Glycine max [L.] Merr.) cultivation is expanding in Central Europe due to the development of early-maturing cultivars and growing demand for plant-based protein produced without the use of genetically modified organisms. However, nitrogen (N) management remains a major challenge in temperate climates, where variable weather conditions can significantly affect nodulation and yield. This study evaluated the effects of three nitrogen fertilisation doses (0, 30, and 60 kg N·ha−1), applied in the form of ammonium nitrate (34% N) and two commercial rhizobial inoculants—HiStick Soy (containing Bradyrhizobium japonicum strain 532C) and Nitragina (including a Polish strain of B. japonicum)—on nodulation, nitrogen uptake, and seed yield. A three-year field experiment (2017–2019) was conducted in southwestern Poland using a two-factor randomized complete block design. Nodulation varied significantly across years, with the highest values recorded under favourable early-season moisture and reduced during drought. In the first year, inoculation with HiStick Soy significantly increased nodule number and seed yield compared to Nitragina and the uninoculated control. Nitrogen fertilisation consistently improved seed yield, although it had no significant effect on nodulation. The highest nitrogen use efficiency was observed with moderate nitrogen input (30 kg N·ha−1) combined with inoculation. These findings highlight the importance of integrating effective rhizobial inoculants with optimized nitrogen fertilisation to improve soybean productivity and nitrogen efficiency under variable temperate climate conditions. Full article
(This article belongs to the Special Issue Strategies to Enhance Nutrient Use Efficiency and Crop Nutrition)
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18 pages, 1640 KiB  
Article
Optimizing Citrus aurantifolia (Christm. Swingle) Production Through Integrated Irrigation and Growth Regulation Strategies
by Adriana Celi Soto, Diana Pincay Sánchez, Laura Pincay Sánchez, Luis Alcívar Zambrano, Ángel Sabando Zambrano, Cristhian Vega Ponce, George Cedeño García, Luis Saltos Rezabala, Liliana Corozo Quiñónez, Francisco Arteaga Alcívar, Edisson Cuenca Cuenca, Ramón Jaimez Arellano, Galo Cedeño García and Margarita Delgado Demera
Agronomy 2025, 15(8), 1853; https://doi.org/10.3390/agronomy15081853 - 31 Jul 2025
Viewed by 179
Abstract
Optimizing irrigation and the targeted use of plant growth regulators are key strategies to improve productivity in citrus systems under water-limited conditions. This study evaluated the effects of three irrigation levels (4.44, 5.18, and 7.77 mm day−1) combined with variable doses [...] Read more.
Optimizing irrigation and the targeted use of plant growth regulators are key strategies to improve productivity in citrus systems under water-limited conditions. This study evaluated the effects of three irrigation levels (4.44, 5.18, and 7.77 mm day−1) combined with variable doses of naphthaleneacetic acid (NAA) and gibberellic acid (GA3) on physiological and productive responses in Citrus aurantiifolia. The treatment with 7.77 mm irrigation and moderate doses of NAA (100 mg L−1) and GA3 (80 mg L−1) increased yield by 38% (6.2 kg/plant), and it enhanced photosystem II photochemical efficiency (Fv/Fm = 0.82), chlorophyll index (SPAD = 62), and fruit weight by 15%. In contrast, high hormone doses under water deficit reduced leaf water potential and impaired physiological performance, leading to lower productivity. These findings support the combined use of regulated deficit irrigation and hormonal biostimulation as a sustainable strategy to enhance key lime yield and resource efficiency in semi-arid environments. Full article
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19 pages, 1913 KiB  
Systematic Review
Innovative but Difficult to Replicate: A Systematic Review of the Reporting Quality of Robotic and Conventional Upper-Limb Interventions in Stroke Rehabilitation Randomized Controlled Trials Using the TIDieR-Rehab Checklist
by Emeline Gomes, Gemma Alder, Kate Boardsworth, Kate L. Anderson, Sharon Olsen and Nada Signal
Appl. Sci. 2025, 15(15), 8487; https://doi.org/10.3390/app15158487 (registering DOI) - 31 Jul 2025
Viewed by 229
Abstract
Background: Upper-limb impairment is a major cause of post-stroke disability, limiting participation in meaningful activities. Robotic rehabilitation may address this by delivering high-dosage, task-oriented training while reducing clinician workload. However, limited clinical translation of robotic interventions may be partly due to poor reporting [...] Read more.
Background: Upper-limb impairment is a major cause of post-stroke disability, limiting participation in meaningful activities. Robotic rehabilitation may address this by delivering high-dosage, task-oriented training while reducing clinician workload. However, limited clinical translation of robotic interventions may be partly due to poor reporting in the literature. This systematic review evaluated the intervention-reporting quality (completeness and consistency) of randomized controlled trials (RCTs) comparing robotic and conventional upper-limb stroke rehabilitation. Methods: Four databases were searched for RCTs investigating robotic upper-limb interventions compared with dose-matched conventional interventions for people with stroke. Intervention reporting was assessed using the TIDieR-Rehab checklist. Trained reviewers independently extracted and evaluated data, resolving discrepancies through consensus. Completeness and consistency were analyzed descriptively. Results: Among 25 RCTs, the overall reporting completeness was low (43%). Robotic interventions were better described (50%) than conventional interventions (36%). While timing and total dose were commonly reported, critical details on provider expertise, active dose, progressive challenge, personalization, and harms were often omitted. Reporting consistency was moderate (68%), with key information dispersed across article sections. Conclusions: Inadequate reporting limits the transparency, replication, and implementation of robotic upper-limb interventions. Adopting structured reporting frameworks like TIDieR-Rehab is essential for advancing the field. Full article
(This article belongs to the Special Issue Current Advances in Rehabilitation Technology)
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14 pages, 958 KiB  
Article
Adverse Childhood Experiences, Genetic Susceptibility, and the Risk of Osteoporosis: A Cohort Study
by Yanling Shu, Chao Tu, Yunyun Liu, Lulu Song, Youjie Wang and Mingyang Wu
Medicina 2025, 61(8), 1387; https://doi.org/10.3390/medicina61081387 - 30 Jul 2025
Viewed by 211
Abstract
Background and Objectives: Emerging evidence indicates that individuals exposed to adverse childhood experiences (ACEs) face elevated risks for various chronic illnesses. However, the association between ACEs and osteoporosis risk remains underexplored, particularly regarding potential modifications by genetic susceptibility. This prospective cohort study aims [...] Read more.
Background and Objectives: Emerging evidence indicates that individuals exposed to adverse childhood experiences (ACEs) face elevated risks for various chronic illnesses. However, the association between ACEs and osteoporosis risk remains underexplored, particularly regarding potential modifications by genetic susceptibility. This prospective cohort study aims to examine the relationship of ACEs with incident osteoporosis and investigate interactions with polygenic risk score (PRS). Materials and Methods: This study analyzed 124,789 UK Biobank participants initially free of osteoporosis. Cumulative ACE burden (emotional neglect, emotional abuse, physical neglect, physical abuse, sexual abuse) was ascertained through validated questionnaires. Multivariable-adjusted Cox proportional hazards models assessed osteoporosis risk during a median follow-up of 12.8 years. Moderation analysis examined genetic susceptibility interactions using a standardized PRS incorporating osteoporosis-related SNPs. Results: Among 2474 incident osteoporosis cases, cumulative ACEs showed dose–response associations with osteoporosis risk (adjusted hazard ratio [HR]per one-unit increase = 1.07, 95% confidence interval [CI] 1.04–1.11; high ACEs [≥3 types] vs. none: HR = 1.26, 1.10–1.43). Specifically, emotional neglect (HR = 1.14, 1.04–1.25), emotional abuse (HR = 1.14, 1.03–1.27), physical abuse (HR = 1.17, 1.05–1.30), and sexual abuse (HR = 1.15, 1.01–1.31) demonstrated comparable effect sizes. Sex-stratified analysis revealed stronger associations in women. Joint exposure to high ACEs/high PRS tripled osteoporosis risk (HR = 3.04, 2.46–3.76 vs. low ACEs/low PRS) although G × E interaction was nonsignificant (P-interaction = 0.10). Conclusions: These results suggest that ACEs conferred incremental osteoporosis risk independent of genetic predisposition. These findings support the inclusion of ACE screening in osteoporosis prevention strategies and highlight the need for targeted bone health interventions for youth exposed to ACEs. Full article
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16 pages, 7401 KiB  
Article
Sitagliptin Mitigates Diabetic Cardiomyopathy Through Oxidative Stress Reduction and Suppression of VEGF and FLT-1 Expression in Rats
by Qamraa H. Alqahtani, Tahani A. ALMatrafi, Amira M. Badr, Sumayya A. Alturaif, Raeesa Mohammed, Abdulaziz Siyal and Iman H. Hasan
Biomolecules 2025, 15(8), 1104; https://doi.org/10.3390/biom15081104 - 30 Jul 2025
Viewed by 271
Abstract
Diabetes mellitus (DM) is a global health challenge marked by chronic hyperglycemia, which can result in complications such as diabetic cardiomyopathy. Sitagliptin, an oral anti-hyperglycemic drug, has demonstrated efficacy in alleviating cardiovascular complications associated with DM. This study explored the impact of Sitagliptin’s [...] Read more.
Diabetes mellitus (DM) is a global health challenge marked by chronic hyperglycemia, which can result in complications such as diabetic cardiomyopathy. Sitagliptin, an oral anti-hyperglycemic drug, has demonstrated efficacy in alleviating cardiovascular complications associated with DM. This study explored the impact of Sitagliptin’s potential as a therapeutic agent, functioning not only to control blood sugar levels but also to enhance vascular health and strengthen cardiac resilience in diabetes. The investigation focused on alterations in the vascular endothelial growth factor (VEGF) and its receptor-1 (FLT-1) signaling pathways, as well as its potential to suppress inflammation and oxidative stress. A number of rats received a single dose of streptozotocin (STZ) 55 mg/kg (i.p.) to induce DM. Sitagliptin was administered orally (100 mg/kg/90 days) to normal and diabetic rats, after which samples were collected for investigation. Sitagliptin significantly mitigated weight loss in diabetic rats. Its administration significantly reduced blood glucose levels and improved serum troponin I and CK-MB levels. Heart sections from diabetic rats showed a marked increase in mTOR, VEGF, and FLT-1 immune reaction, while sitagliptin-treated diabetic rats’ heart sections showed moderate immune reactions. Sitagliptin’s protective effect was also associated with reduced inflammation, and apoptotic markers. In conclusion, Sitagliptin is suggested to offer beneficial effects on the vascular health of cardiac blood vessels, thereby potentially reducing myocardial stress in diabetic patients. Full article
(This article belongs to the Special Issue Pharmacology of Cardiovascular Diseases)
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21 pages, 4059 KiB  
Systematic Review
The Impact of Vitamin D Supplementation on Fasting Plasma Glucose, Insulin Sensitivity, and Inflammation in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
by Enny Probosari, Hertanto W. Subagio, Heri-Nugroho, Banundari Rachmawati, Siti F. Muis, Kevin C. Tjandra, Dwi Adiningsih and Tri I. Winarni
Nutrients 2025, 17(15), 2489; https://doi.org/10.3390/nu17152489 - 30 Jul 2025
Viewed by 354
Abstract
Background/Objectives: Vitamin D supplementation has shown promise in managing type 2 diabetes mellitus (T2DM), while the simultaneous impact on glycemic control and inflammation in T2DM remains poorly understood. This study aimed to investigate the potential role of vitamin D supplementation in managing [...] Read more.
Background/Objectives: Vitamin D supplementation has shown promise in managing type 2 diabetes mellitus (T2DM), while the simultaneous impact on glycemic control and inflammation in T2DM remains poorly understood. This study aimed to investigate the potential role of vitamin D supplementation in managing T2DM using fasting plasma glucose (FPG), insulin levels, HOMA-IR, HOMA-B, HbA1c, and Hs-CRP as the biomarkers. Methods: Original articles from Scopus, Pubmed, Cochrane Library, Epistemonikos, and ScienceDirect published between 2014 and 2024 were the sources. Inclusion criteria included studies conducted as clinical trials or randomized controlled trials involving adult patients diagnosed with T2DM undergoing treatment with vitamin D. The risk of bias was evaluated using the ROB-2 tool and meta-analysis was conducted to quantitatively synthesize the results across the studies using pooled effect sizes and confidence intervals. Results: Nine studies were included in the meta-analysis. Significant differences were found at 12-week follow-up in insulin level (MD(−3.59) [95% CI: −6.93, −0.25]), HOMA-B (MD(−50.35) [95% CI: −92.29, −8.41]), hs-CRP (−2.51 [95% CI: −3.45, −1.57]), and HbA1c level (MD(−0.30) [95% CI: −0.54, −0.06]) and at 24-week follow-up in HOMA-IR (MD(−0.38) [CI: −0.53, −0.24]). The quality of the included studies was generally moderate, with three showing a potential risk of bias. Conclusions: The observed trends in FPG, insulin levels, HOMA-IR, HOMA-B, HbA1c, and hs-CRP indicate that vitamin D may influence glycemic control, insulin sensitivity, and inflammation, but these effects are often modest and may diminish over time. Future studies should explore longer duration randomized trials with standardized dosing and baseline vitamin D status stratification. Full article
(This article belongs to the Section Micronutrients and Human Health)
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15 pages, 1411 KiB  
Article
Enhancing Antibiotic Effect by Photodynamic: The Case of Klebsiella pneumoniae
by Koteswara Rao Yerra and Vanderlei S. Bagnato
Antibiotics 2025, 14(8), 766; https://doi.org/10.3390/antibiotics14080766 - 29 Jul 2025
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Abstract
Background: The effect of antibiotics can be severely affected by external factors. Combining the oxidative impact of photodynamic therapy with antibiotics is largely unexplored, which may result in positive results with great impact on clinical applications. In particular, that can be relevant in [...] Read more.
Background: The effect of antibiotics can be severely affected by external factors. Combining the oxidative impact of photodynamic therapy with antibiotics is largely unexplored, which may result in positive results with great impact on clinical applications. In particular, that can be relevant in the case of antibiotic resistance. Objectives: In this study, we examined the effects of aPDT using the photosensitizers (PSs), methylene blue (MB) or Photodithazine (PDZ), both alone and in combination with the antibiotics ciprofloxacin (CIP), gentamicin (GEN), and ceftriaxone (CEF), against the Gram-negative bacterium Klebsiella pneumoniae. Methods: A standard suspension of K. pneumoniae was subjected to PDT with varying doses of MB and PDZ solutions, using a 75 mW/cm2 LED emitting at 660 nm with an energy of 15 J/cm2. The MICs of CIP, GEN, and CEF were determined using the broth dilution method. We also tested the photosensitizers MB or PDZ as potentiating agents for synergistic combinations with antibiotics CIP, GEN, and CEF against K. pneumoniae. Results: The results showed that MB was more effective in inhibiting survival and killing K. pneumoniae compared to PDZ. The tested antibiotics CIP, GEN, and CEF suppressed bacterial growth (as shown by reduced MIC values) and effectively killed K. pneumoniae (reduced Log CFU/mL). While antibiotic treatment or aPDT alone showed a moderate effect (1 Log10 to 2 Log10 CFU reduction) on killing K. pneumoniae, the combination therapy significantly increased bacterial death, resulting in a ≥3 Log10 to 6 Log10 CFU reduction. Conclusions: Our study indicates that pre-treating bacteria with PDT makes them more susceptible to antibiotics and could serve as an alternative for treating local infections caused by resistant bacteria or even reduce the required antibiotic dosage. This work explores numerous possible combinations of PDT and antibiotics, emphasizing their interdependence in controlling infections and the unique properties each PS-antibiotic combination offers. Clinical application for the combination is a promising reality since both are individually already adopted in clinical use. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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23 pages, 882 KiB  
Review
Toward Precision Medicine: Molecular Biomarkers of Response to Tofacitinib in Inflammatory Bowel Disease
by Anja Bizjak, Boris Gole, Gregor Jezernik, Uroš Potočnik and Mario Gorenjak
Genes 2025, 16(8), 908; https://doi.org/10.3390/genes16080908 - 29 Jul 2025
Viewed by 271
Abstract
Ulcerative colitis (UC), a subtype of inflammatory bowel disease (IBD), is a chronic, relapsing inflammatory condition that significantly impairs the patient’s quality of life. While biologics have transformed disease management, a substantial number of patients remain unresponsive or lose efficacy over time. Tofacitinib [...] Read more.
Ulcerative colitis (UC), a subtype of inflammatory bowel disease (IBD), is a chronic, relapsing inflammatory condition that significantly impairs the patient’s quality of life. While biologics have transformed disease management, a substantial number of patients remain unresponsive or lose efficacy over time. Tofacitinib (TOFA), an oral Janus kinase (JAK) inhibitor, introduces a novel therapeutic class of small-molecule drugs with a unique oral administration route, offering enhanced patient convenience and broader accessibility compared to parenterally administered biologics. As the first oral treatment approved for moderate to severe UC in years, TOFA acts by modulating the JAK/STAT pathway, influencing critical inflammatory mediators such as IL-6, IL-17, and IFN-γ. However, response rates are variable and appear dose-dependent, with up to 60% of patients showing inadequate therapeutic outcomes. This review represents the first comprehensive synthesis focused specifically on biomarkers of TOFA response in UC. Drawing on multi-omics data—epigenomics, transcriptomics, proteomics, and cellular profiling, we highlight emerging predictors of responsiveness, including CpG methylation signatures (e.g., LRPAP1 and FGFR2), transcriptomic regulators (e.g., REG3A and CLDN3), immune and epithelial cell shifts, and the cationic transporter MATE1. TOFA demonstrates a dual mechanism by modulating immune responses while supporting epithelial barrier restoration. Despite being promising, TOFA’s dose-dependent efficacy and interpatient variability underscore the critical need for non-invasive, predictive biomarkers to guide personalized treatment. As the first review of its kind, this work establishes a basis for precision medicine approaches to optimize the clinical utility of TOFA in UC management. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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