Search Results (1,381)

This study aimed to compare the performance of three hydroxyapatite–β-tricalcium phosphate (HA–β-TCP) collagen composite grafts in a canine model for extraction socket preservation. Eight mongrel dogs underwent atraumatic bilateral mandibular premolar extraction, and sockets were randomly grafted with HBC28 (20% high-crystalline HA, 80% β-TCP bovine collagen), HBC37 (30% HA, 70% β-TCP, bovine collagen), or HPC64 (60% HA, 40% β-TCP, porcine collagen). Grafts differed in their HA–β-TCP ratio and collagen origin and content. Animals were sacrificed at 4 and 12 weeks, and the healing sites were evaluated using micro-computed tomography (micro-CT) and histological analysis. At 12 weeks, all groups showed good socket maintenance with comparable new bone formation. However, histological analysis revealed that HBC28 had significantly higher residual graft volume, while HPC64 demonstrated more extensive graft resorption. Histomorphometric analysis confirmed these findings, with statistically significant differences in residual graft area and bone volume fraction. No inflammatory response or adverse tissue reactions were observed in any group. These results suggest that all three HA–β-TCP collagen composites are biocompatible and suitable for socket preservation, with varying resorption kinetics influenced by graft composition. Selection of graft material may thus be guided by the desired rate of replacement by new bone. Full article

Consumer interest in vegetarian, ethical, and clean-label foods is reviving the use of plant-derived milk coagulants. Cardosins from Cynara cardunculus (“thistle”) are aspartic proteases with strong clotting activity, yet their technological impact in cheese remains under-explored. This study compared a commercial thistle extract (PC) with traditional bovine rennet rich in chymosin (AC) during manufacture and 60-day ripening of Caciotta cheese. Classical compositional assays (ripening index, texture profile, color, solubility) were integrated with scanning electron microscopy, three-dimensional surface reconstruction, and descriptive sensory analysis. AC cheeses displayed slower but sustained proteolysis, yielding a higher and more linear ripening index, softer body, greater solubility, and brighter, more yellow appearance. Imaging revealed a continuous protein matrix with uniformly distributed, larger pores, consistent with a dairy-like sensory profile dominated by milky and umami notes. Conversely, PC cheeses underwent rapid early proteolysis that plateaued, producing firmer, chewier curds with lower solubility and darker color. Micrographs showed a fragmented matrix with smaller, heterogeneous pores; sensory evaluation highlighted vegetal, bitter, and astringent attributes. The data demonstrate that thistle coagulant can successfully replace animal rennet but generates cheeses with distinct structural and sensory fingerprints. The optimization of process parameters is therefore required when targeting specific product styles. Full article

Nipah virus (NiV) is a highly pathogenic bat-borne zoonotic pathogen that poses a significant threat to human and animal health, with fatality rates exceeding 70% in some outbreaks. Despite its significant public health impact, there are currently no licensed vaccines or specific therapeutics available. Various virological tools—such as reverse genetics systems, replicon particles, VSV-based pseudoviruses, and recombinant Cedar virus chimeras—have been widely used to study the molecular mechanisms of NiV and to support vaccine development. Building upon these platforms, we developed a replication-competent recombinant vesicular stomatitis virus (rVSVΔG-eGFP-NiV_BD F/G) expressing NiV attachment (G) and fusion (F) glycoproteins. This recombinant virus serves as a valuable tool for investigating NiV entry mechanisms, cellular tropism, and immunogenicity. The virus was generated by replacing the VSV G protein with NiV F/G through reverse genetics, and protein incorporation was confirmed via immunofluorescence and electron microscopy. In vitro, the virus exhibited robust replication, characteristic cell tropism, and high viral titers in multiple cell lines. Neutralization assays showed that monoclonal antibodies HENV-26 and HENV-32 effectively neutralized the recombinant virus. Furthermore, immunization of golden hamsters with inactivated rVSVΔG-eGFP-NiV_BD F/G induced potent neutralizing antibody responses, demonstrating its robust immunogenicity. These findings highlight rVSVΔG-eGFP-NiV_BD F/G as an effective platform for NiV research and vaccine development. Full article

Cardiac arrhythmias remain a major source of morbidity and mortality, often stemming from molecular and structural abnormalities that are insufficiently addressed by current pharmacologic and interventional therapies. Gene therapy has emerged as a transformative approach, offering precise and durable interventions that directly target the arrhythmogenic substrate. Across the spectrum of inherited and acquired arrhythmias—including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, atrial fibrillation, and post-infarction ventricular tachycardia—gene-based strategies such as allele-specific silencing, gene replacement, CRISPR-mediated editing, and suppression-and-replacement constructs are showing growing translational potential. Advances in delivery platforms, including cardiotropic viral vectors, lipid nanoparticle-encapsulated mRNA, and non-viral reprogramming tools, have further enhanced the specificity and safety of these approaches. Additionally, innovative applications such as biological pacemaker development and mutation-agnostic therapies underscore the versatility of genetic modulation. Nonetheless, significant challenges remain, including vector tropism, immune responses, payload limitations, and the translational gap between preclinical models and human electrophysiology. Integration of patient-derived cardiomyocytes, computational simulations, and large-animal studies is expected to accelerate clinical translation. This review provides a comprehensive synthesis of the mechanistic rationale, therapeutic strategies, delivery platforms, and translational frontiers of gene therapy for cardiac arrhythmias. Full article

The replacement of animal fat with unsaturated lipid sources in processed meats enhances nutritional value but introduces challenges regarding oxidative stability and sensory acceptability. In this study, the effects of replacing pork back fat with pre-emulsified walnut, linseed, or algal oils on the proximate composition, fatty acid profile, nutritional indices, lipid oxidation, and sensory properties of chicken frankfurters were investigated. Four formulations were prepared: a control group (25% pork fat) and three groups that were completely reformulated using oil emulsions (ratio inulin/water/oil 1:2:1). The fat substitute significantly reduced total fat, SFA, cholesterol (up to 30%), and calorie density, while Ʃn-3 fatty acids were enriched (p < 0.05). The linseed oil samples had the highest levels of α-linolenic acid (47.53%), while the algal oil had the highest levels of eicosapentaenoic acid (10.98%) and docosahexaenoic acid (64.73%) and the most favourable Ʃn-6/Ʃn-3 ratio (p < 0.05). All reformulated groups showed significantly improved atherogenic and thrombogenic indices and increased hypocholesterolaemic/hypercholesterolaemic ratios, which reached 17.43 in the algal oil samples (p < 0.05). Lipid oxidation was increased in the linseed and algal oil treatments, with the walnut oil group showing moderate TBARS levels and minimal accumulation of secondary oxidation products. Principal component analysis revealed that walnut oil offered the most balanced compromise between nutritional improvement, oxidative stability and sensory acceptability. These findings support a healthier reformulation of meat products by identifying oil-based fat substitutes that improve nutritional value without compromising sensory quality, which is beneficial for both research and industry. Full article

Thyroid hormones (thyroxine, T₄, and triiodothyronine, T₃) are indispensable for sustaining vertebrate life, and their deficiency gives rise to a wide range of symptoms characteristic of hypothyroidism, affecting 5–10% of the world’s population. The precursor for thyroid hormone synthesis is thyroglobulin (Tg), a large iodoglycoprotein consisting of upstream regions I-II-III (responsible for synthesis of most T₄) and the C-terminal CholinEsterase-Like (ChEL) domain (responsible for synthesis of most T₃, which can also be generated extrathyroidally by T₄ deiodination). Using CRISPR/Cas9-mediated mutagenesis, we engineered a knock-in of secretory ChEL into the endogenous TG locus. Secretory ChEL acquires Golgi-type glycans and is properly delivered to the thyroid follicle lumen, where T₃ is first formed. Homozygous knock-in mice are capable of thyroidal T₃ synthesis but largely incompetent for T₄ synthesis such that T₄-to-T₃ conversion contributes little. Instead, T₃ production is regulated thyroidally by thyrotropin (TSH). Compared to cog/cog mice with conventional hypothyroidism (low serum T₄ and T₃), the body size of ChEL-knock-in mice is larger; although, these animals with profound T₄ deficiency did exhibit a marked elevation of serum TSH and a large goiter, despite normal circulating T₃ levels. ChEL knock-in mice exhibited a normal expression of hepatic markers of thyroid hormone action but impaired locomotor activities and increased anxiety-like behavior, highlighting tissue-specific differences in T₃ versus T₄ action, reflecting key considerations in patients receiving thyroid hormone replacement therapy. Full article

Gaucher disease (GD) is an autosomal recessive disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Although enzyme replacement therapy (ERT) remains the standard of care for non-neuropathic GD patients, its high cost significantly limits accessibility. To enhance production efficiency, we developed a lentiviral system encoding a codon-optimized GCase gene driven by the human elongation factor 1a (hEF1α) promoter for stable production in human cell lines. A functional lentiviral vector, LV_EF1α_GBA_Opt, was generated at a titer of 7.88 × 10⁸ LV particles/mL as determined by qPCR. Six transduction cycles were performed at a multiplicity of infection of 30–50. The transduced heterogeneous human cell population showed GCase-specific activity of 307.5 ± 53.49 nmol/mg protein/h, which represents a 3.21-fold increase compared to wild-type 293FT cells (95.58 ± 16.5 nmol/mg protein/h). Following single-cell cloning, two clones showed specific activity of 763.8 ± 135.1 and 752.0 ± 152.1 nmol/mg/h (clones 15 and 16, respectively). These results show that codon optimization, a lentiviral delivery system, and clonal selection together enable the establishment of stable human cell lines capable of producing high levels of biologically active, synthetic recombinant GCase in vitro. Further studies are warranted for the functional validation in GD patient-derived fibroblasts and animal models. Full article

Long-term storage may induce lipid oxidation in brown rice and impact its utilization in animal diets. One-day-old male Ross 308 broiler chickens (with an initial body weight of 20 g) were randomly divided into three groups: corn-based diet (Corn), fresh brown rice-based diet (BR1) and stored brown rice-based diet (BR6), with 8 replicates of 10 birds per pen, in a 42-day feeding trial. The results showed that lipid oxidation indexes increased and fatty acid composition changed significantly in BR6 (p < 0.05). The dietary replacement of corn with brown rice showed no effects on growth performance of broilers (p > 0.05). However, palmitic acid and oleic acid increased, and stearic acid, linoleic acid and docosadienoic acid decreased in the broiler breast muscle of the BR1 and BR6 groups (p < 0.05). Ileum antioxidant enzyme activities increased in the BR1 and BR6 groups compared to the Corn group (p < 0.05), and the activities of α-amylase, trypsin, chymotrypsin and lipase decreased in the BR6 group compared to the BR1 and Corn groups (p < 0.05). Also, compared to the BR1 group, the overall expression of metabolites involved in drug metabolism—cytochrome P450, GnRH secretion and the estrogen signaling pathway in broiler ileum were down-regulated in the BR6 group (p < 0.05). In conclusion, the lipid oxidation of stored brown rice decreased digestive enzyme activities and changed metabolic characteristics in the ileum of broilers. While replacing corn with brown rice did not affect broiler growth performance, it reduced the contents of unsaturated and essential fatty acids in breast muscle and enhanced the ileal antioxidant functions of broilers. Full article

Mycotoxins are secondary metabolites produced by various fungal species that can contaminate food and feed, posing significant risks to human and animal health. In aquaculture, the replacement of fishmeal with alternative protein sources has increased the risk of mycotoxin contamination, becoming a major challenge in fish feed production. Current data highlights that fish are exposed not only to common mycotoxins but also to emerging ones, raising concerns about human exposure through fish consumption. In this review, we draw attention to the toxicity data of key emerging mycotoxins from Fusarium (enniatins, ENNs; beauvericin, BEA) and Alternaria (alternariol monomethyl ether, AME; alternariol, AOH), their occurrence in aquafeeds and in commercially relevant fish species in Europe, and potential biocontrol approaches to prevent/mitigate contaminations. From the present review, it emerged that these mycotoxins exhibit in vitro cytotoxic properties. Their prevalence and concentrations vary widely both among aquafeeds, depending on the sample’s origin, and among fish species. Biocontrol approaches using microorganisms or natural compounds show promise as sustainable solutions to limit contamination. However, further research is essential to address data gaps and to allow for a proper risk assessment and, if necessary, the implementation of effective management measures. Full article

Transmembrane protein 43 (TMEM43 or LUMA) encodes a highly conserved protein found in the nuclear and endoplasmic reticulum membranes of many cell types and the intercalated discs and adherens junctions of cardiac myocytes. TMEM43 is involved in facilitating intra/extracellular signal transduction to the nucleus via the linker of the nucleoskeleton and cytoskeleton complex. Genetic mutations may result in reduced TMEM43 expression and altered TMEM43 protein cellular localization, resulting in impaired cell polarization, intracellular force transmission, and cell–cell connections. The p.S358L mutation causes arrhythmogenic right ventricular cardiomyopathy type-5 and is associated with increased absorption of lipids, fatty acids, and cholesterol in the mouse small intestine, which may promote fibro-fatty replacement of cardiac myocytes. Mutations (p.E85K and p.I91V) have been identified in patients with Emery–Dreifuss Muscular Dystrophy-related myopathies. Other mutations also lead to auditory neuropathy spectrum disorder-associated hearing loss and have a negative association with cancer progression and tumor cell survival. This review explores the pathogenesis of TMEM43 mutation-associated diseases in humans, highlighting animal and in vitro studies that describe the molecular details of disease processes and clinical, histologic, and molecular manifestations. Additionally, we discuss TMEM43 expression-related conditions and how each disease may progress to severe and life-threatening states. Full article

Two trials evaluated the effects of dietary protease inclusion in weaned piglets fed diets with or without crude protein (CP) reduction, focusing on performance, intestinal health, and amino acid digestibility. In Trial I, 270 piglets (21–63 days) received six treatments: control (PC), PC with 100 g/ton protease A (PC+A), CP reduced by 1.0% (NC1) or 1.5% (NC1.5), NC1.5 with 50 g/ton protease A (NC1.5+A), and NC1.5 with 50 g/ton protease B (NC1.5+B). PC+A improved weight gain, feed intake, and feed conversion compared with NC1.5+A. The incidence of diarrhea was reduced in animals fed protease-supplemented diets (PC+A, NC1.5+A and NC1.5+B). PC had greater ileal villus height than NC1.5+B, and PC+A showed a higher jejunal villus-to-crypt ratio than reduced CP groups. NC1.5+B increased jejunal expression of IL-6, TNF-α, and haptoglobin. In Trial II, 12 ileal-cannulated piglets received diets with or without protease A. Protease improved the standardized ileal digestibility (SID) of methionine+cysteine and tryptophan but reduced the SID of glycine and proline. While protease supplementation can improve some amino acids (Met+Cys and Thr) protein digestibility, our findings suggest it cannot fully replace careful amino acid balancing in CP-reduced diets. However, protease-supplemented diets were associated with improved intestinal morphometry and a reduced incidence of diarrhea. Full article

Mitochondria are currently of great interest to scientists. The role of mitochondrial DNA (mtDNA) mutations has been proven in the genesis of more than 200 pathologies, which are called mitochondrial disorders. Therefore, the study of mitochondria and mitochondrial DNA is of great interest not only for understanding cell biology but also for the treatment and prevention of many mitochondria-related pathologies. There are two main trends of mitochondrial therapy: mitochondrial replacement therapy (MRT) and mitochondrial transplantation therapy (MTT). Also, there are two main categories of MRT based on the source of mitochondria. The heterologous approach includes the following methods: pronuclear transfer technique (PNT), maternal spindle transfer (MST), Polar body genome transfer (PBT) and germinal vesicle transfer (GVT). An alternative approach is the autologous method. One promising autologous technique was the autologous germline mitochondrial energy transfer (AUGMENT), which involved isolating oogonial precursor cells from the patient, extracting their mitochondria, and then injecting them during ICSI. Transmission of defective mtDNA to the next generation can also be prevented by using these approaches. The development of a healthy child, free from genetic disorders, and the prevention of the occurrence of lethal mitochondrial disorders are the main tasks of this method. However, a number of moral, social, and cultural objections have restricted its exploration, since humanity first encountered the appearance of a three-parent baby. Therefore, this review summarizes the causes of mitochondrial diseases, the various methods involved in MRT and the results of their application. In addition, a new technology, mitochondrial transplantation therapy (MTT), is currently being actively studied. MTT is an innovative approach that involves the introduction of healthy mitochondria into damaged tissues, leading to the replacement of defective mitochondria and the restoration of their function. This technology is being actively studied in animals, but there are also reports of its use in humans. A bibliographic review in PubMed and Web of Science databases and a search for relevant clinical trials and news articles were performed. A total of 81 publications were selected for analysis. Methods of MRT procedures were reviewed, their risks described, and the results of their use presented. Results of animal studies of the MTT procedure and attempts to apply this therapy in humans were reviewed. MRT is an effective way to minimize the risk of transmission of mtDNA-related diseases, but it does not eliminate it completely. There is a need for global legal regulation of MRT. MTT is a new and promising method of treating damaged tissues by injecting the body’s own mitochondria. The considered methods are extremely good in theory, but their clinical application in humans and the success of such therapy remain a question for further study. Full article

This study aimed to explore Markov decision methods in order to solve the problem of dairy cow replacement, adding the special characteristics of two types of abortions due to different sanitary reasons that influence the economic, production, and reproduction performance of these animals. The model was successfully validated against other models published in the literature. Python code v.3.13 was used to solve the problem and to ease future extensions with the inclusion of new variables. The results constitute tools that allow the veterinarian to explore more realistic scenarios by running a Markov simulation model that avoids the complexities leading to the problem of dimensionality in dynamic optimization models. In our study, the economic value of the herd considering RA and NLA abortions shows that the maximum net benefit is USD 178.77 per cow, and non-pregnant cows are slaughtered upon reaching six months of lactation, a value that is within the range of values reported by the literature that we have identified. At the optimum, the replacement model extended with abortion generates a difference of USD 0.69 per cow per month compared to the model that does not include the special abortion features. The changes in the net present value of each cow according to the month of culling depend on the variability of milk income and slaughter value and heifers’ replacement values, suggesting that any measure that seeks to improve the economic benefit of dairy cows should take greater account of these variables. Full article

This study evaluated the effect of the replacement of AGPs by a probiotic in diets for piglets in the nursery stage. The dietary treatments were as follows: CON-basal diet (BD); ANT-BD+antibiotic; and PRO-BD+probiotic. From d 35–42 of age, the piglets that received ANT-BD showed a higher average daily weight gain (ADWG) (p = 0.0296), followed by those that received PRO and the control. The average daily feed intake (ADFI) was higher (p = 0.0224) for PRO- and ANT-fed piglets when compared to CON. From d 43–56, the ADWG was the highest (p = 0.0207) in piglets fed ANT. The ADFI was also higher (p = 0.0258) in ANT and PRO. Final body weight (BW) was also influenced (p = 0.0291), whereas ANT-fed animals, followed by PRO, showed a higher BW compared to CON. For overall nursery performance, PRO showed the highest (p = 0.046) ADFI compared to all other treatments. Piglets fed PRO and ANT also showed the highest (p = 0.05) end weights. There was no significant difference in the fecal concentration of Escherichia coli. Concentrations for the sugar absorption test were higher on days 34 and 49 (p < 0.05). The inclusion of B. subtilis DSM 32315 does not replace the use of antibiotics with the same level of results but can provide benefits compared to diets without the use of antibiotics. Full article

Many viruses mutate rapidly to adapt to host defenses, and for some of these viruses, the result is long-term infection in individual hosts. The work described here examines the infection and long-term maintenance of a newly identified virus, equine parvovirus-hepatitis (EqPV-H), in an individual horse. This description is possible because of a hypervariable region in the capsid gene; sequence variants were tracked by high-throughput sequencing of serum samples taken over a 16-year period. The data support the hypothesis that EqPV-H infection resulted in a sequence variant bottleneck. The continuing infection evolved into a complex viral population showing a pattern of emergence, dominance, and recession with replacement. This is the first temporal description of the capsid gene evolution of EqPV-H in a single animal. Full article