Search Results (217)

Background/Objectives: Knee osteoarthritis stands as the highest prevalent joint disease worldwide, affecting millions of adults and significantly impairing mobility and quality of life. Pro-inflammatory cells and cytokines are considered key players in the pathophysiology of the disease. In previous work, two anti-inflammatory therapeutic approaches were developed: a secretome enriched in anti-inflammatory cytokines, and nanoliposome-bound TRAIL (LUV-TRAIL), with proven efficacy against rheumatoid arthritis in rabbits. Methods: In this work, we evaluated the ability of these treatments to prevent the development of osteoarthritis (OA) in an ovine model following meniscectomies. Two weeks after the surgeries, knees were treated with several rounds of single or combined therapy, and then sheep were left untreated for several months. Knee damage was followed by X-ray analysis and, after sacrifice, assessed through macroscopic inspection, histological determinations, and inflammatory cytokine measurements. Results: The combined therapy had a significant positive effect against osteoarthritis development. Specifically, the combination is capable of improving knee injury in the first stages of OA in several parameters, such as synovial hyperplasia and tibial plateau damage, which are two of the most frequently damaged areas. Other markers, such as synovial inflammation and X-ray and macroscopic images, also presented a tendency to improved scores. Conclusions: The combination of the secretome with LUV-TRAIL represents a promising therapy worth exploring further in osteoarthritis treatment and/or prevention. Full article

Background: Restenosis and intimal hyperplasia following arterial bypass surgery or percutaneous interventions remain major clinical challenges that significantly impair long-term vessel patency and clinical outcomes, despite substantial technological progress. Preclinical research aimed at understanding the biological mechanisms underlying restenosis and developing effective therapeutic strategies relies heavily on experimental animal models. Methods: A narrative review of the literature was conducted using PubMed, Embase, Web of Science Core Collection, and the Cochrane Library to identify relevant studies describing animal models of restenosis and intimal hyperplasia following percutaneous cardiovascular interventions. Results: The reviewed studies describe a broad range of animal models, including rodents, rabbits, swine, and other large animals, with each species exhibiting distinct anatomical, physiological, and pathological characteristics that influence its suitability for studying restenosis and intimal hyperplasia. Considerable interspecies variability exists in vascular healing responses, inflammatory processes, and translational relevance. Conclusions: Animal models remain indispensable tools for investigating restenosis and intimal hyperplasia and for evaluating novel pharmacological and device-based therapies. Understanding interspecies differences is essential for designing appropriate experimental studies and interpreting findings. Careful animal model selection is critical to improving translational relevance and facilitating successful clinical translation. Full article

During tendon healing, collagen III expression precedes that of collagen I. The collagen I-to-III ratio at a certain time point post-laceration serves as an indicator of the healing status. Consequently, it is crucial to understand how different therapeutic approaches to support tendon healing affect the collagen I-to-III ratio in the extracellular matrix of a healing tendon, particularly across distinct anatomical zones. We compared the impact of a platelet-derived growth factor-BB (PDGF-BB) treatment via controlled release from coaxially electrospun DegraPol^® (Ab medica, Cerro Maggiore, Italy) hollow-fiber mesh with a treatment by the vehicle alone (no PDGF-BB) in the rabbit Achilles tendon full transection model and provide data on the collagen I-to-III ratio 3 weeks post-operation. For this purpose, we compared a dual-color Herovici staining to two single IHC labeling, for collagen I and collagen III, respectively. Herovici staining (HV) was expected to offer a more precise approach (pink-to-blue histogram) than the two separately labeled IHC stainings, both with chromogenic DAB labeling (red-to-green histogram), despite an anticipated positive correlation of the data assessed by these methods. Different zones were compared, i.e., native tendon tissue, reactive zone at interface to implant, hot zone within the core of the healing tendon and the zone within the scaffold, meaning the collagen deposited within the fibers of the implanted DegraPol^® tube, respectively. The analysis revealed that the ratios obtained via HV correlated weakly with the ratios obtained by IHC. Based on HV, PDGF-BB therapy led to higher collagen I-to-III ratios in all zones, except for the zone within the scaffold pores, while IHC did not reveal significant differences. Notably, collagen I-to-III ratios were not higher in immediate proximity, but rather distal from the PDGF-BB releasing implant, specifically in the core of the healing tendon tissue. Hence, a PDGF-BB therapy is suggestive of greater collagen maturation in specific zones of the healing tendon. Full article

Osteoarthritis (OA) is the most common multifactorial joint disease characterized by progressive cartilage degradation and impaired tissue repair. Osteochondral defects represent a major clinical challenge within OA, as damage to cartilage and underlying bone can initiate degenerative changes and contribute to joint deterioration. The Wnt/β-catenin signaling pathway plays an important role in OA pathogenesis, and its dysregulation contributes to chondrocyte catabolism and cartilage loss. NOTUM, an extracellular Wnt inhibitor, has emerged as a potential therapeutic modulator capable of restoring signaling balance and promoting cartilage homeostasis. This study aimed to evaluate the efficacy of NOTUM compared with hyaluronic acid (HA), human adipose-derived mesenchymal stromal cells (hAd-MSCs), and Colchicine in a rabbit osteochondral defect model relevant to osteoarthritis. Twenty-seven New Zealand White rabbits underwent standardized femoral condyle injury and received single-dose treatments. Serum levels of cartilage biomarkers—Procollagen Type IIA N-terminal Propeptide (PIIANP) and Cartilage Oligomeric Matrix Protein (COMP)—were measured by ELISA at 4, 6, and 8 weeks post-surgery, and histological repair at week 12 was assessed using the modified O’Driscoll scoring system. NOTUM treatment significantly increased PIIANP and decreased COMP levels compared with HA, indicating enhanced cartilage synthesis and reduced degradation. Histological scores confirmed superior surface morphology and tissue composition in NOTUM-treated joints. These findings suggest that NOTUM performs a protective and regenerative effect through Wnt/β-catenin modulation, supporting the conclusion that it enhances osteochondral defect repair and motivating further studies of NOTUM as an OA therapy. Full article

Background/Objectives: Alveolitis, or “dry socket,” is a common complication after tooth extraction, associated with pain, inflammation and delayed healing. Standard surgical treatments are often invasive and insufficient. Laser therapy offers antimicrobial, anti-inflammatory and regenerative effects. This study aimed to compare the efficacy of 980 nm monolaser therapy and 980 nm and 1550 nm dual-wavelength therapy on alveolar socket healing in a rabbit model. Methods: In vitro tests evaluated bactericidal effects of 980 nm laser exposure. Eighteen adult male chinchilla rabbits underwent the extraction of the first incisors with the prevention of clot formation to model alveolar socket healing. On day 3, animals were randomized to three groups: mechanical curettage and antiseptic irrigation, 980 nm diode laser therapy, or combined 980 nm + 1550 nm therapy. Clinical parameters (hyperemia, edema, pain, socket closure) were assessed up to day 7. Histological and microbiological analyses were performed on days 7 and 12. Results: Laser therapy showed superior outcomes compared to mechanical treatment. In vitro, 980 nm exposure eradicated microorganisms after 3 s. By day 7, hyperemia decreased to 0.7 ± 0.6 points in the dual-laser group, versus 2.0 ± 0.0 (980 nm) and 3.0 ± 0.0 (mechanical). Complete socket closure occurred in 33% with mechanical treatment and in 67% of sites in the dual-laser group. Pain was fully resolved only after dual-laser therapy. Histology confirmed more organized granulation tissue and angiogenesis in the dual-laser group. Conclusions: Dual-wavelength laser therapy demonstrated superior anti-inflammatory, antimicrobial and regenerative effects compared with diode monotherapy and mechanical treatment. These findings highlight its promise as a minimally invasive approach for managing alveolitis, warranting further clinical evaluation. Full article

Background/Objectives: Burn wound infections caused by Staphylococcus aureus remain a major clinical challenge, leading to delayed healing and high mortality. Natural compounds derived from the Lamiaceae family possess antimicrobial and anti-inflammatory properties that may modulate wound recovery. This study aimed to evaluate the dual modulatory effects of Satureja montana and Origanum vulgare hydrolate-loaded hydrogels on modulation of infection and skin recovery in an experimental rabbit model of S. aureus-infected burns. Methods: Full-thickness (grade IIIa) thermal burns were induced in 25 male New Zealand White rabbits, followed by inoculation with S. aureus (10⁸–10⁹ CFU/mL). Animals were divided into five groups: sham control, burn-infection control, standard-of-care intervention, Satureja montana hydrolate intervention, and Origanum vulgare hydrolate intervention. Treatments were applied twice daily for 14 days. Bacterial load (CFU/g), biochemical markers, histological parameters, and multiplex immunohistochemical indices (Ki-67, CD68, CD163) were analyzed. Results: Both hydrolate-based formulations exhibited pronounced antibacterial effects, significantly reducing S. aureus counts by day 14 compared to untreated burns (p < 0.001). Immunohistochemical analysis revealed enhanced cell proliferation and a rapid shift from pro-inflammatory M1 (CD68+) to reparative M2 (CD163+) macrophages, indicating effective immune resolution. The hydrolate-loaded hydrogels effectively combined antimicrobial activity with tissue-regenerative and immunomodulatory effects. The S. montana formulation demonstrated superior performance, representing a promising adjunctive therapy for infected burn wounds. Conclusions: This study represents the first comparative in vivo evaluation of S. montana and O. vulgare hydrolate-loaded hydrogels in a complex S. aureus-infected burn model. Full article

Enzyme-Linked-Immunosorbent-Spot (ELISpot) is a highly sensitive technique capable of detecting low-level immune responses, offering critical insights into therapy-induced immune activation. Our mouse interferon-gamma (mIFN-γ) ELISpot assay was originally based on a monoclonal capture antibody and a rabbit polyclonal detection antibody. The objective of our study was to replace the polyclonal detection antibody with a monoclonal alternative, using a llama immune library and phage display technology. A llama was immunized with recombinant mIFN-γ, and an immune VHH library was constructed. The library underwent two rounds of panning using the recombinant antigen. Subsequently, 190 clones were screened by Enzyme-Linked-Immunosorbent Assay (ELISA), yielding 27 specific binders to mIFN-γ. Sequence analysis revealed 24 unique clones grouped into four families based on their CDR3-VH sequences. One representative clone from each family was reformatted as VHH-Human Fragment Crystallizable (VHH-hFc) fusion and produced recombinantly for testing in the ELISpot assay. The purified candidates were evaluated in pairs on native mIFN-γ from mouse splenocytes. Two candidates, H3 and G4, were selected for further trial. Comparative analysis of ELISpot performance showed that G4 is a promising substitute for the original rabbit polyclonal antibody, enhancing the overall performance of the mIFN-γ ELISpot assay. This study highlights the potential of VHH antibodies in ELISpot applications and supports their use as a robust, reproducible alternative to polyclonal antibodies. Full article

Colorectal cancer (CRC) is the third most common cancer worldwide, imposing a significant burden on public health. Despite the use of various therapeutic strategies, the prognosis for patients with metastatic and drug-resistant CRC remains poor, which underscores the need for further investigations into cancer mechanisms to develop more effective treatments. Rodents, particularly mice, are the most frequently used animal models for CRC research. However, as the demand for more precise simulations and higher ethical standards in animal experimentation grows, the applicability of rodent models may face increasing limitations. This review highlights a variety of non-rodent animals, including model organisms such as zebrafish (Danio rerio), fruit flies (Drosophila melanogaster), and Caenorhabditis elegans (C. elegans), as well as the chorioallantoic membrane (CAM) model and mammals such as rabbits (Oryctolagus cuniculus), dogs (Canis lupus familiaris), and pigs (Sus scrofa domesticus), which have been utilized in CRC research. Each of these alternatives offers specific advantages in certain areas of cancer research. Their use has enabled new insights into the mechanisms of carcinogenesis, metastasis, and drug resistance in CRC, as well as the development of novel therapies. Full article

Hypoxia-ischemia is a serious perinatal complication affecting neonates globally. Animal models have increased the understanding of its pathophysiology and have been used to investigate potential therapies. Exenatide, clinically used for the treatment of type 2 diabetes mellitus, also protects the rodent brain from hypoxia-ischemia. The rabbit brain has an earlier neurodevelopmental maturation than rodents, as well as similar postnatal maturation to humans. We hereby introduce a new, reproducible hypoxia-ischemia model in rabbit kits at postnatal day (P) 3–4. Following hypoxia-ischemia, rabbit kits received different exenatide concentrations: 170 μg/g (2-dose) or 500 μg/g (1- or 2-dose), or vehicle. The brains were collected seven days later for histological assessment showing that 500 μg/g exenatide, either as a 1- or 2-dose regimen, reduced brain tissue loss by 90% in hypoxia-ischemia experiments both at P3 and P4. A second cohort received a 1-dose 500 μg/g of exenatide or vehicle, and were sacrificed at different early time-points for glucose, ketone bodies, body weight, and temperature measurements. Our results showed a transient 2-fold increase in ketone bodies (0.6 to 1.3 mmol/L) at 6 h. Exenatide did not affect glucose, body temperature or weight gain and appears to be safe and well tolerated in the rabbit model of hypoxia-ischemia. Full article

Background/Objectives: Staphylococcus sciuri, traditionally regarded as a commensal organism in animals and the environment, is increasingly recognized as a potential opportunistic pathogen with zoonotic significance. Its genomic reservoir of methicillin resistance homologues further raises concern regarding its role in antimicrobial resistance dissemination. This study describes the first documented case of S. sciuri isolated from the urinary bladder of a domestic rabbit (Oryctolagus cuniculus) in Romania, emphasizing its clinical relevance and antimicrobial profile. Methods: A seven-year-old intact female rabbit presenting with apathy, dysuria, and hematuria underwent clinical evaluation, ultrasonography, and cystocentesis. The aspirated intravesical content was subjected to bacterial culture, MALDI-TOF MS identification, and antimicrobial susceptibility testing via the VITEK 2 system. Results: Pure colonies of Gram-positive cocci were identified as S. sciuri with high confidence. Antimicrobial susceptibility testing revealed susceptibility to β-lactams, aminoglycosides, glycopeptides, linezolid, rifampicin, fusidic acid, tigecycline, and trimethoprim-sulfamethoxazole, while resistance was observed against fluoroquinolones, macrolides, lincosamides, and tetracycline, indicating a multidrug-resistant phenotype. Treatment with trimethoprim-sulfamethoxazole combined with ultrasound-guided bladder lavage and supportive therapy resulted in complete clinical recovery within 10 days. Conclusions: This case highlights the pathogenic potential of S. sciuri in domestic rabbits and its capacity to exhibit multidrug resistance. The findings underscore the necessity of including rabbits in antimicrobial resistance surveillance programs and reinforce the importance of culture and sensitivity testing in guiding the therapeutic management of exotic companion animals. Full article

Focused ultrasound-stimulated microbubble (MB + FUS) therapy is a promising radiation enhancement strategy, utilizing vascular disruption to enhance radiation efficacy. However, its mechanistic effects in large tumour volumes and clinical translatability remain insufficiently characterized. This study evaluates the synergistic impact of MB + FUS combined with radiation therapy (XRT) in a large-scale, immunosuppressed rabbit xenograft model using a clinically adaptable, MRI-guided 6144-element focused ultrasound (MRgFUS) system. Tumours were treated with MB + FUS, XRT, or both, with real-time image-guided MB activation and evaluation of treatment effects on vascular integrity, proliferation, and cellular stress responses. Assessments included Power Doppler ultrasound, histology, and immunohistochemistry targeting TUNEL, ASMase, Ki-67, Factor VIII, HIF-1α, and VEGF. Combination therapy induced significant vascular collapse, reduced perfusion, and decreased Factor VIII expression, alongside increased nuclear condensation, TUNEL positivity, and ASMase expression, consistent with ASMase-mediated endothelial apoptosis and vascular disruption. Upregulation of HIF-1α and VEGF indicated hypoxia-driven angiogenic signalling, while Ki-67 suppression reflected sustained tumour growth inhibition. Although immune responses were limited by host immunosuppression, the larger tumour burden provided clinically relevant constraints. The MRgFUS platform enabled precise and reproducible MB activation, reinforcing MB + FUS as a potent radio-enhancement modality. These findings support the continued development of MB + FUS toward clinical translation and highlight its potential as a complementary strategy to radiation therapy. Full article

Intervertebral disc degeneration is a leading cause of chronic back pain, with existing treatments focusing on symptom management rather than true tissue repair. Cellular therapies—such as platelet-rich plasma (PRP), autologous chondrocytes, and mesenchymal stem cells (MSCs)—have emerged as promising strategies for disc regeneration. In this study, fifteen New Zealand white rabbits underwent fluoroscopy-guided needle puncture of the L4-L5 discs and were allocated to receive PRP alone, PRP-chondrocytes, or PRP-MSCs eight weeks later, while the L3-L4 disc served as a healthy internal control. At 16 weeks post-injury, histological scoring revealed significant improvements in annular integrity, cellularity, and matrix composition in all treated groups compared with untreated lesions, with the greatest gains observed in the PRP-chondrocytes arm, intermediate effects with PRP-MSCs, and more modest changes with PRP alone. Complementary RT-qPCR analysis of COL2A1 and COL10A1 expression confirmed a shift toward a more regenerative phenotype, marked by enhanced COL2A1 and reduced COL10A1 levels, which was most pronounced in the PRP-chondrocytes arm. Despite these advances, none of the interventions fully restored the healthy disc architecture, underscoring the complexity of disc repair. These findings support the potential of combining PRP with chondrocytes or MSCs for intervertebral disc regeneration and demonstrate the need for further optimization of cell doses, PRP formulations, and delivery protocols before clinical translation. Full article

Calcific aortic valve disease (CAVD) is a prevalent cardiovascular condition and is the most common heart valve disease globally. Hyperlipidemia and aging are key risk factors; consequently, with the aging global population, CAVD incidence continues to rise. Despite extensive research, the pathogenesis of CAVD remains unclear, leading to a lack of effective pharmacological therapies. Consequently, valve replacement surgery persists as the primary treatment option. Establishing suitable animal models is crucial for investigating the complex pathophysiological mechanisms of CAVD in vivo, although an optimal model has yet to be identified. This review provides a concise overview of CAVD pathogenesis and summarizes the application of common animal models—including mice, rats, rabbits, and pigs—in studying valve calcification. We specifically detail the construction of various models and their associated calcific aortic valve phenotypes. Furthermore, we outline common detection methods for assessing aortic valve calcification in these models and suggest future directions for developing improved animal models relevant to CAVD research. Full article

Exposure to ionising radiation may be hazardous to living beings, including humans. Ionising radiation exposure has been shown to cause hepatic dysfunction or even liver cancer in persons receiving radiation therapy who do not have liver disease. Changes in hepatic enzyme values may suggest radiation-induced stress on liver cells. Then this experimental study examined the effect of different doses of radiation on the liver enzymes aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT). Methods: Six equal groups of thirty-six New Zealand white rabbits weighing 3 and 5 kg each were formed. The rabbits received total body radiation doses of 0 Gy (Control group), 0.053 Gy, 0.11 Gy, 0.21 Gy, 0.42 Gy, and 0.84 Gy on days, 1, 3, and 5 and week 1, week 2, week 3, and week 4. Generalised Linear Mixed Models (GLMMs) were used to compare the data statistically. Results: There was a significant rise in the serum liver enzyme levels; aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) all showed a statistically significant time effect after the application of different radiation doses. Based on the group effect of radiation, AST and ALP, but not ALT, showed statistically significant findings. Full article

Background/Objectives: This report documents the first confirmed case in Romania of fatal pneumonia and septicemia in a domestic rabbit caused by multidrug-resistant Escherichia coli, highlighting both its pathogenic potential and One Health implications. Case Study: An 8-month-old male German Giant Spotted rabbit raised on a rural farm under poor husbandry conditions developed acute respiratory distress and died within 48 h. Post-mortem examination revealed severe pulmonary congestion, tracheal inflammation, serofibrinous pericarditis, and systemic vascular lesions. Bacteriological analysis confirmed E. coli from lung, trachea, and bone marrow samples. The isolate demonstrated strong Congo red binding, was confirmed by MALDI-TOF mass spectrometry, and showed resistance to beta-lactams, fluoroquinolones, tetracyclines, sulfonamides, macrolides, and phenicols, remaining susceptible only to aminoglycosides. PCR screening identified virulence genes (fimH, papC, iutA, ompA) linked to adhesion, immune evasion, and iron acquisition, with potential for horizontal gene transfer. Conclusions: This first documented case in Romania emphasizes the clinical threat posed by multidrug-resistant E. coli in rabbits and the importance of early diagnosis, improved biosecurity, and responsible antimicrobial use. The zoonotic and environmental risks in backyard farming underscore the urgent need for integrated surveillance. Alternative control strategies, including phage therapy and probiotics, should be explored to reduce reliance on conventional antibiotics. Full article