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31 pages, 1726 KiB  
Article
The Effects of Artificial UV-B Provision on Positional Sleeping Behaviour and Vitamin D3 Metabolites of Captive Aye-Ayes (Daubentonia madagascariensis)
by Danielle Walker, Paige Bwye and Sarah Richdon
J. Zool. Bot. Gard. 2025, 6(3), 39; https://doi.org/10.3390/jzbg6030039 - 6 Aug 2025
Abstract
Zoological environments aim to promote natural behaviours and optimal welfare conditions. Over the past decade, research on the use of artificial ultraviolet-B (UV-B) exposure has improved vitamin D3 levels and reduced incidences of metabolic bone disease in diurnal primates; however, this has [...] Read more.
Zoological environments aim to promote natural behaviours and optimal welfare conditions. Over the past decade, research on the use of artificial ultraviolet-B (UV-B) exposure has improved vitamin D3 levels and reduced incidences of metabolic bone disease in diurnal primates; however, this has not been investigated in nocturnals. Aye-ayes (Daubentonia madagascariensis), nocturnal lemurs often housed indoors in zoos with little to no exposure to natural sunlight, have been reported to have low vitamin D3 levels. This study aims to investigate the impacts of artificial UV-B as a supplemental healthcare strategy for aye-ayes, examining its influences on vitamin D3 levels and positional sleeping behaviour. The 25-hydroxy-vitamin D3 (25OHD3) blood levels were tested before and after exposure to different levels of artificial UV-B and heat sources. Statistical analysis showed no correlation between UV-B and 25OHD3 at group parameter levels. However, one individual showed a positive correlation. Sleeping position duration analysis showed a potential basking behaviour with the use of increased ear exposure and other thermoregulatory responses. Despite representing 8.06% of the European captive aye-aye population, these findings highlight the need for further research on vitamin D3 parameters and responses to UV-B to optimise captive conditions and support the species’ long-term health. Full article
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17 pages, 4825 KiB  
Article
Tea Polyphenols Mitigate TBBPA-Induced Renal Injury Through Modulation of ROS-PI3K/AKT-NF-κB Signalling in Carp (Cyprinus carpio)
by Fuxin Han, Ran Xu, Hongru Wang, Xuejiao Gao and Mengyao Guo
Animals 2025, 15(15), 2307; https://doi.org/10.3390/ani15152307 - 6 Aug 2025
Abstract
Tetrabromobisphenol A (TBBPA), a widely utilised brominated flame retardant, demonstrates toxicological effects in aquatic organisms. Tea polyphenols (TPs), natural compounds found in tea leaves, exhibit both antioxidant and anti-inflammatory activities. The kidney is one of the major metabolic organs in common carp and [...] Read more.
Tetrabromobisphenol A (TBBPA), a widely utilised brominated flame retardant, demonstrates toxicological effects in aquatic organisms. Tea polyphenols (TPs), natural compounds found in tea leaves, exhibit both antioxidant and anti-inflammatory activities. The kidney is one of the major metabolic organs in common carp and serves as a target organ for toxic substances. This study evaluated the therapeutic potential of TPs in mitigating TBBPA-induced nephrotoxicity in common carp. Common carp were exposed to 0.5 mg/L TBBPA in water and/or fed a diet supplemented with 1 g/kg TPs for 14 days. In vitro, primary renal cells were treated with 60 μM TBBPA and/or 2.5 μg/L TPs for 24 h. Methods included histopathology, TUNEL assay for apoptosis, ROS detection, and molecular analyses. Antioxidant enzymes (SOD, CAT) and inflammatory cytokines (IL-1β, IL-6, TNF-α) were quantified using ELISA kits. Results showed that TBBPA induced oxidative stress, and activated the ROS-PI3K/AKT-NF-κB pathway, thereby resulting in inflammatory responses. TBBPA upregulated apoptosis-related genes (Caspase-3, Bax, and Bcl-2) and induced apoptosis. TBBPA upregulated the expression of RIPK3/MLKL, thereby exacerbating necroptosis. TPs intervention significantly mitigated these effects by reducing ROS, suppressing NF-κB activation, and restoring antioxidant enzyme activities (SOD, CAT). Moreover, TPs attenuated apoptosis and necrosis in the carp kidney, thereby enhancing the survival ability and immunity of common carp. Full article
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19 pages, 6853 KiB  
Article
Metabolomic and Molecular Mechanisms of Glycerol Supplementation in Regulating the Reproductive Function of Kazakh Ewes in the Non-Breeding Season
by Ying Nan, Baihui Jiang, Xingdong Qi, Cuifang Ye, Mengting Xie and Zongsheng Zhao
Animals 2025, 15(15), 2291; https://doi.org/10.3390/ani15152291 - 5 Aug 2025
Abstract
The activation mechanism of the reproductive axis in Kazakh ewes during the non-breeding season was explored by supplementation with glycerol complex (7% glycerol + tyrosine + vitamin B9). The experiment divided 50 ewes into five groups (n = 10). After 90 days [...] Read more.
The activation mechanism of the reproductive axis in Kazakh ewes during the non-breeding season was explored by supplementation with glycerol complex (7% glycerol + tyrosine + vitamin B9). The experiment divided 50 ewes into five groups (n = 10). After 90 days of intervention, it was found that significant changes in serum DL-carnitine, N-methyl-lysine and other differential metabolites were observed in the GLY-Tyr-B9 group (p < 0.05, “p < 0.05” means significant difference, “p < 0.01” means “highly significant difference”). The bile acid metabolic pathway was specifically activated (p < 0.01). The group had a 50% estrus rate, ovaries contained 3–5 immature follicles, and HE staining showed intact granulosa cell structure. Serum E2/P4 fluctuated cyclically (p < 0.01), FSH/LH pulse frequency increased (p < 0.01), peak Glu/INS appeared on day 60 (p < 0.05), and LEP was negatively correlated with body fat percentage (p < 0.01). Molecular mechanisms revealed: upregulation of hypothalamic kiss-1/GPR54 expression (p < 0.01) drove GnRH pulses; ovarian CYP11A1/LHR/VEGF synergistically promoted follicular development (p < 0.05); the HSL of subcutaneous fat was significantly increased (p < 0.05), suggesting involvement of lipolytic supply. Glycerol activates the reproductive axis through a dual pathway—L-carnitine-mediated elevation of mitochondrial β-oxidation efficacy synergizes with kisspeptin/GPR54 signalling enhancement to re-establish HPO axis rhythms. This study reveals the central role of metabolic reprogramming in regulating seasonal reproduction in ruminants. Full article
(This article belongs to the Section Small Ruminants)
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21 pages, 3013 KiB  
Review
Role of Micronutrient Supplementation in Promoting Cognitive Healthy Aging in Latin America: Evidence-Based Consensus Statement
by Carlos Alberto Nogueira-de-Almeida, Carlos A. Cano Gutiérrez, Luiz R. Ramos, Mónica Katz, Manuel Moreno Gonzalez, Bárbara Angel Badillo, Olga A. Gómez Santa María, Carlos A. Reyes Torres, Santiago O’Neill, Marine Garcia Reyes and Lara Mustapic
Nutrients 2025, 17(15), 2545; https://doi.org/10.3390/nu17152545 - 2 Aug 2025
Viewed by 359
Abstract
Background: Cognitive decline is a growing public health concern in Latin America, driven by rapid aging, widespread micronutrient inadequacies, and socioeconomic disparities. Despite the recognized importance of nutrition, many older adults struggle to meet daily dietary micronutrients requirements, increasing the risk of mild [...] Read more.
Background: Cognitive decline is a growing public health concern in Latin America, driven by rapid aging, widespread micronutrient inadequacies, and socioeconomic disparities. Despite the recognized importance of nutrition, many older adults struggle to meet daily dietary micronutrients requirements, increasing the risk of mild cognitive impairment (MCI). This study aimed to establish expert consensus on the role of Multivitamin and Mineral supplements (MVMs) in promoting cognitive healthy aging among older adults in Latin America. Methods: A panel of nine experts in geriatrics, neurology, and nutrition applied a modified Delphi methodology to generate consensus statements. The panel reviewed the literature, engaged in expert discussions, and used structured voting to develop consensus statements. Results: Consensus was reached on 14 statements. Experts agreed that cognitive aging in Latin America is influenced by neurobiological, lifestyle, and socioeconomic factors, including widespread micronutrient inadequacies (vitamins B-complex, C, D, E, and minerals such as zinc, magnesium, chromium, copper, iron and selenium), which were identified as critical for global cognitive function and brain structures, yet commonly inadequate in the elderly. While a balanced diet remains essential, MVMs can be recommended as a complementary strategy to bridge nutritional gaps. Supporting evidence, including the COSMOS-Mind trials, demonstrate that MVM use improves memory and global cognition, and reduces cognitive aging by up to 2 years in older adults. Conclusions: MVMs offer a promising, accessible adjunct for cognitive healthy aging in Latin America’s elderly population, particularly where dietary challenges persist. Region-specific guidelines, public health initiatives, and targeted research are warranted to optimize outcomes and reduce health inequities. Full article
(This article belongs to the Section Nutrition and Neuro Sciences)
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18 pages, 2312 KiB  
Review
Macromycete Edible Fungi as a Functional Poultry Feed Additive: Influence on Health, Welfare, Eggs, and Meat Quality—Review
by Damian Duda, Klaudia Jaszcza and Emilia Bernaś
Molecules 2025, 30(15), 3241; https://doi.org/10.3390/molecules30153241 - 1 Aug 2025
Viewed by 156
Abstract
Over the years, macromycete fungi have been used as a source of food, part of religious rites and rituals, and as a medicinal remedy. Species with strong health-promoting potential include Hericium erinaceus, Cordyceps militaris, Ganoderma lucidum, Pleurotus ostreatus, Flammulina [...] Read more.
Over the years, macromycete fungi have been used as a source of food, part of religious rites and rituals, and as a medicinal remedy. Species with strong health-promoting potential include Hericium erinaceus, Cordyceps militaris, Ganoderma lucidum, Pleurotus ostreatus, Flammulina velutipes, and Inonotus obliquus. These species contain many bioactive compounds, including β-glucans, endo- and exogenous amino acids, polyphenols, terpenoids, sterols, B vitamins, minerals, and lovastatin. The level of some biologically active substances is species-specific, e.g., hericenones and erinacines, which have neuroprotective properties, and supporting the production of nerve growth factor in the brain for Hericium erinaceus. Due to their high health-promoting potential, mushrooms and substances isolated from them have found applications in livestock nutrition, improving their welfare and productivity. This phenomenon may be of particular importance in the nutrition of laying hens and broiler chickens, where an increase in pathogen resistance to antibiotics has been observed in recent years. Gallus gallus domesticus is a key farm animal for meat and egg production, so the search for new compounds to support bird health is important for food safety. Studies conducted to date indicate that feed supplementation with mushrooms has a beneficial effect on, among other things, bird weight gain; bone mineralisation; and meat and egg quality, including the lipid profile and protein content and shell thickness, and promotes the development of beneficial microbiota, thereby increasing immunity. Full article
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19 pages, 3251 KiB  
Article
Effects of Dietary Cinnamaldehyde Supplementation on Growth Performance, Serum Antioxidant Capacity, Intestinal Digestive Enzyme Activities, Morphology, and Caecal Microbiota in Meat Rabbits
by Dongjin Chen, Yuxiang Lan, Yuqin He, Chengfang Gao, Bin Jiang and Xiping Xie
Animals 2025, 15(15), 2262; https://doi.org/10.3390/ani15152262 - 1 Aug 2025
Viewed by 179
Abstract
Cinnamaldehyde (CA) is a potential substitute for antibiotic growth promoters in animal breeding. In this study, we investigated its effects as a dietary supplement on growth performance, serum antioxidant capacity, intestinal digestive enzyme activities, intestinal morphology, and caecal microbiota in meat rabbits. Weaned [...] Read more.
Cinnamaldehyde (CA) is a potential substitute for antibiotic growth promoters in animal breeding. In this study, we investigated its effects as a dietary supplement on growth performance, serum antioxidant capacity, intestinal digestive enzyme activities, intestinal morphology, and caecal microbiota in meat rabbits. Weaned meat rabbits (n = 450) were randomly assigned to five groups, Groups A, B, C, D, and E, and fed 0, 50, 100, 150, and 200 mg/kg CA diets, respectively, for 47 days. Biological samples including serum (antioxidants), duodenal/caecal content (enzymes), intestinal tissue (morphology), and caecal digesta (microbiota) were collected at day 47 postweaning for analysis. Groups C and D showed significantly higher final body weights than Group A, with Group D (150 mg/kg CA) demonstrating superior growth performance including 11.73% longer duodenal villi (p < 0.05), 28.6% higher microbial diversity (p < 0.01), and 62% lower diarrhoea rate versus controls. Digestive enzyme activity as well as serum antioxidant capacity increased with increasing CA dose, Microbiota analysis revealed CA increased fibre-fermenting Oscillospiraceae (+38%, p < 0.01) while reducing Ruminococcaceae (−27%, p < 0.05). Thus, dietary CA supplementation at 150 mg/kg was identified as the optimal CA dose for improving meat rabbit production. These findings highlight CA as a functional feed additive for promoting sustainable rabbit production. Full article
(This article belongs to the Section Animal Nutrition)
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15 pages, 1019 KiB  
Article
Biostimulatory Effects of Bacillus subtilis and Pseudomonas corrugata on Phytochemical and Antioxidant Properties of In Vitro-Propagated Plants of Nardostachys jatamansi (D. Don) DC
by Janhvi Mishra Rawat, Mrinalini Agarwal, Shivani Negi, Jigisha Anand, Prabhakar Semwal, Balwant Rawat, Rajneesh Bhardwaj and Debasis Mitra
Bacteria 2025, 4(3), 38; https://doi.org/10.3390/bacteria4030038 - 1 Aug 2025
Viewed by 106
Abstract
Plant growth-promoting rhizobacteria (PGPRs) are well known for their capacity to enhance the growth and survival of in vitro-grown plants. However, their effect on Nardostachys jatamansi (D. Don) DC., a critically endangered medicinal plant in the Indian Himalayan Region, is still unknown. In [...] Read more.
Plant growth-promoting rhizobacteria (PGPRs) are well known for their capacity to enhance the growth and survival of in vitro-grown plants. However, their effect on Nardostachys jatamansi (D. Don) DC., a critically endangered medicinal plant in the Indian Himalayan Region, is still unknown. In this study, a simple, reproducible protocol for in vitro propagation of N. jatamansi was established using shoot tip explants, cultured on Murashige and Skoog (MS) medium supplemented with different plant growth regulators, including N6-benzylaminopurine, thidiazuron (TDZ), and naphthalene acetic acid (NAA). MS media supplemented with 2.0 μM TDZ and 0.5 µM NAA created a significant shoot induction with an average of 6.2 shoots per explant. These aseptically excised individual shoots produced roots on MS medium supplemented with Indole Butyric Acid or NAA within 14 days of the transfer. The PGPR, viz., Bacillus subtilis and Pseudomonas corrugata, inoculation resulted in improved growth, higher chlorophyll content, and survival of in vitro-rooted plants (94.6%) after transfer to the soil. Moreover, the PGPRs depicted a two-fold higher total phenolics (45.87 mg GAE/g DW) in plants. These results clearly demonstrate the beneficial effects of P. corrugata and B. subtilis on the growth, survival, and phytochemical content of N. jatamansi. Full article
(This article belongs to the Special Issue Harnessing of Soil Microbiome for Sustainable Agriculture)
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18 pages, 2077 KiB  
Article
Impact of Omega-3 and Vitamin D Supplementation on Bone Turnover Markers in Children with Leukemia: Follow-Up During and After Supplementation
by Lourdes Barbosa-Cortés, Sharon B. Morales-Montes, Michelle Maldonado-Alvarado, Jorge A. Martin-Trejo, Salvador Atilano-Miguel, Emmanuel Jiménez-Aguayo, Fabián I. Martínez-Becerril, Víctor M. Cortés-Beltrán, Atzin V. Hernández-Barbosa, Karina A. Solís-Labastida, Jorge Maldonado-Hernández, Benito A. Bautista-Martínez, Azalia Juárez-Moya, Zayra Hernández-Piñón, Juan M. Domínguez-Salgado, Judith Villa-Morales and Israel Domínguez-Calderón
Nutrients 2025, 17(15), 2526; https://doi.org/10.3390/nu17152526 - 31 Jul 2025
Viewed by 286
Abstract
Background/Objective: In patients with acute lymphoblastic leukemia (ALL), it has been demonstrated that the treatment has a negative effect on bone health. The n-3 polyunsaturated fatty acids (LCPUFAs-ω3) may attenuate bone resorption. We evaluated the effects of LCPUFAs-ω3, vitamin D, and [...] Read more.
Background/Objective: In patients with acute lymphoblastic leukemia (ALL), it has been demonstrated that the treatment has a negative effect on bone health. The n-3 polyunsaturated fatty acids (LCPUFAs-ω3) may attenuate bone resorption. We evaluated the effects of LCPUFAs-ω3, vitamin D, and calcium supplementation on bone turnover markers and changes in vitamin D concentrations during 6 weeks of supplementation and during 6 weeks of post-intervention follow-up in pediatric patients with ALL. Methods: Thirty-six pediatric patients with ALL were randomly assigned to the ω-3VDCa group (100 mg/kg/d LCPUFAs-ω3 + 4000 IU vitamin D + 1000 mg calcium) or the VDCa group (4000 IU vitamin D + 1000 mg calcium) for 6 weeks. Blood samples were collected to determine 25(OH)D, PTH, ICTP, and TRAP-5b (biomarkers of bone resorption) and osteocalcin (OC, a biomarker of bone production) levels at baseline, 6 weeks, and 12 weeks after supplementation. The 25(OH)D analysis was performed using ultra-high-performance liquid chromatography coupled to a mass spectrometer, and PTH and bone turnover markers were measured by ELISA. Results: The 25(OH)D concentration increased in both groups (ω3VDCa group: 19.4 ng/mL vs. 44.0 ng/mL, p < 0.0001; VDCa group: 15.3 ng/mL vs. 42.8 ng/mL, p = 0.018) and remained significantly higher at 12 weeks. At 12 weeks, ICTP showed lower concentrations in the ω-3VDCa group than in the VDCa group (0.74 ng/mL vs. 1.05 ng/mL, p = 0.024). Conclusions: Combined omega-3 and 4000 IU vitamin D supplementation for 6 weeks had a positive effect on bone health, as indicated by serum ICTP, with no effect on serum 25(OH)D levels over vitamin D supplementation alone. Full article
(This article belongs to the Special Issue Dietary Supplements and Chronic Diseases)
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22 pages, 1916 KiB  
Article
Freeze-Dried Probiotic Fermented Camel Milk Enriched with Ajwa Date Pulp: Evaluation of Functional Properties, Probiotic Viability, and In Vitro Antidiabetic and Anticancer Activities
by Sally S. Sakr and Hassan Barakat
Foods 2025, 14(15), 2698; https://doi.org/10.3390/foods14152698 - 31 Jul 2025
Viewed by 306
Abstract
Noncommunicable diseases (NCDs) like diabetes and cancer drive demand for therapeutic functional foods. This study developed freeze-dried fermented camel milk (FCM) with Ajwa date pulp (ADP), evaluating its physical and functional properties, probiotic survival, and potential benefits for diabetes and cancer. To achieve [...] Read more.
Noncommunicable diseases (NCDs) like diabetes and cancer drive demand for therapeutic functional foods. This study developed freeze-dried fermented camel milk (FCM) with Ajwa date pulp (ADP), evaluating its physical and functional properties, probiotic survival, and potential benefits for diabetes and cancer. To achieve this target, six FCM formulations were prepared using ABT-5 starter culture (containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Streptococcus thermophilus) with or without Lacticaseibacillus rhamnosus B-1937 and ADP (12% or 15%). The samples were freeze-dried, and their functional properties, such as water activity, dispersibility, water absorption capacity, water absorption index, water solubility index, insolubility index, and sedimentation, were assessed. Reconstitution properties such as density, flowability, air content, porosity, loose bulk density, packed bulk density, particle density, carrier index, Hausner ratio, porosity, and density were examined. In addition, color and probiotic survivability under simulated gastrointestinal conditions were analyzed. Also, antidiabetic potential was assessed via α-amylase and α-glucosidase inhibition assays, while cytotoxicity was evaluated using the MTT assay on Caco-2 cells. The results show that ADP supplementation significantly improved dispersibility (up to 72.73% in FCM15D+L). These improvements are attributed to changes in particle size distribution and increased carbohydrate and mineral content, which facilitate powder rehydration and reduce clumping. All FCM variants demonstrated low water activity (0.196–0.226), indicating good potential for shelf stability. The reconstitution properties revealed that FCM powders with ADP had higher bulk and packed densities but lower particle density and porosity than controls. Including ADP reduced interstitial air and increased occluded air within the powders, which may minimize oxidation risks and improve packaging efficiency. ADP incorporation resulted in a significant decrease in lightness (L*) and increases in redness (a*) and yellowness (b*), with greater pigment and phenolic content at higher ADP levels. These changes reflect the natural colorants and browning reactions associated with ADP, leading to a more intense and visually distinct product. Probiotic survivability was higher in ADP-fortified samples, with L. acidophilus and B. bifidum showing resilience in intestinal conditions. The FCM15D+L formulation exhibited potent antidiabetic effects, with IC50 values of 111.43 μg mL−1 for α-amylase and 77.21 μg mL−1 for α-glucosidase activities, though lower than control FCM (8.37 and 10.74 μg mL−1, respectively). Cytotoxicity against Caco-2 cells was most potent in non-ADP samples (IC50: 82.22 μg mL−1 for FCM), suggesting ADP and L. rhamnosus may reduce antiproliferative effects due to proteolytic activity. In conclusion, the study demonstrates that ADP-enriched FCM is a promising functional food with enhanced probiotic viability, antidiabetic potential, and desirable physical properties. This work highlights the potential of camel milk and date synergies in combating some NCDs in vitro, suggesting potential for functional food application. Full article
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14 pages, 923 KiB  
Article
Mitigating Effects of Rosmarinus officinalis Essential Oil and Sugar Beet Pulp on Immune Response and Growth Performance of Heat-Stressed Lambs
by Maria Giovanna Ciliberti, Rosaria Marino, Mariangela Caroprese, Cristina Stango, Agostino Sevi and Marzia Albenzio
Animals 2025, 15(15), 2241; https://doi.org/10.3390/ani15152241 - 30 Jul 2025
Viewed by 134
Abstract
Dietary supplementation under high ambient temperatures can be considered crucial for supporting immune responses in livestock. In the present paper, Rosmarinus officinalis essential oil (REO) alone and in combination with dried sugar beet pulp (REO + B) was included in the diet of [...] Read more.
Dietary supplementation under high ambient temperatures can be considered crucial for supporting immune responses in livestock. In the present paper, Rosmarinus officinalis essential oil (REO) alone and in combination with dried sugar beet pulp (REO + B) was included in the diet of lambs during the fattening period under heat stress conditions. Environmental conditions and physiological and growth parameters of lambs were monitored throughout the trial. Plasma samples were collected to evaluate cytokine secretion (IL-1β, IL-6, and IL-10). Notably, REO inclusion reduced rectal temperature and respiration rate while increasing pro-inflammatory cytokines (IL-1β and IL-6) at the same time, suggesting an enhanced immune response without compromising growth performance. Full article
(This article belongs to the Section Animal Physiology)
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14 pages, 882 KiB  
Article
Advancing Neonatal Screening for Pyridoxine-Dependent Epilepsy-ALDH7A1 Through Combined Analysis of 2-OPP, 6-Oxo-Pipecolate and Pipecolate in a Butylated FIA-MS/MS Workflow
by Mylène Donge, Sandrine Marie, Amandine Pochet, Lionel Marcelis, Geraldine Luis, François Boemer, Clément Prouteau, Samir Mesli, Matthias Cuykx, Thao Nguyen-Khoa, David Guénet, Aurélie Empain, Magalie Barth, Benjamin Dauriat, Cécile Laroche-Raynaud, Corinne De Laet, Patrick Verloo, An I. Jonckheere, Manuel Schiff, Marie-Cécile Nassogne and Joseph P. Dewulfadd Show full author list remove Hide full author list
Int. J. Neonatal Screen. 2025, 11(3), 59; https://doi.org/10.3390/ijns11030059 - 30 Jul 2025
Viewed by 284
Abstract
Pyridoxine-dependent epilepsy (PDE) represents a group of rare developmental and epileptic encephalopathies. The most common PDE is caused by biallelic pathogenic variants in ALDH7A1 (PDE-ALDH7A1; OMIM #266100), which encodes α-aminoadipate semialdehyde (α-AASA) dehydrogenase, a key enzyme in lysine catabolism. Affected individuals present with [...] Read more.
Pyridoxine-dependent epilepsy (PDE) represents a group of rare developmental and epileptic encephalopathies. The most common PDE is caused by biallelic pathogenic variants in ALDH7A1 (PDE-ALDH7A1; OMIM #266100), which encodes α-aminoadipate semialdehyde (α-AASA) dehydrogenase, a key enzyme in lysine catabolism. Affected individuals present with seizures unresponsive to conventional anticonvulsant medications but responsive to high-dose of pyridoxine (vitamin B6). Adjunctive lysine restriction and arginine supplementation have also shown potential in improving neurodevelopmental outcomes. Given the significant benefit of early intervention, PDE-ALDH7A1 is a strong candidate for newborn screening (NBS). However, traditional biomarkers are biochemically unstable at room temperature (α-AASA and piperideine-6-carboxylate) or lack sufficient specificity (pipecolate), limiting their utility for biomarker-based NBS. The recent identification of two novel and stable biomarkers, 2S,6S-/2S,6R-oxopropylpiperidine-2-carboxylate (2-OPP) and 6-oxo-pipecolate (oxo-PIP), offers renewed potential for biochemical NBS. We evaluated the feasibility of incorporating 2-OPP, oxo-PIP, and pipecolate into routine butylated FIA-MS/MS workflows used for biochemical NBS. A total of 9402 dried blood spots (DBS), including nine confirmed PDE-ALDH7A1 patients and 9393 anonymized controls were analyzed using a single multiplex assay. 2-OPP emerged as the most sensitive biomarker, identifying all PDE-ALDH7A1 patients with 100% sensitivity and a positive predictive value (PPV) of 18.4% using a threshold above the 99.5th percentile. Combining elevated 2-OPP (above the 99.5th percentile) with either pipecolate or oxo-PIP (above the 85.0th percentile) as secondary marker detected within the same multiplex FIA-MS/MS assay further improved the PPVs to 60% and 45%, respectively, while maintaining compatibility with butanol-derivatized method. Notably, increasing the 2-OPP threshold above the 99.89th percentile, in combination with either pipecolate or oxo-PIP above the 85.0th percentile resulted in both 100% sensitivity and 100% PPV. This study supports the strong potential of 2-OPP-based neonatal screening for PDE-ALDH7A1 within existing NBS infrastructures. The ability to multiplex 2-OPP, pipecolate and oxo-PIP within a single assay offers a robust, practical, high-throughput and cost-effective approach. These results support the inclusion of PDE-ALDH7A1 in existing biochemical NBS panels. Further prospective studies in larger cohorts are needed to refine cutoffs and confirm clinical performance. Full article
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30 pages, 3414 KiB  
Article
In Vitro Neuroprotective Effects of a Mixed Extract of Bilberry, Centella asiatica, Hericium erinaceus, and Palmitoylethanolamide
by Rebecca Galla, Sara Ferrari, Ivana Miletto, Simone Mulè and Francesca Uberti
Foods 2025, 14(15), 2678; https://doi.org/10.3390/foods14152678 - 30 Jul 2025
Viewed by 355
Abstract
Oxidative stress, driven by impaired antioxidant defence systems, is a major contributor to cognitive decline and neurodegenerative processes in brain ageing. This study investigates the neuroprotective effects of a natural compound mixture—composed of Hericium erinaceus, Palmitoylethanolamide, Bilberry extract, and Centella asiatica—using [...] Read more.
Oxidative stress, driven by impaired antioxidant defence systems, is a major contributor to cognitive decline and neurodegenerative processes in brain ageing. This study investigates the neuroprotective effects of a natural compound mixture—composed of Hericium erinaceus, Palmitoylethanolamide, Bilberry extract, and Centella asiatica—using a multi-step in vitro strategy. An initial evaluation in a 3D intestinal epithelial model demonstrated that the formulation preserves barrier integrity and may be bioaccessible, as evidenced by transepithelial electrical resistance (TEER) and the expression of tight junctions. Subsequent analysis in an integrated gut–brain axis model under oxidative stress conditions revealed that the formulation significantly reduces inflammatory markers (NF-κB, TNF-α, IL-1β, and IL-6; about 1.5-fold vs. H2O2), reactive oxygen species (about 2-fold vs. H2O2), and nitric oxide levels (about 1.2-fold vs. H2O2). Additionally, it enhances mitochondrial activity while also improving antioxidant responses. In a co-culture of neuronal and astrocytic cells, the combination upregulates neurotrophic factors such as BDNF and NGF (about 2.3-fold and 1.9-fold vs. H2O2). Crucially, the formulation also modulates key biomarkers associated with cognitive decline, reducing APP and phosphorylated tau levels (about 98% and 1.6-fold vs. H2O2) while increasing Sirtuin 1 and Nrf2 expression (about 3.6-fold and 3-fold vs. H2O2). These findings suggest that this nutraceutical combination may support the cellular pathways involved in neuronal resilience and healthy brain ageing, offering potential as a functional food ingredient or dietary supplement. Full article
(This article belongs to the Section Food Nutrition)
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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 375
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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20 pages, 15855 KiB  
Article
Resistance Response and Regulatory Mechanisms of Ciprofloxacin-Induced Resistant Salmonella Typhimurium Based on Comprehensive Transcriptomic and Metabolomic Analysis
by Xiaohan Yang, Jinhua Chu, Lulu Huang, Muhammad Haris Raza Farhan, Mengyao Feng, Jiapeng Bai, Bangjuan Wang and Guyue Cheng
Antibiotics 2025, 14(8), 767; https://doi.org/10.3390/antibiotics14080767 - 29 Jul 2025
Viewed by 313
Abstract
Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, [...] Read more.
Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, ciprofloxacin was used for in vitro induction to develop the drug-resistant strain H1. Changes in the minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined using the broth microdilution method. Transcriptomic and metabolomic analyses were conducted to investigate alterations in gene and metabolite expression. A combined drug susceptibility test was performed to evaluate the potential of exogenous metabolites to restore antibiotic susceptibility. Results: The MICs of strain H1 for ofloxacin and enrofloxacin increased by 128- and 256-fold, respectively, and the strain also exhibited resistance to ceftriaxone, ampicillin, and tetracycline. A single-point mutation of Glu469Asp in the GyrB was detected in strain H1. Integrated multi-omics analysis showed significant differences in gene and metabolite expression across multiple pathways, including two-component systems, ABC transporters, pentose phosphate pathway, purine metabolism, glyoxylate and dicarboxylate metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and coenzyme A biosynthesis, pyrimidine metabolism, arginine and proline biosynthesis, and glutathione metabolism. Notably, the addition of exogenous glutamine, in combination with tetracycline, significantly reduced the resistance of strain H1 to tetracycline. Conclusion: Ciprofloxacin-induced Salmonella resistance involves both target site mutations and extensive reprogramming of the metabolic network. Exogenous metabolite supplementation presents a promising strategy for reversing resistance and enhancing antibiotic efficacy. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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20 pages, 1780 KiB  
Systematic Review
Morphological Variations of the Anterior Cerebral Artery: A Systematic Review with Meta-Analysis of 85,316 Patients
by George Triantafyllou, Ioannis Paschopoulos, Katerina Kamoutsis, Panagiotis Papadopoulos-Manolarakis, Juan Jose Valenzuela-Fuenzalida, Juan Sanchis-Gimeno, Alejandro Bruna-Mejias, Andres Riveros-Valdés, Nikolaos-Achilleas Arkoudis, Alexandros Samolis, George Tsakotos and Maria Piagkou
Diagnostics 2025, 15(15), 1893; https://doi.org/10.3390/diagnostics15151893 - 28 Jul 2025
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Abstract
Background: The anterior cerebral artery (ACA), a critical component of the cerebral arterial circle, exhibits substantial morphological variability. While previous studies have explored ACA morphology using cadaveric and imaging methods, a comprehensive meta-analysis incorporating the latest evidence is lacking. Methods: Following [...] Read more.
Background: The anterior cerebral artery (ACA), a critical component of the cerebral arterial circle, exhibits substantial morphological variability. While previous studies have explored ACA morphology using cadaveric and imaging methods, a comprehensive meta-analysis incorporating the latest evidence is lacking. Methods: Following current guidelines, a systematic review and meta-analysis were performed across four major databases, supplemented by the gray literature and targeted journal searches. Ninety-nine studies, encompassing 85,316 patients, met the inclusion criteria. Statistical analyses were conducted using R, applying random effects models to estimate pooled prevalence and morphometric parameters. Results: The pooled prevalence of typical ACA morphology was 93.75%, whereas variants were noted in 6.25% of cases. The predominant variation identified was the accessory ACA (aACA) (1.99%), followed by unilateral absence of the A1 segment (1.78%), with the latter being more frequently recognized in imaging studies (p < 0.0001). Rare variants encompassed azygos ACA (azACA) (0.22%), fenestrated ACA (fACA) (0.02%), and bihemispheric ACA (bACA) (0.02%). The mean diameter and length of the A1 segment were measured at 2.10 mm and 14.24 mm, respectively. Hypoplasia of the A1 segment (<1 mm diameter) was recorded in 3.15% of cases. The influences of imaging modality, laterality, and population distribution on prevalence estimates were minimal. No significant publication bias was detected. Conclusions: Although infrequent, variants of the ACA possess significant clinical importance attributable to their correlation with aneurysm formation and the impairment of collateral circulation. The aACA and the absence of the A1 segment emerged as the most common variations. This meta-analysis presents an updated and high-quality synthesis of ACA morphology, serving as a valuable reference for clinicians and anatomists. Full article
(This article belongs to the Special Issue Advances in Anatomy—Third Edition)
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