New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation

The contemporary strategy for spinal cord injury (SCI) therapy aims to combine multiple approaches to control pathogenic mechanisms of neurodegeneration and stimulate neuroregeneration. In this study, a novel regenerative approach using an autologous leucoconcentrate enriched with transgenes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) combined with supra- and sub-lesional epidural electrical stimulation (EES) was tested on mini-pigs similar in morpho-physiological scale to humans. The complex analysis of the spinal cord recovery after a moderate contusion injury in treated mini-pigs compared to control animals revealed: better performance in behavioural and joint kinematics, restoration of electromyography characteristics, and improvement in selected immunohistology features related to cell survivability, synaptic protein expression, and glial reorganization above and below the injury. These results for the first time demonstrate the positive effect of intravenous infusion of autologous genetically-enriched leucoconcentrate producing recombinant molecules stimulating neuroregeneration combined with neuromodulation by translesional multisite EES on the restoration of the post-traumatic spinal cord in mini-pigs and suggest the high translational potential of this novel regenerative therapy for SCI patients.

Innovative transdermal delivery of insulin using gelatin methacrylate-based Microneedle Patches in Mice and Mini-pigs

Painless and controlled on-demand drug delivery is the ultimate goal for the management of various chronic diseases, including diabetes. To achieve this purpose, microneedle patches are gaining increased attention. While...

Impacts of Betaine Addition in Sow and Piglet's Diets on Growth Performance, Plasma Hormone, and Lipid Metabolism of Bama Mini-Pigs

The present study evaluated the effects of betaine addition in sow and piglet's diets on growth performance, plasma hormone, and lipid metabolism of Bama mini-pigs. A total of 26 pregnant Bama mini-pigs and 104 weaned piglets were selected and divided into different dietary treatment groups (details in “Materials and Methods”). Blood and muscle samples were collected at 65-, 95-, and 125-day-old, respectively. The results showed that betaine addition in sow-offspring diets increased (P < 0.05) the body weight at 125-day-old, average daily gain from 35- to 65-day-old, and average daily feed intake at 35–65 and 35–95 days old of pigs compared with the control group. Betaine addition in sow-offspring diets increased (P < 0.05) the plasma gastrin level at 95-day-old, while betaine addition in sow diets decreased (P < 0.05) the plasma peptide YY and leptin levels at 65-day-old pigs. In the longissimus dorsi muscle of pigs, betaine addition in sow and sow-offspring diets increased (P < 0.05) the C12:0 content at 65-day-old while decreased at 95-day-old. Moreover, betaine addition in sow-offspring diets increased the C24:0 content and decreased the C18:1n9t content at 125-day-old (P < 0.05). In the biceps femoris muscle, the contents of C12:0 at 65-day-old and C20:4n6 at 125-day-old were decreased (P < 0.05) after the betaine addition in both sow and piglet's diets. In addition, betaine addition in sow diets decreased (P < 0.05) the C20:0 content at 125-day-old, while betaine addition in sow-offspring diets increased the C18:3n6 and decreased C24:0 contents at 65-day-old pigs (P < 0.05). In the psoas major muscle, betaine addition in sow and sow-offspring diets decreased (P < 0.05) the contents of C18:1n9t at 65-day-old and C20:1 at 95-day-old, while betaine addition in sow diets decreased (P < 0.05) the intramuscular fat content at 125-day-old. Moreover, betaine addition in sow-offspring diets was also associated with muscle lipid deposition and metabolisms by regulating the gene expressions related to fatty acid metabolism. These findings suggested that betaine addition in sow-offspring diets could improve the growth performance, whereas betaine addition in both sow and sow-offspring diets could enhance lipid quality by altering plasma hormone level and fatty acid composition and regulating the gene expressions related to fatty acid metabolism.

Effects of Different Dietary Protein Levels on the Growth Performance, Serum Biochemical Parameters, Fecal Nitrogen, and Carcass Traits of Huanjiang Mini-Pigs

The Huanjiang mini-pig is a Chinese local breed and, the optimal dietary crude protein (CP) level for this breed is still unknown. Therefore, the present study was conducted to investigate its optimum dietary CP level upon the growth performance, serum biochemical parameters, fecal nitrogen content, and carcass traits. Three independent trials with 360 pigs were included. A total of 220 pigs (5.32 ± 0.46 kg) were fed ad libitum, either a 14, 16, 18, 20, or 22% CP diet from about 5- to 10-kg (trial 1); 84 pigs (11.27 ± 1.43 kg) were fed either a 12, 14, 16, 18, or 20% CP diet from about 10- to 20-kg (trial 2); and 56 pigs (18.80 ± 2.21 kg) were fed either a 10, 12, 14, 16, or 18% CP diet from about 20- to 30-kg (trial 3). In trial 1, as dietary CP levels increased, the feed-to-gain ratio (F/G) quadratically decreased (p < 0.05) and was minimal at the 18.42% CP level. The average daily feed intake (ADFI) and final body weight (BW) were not affected by dietary CP levels while the fat percentage decreased (p < 0.05). Besides, a linear decrease in slaughter rate (p = 0.06) and a linear increase in bone percentage (p < 0.05), serum urea nitrogen (UN) (P < 0.05), and fecal nitrogen content (p = 0.07) of pigs were observed. In trial 2, as dietary CP levels increased, the average daily gain quadratically increased (p < 0.05) and was maximum at the 16.70% CP level. The slaughter rate linearly decreased (p < 0.05) whereas the skin rate, serum UN, and NH3-N increased (p < 0.05) linearly, as well as fecal nitrogen content (p = 0.06). In trial 3, as dietary CP levels increased, the F/G increased (p < 0.05), while the ADFI and ADG quadratically decreased (p < 0.05) and was maximum at nearly 14.00% CP level. The bone percentage and serum UN increased (p < 0.05) linearly but the slaughter rate decreased (P < 0.05) linearly, and the fecal nitrogen content quadratically decreased (p = 0.07) whereas the albumin increased (p < 0.05) quadratically. Taken together, the optimal dietary CP levels for growth performance of Huanjiang mini-pigs from 5- to 10-kg, 10- to 20-kg, and 20- to 30-kg were 18.42, 16.70, and 14.00%, respectively.

Review of Animal Models to Study Urinary Bladder Function

The urinary bladder (UB) serves as a storage and elimination organ for urine. UB dysfunction can cause multiple symptoms of failure to store urine or empty the bladder, e.g., incontinence, frequent urination, and urinary retention. Treatment of these symptoms requires knowledge on bladder function, which involves physiology, pathology, and even psychology. There is no ideal animal model for the study of UB function to understand and treat associated disorders, as the complexity in humans differs from that of other species. However, several animal models are available to study a variety of other bladder disorders. Such models include animals from rodents to nonhuman primates, such as mice, rats, rabbits, felines, canines, pigs, and mini pigs. For incontinence, vaginal distention might mimic birth trauma and can be measured based on leak point pressure. Using peripheral and central models, inflammation, bladder outlet obstruction, and genetic models facilitated the study of overactive bladder. However, the larger the animal model, the more difficult the study is, due to the associated animal ethics issues, laboratory facility, and budget. This review aims at facilitating adapted animal models to study bladder function according to facility, priority, and disease.

A Mix of Dietary Fibres Changes Interorgan Nutrients Exchanges and Muscle-Adipose Energy Handling in Overfed Mini-Pigs

This study evaluates the capacity of a bread enriched with fermentable dietary fibres to modulate the metabolism and nutrients handling between tissues, gut and peripheral, in a context of overfeeding. Net fluxes of glucose, lactate, urea, short chain fatty acids (SCFA), and amino acids were recorded in control and overfed female mini-pigs supplemented or not with fibre-enriched bread. SCFA in fecal water and gene expressions, but not protein levels or metabolic fluxes, were measured in muscle, adipose tissue, and intestine. Fibre supplementation increased the potential for fatty acid oxidation and mitochondrial activity in muscle (acox, ucp2, sdha and cpt1-m, p < 0.05) as well as main regulatory transcription factors of metabolic activity such as pparα, pgc-1α and nrf2. All these features were associated with a reduced muscle fibre cross sectional area, resembling to controls (i.e., lean phenotype). SCFA may be direct inducers of these cross-talk alterations, as their feces content (+52%, p = 0.05) was increased in fibre-supplemented mini-pigs. The SCFA effects could be mediated at the gut level by an increased production of incretins (increased gcg mRNA, p < 0.05) and an up-regulation of SCFA receptors (increased gpr41 mRNA, p < 0.01). Hence, consumption of supplemented bread with fermentable fibres can be an appropriate strategy to activate muscle energy catabolism and limit the establishment of an obese phenotype.

Introducing a Novel Experimental Model for Osseo-Disintegration of Titanium Dental Implants Induced by Monobacterial Contamination: An In-Vivo Feasibility Study

Background and Objectives: The aim of the current study was to establish an osseo-disintegration model initiated with a single microorganism in mini-pigs. Materials and Methods: A total of 36 titanium dental implants (3.5 mm in diameter, 9.5 mm in length) was inserted into frontal bone (n: 12) and the basis of the corpus mandible (n: 24). Eighteen implants were contaminated via inoculation of Enterococcus faecalis. Six weeks after implant insertion, bone-to-implant contact (BIC) ratio, interthread bone density (ITBD), and peri-implant bone density (PIBD) were examined. In addition to that, new bone formation was assessed via fluorescence microscopy, histomorphometry, and light microscopical examinations. Results: Compared to the sterile implants, the contaminated implants showed significantly reduced BIC (p < 0.001), ITBD (p < 0.001), and PBD (p < 0.001) values. Around the sterile implants, the green and red fluorophores were overlapping and surrounding the implant without gaps, indicating healthy bone growth on the implant surface, whereas contaminated implants were surrounded by connective tissue. Conclusions: The current experimental model could be a feasible option to realize a significant alteration of dental-implant osseointegration and examine novel surface decontamination techniques without impairing local and systemic inflammatory complications.

Dietary Addition With Clostridium butyricum and Xylo-Oligosaccharides Improves Carcass Trait and Meat Quality of Huanjiang Mini-Pigs

This study was conducted to investigate the effects of dietary addition with Clostridium butyricum (CB) and xylo-oligosaccharides (XOS) on growth performance, carcass trait, and meat quality of pigs. A total of 128 Huanjiang mini-pigs with an initial body weight of 9.5 ± 0.1 kg were randomly assigned to one of four groups. The pigs in control (Con) group were fed a basal diet and those in the experimental groups were fed the basal diet supplemented with 0.05% CB (CB group), 0.02% XOS (XOS group), or 0.05% CB + 0.02% XOS (CB + XOS group). Eight replicate pens were used per group with four pigs per pen. On days 28, 56, and 84 of the trial, the growth performance, carcass trait, and meat quality were evaluated. The results showed that dietary CB addition decreased (p &lt; 0.05) the average daily gain and increased (p &lt; 0.05) the ratio of feed intake to body weight gain at day 28 of the trial; CB, XOS, and CB + XOS addition increased (p &lt; 0.05) the backfat thickness at day 84 of the trial compared with the Con group. Dietary CB, XOS, and CB + XOS addition increased (p &lt; 0.05) the pH45min, while decreased (p &lt; 0.05) the marbling score at day 28 of the trial compared with the Con group. Dietary CB + XOS addition increased (p &lt; 0.05) the contents of Ala, Arg, Asp, Gly, His, Leu, Lys, Met, Phe, Ser, Thr, Tyr, and Val in muscle at day 56 of the trial. At day 84 of the trial, dietary CB addition increased the contents of nonessential amino acid (NEAA), total amino acid (TAA), and monounsaturated fatty acid (MUFA), while decreased (p &lt; 0.05) the percentage of C20:1 in muscle compared with the Con group. Collectively, dietary addition with 0.05% CB and 0.02% XOS could not alter the growth performance, but increase carcass trait, meat quality, and muscular nutrient contents in Huanjiang mini-pigs.

Probiotics or Synbiotics Addition in Bama Mini-pigs’ Diets Improves Growth Performance, Carcass Traits, and Meat Quality by Altering Plasma Metabolites and Related Gene Expression of Offspring Pigs

Background: The present study evaluated the effects of maternal probiotics or synbiotics addition on growth performance, carcass traits, meat quality, plasma metabolites, and related gene expression of their offspring pigs. Methods: A total of 64 Bama mini-pigs were used and randomly divided into the control, antibiotic, probiotics, or synbiotics groups, and fed experimental diets during pregnancy and lactation. After weaning, two piglets per litter and eight piglets per group were selected and fed a basal diet. At 65-, 95-, and 125-day-old, eight pigs per group were selected for analysis. Results: The results showed that probiotics addition increased the ADFI of pigs during the 66-95 day-old and the backfat thickness at 65- and 125-day-old, whereas synbiotics addition increased backfat thickness and decreased muscle percentage and loin-eye area at 125-day-old. In meat quality, probiotics or synbiotics addition increased cooking yield, pH 45min , and meat color, while decreased drip loss and shear force at different stages. However, maternal antibiotic addition showed an increased shear force at 125-day-old. Dietary probiotics or synbiotics addition in sow diets increased several amino acids (AA) contents in the plasma and longissimus thoracis (LT) muscle, including total AA (TAA), His, Met, Asp, Arg, and Leu, while decreased Gly, Pro, Ile, α-AAA, α-ABA, β-Ala, and γ-ABA at different stages. In the LT muscle fatty acid (FA) analysis, the contents of saturated FA (SFA; including C16:0, C17:0, and C20:0) and C18:1n9t were decreased, and the contents of C18:2n6c, MUFA (C16:1 and C20:1) and UFA were increased in the probiotics group, while the contents of SFA (C10:0, C12:0, and C14:0 at 65-day-old) were increased and the contents of C20:1 and C18:1n9t were decreased in the synbiotics group. Plasma biochemical analysis revealed that maternal probiotics or synbiotics addition decreased plasma AMM, UN, and GLU, while synbiotics addition increased plasma ALT, HDL-C, and TC at different stages. Moreover, maternal probiotics or synbiotics regulated muscle fiber-type, myogenic regulatory, and lipid metabolism-related gene expressions of offspring pigs. Conclusions: In conclusion, maternal probiotics or synbiotics addition, as a nutritional intervention strategy, improved feed intake and meat quality by altering the body's metabolism of offspring pigs and gene expressions related to meat quality.