Zealand Rabbits Research Articles

Effect of radiation cross-linked collagen scaffold in alveolar ridge preservation of extraction socket.

This study aimed to evaluate the properties of radiation cross-linked collagen scaffold (RCS) and its efficacy for alveolar ridge preservation (ARP). RCS was prepared from collagen dispersion by electron beam irradiation and freeze-drying. The microstructure, swelling ratio, area alteration and mechanical properties of RCS were characterized. Fifty-four New Zealand rabbits performing incisor extraction on maxilla and mandible were randomly assigned into positive, sham operation or treatment groups. Micro-computed tomography (micro-CT) scans, performed after 1, 4, and 12 weeks of surgery, were to assess changes in ridge height at buccal and palatal side, in ridge width and in micromorphological parameters. Histological analysis accessed socket microarchitecture. The results showed that RCS had stable mechanical properties and morphologic features that provided a reliable physical support for ARP. Dimensional changes in treatment group revealed significantly greater vertical height at buccal (5.32 [3.37, 7.26] mm, p < .0001) and palatal (4.37 [2.66, 6.09] mm, p < .0001) side, and horizontal width at the maxilla (0.16 [0.04, 0.28] mm, p < .01) and mandible (0.33 [0.11, 0.54] mm, p < .01) than those in sham operation group after 12 weeks. The treatment group had advantage than positive group in vertical height preservation, quantitatively. The order and density of bone trabeculae were improved in treatment group. These findings indicated that RCS had the potential to serve as an effective scaffold for ARP.

The ACE2/Ang-(1-7)/MasR axis alleviates brain injury after cardiopulmonary resuscitation in rabbits by activating PI3K/Akt signaling.

Death among resuscitated patients is mainly caused by brain injury after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The angiotensin converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor (MasR) axis has beneficial effects on brain injury. Therefore, we examined the roles of the ACE2/Ang-(1-7)/MasR axis in brain injury after CA/CPR. We used a total of 76 male New Zealand rabbits, among which 10 rabbits underwent sham operation and 66 rabbits received CA/CPR. Neurological functions were determined by assessing serum levels of neuron-specific enolase and S100 calcium-binding protein B and neurological deficit scores. Brain water content was estimated. Neuronal apoptosis in the hippocampus was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assays. The expression levels of various genes were measured by enzyme-linked immunosorbent assay and western blotting. Ang-(1-7) (MasR activator) alleviated CA/CPR-induced neurological deficits, brain edema, and neuronal damage, and A779 (MasR antagonist) had the opposite functions. The stimulation of ACE2/Ang-(1-7)/MasR inactivated the ACE/Ang II/AT1R axis and activated PI3K/Akt signaling. Inhibiting PI3K/Akt signaling inhibited Ang-(1-7)-mediated protection against brain damage after CA/CPR. Collectively, the ACE2/Ang-(1-7)/MasR axis alleviates CA/CPR-induced brain injury through attenuating hippocampal neuronal apoptosis by activating PI3K/Akt signaling.

Enhancing the hypotensive effect of latanoprost by combining synthetic phosphatidylcholine liposomes with hyaluronic acid and osmoprotective agents.

The first line of glaucoma treatment focuses on reducing intraocular pressure (IOP) through the prescription of topical prostaglandin analogues, such as latanoprost (LAT). Topical ophthalmic medicines have low bioavailability due to their rapid elimination from the ocular surface. Nanotechnology offers innovative ways of enhancing the ocular bioavailability of antiglaucoma agents while reducing administration frequency. This study aims to combine LAT-loaded synthetic phosphatidylcholine liposomes with hyaluronic acid (0.2%w/v) and the osmoprotectants betaine (0.40%w/v) and leucine (0.90%w/v) (LAT-HA-LIP) to extend the hypotensive effect of LAT while protecting the ocular surface. LAT-HA-LIP was prepared as a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, cholesterol and α-tocopherol acetate. LAT-HA-LIP exhibited high drug-loading capacity (104.52 ± 4.10%), unimodal vesicle sizes (195.14 ± 14.34nm) and a zeta potential of -13.96 ± 0.78mV. LAT-HA-LIP was isotonic (284.00 ± 1.41mOsmL-1), had neutral pH (7.63 ± 0.01) and had suitable surface tension (44.07 ± 2.70mNm-1) and viscosity (2.69 ± 0.15mPas-1) for topical ophthalmic administration. LAT-HA-LIP exhibited optimal in vitro tolerance in human corneal and conjunctival epithelial cells. No signs of ocular alteration or discomfort were observed when LAT-HA-LIP was instilled in albino male New Zealand rabbits. Hypotensive studies revealed that, after a single eye drop, the effect of LAT-HA-LIP lasted 24h longer than that of a marketed formulation and that relative ocular bioavailability was almost three times higher (p < 0.001). These findings indicate the potential ocular protection and hypotensive effect LAT-HA-LIP offers in glaucoma treatment.

Calcium hydroxide nanoparticles synthesized with medicinal plants extract as surface coating for titanium alloy bone implants using a simple method: Characterization and biomechanical evaluation

Advanced techniques have been developed to enhance the bioactivity and efficacy of biomedical titanium implants by modifying their surfaces. One such approach involves coating the titanium surface with biomaterials at the nanoscale level. In recent times, medicinal plant extracts have generated attention for nanoparticle synthesis due to their advantageous biomedical properties. Greenly synthesized carob-mediated calcium hydroxide nanoparticles exhibited promising results concerning both anti-inflammatory and osteogenic potentials during in vitro investigations. This study aimed to deposit these nanoparticles onto titanium-alloy bone implants through modifications to the established eco-friendly drop-casting method, characterize the surface, and biomechanically test it on rabbit tibias using torque removal analysis. Surface characterization utilizing scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction analysis successfully coated titanium implants with this material. A biomechanical study conducted on New Zealand rabbits revealed significantly higher peak torque removal values of the coated implants compared to uncoated implants (p < 0.01), suggesting enhanced osseointegration. The drop-casting method employed in this study is a straightforward, cost-efficient, and simple technique for coating various biomaterials onto titanium surfaces. This research lays the groundwork for further exploration of the potential benefits of using calcium hydroxide nanoparticles as titanium bone implant coatings, including their impact on bone healing, bactericidal capabilities, hemostatic potentials, and cellular activities.

Radiological, histological and clinical side effects of incisor trimming in rabbits.

Incisor malocclusion in rabbits (Oryctolagus cuniculus) is a common clinical problem seen in general practice. Given that the growth rate is about 2 mm per week, a lack of wear quickly leads to feeding difficulties and soft tissue injuries. Therefore, pathologically elongated incisors must be shortened every three to six weeks. The goal of this study was to assess the potential adverse effects on dental and periodontal tissues associated with the three most commonly used trimming methods: nail cutter, diamond-coated cutting disc and diamond burr. The left mandibular incisor of 28 healthy New Zealand rabbits was subjected to four trimmings with one of the three cutting methods. After the fattening period, the mandibles were collected and both mandibular incisors were investigated on dental radiographs, micro-computed tomography scans and histological sections. Dental and periodontal tissue changes were evaluated. This study allowed a more accurate statement of the potential short-term adverse effects of the three trimming methods. At the clinical level, the nail cutter caused the formation of an irregular occlusal surface with sharp edges. Both engine-drive methods allowed the attainment of a smooth surface but the disc was less accurate. Histological evaluation revealed that the primary modifications, including coronal fractures, periodontal ligament widening and inflammation, reparative osteodentine, paracementosis and biofilm accumulation, were found in the nail cutter group.

Formulation of Metoclopramide Hydrochloride-Loaded Lipid Carriers by QbD Approach for Combating Nausea: Safety and Bioavailability Evaluation in New Zealand Rabbit.

The focus of the research was to overcome the limitations of metoclopramide (MTC) when administered intranasally. The aim was to improve its bioavailability, increase patient compliance, and prolong its residence time in the nasal cavity. MTC-loaded liposomes were prepared by applying the film hydration method. A study was conducted to determine how formulation variables affected encapsulation efficiency (EE %), mean particle size (MPS), and zeta potential (ZP). The MTC-liposomes were further loaded into the in situ gel (gellan gum) for longer residence times following intranasal administration. pH, gelling time, and in vitro release tests were conducted on the formulations produced. In vivo performance of the MTC-loaded in situ gels was appraised based on disparate parameters such as plasma peak concentration, plasma peak time, and elimination coefficient compared to intravenous administration. When the optimal liposome formulation contained 1.98% of SPC, 0.081% of cholesterol, 97.84% of chloroform, and 0.1% of MTC, the EE of MTC was 83.21%, PS was 107.3 nm. After 5 h, more than 80% of the drug was released from MTC-loaded liposome incorporated into gellan gum in situ gel formulation (Lip-GG), which exhibited improved absorption and higher bioavailability compared to MTC loaded into gellan gum in situ gel (MTC-GG). Acceptable cell viability was also achieved. It was found out that MTC-loaded liposomal in situ gel formulations administered through the nasal route could be a better choice than other options due to its ease of administration, accurate dosing, and higher bioavailability in comparison with MTC-GG.

Design, synthesis, characterization and evaluation of methionine-ABO based TSPO ligand

A novel series of molecules based on the acetamidobenzoxazolone (ABO) skeleton has been developed for diagnosing pathological conditions characterized by over-expression of the 18 kDa translocator protein (TSPO) in organs. To enhance the targeting of TSPO, methionine methyl ester was incorporated into the ABO structure, yielding ABMO 2-[2-(2-oxo-benzoxazol-3-yl)-acetylamino]-4-methylsulfanyl-butyric acid methyl ester, for potential biomedical applications. Two analogs, ABMO-Br and ABMO-Cl, with halogen substitutions at the 5th position of benzoxazolone, were designed and validated in silico for their pharmacokinetic properties, adherence to drug-like criteria, and blood-brain barrier penetration ability.Docking studies revealed the affinity of the designed molecules towards both native and mutant forms of TSPO. Based on in silico analysis, halogen derivatives were selected for synthesis. An efficient three-step synthetic procedure was employed to produce ABMO-Cl/Br, which were purified by column chromatography and characterized by NMR spectroscopy.The resultant ligands were radiolabeled with 99mTc, exhibiting significant stability in saline solution for up to 24 hours. Blood kinetic studies conducted on New Zealand rabbits demonstrated substantial clearance from blood within 1 hr. Ex vivo and in vivo biodistribution studies confirmed uptake of the ligands in TSPO-rich organs. In conclusion, these studies validated the ability of these compounds to cross the blood-brain barrier in animal models. These findings underscore the potential of ABMO-Cl/Br as SPECT markers targeting TSPO. Further investigations using animal models are warranted to fully elucidate the utility of these ligands in diagnosing TSPO-related conditions.

Biomimicking Covalent Organic Frameworks Nanocomposite Coating for Integrated Enhanced Anticorrosion and Antifouling Properties of a Biodegradable Magnesium Stent

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), constituting a multiscale crosslinked network that modifies the stent's surface microstructure. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. Statement of SignificanceBiodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications.

Myocardial Expression of Pluripotency, Longevity, and Proinflammatory Genes in the Context of Hypercholesterolemia and Statin Treatment.

Background: This study sought to assess the effect of statin therapy on myocardial inflammation in a White New Zealand rabbit model of atherogenesis. Methods: The mRNA expression levels of pro-inflammatory, pluripotency, and aging-related markers were quantified following a controlled feeding protocol and statin treatments. Results: Following high-cholesterol diet induction, we observed significant upregulation in the myocardial mRNA levels of MYD88, NF-κB, chemokines (CCL4, CCL20, and CCR2), IFN-γ, interleukins (IL-1β, IL-2, IL-4, IL-8, IL-10, and IL-18), and novel markers (klotho, KFL4, NANOG, and HIF1α). In contrast, HOXA5 expression was diminished following a hyperlipidemic diet. Both statin treatments significantly influenced the markers studied. Nevertheless, rosuvastatin administration resulted in a greater reduction in MYD88, NF-kB, chemokines (CCL4, CCL20, and CCR2), and interleukins IL-1β, IL-8, KLF4, NANOG, and HIF1α than fluvastatin. Fluvastatin, on the other hand, led to a stronger decrease in IL-4. Downregulation of IL-2 and IL-18 and upregulation of IFNβ and HOXA5 were comparable between the two statins. Notably, rosuvastatin had a stronger effect on the upregulation of klotho and IL-10. Conclusion: Overall, statin therapy significantly attenuated inflammatory, pluripotency, and klotho expression in myocardial tissue under atherogenic conditions. Our findings also highlight the differential efficacy of rosuvastatin over fluvastatin in curtailing proatherogenic inflammation, which could have profound implications for the clinical management of cardiovascular disease.

Niche partitioning and competition between different rabbit breeds using stable isotopes

Stable isotope analysis (SIA) is an evolving method for determining diet, understanding food web and resolving biogeochemical issues in the ecosystem. This study aims to trace out ecological niche preferences/partitioning and competition among the lagomorphs, including two different breeds of European rabbit (Oryctolagus cuniculus), New Zealand rabbit and American Dutch rabbit, using SIA. Thirty-two samples of tooth enamel were analysed, which were collected from different districts of Punjab, Pakistan, including Okara, Sahiwal and Kasur. Among these samples, 16 belonged to the New Zealand breed (08 male and 08 female rabbits) and 16 to the American Dutch breed (08 male and 08 female rabbits). Significant (P&lt;0.001) intergender differences in the isotope content of δ13C in the enamel for New Zealand and American Dutch rabbit were found. The European rabbits showed significant differences for both genders in the stable isotope of oxygen in the enamel (δ18O) values (P=0.05). Nitrogen stable isotope results showed no significant intergender differences between American Dutch and New Zealand rabbits (P=0.24). The stable isotope results for δ13C, δ15N, and δ18O indicate that the trophic niche partitioning of both breeds overlaps, which can potentially cause competition for resources, whereas the water intake may differ among different genders, which may reflect differential gender-related activities. The archaeological and fossilised data of lagomorphs is present, but there is no significant literature available for living lagomorphs (rabbits). In general, this study provides a basic and first dataset for δ13C, δ15N, and δ18O of living lagomorphs, which can serve as a comparative dataset for future studies.

First Detection and Circulation of RHDV2 in New Zealand

Rabbit haemorrhage disease virus 2 (RHDV2) is a highly pathogenic lagovirus that causes lethal disease in rabbits and hares (lagomorphs). Since its first detection in Europe in 2010, RHDV2 has spread worldwide and has been detected in over 35 countries so far. Here, we provide the first detailed report of the detection and subsequent circulation of RHDV2 in New Zealand. RHDV2 was first detected in New Zealand in 2018, with positive samples retrospectively identified in December 2017. Subsequent time-resolved phylogenetic analysis suggested a single introduction into the North Island between March and November 2016. Genetic analysis identified a GI.3P-GI.2 variant supporting a non-Australian origin for the incursion; however, more accurate identification of the source of the incursion remains challenging due to the wide global distribution of the GI.3P-GI.2 variant. Furthermore, our analysis suggests the spread of the virus between the North and South Islands of New Zealand at least twice, dated to mid-2017 and around 2018. Further phylogenetic analysis also revealed a strong phylogeographic pattern. So far, no recombination events with endemic benign New Zealand rabbit caliciviruses have been identified. This study highlights the need for further research and surveillance to monitor the distribution and diversity of lagoviruses in New Zealand and to detect incursions of novel variants.

Abstract 3187: Enhancing STING activation by cyclic dinucleotide-manganese particles for systemic cancer immunotherapy

Abstract Background: Activating the innate immune pathway of stimulator of interferon genes (STING) can elicit potent anti-tumor immunity via the production of type-I interferons (IFN-I). However, cyclic-dinucleotide (CDN) STING agonists have undesirable pharmacological properties. Most CDNs in clinical development are administered intratumorally, thus precluding their utility against advanced cancer. Here, we report the development of a new nanoparticle system for the systemic delivery of CDN STING agonists with potent efficacy, favorable pharmaceutical properties, and acceptable safety profiles. Methods: Various metal ions were screened for synergy with CDNs for IFN-I response from bone marrow-derived dendritic cells. Lipid nanoparticles carrying CDN and manganese ions (termed SNP) were synthesized. Mice bearing syngenetic tumors (including CT26 and B16F10) as well as genetically engineered mouse models were treated by intravenous administration of SNP, followed by tumor monitoring and immune profiling of the tumor microenvironment. White New Zealand rabbits bearing VX2 tumors as well as healthy mongrel dogs were treated with SNP and evaluated. Lastly, human tumor biopsies derived from head and neck squamous cell carcinoma (HNSCC) patients were incubated with SNP or soluble STING agonists and analyzed for immune activation. Results: We identified that Mn2+ achieved strong synergy with CDN STING agonists for inducing IFN-I production. SNP carrying CDN and Mn2+ was dosed intravenously in mice, leading to robust IFN-I response, remodeling of the immunosuppressive tumor microenvironment, and expansion of anti-tumor CD8+ T cells. Intravenous SNP therapy resulted in robust anti-tumor efficacy in multiple murine tumor models, including CT26, B16F10, and a genetically engineered mouse model of MMTV-PyMT triple-negative breast cancer. We have also observed robust anti-tumor efficacy of SNP against VX2 squamous carcinomas in rabbits and have demonstrated the safety of intravenous SNP therapy in healthy dogs. Mechanistically, the efficacy of SNP therapy was dependent on the host STING expression but independent of the tumor STING expression. In addition, the anti-tumor efficacy of SNP was decreased in mice lacking Ifnar1 or Ifngr1 expression in the B16F10 melanoma model, showing the crucial effects of IFN-I and IFN-II responses. Moreover, SNP treatment led to robust IFN-I responses from fresh human tumor biopsies derived from HNSCC patients. Conclusions: SNP empowers highly effective systemic cancer immunotherapy via nanotechnology. It also underscores the potential of utilizing metal ions for immune-mediated disease treatment. Citation Format: Xingwu Zhou, Xiaoqi Sun, Wang Gong, Ziye Wan, Teresa Krieger-Burke, Vilma Yuzbasiyan-Gurkan, Yu Leo Lei, James Moon. Enhancing STING activation by cyclic dinucleotide-manganese particles for systemic cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3187.

Total meniscus replacement with a 3D printing of network hydrogel composite scaffold in a rabbit model.

The aim of this study was to evaluate the role of a novel total meniscal implant in promoting meniscal regeneration and protecting articular cartilage in a rabbit model for 3 and 6 months. Thirty-six New Zealand rabbits were selected and divided into poly(ɛ-caprolactone) (PG-Pg) scaffold group, meniscectomy group and sham group. In this study, it was investigated whether PG-Pg scaffold can prevent articular cartilage degeneration and promote tissue degeneration, and its mechanical properties at 3 and 6 months after surgery were also explored. The degree of articular cartilage degeneration was significantly lower in the PG-Pg scaffold group than in the meniscectomy group. The number of chondrocytes increased in the PG-Pg scaffold at 3 and 6 months, while a gradual increase in the mechanical properties of the PG-Pg stent was observed from 6 months. The PG-Pg scaffold slows down the degeneration of articular cartilage, promotes tissue regeneration and improves biomechanical properties after meniscectomy. This novel meniscus scaffold holds promise for enhancing surgical strategies and delivering superior long-term results for individuals with severe meniscus tears. NA.

A nontoxic strontium nanoparticle that holds the potential to act upon osteocompetent cells: An in vitro and in vivo characterization.

Estrogen deficiency, long-term immobilization, and/or aging are commonly related to bone mass loss, thus increasing the risk of fractures. One option for bone replacement in injuries caused by either traumas or pathologies is the use of orthopedic cement based on polymethylmethacrylate (PMMA). Nevertheless, its reduced bioactivity may induce long-term detachment from the host tissue, resulting in the failure of the implant. In view of this problem, we developed an alternative PMMA-based porous cement (pPMMA) that favors cell invasion and improves osteointegration with better biocompatibility. The cement composition was changed by adding bioactive strontium-nanoparticles that mimic the structure of bone apatite. The nanoparticles were characterized regarding their physical-chemical properties, and their effects on osteoblasts and osteoclast cultures were assessed. Initial in vivo tests were also performed using 16 New Zealand rabbits as animal models, in which the pPMMA-cement containing the strontium nanoparticles were implanted. We showed that the apatite nanoparticles in which 90% of Ca2+ ions were substituted by Sr2+ (NanoSr 90%) upregulated TNAP activity and increased matrix mineralization. Moreover, at the molecular level, NanoSr 90% upregulated the mRNA expression levels of, Sp7, and OCN. Runx2 was increased at both mRNA and protein levels. In parallel, in vivo tests revealed that pPMMA-cement containing NanoSr 90%, upregulated two markers of bone maturation, OCN and BMP2, as well as the formation of apatite minerals after implantation in the femur of rabbits. The overall data support that strontium nanoparticles hold the potential to up-regulate mineralization in osteoblasts when associated with synthetic biomaterials.

Moringa oleifera leaf extract promotes the healing of critical sized bone defects in the mandibles of rabbits

ObjectiveThe search for an osteopromotive material that enhances the efficacy of alloplasts in reconstructive surgeries has been going on for years. This study aimed to histologically and histomorphometrically evaluate the efficiency of Moringa oleifera leaf extract as an osteopromotive biomaterial.DesignThe study is a prospective randomized controlled animal study. 24 adult male New Zealand rabbits were equally allocated into test and control groups. Critical-sized bone defects were created in the edentulous areas of the mandibles of rabbits. The defects of the control group were filled with Beta-tricalcium Phosphate, while the defects of the test group were filled with Beta-tricalcium Phosphate combined with Moringa oleifera leaf extract. The results were evaluated histologically and histomorphometrically.ResultsHistological and histomorphometric analysis showed a significant increase in the surface area of bone and the number of osteoblasts in test groups compared to those in the control groups.ConclusionMoringa oleifera leaf extract has a positive effect on bone regeneration in critical-sized bone defects.

4D label-free quantitative proteomic analysis identifies CRABP1 as a novel candidate gene for litter size in rabbits.

In commercial rabbit breeding, litter size is a crucial reproductive trait. This trait directly determines the reproductive ability of female rabbits and is crucial for evaluating the production efficiency. We here compared differentially expressed proteins of in the ovary tissue from New Zealand female rabbits with high (H) and low (L) litter sizes by using 4D label-free quantitative proteomic technology and identified 92 differential proteins. The biological functions of these proteins were revealed through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Most distributions of GO and KEGG were related to reproduction, growth development, and metabolism. Furthermore, a novel candidate gene Cellular Retinoic Acid Binding Protein-1 (CRABP1), which was highly expressed in the L group, was selected for further biological function verification. The Cell Counting Kit-8 assay and flow cytometry analysis revealed that CRABP1 can promote granulosa cell (GC) apoptosis and inhibit GC proliferation. Furthermore, qRT-PCR and western blotting analysis revealed that CRABP1 regulates the genes (HSD17B1, Wnt-10b, FSHR, TAF4B, BMP15, and BMP6) and protein (Wnt-10b) associated with steroid hormone synthesis and follicle development. The PCR product direct sequencing method revealed single nucleotide polymorphisms in the core promoter region of CRABP1. Luciferase activity assays revealed that the transcriptional activity of the GG genotype was significantly higher than that of the TT or TG genotype. Different genotypes are accompanied by changes in transcription factors, which indicates that T-359G polymorphism can regulate CRABP1 expression. In general, we identified litter size-related genes and revealed the mechanism underlying the effect of CRABP1 on litter size. CRABP1 serves as a key factor in the reproductive capacity of rabbits and can act as a molecular biomarker for the breeding of New Zealand rabbits.

Interaction Between Microbubbles and Microwave Ablation: A Phantom and Rabbit Model.

This study aimed to explore the interactions between microbubbles and microwave ablation (MWA). The study employed custom-made phantoms (in vitro) and white New Zealand rabbits (in vivo). MWA was performed with or without microbubbles in the phantoms (2 × 105 particles mL-1 ) and rabbit livers (intravenous injection of 0.05 mL/kg SonoVue). During the MWA, K-type thermocouple probes were used to monitor the MWA-induced temperature increase. Contrast-enhanced ultrasound imaging (CEUS) was used to monitor and analyze the microbubbles signal intensity. After MWA, the ablation-zone volumes were evaluated and compared between the groups with and without microbubbles. In both the phantom models and rabbits, microbubbles showed no significant influence on MWA, including the ablation range and MWA-induced temperature increase. In phantoms and rabbit livers filled with microbubbles, MWA caused the formation of a gradually expanding microbubble-defect region over the ablation time. An increase in the temperature caused microbubble destruction. Microbubbles had no significant influence on MWA. However, MWA induced the destruction of microbubbles in a temperature-dependent manner. Thus, the poor thermotolerance of microbubbles is a non-negligible barrier when using CEUS to monitor the ablation range during MWA in real-time.

Mesenchymal stromal cells from human Wharton's jelly modulate the intraocular immune response in a glucocorticoid hypertension model: an exploratory analysis.

Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells. Recent research suggests that immunological changes such as cytokine imbalance may play a role in its pathophysiology. This implies that immunomodulation, similar to that produced by mesenchymal cells, could be a potential therapeutic avenue for this disease. However, the effects of intravitreal injections of human Wharton's jelly derived mesenchymal stromal cells(hWJ-MSCs) on intraocular immune response have not been assessed in ocular hypertension (OH) models. We measured explored this by measuring cytokine levels and expression of other markers, such as glial fibrillary acidic protein (GFAP) and T cells, in 15 randomly divided New Zealand rabbits: G1: OH; G2: hWJ-MSCs; and G3: OH+hWJ-MSCs. We analyzed the aqueous humor (IL-6, IL-8, and TNF-α) and vitreous humor (IFN-γ, IL-10, and TGF-β) using ELISA and flow cytometry (cell populations), as well as TCD3+, TCD3+/TCD4+, and TCD3+/TCD8+ lymphocytes, and GFAP in the retina and optic nerve through immunohistochemistry. We found a decrease in TNF-α, IL-6, IFN-γ, IL-10, and IL-8 in G3 compared to G1 and an increase in TGF-β in both G2 and G3. TCD3+ retinal infiltration in all groups was primarily TCD8+ rather than TCD4+ cells, and strong GFAP expression was observed in both the retina and optic nerves in all groups. Our results suggest that cellular and humoral immune responses may play a role in glaucomatous optic neuropathy, and that intravitreal hWJ-MSCs can induce an immunosuppressive environment by inhibiting proinflammatory cytokines and enhancing regulatory cytokines.

EFFECT OF PEGYLATED POLYPROPYLENE IMINE DENDRITIC ARCHITECTURE ON PHARMACOKINETICS OF PYRAZINAMIDE ON RABBITS

Objective: This study sought to investigate the impact of pegylated polypropylene imine dendrimer-loaded pyrazinamide on drug delivery and assess this novel formulation's pharmacokinetic parameters. Methods: Various concentrations of pyrazinamide-loaded dendrimers were formulated in four distinct batches, with the most promising formulation selected for administration to New Zealand rabbits. Plasma concentrations of the drug were subsequently compared to those of the pure drug. Pharmacokinetic parameters, including maximum plasma concentration (Cmax), time to reach Cmax (tmax), the area under the curve (AUC), the area under the first moment curve (AUMC), elimination rate constant (λz), biological half-life (t1/2), and mean residence time (MRT), were meticulously determined. Results: The plasma drug concentration Vs time profile illustrated a sustained release pattern for the pyrazinamide drug-loaded dendrimer formulation compared to the pure drug. While a minor alteration was observed in peak plasma concentration, a notable divergence was noted in all other pharmacokinetic parameters. The AUC demonstrated a fourfold increase for pyrazinamide drug-loaded dendrimers, rising from 8657.94±295.10 to 34663.89±702.89 (ng/ml/h), and the mean residence time nearly doubled when compared to the pure drug. Conclusion: Pyrazinamide drug-loaded dendrimers exhibit significant potential for enhancing drug release compared to the pure drug. This novel formulation promises a substantial and sustained drug release profile, holding promise for improving therapeutic outcomes and patient compliance in the treatment of relevant conditions.

Experimental Study on Transverse-Axis Neovascularization of Acellular Dermal Matrix Using Platelet-Rich Plasma

Background: Acellular dermal matrices (ADMs) have shown promise in promoting tissue regeneration; however, their integration in challenging cases with limited vertical-axis neovascularization remains difficult. This study investigates whether clinically meaningful transverse-axis neovascularization is identified in ADM engraftment and whether this can be further accelerated by platelet-rich plasma (PRP).Methods: ADM and PRP-soaked ADM were implanted into New Zealand rabbits, and histological analysis was performed at different periods to compare neovascularization.Results: Histological analysis revealed that among 32 biopsy sites, there was transverse-axis neovascularization with an average length of 606.89 μm. When divided into two groups for assessing the impact of PRP on transverse-axis neovascularization, the extent of such neovascularization was measured as 582.99 μm in the control group and 630.79 μm in the experimental group. However, there was no statistically significant difference between the two groups (P=0.693).Conclusion: The results of the present study indicate that achieving meaningful transverse-axis neovascularization in implanted ADMs remains a challenge, warranting further investigation into ADM structure and vertical-axis neovascularization.