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Background: Animals serve as important models for exploring the pathology, diagnosis, and therapy of different diseases and injuries. While smaller animals are preferred for bulk cohort studies, larger animals offer opportunities to investigate surgical procedures at proportions close to the human situation. Therefore, in a feasibility study, we investigated urethral sphincter deficiency in German landrace gilts and Göttingen minipigs to develop a model of urinary incontinence as a basis for future preclinical studies of incontinence therapies. Urethral sphincter deficiency was induced surgically by transurethral electrocautery and balloon dilatation, and the deficiency was determined by urodynamics after injury and during follow-up. In cryosections, sphincter injury was visualized by histochemistry., Results: Sphincter deficiency was induced in two cohorts and groups of four female Göttingen minipigs each (total n = 20) by two different treatments. One cohort of minipigs showed an initially significant urethral sphincter deficiency (treatment 1; n = 16, p < 0.001). However, spontaneous sphincter regeneration was observed within one to two weeks. The other cohort of minipigs (treatment 2; n = 4) displayed a non-significant reduction of urethral sphincter pressure and an increase in muscle strength over time as well. In contrast, German landrace gilts presented immediately after treatment with significant sphincter deficiency (treatment 1; n = 6, 21%, p < 0.001) and suffered from significant loss of sphincter function for at least five weeks (67%, p < 0.01)., Conclusion: Göttingen minipigs inherit significantly superior sphincter regeneration capacities compared to landrace pigs. This difference may bias preclinical studies in urology and other fields and explain in part seemingly contradictory results from different animal studies., Competing Interests: Declarations. Ethics approval and consent to partcipate: Not applicable. Consento for publication: No human materials used. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The objective of this study was to identify genomic regions and candidate genes associated with productive traits using a total of 37,099 productive records and 6,683 single nucleotide polymorphism (SNP) data obtained from five Great-Grand-Parents (GGP) farms in Landrace. The estimated of heritabilities for days to 105 kg (AGE), average daily gain (ADG), backfat thickness (BF), and eye muscle area (EMA) were 0.49, 0.49, 0.56, and 0.23, respectively. We identified a genetic window that explained 2.05%-2.34% for each trait of the total genetic variance. We observed a clear partitioning of the four traits into two groups, and the most significant genomic region for AGE and ADG were located on the Sus scrofa chromosome (SSC) 1, while BF and EMA were located on SSC 2. We conducted Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), which revealed results in three biological processes, four cellular component, three molecular function, and six KEGG pathway. Significant SNPs can be used as markers for quantitative trait loci (QTL) investigation and genomic selection (GS) for productive traits in Landrace pig., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2024 Korean Society of Animal Science and Technology.)

Breast milk, an indispensable source of immunological and nutrient components, is essential for the growth and development of newborn mammals. MicroRNAs (miRNAs) are present in various tissues and body fluids and are selectively packaged inside exosomes, a type of membrane vesicle. Milk exosomes have potential regulatory effects on the growth, development, and immunity of newborn piglets. To explore the differences in milk exosomes related to the breed and milk type, we isolated exosomes from colostrum and mature milk from domestic Bamei pigs and foreign Landrace pigs by using density gradient centrifugation and then characterized them by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Furthermore, the profiles and functions of miRNAs in the two types of pig milk exosomes were investigated using miRNA-seq and bioinformatics analysis. We identified a total of 1081 known and 2311 novel miRNAs in pig milk exosomes from Bamei and Landrace pigs. These differentially expressed miRNAs (DE-miRNAs) are closely associated with processes such as cell signaling, cell physiology, and immune system development. Functional enrichment analysis showed that DE-miRNA target genes were significantly enriched in endocytosis, the T cell receptor signaling pathway, and the Th17 cell differentiation signaling pathway. The exosomal miRNAs in both the colostrum and mature milk of the two pig species showed significant differences. Based on related signaling pathways, we found that the colostrum of local pig breeds contained more immune-system-development-related miRNAs. This study provides new insights into the possible function of milk exosomal miRNAs in the development of the piglet immune system.

Objective: The study aimed to determine the effect of giving concentrate protein from closed-house (CP-CH) broiler farm waste in rations on the meat quality (physical-chemical) and blood profile of landrace crossbreed pigs., Materials and Methods: The study used a completely randomized design (CRD) with 3 treatments and 4 replications with 12 finisher-phase landrace pigs with an average body weight of 63.42 ± 2.39 kg. The treatments were: A (control): use of 0% CP-CH + 24% CP-152 concentrate; B: 12% CP-CH + 12% CP-152 concentrate; and C: 24% CP-CH + 0% CP-152 concentrate. The research parameters were meat quality (physical-chemical meat) and blood lipid profile [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TGs)]., Results: The results showed that treatment group B obtained physical meat quality (pH, drip loss, cooking loss, and water holding capacity) and meat chemical quality (moisture, protein, fat, and ash content) that were almost the same as the control ( p > 0.05). By administering 24% CP-CH + 0% CP-152 (C) concentrate, there was a significant decrease in the physical and chemical quality of crossbreed landrace pigs ( p < 0.05). Administration of CP-CH at 12%-24% did not affect total cholesterol, HDL, LDL, or blood TGs in landrace-crossbreed pigs., Conclusion: Giving 12% CP-CH (B) obtained meat quality (physical and chemical) almost the same as the control group. Treatment group C significantly reduced the physical and chemical quality of the meat. Administration of CP-CH at 12%-24% did not affect the blood profile of landrace crosses., Competing Interests: There is no conflict of interest between the authors., (Copyright: © Journal of Advanced Veterinary and Animal Research.)

Traditionally, the p -value is the criterion for the cutoff threshold to determine significant markers in genome-wide association studies (GWASs). Choosing the best subset of markers for the best linear unbiased prediction (BLUP) for improved prediction ability (PA) has become an interesting issue. However, when dealing with many traits having the same marker information, the p -values' themselves cannot be used as an obvious solution for having a confidence in GWAS and BLUP. We thus suggest a genomic estimated breeding value-assisted reduction method of the single nucleotide polymorphism (SNP) set (GARS) to address these difficulties. GARS is a BLUP-based SNP set decision presentation. The samples were Landrace pigs and the traits used were back fat thickness (BF) and daily weight gain (DWG). The prediction abilities (PAs) for BF and DWG for the entire SNP set were 0.8 and 0.8, respectively. By using the correlation between genomic estimated breeding values (GEBVs) and phenotypic values, selecting the cutoff threshold in GWAS and the best SNP subsets in BLUP was plausible as defined by GARS method. 6,000 SNPs in BF and 4,000 SNPs in DWG were considered as adequate thresholds. Gene Ontology (GO) analysis using the GARS results of the BF indicated neuron projection development as the notable GO term, whereas for the DWG, the main GO terms were nervous system development and cell adhesion., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Closed-pig line breeding could change the genetic structure at a genome-wide scale because of the selection in a pig breeding population. We investigated the changes in population structure among generations at a genome-wide scale and the selected loci across the genome by comparing the observed and expected allele frequency changes in mycoplasma pneumonia of swine (MPS)-selected pigs. Eight hundred and seventy-four Landrace pigs, selected for MPS resistance without reducing average daily gain over five generations, had 37,299 single nucleotide polymorphisms (SNPs) and were used for genomic analyses. Regarding population structure, individuals in the first generation were the most widely distributed and then converged into a specific group, as they were selected over five generations. For allele frequency changes, 96 and 14 SNPs had higher allele frequency changes than the 99.9% and 99.99% thresholds of the expected changes, respectively. These SNPs were evenly spread across the genome, and a few of these selected regions overlapped with previously detected quantitative trait loci for MPS and immune-related traits. Our results indicated that the considerable changes in allele frequency were identified in many regions across the genome by closed-pig line breeding based on estimated breeding value., (© 2023 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.)

Lower body negative pressure (LBNP) has been implemented as a tool to simulate systemic effects of hypovolemia, understand orthostatic challenges and study G load stress in humans. However, the exact hemodynamic mechanisms of graded LBNP followed by its abrupt release have not been characterized in detail, limiting its potential applications in humans. Here, we set out to investigate the immediate hemodynamic alterations occurring during LBNP in healthy Landrace pigs. Invasive cardiac monitoring via extensive pressure volume loop analysis was carried out during application of incremental LBNP up to life threatening levels from -15 to -45 mmHg as well as during its abrupt release. Three different sealing positions were evaluated. Incremental LBNP consistently induced a preload dependent depression of systemic hemodynamics according to the Frank-Starling mechanism. Overall, the pressure-volume loop progressively shifted leftwards and downwards with increasing LBNP intensity. The abrupt release of LBNP reverted the above-described hemodynamic changes to baseline values within only three respiratory cycles. These data provide quantitative translational insights into hemodynamic mechanisms of incremental and very high levels of LBNP, levels of seal and effect of abrupt release for future human applications, such as countermeasure development for long spaceflight.

Background: Myocardial efficiency should be maintained stable under light-to-moderate stress conditions, but ischemia puts the myocardium at risk for impaired functionality. Additionally, the measurement of such efficiency typically requires invasive heart catheterization and exposure to ionizing radiation. In this work, we aimed to non-invasively assess myocardial power and the resulting efficiency during pharmacological stress testing and ischemia induction. Methods: In a cohort of n = 10 healthy Landrace pigs, dobutamine stress testing was performed, followed by verapamil-induced ischemia alongside cardiac magnetic resonance (CMR) imaging. External myocardial power, internal myocardial power, and myocardial efficiency were assessed non-invasively using geometrical and functional parameters from CMR volumetric as well as blood flow and pressure measurements. Results: External myocardial power significantly increased under dobutamine stress [2.3 (1.6-3.1) W/m 2 vs. 1.3 (1.1-1.6) W/m 2 , p = 0.005] and significantly decreased under verapamil-induced ischemia [0.8 (0.5-0.9) W/m 2 , p = 0.005]. Internal myocardial power [baseline: 5.9 (4.6-8.5) W/m 2 ] was not affected by dobutamine [7.5 (6.9-9.0) W/m 2 , p = 0.241] nor verapamil [5.8 (4.7-8.8) W/m 2 , p = 0.878]. Myocardial efficiency did not change from baseline to dobutamine [21% (15-27) vs. 31% (20-44), p = 0.059] but decreased significantly during verapamil-induced ischemia [10% (8-13), p = 0.005]. Conclusion: In healthy Landrace pigs, dobutamine stress increased external myocardial power, whereas myocardial efficiency was maintained stable. On the contrary, verapamil-induced ischemia substantially decreased external myocardial power and myocardial efficiency. Non-invasive CMR was able to quantify these efficiency losses and might be useful for future clinical studies evaluating the effects of therapeutic interventions on myocardial energetics., Competing Interests: BP reports having received consultancy and lecture honoraria from Bayer Daiichi Sankyo, MSD, Novartis, Sanofi-Aventis, Stealth Peptides, and Vifor Pharma and editor honoraria from the Journal of the American College of Cardiology. SK reports receiving grants from Philips Healthcare and speaker honoraria from Medis. CS and BS are employees of Philips Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Faragli, Alogna, Lee, Zhu, Ghorbani, Lo Muzio, Schnackenburg, Stehning, Kuehne, Post, Goubergrits, Nagel, Pieske, Kelle and Kelm.)

The pig has been increasingly used as a reliable preclinical model for assessing and predicting the in vivo bioavailability of different formulation strategies. Nevertheless, differences in the composition between porcine and human intestinal fluids, may impact on the solubility and dissolution behaviour of drugs, in particular BCS II/IV drugs. Recently, a porcine fasted simulated intestinal fluid (FaSSIFp) was developed to mimic the composition in the lumen of landrace pigs under fasted state conditions. In this work, we present the utilization of FaSSIFp to compare solubility against human FaSSIF & FeSSIF and further combine species specific in vitro testing with in silico predictive modelling. Venetoclax was chosen as a model drug, representing a BCS class IV drug, with a reported clinically significant positive food effect, where bioavailability is increased up to approximately five-fold when administered with a high-fat meal. Biorelevant species specific in vitro testing was a promising tool for integrating in vitro data into in silico models, using FaSSIFp resulted in reliable predictions of the plasma concentration profile in fasted pigs, based on a porcine physiologically based absorption model. The porcine physiologically based absorption model was used to prospectively simulate the impact of food on the bioavailability of venetoclax. The use of luminal solubility estimates in combination with dissolution data for venetoclax, measured in species specific simulated fluids, correctly predict the observed pig plasma concentration profile and food effect. Overall, integrating species specific in vitro - in silico models led to accurate prediction of in vivo absorption of venetoclax in a preclinical stage, which can support guidance in early decisions of drug product development. In addition, the study further demonstrated the utility of the pig model to predict the food effects of venetoclax in humans., (Copyright © 2021. Published by Elsevier B.V.)

Digestive enzyme activity is involved in the regulation of growth performance because digestive enzymes function to improve the feed efficiency by digestion and in turn to modulate the process of nutrient metabolism. The objective of this study was to investigate the differences of the digestive enzyme activities and expression of nutrient transporters in the intestinal tract between Jinhua and Landrace pigs and to explore the potential breed-specificity in digestion and absorption. The pancreas segments and the digesta and mucosa of the duodenum, jejunum, and ileum were collected from 10 Jinhua pigs and Landrace pigs, respectively. The activities of trypsin, chymotrypsin, amylase, maltase, sucrase, and lipase were measured and the expression levels of PepT1 , GLUT2 , SGLT1 , FABP1 , FABP2 , and FABP4 were examined. Results showed that the trypsin activity in the pancreas of Jinhua pigs was higher than that in Landrace pigs, but was lower in the small intestine, except for in the jejunal mucosa. The chymotrypsin activity in the small intestine of Jinhua pigs was higher than that in Landrace pigs, except for in jejunal mucosa and contents. Compared with Landrace pigs, the amylase and maltase activity in the small intestine of Jinhua pigs was lower, except for in ileal mucosa. The sucrase activity in the small intestine of Jinhua pigs was also lower than Landrace pigs, except for in jejunal mucosa. Furthermore, the lipase activity in the small intestine of Jinhua pigs was higher than that in Landrace pigs. The mRNA levels of PepT1 and GLUT2 in duodenal, jejunal and ileal mucosa showed no difference between Jinhua and Landrace pigs, whereas SGLT1 in ileal mucosa was lower in Jinhua pigs. The mRNA levels of FABP1 , FABP2 and FABP4 in the small intestinal mucosa of Jinhua pigs were higher than in Landrace pigs. These findings indicate that there is a certain difference in the digestibility and absorption of nutrients in small intestine of Jinhua and Landrace pigs, partially resulting in their differences in growth development and fat deposition., Competing Interests: LL and KL were employed by the company Zhejiang Goshine Test Technologies Co., Ltd. BD was the boss of the company Zhejiang Goshine Test Technologies Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Lyu, Liu, Lv, Zheng, Wang, Chen, Dai, Yang and Xiao.)

Validation and characterisation of in vitro and pre-clinical animal models to support bio-enabling formulation development is of paramount importance. In this work, post-mortem gastric and small intestinal fluids were collected in the fasted, fed state and at five sample-points post administration of a placebo Self-Emulsifying Drug Delivery System (SEDDS) in the fasted state to pigs. Cryo-TEM and Negative Stain-TEM were used for ultrastructure characterisation. Ex vivo solubility of fenofibrate was determined in the fasted-state, fed-state and post-SEDDS administration. Highest observed ex vivo drug solubility in intestinal fluids after SEDDS administration was used for optimising the biorelevant in vitro conditions to determine maximum solubility. Under microscopic evaluation, fasted, fed and SEDDS fluids resulted in different colloidal structures. Drug solubility appeared highest 1 hour post SEDDS administration, corresponding with presence of SEDDS lipid droplets. A 1:200 dispersion of SEDDS in biorelevant media matched the highest observed ex vivo solubility upon SEDDS administration. Overall, impacts of this study include increasing evidence for the pig preclinical model to mimic drug solubility in humans, observations that SEDDS administration may poorly mimic colloidal structures observed under fed state, while microscopic and solubility porcine assessments provided a framework for increasingly bio-predictive in vitro tools., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Increasing numbers of beyond Rule-of-Five drugs are emerging from discovery pipelines, generating a need for bio-enabling formulation approaches, such as lipid-based formulations (LBF), to ensure maximal in vivo exposure. However, many drug candidates display insufficient lipid solubility, leading to dose-loading limitations in LBFs. The aim of this study was to explore the potential of supersaturated LBFs (sLBF) for the beyond Rule-of-Five drug venetoclax. Temperature-induced sLBFs of venetoclax were obtained in olive oil, Captex ® 1000, Peceol ® and Capmul MCM ® , respectively. A Peceol ® -based sLBF displayed the highest drug loading and was therefore evaluated further. In vitro lipolysis demonstrated that the Peceol ® -based sLBF was able to generate higher venetoclax concentrations in the aqueous phase compared to a Peceol ® -based suspension and an aqueous suspension. A subsequent bioavailability study in pigs demonstrated for sLBF a 3.8-fold and 2.1-fold higher bioavailability compared to the drug powder and Peceol ® -based suspension, respectively. In conclusion, sLBF is a promising bio-enabling formulation approach to enhance in vivo exposure of beyond Rule-of-Five drugs, such as venetoclax. The in vitro lipolysis results correctly predicted a higher exposure of the sLBF in vivo. The findings of this study are of particular relevance to pre-clinical drug development, where maximum exposure is required.

Mycoplasma pneumonia of swine (MPS) is caused by Mycoplasma hyopneumoniae (M.hp) and is a common chronic respiratory disease of pigs. Recently, a genetically selected variant of the Landrace pig (Miyagino L2) has a lower incidence of pulmonary MPS lesions. We investigated the pathological and immunological characteristics of MPS resistance in these pigs (n = 24) by comparing with the normal landrace pig (control: n = 24). The pathological MPS lung lesion score in MPS-selected landrace pigs was significantly lower than in the control. The gene expression of interleukin (IL)-12p40, which acts as a chemoattractant and a component of the bioactive cytokines IL-12 and IL-23, was significantly higher at the hilar lymph nodes, lung, and spleen in MPS-selected landrace pigs than in control landrace pigs, and these were negatively correlated with the macroscopic MPS lung lesion score. In summary, we demonstrate that resistance against MPS in Miyagino L2 pigs is associated with IL-12p40 up-regulation, in comparison with normal landrace pigs without the MPS vaccine. In addition, a comparative study of macroscopic MPS lung lesions and IL-12p40 gene expression in lung and hilar lymph nodes may lead to beneficial selection traits for the genetic selection for MPS resistance in pigs., (© 2020 Japanese Society of Animal Science.)

A preclinical porcine model that reliably predicts human food effect of fenofibrate was developed. Fenofibrate was administered to pigs as model compound with a positive food effect. Two different types of fed conditions were explored: a FDA style breakfast and a standard pig pellet feed. In order to assess if complete stomach emptying had been achieved under the employed fasting protocol, the amount of gastric and intestinal content was evaluated post-mortem. In addition, the protocol was designed to evaluate gastric emptying in the pre- and postprandial state using paracetamol as a marker. The study confirmed that micronized fenofibrate displayed a positive food effect with a similar fold difference to humans in FDA style fed state. Post-mortem assessment of stomach and intestinal content confirmed significantly lower content in the fasted compared to the pig pellet fed state. In the case of paracetamol, a delayed gastric emptying in the fed state was not observed, which may suggest that the Magenstrasse phenomena reported in humans, may also occur in landrace pigs. The study demonstrated the utility of a food effect protocol in landrace pigs as a pre-clinical approach to predict human food effects and provided new insights into gastric emptying in pigs., Competing Interests: None.

Although there have been plenty of dominance deviation analysis, few studies have dealt with multiple phenotypes. Because researchers focused on multiple phenotypes (final weight and backfat thickness) of Landrace pigs, the classification of the genes was possible. With genome-wide association studies (GWASs), we analyzed the additive and dominance effects of the single nucleotide polymorphisms (SNPs). The classification of the pig genes into four categories (overdominance in final weight, overdominance in backfat thickness and overdominance in final weight, underdominance in backfat thickness, etc.) can enable us not only to analyze each phenotype's dominant effects, but also to illustrate the gene ontology (GO) analysis with different aspects. We aimed to determine the additive and dominant effect in backfat thickness and final weight and performed GO analysis. Using additive model and dominance deviation analysis in GWASs, Landrace pigs' overdominant and underdominant SNP effects in final weight and backfat thickness were surveyed. Then through GO analysis, we investigated the genes that were classified in the GWASs. The major GO terms of the underdominant effects in final weight and overdominant effects in backfat thickness were ion transport with the SLC8A3, KCNJ16, P2RX7 and TRPC3 genes. Interestingly, the major GO terms in the underdominant effects in the final weight and the underdominant effects in the backfat thickness were the regulation of ion transport with the STAC, GCK, TRPC6, UBASH3B, CAMK2D, CACNG4 and SCN4B genes. These results demonstrate that ion transport and ion transport regulation genes have distinct dominant effects. Through GWASs using the mode of linear additive model and dominance deviation, overdominant effects and underdominant effects in backfat thickness was contrary to each other in GO terms (ion transport and ion transport regulation, respectively). Additionally, because ion transport and ion transport regulation genes are associative with adipose tissue accumulation, we could infer that these two groups of genes had to do with unique fat accumulation mechanisms in Landrace pigs.

We recently developed a Landrace line that is resistant to mycoplasmal pneumonia of swine (MPS) infection by genetic selection for five generations, and we reported that the immunophenotype of this line is different from that of the non-selected line in terms of changes in peripheral blood leukocyte population after MPS vaccination. This study followed up previous findings demonstrating changes in soluble factors in blood, namely, hormones, Mycoplasma hyopneumoniae-specific immunoglobulin G (IgG), and cytokines. These two lines were injected with MPS vaccine on days -7 and 0 after blood sampling on those days, and blood samples were collected on days -14, -7, 0, 2, 7 and 14. We found changes in the levels of many hormones and cytokines in both lines. However, we found that only growth hormone (GH) and interferon (IFN)-γ levels were statistically different between these two lines. GH concentration was reduced (day 0) and IFN-γ concentration was increased (day 14) in the MPS-selected line compared with the non-selected line, despite unchanged IFN-γ messenger RNA expression in blood cells. Although detailed mechanisms underlying these phenotypes remain unsolved, these traits would be useful to improve MPS resistance in pig production and provide an insight into MPS infection., (© 2013 Japanese Society of Animal Science.)

This study was conducted to evaluate immunological changes in peripheral blood leukocytes in pigs that were genetically selected for their improved resistance to mycoplasmal pneumonia of swine (MPS), using MPS vaccine as an antigen. Twelve castrated MPS-selected Landrace pigs were compared with the same number of pigs from a nonselected line by using a time-course analysis at the hematological level. After the second sensitization with MPS vaccine, the percentages of B cells, CD4(+) T cells, and natural killer (NK) cells in total leukocytes were lower in the selected line than in the nonselected line, whereas the percentage of granulocytes in total leukocytes increased in the MPS-selected line. We also assessed the proliferative ability of peripheral blood mononuclear cells (PBMCs) stimulated with Mycoplasma hyopneumoniae, lipopolysaccharide or concanavalin A, and found that although the proliferative ability of the PBMC was not different between the two lines at a steady state, the nonselected line showed a significantly higher proliferative ability after sensitization with MPS vaccine than the selected line regardless of antigens used. These results thus indicate that the selection of pigs on the basis of MPS resistance changes their immunophenotype, and would give us beneficial information for the prevention of MPS infection., (© 2013 Japanese Society of Animal Science.)