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BACKGROUND: Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD. METHODS: Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models. RESULTS: Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found. LIMITATIONS: This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores. CONCLUSIONS: Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD.

Neuroaxonal dystrophy (NAD) is a neurodegenerative disease characterized by spheroid (swollen axon) formation in the nervous system. In the present study, we focused on a newly established autosomal recessive mutant strain of F344-kk/kk rats with hind limb gait abnormalities and ataxia from a young age. Histopathologically, a number of axonal spheroids were observed throughout the central nervous system, including the spinal cord (mainly in the dorsal cord), brain stem, and cerebellum in F344-kk/kk rats. Transmission electron microscopic observation of the spinal cord revealed accumulation of electron-dense bodies, degenerated abnormal mitochondria, as well as membranous or tubular structures in the axonal spheroids. Based on these neuropathological findings, F344-kk/kk rats were diagnosed with NAD. By a positional cloning approach, we identified a missense mutation (V95E) in the Hspa8 (heat shock protein family A (Hsp70) member 8) gene located on chromosome 8 of the F344-kk/kk rat genome. Furthermore, we developed the Hspa8 knock-in (KI) rats with the V95E mutation using the CRISPR-Cas system. Homozygous Hspa8-KI rats exhibited ataxia and axonal spheroids similar to those of F344-kk/kk rats. The V95E mutant HSC70 protein exhibited the significant but modest decrease in the maximum hydrolysis rate of ATPase when stimulated by co-chaperons DnaJB4 and BAG1 in vitro, which suggests the functional deficit in the V95E HSC70. Together, our findings provide the first evidence that the genetic alteration of the Hspa8 gene caused NAD in mammals.

The first International Conference on Unconventional Animal Models of Alzheimers Disease and Aging (UAMAA) took place on December 13-16, 2023, in Santiago, Chile. The Alzheimers disease (AD) research field is currently in search for new and unconventional models that could hold greater translational potential than transgenic mouse models. Thus this UAMAA conference is timely and significant. The event consisted of 6 sessions with talks from 28 world-class scientists from all over the world. These animal models of interest include the degu (Octodon degu), the dog (Canis familiaris), and certain species of nonhuman primates that may better recapitulate neuropathology and cognitive impairments in human AD. Our conference has provided a formal forum to discuss and highlight new research directions, alternative animal models, and innovative approaches for the AD and aging research field.

ABSTRACT Objective Materials and Methods Results Conclusions To determine the effect of polydeoxyribonucleotide (PDRN) on endosinus bone regeneration in a rabbit sinus model at sequential healing time points.Eighteen New Zealand white rabbits were used. Bilateral sinus floor elevation (SFE) was performed. Two groups were randomly assigned to each sinus: (1) test group, in which SFE was performed using collagenated bone substitute material soaked with PDRN (concentration 2.0 mg/mL, dose 0.5 mL), and (2) control group, in which SFE was performed using collagenated bone substitute material only. The experimental animals were sacrificed at 2, 4, and 8 weeks (n = 6 at each healing time point). Microcomputed tomography (micro‐CT), histologic, and histomorphometric analyses were performed.The micro‐CT analysis revealed statistically significant increases in the mineralized tissue volume between 4 and 8 weeks (p < 0.05). Histologically, no specific intergroup difference was found in the pattern of new bone formation. Histomorphometrically, the area of newly formed bone (NB) was larger in the test group than in the control group at all healing time points (1.4 vs. 1.2 mm2 at 2 weeks, 3.4 vs. 1.9 mm2 at 4 weeks, and 5.7 vs. 4.5 mm2 at 8 weeks; median value), but the difference was statistically significant only at 4 weeks (p < 0.05). NB in set regions of interest (ROI_C, ROI_W, and ROI_M) tended to be greater in the test group than in the control group without statistical significance (p > 0.05).PDRN appeared to enhance new bone formation at all healing time points, but the improvement was statistically significant only at 4 weeks. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic cardiomyopathy (DCM) is a significant complication of diabetes, characterized primarily by the development of heart failure in individuals with diabetes. Numerous animal studies have indicated that resveratrol enhances cardiac function in diabetic cardiomyopathy; however, its reliability and underlying mechanism remain unclear. This study aims to assess the cardioprotective effects of resveratrol on DCM and explore its potential mechanism. Methods: We searched PubMed, EMBASE, WOS, Cochrane Library, CNKI, CBM, Chinese VIP, and Wan Fang Database until March 31st, 2024, without language restrictions. Continuous outcome measures were analyzed using weighted mean difference or standardized mean difference, and heterogeneity was assessed with I2. The risk of bias in animal experiments was evaluated using the SYRCLE tool, and evidence reliability was determined with the GRADE tool. All data were analyzed using Review Manager 5.4.1 and Stata 17. This study has been registered on the PROSPERO (CRD42024523944). Results: A total of 18 studies meeting the criteria were identified. The analysis revealed that the resveratrol intervention group exhibited significant improvements in LVEF (WMD = 17.88), LVFS (WMD = 8.77), HW/BW (SMD=-2.92), SOD (SMD = 4.53), and MDA (SMD=-5.07) compared to the control group. The GRADE grading assessment indicated moderate certainty for LVEF, HW/BW, and MDA, while certainty for other factors was considered low. Conclusion: Our research suggests that resveratrol may protect cardiac function in DCM through anti-inflammatory and anti-oxidative stress effects. However, these findings are based on preclinical data, and further extensive trials are needed to confirm their effectiveness and safety before clinical application. [ABSTRACT FROM AUTHOR]

The objective of this research was to investigate the calcium bioavailability and the influence of substituting synthetic calcium carbonate (CaCO3) with grouper bone nano‐calcium (GBN), and medium‐chain triglyceride (MCT) with long‐chain triglyceride (LCT) in the diet of ovariectomized rats maintained for 8 weeks. Twenty rats were randomly divided into four distinct groups: (1) The OX‐C group: AIN‐93M standard + synthetic CaCO3; (2) the OX‐D group: AIN‐93M standard + no calcium; (3) the OX‐1 group: AIN‐93M standard + GBN; and (4) the OX‐2 group: AIN‐93M with MCT as lipid source + GBN. The test parameters conducted encompassed the evaluation of the rat's body weight, levels of calcium, phosphorus, and alkaline phosphatase in rat blood serum, examination of the microstructure of rat tibiae by histomorphometry and femora bones by means of 3D micro‐CT image analysis, and assessment of the strength of rat femora bones by the three‐point bending. The results indicated that the GBN calcium diet groups (OX‐1 and OX‐2) were successful substitutes for synthetic CaCO3 of the OX‐C group. GBN calcium diet groups have shown superiority in terms of trabeculae thickness (Tb.Th), bone volume (BV/TV), bone mineral density (BMD), and particularly in bone strength evaluations. The GBN calcium diet groups exhibited serum calcium, serum phosphorus, and alkaline phosphatase levels that were comparable to those of synthetic CaCO3 calcium. As the calcium‐deficient group, OX‐D revealed a much lower and distinct performance than other groups. This research demonstrated that MCT exhibit comparable performance to LCT; however, it did not establish that substituting LCT for MCT was superior. [ABSTRACT FROM AUTHOR]

Background: Near-infrared fluorescence (NIRF) imaging is an excellent choice for image-guided surgery due to its simple operation and non-invasiveness. Developing tumor-specific fluorescent molecular probes is key to fluorescence imaging-guided surgery. EGFR (epidermal growth factor receptor) is closely related to the proliferation and growth of tumor cells and is highly expressed in epithelial ovarian cancer (EOC). The study aims to construct a NIR fluorescent molecular probe using cetuximab (an EGFR monoclonal antibody) and investigate its feasibility for targeting EOC in vivo through fluorescence imaging. Methods: We determined the expression of EGFR in EOC. NIR fluorescent molecular probe with cetuximab (cetuximab-Cy7) was chemically engineered and identified. The subcutaneous xenografted tumor model of EOC was induced using SKOV3-Luc cell line with positive expression of EGFR. Cetuximab-Cy7 was used for in vivo fluorescence imaging, and phosphate-buffered saline, free Cy7 dye and mouse isotype immunoglobulin G-Cy7 were used as controls. NIRF imaging system was performed to study the distribution and targeting of the probes. Tumors were imaged in situ and ex vivo, and fluorescent intensity was quantified. Resected specimens were analyzed to confirm diagnosis, and immunohistochemical (IHC) staining was used to identify EGFR expression. Results: EGFR expression was increased in EOC tissues than fallopian tube tissues. The high expression of EGFR was significantly correlated with well-differentiation, residual lesions ≤ 1 cm, no recurrence and increased survival. NIRF imaging showed that the cetuximab-Cy7 enabled detection of tumor lesions in EOC-bearing mice with the optimal dose of 30 µg. The suitable imaging time window may be 24–96 h post-injection. Ex vivo fluorescence imaging indicated that fluorescent signal was mainly detected in the tumor and the lung. IHC results confirmed that xenografts were EGFR positive. Conclusion: Cetuximab-Cy7 can specifically target the tumors of EOC xenografted nude mice. This research lays the foundation for future studies on EOC surgery navigation. [ABSTRACT FROM AUTHOR]

Background: Clinical and preclinical studies have shown that extra virgin olive oil (EVOO), a major component of the Mediterranean diet, has beneficial effects on brain aging and cognition. Individuals with Down syndrome develop age-dependent cognitive decline and synaptic dysfunction. However, whether EVOO intake is beneficial in Down syndrome is not known. Objective: In this study, by implementing a mouse model of Down syndrome, we aimed to investigate the effect that chronic administration of EVOO has on memory, synaptic function, and neuroinflammation. Methods: Starting at 4 months of age Ts65dn mice were randomized to receive EVOO for 5 months in their diet, after which they were tested for learning and memory impairment. After euthanasia, synaptic function was measured in freshly obtained hippocampal slices, whereas brain tissues were assessed for inflammatory biomarkers. Results: Compared with controls, mice receiving EVOO had a significant improvement in learning and spatial memory. Additionally, field potential recordings showed that treated mice had an improvement in synaptic function. Finally, array analysis showed that EVOO modulated the expression levels of several inflammatory biomarkers. Conclusions: Chronic administration of EVOO to a mouse model of Down syndrome has beneficial effects on memory impairments, synaptic function deficits and neuroinflammation. Our findings provide additional support for the potential therapeutic effects of EVOO also in individuals with Down syndrome. [ABSTRACT FROM AUTHOR]

Children with neurodevelopmental disorders, such as developmental coordination disorder (DCD), exhibit gross to fine sensorimotor impairments, reduced physical activity and interactions with the environment and people. This disorder co‐exists with cognitive deficits, executive dysfunctions and learning impairments. Previously, we demonstrated in rats that limited amounts and atypical patterns of movements and somatosensory feedback during early movement restriction manifested in adulthood as degraded postural and locomotor abilities, and musculoskeletal histopathology, including muscle atrophy, hyperexcitability within sensorimotor circuitry and maladaptive cortical plasticity, leading to functional disorganization of the primary somatosensory and motor cortices in the absence of cortical histopathology. In this study, we asked how this developmental sensorimotor restriction (SMR) started to impact the integration of multisensory information and the emergence of sensorimotor reflexes in rats. We also questioned the enduring impact of SMR on motor activities, pain and memory. SMR led to deficits in the emergence of swimming and sensorimotor reflexes, the development of pain and altered locomotor patterns and posture with toe‐walking, adult motor performance and night spontaneous activity. In addition, SMR induced exploratory hyperactivity, short‐term impairments in object‐recognition tasks and long‐term deficits in object‐location tasks. SMR rats displayed minor alterations in histological features of the hippocampus, entorhinal, perirhinal and postrhinal cortices yet no obvious changes in the prefrontal cortex. Taken all together, these results show similarities with the symptoms observed in children with DCD, although further exploration seems required to postulate whether developmental SMR corresponds to a rat model of DCD. [ABSTRACT FROM AUTHOR]

Animal models of peripheral nerve injury (PNI) serve as the fundamental basis for the investigations of nerve injury, regeneration, and neuropathic pain. The injury properties of such models, including the intensity and duration, significantly influence the subsequent pathological changes, pain development, and therapeutic efficacy. However, precise control over the intensity and duration of nerve injury remains challenging within existing animal models, thereby impeding accurate and comparative assessments of relevant cases. Here, a new model that provides quantitative and off‐body controllable injury properties via a magnetically controlled clamp, is presented. The clamp can be implanted onto the rat sciatic nerve and exert varying degrees of compression under the control of an external magnetic field. It is demonstrated that this model can accurately simulate various degrees of pathology of human patients by adjusting the magnetic control and reveal specific pathological changes resulting from intensity heterogeneity that are challenging to detect previously. The controllability and quantifiability of this model may significantly reduce the uncertainty of central response and inter‐experimenter variability, facilitating precise investigations into nerve injury, regeneration, and pain mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review and meta-analysis sought to assess whether ultra-high dose rate (UHDR) ion irradiations can induce the FLASH effect in animal models. Methods: A comprehensive search of the Web of Science, PubMed, and EMBASE databases was conducted from inception until March 20, 2023, to identify studies involving irradiated animals subjected to proton or carbon ion beams at varying dose rates. The research content should include various indicators that can reflect the effect and safety of radiation, such as survival, normal tissue toxicity, inflammatory response, tumor volume, etc Results: Compared to conventional dose rate (CONV) ion irradiations, UHDR ion irradiations can significantly improve mouse survival (HR 0.48, 95% CI 0.29 to 0.78, I 2 = 0%) and maintain comparable tumor control. There was no significant impact of different dose rates on the survival of zebrafish embryos (SMD 0.11, 95% CI −0.31 to 0.53, I 2 = 85%). Subgroup analysis showed that radiation dose was an important factor affecting the survival of zebrafish embryos. Achieving normal tissue sparing may require higher radiation dose under UHD.In mouse and zebrafish embryo models, normal tissue sparing did not always occur after UHDR ion irradiations. In addition, only a limited number of cytokines (CXCL1, IL-6, GM-CSF, G-CSF, HMGB1, and TGF-β) and immune cells (microglia and myeloid cells) showed differences at different dose rates. Conclusions: UHDR ion irradiation can achieve FLASH effect, but the reproducibility of normal tissue sparing remains a challenge. Compared to CONV irradiation, UHDR ion irradiations demonstrated equivalent or even superior tumor control. [ABSTRACT FROM AUTHOR]

Background: While the benefits of sonication for improving periprosthetic joint infection (PJI) are well-documented, its potential therapeutic effect against bacterial biofilm remains unstudied. This study aimed to investigate the safety and efficacy of a novel nanoparticle ultrasonication process on methicillin-resistant Staphylococcus aureus (MRSA) bacterial biofilm formation in a PJI rat model. Methods: This novel ultrasonication process was designed to remove attached bacterial biofilm from implant and peri-articular tissues, without damaging native tissues or compromising implant integrity. Twenty-five adult Sprague–Dawley rats underwent a surgical procedure and were colonized with intra-articular MRSA, followed by the insertion of a titanium screw. Three weeks after the index surgery, the animals received a second procedure during which the screws were explanted, and soft tissue was sampled. The intraoperative use of the nanoparticle sonication treatment was employed to assess the device's safety, while ex vivo treatment on the retrieved tissue and implants was used to evaluate its efficacy. Results: Clinical and histological assessments did not indicate any macro- or micro-damage to the host tissue. Sonication of the retrieved tissues demonstrated an average bacterial removal of 2 × 103 CFU/mL and 1 × 104 CFU/gram of tissue. Compared to the standard-of-care group (n = 10), implants treated with sonication (n = 15) had significantly lower remaining bacteria, as indicated by crystal violet absorbance measurements (P = 0.012). Conclusions: This study suggests that nanoparticle sonication technology can successfully remove attached bacterial biofilms from explanted orthopedic hardware and the joint capsule, without negatively affecting native tissue. The study provides initial results supporting the potential of nanoparticle sonication as an adjuvant treatment option during a DAIR (debridement, antibiotics, and implant retention) procedure for PJI, paving the way for future clinical trials. [ABSTRACT FROM AUTHOR]

Ectopic pregnancy affects ~ 2% of pregnancies annually in the United States, with no current treatments allowing for the continuation of the pregnancy. Thus, this study sought to initiate an investigation into the potential design of a surgical technique, in an animal model, that could serve as a foundation for future research into the potential of relocating an ectopic embryo into the uterus at the human level. Female Long-Evans rats were randomly assigned to one of two groups: Embryo Relocation (ER; n = 12; underwent embryo relocation surgery) and Normal Pregnancy (NP; n = 12; carried a normal pregnancy; no surgery). Eight rats/group were allowed to carry their pregnancy to term and deliver, while four had their uteri collected at the end of gestation. Briefly, for the ER group, a uterine horn containing 1–2 embryos was translocated to the contralateral horn, which had been incised and cleared of its contents, prior to being wrapped around the relocated horn. Rat weight, food consumption and vaginal impedance of the mothers were measured throughout the experiment. Ultrasounds were performed and fetal heart rates measured on day 20–21 of gestation. Additionally, rat weight of all offspring was measured at adulthood. Our findings indicate that, in the ER group, 15/15 (100%) of the relocated embryos had detectable heart rates at the end of gestation (within the normal range), 14/15 (93%) were delivered vaginally, and 12/14 (86%) survived until adulthood. A significant decrease in rat weight and food consumption was observed only on the day following surgery. Fertility, as measured by vaginal impedance, was minimally impacted by surgery. Moreover, there was no significant difference between groups in average body weight of offspring at adulthood. Histological analysis indicated a thicker placenta in the ER group, attributable to the fetal part of the placenta, potentially indicating compensatory mechanisms. Our findings reflect a successful transuterine embryo relocation followed by vaginal birth and survival of offspring to adulthood, in a rat model. Such findings lay the foundation for future preclinical research in higher animals, with potential implications on a procedure relevant to human ectopic embryo relocation. [ABSTRACT FROM AUTHOR]

I outline the perspective that searching the contents of memory is a form of mental time travel (MTT) in non-humans that is relatively tractable because it focuses on the contents of memory. I propose that an animal model of MTT requires three elements: (i) the animal remembers multiple events using episodic memory, (ii) the order of events in time is included in the representation, and (iii) the sequence of events can be searched to find a target that occurred at a particular time. I review experiments suggesting that rats represent multiple items in episodic memory (element 1) in order of occurrence (element 2) and engage in memory replay to search representations in episodic memory in sequential order to find information at particular points in the sequence (element 3). The cognitive building blocks needed for MTT may be quite old in the evolutionary timescale. This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'. [ABSTRACT FROM AUTHOR]

Background: Animal models focusing on neuromuscular outcomes are crucial for understanding the mechanisms of intensive care unit-acquired weakness (ICU-AW) and exploring potential innovative prevention and treatment strategies. Aim: To analyse and evaluate preclinical ICU-AW models. Methods: We manually searched five English and four Chinese databases from 1 January 2002, to 1 February 2024, and reviewed related study references. Full-text publications describing animal models of muscle weakness and atrophy in critical illness were included. Detailed information about model types, animal species, sex, age, induction methods, outcome measures, drawbacks and strengths was extracted from each included study. Results: A total of 3,451 citations were initially retrieved, with 84 studies included in the final analysis. The most frequently studied animal model included rodents (86.9%), 64.3% of which were male animals. ICU-AW animal models were mostly induced by comprehensive intensive care unit (ICU) interventions (38.1%) and sepsis (51.2%). Most studies focused on limb muscles (66.7%), diaphragm muscles (21.4%) or both (9.5%). Reported outcomes primarily included muscular pathological changes (83.3%), electrophysiological examinations of muscles (57.1%) and animal grip strength (16.6%). However, details such as animal age, mortality data, experimental design, randomisation, blinding, sample size and interventions for the experimental group and/or control group were inadequately reported. Conclusion: Many preclinical models are used to study ICU-AW, but the reporting of methodological details is often incomplete. Although current ICU animal models can mimic the characteristics of human ICU-AW, there is no standard model. Future preclinical studies should develop a standard ICU-AW animal model to enhance reproducibility and improve scientific rigor in exploring the mechanisms and potential treatment of ICU-AW. [ABSTRACT FROM AUTHOR]

Membranous nephropathy (MN) is an antibody-mediated autoimmune glomerular disease in which PLA2R1 is the main autoantibody. It has become the most common cause of adult nephrotic syndrome, and about one-third of patients can progress to end-stage kidney disease, but its pathogenesis is still unclear. Animal models can be used as suitable tools to study the pathogenesis and treatment of MN. The previous Heymann nephritis rat model and C-BSA animal model are widely used to study the pathogenesis of MN. However, the lack of target antigen expression in podocytes of model animals (especially rodents) restricts the application. In recent years, researchers constructed animal models of antigen-specific MN, such as THSD7A, PLA2R1, which more truly simulate the pathogenesis and pathological features of MN and provide more choices for the follow-up researchers. When selecting these MN models, we need to consider many aspects, including cost, difficulty of model preparation, labor force, and whether the final model can answer the research questions. This review is to comprehensively evaluate the mechanism, advantages and disadvantages and feasibility of existing animal models, and provide new reference for the pathogenesis and treatment of MN. [ABSTRACT FROM AUTHOR]

Background: Neuroaxonal dystrophy (NAD) is a group of inherited neurodegenerative disorders characterized primarily by the presence of spheroids (swollen axons) throughout the central nervous system. In humans, NAD is heterogeneous, both clinically and genetically. NAD has also been described to naturally occur in large animal models, such as dogs. A newly recognized disorder in Miniature American Shepherd dogs (MAS), consisting of a slowly progressive neurodegenerative syndrome, was diagnosed as NAD via histopathology. Objectives: To describe the clinical and pathological phenotype together with the identification of the underlying genetic cause. Methods: Clinical and postmortem evaluations, together with a genome‐wide association study and autozygosity mapping approach, followed by whole‐genome sequencing. Results: Affected dogs were typically young adults and displayed an abnormal gait characterized by pelvic limb weakness and ataxia. The underlying genetic cause was identified as a 1‐bp (base pair) deletion in RNF170 encoding ring finger protein 170, which perfectly segregates in an autosomal recessive pattern. This deletion is predicted to create a frameshift (XM_038559916.1:c.367delG) and early truncation of the RNF170 protein (XP_038415844.1:(p.Ala123Glnfs*11)). The age of this canine RNF170 variant was estimated at ~30 years, before the reproductive isolation of the MAS breed. Conclusions: RNF170 variants were previously identified in human patients with autosomal recessive spastic paraplegia‐85 (SPG85); this clinical phenotype shows similarities to the dogs described herein. We therefore propose that this novel MAS NAD could serve as an excellent large animal model for equivalent human diseases, particularly since affected dogs demonstrate a relatively long lifespan, which represents an opportunity for therapeutic trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background and Purpose: Carotid artery stenosis is a major risk factor for ischemic stroke. Despite carotid artery stenting, in‐stent restenosis (ISR) remains challenging. Pigs serve as an ideal ISR model. This study aims to establish a novel porcine model of carotid ISR using open‐loop and closed‐loop stents and to assess ISR with optical coherence tomography (OCT) and histopathology, comparing incidence and vascular response between stent types. Methods: Twelve adult male Bama miniature pigs underwent carotid stenting with either open‐loop or closed‐loop stents. The animals received antiplatelet therapy pre‐ and postimplantation. Postimplantation evaluations at 90 days included carotid digital subtraction angiography (DSA), OCT, histopathological examination, and electron microscopy. Results: Both stent types showed ISR as detected by OCT and DSA. OCT revealed comparable neointimal proliferation within stent struts for both types, with no significant differences in stent, lumen, and neointimal dimensions. Histopathological analysis and electron microscopy provided insights into tissue responses and healing processes following stent implantation. No significant difference in ISR incidence was found between the stent types based on a χ2 test (p =.110). OCT and hematoxylin‐eosin staining exhibit the highest consistency in evaluating neointimal area. Conclusions: The novel porcine ISR model demonstrated similar ISR outcomes for open‐loop and closed‐loop stents. OCT proved to be a highly consistent and valuable tool for evaluating stent and arterial conditions, comparable to histopathological findings. However, due to a small sample size, the validity of these preliminary findings requires further investigation to be confirmed. [ABSTRACT FROM AUTHOR]

Introduction Warfighters are issued hard body armor designed to defeat ballistic projectiles. The resulting backface deformation can injure different thoracoabdominal organs. Developed over decades ago, the behind armor blunt impact criterion of maximum 44 mm depth in clay continues to be used independent of armor type or impact location on the thoracoabdominal region covered by the armor. Because thoracoabdominal components have different energy absorption capabilities, their mode of failures and mechanical properties are different. These considerations underscore the lack of effectiveness of using the single standard to cover all thoracoabdominal components to represent the same level of injury risk. The objective of this pilot study is to conduct cardiac impact tests with a live animal model and analyze biomechanical injury candidate metrics for behind armor blunt trauma applications. Materials and Methods Live swine tests were conducted after obtaining approvals from the U.S. DoD. Trachea tubes. An intravenous line were introduced into the swine before administering anesthesia. Pressure transducers were inserted into lungs and aorta. An indenter simulating backface deformation profiles produced by body armor from military-relevant ballistics to human cadavers delivered impact to the heart region. The approved test protocol included 6-hour monitoring and necropsies. Indenter accelerometer signals were processed to compute the velocity and deflection, and their peak magnitudes were obtained. The deflection-time signal was normalized with respect to chest depth along the impact axis. The peak magnitude of the viscous criterion, kinetic energy, force, momentum and stiffness were obtained. Results Out of the 8 specimens, 2 were sham controls. The mean total body mass and soft tissue thickness at the impact site were 81.1 ± 4.1 kg and 3.8 ± 1.1 cm. The peak velocities ranged from 30 to 59 m/s, normalized deflections ranged from 15 to 21%, and energies ranged from 105 to 407 J. The range in momentum and stiffness were 7.0 to 13.9 kg-m/s and 22.3 to 79.9 N/m. The maximum forces and impulse data ranged from 2.9 to 11.7 kN and 1.9 to 5.8 N-s. The peak viscous criterion ranged from 2.0 to 5.3 m/s. One animal did not sustain any injuries, 2 had cardiac injuries, and others had lung and skeletal injuries. Conclusions The present study applied blunt impact loads to the live swine cardiac region and determined potential candidate injury metrics for characterization. The sample size of 6 swine produced injuries ranging from none to pure skeletal to pure organ trauma. The viscous criterion metric associated with the response of the animal demonstrated a differing pattern than other variables with increasing velocity. These findings demonstrate that our live animal experimental design can be effectively used with testing additional samples to develop behind armor blunt injury criteria for cardiac trauma in the form of risk curves. Injury criteria obtained for cardiac trauma can be used to enhance the effectiveness of the body armor, reduce morbidity and mortality, and improve warfighter readiness in combat operations. [ABSTRACT FROM AUTHOR]

Introduction Acute respiratory distress syndrome (ARDS) is a widespread and often fatal clinical syndrome marked by the acute onset of pulmonary edema and inflammatory-mediated disruptions in alveolar-capillary permeability resulting in impaired gas exchange and tissue oxygenation with subsequent acute respiratory failure that accounts for 10.4% of all intensive care unit admissions worldwide and boasts a mortality rate of 38.5%. The current treatment for ARDS remains largely supportive. This is largely because of the many challenges of achieving a stable and sustainable animal model that recreates the pathophysiology of ARDS experimentally in a controlled setting to allow research to elucidate potential treatments of ARDS moving forward. Materials and Methods The bronchoalveolar lavage and oleic acid models are currently the 2 most frequently used experimental models in inducing ARDS in animal models. This study demonstrated that combining them into a "two-hit model" can produce sustained ARDS in swine models per the Horowitz index (PaO2/FiO2 ratio of ≤300 mmHg). Additionally, expected changes in pH, pCO2, lung compliance, cytokines, and tissue histopathology were observed and add to our confidence and reliability that the "two-hit model" produces symptomatic ARDS in a manner very similar to that observed in humans. Results and Conclusions In conclusion, we demonstrated a viable animal model of human ARDS that is maintained for a prolonged period, suitable for continuous monitoring of the progression, and evaluation of potential future treatments and procedures to reduce patient morbidity and mortality. To carry out this two-hit model, lung injury was induced through a combination of bronchoalveolar lavage and oleic acid administration and the disease process of ARDS is subsequently tracked through clinically relevant parameters such as respiratory mechanics, cytokine response, aretrial blood gas (ABG) changes, and observation of postmortem histopathologic changes. This promising new model has the capacity to successfully replicate human ARDS which is a well-known and notoriously multifactorial pathogenic process to reproduce experimentally for an extended period of time. The "two-hit model" is a viable and appropriate model for the research of novel treatments for ARDS. [ABSTRACT FROM AUTHOR]

There is an estimated 35–45% loss of striatal dopamine at the time of diagnosis of Parkinson's disease (PD), and cases clinically diagnosed in the early stages may already be pathologically in advanced stages. Recent large-scale clinical trials of disease-modifying therapies (DMT) also suggest the necessity of targeting patients at earlier stages of the disease. From this perspective, the prodromal phase of PD is currently the focus of attention, emphasizing the need for a prodromal mouse model that accurately reflects the pathophysiology, along with early biomarkers. To establish prodromal animal model of PD with high face validity that reflects the disease state, the model must possess high construct validity that accurately incorporates clinical and pathological features in the prodromal phase. Furthermore, as a preclinical model of DMT, the model must possess high predictive validity to accurately evaluate the response to intervention. This review provides an overview of animal models which reflect the characteristics of prodromal PD, including alpha-synuclein (aS) accumulation and associated early non-motor symptoms, with a focus on the aS propagation model and genetic model. In addition, we discuss the challenges associated with these models. The genetic model often fails to induce motor symptoms, while aS propagation models skip the crucial step of initial aS aggregate formation, thereby not fully replicating the entire natural course of the disease. Identifying factors that induce the transition from prodromal to symptomatic phase is important as a preclinical model for DMT to prevent or delay the onset of the disease. [ABSTRACT FROM AUTHOR]

Objective: We investigated genetic parameters of calving ease (CE) using several animal models in Korean Holstein and searched for suitable models for routine evaluation of CE. Methods: Two phenotypic datasets of CE (DS5 and DS10) on first-parity Korean Holstein calves were prepared. DS5 and DS10 included at least 5 and 10 CE records per herd-year level and comprised 117,921 and 80,389 observations, respectively. The CE phenotypes ranged from 1 to 4, from a normal to extreme difficulty calving scale. The CE was defined as a trait of the calf. The BLUPF90+ software was used for (co)variances estimation through four animal models with a maternal effect (M1 to M4), where all models included effects of a fixed calf-sex, a fixed dam calving age (covariate), and one or more fixed contemporary group (CG) terms. The CG effects were different across models--a herd-year-season (M1, HYS), a herd-year and year-season (M2, HY+YS), a herd-year and season (M3, HY+S), and a herd and year-season (M4, H+YS). Results: Direct heritability (h2) estimates of CE ranged from 0.005 to 0.234 across models and datasets. Maternal h2 values were low (0.001 to 0.090). Genetic correlations between direct and maternal effects were strongly negative to lowly positive (-0.814 to 0.078), further emphasizing its importance in CE evaluation models. These genetic parameter estimates also indicate slower future selection progress of CE in Korean Holsteins. The M1 fitted many levels with fewer observations per level deriving unreliable parameters, and the M4 did not account for confounded herd and animal structures. The M2 and M3 were deemed more realistic for implementation, and they were better able to account for data structure issues (incompleteness and confounding) than other models. Conclusion: As the pioneering study to employ animal models in Korean Holstein CE evaluation, our findings hold significant potential for this breed's future and routine evaluation development. [ABSTRACT FROM AUTHOR]

Chronic pain is a constantly recurring and persistent illness, presenting a formidable healthcare challenge for patients and physicians alike. Current first‐line analgesics offer only low‐modest efficacy when averaged across populations, further contributing to this debilitating disease burden. Moreover, many recent trials for novel analgesics have not met primary efficacy endpoints, which is particularly striking considering the pharmacological advances have provided a range of highly relevant new drug targets. Heterogeneity within chronic pain cohorts is increasingly understood to play a critical role in these failures of treatment and drug discovery, with some patients deriving substantial benefits from a given intervention while it has little‐to‐no effect on others. As such, current treatment failures may not result from a true lack of efficacy, but rather a failure to target individuals whose pain is driven by mechanisms which it therapeutically modulates. This necessitates a move towards phenotypical stratification of patients to delineate responders and non‐responders in a mechanistically driven manner. In this article, we outline a bench‐to‐bedside roadmap for this transition to mechanistically informed personalised pain medicine. We emphasise how the successful identification of novel analgesics is dependent on rigorous experimental design as well as the validity of models and translatability of outcome measures between the animal model and patients. Subsequently, we discuss general and specific aspects of human trial design to address heterogeneity in patient populations to increase the chance of identifying effective analgesics. Finally, we show how stratification approaches can be brought into clinical routine to the benefit of patients. [ABSTRACT FROM AUTHOR]

Aim: To assess the possibility of vertical alveolar ridge augmentation by means of activation of the periosteum. Materials and Methods: Six adult male Beagle dogs were used for the study. All premolars and first molars were extracted, and one vertical saucer‐shaped bony defect was created on each side of the mandible. After 3 months of healing, full‐thickness muco‐periosteal flaps were elevated, and one distraction device was placed on each side of the mandible. The distraction plate was left submerged, and the activation mechanism connected to the distraction rod was exposed intra‐orally. The protocol of periosteal activation (PP: periosteal 'pumping') was initiated after a latency of 7 days. The alternation of activation and relaxation at the rate of 0.35 mm/12 h during 5 days was followed by the sole activation of 0.35 mm/12 h for 5 days (PP group). Devices were left inactivated on the contralateral control side of the mandible (C group). All animals were euthanized after 8 weeks of consolidation. Samples were analysed histologically and by means of micro‐CT. Results: New mature lamellar bone was formed over the pristine bone in all groups. More intensive signs of bone modelling and remodelling were observed in the PP group compared to the C group. Mean new bone, bone marrow, connective tissue and total volumetric densities were greater in the PP group (p < 0.001, p = 0.001, p = 0.003 and p < 0.001, respectively). No differences were observed in the relative area parameters. Total tissue volume and bone volume were higher in the PP group (p = 0.031 and p = 0.076, respectively), while the bone mineral densities were higher in the C group (p = 0.041 and p = 0.003, respectively). Trabecular number, trabecular thickness and trabecular separation values were similar between the two groups. Conclusions: Regeneration of vertical alveolar bone ridge defects may be enhanced by activation of the periosteum, without the application of bone grafting materials. [ABSTRACT FROM AUTHOR]

Objectives: To date, few studies have considered the influence of psychological factors on chronic prostatitis (PRO) models. Here, we aimed to refine a murine PRO model combining chemically induced prostatitis with psychological stress. Methods: A total of 40 mice were randomly divided into four groups: normal control (NC) group, PRO group, water avoidance stress (WAS) group, and PRO + WAS group. Ten mice were assigned to each group: five for cystometrograms (CMGs) and five for von Frey testing and histological analysis. PRO was induced through a prostatic injection of 10% paraformaldehyde. The WAS mice were placed on the middle platform for 1 h per day for 10 consecutive days. Results: The results of the von Frey test demonstrated that both WAS and PRO induced bladder hyperalgesia in mice, and the WAS + PRO group showed significant pelvic pain symptoms either. The CMG results suggested that the PRO group, the WAS group, and the PRO + WAS group all exhibited bladder overactivity, presented as a shortened micturition interval and decreased threshold pressure evoking bladder contraction. The symptoms of the PRO group and the PRO + WAS group were more severe than those of the WAS group. The tissue staining results indicated that WAS itself caused only mild prostatic inflammation but could significantly aggravate chemical‐induced prostatic inflammation, as well as the total number of mast cells and proportion of activated mast cells. Conclusions: Our refined murine PRO model could manifest persistent bladder overactivity, pelvic hyperalgesia and prostatic inflammation. WAS could induce mild prostatic inflammation and aggravate primary prostatic inflammation. [ABSTRACT FROM AUTHOR]

Brain metastases are one of the common complications of advanced malignant tumors. The study of their occurrence, development and therapeutic mechanisms is essential to improve patient survival. The development of animal models provides an important tool for in-depth exploration of brain metastasis mechanisms and facilitates the development and evaluation of novel therapeutic strategies. This article reviews the latest research progress in the construction and application of animal models of brain metastasis,covering different types of models, including homozygous transplantation models, xenograft models, and genetically engineered mouse models. These models play an important role in simulating the process of brain metastasis,analyzing the regulatory mechanism of brain metastasis and evaluating the efficacy of drugs. In addition, the paper discusses the advantages and disadvantages of the existing models, and looks forward to the potential application of animal models of brain metastasis in the future to enhance clinical relevance and promote individualized treatment. [ABSTRACT FROM AUTHOR]

Background: Escherichia coli is the most common cause of human bloodstream infections and bacterial sepsis/septic shock. However, translation of preclinical septic shock resuscitative therapies remains limited mainly due to low-fidelity of available models in mimicking clinical illness. To overcome the translational barrier, we sought to replicate sepsis complexity by creating an acutely critically-ill preclinical bacterial septic shock model undergoing active 48-h intensive care management. Aim: To develop a clinically relevant large-animal (ovine) live-bacterial infusion model for septic shock. Methods: Septic shock was induced by intravenous infusion of the live antibiotic resistant extra-intestinal pathogenic E. coli sequence type 131 strain EC958 in eight anesthetised and mechanically ventilated sheep. A bacterial dose range of 2 × 105–2 × 109 cfu/mL was used for the dose optimisation phase (n = 4) and upon dose confirmation the model was developed (n = 5). Post-shock the animals underwent an early-vasopressor and volume-restriction resuscitation strategy with active haemodynamic management and monitoring over 48 h. Serial blood samples were collected for testing of pro-inflammatory (IL-6, IL-8, VEGFA) and anti-inflammatory (IL-10) cytokines and hyaluronan assay to assess endothelial integrity. Tissue samples were collected for histopathology and transmission electron microscopy. Results: The 2 × 107 cfu/mL bacterial dose led to a reproducible distributive shock within a pre-determined 12-h period. Five sheep were used to demonstrate consistency of the model. Bacterial infusion led to development of septic shock in all animals. The baseline mean arterial blood pressure reduced from a median of 91 mmHg (71, 102) to 50 mmHg (48, 57) (p = 0.004) and lactate levels increased from a median of 0.5 mM (0.3, 0.8) to 2.1 mM (2.0, 2.3) (p = 0.02) post-shock. The baseline median hyaluronan levels increased significantly from 25 ng/mL (18, 86) to 168 ng/mL (86, 569), p = 0.05 but not the median vasopressor dependency index which increased within 1 h of resuscitation from zero to 0.39 mmHg−1 (0.06, 5.13), p = 0.065, and. Over the 48 h, there was a significant decrease in the systemic vascular resistance index (F = 7.46, p = 0.01) and increase in the pro-inflammatory cytokines [IL-6 (F = 8.90, p = 0.02), IL-8 (F = 5.28, p = 0.03), and VEGFA (F = 6.47, p = 0.02)]. Conclusions: This critically ill large-animal model was consistent in reproducing septic shock and will be applied in investigating advanced resuscitation and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background Objectives Materials and methods Results Discussion and conclusion Testicular torsion is a common urological emergency in children and teenagers that, in most cases, requires surgical exploration and detorsion. However, even after a successful intervention, a high number of patients still develop irreversible damage.To investigate whether the administration of phosphodiesterase inhibitors (PDE) in animal models of testicular torsion can reduce damages caused by the ischemia–reperfusion syndrome.A systematic search of the Medline, Web of Science, Embase, and Ovid databases for studies up to December 2023 was performed using PRISMA guidelines. A detailed search was conducted using the following key terms: “testicles,” “ischemia,” “reperfusion,” and “phosphodiesterase inhibitors.” There was no restriction regarding language or year of publication. We investigated spermatogenesis by the Johnsen's biopsy score (JTBS) and histological damage by the Cosentino's biopsy score (CBS). Malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione peroxidase (GPx) testicular levels were also analyzed.Initially, 296 articles were identified. However, only 20 studies met the inclusion criteria. PDE inhibitors improved JTBS (MD = 2.53, CI = 1.94 to 3.13), CBS (MD = −1.11, CI = −1.25 to −0.97) and SOD (SMD = 3.27, CI = 1.59 to 4.95) outcomes. PDE did not improve MDA (SMD = −0.93, CI = −2.19 to 0.34), NO (SMD = −0.54, CI = −1.56 to 0.48), and GPx (SMD = 0.77, CI = −0.38 to 1.92) outcomes. A higher dose of PDE inhibitors only improved CBS outcome.This review indicates that the administration of PDE inhibitors in rats ameliorated the outcomes, representing a promising complementary strategy for spermatogenesis recovery following testicular torsion. Our review suggests that JTBS and CBS could be translated into future human studies, validating and extending these findings within the context of human physiopathology, while providing applicability of interventions in real clinical practice. [ABSTRACT FROM AUTHOR]

Changes in neurovascular unit components and their interactions play a crucial role in epileptogenesis and the pathological process of epilepsy. Currently, there is a lack of animal models that can accurately reflect the etiological impact of cerebrovascular lesions on epilepsy. In this study, we constructed cyclindependent kinase 5 conditional knockout mice in Cspg4 (pericyte marker)- positive cells using the Cre-LoxP system. The results revealed that this strain of mice exhibited significant seizure behaviors and epileptiform brain waves, loss of hippocampal and amygdala neurons, astrogliosis, decreased pericyte coverage, and reduced AQP4 polar distribution. Herein, we have developed a novel mouse model of spontaneous epilepsy, providing a critical animal model for studying the involvement of neurovascular unit factors in the development and progression of epilepsy. [ABSTRACT FROM AUTHOR]

Introduction: Up to 40% of patients with typical hemolytic-uremic syndrome (HUS), characterized by microangiopathic hemolytic anemia and acute kidney injury (AKI), develop long-term consequences, most prominently chronic kidney disease (CKD). The transition from AKI to CKD, particularly in the context of HUS, is not yet fully understood. The objective of this study was to establish and characterize a Shiga toxin (Stx)-induced long-term HUS model to facilitate the study of mechanisms underlying the AKI-to-CKD transition. Methods: C57BL/6J mice were subjected to 5, 10, 15, or 20 ng/kg Stx on days 0, 3, and 6 of the experiment and were sacrificed on day 14 or day 21 to identify the critical time of turnover from the acute to the chronic state of HUS disease. Results: Acute disease, indicated by weight loss, plasma neutrophil gelatinaseassociated lipocalin (NGAL) and urea, and renal neutrophils, diminished after 14 days and returned to sham level after 21 days. HUS-associated hemolytic anemia transitioned to non-hemolytic microcytic anemia along with unchanged erythropoietin levels after 21 days. Renal cytokine levels indicated a shift towards pro-fibrotic signaling, and interstitial fibrosis developed concentration-dependently after 21 days. While Stx induced the intrarenal invasion of pro-inflammatory M1 and pro-fibrotic M2 macrophages after 14 days, pro-fibrotic M2 macrophages were the dominant phenotype after 21 days. Conclusion: In conclusion, we established and characterized the first Stxinduced long-term model of HUS. This tool facilitates the study of underlying mechanisms in the early AKI-to-CKD transition following HUS and allows the testing of compounds that may protect patients with AKI from developing subsequent CKD. [ABSTRACT FROM AUTHOR]

Most scientists agree that subjective tinnitus is the pathological result of an interaction of damage to the peripheral auditory system and central neuroplastic adaptations. Here we investigate such tinnitus related adaptations in the primary auditory cortex (AC) 7 and 13 days after noise trauma induction of tinnitus by quantifying the density of the extracellular matrix (ECM) in the AC of Mongolian gerbils (Meriones unguiculatus). The ECM density has been shown to be relevant for neuroplastic processes and synaptic stability within the cortex. We utilized a mild monaural acoustic noise trauma in overall 22 gerbils to induce tinnitus and a sham exposure in 16 control (C) animals. Tinnitus was assessed by a behavioral response paradigm. Animals were separated for a presence (T) or absence (NT) of a tinnitus percept by a behavioral task. The ECM density 7 and 13 days after trauma was quantified using immunofluorescence luminance of Wisteria floribunda lectin-fluoresceine-5-isothiocyanate (WFA-FITC) on histological slices of the primary AC, relative to the non-auditory brainstem as a reference area. At both timepoints, we found that the WFA-FITC luminance of the AC of NT animals was not significantly different from that of C animals. However, we found a significant increase of luminance in T animals' ACs compared to NT or C animals' cortices. This effect was found exclusively on the AC side contralateral to the trauma ear. These results point to a hemisphere specific process of stabilization of synaptic connections in primary AC, which may be involved in the chronic manifestation of tinnitus. [ABSTRACT FROM AUTHOR]

Progressive Supranuclear Palsy (PSP) is a rare and fatal neurodegenerative tauopathy which, with a rapid clinical progression coupled to a strong degree of clinico-pathologic correlation, has been suggested to be a "frontrunner" in translational development for neurodegenerative proteinopathies. Elegant studies in animals have contributed greatly to our understanding of disease pathogenesis in PSP. However, presently no animal model replicates the key anatomical and cytopathologic hallmarks, the spatiotemporal spread of pathology, progressive neurodegeneration, or locomotor and cognitive symptoms that characterize PSP. Current models therefore likely fail to recapitulate the key mechanisms that underly the pathological progression of PSP, impeding their translational value. Here we review what we have learned about PSP from work in animals to date, examine the gaps in modeling the disease and discuss strategies for the development of refined animalmodels that will improve our understanding of disease pathogenesis and provide a critical platform for the testing of novel therapeutics for this devastating disease. [ABSTRACT FROM AUTHOR]

Purpose: Cumulating evidence supports the close association between periodontal diseases, neuroinflammation and neurodegenerative pathologies, except for peri-implantitis (PI). Thus, this study explored the association between experimental PI and neuropathological changes in the rat brain. Materials and methods: After bilateral first molars extraction, experimental PI was induced at titanium implants placed in the maxillae by lipopolysaccharide injections and ligature placement. Following 28-weeks of disease progression, the maxillae and brains were retrieved from 6 rats. Healthy brains from 3 rats were used as control. Brains were analyzed by immunohistochemistry to detect signs of neuroinflammation (interleukin (IL)-6 and tumor necrosis factor (TNF)-α)), microglial activation (IBA-1) and astrogliosis (GFAP). To explore signs of neurodegeneration, hematoxylin/eosin and Nissl stainings were used. Also, four different antibodies against amyloid beta (Aβ 1–42) were tested. Results: Chronic PI lesions showed peri-implant bone resorption accompanied by large inflammatory infiltrates. IL-6+ and TNF-α+ cells were found within the CA1 and Dentate Gyrus regions of the hippocampus of the PI-affected group, while almost no immune-positivity was detected in the control (p < 0.05). Detection of activated GFAP+ microglia and IBA-1+ astrocytes surface were significantly higher at the CA areas, and cerebral cortex of the PI-affected group, in comparison with control (p < 0.05). Shrunk neurons with pyknotic nuclei were inconsistently found among the PI-affected group, and these were almost not detected in control. No positive Aβ reactivity was detected in any of the samples. Conclusion: Chronic experimental PI lesions led to an increased detection of IL-6 and TNF-α, GFAP+ microgliosis and IBA-1+ astrocytosis, and in some cases, neurodegeneration, in the rat brain. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI), a major cause of death and disability among young people, leads to significant public health and economic challenges. Despite its frequency, treatment options remain largely unsuitable. However, examination of the blood–brain barrier (BBB) can assist with understanding the mechanisms and dynamics of brain dysfunction, which affects TBI sufferers secondarily to the injury. Here, we present a rat model of TBI focused on two standard BBB assessment markers, high- and low-molecular-weight complexes, in order to understand BBB disruption. In addition, we tested a new technique to evaluate BBB disruption on a single brain set, comparing the new technique with neuroimaging. A total of 100 Sprague–Dawley rats were separated into the following five groups: naive rats (n = 20 rats), control rats with administration (n = 20 rats), and TBI rats (n = 60 rats). Rats were assessed at different time points after the injury to measure BBB disruption using low- and high-molecular-weight complexes. Neurological severity score was evaluated at baseline and at 24 h following TBI. During the neurological exam after TBI, the rats were scanned with magnetic resonance imaging and euthanized for assessment of the BBB permeability. We found that the two markers displayed different examples of BBB disruption in the same set of brain tissues over the period of a week. Our innovative protocol for assessing BBB permeability using high- and low-molecular-weight complexes markers in a single brain set showed appropriate results. Additionally, we determined the lower limit of sensitivity, therefore demonstrating the accuracy of this method. [ABSTRACT FROM AUTHOR]

Preterm infants are most at risk of iron deficiency. However, our knowledge of the regulation of iron homeostasis in preterm infants is poor. The main goal of our research was to develop and validate an animal model of human prematurity to assess iron status in preterm infants. We performed a cesarean section on sows on the 109th day of pregnancy, which corresponds to the last trimester of human pregnancy. Preterm piglets showed decreased body weight, red blood cell indices, plasma iron level and transferrin saturation. Interestingly, higher hepatic and splenic non-heme iron content and plasma and hepatic ferritin levels were found in premature piglets compared with term ones. In addition, premature piglets showed higher mRNA levels of iron-regulatory hormone hepcidin in the liver than term animals, which have not been reflected in higher plasma hepcidin-25 levels. We also showed changes in hepcidin regulators, including hepatic bone morphogenetic protein 6, plasma erythroferrone and growth differentiation factor 15 in preterm piglets. Consequently, no difference was observed in iron-exporter ferroportin levels in the spleen and liver. Overall, it seems that premature piglets show a pattern of iron metabolism characteristic of functional iron deficiency and iron accumulation in the tissue. [ABSTRACT FROM AUTHOR]

Background: Information about the volumizing effects of dermal fillers is critical for physicians' understanding of product features and prudent decision-making in clinical practice. It is important for material engineers to develop and optimize new dermal fillers, especially when comparing the physiochemical properties of a new product with those of existing fillers that are used worldwide. Objective: This study aimed to establish a reliable, noninvasive method for in vivo quantitative evaluation of the filling effect in order to predict possible effectiveness after filler injection and to evaluate the degradation trend over time. Methods: A rabbit model of ear injection with dermal fillers was established. Hyaluronic acid (HA) filler was injected into the subcutaneous layer of rabbit ears, resulting in a stable skin bulge. Ultrasonography was used to noninvasively measure the skin bulge for volume calculation; the volume change was analyzed periodically until 38 weeks. Pathological examination, the gold standard, was performed to confirm degradation. Results: The immediate volumizing effect of HA filler injection was macroscopically observed as a local skin bulge. Ultrasound was able to precisely detect the shape of the filler and calculate the length, width, and height of the skin bulge at each time point. The degree of uplift and amount of residual samples in the pathological evaluation were consistent with the results of morphological observation using ultrasound. Conclusion: Evaluation of the volume impact of dermal filler through the rabbit ear injection model evaluation enables material science evaluation in the early stage of material development, and has certain clinical reference value. Level of Evidence I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Background: Animal models focusing on neuromuscular outcomes are crucial for understanding the mechanisms of intensive care unit-acquired weakness (ICU-AW) and exploring potential innovative prevention and treatment strategies. Aim: To analyse and evaluate preclinical ICU-AW models. Methods: We manually searched five English and four Chinese databases from 1 January 2002, to 1 February 2024, and reviewed related study references. Fulltext publications describing animal models of muscle weakness and atrophy in critical illness were included. Detailed information about model types, animal species, sex, age, induction methods, outcome measures, drawbacks and strengths was extracted from each included study. Results: A total of 3,451 citations were initially retrieved, with 84 studies included in the final analysis. The most frequently studied animal model included rodents (86.9%), 64.3% of which were male animals. ICU-AW animal models were mostly induced by comprehensive intensive care unit (ICU) interventions (38.1%) and sepsis (51.2%). Most studies focused on limb muscles (66.7%), diaphragm muscles (21.4%) or both (9.5%). Reported outcomes primarily included muscular pathological changes (83.3%), electrophysiological examinations of muscles (57.1%) and animal grip strength (16.6%). However, details such as animal age, mortality data, experimental design, randomisation, blinding, sample size and interventions for the experimental group and/or control group were inadequately reported. Conclusion: Many preclinical models are used to study ICU-AW, but the reporting of methodological details is often incomplete. Although current ICU animal models can mimic the characteristics of human ICU-AW, there is no standard model. Future preclinical studies should develop a standard ICU-AW animal model to enhance reproducibility and improve scientific rigor in exploring the mechanisms and potential treatment of ICU-AW. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a complex condition characterized by fat accumulation, dyslipidemia, impaired glucose control and hypertension. In this study, rats were fed a high-fat high-fructose (HFF) diet in order to develop MetS. After ten weeks, the dietary-induced MetS was confirmed by higher body fat percentage, lower HDL-cholesterol and increased blood pressure in the HFF-fed rats compared to the normal-fed control animals. However, the effect of MetS development on the lipidomic signature of the dietary-challenged rats remains to be investigated. To reveal the contribution of specific lipids to the development of MetS, the lipid profiling of rat tissues particularly susceptible to MetS was performed using untargeted UHPLC-QTOF-MS/MS lipidomic analysis. A total of 37 lipid species (mainly phospholipids, triglycerides, sphingolipids, cholesterol esters, and diglycerides) in plasma, 43 lipid species in liver, and 11 lipid species in adipose tissue were identified as dysregulated between the control and MetS groups. Changes in the lipid signature of selected tissues additionally revealed systemic changes in the dietary-induced rat model of MetS. [ABSTRACT FROM AUTHOR]

Aim Methodology Results Conclusions Fluoride is widely used in dentistry for its caries prevention. To reduce dental caries, the optimal fluoride concentration of public water supplies in the United States is 0.7 ppm. However, excessive systemic fluoride consumption can lead to dental/enamel fluorosis. Numerous studies have explored the effects of fluoride on enamel and enamel‐forming cells. However, research on systemic fluoride's impact on dentine is limited, particularly the effect of fluoride on the structure of the dentine–pulp complex. Therefore, this study aimed to identify how excessive fluoride affects dentine microstructure using an experimental mouse model.C57BL6/J male mice (6–9 weeks old) were randomized into four groups (Fluoride at 0, 50, 100, or 125 ppm in drinking water) (n = 4/group). Mice were provided water ad libitum for 6 weeks along with fluoride‐free food. Thereafter, mandibular incisors were analysed. Enamel phenotypes were evaluated using light microscopy and quantitative light‐induced fluorescence (QLF) to measure fluorosis levels. Dentine morphology was evaluated using micro‐CT, scanning electron microscopy (SEM), SEM–EDX (energy‐dispersive X‐ray), microhardness test and histological imaging. Data were analysed using one‐way ANOVA with Dunnett's multiple comparisons as a post hoc test and the Kruskal–Wallis test with Dunn's multiple comparisons post hoc test (p < .05).Mice treated with fluoride at 50–125 ppm developed enamel hypoplasia in their erupting incisors and micro‐CT imaging revealed that fluoride 125 ppm caused external resorption of the growing incisor. Dentine mineral density, dentine volume decreased compared with the 0 ppm control, while pulp volume increased compared with the 0 ppm control group. SEM showed wider predentine layer and abnormalities in calcified matrix vesicles derived from odontoblasts in fluoride 100 and 125 ppm groups. Vickers microhardness of dentine significantly decreased in the high‐dose group. Fluoride‐induced dentine hypoplasia in a dose‐dependent manner. Histological evaluation showed excessive fluoride 125 ppm induced micro abscess formation and inflammatory cell infiltration. Fluoride induced dentine dysplasia with a dentine microstructure resembling hypophosphatasia.High doses of systemic fluoride can cause dentine dysplasia. Both three‐dimensional and microstructural analyses showed the structural, chemical and mechanical changes in the dentine and the mineralized tissue components, along with external resorption and pulp inflammation. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of intranasal (IN) and intramuscular (IM) administrations of azaperone (3 mg kg-1), midazolam (0. 3 mg kg-1), and ketamine (7 mg kg-1) combination (AMK) in pigs. Study design: Randomized clinical trial. Animals: sixteen adult male pigs, immunocastrated, of mixed lineage. Methods: In phase I, these animals were randomly assigned to intranasal (GIN, n = 8) and intramuscular (GIM, n = 8) groups for arterial blood sample collection at 10, 20, 30, 45, 60, and 90 min after AMK administrations for gas and electrolyte analysis. In phase II, performed 1 week after phase I, the 16 pigs were allocated to both groups (GIM, n = 16/GIN, n = 16) and submitted to the same chemical restraint (CR) protocol, with a 96-h interval between administrations. Behavioral parameters (degree of CR, muscle relaxation, loss of postural reflex, and sound stimulus response) and vital parameters (pulse rate, respiratory rate, oxygen saturation, and rectal temperature) were evaluated after recumbency (Trec) and at 5, 15, 30, 45, 60, and 90 min after administrations. In addition, the latency period and duration of CR were determined. Results: Latency to recumbency and duration of CR in GIN were shorter. CR scores did not vary between groups. Muscle relaxation was more intense in GIN at Trec. An initial tachycardia was observed, followed by a reduction in heart rate from T5 to T90 in both treatments (p < 0.05). The respiratory rate was higher at T45, T60, and T90 in GIN compared to baseline. Rectal temperature reduced in GIM from T45 onwards. PaCOt2 elevated at T90 in the GIM (p < 0.05) and there was an incidence of mild hypoxemia in 47% of the animals in the GIM. Conclusions and clinical relevance: IN administration was as effective as IM administration in promoting safe chemical restraint, with minimal changes in homeostasis, with a shorter duration and latency period. [ABSTRACT FROM AUTHOR]

Background: During the development of disease-modifying intervertebral disc degeneration (IDD) drugs, the rat model of IDD is frequently used for disease progression assessment. The aim of this study was to describe a magnetic resonance (MRI) scoring system for the assessment of different disc conditions in puncture-induced IDD, allowing standardization and comparison of results obtained by different investigators. Methods: A total of 36 Sprague-Dawley rats were utilized in the present study. The animals were divided into two groups: a sham group and an IDD group caused by puncture. The rats in the IDD group were subsequently divided into six categories based on time frames, with five rats in each category. The sham group was divided into two sub-groups (n = 3) for 28 and 56 days, respectively. T2-weighted images of rats consecutively studied with MRI of the coccygeal discs were classified according to the time course using the corresponding histological data. Additional scoring of the micro-CT was employed to identify the progression of bone destruction of the rat model of IDD. Results: A comparison of the MRI results between the sham group and the IDD group revealed a significant reduction in NP height, area, T2WI value, and DHI in the latter group (P < 0.05). The micro-CT results demonstrated that following acupuncture, there was a notable decline in the BV, Tb.N, and height of the coccygeal vertebra, while the BS/BV and Tb.Sp exhibited a significant increase (P < 0.05). The histological results were analogous to the MRI results, indicating a progressive exacerbation of IDD and a corresponding increase in NP score (P < 0.05). The results of the MRI were found to be consistent with those of the micro-CT and histological analyses (P < 0.05). The results of the study demonstrate a robust correlation between MRI analysis and histological findings. Live animals are employed for MRI analysis to improve experiment comparability. The reliability of the MRI scoring system ensures assessment of disease progression in live animals, while promoting cost savings and animal welfare by avoiding the sacrifice of animals at different times. Conclusions: The described scoring paradigm has quantitatively been found to differentiate IDD disease progression in an in vivo rat model. Hence, we suggest employing it to evaluate the rat IDD model and assess the effects of treatments in this model. [ABSTRACT FROM AUTHOR]

Background: Shoulder pain and disability from rotator cuff tears remain challenging clinical problem despite advancements in surgical techniques and materials. To advance our understanding of injury progression and develop effective therapeutics using tissue engineering and regenerative medicine approaches, it is crucial to develop and utilize animal models that closely resemble the anatomy and display the pathophysiology of the human rotator cuff. Among various animal models, the rabbit shoulder defect model is particularly favored due to its similarity to human rotator cuff pathology. However, a standardized protocol for creating a massive rotator cuff defect in the rabbits is not well defined. Therefore, the objective of our study was to establish a robust and reproducible model of a rotator cuff defect to evaluate the regenerative efficacy of scaffolds. Results: In our study, we successfully developed a rabbit model with a massive supraspinatus tendon defect that closely resembles the common rotator cuff injuries observed in humans. This defect involved a complete transection of the tendon, spanning 10 mm in length and encompassing its full thickness and width. To ensure stable scaffolding, we employed an innovative bridging suture technique that utilized a modified Mason-Allen suture as a structural support. Moreover, to assess the therapeutic effectiveness of the model, we utilized different scaffolds, including a bovine tendon extracellular matrix (ECM) scaffold and a commercial acellular dermal matrix (ADM) scaffold. Throughout the observation period, no scaffold damage was observed. Notably, comprehensive histological analysis demonstrated that the regenerative tissue in the tendon ECM scaffold group exhibited an organized and aligned fiber structure, indicating tendon-like tissue regeneration while the tissue in the ADM group showed comparatively less organization. Conclusions: This study presents a comprehensive description of the implemented procedures for the development of a highly reproducible animal model that induces massive segmental defects in rotator cuff tendons. This protocol can be universally implemented with alternative scaffolds to investigate extensive tendon defects and evaluate the efficacy of regenerative treatments. The application of our animal model offers a standardized and reproducible platform, enabling researchers to systematically evaluate, compare, and optimize scaffold designs. This approach holds significant importance in advancing the development of tissue engineering strategies for effectively repairing extensive tendon defects. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of systemic administration of propranolol on the severity of apical periodontitis (AP) in chronically stressed rats. Methodology: Twenty‐four 70‐day‐old male Wistar rats (Rattus norvegicus, albinus) were distributed into three groups (n = 8): rats with AP without stressful conditions (AP‐Control), rats with AP and submitted to a chronic unpredictable stress (CUS) protocol (AP + S) and rats with AP and submitted to a CUS protocol treated with propranolol (AP + S + PRO). Stress procedures were applied daily until the end of the experiment. After 3 weeks of CUS, AP was induced in all groups by exposing the pulpal tissue of mandibular and maxillary first molars to the oral environment. Propranolol treatment was administered orally once a day for the entire period of the experiment. Rats were sacrificed at 42 days, and the blood was collected for stress biomarkers serum dosage by multiplex assay. Mandibles were removed and submitted to microtomography and histopathological analyses. Periapical tissue surrounding the upper first molar was homogenized and subjected to RT‐PCR analysis to evaluate the mRNA expression of RANKL, TRAP and OPG. Parametric data were assessed using one‐way ANOVA followed by Tukey's test while the nonparametric data were analysed by the Kruskal–Wallis followed by Dunn's test. Significance level was set at 5% (p <.05) for all assessed parameters. Results: Micro‐CT revealed statistically significant differences in bone resorption which was greater in the AP + S group (p <.05), but no differences were observed between the Control and AP + S + PRO groups (p >.05). The AP + S + PRO group had a lower intensity and extent of inflammatory infiltrate compared to the AP + S group with smaller areas of bone loss (p < 0.05). The gene expression of RANKL and TRAP was significantly higher in the stressed group AP + S compared to the control group (p <.05), and a significantly higher OPG expression was observed in AP + S + PRO compared to the AP + S group (p <.05). Conclusions: Oral administration of propranolol had a significant effect on the AP severity in stressed rats, suggesting an anti‐inflammatory effect and a protective role on bone resorption of AP in stressed animals. Further research is necessary to fully comprehend the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Current animal models of sensitive skin do not adequately reflect the objective symptoms or physiological manifestations observed in human sensitive skin. Objective: To construct and validate a sensitive skin model in mice. Methods: Tape stripping (TS) was used to induce partial mechanical disruption of the lipid film and stratum corneum. Subsequently, propylene glycol (PG) was applied to disrupt the lipid structure in the skin barrier, and capsaicin (CS) activate transient receptor potential vanilloid 1 (TRPV1) receptors of keratinocytes to simulate the formation of sensitive skin. Evident itching and tingling sensations, scaly skin, vasodilation, local congestion, increased transepidermal water loss (TEWL), elevated TRPV1 expression, and inflammatory symptoms were subsequently evaluated. Results: TS combined with PG and CS application resulted in skin flakes; skin barrier disruption; vascular dilation; increased itching, stinging, and inflammation; TRPV1 upregulation in the epidermis; and a significant increase in lactic acid‐induced itching and stinging. Conclusion: Using a combination of TS and PG, and CS application, a mouse model of sensitive skin was successfully established involving various skin phenotypes and physiological manifestations, including skin flakes, vasodilation, increased blood flow and TEWL, itching and stinging sensations, inflammation, and elevated TRPV1 expression. [ABSTRACT FROM AUTHOR]

Background: Adenosinergic system has been implicated in the pathophysiology of bipolar disorder and drugs that affect adenosine neurotransmission have shown some efficacy as add‐on therapy in manic patients. Objective: Thus, the aim of the present study was to screen adenosinergic drugs for antimanic‐like effect in methylphenidate (MPH)‐induced hyperlocomotion in mice. Methods: Male and female Swiss mice received a single allopurinol (50 and 200 mg/kg, ip), dipyridamole (20 mg/kg, ip), or inosine (50 mg/kg, ip) administration before an acute MPH challenge (5 mg/kg, sc). In experiments with repeated treatment, male mice received a daily administration of allopurinol (25 and 50 mg/kg, ip), dipyridamole (20 mg/kg, ip), or inosine (50 mg/kg, ip) for 14 days. Finally, pretreatment with aminophylline (2 mg/kg, sc), an unspecific adenosine receptor antagonist, was used to evaluate a putative adenosinergic mediation. Locomotor activity was measured in the automated activity chamber for 20 min. Results: Acute and repeated dipyridamole reduced the increase in locomotor activity induced by MPH, while allopurinol and inosine had no effect. Aminophylline blocked the effect of dipyridamole in MPH‐induced hyperlocomotion. Conclusion: The present results suggest that dipyridamole may have an antimanic‐like effect through adenosine receptors and reinforce the proposal that the adenosine system may be an interesting target for new antimanic drugs. [ABSTRACT FROM AUTHOR]

Beneficial effects of hazelnuts on human health are well known, and recent research on heart health has generated more interest. However, studies based on its oxidative damage preventive effect are not well explained in patients with diabetes mellitus (DM). Therefore, the aim of this study was to investigate the protective effect of hazelnut against oxidative stressinduced damage in hepatic ischemia/reperfusion (I/R) injury in rats induced by streptozotocin (STZ). Rats were divided into four groups (Control, DM, DM+I/R, DH; n=6 in each). The I/R model was created four weeks after DM was induced in rats. In four weeks until the I/R model was created, the DM+I/R+Hazelnut group was fed with pellet feed (2 g/100 g/day) prepared with hazelnut. At the end of experiment, glutathione (GSH) and malondialdehyde (MDA) levels in liver tissue, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) levels were measured in serum. The results showed that TNF-α, IL-6, and MDA levels increased significantly in the DM+I/R group, while this increase was less in the DM+I/R+Hazelnut group. It is concluded that hepatic I/R damage caused increased inflammatory response and oxidative stress in diabetic rats, and this response was decreased/modulated by the pre-treatment with hazelnuts. [ABSTRACT FROM AUTHOR]

Objective To establish a weightlessness simulation animal model using miniature pigs, leveraging the characteristic of multiple systems’ tissue structures and functions similar to those of humans, and to observe pathophysiological changes, providing a new method for aerospace research. Methods Nine standard-grade miniature pigs were selected and randomly divided into an experimental group (n=7) and a control group (n=2). The experimental group was fixed using customized metal cages, with canvas slings suspending their hind limbs off the ground, and the body positioned at a -20° angle relative to the ground to simulate unloading for 30 days (24 hours a day). Data on body weight, blood volume, and blood biochemistry indicators were collected at different time points for statistical analysis of basic physiological changes. After the experiment, the miniature pigs were euthanized and tissue samples were collected for histopathological observation of the cardiovascular, skeletal and muscle systems HE and Masson staining. Statistical analysis was also conducted on the thickness of arterial vessels and the diameter of skeletal muscle fibers. Additionally, western blotting was employed to detect the expression levels of skeletal muscle atrophy-related proteins, including muscle-specific RING finger protein 1 (MuRf-1) and muscle atrophy F-box (MAFbx, as known as Atrogin-1), while immunohistochemistry was used to detect the expression of glial fibrillary acidic protein (GFAP), an indicator of astrocyte activation in the brain, reflecting the pathophysiological functional changes across systems. Results After hindlimb unloading, the experimental group showed significant decreases in body weight (P<0.001) and blood volume (P<0.01). During the experiment, hemoglobin, hematocrit, and red blood cell count levels significantly decreased (P<0.05) but gradually recovered. The expression levels of alanine aminotransferase and γ -glutamyltransferase initially decreased (P<0.05) before rebounding, while albumin significantly decreased (P<0.001) and globulin significantly increased (P<0.01). Creatinine significantly decreased (P<0.05). The average diameter of gastrocnemius muscle fibers in the experimental group significantly shortened (P<0.05), with a leftward shift in the distribution of muscle fiber diameters and an increase in small-diameter muscle fibers. Simultaneously, Atrogin-1 expression in the gastrocnemius and paravertebral muscles significantly increased (P<0.05). These changes are generally consistent with the effects of weightlessness on humans and animals in space. Furthermore, degenerative changes were observed in some neurons of the cortical parietal lobe, frontal lobe, and hippocampal regions of the experimental group, with a slight reduction in the number of Purkinje cells in the cerebellar region, and a significant enhancement of GFAP-positive signals in the hippocampal area (P<0.05). Conclusion Miniature pigs subjected to a -20° angle hind limb unloading for 30 days maybe serve as a new animal model for simulating weightlessness, applicable to related aerospace research. [ABSTRACT FROM AUTHOR]

In recent years, a significant research effort has been underway to explore the effects of low-dose radiation (LDR). Animal models play a key role in various fields of research, including biomedicine, pharmaceutical, environmental, and behavioral studies. The use of animal models has been an invaluable tool in radiation research for understanding radiation biology, assessing radiation risks, and developing strategies for radiation protection and medical management. In the present review, the initial part focuses on the deleterious effects of high-dose radiation, and in correlation to that, in the later part of the review, the emphasis has been given to experimental approaches to explore the beneficial effects of LDR using animal models. This review could help explore the innovative approach for future research targeting the therapeutic role of LDR in various diseases, including depression, Cancer, Parkinson's disease, and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

OBJECTIVES Colchicine, an anti-inflammatory agent, has been reported to improve myocardial infarction prognosis by inhibiting neutrophil extracellular traps (NETs) release. However, its role in cardiac surgery and the mechanisms behind NETs suppression remain unclear. This study aimed to explore colchicine's cardioprotective effects against perioperative myocardial injury in cardiac surgery, focusing on NETs inhibition as a novel therapeutic strategy. METHODS Male Sprague-Dawley rats were pre-treated with colchicine (0.1 mg/kg/day) or CI-amidine (10 mg/kg/day) for 7 days before undergoing cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. The model was created by subjecting the rats to cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. Under 4.0% sevoflurane anaesthesia, cardiopulmonary bypass was initiated by cannulating the tail artery and right atrium, and perfusion was maintained for 4 h. Immunofluorescence detected NETs, and haematoxylin and eosin staining assessed inflammatory cell. RESULTS We found colchicine treatment significantly reduced perioperative myocardial injury in rats. Furthermore, we observed a notable elevation of NETs in the myocardial tissue of animal models. Moreover, suppressing peptidylarginine deiminase 4 was found to markedly diminish perioperative myocardial injury in rats. Additionally, colchicine can mitigate the release of NETs by inhibiting peptidylarginine deiminase 4. CONCLUSIONS NETs were significantly elevated during the perioperative period of cardiac surgery. Colchicine significantly mitigated myocardial injury in cardiac surgery by inhibiting NETs formation, with peptidylarginine deiminase 4 inhibition being one of its mechanisms. [ABSTRACT FROM AUTHOR]

Background: Bones are biological reservoirs for minerals and cells, offering protection to the other organs and contributing to the structural form of the body. Osteoporosis is a prevalent bone condition that significantly impacts people's quality of life. Treatments utilizing natural products and medicinal plants have gained important attention in the management of osteoporosis and its associated implications, such as osteoporotic fractures. Even though thousands of plants grow in the Mediterranean region, the use of medicinal plants as an alternative therapy for osteoporosis is still limited. Methods: This article provides a comprehensive overview of seven Mediterranean medicinal plants that are used in osteoporosis and osteoporotic fractures in in vitro, in vivo, and clinical trials. The mechanism of action of the medicinal plants and their bioactive compounds against diseases are also briefly discussed. Results: The findings clearly indicate the ability of the seven medicinal plants (Ammi majus, Brassica oleracea, Ceratonia siliqua L., Foeniculum vulgare, Glycyrrhiza glabra, Salvia officinalis, and Silybum marianum) as anti-osteoporosis agents. Xanthotoxin, polyphenols, liquiritin, formononetin, silymarin, and silibinin/silybin were the main bioactive compounds that contributed to the action against osteoporosis and osteoporotic fractures. Conclusions: In this review, the Mediterranean medicinal plants prove their ability as an alternative agent for osteoporosis and osteoporotic fractures instead of conventional synthetic therapies. Thus, this can encourage researchers to delve deeper into this field and develop medicinal-plant-based drugs. [ABSTRACT FROM AUTHOR]