Minipig Research Articles

Review of Animal Models to Study Urinary Bladder Function.

Simple SummaryThe treatment of urinary bladder dysfunction requires the knowledge of bladder function, which involves physiology, pathology, and even psychology. Several animal models are available to study a variety of bladder disorders. These models include animals from rodents, such as mice and rats, to nonhuman primates, such as rabbits, felines, canines, pigs, and mini pigs. This review adapted animal models to study bladder function according to facility, priority, and disease.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.

Effect of conditioned medium from adipose derived mesenchymal stem cells on endoplasmic reticulum stress and lipid metabolism after hepatic ischemia reperfusion injury and hepatectomy in swine

AimsHepatic ischemia reperfusion injury (HIRI) is associated with liver failure after liver transplantation and hepatectomy. Thus, this study aims to explore the effect of conditioned medium from adipose derived stem cells (ADSC-CM) on endoplasmic reticulum stress (ERS) and lipid metabolism after HIRI combined with hepatectomy in miniature pigs. Main methodsA model of HIRI combined with hepatectomy in miniature pigs was established. The expression of ERS-related proteins and lipid metabolism related genes, as well as triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL), very low density lipoprotein (VLDL) and acetyl-CoA carboxylase 1 (ACC1) level were measured in liver tissues. Key findingsBoth ADSCs and ADSC-CM could improve the damage in the ultrastructure of hepatocytes. ADSC-CM significantly decreased the protein expression of GRP78, ATF6, XBP1, p-eIF2α, ATF4, p-JNK and CHOP. Oil red O staining revealed that the degree of hepatocyte steatosis was also significantly reduced after treatment with ADSC-CM. In addition, ADSC-CM remarkably decreased TG, TC, HDL and ACC1 level in liver tissues, while enhanced VLDL content. Finally, SREBP1, SCAP, FASN, ACC1, HMGCR and HMGCS1 mRNA expression was also markedly downregulated in liver tissues. SignificanceInjection of ADSC-CM into the hepatic parenchymal could represent a novel cell-free therapeutic approach to improve HIRI combined with hepatectomy injury. The inhibition of ERS and the improvement of lipid metabolism in the hepatocytes might be a potential mechanism used by ADSC-CM to prevent liver injury from HIRI combined with hepatectomy.

A Dystrophin Exon-52 Deleted Miniature Pig Model of Duchenne Muscular Dystrophy and Evaluation of Exon Skipping.

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder caused by mutations in the DMD gene and the subsequent lack of dystrophin protein. Recently, phosphorodiamidate morpholino oligomer (PMO)-antisense oligonucleotides (ASOs) targeting exon 51 or 53 to reestablish the DMD reading frame have received regulatory approval as commercially available drugs. However, their applicability and efficacy remain limited to particular patients. Large animal models and exon skipping evaluation are essential to facilitate ASO development together with a deeper understanding of dystrophinopathies. Using recombinant adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer, we generated a Yucatan miniature pig model of DMD with an exon 52 deletion mutation equivalent to one of the most common mutations seen in patients. Exon 52-deleted mRNA expression and dystrophin deficiency were confirmed in the skeletal and cardiac muscles of DMD pigs. Accordingly, dystrophin-associated proteins failed to be recruited to the sarcolemma. The DMD pigs manifested early disease onset with severe bodywide skeletal muscle degeneration and with poor growth accompanied by a physical abnormality, but with no obvious cardiac phenotype. We also demonstrated that in primary DMD pig skeletal muscle cells, the genetically engineered exon-52 deleted pig DMD gene enables the evaluation of exon 51 or 53 skipping with PMO and its advanced technology, peptide-conjugated PMO. The results show that the DMD pigs developed here can be an appropriate large animal model for evaluating in vivo exon skipping efficacy.

Double anchor lock fixing method to prevent stent displacement in endoscopic ultrasound-guided gastroenterostomy: a porcine study.

Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is widely used in patients with gastric outlet obstruction (GOO). Recurrence of obstruction symptoms caused by stent migration is the major reason for reintervention in EUS-GE. To solve this problem, we proposed developing a double anchor lock (DAL) fixing stent method for EUS-GE. The safety and efficacy of the DAL fixing stent method were evaluated in this study. Sixteen Bama miniature pigs were randomly divided into an experimental group (n = 8) and a control group (n = 8). A gastric outlet obstruction model was established for all the pigs. The experimental group was treated with the DAL fixing stent method for EUS-GE, while the control group was treated with EUS-GE. Three-month stent migration rate, remission rate of GOO, re-occlusion intervention rate, weight change, and incidence of procedure-related complications of EUS-GE were analyzed and estimated in the two groups. EUS-GE was successfully completed in every subject in both groups. Symptoms of digestive tract obstruction can be relieved in all animals. The stent existence rate in the 3months was higher in the experimental group than in the control group (87.5% vs. 12.5%, P = 0.012). Except for one animal in the experimental group in which there was pneumoperitoneum due to a stent insertion failure, no animal experienced bleeding or perforation. The DAL fixing stent method, which can effectively prevent stent migration, is safe and simple. EUS-GE can effectively relieve the symptoms of digestive tract obstruction.

Integrated analysis of DNA methylome and transcriptome reveals the differences in biological characteristics of porcine mesenchymal stem cells

BackgroundBone marrow (BM) and umbilical cord (UC) are the main sources of mesenchymal stem cells (MSCs). These two MSCs display significant differences in many biological characteristics, yet the underlying regulation mechanisms of these cells remain largely unknown.ResultsBMMSCs and UCMSCs were isolated from inbred Wuzhishan miniature pigs and the first global DNA methylation and gene expression profiles of porcine MSCs were generated. The osteogenic and adipogenic differentiation ability of porcine BMMSCs is greater than that of UCMSCs. A total of 1979 genes were differentially expressed and 587 genes were differentially methylated at promoter regions in these cells. Integrative analysis revealed that 102 genes displayed differences in both gene expression and promoter methylation. Gene ontology enrichment analysis showed that these genes were associated with cell differentiation, migration, and immunogenicity. Remarkably, skeletal system development-related genes were significantly hypomethylated and upregulated, whereas cell cycle genes were opposite in UCMSCs, implying that these cells have higher cell proliferative activity and lower differentiation potential than BMMSCs.ConclusionsOur results indicate that DNA methylation plays an important role in regulating the differences in biological characteristics of BMMSCs and UCMSCs. Results of this study provide a molecular theoretical basis for the application of porcine MSCs in human medicine.

Renal Interstitial Fibrosis Is Reduced in High-Fat Diet-Induced Obese Pigs following Renal Denervation from the Intima and Adventitia of the Renal Artery

Background: This study aims to compare whether 2 different routes of renal denervation (RDN) from the intima and adventitia of the renal artery can reduce renal fibrosis in a pig model of hypertension induced by a high-fat diet and to explore possible molecular mechanisms. Methods: Twenty-four Bama miniature pigs were randomly divided into a control group (normal diet, n = 6) or a hypertension model group (high-fat diet, n = 18). The model group was randomly divided into the intima-RDN group (n = 6), the adventitia-RDN group (n = 6), or the renal arteriography-only group (sham group, n = 6). All animals were fed separately. The model group was fed a high-fat diet after the operation, and the control group was fed conventionally for 6 months. After 6 months, renal artery angiography was performed again to observe the condition of the renal arteries, after which all animals were euthanized. The blood pressure and blood biochemical results of each group were evaluated 6 months after the operation; kidney tissue morphology and collagen fiber content were examined by hematoxylin-eosin staining and Masson staining; superoxide dismutase activity and the malondialdehyde content of kidney tissue were assessed by a biochemical enzyme method; the protein expression level of transforming growth factor-β 1 (TGF-β1), α-smooth muscle actin (α-SMA), and Smad3 was assessed by Western blot, and electron microscopy was used to examine changes in the kidney microstructure. Results: After 6 months of a high-fat diet, the blood lipid levels of the model group were significantly higher compared to baseline and to that of the control group during the same period (all showed p < 0.05); the blood lipid levels of the control group did not change significantly from baseline (p > 0.05). The degree of glomerular damage caused by hyperlipidemia in the intima-RDN group and the adventitia-RDN group was significantly lower than that of the sham and control groups, and the renal fibrosis area percentage was also significantly lower (p < 0.05). Electron microscopy showed that both the intima-RDN group and the adventitia-RDN group had a more even distribution of chromosomes and less mitochondrial swelling compared with the sham group. Conclusion: RDN from the adventitia of the renal artery and RDN from the intima of the renal artery have the similar advantages of delaying high-fat-induced renal fibrosis. The antifibrotic effect of RDN may be related to inhibition of the TGF-β1/Smad3 pathway.

Development of the temporomandibular joint in miniature pig embryos.

The temporomandibular joint (TMJ) is a synovial joint involved in sliding and hinge movements of lower jaw in mammals. Studies on TMJ development in embryos have been mainly performed using rodents. However, the TMJ structure in rodents differs in several aspects from that in humans. There are few studies on the embryonic development of TMJ in large mammals. In the present study, we investigated the embryonic developmental characteristics of the TMJ in pigs histologically. Embryonic day 35 (E35), E45, E55, E75, E90, and postnatal day 1(P1) embryos/fetuses from the pigs were used for the study. The results showed condensation of mesenchymal cells on E35. The inferior articular cavity was formed on E45, together with a narrow crack in the superior articular cavity region. The superior and inferior articular cavities and articular disc of the TMJ were completely formed on E55. On E75, the condyle showed an obvious conical shape and the superior and inferior joint cavities were enlarged. Furthermore, the mandibular ramus and mandibular body under the neck of the condyle were ossified from E75 to P1 day. The chondrocyte layer of the condyle was significantly thinner from E75 to P1. It is speculated that the spatiotemporal development of the TMJ in miniature pig embryos is similar to that in humans. Embryonic development of the pig TMJ is an important bridge for translating the results of rodent research to medical applications.

Effect of increased positive end-expiratory pressure on intracranial pressure and cerebral oxygenation: impact of respiratory mechanics and hypovolemia

BackgroundTo evaluate the impact of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) in animals with different respiratory mechanics, baseline ICP and volume status.MethodsA total of 50 male adult Bama miniature pigs were involved in four different protocols (n = 20, 12, 12, and 6, respectively). Under the monitoring of ICP, brain tissue oxygen tension and hemodynamical parameters, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O. Measurements were taken in pigs with normal ICP and normovolemia (Series I), or with intracranial hypertension (via inflating intracranial balloon catheter) and normovolemia (Series II), or with intracranial hypertension and hypovolemia (via exsanguination) (Series III). Pigs randomized to the control group received only hydrochloride instillation while the intervention group received additional chest wall strapping. Common carotid arterial blood flow before and after exsanguination at each PEEP level was measured in pigs with intracranial hypertension and chest wall strapping (Series IV).ResultsICP was elevated by increased PEEP in both normal ICP and intracranial hypertension conditions in animals with normal blood volume, while resulted in decreased ICP with PEEP increments in animals with hypovolemia. Increasing PEEP resulted in a decrease in brain tissue oxygen tension in both normovolemic and hypovolemic conditions. The impacts of PEEP on hemodynamical parameters, ICP and brain tissue oxygen tension became more evident with increased chest wall elastance. Compare to normovolemic condition, common carotid arterial blood flow was further lowered when PEEP was raised in the condition of hypovolemia.ConclusionsThe impacts of PEEP on ICP and cerebral oxygenation are determined by both volume status and respiratory mechanics. Potential conditions that may increase chest wall elastance should also be ruled out to avoid the deleterious effects of PEEP.

Six genes modified transgenic pigs based on PERVc-negative Yucatan miniature pigs for xenotransplantation by CRISPR-Cas9 and 2A-peptide.

Six genes modified transgenic pigs based on PERVc-negative Yucatan miniature pigs for xenotransplantation by CRISPR-Cas9 and 2A-peptide.

Health status of free-ranging pure and cross-mixed miniature swine population from Northeast Spain.

BackgroundMiniature pigs have gained popularity as companion animals in the recent years in Spain. Due to the fact that their abandonment and crossing breeds with wild boars can cause severe problems, investigation about the health status is needed.ObjectivesThe aim of this study was to determine their health status according to the clinical findings during physical examination and the results of antibody serology tests against selected infectious diseases.MethodsTwo‐hundred and eleven miniature pigs (Sus scrofa) were included in the study. Their origin, age, sex, housing conditions and diet were recorded.ResultsThe housing of the animals ranged from wild animals to ones living in animal sanctuaries. The diet varied from a natural one in the wild to commercial and homemade food. Thirty animals out of two‐hundred and eleven were hybrids between miniature pigs and wild boars according to morphological characteristics. Antibody serology techniques of Influenza A virus, Hepatitis E virus, brucellosis, tuberculosis, African swine fever, Classical swine fever and Aujeszky's disease was performed. The prevalence for Influenza A was 5.30%, for Hepatitis E was 5.35% and the rest tested negative. It is important to control and monitor these zoonotic infections to prevent Public Health problems.ConclusionsThe results obtained from this investigation demonstrated that the animals' health status in this study is optimal and the diseases prevalence is similar or minor when compared to previous studies. This study confirms the hybridization of miniature pig and wild boar in Catalonia.

Effects of Dietary Tea Powder on the Growth Performance, Carcass Traits, and Meat Quality of Tibetan Pig × Bama Miniature Pigs.

Simple SummaryIn China, and even the world, the animal husbandry industry is facing the problem of a shortage of feed ingredients, and even humans and animals compete for food. The development of unconventional feed resources is an urgent task. In our previous work, we analyzed the nutritional value of tea powder and believed that it has development potential. This study investigated the effects of supplementing different levels of tea powder in diets on pig growth performance, meat quality, and antioxidant properties. These results provide a preliminary basis for the application of tea powder as a supplement in animal husbandry.This study was conducted to evaluate the effects of tea powder in diets on the growth performance, meat quality, muscular amino acid, fatty acid profile, and serum biochemical indices of pigs. A total of 120 local Chinese pigs (Tibetan × Bama miniature pigs) were randomly assigned to five treatment groups, each with six pens and four pigs per pen. During a 60-day experiment, these groups of pigs were fed the normal diet and the diet supplemented with 1%, 2%, 4%, and 6% tea powder, respectively. The results showed that the supplementation of tea powder did not affect the growth performance of pigs. However, the dietary tea powder inclusion decreased (p < 0.05) the average fat thickness, total fat, and abdominal fat, and increased (p < 0.05) the total muscle as well. In addition, the dietary 2% tea powder decreased (p < 0.05) the muscle lightness (L*) and yellowness (b*). Compared with the control group, the dietary supplementation with 1%, 2%, and 4% tea powder raised (p < 0.05) the total amino acids (TAA) and essential amino acids (EAA), and dietary 4% and 6% tea powder increased (p < 0.05) the C20:5n3 in the muscle tissue. Furthermore, the serum lipid metabolism-related biochemical indices and mRNA expression levels were improved with the addition of tea powder. These results indicated that dietary tea powder might improve the carcass traits and meat quality of the Chinese native finishing pigs, but it does not affect their growth performance. Tea powder could be fully developed and reasonably applied as a dietary supplement.

The Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor

This study aimed to investigate the effects of the human macrophage (MP) secretome in cellular xenograft rejection. The role of human nucleoside diphosphate kinase A (hNME1), from the secretome of MPs involved in the neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem cells (mp AD-MSCs), was evaluated by proteomic analysis. Herein, we first demonstrate that hNME1 strongly binds to porcine ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (pST8SIA1), which is a ganglioside GD3 synthase. When hNME1 binds with pST8SIA1, it induces degradation of pST8SIA1 in mp AD-MSCs, thereby inhibiting the expression of ganglioside GD3 followed by decreased neuronal differentiation of mp AD-MSCs. Therefore, we produced nanobodies (NBs) named NB-hNME1 that bind to hNME1 specifically, and the inhibitory effect of NB-hNME1 was evaluated for blocking the binding between hNME1 and pST8SIA1. Consequently, NB-hNME1 effectively blocked the binding of hNME1 to pST8SIA1, thereby recovering the expression of ganglioside GD3 and neuronal differentiation of mp AD-MSCs. Our findings suggest that mp AD-MSCs could be a potential candidate for use as an additive, such as an immunosuppressant, in stem cell transplantation.

Surface structure change properties: Auto-soft bionic fibrous membrane in reducing postoperative adhesion

Peritoneal adhesion is the most common adverse effect following abdominal surgery or inflammation. The occurrence in clinical trials has been successfully reduced using barriers. However, the shortcomings of frequently used adhesion barriers, such as rapid degradation rate of gel barrier and inadequate operation ability of solid barrier, cannot be ignored. In this study, a fibrous membrane with an ECM-like structure was prepared. The adhesion properties were reduced significantly by changing the surface structure. The fibrous membrane caused less inflammatory response and much less peripheral adhesion and intestinal obstruction compared to the casting film and the commercial film with smooth surface, though with the same components. Because of the auto-soft bionic structure and similarity in the mechanical modulus of the tissues, the fibrous membrane was more flexible when it adhered to the tissues, showed excellent effectiveness and biocompatibility. In addition to the rat and miniature pig models, a randomized, placebo-controlled, and multicenter clinical pilot study with 150 patients confirmed that because of its flexibility, biodegradability, and similarity to mechanical modulus and structure with tissues involved, the fibrous membrane served as a favorable implant for preventing post-operation adhesion.

Six-Month Outcomes of Clinically Relevant Meniscal Injury in a Large-Animal Model.

Background:The corrective procedures for meniscal injury are dependent on tear type, severity, and location. Vertical longitudinal tears are common in young and active individuals, but their natural progression and impact on osteoarthritis (OA) development are not known. Root tears are challenging and they often indicate poor outcomes, although the timing and mechanisms of initiation of joint dysfunction are poorly understood, particularly in large-animal and human models.Purpose/Hypothesis:In this study, vertical longitudinal and root tears were made in a large-animal model to determine the progression of joint-wide dysfunction. We hypothesized that OA onset and progression would depend on the extent of injury-based load disruption in the tissue, such that root tears would cause earlier and more severe changes to the joint.Study Design:Controlled laboratory study.Methods:Sham surgeries and procedures to create either vertical longitudinal or root tears were performed in juvenile Yucatan mini pigs through randomized and bilateral arthroscopic procedures. Animals were sacrificed at 1, 3, or 6 months after injury and assessed at the joint and tissue level for evidence of OA. Functional measures of joint load transfer, cartilage indentation mechanics, and meniscal tensile properties were performed, as well as histological evaluation of the cartilage, meniscus, and synovium.Results:Outcomes suggested a progressive and sustained degeneration of the knee joint and meniscus after root tear, as evidenced by histological analysis of the cartilage and meniscus. This occurred in spite of spontaneous reattachment of the root, suggesting that this reattachment did not fully restore the function of the native attachment. In contrast, the vertical longitudinal tear did not cause significant changes to the joint, with only mild differences compared with sham surgery at the 6-month time point.Conclusion:Given that the root tear, which severs circumferential connectivity and load transfer, caused more intense OA compared with the circumferentially stable vertical longitudinal tear, our findings suggest that without timely and mechanically competent fixation, root tears may cause irreversible joint damage.Clinical Relevance:More generally, this new model can serve as a test bed for experimental surgical, scaffold-based, and small molecule–driven interventions after injury to prevent OA progression.

THE EFFECTIVENESS OF STEM CELLS GRAFTING ON REGENERATION OF DENTAL PULP: A SYSTEMATIC REVIEW AND META-ANALYSIS

Background: Great advances in tissue engineering open a new biological path to regenerate the damaged pulpal tissue. The new approach of stem cell transplantation to regeneration of tissues had been used in many medical fields with promising results including dental therapy. Aim of this istoreviewthe efficacy of stem cell grafting in regeneration of dental pulp from available animal and human studies for a systematic and meta-analysisreview. Methodology: AComprehensive electronic search with time and language restrictions was conducted. Several known databases were included Ex: PubMed, The Cochrane Library, Web of Science from 2000 to 2020.We combined the search terms and limited the study to the English language. Depending on PRISMA checklist, we removed duplicates, articles were screened based on title, abstract, and full text. The search resulted in 325 hits which after removing duplicates, exclusion studies the number of studies became 10. Results:In this review, The total samples used in this review was 40 samples from which 13 human patients had been included (mean age of 26.8 years old), 12 dogs, 3 mice and 12 inbred male miniature pigs using 94 teeth and molar. Moreover, all the used stem cells for dentine regeneration were adult mesenchymal stem cells however, the source of harvesting these stem cell differs between studies including adipose tissue and pulp CD31-SP, DPSCS, PDLSCs, Gdf11 gene,bone morphogenetic protein-2 (BMP-2),MDPSCs and SCAP. Furthermore, all types showed promising results however, some types gave better results over other including superior of adipose tissue CD31 SP over bone marrow CD31 SP and pulp stem progenitor (CD 105) cells over adipose CD105 cell. Conclusion: It was observed that stem cell grafting shows promising results in the regeneration of dental pulp in both animal and human studies with no side effect or toxicity. Therefore, we recommend widening the application of these techniques in human trials because of its safety and efficacy. Choice of carriers or type of stem cells up to our review should depend on the expenses, as there are no significant differences between them in both safety of efficacy profiles.

Porcine ZBED6 regulates growth of skeletal muscle and internal organs via multiple targets.

ZBED6 (zinc finger BED domain containing protein 6) is a transcription factor unique to placental mammals and its interaction with the IGF2 (insulin-like growth factor 2) locus plays a prominent role in the regulation of postnatal skeletal muscle growth. Here, we generated lean Bama miniature pigs by generating ZBED6-knockout (ZBED6−/−) and investigated the mechanism underlying ZBED6 in growth of muscle and internal organs of placental mammals. ZBED6−/− pigs show markedly higher lean mass, lean mass rate, larger muscle fiber area and heavier internal organs (heart and liver) than wild-type (WT) pigs. The striking phenotypic changes of ZBED6-/- pigs coincided with remarkable upregulation of IGF2 mRNA and protein expression across three tissues (gastrocnemius muscle, longissimus dorsi, heart). Despite a significant increase in liver weight, ZBED6-/- pigs show comparable levels of IGF2 expression to those of WT controls. A mechanistic study revealed that elevated methylation in the liver abrogates ZBED6 binding at the IGF2 locus, explaining the unaltered hepatic IGF2 expression in ZBED6-/- pigs. These results indicate that a ZBED6-IGF2-independent regulatory pathway exists in the liver. Transcriptome analysis and ChIP-PCR revealed new ZBED6 target genes other than IGF2, including cyclin dependent kinase inhibitor 1A (CDKN1A) and tsukushi, small leucine rich proteoglycan (TSKU), that regulates growth of muscle and liver, respectively.

Investigation of the adjuvant properties of nanoparticles from a birch bark extract used for immunization of mini pigs of the Svetlogorsk population

The adjuvant properties of nanoparticles derived from a dry birch bark extract were studied. Immunization experiments were carried out on mini pigs of the Svetlogorsk population, a human biomodel. Animals received two subcutaneous injections of the antigen at a dose of 0.1 mg/kg with an interval of 14 days. The addition of an aqueous suspension of nanoparticles to the immunogen samples up to a final concentration of 0.5 mg/ml led to an increase in the immune response. No side effects were observed. The antibody titers in blood sera on the 60th and 90th days from the start of immunization were comparable to those obtained under similar conditions using Freund’s adjuvant (1:4000).

Preclinical evaluation of the new EDGE SP 1000 single-port robotic surgical system in gynecology minimal access surgery.

The aim of this study is to evaluate the feasibility and safety of a new single-port robotic surgical system for gynecological surgery in the porcine model. Six female Tibetan miniature pigs underwent robot-assisted single-port laparoscopic total hysterectomy with the newly developed single-port EDGE SP1000 platform. Estimated blood loss (EBL), docking time, operative time, and intraoperative and postoperative complications were recorded. Postoperative pain was assessed by VAS (visual analog scale) score at 6h, 12h, 24h, and 48h. Then the experimental animals were observed for one week after surgery to assess their mental status, incisional infections and finally euthanized for necropsy to assess the recovery of the vaginal stump. Six hysterectomies of pigs were successfully completed. There were no significant intraoperative complications in the six surgeries. The average total operation time was 113.33min (95-143min), and the average docking time was 5.5min (4-7min). The average EBL was 10ml (5 ~ 20ml). The mean VAS scores at 6, 12, 24, and 48h postoperatively were 6.3, 5.7, 5, 3, respectively. At 7days postoperatively, no significant incisional infections or other complications were observed. Post-euthanasia examination of the pelvis showed no significant abnormalities in the vaginal stump. This preclinical study of a new single-port surgical system for gynecologic procedures demonstrated the safety and feasibility of the EDGE SP1000 system in porcine models. Further studies are required to assess its clinical utility in the future.

MRI Assessment of Cardiac Radioablation Lesion at the Cavotricuspid Isthmus in Mini Pigs

Stereotactic body radiotherapy (SBRT) is an emerging non-invasive treatment in the management of cardiac arrhythmias. The purpose of this research is to evaluate the MR imaging in the detection of radioablation lesion at the cavotricuspid isthmus (CTI) in mini pigs.Four mini pigs underwent magnetic resonance (MR) evaluation of heart function and invasive electrophysiology assessment using electroanatomical mapping (EAM) before and 3 months after SBRT with single-fraction doses of 25Gy at the CTI. SBRT simulation, planning, and treatments were performed with the use of standard techniques. MR examination, including diffusion-weighted MRI, dynamic Gd-enhanced MRI, MR spectroscopy, and T2-weighted MRI were performed before and 3 months after SBRT, followed by histopathologic examination. One radiation oncologist and one radiologist evaluated the detectability and image quality for the irradiated site. MRI findings of the CTI radioablation lesion was compared to electrophysiology and histopathology findings.A total dose of 25 Gy was delivered to the CTI (median volume of 25 cc) in a single procedure according to the radiation therapy oncology group. The mean radiation dose to the heart was 7 Gy. The maximal doses (< 0.05 cc) to the left and right coronary arteries were 14 Gy and 13 Gy, respectively. EAM visualized the irradiated site and confirmed clockwise conduction block across the CTI. Gd-enhanced T1-weighted imaging could only detect the irradiated site. There were no statistical differences in the image quality of the all MR images.These data demonstrated the feasibility of SBRT for creating conduction block across the CTI in mini pigs. Gd-enhanced T1-weighted imaging was essential in assessing the radioablation lesion.

Experimental Pulp-Capping Agent Radiopaque Dicalcium Silicate Cement Facilitates Dentinogenesis

This study was designed to comparatively evaluate an experimental pulp-capping agent radiopaque dicalcium silicate cement (RDSC), white-colored mineral trioxide aggregate (WMTA), iRoot BP Plus and Biodentine both ex vivo and in vivo. Fourier Transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) were utilized to analyze the phase composition of pulp-capping agents. The surface morphology and element analysis were finished by Scanning electron microscopy (SEM) and Energy Dispersive X-Ray Spectroscopy (EDX). Color stability of the cements and pulp responses induced by different cements were examined by ex-vivo human tooth culture model and in-vivo miniature pig model. Micro-computed tomography was used for quantitative evaluation of the newly formed mineralized tissue. RDSC exhibited discoloration in both models, while WMTA exhibited more visible discoloration. The occurrence of discoloration for WMTA was significantly higher than that of RDSC (p &amp;lt; 0.05), iRoot BP Plus and Biodentine on the 7th day, also higher (p &amp;lt; 0.05) than that of iRoot BP Plus and Biodentine on the 70th day. Mineralized foci were noted in all 7-days groups except the control group both ex vivo and in vivo. Intact and complete reparative dentin bridge formation which possessed tubular structures was noted in all 70-days groups in vivo. RDSC appeared to induce the thickest dentin bridge formation among all these pulp-capping agents which showed statistically significant difference to that of Biodentine (p &amp;lt; 0.05). With decent biological properties, RDSC may have the potential to be a pulp-capping agent recommended in the non-aesthetic area alternative to WMTA, Biodentine and iRoot BP Plus.