Assessment of acute, subacute genetic toxicities and immunomodulatory activity of palm (Trachycarpus fortunei) buds.

ETHNOPHARMACOLOGY RELEVANCE: Palm buds are a natural green resource of the forest, which are not only rich in nutrients but contain a large number of phenolic acids and flavonoids, among other components. It has a variety of biological activities such as antioxidant and uterine smooth muscle stimulation. AIM OF THE STUDY: To evaluate the safety of palm buds for use as a nutraceutical product and food by evaluating the toxicity, subacute toxicity and genotoxicity of the young palm buds. Also studied for its immune-enhancing activity. MATERIALS AND METHODS: Acute toxicity tests were performed in mice using the maximum tolerance method, and the manifestations of toxicity and deaths were recorded after administration of 10,000 mg/mL for 14 consecutive d (days) of observations. To assess subacute toxicity, mice were treated with palm buds (750, 1500, or 3000 mg/mL) daily for 28 days. The teratogenicity of palm buds was assessed by the Ames test, the mouse bone marrow cell micronucleus test, and the mouse spermatozoa malformation test. In addition, we evaluated the immune-enhancing ability of palm buds by the mouse carbon profile test, delayed-type metamorphosis reaction, and serum hemolysin assay. RESULTS: In the acute toxicity study, the Median Lethal Dose (LD50) was greater than 10,000 mg/kg bw in both male and female rats. There were also no deaths or serious toxicities in the subacute study. The no-observed-adverse-effect level (NOAEL) was 3000 mg/kg bw. However, the mice's food intake decreased after one week. The medium and high dose groups had a reducing effect on body weight in mice of both sexes. In addition, the changes in organ coefficients of the liver, kidney and stomach in male mice were significantly higher in the high-dose group (3.23 ± 0.35, 0.75 ± 0.05, 0.57 ± 0.05 g) than in the control group (2.94 ± 0.18, 0.58 ± 0.05, 0.50 ± 0.02 g). Hematological analyses showed that all the indices of the rats in each palm sprout dose group were within the normal range. The results of blood biochemical indicators showed that there was a significant reduction in TP in the blood of male mice in the high-dose group (44.6 ± 7.8 g/L) compared to the control group (58.3 ± 15.1 g/L). In histopathological analysis, none of the significant histopathological changes were observed. The results of the immunological experiment in mice showed that the liver coefficient and thymus coefficient of the high-dose group (8400 mg/kg) were significantly lower than the control group. There was no remarkable difference in auricle swelling between each dose palm bud group (1400, 2800, or 8400 mg/kg) and the control group. The anti-volume number of the high-dose group was significantly increased. CONCLUSION: Palm buds have non-toxic effects in vivo and have little effect on non-specific and cellular immunity in the test mice within the dose range of this experiment. The immunoenhancement in mice is mainly achieved through humoral immunity. In conclusion, our results suggest that palm buds are safe for use as healthcare products and food.

Metabolic profiling of pea (Pisum sativum) cultivars in changing environments: Implications for nutritional quality in animal feed.

Field pea seeds have long been recognized as valuable feed ingredients for animal diets, due to their high-quality protein and starch digestibility. However, the chemical composition of pea cultivars can vary across different growing locations, consequently impacting their nutrient profiles. This study employs untargeted metabolomics in conjunction with the quantification of fatty acids and amino acids to explore the influence of three different growing locations in Spain (namely Andalusia, Aragon and Asturias), on the nutritional characteristics of seeds of various pea cultivars. Significant interactions between cultivar and environment were observed, with 121 metabolites distinguishing pea profiles. Lipids, lipid-like molecules, phenylpropanoids, polyketides, carbohydrates, and amino acids were the most affected metabolites. Fatty acid profiles varied across locations, with higher C16:0, C18:0, and 18:1 n-9 concentration in Aragón, while C18:2 n-6 predominated in Asturias and C18:3 n-3 in Andalusia. Amino acid content was also location-dependent, with higher levels in Asturias. These findings underscore the impact of environmental factors on pea metabolite profiles and emphasize the importance of selecting pea cultivars based on specific locations and animal requirements. Enhanced collaboration between research and industry is crucial for optimizing pea cultivation for animal feed production.

Potential interventions and interactions of bioactive polyphenols and functional polysaccharides to alleviate inflammatory bowel disease - A review.

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.

Establishment of a swine model of delayed bleeding after endoscopic procedure.

Objectives: Although delayed bleeding after endoscopic procedures has become a problem, currently, there are no appropriate animal models to validate methods for preventing it. This study aimed to establish an animal model of delayed bleeding after endoscopic procedures of the gastrointestinal tract. Methods: Activated coagulation time (ACT) was measured using blood samples drawn from a catheter inserted into the external jugular vein of swine (n = 7; age, 6 months; mean weight, 13.8 kg) under general anesthesia using the cut-down method. An upper gastrointestinal endoscope was inserted orally, and 12 mucosal defects were created in the stomach by endoscopic mucosal resection using a ligating device. Hemostasis was confirmed at this time point. The heparin group (n = 4) received 50 units/kg of unfractionated heparin via a catheter; after confirming that the ACT was ≥200 s 10 min later, continuous heparin administration (50 units/kg/h) was started. After 24 h, an endoscope was inserted under general anesthesia to evaluate the blood volume in the stomach and the degree of blood adherence at the site of the mucosal defect. Results: Delayed bleeding was observed in three swine (75%) in the heparin-treated group, who had a maximum ACT of >220 s before the start of continuous heparin administration. In the non-treated group (n = 3), no prolonged ACT or delayed bleeding was observed at 24 h. Conclusion: An animal model of delayed bleeding after an endoscopic procedure in the gastrointestinal tract was established using a single dose of heparin and continuous heparin administration after confirming an ACT of 220 s.

The role of neophobia in a pioneer olfactory enrichment for amazons, macaws, and toucans / El papel de la neofobia en un enriquecimiento olfativo pionero para guacamayos, loros y tucanes

Abstract Introduction: Despite sensory enrichment being critical for ensuring the well-being of captive wild animals, smells are not being included in enrichment protocols for birds. For this group, neophobia can be a problem when it comes to implementing new enrichment devices. Objective: To explore how participation in an olfactory enrichment and latency times varies between bird taxonomic groups (Amazona spp. / Ara spp. / Ramphastos spp.). Methods: We exposed 257 birds to a scent enrichment, and we recorded which individuals engaged with it and the time they took to interact with it. Results: We discovered that participation by toucans in the enrichment was higher compared to amazons and macaws. Furthermore, latency time to interact with the enrichment was higher in amazons that in the other species. Our findings could suggest that toucans are neophilic species which could benefit from higher exploration rates. Amazons on the contrary seem to be particularly neophobic, possibly because of their less opportunistic feeding habits compared to toucans and their higher vulnerability to predation compared to macaws. Conclusion: These results point out that toucans would be more inclined to engage in environmental enrichments, while a more natural design using smells inside familiar objects could be a more successful enrichment for psittacids.

Resumen Introducción: A pesar de que el enriquecimiento sensorial es fundamental para garantizar el bienestar de los animales silvestres en cautiverio, los olores no son incluidos de forma rutinaria en los protocolos de enriquecimiento para aves. Además, en el caso de estos animales, la neofobia puede ser un problema a la hora de implementar nuevos dispositivos de enriquecimiento. Objetivo: Explorar cómo varía la participación y la latencia en la interacción con un enriquecimiento olfativo entre grupos taxonómicos de aves (Amazona spp. / Ara spp. / Ramphastos spp.). Métodos: Expusimos a 257 aves a un enriquecimiento olfativo y registramos qué individuos participaron y el tiempo que tardaron en interactuar con él. Resultados: La participación en el enriquecimiento fue mayor en los tucanes en comparación con las amazonas y los guacamayos. Además, el tiempo de latencia para interactuar con el enriquecimiento fue mayor en las amazonas que en las otras especies. Nuestros hallazgos sugieren que los tucanes son especies neofílicas que podrían beneficiarse de tasas de exploración más altas. Por otro lado, las amazonas parecen ser particularmente neofóbicas, posiblemente debido a sus hábitos alimenticios menos oportunistas en comparación con los tucanes y a su mayor vulnerabilidad a la depredación en comparación con los guacamayos. Conclusión: Estos resultados señalan que los tucanes serían más proclives a participar en enriquecimientos ambientales, mientras que un diseño que utilice olores dentro de objetos más naturales o familiares podría ser más exitoso para las psitácidas.

Transcriptome meta-analysis of Kawasaki disease in humans and mice.

Kawasaki Disease (KD) affects young children less than five years old with severe blood vessel inflammation. Despite being treatable, the causes and mechanisms remain elusive. This study conducted a meta-analysis of RNA sequencing (RNA-seq) data from human and animal models to explore KD's transcriptomic profile and evaluate animal models. We retrieved bulk and single-cell RNA-seq data from Gene Expression Omnibus, with blood and coronary artery samples from KD patients, aorta samples from KD mouse models (Lactobacillus casei cell wall extract-injected mice), and their controls. Upon consistent quality control, we applied Fisher's exact test to assess differential gene expression, followed by an enrichment analysis of overlapping genes. These studies identified 400 differentially expressed genes in blood samples of KD patients compared to controls and 413 genes in coronary artery samples. The data from KD blood and KD coronary artery samples shared only 16 differentially expressed genes. Eighty-one genes overlapped between KD human coronary arteries and KD mouse aortas, and 67 of these 81 genes were regulated in parallel in both humans and mice: 30 genes were up-regulated, and 37 were down-regulated. These included previously identified KD-upregulated genes: CD74, SFRP4, ITGA4, and IKZF1. Gene enrichment analysis revealed significant alterations in the cardiomyopathy pathway. Single-cell RNAseq showed a few significant markers, with known KD markers like S100A9, S100A8, CD74, CD14, IFITM2, and IFITM3, being overexpressed in KD cohorts. Gene profiles obtained from KD human coronary artery are more compatible with data from aorta samples of KD mice than blood samples of KD humans, validating KD animal models for identifying therapeutic targets. Although blood samples can be utilized to discover novel biomarkers, more comprehensive single-cell sequencing is required to detail gene expression in different blood cell populations. This study identifies critical genes from human and mouse tissues to help develop new treatment strategies for KD.

Rearing pigs with play opportunities: the effects on disease resilience in pigs experimentally inoculated with PRRSV.

Positive emotions can reduce disease susceptibility during infectious challenges in humans, and emerging evidence suggests similar effects in farm animals. Because play behaviour may support a positive emotional state in pigs, this study investigates whether rearing pigs with regular intermittent play opportunities enhances disease resilience when challenged with porcine reproductive and respiratory syndrome virus (PRRSV). Litters were assigned to either play (PLY; n = 5 L) or control (CON; n = 4 L) treatments at birth. In PLY, play was promoted with extra space and enrichment items for three hours daily from five days of age (doa). At weaning (25 ± 2 doa; mean ± SD), 28 pigs (14/treatment) were selected for a disease challenge, based on weight, sex, and sow. The pigs were transported to a disease containment facility and at 43 ± 2 doa (day 0 post-inoculation, DPI) inoculated with PRRSV. Skin lesions, blood, rectal temperature, clinical signs, body weight, and behaviour were collected pre- and post-inoculation. Play opportunities for PLY continued every other day until euthanasia of all pigs at 65 ± 2 doa (22 DPI). PLY pigs exhibited fewer skin lesions following transport and throughout the infection compared to CON. Although the viral load did not differ between treatments, PLY pigs had a lower probability of experiencing moderate and severe respiratory distress, with a shorter duration. PLY also performed better throughout the infection, showing higher ADG and greater feed efficiency. The immune response differed as well. PLY pigs had fewer monocytes on 8 DPI than CON, with levels returning to baseline by 21 DPI, whereas CON levels exceeded baseline. Regardless of day of infection, lymphocyte counts tended to be lower in PLY than in CON, and white blood cells and neutrophils were also lower, but only in slow-growing pigs. PLY pigs continued to play during the infection, demonstrating less sickness behaviour and emphasizing the rewarding properties of play. Results suggest that PLY pigs were less affected by PRRSV and developed increased resilience to PRRSV compared to CON. This study demonstrates that rearing pigs in an environment supporting positive experiences through provision of play opportunities can enhance resilience against common modern production challenges, underscoring the value of positive welfare in intensive pig farming.

Comparative transcatheter occlusion of patent ductus arteriosus: multicenter collaborative study across pediatric and veterinary cardiology centers.

INTRODUCTION/OBJECTIVE: Transcatheter therapeutics have revolutionized treatment of patent ductus arteriosus (PDA). Greater understanding of corrective interventions across species can advance best practices, protocols, and outcomes while minimizing adverse events. The objective of this study was to describe characteristics and outcomes in children and dogs undergoing transcatheter PDA occlusion. ANIMALS, MATERIALS AND METHODS: This was a multicenter, retrospective cohort study from two pediatric and three veterinary centers. Demographics, procedural characteristics, and outcomes were assessed. RESULTS: Data included 202 children and 106 dogs treated from July 2019 to June 2021. Forty-five (23%) children and 19 (18%) dogs had congestive heart failure prior to catheterization. Transvenous and transarterial approaches for deployment were most used in children and dogs, respectively. All children had percutaneous vascular access compared to 17 (16%) dogs. Intraprocedural anticoagulation was standard for children (100% of 165 reported), but not for dogs (2/103). The median (interquartile range) pulmonary ostium diameter in children was 2.2 mm (1.5-3.0 mm) and 3.0 mm (2.0-4.2 mm) in dogs when all body sizes were considered (P<0.001). Amplatzer™ Duct Occluder was most commonly used in children (64/202, 32%); the Amplatz® Canine Duct Occluder was used in dogs (96/100, 96%). Closure was manual compression in all children, whereas vessel ligation was most used in dogs (74/104, 73%). Successful device deployment was achieved in 197 (98%) children and 98 (93%) dogs (P=0.03). Major reasons for failure included device embolization in six (2.9%) children and PDA morphology concerns in four (3.8%) dogs. CONCLUSIONS: Transcatheter PDA occlusion is successful in children and dogs. Study data might be useful for optimizing transcatheter therapeutics and animal models for interventional cardiology.

Osteochondral regeneration with a tri-layered biomimetic resorbable scaffold: In vivo study in a sheep model up to 12 months of follow-up.

The treatment of osteochondral joint lesions requires the regeneration of both articular cartilage and subchondral bone tissue. Scaffold-based strategies aimed at mimicking the native osteochondral structure have been explored with mixed results. The aim of this study was to evaluate the regenerative potential of a tri-layered osteochondral cell-free scaffold in a large animal model at both 6 and 12 months of follow-up. Bilateral critical-sized osteochondral defects were created in 22 sheep. One defect was filled with the scaffold, whereas the contralateral was left empty. The repair tissue quality was evaluated at 6 and 12 months of follow-up in terms of macroscopic appearance, histology, trabecular bone formation, and inflammation grade. The mean global ICRS II score in the scaffold and control groups was 41 ± 11 vs 30 ± 6 at 6 months (p = 0.004) and 54 ± 13 vs 37 ± 11 at 12 months (p = 0.002), respectively. A higher percentage of bone was found in the treatment group compared to controls both at 6 (BV/TV 48.8 ± 8.6 % vs 37.4 ± 9.5 %, respectively; p < 0.001) and 12 months (BV/TV 51.8 ± 8.8 % vs 42.1 ± 12.6 %, respectively; p = 0.023). No significant levels of inflammation were seen. These results demonstrated the scaffold safety and potential to regenerate both cartilage and subchondral tissues in a large animal model of knee osteochondral lesions.

The effect of animal-assisted intervention on fear in children in the emergency department: A randomized controlled trial.

AIM: This study aimed to determine the effect of animal-assisted intervention on the fears of hospitalized children in the emergency department (ED). MATERIALS AND METHODS: The randomized controlled trial was conducted between April and June 2023 in the Central Black Sea Region of Turkiye. The study included 70 children aged 5 to 7 years old (the study group was 35, and the control group was 35). The study and control groups were randomly assigned to strata using simple randomization. While goldfish were used for animal-assisted intervention in the study group, routine care was continued in the control group. The "Child Fear Scale" and "The Scale of Children's Fear of Nursing Interventions and Instruments Used in Hospital" were used as data collection tools. RESULTS: The mean score of the fear scale in the post-test scores of the study group children was significantly lower than the control group (p < 0.001). After the animal-assisted intervention, the mean fear scores of the children in the care study group toward nursing interventions and the materials used decreased significantly (p < 0.001). Furthermore, when the two groups were compared, the difference between the post-test scores was not significant (p > 0.05). CONCLUSION: Animal-assisted intervention was determined to be effective in decreasing the fear levels of the children in the study group. PRACTICE IMPLICATIONS: During hospitalization in the emergency department, methods appropriate to the child's developmental level and animal-assisted interventions were found to be effective in reducing children's fear levels.

In vitro 3D skin culture and its sustainability in toxicology: a narrative review.

In current toxicological research, 2D cell cultures and animal models are well- accepted and commonly employed methods. However, these approaches have many drawbacks and are distant from the actual environment in human. To embrace this, great efforts have been made to provide alternative methods for non-animal skin models in toxicology studies with the need for more mechanistically informative methods. This review focuses on the current state of knowledge regarding the in vitro 3D skin model methods, with different functional states that correspond to the sustainability in the field of toxicology testing. We discuss existing toxicology testing methods using in vitro 3D skin models which provide a better understanding of the testing requirements that are needed. The challenges and future landscape in using the in vitro 3D skin models in toxicology testing are also discussed. We are confident that the in vitro 3D skin models application may become an important tool in toxicology in the context of risk assessment.

Aflatoxin B1 in compound feed and feed ingredients from Khyber Pakhtunkhwa.

A large-scale study was conducted to explore AFB1 contamination in feed samples using Thin Layer Chromatography, following an AOAC protocol. Samples were identified which were not compliant with the maximum limits for AFB1 as regulated in the United States and Pakistan. Of a total of 923 samples, 51 samples (5.5%) were not compliant according to Pakistan and 267 (28.9%) were not compliant with US-FDA standards. The overall prevalence of non-compliant samples of compound feed was 26.2% (n = 117) according to US-FDA standards, while none of the samples were non-compliant according to Pakistan standards. Among feed ingredients, the overall prevalence of non-compliant samples was 10.7% (n = 51) and 31.4% (n = 150) according to Pakistan and USFDA standards, respectively. Non-compliant feed with respect to AFB1 contamination was highly prevalent in Khyber Pakhtunkhwa, posing a serious threat to production performance and animals health.

Prevalence of discospondylitis and association with congenital vertebral body malformations in English and French bulldogs.

BACKGROUND: Limited current information exists regarding discospondylitis within breeds commonly affected by congenital vertebral body malformations. HYPOTHESIS/OBJECTIVES: Report the prevalence of discospondylitis in English and French bulldogs and investigate for possible associations of discospondylitis with congenital vertebral body malformations. ANIMALS: 108 client-owned dogs. METHODS: Retrospective multi-institutional study between June 2010 and 2020. Cases with a diagnosis of discospondylitis on computed tomography (CT) or magnetic resonance imaging (MRI) and complete medical records included. Signalment, discospondylitis location, presence of congenital vertebral body malformations, and the site of maximal kyphosis were recorded. RESULTS: The prevalence of discospondylitis was 3.4 (1.6-6.7, 95% confidence interval [CI]) times higher in French bulldogs (P < .001) and 4.3 (1.7-9.8, 95% CI) times higher in English bulldogs (<.001), compared with the overall hospital cohort. One or more vertebral malformations were present in 12 French bulldogs (92.3%), 6 English bulldogs (75.0%), and 1 "other" breed dog (1.1%). Discospondylitis was diagnosed adjacent to congenital vertebral body malformations in 12 (80%) intervertebral discs in French bulldogs and 5 (50%) intervertebral discs in English bulldogs. The median age at presentation was significantly younger in French bulldogs (1.1 years; range, 0.5-9.2 years) and English bulldogs (1.0 years; range, 0.4-7.0 years), compared with "other" breed dogs (7.3 years; range, 0.3-14.0 years; both P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Congenital vertebral body malformations were frequently associated with discospondylitis in French and English bulldogs, with clinical signs commonly encountered at a significantly younger age.

Animal-assisted services for adults with acquired neurogenic communication disorders: A scoping review.

BACKGROUND: There is increasing interest in the incorporation of animal-assisted services (AAS) in therapy for adults with acquired neurogenic communication disorders. AAS have the potential to enhance speech and language therapy engagement and outcomes. However, a greater understanding of the nature and potential benefits of these interventions is needed. AIMS: To describe the existing evidence for the incorporation of AAS in therapy with adults with acquired neurogenic communication disorders and to identify areas for future research. METHODS & PROCEDURES: A scoping review was conducted and reported in alignment with the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist extension for scoping reviews (PRISMA-ScR). Seven databases (PubMed, Embase, CINAHL, PsycINFO, Cochrane, Scopus, Web of Science) and grey literature (Google) were searched. Two reviewers independently screened titles, abstracts and full texts against eligibility criteria using Covidence software. The Template for Intervention Description and Replication (TIDieR) checklist guided extraction of intervention data. MAIN CONTRIBUTIONS: A total of 17 studies with adults with aphasia, apraxia of speech and cognitive-communication disorders were included. While terminology varied, most interventions met the definition of animal-assisted therapy or animal-assisted activity and used therapy dogs. Across studies, a range of outcomes were targeted, and positive benefits were reported for participant mood, emotions, motivation and satisfaction. There were mixed, but mostly positive, benefits on social behaviour, communication and participation. CONCLUSIONS & IMPLICATIONS: AAS has been incorporated in therapy for adults with acquired neurogenic communication disorders, predominately with people with dementia. Across studies, communication impairments and AAS interventions were insufficiently or inconsistently described. Improved reporting would assist understanding of the potential benefits of AAS as an adjunct therapy. A quality appraisal of existing studies, and meta-analysis of findings, is needed to draw conclusions about the effectiveness of AAS as a complementary therapy for people with acquired neurogenic communication disorders. WHAT THIS PAPER ADDS: What is already known on this subject There is increasing interest and research in AAS as an adjunct to traditional speech and language therapy. Several clinical populations have been shown to benefit from the incorporation of AAS as a complementary therapy approach, including adults with acquired neurogenic communication disorders. To date there has not been a comprehensive review of literature in the area. What this paper adds to the existing knowledge This review aimed to describe what is known about AAS as an adjunct intervention for adults with acquired neurogenic communication disorders. A total of 17 studies were identified, the majority conducted with people living with dementia. Overall, consistent positive benefits of AAS were reported on participant mood, positive emotions, motivation, and satisfaction. There were mixed, but mostly positive, benefits of AAS on social behaviour, including both verbal and non-verbal communication outcomes, and participation. What are the practical and clinical implications of this work? These results suggest a potential therapeutic benefit for the inclusion of AAS into traditional modalities used by speech-language therapists with people with acquired neurogenic communication disorders. However, clinicians should view these findings with caution. Studies were often insufficiently or inconsistently reported, and a quality appraisal and meta-analysis of existing studies would be needed to draw clear conclusions on the effectiveness of AAS as a complementary approach for people with acquired neurogenic communication disorders.

Multi-loaded PLGA microspheres as neuroretinal therapy in a chronic glaucoma animal model.

This work focused on the co-encapsulation and simultaneous co-delivery of three different neuroprotective drugs in PLGA (poly(lactic-co-glycolic acid) microspheres for the treatment of glaucoma. For formulation optimization, dexamethasone (anti-inflammatory) and ursodeoxycholic acid (anti-apoptotic) were co-loaded by the solid-in-oil-in-water emulsion solvent extraction-evaporation technique as a first step. The incorporation of a water-soluble co-solvent (ethanol) and different amounts of dexamethasone resulted critical for the encapsulation of the neuroprotective agents and their initial release. The optimized formulation was obtained with 60 mg of dexamethasone and using an 80:20 dichloromethane:ethanol ratio. In the second step in the microencapsulation process, the incorporation of the glial cell line-derived neurotrophic factor (GDNF) was performed. The final prototype showed encapsulation efficiencies for each component above 50% with suitable properties for long-term application for at least 3 months. Physicochemical studies were performed by SEM, TEM, DSC, XRD, and gas chromatography. The evaluation of the kinetic release by the Gallagher-Corrigan analysis with Gorrasi correction helped to understand the influence of the co-microencapsulation on the delivery of the different actives from the optimized formulation. The final prototype was tested in a chronic glaucoma animal model. Rats received two intravitreal injections of the neuroprotective treatment within a 24-week follow-up study. The proposed formulation improved retinal ganglion cell (RGC) functionality examined by electroretinography. Also, it was able to maintain a neuroretinal thickness similar to that of healthy animals scanned by in vivo optical coherence tomography, and a higher RGC count on histology compared to glaucomatous animals at the end of the study.

How life events may confer vulnerability to addiction: the role of epigenetics.

Substance use disorder (SUD) represents a large and growing global health problem. Despite the strong addictive potency of drugs of abuse, only a minority of those exposed develop SUDs. While certain life experiences (e.g., childhood trauma) may increase subsequent vulnerability to SUDs, mechanisms underlying these effects are not yet well understood. Given the chronic and relapsing nature of SUDs, and the length of time that can elapse between prior life events and subsequent drug exposure, changes in SUD vulnerability almost certainly involve long-term epigenetic dysregulation. To validate this idea, functional effects of specific epigenetic modifications in brain regions mediating reinforcement learning (e.g., nucleus accumbens, prefrontal cortex) have been investigated in a variety of animal models of SUDs. In addition, the effects of epigenetic modifications produced by prior life experiences on subsequent SUD vulnerability have been studied, but mostly in a correlational manner. Here, we review how epigenetic mechanisms impact SUD-related behavior in animal models and summarize our understanding of the relationships among life experiences, epigenetic regulation, and future vulnerability to SUDs. Despite variations in study design, epigenetic modifications that most consistently affect SUD-related behavior are those that produce predominantly unidirectional effects on gene regulation, such as DNA methylation and histone phosphorylation. Evidence explicitly linking environmentally induced epigenetic modifications to subsequent SUD-related behavior is surprisingly sparse. We conclude by offering several directions for future research to begin to address this critical research gap.

The glutamatergic system in the development of stress-induced depression.

Major depression is one of the most prevalent neuropsychological disorders and affects millions worldwide. In response, the monoaminergic system has been proposed to be one of the major focuses for conventional drugs in the treatment of depression, such as selective serotonin reuptake inhibitor (SSRI). Meanwhile, accumulating evidence suggests a paradigm shift from the monoamine system towards the glutamatergic system (Gerard Sanacora, Giulia Treccani, and Maurizio Popoli 2012) due to the long onset of the monoamine system targeting anti-depressant drugs. Both clinical and pre-clinical data support that glutamatergic system dysfunction were involved in the development of depression. Furthermore, therapeutic approaches that manipulating neuronal activity and N-methyl-D-aspartic acid (NMDA) receptor antagonist were shown to have profound effects in the treatment of depression. Here, I systematically reviewed our current understanding of the involvement of glutamatergic system dysregulation in the development of depression, which potentially could provide the mechanistic basis for future treatment development.

Plant-based diets-impacts of consumption of little or no animal-source foods on human health.

The world, in 2024, faces both climate and biodiversity crises, and the food system does contribute significantly to these crises. For some, the solution is simple - intakes of animal source foods (ASFs) should be considerably reduced, and consumption of plant-source foods (PSFs) should be greatly increased. Advocates for such a dietary transformation express confidence that plant-based diets will not only benefit planetary health, but will provide nutrient adequacy for all, and will also result in considerable protection from chronic non-communicable diseases (NCDs). However, as described in this perspective, the dramatic reductions in ASFs, entailed by many plant-based diets, will worsen already prevalent micronutrient and protein deficiencies. The protections provided by plant-based diets against NCDs appear to be more strongly associated with reduced intakes of calories and salt, and increased intakes of fruit, vegetables, nuts and whole grains, rather than with reduced intakes of ASFs. Any possible absolute adverse effects of red and processed meat consumption on NCDs are very small and uncertain. Other ASFs either appear to have no impact on NCDs (poultry meat and eggs), or are associated with protections against obesity, cardiovascular events, brain disorders and some cancers (seafood and dairy). Rigorous randomized controlled trials of all newly proposed environmentally-protective plant-based diets are required, so as to provide clear-cut evidence of micronutrient and protein adequacy, with or without, supplementation, fortification and/or biofortification. In the meantime, dietary guidelines should advise moderating excessive consumption, rather than substantially limiting or excluding ASFs from the human diet.