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26 pages, 3951 KiB  
Article
Exploring the Bioactive Potential and Chemical Profile of Schinus molle Essential Oil: An Integrated In Silico and In Vitro Evaluation
by Rómulo Oses, Matías Ferrando, Flavia Bruna, Patricio Retamales, Myriam Navarro, Katia Fernández, Waleska Vera, María José Larrazábal, Iván Neira, Adrián Paredes, Manuel Osorio, Osvaldo Yáñez, Martina Jacobs and Jessica Bravo
Plants 2025, 14(15), 2449; https://doi.org/10.3390/plants14152449 - 7 Aug 2025
Abstract
Chilean Schinus molle has been used in traditional medicine for effects such as antibacterial, antifungal, anti-inflammatory, analgesic, antiviral, antitumoral, antioxidant, antispasmodic, astringent, antipyretic, cicatrizant, cytotoxic, diuretic, among others. In this study, we evaluated the pharmacological potential of Schinus molle seed essential oil extract [...] Read more.
Chilean Schinus molle has been used in traditional medicine for effects such as antibacterial, antifungal, anti-inflammatory, analgesic, antiviral, antitumoral, antioxidant, antispasmodic, astringent, antipyretic, cicatrizant, cytotoxic, diuretic, among others. In this study, we evaluated the pharmacological potential of Schinus molle seed essential oil extract (SM_EO) through in vitro and in silico approaches. In vitro, the antioxidant potential was analyzed, and antitumor activity was evaluated in non-tumor and human epithelial tumor cell lines. Caenorhabditis elegans was used as a model for evaluating toxicity, and the chemical composition of the SM_EO was analyzed using gas chromatography–mass spectrometry. The oil contained four major monoterpenes: α-phellandrene (34%), β-myrcene (23%), limonene (13%), and β-phellandrene (7%). Based on quantum mechanical calculations, the reactivity of the molecules present in the SM_EO was estimated. The results indicated that α- phellandrene, β-phellandrene, and β-myrcene showed the highest nucleophilic activity. In addition, the compounds following these as candidates for antioxidant and antiproliferative activities were α-phellandrene, β-phellandrene, ρ-cymene, sabinene, caryophyllene, l-limonene, and α-pinene, highlighting β-myrcene. Based on ADME-Tox properties, it is feasible to use these compounds as new drug candidates. Moreover, the antibacterial activity MIC value obtained for B. cereus was equivalent to 2 μg/mL, and for Y. enterocolitica, S. enteritidis, and S. typhimurium, the MIC value was 32.5 μg/μL. SM_EO could selectively inhibit the proliferation of human epithelial mammary tumor MCF7 cells treated with SM_EOs at 64 and 16 ug/mL—a significant increase in BCL-2 in a dose-dependent manner—and showed low toxicity against Caenorhabditis elegans (from 10 to 0.078 mg·mL−1). These findings suggest that SM_EO may be a potential source of bioactive compounds, encouraging further investigation for applications in veterinary medicine, cosmetics, and sanitation. Full article
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7 pages, 1045 KiB  
Proceeding Paper
Surveillance of Antimicrobial Use in Animal Production: A Cross-Sectional Study of Kaduna Metropolis, Nigeria
by Aliyu Abdulkadir, Marvelous Oluwashina Ajayi and Halima Abubakar Kusfa
Med. Sci. Forum 2025, 35(1), 4; https://doi.org/10.3390/msf2025035004 - 4 Aug 2025
Viewed by 19
Abstract
Measuring antimicrobial use (AMU) in animal production can provide useful data for monitoring AMU over time, which will promote antimicrobial resistance (AMR) reduction. This study involved the daily collation and validation of active primary drug sales and prescription data from veterinary outlets and [...] Read more.
Measuring antimicrobial use (AMU) in animal production can provide useful data for monitoring AMU over time, which will promote antimicrobial resistance (AMR) reduction. This study involved the daily collation and validation of active primary drug sales and prescription data from veterinary outlets and clinics of the Kaduna metropolis. In total, 83.7% of the identified antimicrobials were in the form of oral medication, and most were registered antibiotics (52.8%). Parenteral and topical forms were also identified, with 94% also being antibiotics. The estimated AMU was 282 mg/kg population correction unit (PCU). Poultry represented the most significant population, constituting 99% (31,502,004) of the study population. The class-specific AMU was antibiotics, with 274 mg/kg PCU. The antiprotozoal AMU was 418 mg/kg PCU. The anthelminthic AMU was the highest at 576 mg/kg PCU. This study has provided useful and practical information on the trends in antimicrobial use in animals, with poultry being the most important animal population involved in AMU and oxytetracycline being the most abused antibiotic in animal production. Antimicrobial stewardship (AMS) should be targeted at poultry populations, with an emphasis on reducing antibiotic use/consumption. Full article
(This article belongs to the Proceedings of The 4th International Electronic Conference on Antibiotics)
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16 pages, 775 KiB  
Article
Residue Elimination Patterns and Determination of the Withdrawal Times of Seven Antibiotics in Taihang Chickens
by Huan Chen, Cheng Zhang, Nana Gao, Guohua Yan, Yandong Li, Xuejing Wang, Liyong Wu, Heping Bai, Hongyu Ge, Huage Liu and Juxiang Liu
Animals 2025, 15(15), 2219; https://doi.org/10.3390/ani15152219 - 28 Jul 2025
Viewed by 201
Abstract
Antibiotic residues in poultry pose health and resistance risks, necessitating breed-specific WDTs. In this study, the residue elimination patterns of seven antibiotics in Taihang chicken tissues under free-range conditions were studied and the appropriate WDT was formulated. A total of 240 healthy Taihang [...] Read more.
Antibiotic residues in poultry pose health and resistance risks, necessitating breed-specific WDTs. In this study, the residue elimination patterns of seven antibiotics in Taihang chicken tissues under free-range conditions were studied and the appropriate WDT was formulated. A total of 240 healthy Taihang chickens aged 100 days were randomly divided into 8 groups, each comprising 30 chickens. Chickens in groups 1 to 7 were administered oxytetracycline, chlortetracycline, erythromycin, tylosin, tylvalosin, lincomycin, and tiamulin, respectively. Regarding the administration method, we adopted the highest dose and maximum course of treatment recommended by the Veterinary Pharmacopoeia of the People’s Republic of China. Group 8 served as the control group. Muscle, sebum, liver, and kidney samples were collected at 4 h, 1 d, 2 d, 3 d, 5 d, 7 d, 10 d, 13 d, and 16 d after drug withdrawal. Our results demonstrated that the drug residues after drug withdrawal gradually decreased with the increase in drug withdrawal days, and the elimination rate in the early stage of drug withdrawal was significantly faster than that in the later stage. At 4 h after drug withdrawal, the drug residues in various tissues reached their highest values. In most cases, the drug concentrations in the kidney and liver were higher than those in the muscles and sebum; however, some drugs also exhibited concentration peaks in the sebum. On the first day of drug withdrawal, the amount of residues in various tissues decreased rapidly. In general, the elimination rate of various drugs in the muscles, liver, and kidneys is faster but slower in the sebum. Based on the WDT calculation software WT1.4, the recommended WDTs for oxytetracycline, chlortetracycline, erythromycin, tylosin, tylvalosin, lincomycin, and tiamulin chickens are 4 d, 5 d, 11 d, 8 d, 13 d, 13 d, and 7 d, respectively. These findings support food safety and industry development. Full article
(This article belongs to the Section Poultry)
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21 pages, 319 KiB  
Review
The Role of the Endocannabinoid System in Oncology and the Potential Use of Cannabis Derivatives for Cancer Management in Companion Animals
by Giorgia della Rocca, Alessandra Di Salvo, Erica Salucci, Michela Amadori, Giovanni Re and Cristina Vercelli
Animals 2025, 15(15), 2185; https://doi.org/10.3390/ani15152185 - 24 Jul 2025
Viewed by 247
Abstract
The last decades of research have shown that the endocannabinoid system may be a promising therapeutic target for the pharmacological treatment of cancer in human medicine and possibly in veterinary medicine as well. Compared with the original cells, the expression of gene encoding [...] Read more.
The last decades of research have shown that the endocannabinoid system may be a promising therapeutic target for the pharmacological treatment of cancer in human medicine and possibly in veterinary medicine as well. Compared with the original cells, the expression of gene encoding for receptors and enzymes belonging to the endocannabinoid system has been found to be altered in several tumor types; it has been hypothesized that this aberrant expression may be related to the course of the neoplasm as well as to the patient’s prognosis. Several studies, conducted both in vitro and in vivo, suggest that both endo- and phytocannabinoids can modulate signaling pathways, controlling cell proliferation and survival. In the complex process of carcinogenesis, cannabinoids seem to intervene at different levels by stimulating cell death, inhibiting the processes of angiogenesis and metastasis, and regulating antitumor immunity. Although the molecular mechanisms by which cannabinoids act are not always clear and defined, their synergistic activity with the most used antineoplastic drugs in clinical oncology is showing promising results, thus providing veterinary medicine with alternative therapeutic targets in disease control. This review aims to summarize current knowledge on the potential role of the endocannabinoid system and exogenous cannabinoids in oncology, with specific reference to the molecular mechanisms by which cannabinoids may exert antitumor activity. Additionally, it explores the potential synergy between cannabinoids and conventional anticancer drugs and considers their application in veterinary oncology. Full article
12 pages, 354 KiB  
Article
Comparison of Intravenous and Oral Meloxicam Pharmacokinetics in Female and Male Saanen Goats
by Zeynep Ozdemir Kutahya, Busra Aslan Akyol, Selen Mamuk, Petek Piner Benli and Cengiz Gokbulut
Vet. Sci. 2025, 12(8), 686; https://doi.org/10.3390/vetsci12080686 - 23 Jul 2025
Viewed by 347
Abstract
This study aimed to investigate the effect of gender on the pharmacokinetics of meloxicam in goats following intravenous (IV, 0.5 mg/kg) and oral (PO, 1.0 mg/kg) administration. A crossover design was used with 12 clinically healthy Saanen goats (six females and six males). [...] Read more.
This study aimed to investigate the effect of gender on the pharmacokinetics of meloxicam in goats following intravenous (IV, 0.5 mg/kg) and oral (PO, 1.0 mg/kg) administration. A crossover design was used with 12 clinically healthy Saanen goats (six females and six males). Plasma samples were collected up to 96 h post-administration and analyzed with an HPLC for meloxicam concentrations. Pharmacokinetic parameters were calculated and statistically compared between genders and administration routes. The results show that male goats exhibited significantly longer terminal half-life (T1/2λz), a greater mean residence time (MRT0–∞), and higher systemic exposure (AUC0–∞) than females, particularly after oral administration. Oral bioavailability was calculated as 77.43% in females and 104.73% in males. These differences may be linked to gender-based variations in hepatic metabolism, enterohepatic recirculation, and the hormone-mediated modulation of cytochrome P450 activity. The findings are consistent with previous research demonstrating that gender can influence drug disposition through hormonal and enzymatic mechanisms. This study underscores the importance of considering gender as a biological variable in pharmacokinetic assessments of veterinary drugs, especially those used in food-producing animals, to optimize dosing strategies and ensure both therapeutic efficacy and food safety. Full article
(This article belongs to the Topic Recent Advances in Veterinary Pharmacology and Toxicology)
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11 pages, 520 KiB  
Article
Hemodynamic and Morpho-Biochemical Parameters of Rabbit Blood After Injection of Enzyme Preparations
by V. G. Vertiprakhov, N. A. Sergeenkova, S. V. Karamushkina and B. Sh. Dashieva
Biomolecules 2025, 15(7), 1049; https://doi.org/10.3390/biom15071049 - 18 Jul 2025
Viewed by 380
Abstract
The anti-inflammatory effect of trypsin in animals and humans is the basis for the development of new veterinary and medical drugs and alternatives to antibiotics. The current experiment analyzed the effect of pig pancreatic tissue lyophilizate and crystalline trypsin on the hemodynamic and [...] Read more.
The anti-inflammatory effect of trypsin in animals and humans is the basis for the development of new veterinary and medical drugs and alternatives to antibiotics. The current experiment analyzed the effect of pig pancreatic tissue lyophilizate and crystalline trypsin on the hemodynamic and morpho-biochemical parameters of rabbit blood. The experiments were carried out on 20 rabbits of the Soviet chinchilla breed of 6–8 months of age. Animals were intramuscularly injected with sterile solution of 0.9% NaCl in 0.5 mL (group 1, n = 5), sterile solution of crystalline trypsin in 0.9% NaCl at a concentration of 0.25 mg/kg body weight (group 2, n = 5), sterile solution of crystalline trypsin in 0, 9% NaCl at a concentration of 0.5 mg/kg body weight (group 3, n = 5), or sterile suspension of pig pancreas lyophilizate at a concentration of 1 mg/kg body weight (group 4, n = 5). Animals were injected once daily for five consecutive days. Significant changes in arterial blood pressure, serum enzymes activity, and the count of various blood cellular components were induced by the administration of different trypsin preparations. All data obtained indicate the presence of a biologically active substance in the lyophilizate, the effect of which requires further animal studies to create a prototype for the development of new drugs for human and animal use. Full article
(This article belongs to the Special Issue Digestive Enzymes in Health and Disease)
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17 pages, 3780 KiB  
Article
Selenomethionine Counteracts T-2 Toxin-Induced Liver Injury by Mitigating Oxidative Stress Damage Through the Enhancement of Antioxidant Enzymes
by Yan Wang, Mingxia Zhou, Suisui Gao, Pishun Li, Xiaofeng Zheng, Di Tu and Lingchen Yang
Antioxidants 2025, 14(7), 866; https://doi.org/10.3390/antiox14070866 - 15 Jul 2025
Viewed by 335
Abstract
T-2 toxin, a highly toxic feed contaminant, poses a significant health risk to both humans and animals, particularly targeting the liver. This study aimed to investigate the protective effects and underlying mechanisms of selenomethionine (SeMet) against T-2-induced liver injury in mice. We pretreated [...] Read more.
T-2 toxin, a highly toxic feed contaminant, poses a significant health risk to both humans and animals, particularly targeting the liver. This study aimed to investigate the protective effects and underlying mechanisms of selenomethionine (SeMet) against T-2-induced liver injury in mice. We pretreated mice with SeMet before exposing them to an acute liver injury model induced by T-2. By assessing indicators related to liver injury, oxidative stress, inflammatory response, and mitochondrial disorder, we found that SeMet mitigated T-2-induced liver damage. Specifically, SeMet upregulated the gene expression and activity of antioxidant enzymes like glutathione peroxidase 1 (GPX1), which consequently reduced reactive oxygen species (ROS), inflammatory cytokines levels, and normalized mitochondrial biogenesis. Conclusively, SeMet effectively alleviated T-2-induced mitochondrial overproduction, inflammatory responses, and oxidative stress damage in hepatocyte primarily by enhancing GPX1 and other antioxidant enzymes, thereby exerting a protective effect on the liver. This study provides theoretical and experimental support for further research and application of SeMet in the livestock industry. Full article
(This article belongs to the Special Issue Oxidative Stress in Hepatic Diseases)
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18 pages, 4199 KiB  
Article
Effects of Antibiotic Residues on Fecal Microbiota Composition and Antimicrobial Resistance Gene Profiles in Cattle from Northwestern China
by Wei He, Xiaoming Wang, Yuying Cao, Cong Liu, Zihui Qin, Yang Zuo, Yiming Li, Fang Tang, Jianjun Dai, Shaolin Wang and Feng Xue
Microorganisms 2025, 13(7), 1658; https://doi.org/10.3390/microorganisms13071658 - 14 Jul 2025
Viewed by 343
Abstract
Grazing is a free-range farming model commonly practiced in low-external-input agricultural systems. The widespread use of veterinary antibiotics in livestock farming has led to significant environmental accumulation of antibiotic residues and antibiotic resistance genes (ARGs), posing global health risks. This study investigated the [...] Read more.
Grazing is a free-range farming model commonly practiced in low-external-input agricultural systems. The widespread use of veterinary antibiotics in livestock farming has led to significant environmental accumulation of antibiotic residues and antibiotic resistance genes (ARGs), posing global health risks. This study investigated the antibiotic residues, bacterial community, ARG profiles, and mobile genetic elements (MGEs) in cattle feces from three provinces in western China (Ningxia, Xinjiang, and Inner Mongolia) under grazing modes. The HPLC-MS detection showed that the concentration of tetracycline antibiotics was the highest in all three provinces. Correlation analysis revealed a significant negative correlation between antibiotic residues and the diversity and population abundance of intestinal microbiota. However, the abundance of ARGs was directly proportional to antibiotic residues. Then, the Sankey analysis revealed that the ARGs in the cattle fecal samples were concentrated in 15 human pathogenic bacteria (HPB) species, with 9 of these species harboring multiple drug resistance genes. Metagenomic sequencing revealed that carbapenemase-resistant genes (blaKPC and blaVIM) were also present in considerable abundance, accounting for about 10% of the total ARGs detected in three provinces. Notably, Klebsiella pneumoniae strains carrying blaCTX-M-55 were detected, which had a possibility of IncFII plasmids harboring transposons and IS19, indicating the risk of horizontal transfer of ARGs. This study significantly advances the understanding of the impact of antibiotic residues on the fecal microbiota composition and ARG profiles in grazing cattle from northwestern China. Furthermore, it provides critical insights for the development of rational antibiotic usage strategies and comprehensive public health risk assessments. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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16 pages, 990 KiB  
Review
Repurposing Rafoxanide: From Parasite Killer to Cancer Fighter
by Teresa Pacifico, Lorenzo Tomassini, Livia Biancone, Giovanni Monteleone, Carmine Stolfi and Federica Laudisi
Biomedicines 2025, 13(7), 1686; https://doi.org/10.3390/biomedicines13071686 - 9 Jul 2025
Viewed by 460
Abstract
Rafoxanide, originally developed as a veterinary anthelmintic for the treatment of parasitic infections in livestock, has recently emerged as a promising therapeutic prospect in oncology. This compound has demonstrated notable antineoplastic effects against a variety of cancers, including skin, gastric, colorectal, and lung [...] Read more.
Rafoxanide, originally developed as a veterinary anthelmintic for the treatment of parasitic infections in livestock, has recently emerged as a promising therapeutic prospect in oncology. This compound has demonstrated notable antineoplastic effects against a variety of cancers, including skin, gastric, colorectal, and lung cancers, as well as hematological malignancies such as multiple myeloma. Rafoxanide exerts its anticancer activity through multiple complementary mechanisms, including the induction of endoplasmic reticulum stress, cell cycle arrest, apoptosis, and immunogenic cell death. Furthermore, the drug has been reported to inhibit key oncogenic signaling pathways (e.g., STAT3, NF-κB, c-FLIP, survivin) that contribute to tumor growth and metastasis. Preclinical studies in murine models have demonstrated significant reductions in tumor volume of up to 50% and a tumor-free rate exceeding 80%, with effective doses ranging from 7.5 to 40 mg/kg. This multitargeted mode of action distinguishes rafoxanide from conventional therapies and may help overcome resistance mechanisms that often limit the efficacy of cancer treatments. In this review, we summarize and discuss the growing body of evidence supporting rafoxanide’s therapeutic potential in oncology, as well as its possible applications in cancer treatment. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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22 pages, 3291 KiB  
Article
Matrix Interference Removal Using Fe3O4@SiO2-PSA-Based Magnetic Dispersive Solid-Phase Extraction for UPLC-MS/MS Analysis of Diazepam in Aquatic Products
by Mengqiong Yang, Guangming Mei, Daoxiang Huang, Xiaojun Zhang, Pengfei He and Si Chen
Foods 2025, 14(14), 2421; https://doi.org/10.3390/foods14142421 - 9 Jul 2025
Viewed by 310
Abstract
A sensitive method was developed for detecting diazepam residues in aquatic products using magnetic dispersive solid-phase extraction (MDSPE) coupled with ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Samples extracted with 1% ammonia–acetonitrile were purified using synthesized Fe3O4@SiO2-PSA nanoparticles [...] Read more.
A sensitive method was developed for detecting diazepam residues in aquatic products using magnetic dispersive solid-phase extraction (MDSPE) coupled with ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Samples extracted with 1% ammonia–acetonitrile were purified using synthesized Fe3O4@SiO2-PSA nanoparticles via MDSPE before UPLC-MS/MS analysis. Separation was performed on a C18 column with gradient elution using 0.1% formic acid–2 mM ammonium acetate/methanol. Detection employed positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode. Characterization confirmed Fe3O4@SiO2-PSA’s mesoporous structure with excellent adsorption capacity and magnetic properties. The method showed good linearity (0.1–10 μg/L, r > 0.99) with an LOD and LOQ of 0.20 μg/kg and 0.50 μg/kg, respectively. Recoveries at 0.5–15.0 µg/kg spiking levels were 74.9–109% (RSDs 1.24–11.6%). This approach provides rapid, accurate, and high-precision analysis of diazepam in aquatic products, meeting regulatory requirements. Full article
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14 pages, 840 KiB  
Article
Veterinary Prescriptions of Antibiotics Approved for Human Use: A Five-Year Analysis of Companion Animal Use and Regulatory Gaps in Brazil
by Rana Zahi Rached, Regina Albanese Pose, Érika Leão Ajala Caetano, Joana Garrossino Magalhães and Denise Grotto
Vet. Sci. 2025, 12(7), 652; https://doi.org/10.3390/vetsci12070652 - 9 Jul 2025
Viewed by 609
Abstract
Antimicrobial resistance (AMR) is a growing global concern, influenced by antibiotic use in both human and veterinary medicine, especially in companion animals. In low- and middle-income countries, regulatory oversight on veterinary prescriptions is often limited, creating gaps that can accelerate AMR. This study [...] Read more.
Antimicrobial resistance (AMR) is a growing global concern, influenced by antibiotic use in both human and veterinary medicine, especially in companion animals. In low- and middle-income countries, regulatory oversight on veterinary prescriptions is often limited, creating gaps that can accelerate AMR. This study aimed to characterize the use of antibiotics approved for human use that are prescribed by veterinarians for companion animals in Brazil, a country representative of broader regulatory challenges. We conducted a retrospective analysis of five years (2017–2021) of national sales data recorded by the National System for the Management of Controlled Products (SNGPC), maintained by the Brazilian Health Regulatory Agency (ANVISA). A total of 789,893 veterinary antibiotic prescriptions were analyzed over the five-year period, providing a comprehensive overview of prescribing patterns. The dataset included all oral and injectable antibiotics purchased in human pharmacies with veterinary prescriptions. Data wrangling and cleaning procedures were applied to extract information on volume, antibiotic classes, seasonal variation, and regional distribution. The results revealed a predominance of penicillins, first- and second-generation cephalosporins, and a marked increase in macrolide use, especially azithromycin. Notable regional disparities were observed, with the southeastern region leading in prescription volume. The findings, particularly the disproportionate use of azithromycin and the marked regional disparities, highlight the need for targeted monitoring policies and a stricter regulation of off-label antibiotic use in veterinary medicine. They also offer insights applicable to other countries facing similar AMR threats due to limited surveillance and regulatory frameworks. Full article
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16 pages, 3597 KiB  
Article
Towards a Customized Oral Drug Therapy for Pediatric Applications: Chewable Propranolol Gel Tablets Printed by an Automated Extrusion-Based Material Deposition Method
by Kristiine Roostar, Andres Meos, Ivo Laidmäe, Jaan Aruväli, Heikki Räikkönen, Leena Peltonen, Sari Airaksinen, Niklas Sandler Topelius, Jyrki Heinämäki and Urve Paaver
Pharmaceutics 2025, 17(7), 881; https://doi.org/10.3390/pharmaceutics17070881 - 4 Jul 2025
Viewed by 445
Abstract
Background: Automated semi-solid extrusion (SSE) material deposition is a promising new technology for preparing personalized medicines for different patient groups and veterinary applications. The technology enables the preparation of custom-made oral elastic gel tablets of active pharmaceutical ingredient (API) by using a semi-solid [...] Read more.
Background: Automated semi-solid extrusion (SSE) material deposition is a promising new technology for preparing personalized medicines for different patient groups and veterinary applications. The technology enables the preparation of custom-made oral elastic gel tablets of active pharmaceutical ingredient (API) by using a semi-solid polymeric printing ink. Methods: An automated SSE material deposition method was used for generating chewable gel tablets loaded with propranolol hydrochloride (-HCl) at three different API content levels (3.0 mg, 4.0 mg, 5.0 mg). The physical appearance, surface morphology, dimensions, mass and mass variation, process-derived solid-state changes, mechanical properties, and in-vitro drug release of the gel tablets were studied. Results: The inclusion of API (1% w/w) in the semi-solid CuraBlendTM printing mixture decreased viscosity and increased fluidity, thus promoting the spreading of the mixture on the printed (material deposition) bed and the printing performance of the gel tablets. The printed gel tablets were elastic, soft, jelly-like, chewable preparations. The mechanical properties of the gel tablets were dependent on the printing ink composition (i.e., with or without propranolol HCl). The maximum load for the final deformation of the CuraBlend™-API (3.0 mg) gel tablets was very uniform, ranging from 73 N to 80 N. The in-vitro dissolution test showed that more than 85% of the drug load was released within 15–20 min, thus verifying the immediate-release behavior of these drug preparations. Conclusions: Automated SSE material deposition as a modified 3D printing method is a feasible technology for preparing customized oral chewable gel tablets of propranolol HCl. Full article
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11 pages, 1397 KiB  
Article
Differential Emodepside Efficacy in Drug-Resistant and Drug-Susceptible Ancylostoma caninum Highlights Variability in Potassium Channel Activity
by Catherine A. Jackson, Elise L. McKean and John M. Hawdon
Trop. Med. Infect. Dis. 2025, 10(7), 181; https://doi.org/10.3390/tropicalmed10070181 - 27 Jun 2025
Viewed by 338
Abstract
Multi-anthelmintic resistance in hookworms poses a significant challenge to both human and veterinary health, underscoring the need for novel treatment strategies. In this study, we evaluated the in vitro efficacy of three anthelmintics—pyrantel, ivermectin, and emodepside—against L3 larvae of drug-susceptible (WMD) and triple-anthelmintic-resistant [...] Read more.
Multi-anthelmintic resistance in hookworms poses a significant challenge to both human and veterinary health, underscoring the need for novel treatment strategies. In this study, we evaluated the in vitro efficacy of three anthelmintics—pyrantel, ivermectin, and emodepside—against L3 larvae of drug-susceptible (WMD) and triple-anthelmintic-resistant (BCR) isolates of Ancylostoma caninum. While pyrantel was largely ineffective and ivermectin induced high mortality in both isolates, emodepside displayed a surprising trend: the drug-resistant BCR isolate was more susceptible than the drug-susceptible WMD isolate. To explore the underlying mechanism, we performed survival assays in the presence of penitrem A, a BK channel (SLO-1) inhibitor. The addition of penitrem A reversed the enhanced emodepside sensitivity in BCR, implicating elevated basal expression of SLO-1 channels as a potential factor. These findings suggest that emodepside, via its action on SLO-1, may offer a promising therapeutic avenue to combat multidrug-resistant hookworm infections. Full article
(This article belongs to the Special Issue Advances in Parasitic Neglected Tropical Diseases)
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18 pages, 6292 KiB  
Article
The Structural Basis of Binding Stability and Selectivity of Sarolaner Enantiomers for Ctenocephalides felis RDL Receptors
by Xiaojiao Zheng, Xin Wang, Xiulian Ju, Zhichao Ma and Genyan Liu
Molecules 2025, 30(13), 2756; https://doi.org/10.3390/molecules30132756 - 26 Jun 2025
Viewed by 300
Abstract
The ionotropic γ-aminobutyric acid (GABA) receptor (GABAR) is a key target for the development of antiparasitic agents, particularly against ectoparasites, such as fleas and ticks. Binding stability and selectivity of sarolaner enantiomers for Ctenocephalides felis RDL receptors (RDLR) were investigated in the current [...] Read more.
The ionotropic γ-aminobutyric acid (GABA) receptor (GABAR) is a key target for the development of antiparasitic agents, particularly against ectoparasites, such as fleas and ticks. Binding stability and selectivity of sarolaner enantiomers for Ctenocephalides felis RDL receptors (RDLR) were investigated in the current study. Wild-type (WT) C. felis RDLR and its A285S mutant were constructed using homology-based, fragment-based threading and AI-driven approaches, of which, SWISS-MODEL generated the most reliable structures. Molecular docking showed that the sarolaner S-enantiomer had higher binding affinity for both receptors than the R-enantiomer, primarily due to hydrogen bonding with Ile256, π–π stacking with Phe326, and hydrophobic interactions with Ile267 and Ile268. Molecular dynamics simulations confirmed the binding stability of the S-enantiomer-receptor complex in which key residues maintained interactions throughout the trajectories. Binding free energy analysis supported these results and highlighted the role of nonpolar interactions in binding stability. The A285S mutation had minimal impact on the binding pocket, and the S-enantiomer remained selective for and bound to the mutant receptor. Insights into the insecticidal mechanism of sarolaner enantiomers are given, and the current findings may inform the development of veterinary drugs from novel isoxazoline-based NAMs targeting insect GABARs. Full article
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17 pages, 2821 KiB  
Article
The Anti-Metastatic Properties of Glutathione-Stabilized Gold Nanoparticles—A Preliminary Study on Canine Osteosarcoma Cell Lines
by Sylwia S. Wilk, Klaudia I. Kukier, Arkadiusz M. Michałowski, Marek Wojnicki, Bartosz Smereczyński, Michał Wójcik and Katarzyna A. Zabielska-Koczywąs
Int. J. Mol. Sci. 2025, 26(13), 6102; https://doi.org/10.3390/ijms26136102 - 25 Jun 2025
Viewed by 528
Abstract
Osteosarcoma (OSA) is the most common primary bone malignancy in dogs, characterized by aggressive growth and high metastatic potential. Despite advances in treatment, the prognosis for affected animals remains poor, mainly due to metastatic disease. Metastasis is a complex process that involves forming [...] Read more.
Osteosarcoma (OSA) is the most common primary bone malignancy in dogs, characterized by aggressive growth and high metastatic potential. Despite advances in treatment, the prognosis for affected animals remains poor, mainly due to metastatic disease. Metastasis is a complex process that involves forming new blood vessels in the primary tumor (angiogenesis), intravasation, the transport of cancer cells to other locations, extravasation, and the growth of cancer cells in the secondary site. Gold nanoparticles (AuNPs), due to their unique physicochemical properties, are considered promising tools in cancer therapy, both as drug delivery systems and potential anti-metastatic agents. Previously, it has been demonstrated that 500 µg/mL glutathione-stabilized gold nanoparticles (Au-GSH NPs) inhibit cancer cell extravasation—one of the steps of the metastatic cascade. This study aimed to evaluate the anti-metastatic properties of Au-GSH NPs through their influence on OSA cell migration, proliferation, and colony formation in vitro, as well as their antiangiogenic properties on the chick embryo chorioallantoic (CAM) model. Additionally, we investigated whether these effects are associated with changes in alpha-2-macroglobulin (A2M) expression, as it was previously demonstrated to play an essential role in the metastatic cascade. Au-GSH NPs significantly inhibited migration and colony formation in canine osteosarcoma cells (from OSCA-8, OSCA-32, and D-17 cell lines) at 200 µg/mL concentrations. Interestingly, at 500 µg/mL, Au-GSH NPs inhibited angiogenesis on the CAM model and cancer cell migration, but fewer colonies were formed. These results may be directly related to the higher efficiency of Au-GSH NPs uptake by OSA cells at the dose of 200 μg/mL than at the dose of 500 μg/mL, as demonstrated using Microwave Plasma Atomic Emission Spectroscopy (MP-AES). Moreover, this is the first study that demonstrates a significant increase in A2M expression in cancer cells after Au-GSH NPs treatment. This study provides new insight into the potential use of Au-GSH NPs as anti-metastatic agents in canine osteosarcoma, indicating that their anti-metastatic properties may be related to A2M. However, further in vitro and in vivo studies are needed to explore the molecular mechanism underlying these effects and to evaluate the clinical relevance of AuNPs in veterinary oncology. Full article
(This article belongs to the Special Issue Nanoparticles for Cancer Treatment)
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