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17 pages, 1416 KiB  
Article
Humic Substances Promote the Activity of Enzymes Related to Plant Resistance
by Rakiely M. Silva, Fábio L. Olivares, Lázaro E. P. Peres, Etelvino H. Novotny and Luciano P. Canellas
Agriculture 2025, 15(15), 1688; https://doi.org/10.3390/agriculture15151688 - 5 Aug 2025
Abstract
The extensive use of pesticides has significant implications for public health and the environment. Breeding crop plants is the most effective and environmentally friendly approach to improve the plants’ resistance. However, it is time-consuming and costly, and it is sometimes difficult to achieve [...] Read more.
The extensive use of pesticides has significant implications for public health and the environment. Breeding crop plants is the most effective and environmentally friendly approach to improve the plants’ resistance. However, it is time-consuming and costly, and it is sometimes difficult to achieve satisfactory results. Plants induce defense responses to natural elicitors by interpreting multiple genes that encode proteins, including enzymes, secondary metabolites, and pathogenesis-related (PR) proteins. These responses characterize systemic acquired resistance. Humic substances trigger positive local and systemic physiological responses through a complex network of hormone-like signaling pathways and can be used to induce biotic and abiotic stress resistance. This study aimed to assess the effect of humic substances on the activity of phenylalanine ammonia-lyase (PAL), peroxidase (POX), and β-1,3-glucanase (GLU) used as a resistance marker in various plant species, including orange, coffee, sugarcane, soybeans, maize, and tomato. Seedlings were treated with a dilute aqueous suspension of humic substances (4 mM C L−1) as a foliar spray or left untreated (control). Leaf tissues were collected for enzyme assessment two days later. Humic substances significantly promoted the systemic acquired resistance marker activities compared to the control in all independent assays. Overall, all enzymes studied in this work, PAL, GLUC, and POX, showed an increase in activity by 133%, 181%, and 149%, respectively. Among the crops studied, citrus and coffee achieved the highest activity increase in all enzymes, except for POX in coffee, which showed a decrease of 29% compared to the control. GLUC exhibited the highest response to HS treatment, the enzyme most prominently involved in increasing enzymatic activity in all crops. Plants can improve their resistance to pathogens through the exogenous application of HSs as this promotes the activity of enzymes related to plant resistance. Finally, we consider the potential use of humic substances as a natural chemical priming agent to boost plant resistance in agriculture Full article
(This article belongs to the Special Issue Biocontrol Agents for Plant Pest Management)
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23 pages, 2663 KiB  
Article
Antimicrobial and Anticancer Activities of Lactiplantibacillus plantarum Probio87 Isolated from Human Breast Milk
by Pei Xu, Mageswaran Uma Mageswary, Azka Ainun Nisaa, Xiang Li, Yi-Jer Tan, Chern-Ein Oon, Cheng-Siang Tan, Wen Luo and Min-Tze Liong
Nutrients 2025, 17(15), 2554; https://doi.org/10.3390/nu17152554 - 5 Aug 2025
Abstract
Background/Objectives: This study evaluated the in vitro probiotic potential of Lactiplantibacillus plantarum Probio87 (Probio87), focusing on its physiological robustness, safety, antimicrobial properties, and anticancer activity, with relevance to vaginal and cervical health. Methods: Tests included acid and bile salt tolerance, mucin adhesion, and [...] Read more.
Background/Objectives: This study evaluated the in vitro probiotic potential of Lactiplantibacillus plantarum Probio87 (Probio87), focusing on its physiological robustness, safety, antimicrobial properties, and anticancer activity, with relevance to vaginal and cervical health. Methods: Tests included acid and bile salt tolerance, mucin adhesion, and carbohydrate utilization. Prebiotic preferences were assessed using FOS, GOS, and inulin. Antibiotic susceptibility was evaluated per EFSA standards. Antimicrobial activity of the cell-free supernatant (CFS) was tested against Staphylococcus aureus, Escherichia coli, and Candida species. Effects on Lactobacillus iners and L. crispatus were analyzed. Anticancer properties were assessed in HeLa, CaSki (HPV-positive), and C-33A (HPV-negative) cervical cancer cell lines through proliferation, apoptosis, angiogenesis, and cell cycle assays. Results: Probio87 showed strong acid and bile tolerance, efficient mucin adhesion, and broad carbohydrate utilization, favoring short-chain prebiotics like FOS and GOS over inulin. It met EFSA antibiotic safety standards. The CFS exhibited potent antimicrobial activity, including complete inhibition of Candida albicans. Probio87 selectively inhibited L. iners without affecting L. crispatus, indicating positive modulation of vaginal microbiota. In cervical cancer cells, the CFS significantly reduced proliferation and angiogenesis markers (p < 0.05), and induced apoptosis and cell cycle arrest in HPV-positive cells, with minimal effects on HPV-negative C-33A cells. Conclusions: Probio87 demonstrates strong probiotic potential, with safe, selective antimicrobial and anticancer effects. Its ability to modulate key microbial and cancer-related pathways supports its application in functional foods or therapeutic strategies for vaginal and cervical health. Full article
(This article belongs to the Section Prebiotics and Probiotics)
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14 pages, 1181 KiB  
Article
Effects of Ultrafine Bubble Water on Gut Microbiota Composition and Health Markers in Rats
by John Nicholas Jackowetz, Carly S. Hanson, Minto Michael, Kiriako Tsoukalas, Cassandra Villanueva and Peter A. Kozak
Nanomaterials 2025, 15(15), 1193; https://doi.org/10.3390/nano15151193 - 5 Aug 2025
Abstract
Ultrafine bubbles (UFBs) represent an emerging technology with unique physicochemical properties. This study investigated the effects of air-filled UFBs infused in drinking water on gut microbiota composition and the associated health markers in Sprague Dawley rats over a 12-week period. Using a two-phase [...] Read more.
Ultrafine bubbles (UFBs) represent an emerging technology with unique physicochemical properties. This study investigated the effects of air-filled UFBs infused in drinking water on gut microbiota composition and the associated health markers in Sprague Dawley rats over a 12-week period. Using a two-phase design, UFB concentration was increased from 1.7 × 106 to 6.5 × 109 UFBs/mL at week 7 to assess dose-dependent effects. Administration of UFBs in drinking water induced significant shifts in gut microbiome populations, characterized by increased Bacteroidetes (+122% weeks 8–12) and decreased Firmicutes (−43% weeks 8–12) compared to controls. These microbial shifts coincided with enhanced short-chain fatty acid production (butyrate +56.0%, p ≤ 0.001; valerate +63.1%, p ≤ 0.01) and reduced inflammatory markers (TNF-α −84.0%, p ≤ 0.05; IL-1β −41.0%, p ≤ 0.05; IL-10 −69.8%, p ≤ 0.05). UFB effects demonstrated systematic concentration-dependent threshold responses, with 85.7% of parameters exhibiting directional reversals between low (1.7 × 106 UFBs/mL) and high (6.5 × 109 UFBs/mL) concentration phases rather than linear dose–response relationships. The systematic nature of these threshold effects, with 71.4% of parameters achieving statistical significance (p ≤ 0.05), indicates concentration-dependent biological mechanisms rather than random effects on gut biology. Despite current metagenomic techniques identifying only 25% of the total gut microbiome, the observed changes in characterized species and metabolites demonstrate UFB technology’s therapeutic potential for conditions requiring microbiome modulation, providing new insights into UFB influence on complex biological systems. Full article
(This article belongs to the Special Issue Nanobubbles and Nanodroplets: Current State-of-the-Art)
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15 pages, 1474 KiB  
Article
Decline in Serum Lysophosphatidylcholine Species in Patients with Severe Inflammatory Bowel Disease
by Hauke Christian Tews, Tanja Elger, Muriel Huss, Johanna Loibl, Arne Kandulski, Martina Müller, Marcus Höring, Gerhard Liebisch and Christa Buechler
J. Clin. Med. 2025, 14(15), 5485; https://doi.org/10.3390/jcm14155485 - 4 Aug 2025
Abstract
Background/Objectives: Lysophosphatidylcholine (LPC) is composed of various lipid species, some of which exert pro-inflammatory and others anti-inflammatory activities. However, most of the LPC species analyzed to date are reduced in the serum of patients with inflammatory bowel disease (IBD) compared to healthy [...] Read more.
Background/Objectives: Lysophosphatidylcholine (LPC) is composed of various lipid species, some of which exert pro-inflammatory and others anti-inflammatory activities. However, most of the LPC species analyzed to date are reduced in the serum of patients with inflammatory bowel disease (IBD) compared to healthy controls. To our knowledge, the correlation between serum LPC species levels and measures of inflammation, as well as their potential as markers for monitoring IBD activity, has not yet been investigated. Methods: Thirteen LPC species, varying in acyl chain length and number of double bonds, were measured in the serum of 16 controls and the serum of 57 patients with IBD. Associations with C-reactive protein (CRP) and fecal calprotectin levels as markers of IBD severity were assessed. Results: Serum levels of LPC species did not differ between the healthy controls and the entire patient cohort. In patients with IBD, serum levels of LPC 16:1, 18:0, 18:3, 20:3, and 20:5, as well as total LPC concentrations, showed inverse correlations with both CRP and fecal calprotectin levels, indicating an association with inflammatory activity. Nine LPC species were significantly reduced in patients with high fecal calprotectin compared to those with low values. LPC species with 22 carbon atoms and 4 to 6 double bonds were not related to disease activity. Stool consistency and gastrointestinal symptoms did not influence serum LPC profiles. Corticosteroid treatment was associated with lower serum LPC 20:3 and 22:5 levels, while mesalazine, anti-TNF, and anti-IL-12/23 therapies had no significant impact on LPC concentrations. There was a strong positive correlation between LPC species containing 15 to 18 carbon atoms and serum cholesterol, triglycerides, and phosphatidylcholine levels. However, there was no correlation with markers of liver disease. Conclusions: Shorter-chain LPC species are reduced in patients with active IBD and reflect underlying hypolipidemia. While these lipid alterations provide insight into IBD-associated metabolic changes, they appear unsuitable as diagnostic or disease monitoring biomarkers. Full article
(This article belongs to the Special Issue Inflammatory Bowel Disease: Pathogenesis and Management Strategies)
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16 pages, 2547 KiB  
Article
Formation and Biological Characteristics Analysis of Artificial Gynogenetic WuLi Carp Induced by Inactivated Sperm of Megalobrama Amblycephala
by Xiaowei Xu, Enkui Hu, Qian Xiao, Xu Huang, Chongqing Wang, Xidan Xu, Kun Zhang, Yue Zhou, Jinhai Bai, Zhengkun Liu, Yuchen Jiang, Yan Tang, Xinyi Deng, Siyang Li, Wanjing Peng, Ling Xiong, Yuhan Yang, Zeyang Li, Ming Ma, Qinbo Qin and Shaojun Liuadd Show full author list remove Hide full author list
Biology 2025, 14(8), 994; https://doi.org/10.3390/biology14080994 (registering DOI) - 4 Aug 2025
Viewed by 15
Abstract
Artificial gynogenesis is an essential technique for aquaculture breeding. Fertile offspring of the WuLi carp (Cyprinus carpio var. Quanzhounensis, 2n = 100, WLC) were successfully produced via gynogenesis using ultraviolet-irradiated sperm from the blunt snout bream (Megalobrama amblycephala, 2 [...] Read more.
Artificial gynogenesis is an essential technique for aquaculture breeding. Fertile offspring of the WuLi carp (Cyprinus carpio var. Quanzhounensis, 2n = 100, WLC) were successfully produced via gynogenesis using ultraviolet-irradiated sperm from the blunt snout bream (Megalobrama amblycephala, 2n = 48, BSB). As anticipated, gonadal section examination confirmed that all gynogenetic WuLi carp (2n = 100, GWB) were female. To investigate whether paternal DNA fragments from BSB were integrated into the GWB genome, comparative analyses of morphological traits, DNA content, chromosomal numbers, 5S rDNA sequences, microsatellite DNA markers, fluorescence in situ hybridization (FISH), growth performance and nutritional composition were systematically conducted between GWB and maternal WLC. The results revealed pronounced maternal inheritance patterns across morphological characteristics, DNA quantification, chromosomal configurations, 5S rDNA sequences and FISH signals, while microsatellite detection unequivocally confirmed paternal BSB DNA fragment integration into the GWB genome. Remarkably, GWB demonstrated significantly superior growth performance and elevated unsaturated fatty acid content relative to the maternal line. This approach not only addressed germplasm degradation in WLC but also provided valuable theoretical foundations for breeding programs in this commercially significant species. Full article
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11 pages, 1077 KiB  
Article
Expression of 15-PGDH Regulates Body Weight and Body Size by Targeting JH in Honeybees (Apis mellifera)
by Xinying Qu, Xinru Zhang, Hanbing Lu, Lingjun Xin, Ran Liu and Xiao Chen
Life 2025, 15(8), 1230; https://doi.org/10.3390/life15081230 - 3 Aug 2025
Viewed by 106
Abstract
Honeybees (Apis mellifera) are pollinators for most crops in nature and a core species for the production of bee products. Body size and body weight are crucial breeding traits, as colonies possessing individuals with large body weight tend to be healthier [...] Read more.
Honeybees (Apis mellifera) are pollinators for most crops in nature and a core species for the production of bee products. Body size and body weight are crucial breeding traits, as colonies possessing individuals with large body weight tend to be healthier and exhibit high productivity. In this study, small interfering RNA (siRNA) targeting 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) was incorporated into the feed for feeding worker bee larvae, thereby achieving the silencing of this gene’s expression. The research further analyzed the impact of the RNA expression level of the 15-PGDH gene on the juvenile hormone (JH) titer and its subsequent effects on the body weight and size of worker bees. The results show that inhibiting the expression of 15-PGDH in larvae could significantly increase JH titer, which in turn led to an increase in the body weight of worker bees (1.13-fold higher than that of the control group reared under normal conditions (CK group); p < 0.01; SE: 7.85) and a significant extension in femur (1.08-fold longer than that of the CK group; p < 0.01; SE: 0.18). This study confirms that 15-PGDH can serve as a molecular marker related to body weight and size in honey bees, providing an important basis for molecular marker-assisted selection in honey bee breeding. Full article
(This article belongs to the Section Animal Science)
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27 pages, 15012 KiB  
Article
New Insights in the Helicellini Ihering, 1909 with Description of Kherattolactea Gen. Nov. and the First Record of Orexana Chueca, Gómez-Moliner, Madeira & Pfenninger, 2018 from Algeria
by Issaad Kawther Ezzine, Houria Bouaziz-Yahiatene, Willy De Mattia and Eike Neubert
Diversity 2025, 17(8), 550; https://doi.org/10.3390/d17080550 - 2 Aug 2025
Viewed by 186
Abstract
Recent sampling efforts in northern Algeria and the investigation of some collection material has revealed the presence of taxa with conchological and genital morphological similarities to the Candidula-like group. A detailed investigation of the anatomy of the genitalia combined with the analysis [...] Read more.
Recent sampling efforts in northern Algeria and the investigation of some collection material has revealed the presence of taxa with conchological and genital morphological similarities to the Candidula-like group. A detailed investigation of the anatomy of the genitalia combined with the analysis of two mitochondrial and two nuclear markers of representatives of the known genera as well as two Algerian taxa has been conducted. The result confirms the affiliation of the latter in the Candidula-like complex. Comparative anatomical analysis led to the description of a new genus, Kherattolactea gen. nov., endemic to northern Algeria with Xerophila keratae, Kobelt, 1892 as the type species. The anatomical distinction corroborates the result of the molecular analysis that reveals apomorphic nucleotide substitution. Moreover, the result of the combined analysis provides the first confirmed record of the genus Orexana Chueca, Gómez-Moliner, Madeira & Pfenninger, 2018, in north Africa, represented by the species Orexana lemoinei Kobelt, 1882 nov. comb. A new Xerogyra species, Xerogyra halgassi nov. sp., from the Apennine Mountain has been described based on the combination of morphoanatomical and molecular traits. For the first time, the morphoanatomical description of the known Xerogyra species has been presented. Full article
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19 pages, 2656 KiB  
Article
Circulating Lipid Profiles Indicate Incomplete Metabolic Recovery After Weight Loss, Suggesting the Need for Additional Interventions in Severe Obesity
by Alina-Iuliana Onoiu, Vicente Cambra-Cortés, Andrea Jiménez-Franco, Anna Hernández-Aguilera, David Parada, Francesc Riu, Antonio Zorzano, Jordi Camps and Jorge Joven
Biomolecules 2025, 15(8), 1112; https://doi.org/10.3390/biom15081112 - 1 Aug 2025
Viewed by 117
Abstract
The effects of long-term adjustments in body weight on the lipid balance in patients with severe obesity are not well understood. This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies [...] Read more.
The effects of long-term adjustments in body weight on the lipid balance in patients with severe obesity are not well understood. This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies before and after weight loss. Using mass spectrometry, 275 lipid species were analysed in non-obese controls, patients with severe obesity, and patients one year after bariatric surgery. The results showed that severe obesity disrupts lipid pathways, contributing to lipotoxicity, inflammation, mitochondrial stress, and abnormal lipid metabolism. Although weight loss improved these disturbances, surgery did not fully normalise the lipid profiles of all patients. Outcomes varied depending on their baseline liver health and genetic differences. Persistent alterations in cholesterol handling, membrane composition, and mitochondrial function were observed in partial responders. Elevated levels of sterol lipids, glycerophospholipids, and sphingolipids emerged as markers of complete metabolic recovery, identifying candidates for targeted post-surgical interventions. These findings support the use of lipidomics to personalise obesity treatment and follow-up. Full article
(This article belongs to the Section Molecular Biomarkers)
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36 pages, 3621 KiB  
Review
Harnessing Molecular Phylogeny and Chemometrics for Taxonomic Validation of Korean Aromatic Plants: Integrating Genomics with Practical Applications
by Adnan Amin and Seonjoo Park
Plants 2025, 14(15), 2364; https://doi.org/10.3390/plants14152364 - 1 Aug 2025
Viewed by 338
Abstract
Plant genetics and chemotaxonomic analysis are considered key parameters in understanding evolution, plant diversity and adaptation. Korean Peninsula has a unique biogeographical landscape that supports various aromatic plant species, each with considerable ecological, ethnobotanical, and pharmacological significance. This review aims to provide a [...] Read more.
Plant genetics and chemotaxonomic analysis are considered key parameters in understanding evolution, plant diversity and adaptation. Korean Peninsula has a unique biogeographical landscape that supports various aromatic plant species, each with considerable ecological, ethnobotanical, and pharmacological significance. This review aims to provide a comprehensive overview of the chemotaxonomic traits, biological activities, phylogenetic relationships and potential applications of Korean aromatic plants, highlighting their significance in more accurate identification. Chemotaxonomic investigations employing techniques such as gas chromatography mass spectrometry, high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy have enabled the identification of essential oils and specialized metabolites that serve as valuable taxonomic and diagnostic markers. These chemical traits play essential roles in species delimitation and in clarifying interspecific variation. The biological activities of selected taxa are reviewed, with emphasis on antimicrobial, antioxidant, anti-inflammatory, and cytotoxic effects, supported by bioassay-guided fractionation and compound isolation. In parallel, recent advances in phylogenetic reconstruction employing DNA barcoding, internal transcribed spacer regions, and chloroplast genes such as rbcL and matK are examined for their role in clarifying taxonomic uncertainties and inferring evolutionary lineages. Overall, the search period was from year 2001 to 2025 and total of 268 records were included in the study. By integrating phytochemical profiling, pharmacological evidence, and molecular systematics, this review highlights the multifaceted significance of Korean endemic aromatic plants. The conclusion highlights the importance of multidisciplinary approaches including metabolomics and phylogenomics in advancing our understanding of species diversity, evolutionary adaptation, and potential applications. Future research directions are proposed to support conservation efforts. Full article
(This article belongs to the Special Issue Applications of Bioinformatics in Plant Science)
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14 pages, 939 KiB  
Review
Revisiting Male Fertility in Livestock: The Case of Bull Sperm RNA
by Rene A. Ramírez-Sosa, Francisco J. Jahuey-Martínez, Monserrath Felix-Portillo and José A. Martínez-Quintana
Biology 2025, 14(8), 969; https://doi.org/10.3390/biology14080969 (registering DOI) - 1 Aug 2025
Viewed by 282
Abstract
To achieve the goals of productivity and sustainability across diverse livestock systems, reproductive factors play a pivotal role. Historically, reproductive research has primarily focused on females, as they are responsible for maintaining pregnancy and delivering offspring following oocyte fertilization. However, since the early [...] Read more.
To achieve the goals of productivity and sustainability across diverse livestock systems, reproductive factors play a pivotal role. Historically, reproductive research has primarily focused on females, as they are responsible for maintaining pregnancy and delivering offspring following oocyte fertilization. However, since the early 2000s, the biological significance of sperm RNAs has been increasingly recognized in various livestock species. These RNAs contribute both genetically and epigenetically at the time of fertilization and during early embryonic development. Multiple types of sperm RNA have been identified in bovine, porcine, ovine, buffalo, and caprine spermatozoa. Notably, transcriptomic profiling has shown potential to differentiate between high- and low-fertility males, even when conventional semen quality values appear normal in both groups. This opens the possibility for more accurate identification of highly fertile sires. Nevertheless, a definitive marker or set of markers has yet to be established, likely due to the transcriptome’s sensitivity to environmental conditions and to the variability in evaluation methodologies. Therefore, global scientific efforts should aim to establish standardized, robust protocols, as sperm RNA represents a promising avenue for enhancing the sustainability of animal production systems. Full article
(This article belongs to the Special Issue The Biology of Animal Reproduction)
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13 pages, 250 KiB  
Article
Evaluation of Depth of Anesthesia Sleep Quality in Swine Undergoing Hernia Repair: Effects of Romifidine/Ketamine-Diazepam Protocols with and Without Tramadol and the Potential Role of Serotonin as a Biomarker
by Fabio Bruno, Fabio Leonardi, Filippo Spadola, Giuseppe Bruschetta, Patrizia Licata, Veronica Cristina Neve and Giovanna Lucrezia Costa
Vet. Sci. 2025, 12(8), 722; https://doi.org/10.3390/vetsci12080722 - 31 Jul 2025
Viewed by 182
Abstract
Sedation and anesthesia are essential for ensuring animal welfare during surgical procedures such as hernia repair in swine. However, the number of sedative and anesthetic agents officially approved for livestock use remained limited. This study evaluated the sedative efficacy and serotonergic effects of [...] Read more.
Sedation and anesthesia are essential for ensuring animal welfare during surgical procedures such as hernia repair in swine. However, the number of sedative and anesthetic agents officially approved for livestock use remained limited. This study evaluated the sedative efficacy and serotonergic effects of a romifidine/ketamine/diazepam protocol, with and without the addition of tramadol, in swine undergoing umbilical hernia repair. Sixty-six crossbred Large White swine were randomly allocated to three groups: LL (lidocaine 4 mg/kg by infiltration), LT (lidocaine 2 mg/kg by infiltration + tramadol 2 mg/kg intraperitoneally), and TT (lidocaine2 mg/kg by infiltration + tramadol 4 mg/kg intraperitoneally). The physiological parameters heart rate, arterial pressure, oxygen saturation, rectal body temperature, and respiratory rate were assessed. The depth of intraoperative anesthesia and postoperative sedation was assessed using an ordinal scoring system (0–3). Plasma serotonin (5-HT) concentration was measured at baseline and 24 h post-surgery. Physiological parameters remained within species-specific reference ranges throughout the procedure. Anesthesia depth scores significantly decreased over time in all groups (p ≤ 0.001), with the tramadol-treated groups (LT and TT) showing more prolonged deeper anesthesia. Postoperative sedation was significantly higher in the TT group (p ≤ 0.001). Serotonin concentration decreased in LL, increased in LT, and remained stable in TT. These findings suggest that tramadol may enhance sedation and recovery, potentially through serotonergic modulation. Moreover, serotonin could serve as a physiological marker warranting further investigation in future studies of anesthetic protocols in veterinary medicine. Full article
(This article belongs to the Special Issue Anesthesia and Pain Management in Large Animals)
55 pages, 6122 KiB  
Review
Isorhamnetin: Reviewing Recent Developments in Anticancer Mechanisms and Nanoformulation-Driven Delivery
by Juie Nahushkumar Rana, Kainat Gul and Sohail Mumtaz
Int. J. Mol. Sci. 2025, 26(15), 7381; https://doi.org/10.3390/ijms26157381 - 30 Jul 2025
Viewed by 198
Abstract
Natural compounds, particularly flavonoids, have emerged as promising anticancer agents due to their various biological activities and no or negligible toxicity towards healthy tissues. Among these, isorhamnetin, a methylated flavonoid, has gained significant attention for its potential to target multiple cancer hallmarks. This [...] Read more.
Natural compounds, particularly flavonoids, have emerged as promising anticancer agents due to their various biological activities and no or negligible toxicity towards healthy tissues. Among these, isorhamnetin, a methylated flavonoid, has gained significant attention for its potential to target multiple cancer hallmarks. This review comprehensively explores the mechanisms by which isorhamnetin exerts its anticancer effects, including cell cycle regulation, apoptosis, suppression of metastasis and angiogenesis, and modulation of oxidative stress and inflammation. Notably, isorhamnetin arrests cancer cell proliferation by regulating cyclins, and CDKs induce apoptosis via caspase activation and mitochondrial dysfunction. It inhibits metastatic progression by downregulating MMPs, VEGF, and epithelial–mesenchymal transition (EMT) markers. Furthermore, its antioxidant and anti-inflammatory properties mitigate reactive oxygen species (ROS) and pro-inflammatory cytokines, restricting cancer progression and modulating tumor microenvironments. Combining isorhamnetin with other treatments was also discussed to overcome multidrug resistance. Importantly, this review integrates the recent literature (2022–2024) and highlights isorhamnetin’s roles in modulating cancer-specific signaling pathways, immune evasion, tumor microenvironment dynamics, and combination therapies. We also discuss nanoformulation-based strategies that significantly enhance isorhamnetin’s delivery and bioavailability. This positions isorhamnetin as a promising adjunct in modern oncology, capable of improving therapeutic outcomes when used alone or in synergy with conventional treatments. The future perspectives and potential research directions were also summarized. By consolidating current knowledge and identifying critical research gaps, this review positions Isorhamnetin as a potent and versatile candidate in modern oncology, offering a pathway toward safer and more effective cancer treatment strategies. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Cancer and Inflammation, 2nd Edition)
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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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14 pages, 1365 KiB  
Article
Molecular Genetic Basis of Reproductive Fitness in Tibetan Sheep on the Qinghai-Tibet Plateau
by Wangshan Zheng, Siyu Ge, Zehui Zhang, Ying Li, Yuxing Li, Yan Leng, Yiming Wang, Xiaohu Kang and Xinrong Wang
Genes 2025, 16(8), 909; https://doi.org/10.3390/genes16080909 - 29 Jul 2025
Viewed by 203
Abstract
Background: Complete environmental adaptation requires both survival and reproductive success. The hypoxic Qinghai-Tibet Plateau (>3000 m) challenges reproduction in indigenous species. Tibetan sheep, a key plateau-adapted breed, possess remarkable hypoxic tolerance, yet the genetic basis of their reproductive success remains poorly understood. [...] Read more.
Background: Complete environmental adaptation requires both survival and reproductive success. The hypoxic Qinghai-Tibet Plateau (>3000 m) challenges reproduction in indigenous species. Tibetan sheep, a key plateau-adapted breed, possess remarkable hypoxic tolerance, yet the genetic basis of their reproductive success remains poorly understood. Methods: We integrated transcriptomic and genomic data from Tibetan sheep and two lowland breeds (Small-tailed Han sheep and Hu sheep) to identify Tibetan sheep reproduction-associated genes (TSRGs). Results: We identified 165 TSRGs: four genes were differentially expressed (DEGs) versus Small-tailed Han sheep, 77 DEGs versus Hu sheep were found, and 73 genes were annotated in reproductive pathways. Functional analyses revealed enrichment for spermatogenesis, embryonic development, and transcriptional regulation. Notably, three top-ranked selection signals (VEPH1, HBB, and MEIKIN) showed differential expression. Murine Gene Informatics (MGI) confirmed that knockout orthologs exhibit significant phenotypes including male infertility, abnormal meiosis (male/female), oligozoospermia, and reduced neonatal weight. Conclusions: Tibetan sheep utilize an evolved suite of genes underpinning gametogenesis and embryogenesis under chronic hypoxia, ensuring high reproductive fitness—a vital component of their adaptation to plateaus. These genes provide valuable genetic markers for the selection, breeding, and conservation of Tibetan sheep as a critical genetic resource. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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36 pages, 539 KiB  
Review
Genomic Adaptation, Environmental Challenges, and Sustainable Yak Husbandry in High-Altitude Pastoral Systems
by Saima Naz, Ahmad Manan Mustafa Chatha, Qudrat Ullah, Muhammad Farooq, Tariq Jamil, Raja Danish Muner and Azka Kiran
Vet. Sci. 2025, 12(8), 714; https://doi.org/10.3390/vetsci12080714 - 29 Jul 2025
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Abstract
The yak (Bos grunniens) is a key species in high-altitude rangelands of Asia. Despite their ecological and economic importance, yak production faces persistent challenges, including low milk yields, vulnerability to climate changes, emerging diseases, and a lack of systematic breeding programs. [...] Read more.
The yak (Bos grunniens) is a key species in high-altitude rangelands of Asia. Despite their ecological and economic importance, yak production faces persistent challenges, including low milk yields, vulnerability to climate changes, emerging diseases, and a lack of systematic breeding programs. This review presents the genomic, physiological, and environmental dimensions of yak biology and husbandry. Genes such as EPAS1, which encodes hypoxia-inducible transcription factors, underpin physiological adaptations, including enlarged cardiopulmonary structures, elevated erythrocyte concentrations, and specialized thermoregulatory mechanisms that enable their survival at elevations of 3000 m and above. Copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) present promising markers for improving milk and meat production, disease resistance, and metabolic efficiency. F1 and F2 generations of yak–cattle hybrids show superior growth and milk yields, but reproductive barriers, such as natural mating or artificial insemination, and environmental factors limit the success of these hybrids beyond second generation. Infectious diseases, such as bovine viral diarrhea and antimicrobial-resistant and biofilm-forming Enterococcus and E. coli, pose risks to herd health and food safety. Rising ambient temperatures, declining forage biomass, and increased disease prevalence due to climate changes risk yak economic performance and welfare. Addressing these challenges by nutritional, environmental, and genetic interventions will safeguard yak pastoralism. This review describes the genes associated with different yak traits and provides an overview of the genetic adaptations of yaks (Bos grunniens) to environmental stresses at high altitudes and emphasizes the need for conservation and improvement strategies for sustainable husbandry of these yaks. Full article
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