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Inorganic arsenic (iAs) is an environmental toxicant that can lead to severe health consequences, which can be exacerbated if exposure occurs early in development. Here, we evaluated the impact of oral iAs treatment on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) mice. We found that oral administration of iAs to neonatal hUGT1 mice that display severe neonatal hyperbilirubinemia leads to induction of intestinal UGT1A1 and a reduction in total serum bilirubin values. Oral iAs administration accelerates neonatal intestinal maturation, an event that is directly associated with UGT1A1 induction. As a reactive oxygen species producer, oral iAs treatment activated the Keap-Nrf2 pathway in the intestinal tract and liver. When Nrf2-deficient hUGT1 mice (hUGT1/Nrf2-/-) were treated with iAs, it was shown that activated Nrf2 contributed significantly toward intestinal maturation and UGT1A1 induction. However, hepatic UGT1A1 was not induced upon iAs exposure. We previously demonstrated that the nuclear receptor PXR represses liver UGT1A1 in neonatal hUGT1 mice. When PXR was deleted in hUGT1 mice (hUGT1/Pxr-/-), derepression of UGT1A1 was evident in both liver and intestinal tissue in neonates. Furthermore, when neonatal hUGT1/Pxr-/- mice were treated with iAs, UGT1A1 was superinduced in both tissues, confirming PXR release derepressed key regulatory elements on the gene that could be activated by iAs exposure. With iAs capable of generating reactive oxygen species in both liver and intestinal tissue, we conclude that PXR deficiency in neonatal hUGT1/Pxr-/- mice allows greater access of activated transcriptional modifiers such as Nrf2 leading to superinduction of UGT1A1.

Women who contract a viral or bacterial infection during pregnancy have an increased risk of giving birth to a child with a neurodevelopmental or psychiatric disorder. The effects of maternal infection are likely mediated by the maternal immune response, as preclinical animal models have confirmed that maternal immune activation (MIA) leads to long lasting changes in offspring brain and behavior development. The present study sought to determine the impact of MIA-exposure during the first or second trimester on neuronal morphology in dorsolateral prefrontal cortex (DLPFC) and hippocampus from brain tissue obtained from MIA-exposed and control male rhesus monkey (Macaca mulatta) during late adolescence. MIA-exposed offspring display increased neuronal dendritic branching in pyramidal cells in DLPFC infra- and supragranular layers relative to controls, with no significant differences observed between offspring exposed to maternal infection in the first and second trimester. In addition, the diameter of apical dendrites in DLPFC infragranular layer is significantly decreased in MIA-exposed offspring relative to controls, irrespective of trimester exposure. In contrast, alterations in hippocampal neuronal morphology of MIA-exposed offspring were not evident. These findings demonstrate that a maternal immune challenge during pregnancy has long-term consequences for primate offspring dendritic structure, selectively in a brain region vital for socioemotional and cognitive development.

Abstract The Crumbs protein (CRB) family plays a crucial role in maintaining the apical–basal polarity and integrity of embryonic epithelia. The family comprises different isoforms in different animals and possesses diverse structural, localization, and functional characteristics. Mutations in the human CRB1 or CRB2 gene may lead to a broad spectrum of retinal dystrophies. Various CRB-associated experimental models have recently provided mechanistic insights into human CRB-associated retinopathies. The knowledge obtained from these models corroborates the importance of CRB in retinal development and maintenance. Therefore, complete elucidation of these models can provide excellent therapeutic prospects for human CRB-associated retinopathies. In this review, we summarize the current animal models and human-derived models of different CRB family members and describe the main characteristics of their retinal phenotypes.

Abstract We tested the ability of a physiologically driven minimally invasive closed-loop algorithm, called Resuscitation based on Functional Hemodynamic Monitoring (ReFit), to stabilize for up to 3 h a porcine model of noncompressible hemorrhage induced by severe liver injury and do so during both ground and air transport. Twelve animals were resuscitated using ReFit to drive fluid and vasopressor infusion to a mean arterial pressure (MAP) > 60 mmHg and heart rate

Abstract Low-frequency transcranial ultrasound stimulation (TUS) allows to alter brain functioning with a high spatial resolution and to reach deep targets. However, the time-course of TUS effects remains largely unknown. We applied TUS on three brain targets for three different monkeys: the anterior medial prefrontal cortex, the supplementary motor area and the perigenual anterior cingulate cortex. For each, one resting-state fMRI was acquired between 30 and 150 min after TUS as well as one without stimulation (control). We captured seed-based brain connectivity changes dynamically and on an individual basis. We also assessed between individuals and between targets homogeneity and brain features that predicted TUS changes. We found that TUS prompts heterogenous functional connectivity alterations yet retain certain consistent changes; we identified 6 time-courses of changes including transient and long duration alterations; with a notable degree of accuracy we found that brain alterations could partially be predicted. Altogether, our results highlight that TUS induces heterogeneous functional connectivity alterations. On a more technical point, we also emphasize the need to consider brain changes over-time rather than just observed during a snapshot; to consider inter-individual variability since changes could be highly different from one individual to another.

Abstract Background Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. Methods This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. Results Pulmonary pressures increased after the initial PE administration (p

Abstract Postoperative intra-abdominal adhesions represent a significant post-surgical problem. Its complications can cause a considerable clinical and cost burden. Herein, our study aimed to investigate the effect of Everolimus on peritoneal adhesion formation after inducing adhesions in rats. In this experimental study, adhesion bands were induced by intraperitoneal injection of 3 ml of 10% sterile talc solution in 64 male albino rats. The first group served as the control group. The second one received oral Prednisolone (1 mg/kg/day), the third received Everolimus (0.1 mg/kg/day), and group four received both drugs with similar dosages for four consecutive weeks. The formation of adhesion bands was qualitatively graded according to the Nair classification. The rats in the control group had extensive adhesions between the abdominal wall and the organs. Regarding substantial adhesion formation, 50% (8/16) of animals in the control group had substantial adhesions, while this rate in the groups receiving Prednisolone, Everolimus, and combination treatment was 31%, 31%, and 31%, respectively. Also, 68.75% (5/11) of the Prednisolone recipients had insubstantial adhesions, the same as Everolimus recipients, while in the combination group, 66.66% (10/15) rats had insubstantial adhesions. Everolimus demonstrated satisfactory results in reducing the rates of induced peritoneal adhesion in an experimental model, similar to Prednisolone and superior to a combination regime.

Abstract Introduction Immune checkpoint inhibitors (ICIs) induce acute interstitial nephritis (AIN) in 2–5% of patients, with a clearly higher incidence when they are combined with platinum derivatives. Unfortunately, suitable disease models and non-invasive biomarkers are lacking. To fill this gap in our understanding, we investigated the renal effects of cisplatin and anti-PD-L1 antibodies in mice, assessing PD-1 renal expression and cytokine levels in mice with AIN, and then we compared these findings with those in AIN-diagnosed cancer patients. Methods Twenty C57BL6J mice received 200 µg of anti-PD-L1 antibody and 5 mg/kg cisplatin intraperitoneally and were compared with those receiving cisplatin (n = 6), anti-PD-L1 (n = 7), or saline (n = 6). After 7 days, the mice were euthanized. Serum and urinary concentrations of TNFα, CXCL10, IL-6, and MCP-1 were measured by Luminex. The kidney sections were stained to determine PD-1 tissue expression. Thirty-nine cancer patients with AKI were enrolled (AIN n = 33, acute tubular necrosis (ATN) n = 6), urine MCP-1 (uMCP-1) was measured, and kidney sections were stained to assess PD-1 expression. Results Cisplatin and anti PD-L1 treatment led to 40% AIN development (p = 0.03) in mice, accompanied by elevated serum creatinine and uMCP1. AIN-diagnosed cancer patients also had higher uMCP1 levels than ATN-diagnosed patients, confirming our previous findings. Mice with AIN exhibited interstitial PD-1 staining and stronger glomerular PD-1 expression, especially with combination treatment. Conversely, human AIN patients only showed interstitial PD-1 positivity. Conclusions Only mice receiving cisplatin and anti-PDL1 concomitantly developed AIN, accompanied with a more severe kidney injury. AIN induced by this drug combination was linked to elevated uMCP1, consistently with human AIN, suggesting that uMCP1 can be potentially used as an AIN biomarker.

Oxidative stress and inflammation play a central role in the progression of nonalcoholic steatohepatitis (NASH), which can lead to liver cirrhosis. Barley bran has potential bioactivities due to its high content of functional substances, such as anthocyanins, with anti-inflammatory and anti-oxidative properties. Here, we investigated whether barley bran polyphenol-rich extracts (BP) can prevent NASH in Sprague–Dawley rats fed a high-fat and high-cholesterol diet including 1.25% or 2.5% cholesterol for 9 weeks. In the rat model of NASH with advanced hepatic fibrosis, BP prevented NASH development by ameliorating the histopathological findings of lobular inflammation. The BP also tended to attenuate serum aspartate aminotransferase level in this model. In the rat model of NASH with mild-to-moderate hepatic fibrosis, BP tended to attenuate the serum levels of transaminases. BP-dose-dependent effects were revealed for several parameters, including monocyte chemoattractant protein-1, transforming growth factor-β, and manganese superoxide dismutase gene expressions in the liver. These results suggest that BP may prevent NASH development or progression, presumably due to its anti-inflammatory and anti-oxidative properties.

The etiology of autism spectrum disorder (ASD) has been linked to both genetic and epigenetic factors. Among the epigenetic factors, exposure to valproic acid (VPA), an antiepileptic and mood-modulating drug, has been shown to induce characteristic traits of ASD when exposed to during embryogenesis. Conversely, in animal models, enriched environment (EE) has demonstrated positive behavioral and neural effects, suggesting its potential as a complementary treatment to pharmacological approaches in central nervous system disorders. In this study, we utilized zebrafish to model ASD characteristics induced by VPA and hypothesized that sensory stimulation through EE could ameliorate the behavioral and neuroanatomical features associated with ASD. To test this hypothesis, we assessed social behavior, cerebellar volume, and Purkinje cell populations via histology and immunohistochemistry after exposing the fish to EE. The results revealed that zebrafish exposed to VPA exhibited social deficits, reduced cerebellar cortex volume, and a decrease in c-Fos-positive cells in the Purkinje layer. In contrast, VPA-exposed fish treated with EE showed increased socialization, augmented cerebellar cortex volume, and an elevation in c-Fos-positive Purkinje cells. These findings suggest that alterations induced by VPA may be ameliorated through EE treatment, highlighting the potential therapeutic impact of sensory stimulation in conditions related to ASD.

Obstructive sleep apnea (OSA) is a common sleep disorder, and its pathophysiological mechanism complex and not fully understood. This article elaborately explores three categories of OSA animal models: natural, direct and indirect, emphasizing their advantages and disadvantages in simulating OSA pathophysiological processes. Natural OSA models primarily focus on spontaneous upper airway obstructions. Direct OSA models induce OSA through direct obstruction of the airway, while indirect OSA models mainly investigate the impacts of chronic intermittent hypoxia (IH) and sleep deprivation (SD) on the organism. Although these models have played a pivotal role in studying the pathophysiological mechanisms of OSA and developing new therapeutic methods, they also present certain limitations and challenges. Future research directions include the development of non-invasive monitoring technologies, establishing OSA-combined models, and the application of gene-editing technologies, aiming to more comprehensively and accurately simulate the complexity and diversity of human OSA, providing more insights into its mechanisms and developing new therapeutic methods.

The 2023 China Health Report on Spine Degeneration noted a significant increase in lumbar surgery among patients under 35 years old in recent years, indicating a trend towards younger onset of cervical and lumbar diseases. Lumbar intervertebral disc herniation has become a major concern, making the study of disc degeneration pathogenesis and treatment methods clinically significant. At present, human intervertebral disc diseases are primarily diagnosed through imaging due to the challenges of obtaining tissue samples from the spine. Therefore, experimental animals have emerged as alternative research subjects because they are cost-effective, have short experimental cycles, and are easily accessible. Given the structural and physiological differences between human and other animal intervertebral discs, comparing their anatomy and histological characteristics forms the foundation of research into human disc degeneration. The purpose of this paper is to collect and review relevant studies on anatomical and histological structures of intervertebral discs in different animals and conduct a comparative analysis from four aspects, namely, intervertebral disc height, lumbar disc geometry, lumbar disc cartilaginous endplate characteristics, and extracellular matrix components. The results show that humans, kangaroos, sheep, pigs, and rats exhibit similar relative heights between the sixth and seventh cervical vertebrae. Mice possess lumbar disc geometries most akin to humans. Compared to other animals, humans have the thickest cartilaginous endplates and the lowest cell densities. The collagen within the fibrous annulus differs most notably in pigs compared to humans, while water content in the nucleus pulposus is consistent across pigs, sheep, rabbits, rats, and humans. Additionally, this paper describes the commonalities and discrepancies in disc degeneration manifestations between humans and animals, and summarizes modeling methods for disc degeneration in different experimental animals. Ultimately, the aims of this paper is to provide fundamental data for selecting suitable experimental animal models for the study of intervertebral disc degeneration.

Uric acid (UA), the final product of human purine metabolism, can cause hyperuricemia (HUA) when excessively accumulated. HUA is closely linked to chronic kidney diseases (CKD) and is considered an independent risk factor. Hyperuricemic nephropathy, a form of CKD induced by HUA, has seen significant advances in understanding through research into the pathogenic roles of uric acid and the development of HUA animal models. Although progress has been made in understanding the pathophysiological mechanisms by which UA induces CKD, much remains to be learned about its pathological molecular mechanisms. New approaches in animal modeling or the selection of model animals may potentially lead to significant breakthroughs in research on hyperuricemia as well as related CKD. This paper reviews the research progress on the molecular mechanisms of hyperuricemic nephropathy, focusing on oxidative stress, inflammation, autophagy, fibrosis, and gut microbiota. Oxidative stress is induced by uric acid intracellularly through xanthine oxidase, NADPH oxidases, and mitochondria, leading to cellular damage. In terms of inflammation, uric acid crystals can activate the NLRP3 inflammasome, triggering an inflammatory cascade. The role of free uric acid as a pro-inflammatory agent, however, remains controversial. Depending on the study conducted, autophagy has been found to either alleviate or exacerbate inflammation induced by uric acid. Fibrosis, particularly through epithelial-mesenchymal transition (EMT), is a major mechanism by which uric acid causes glomerulosclerosis and tubulointerstitial fibrosis. Extensive research has explored various signaling pathways involved in uric acid-induced EMT. Beneficial gut microbiota protect the kidneys by synthesizing short-chain fatty acids, reducing urea’s enterohepatic circulation, and decreasing uric acid production. This paper aims to enhance understanding of the complex relationships between HUA and CKD, serving as a reference for further research and new drug development.

Aims: Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells. Methods: HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential. Results: Vorinostat, a HDACi compound, blocked the adipogenic transformation of muscle-associated FAPs in culture, promoting myogenic progression of the satellite cells. Furthermore, it protected muscle from degeneration after acute RC in mice in the earlier muscle degenerative stage after tenotomy. Conclusion: The HDACi vorinostat may be a candidate to prevent early muscular degeneration after RC injury. Cite this article: Bone Joint Res 2024;13(4):169–183.

Abstract Scientific progress heavily relies on rigorous research, adherence to scientific standards, and transparent reporting. Animal models play a crucial role in advancing biomedical research, especially in the field of gene therapy. Animal models are vital tools in preclinical research, allowing scientists to predict outcomes and understand complex biological processes. The selection of appropriate animal models is critical, considering factors such as physiological and pathophysiological similarities, availability, and ethical considerations. Animal models continue to be indispensable tools in preclinical gene therapy research. Advancements in genetic engineering and model selection have improved the fidelity and relevance of these models. As gene therapy research progresses, careful consideration of animal models and transparent reporting will contribute to the development of effective therapies for various genetic disorders and diseases. This comprehensive review explores the use of animal models in preclinical gene therapy studies for approved products up to September 2023. The study encompasses 47 approved gene therapy products, with a focus on preclinical trials. This comprehensive analysis serves as a valuable reference for researchers in the gene therapy field, aiding in the selection of suitable animal models for their preclinical investigations.

Abstract Acute thrombosis secondary to atherosclerotic plaque rupture is the main cause of acute cardiac and cerebral ischemia. An animal model of unstable atherosclerotic plaques is highly important for investigating the mechanism of plaque rupture and thrombosis. However, current animal models involve complex operations, are costly, and have plaque morphologies that are different from those of humans. We aimed to establish a simple animal model of vulnerable plaques similar to those of humans. Rabbits were randomly divided into three groups. Group A was given a normal formula diet for 13 weeks. Group C underwent surgery on the intima of the right carotid artery with – 80 °C cryofluid-induced injury after 1 week of a high-fat diet and further feeding a 12-week high-fat diet. Group B underwent the same procedure as Group C but without the – 80 °C cryofluid. Serum lipid levels were detected via ELISA. The plaque morphology, stability and degree of stenosis were evaluated through hematoxylin–eosin (HE) staining, Masson trichrome staining, Elastica van Gieson staining (EVG), and oil red O staining. Macrophages and inflammatory factors in the plaques were assessed via immunohistochemical analysis. The serum low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) levels in groups B and C were significantly greater than those in group A. No plaque formation was observed in group A. The plaques in group B were very small. In group C, obvious plaques were observed in the blood vessels, and the plaques exhibited a thin fibrous cap, a large lipid core, and partially visible neovascularization, which is consistent with the characteristics of vulnerable plaques. In the plaques of group C, a large number of macrophages were present, and matrix metalloproteinase 9 (MMP-9) and lectin-like oxidized LDL receptor 1 (LOX-1) were abundantly expressed. We successfully established a rabbit model of vulnerable carotid plaque similar to that of humans through the combination of cryofluid-induced endothelial injury and a high-fat diet, which is feasible and cost effective.

Zih-Chan Lin,1 Chi-Feng Hung,2– 4 Ibrahim A Aljuffali,5 Ming-Hsien Lin,6 Jia-You Fang7– 9 1Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi, Chiayi, Taiwan; 2School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 3Program in Pharmaceutical Biotechnology, Fu Jen Catholic University, New Taipei City, Taiwan; 4School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 6Department of Dermatology, Chi Mei Medical Center, Tainan, Taiwan; 7Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; 8Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; 9Department of Anesthesiology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, TaiwanCorrespondence: Ming-Hsien Lin, Department of Dermatology, Chi Mei Medical Center, 901 Zhonghua Road, Yongkang, Tainan, Taiwan, Email i5483123@nckualumni.org.tw Jia-You Fang, Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan, 333, Taiwan, Email fajy@mail.cgu.edu.twAbstract: Psoriasis presents as a complex genetic skin disorder, characterized by the interaction between infiltrated immune cells and keratinocytes. Substantial progress has been made in understanding the molecular mechanisms of both coding and non-coding genes, which has positively impacted clinical treatment approaches. Despite extensive research into the genetic aspects of psoriasis pathogenesis, fully grasping its epigenetic component remains a challenging endeavor. In response to the pressing demand for innovative treatments to alleviate inflammatory skin disorders, various novel strategies are under consideration. These include gene therapy employing antisense nucleotides, silencing RNA complexes, stem cell therapy, and antibody-based therapy. There is a pressing requirement for a psoriasis-like animal model that replicates human psoriasis to facilitate early preclinical evaluations of these novel treatments. The authors conduct a comprehensive review of various gene therapy in different psoriasis-like animal models utilized in psoriasis research. The animals included in the list underwent skin treatments such as imiquimod application, as well as genetic and biologic injections, and the results of these interventions are detailed. Animal models play a crucial role in translating drug discoveries from the laboratory to clinical practice, and these models aid in improving the reproducibility and clinical applicability of preclinical data. Numerous animal models with characteristics similar to those of human psoriasis have proven to be useful in understanding the development of psoriasis. In this review, the article focuses on RNA-based gene therapy exploration in different types of psoriasis-like animal models to improve the treatment of psoriasis.Keywords: psoriasis, animal model, gene therapy, siRNA, miRNA

Abstract Background Although radiotherapy is commonly used to treat head and neck cancer, it may lead to radiation-associated dysphagia (RAD). There are various causes of RAD, however, the mechanism has not yet been fully identified. Currently, the only effective treatment for RAD is rehabilitation. Additionally, there are few available animal models of RAD, necessitating the development of new models to establish and evaluate RAD treatments. We hypothesize that radiation-induced neck muscle fibrosis could be one of the causes of RAD due to impairment of laryngeal elevation. Therefore, in this study, we focused on the changes in inflammation and fibrosis of the strap muscles (Sternohyoid, Sternothyroid, and Thyrohyoid muscles) after a single-dose irradiation. This research aims to provide a reference animal model for future studies on RAD. Results Compared to control mice, those treated with 72-Gy, but not 24-Gy, irradiation had significantly increased tumor necrosis factor-α (TNF-α) (p

Abstract Background There have been no reports on the successful implementation of stellate ganglion block (SGB) in mice. Objectives This study aims to investigate a new method for implementing SGB in mice by placing them in a supine position with abducted upper limbs and touching the trachea and sternoclavicular joint with the hand. Methods Fifty BABL/C mice, 8–10 weeks, were selected and randomly divided into four groups: control group (n = 5); SGB-R group (n = 15); SGB-L group (n = 15); and SGB-L + R (group n = 15). SGB was administered with 0.15% ropivacaine solution in a volume of 0.1 mL. The control group received equal volumes of saline. Horner's syndrome, heart rate, and complications such as brachial plexus block, vascular injury, pneumothorax, local anesthetic toxicity, and death were observed. Results Horner's syndrome developed in 100% of SGB surviving mice; no difference was seen in the time to onset (100.4 ± 13.4 vs 96.7 ± 12.4, mean ± SD, seconds) and duration (264.1 ± 40.5 vs 296.3 ± 48.0, mean ± SD, min) of Horner's syndrome in the left and right SGB (P > 0.05). Compared with the control group (722 [708–726], median [IQR], bpm), the heart rate was significantly slowed down in the right SGB (475 [451.5–491], median [IQR], bpm) (P 0.05). The overall complication rate was 18.4%, with a brachial plexus block rate of 12.3%, a vascular injury rate of 4.6%, and a mortality rate of 1.5%, as well as no local anesthetic toxicity (includes bilateral implementation of SGB) or pneumothorax manifestations were found. Conclusions This method allows for the successful implementation of SGB in a mouse model.

Abstract Vesicovaginal fistula lacks a standard, established animal model, making surgical innovations for this condition challenging. Herein, we aimed to non-surgically establish vesicovaginal fistula using the magnetic compression technique, and the feasibility of this method was explored using eight female Beagle dogs as model animals. In these dogs, cylindrical daughter and parent magnets were implanted into the bladder and vagina, respectively, after anesthesia, and the positions of these magnets were adjusted under X-ray supervision to make them attract each other, thus forming the structure of daughter magnet-bladder wall-vaginal wall-parent magnet. Operation time and collateral damage were recorded. The experimental animals were euthanized 2 weeks postoperatively, and the vesicovaginal fistula gross specimens were obtained. The size of the fistula was measured. Vesicovaginal fistula was observed by naked eye and under a light microscope. Magnet placement was successful in all dogs, and remained in the established position for the reminder of the experiment. The average operation time was 14.38 min ± 1.66 min (range, 12–17 min). The dogs were generally in good condition postoperatively and were voiding normally, with no complications like bleeding and urine retention. The magnets were removed from the vagina after euthanasia. The vesicovaginal fistula was successfully established according to gross observation, and the fistula diameters were 4.50–6.24 mm. Histological observation revealed that the bladder mucosa and vaginal mucosa were in close contact on the internal surface of the fistula. Taken together, magnetic compression technique is a simple and feasible method to establish an animal model of vesicovaginal fistula using Beagle dogs. This model can help clinicians study new surgical techniques and practice innovative approaches for treating vesicovaginal fistula.

Since the identification of the poliovirus in 1908, over a hundred serotypes of enteroviruses have been discovered, capable of causing a range of diseases including hand, foot, and mouth disease, newborn sepsislike syndrome, aseptic meningitis, acute flaccid paralysis, respiratory disorders, and acute hemorrhagic conjunctivitis. In recent years, enteroviruses such as EV-A71 and EV-D68 have exhibited globalized periodic outbreaks, emerging as a significant and indisputable challenge in the field of public health. However, the current preventive and control measures for enteroviruses remain notably limited, necessitating a pressing need to delve deeper into the molecular mechanisms responsible for enteroviral pathogenesis. This will facilitate the development of novel targets and methodologies for the creation of effective, safe, and broad-spectrum antiviral drugs. This comprehensive review focuses on the classification, epidemiology, structure, life cycle, interplay between viral proteins and host factors, pathogenic mechanisms, clinical treatments, and the establishment and application of animal infection models relevant to enteric viruses. The aim is to serve as a theoretical referential basis for the prevention and control of enteroviruses, offering novel perspectives for the development of drugs and the establishment of a vaccine repository dedicated to combating enteroviruses.

Abstract Background Patellofemoral osteoarthritis (PFJOA) is a subtype of knee OA, which is one of the main causes of anterior knee pain. The current study found an increased prevalence of OA in postmenopausal women, called postmenopausal OA. Therefore, we designed the ovariectomized rat model of patella baja-induced PFJOA. Alendronate (ALN) inhibits osteoclast-mediated bone loss, and has been reported the favorable result of a potential intervention option of OA treatment. However, the potential effects of ALN treatment on PFJOA in the ovariectomized rat model are unknown and need further investigation prior to exploration in the clinical research setting. In this study, the effects of ALN on articular cartilage degradation and subchondral bone microstructure were assessed in the ovariectomized PFJOA rat model for 10 weeks. Methods Patella baja and estrogen withdrawal were induced by patellar ligament shortening (PLS) and bilateral ovariectmomy surgeries in 3-month-old female Sprague–Dawley rats, respectively. Rats were randomly divided into five groups (n = 8): Sham + V; OVX + V, Sham + PLS + V, OVX + PLS + V, OVX + PLS + ALN (ALN: 70 μg/kg/week). Radiography was performed to evaluate patellar height ratios, and the progression of PFJOA was assessed by macroscopic and microscopic analyses, immunohistochemistry and micro-computed tomography (micro-CT). Results Our results found that the patella baja model prepared by PLS can successfully cause degeneration of articular cartilage and subchondral bone, resulting in changes of PFJOA. OVX caused a decrease in estrogen levels in rats, which aggravated the joint degeneration caused by PFJOA. Early application of ALN can delay the degenerative changes of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent, improve and maintain the micrometabolism and structural changes of cartilage and subchondral bone. Conclusion The early application of ALN can delay the destruction of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent.

Background and aim: The liver is susceptible to ischemia-reperfusion injury (IRI) during hepatic surgery, when the vessels are compressed to control bleeding, or liver transplantation, when there is an obligate period of ischemia. The hallmark of IRI comprises mitochondrial dysfunction, which generates reactive oxygen species, and cell death through necrosis or apoptosis. Cyclosporine (CsA), which is a well-known immunosuppressive agent that inhibits calcineurin, has the additional effect of inhibiting the mitochondrial permeability transition pore (mPTP), thereby, preventing mitochondrial swelling and injury. NIM-811, which is the nonimmunosuppressive analog of CsA, has a similar effect on the mPTP. In this study, we tested the effect of both agents on mitigating warm hepatic IRI in a murine model. Materials and methods: Before ischemic insult, the mice were administered with intraperitoneal normal saline (control); CsA at 2.5, 10, or 25 mg/kg; or NIM-811 at 10 mg/kg. Thereafter, the mice were subjected to partial warm hepatic ischemia by selective pedicle clamping for 60 min, followed by 6 h of recovery after reperfusion. Serum alanine transaminase (ALT) was measured, and the liver tissue was examined histologically for the presence of apoptosis and the levels of inflammatory cytokines. Results: Compared with the control mice, the mice treated with 10 and 25 mg/kg of CsA and NIM-811 had significantly lower ALT levels (P

视网膜中央动脉阻塞是血管神经眼科急症，表现为急性无痛性单眼视力丧失，是中老年致盲的主要病因之一。目前关于视网膜中央动脉阻塞的具体发病机制和病理生理机制尚不明确，选择合适的动物模型进行视网膜中央动脉阻塞发病机制的研究和治疗药物的筛选尤为重要。本文对视网膜中央动脉阻塞动物模型的造模方法和研究进展加以综述，以期为视网膜中央动脉阻塞的精准诊疗提供依据。 Abstract: Central retinal artery occlusion (CRAO) is a vascular neuro-ophthalmic emergency, characterized by acute painless monocular vision loss, which is one of the main causes of blindness in middle-aged and elderly people. Currently, the pathogenesis and pathophysiological mechanism of CRAO is unclear, making the selection of appropriate animal models particularly important for the research on CRAO pathogenesis and the screening of therapeutic drugs. This paper mainly reviews the modeling methods and research progress of CRAO animal models, aiming to provide a reference basis for accurate diagnosis and treatment of CRAO.

Prabhjot Kaur Juttla,1 Boniface Mwangi Chege,2 Peter Waweru Mwangi,1 Frederick Bukachi1 1Department of Medical Physiology, University of Nairobi, Nairobi, Kenya; 2School of Health Sciences, Dedan Kimathi University of Technology, Nyeri, KenyaCorrespondence: Prabhjot Kaur Juttla, Department of Medical Physiology, University of Nairobi, P.O. Box 30197 – 00100, Nairobi, Kenya, Email pkjuttla13@gmail.comPurpose: Dapagliflozin exerts cardioprotective effects in Type 2 Diabetes Mellitus (T2DM). However, whether these effects prevent electrocardiographic changes associated with T2DM altogether remain unknown. Our aim was to investigate the prophylactic effect of dapagliflozin pretreatment on the rat ECG using a high-fat, high-fructose (HFHf) diet and a low dose streptozotocin (STZ) model of T2DM.Methods: Twenty-five (25) rats were randomized into five (5) groups: normal control receiving a normal diet while the other groups received an 8-week HFHf and 40mg/kg STZ on day 42, and either: saline for the diabetic control (1 mg/kg/d), low dose (1.0 mg/kg/d) and high dose dapagliflozin (1.6 mg/kg/d), or metformin (250 mg/kg/d). Oral glucose tolerance (OGT), electrocardiograms (ECGs), paracardial adipose mass, and left ventricular fibrosis were determined. Data were analyzed using GraphPad version 9.0.0.121, with the level of significance at p < 0.05.Results: Compared to the diabetic control group, a high dose of dapagliflozin preserved the OGT (p = 0.0001), QRS-duration (p = 0.0263), QT-interval (p = 0.0399), and QTc intervals (p = 0.0463). Furthermore, the high dose dapagliflozin group had the lowest paracardial adipose mass (p = 0.0104) and fibrotic area (p = 0.0001). In contrast, while metformin showed favorable effects on OGT (p = 0.0025), paracardial adiposity (p = 0.0153) and ventricular fibrosis (p = 0.0291), it did not demonstrate significant antiarrhythmic effects.Conclusion: Pretreatment with higher doses of Dapagliflozin exhibits prophylactic cardioprotective characteristics against diabetic cardiomyopathy that include antifibrotic and antiarrhythmic qualities. This suggests that higher doses of dapagliflozin could be a more effective initial therapeutic option in T2DM.Keywords: electrocardiogram, diabetic cardiomyopathy, sodium glucose co-transporter inhibitors, prophylaxis, animal model

Abstract Inflammatory bowel disease (IBD) is a prevalent chronic relapsing‐remitting disease that affects the digestive tract and reduces patients’ quality of life. Food bioactive compounds are a promising approach for nutritional intervention of IBD with minimal side effects. To evaluate their potential, researchers have developed various animal models that simulate human IBD, including chemically induced, spontaneous, genetically engineered, and adoptive transfer models. In this work, the main animal models, pathogenesis, symptoms, strengths, and limitations of IBD were discussed. Although these models could not perfectly replicate human IBD, they provided useful tools to study the disease's progression and therapeutic processes. In addition, taking these IBD animals as models, the specific experimental methods, intervention results, and mechanisms of food bioactive compounds to prevent or treat IBD were described in detail. The continuous improvement of animal models is crucial to gain a better understanding of IBD's etiology and pathogenesis and to evaluate the efficacy of food bioactive compounds for the effective control of IBD.

Objective: Fracture-related infection (FRI) remains a major concern in orthopaedic trauma. Functionalizing implants with antibacterial coatings are a promising strategy in mitigating FRI. Numerous implant coatings have been reported but the preventive and therapeutic effects vary. This systematic review aimed to provide a comprehensive overview of current implant coating strategies to prevent and treat FRI in animal fracture and bone defect models. Methods: A literature search was performed in three databases: PubMed, Web of Science and Embase, with predetermined keywords and criteria up to 28 February 2023. Preclinical studies on implant coatings in animal fracture or defect models that assessed antibacterial and bone healing effects were included. Results: A total of 14 studies were included in this systematic review, seven of which used fracture models and seven used defect models. Passive coatings with bacteria adhesion resistance were investigated in two studies. Active coatings with bactericidal effects were investigated in 12 studies, four of which used metal ions including Ag+ and Cu2+; five studies used antibiotics including chlorhexidine, tigecycline, vancomycin, and gentamicin sulfate; and the other three studies used natural antibacterial materials including chitosan, antimicrobial peptides, and lysostaphin. Overall, these implant coatings exhibited promising efficacy in antibacterial effects and bone formation. Conclusion: Antibacterial coating strategies reduced bacterial infections in animal models and favored bone healing in vivo. Future studies of implant coatings should focus on optimal biocompatibility, antibacterial effects against multi-drug resistant bacteria and polymicrobial infections, and osseointegration and osteogenesis promotion especially in osteoporotic bone by constructing multi-functional coatings for FRI therapy. The translational potential of this paper: The clinical treatment of FRI is complex and challenging. This review summarizes novel orthopaedic implant coating strategies applied to FRI in preclinical studies, and offers a perspective on the future development of orthopaedic implant coatings, which can potentially contribute to alternative strategies in clinical practice.

Introduction. The prevalence of patients with extended ureteral strictures has been steadily increasing over the past decades. When it is not possible to perform reconstruction with the tissues of the urinary system, the best solution is intestinal replacement plasty. However, despite the great world experience, the search for the optimal method of intestinal reconstruction does not stop, which determines the relevance of conducting an experimental prospective study.Objective. To evaluate morphological changes in renal parenchyma after ureteral replacement reconstruction by segments of small and large intestine.Materials & methods. Fifteen white giant rabbits (6-months-old, weighing 5 kg) were divided into three groups. Group A (n = 5) underwent small intestine [ilealplasty] replacement plasty. Group B (n = 5) double-flap ileoplasty using the Yang-Monti technique. Group C (n = 5) – large intestine [coloplasy] ureteral reconstruction. Before the operation and before withdrawal from the experiment, the level of creatinine and electrolytes was assessed, kidney ultrasound was performed on days 2, 5, 10. Excretory urography was performed to assess the patency of the anastomoses. Animals were withdrawn from the experiment from day 10 to 30. The material used for morphological study included kidneys from the operated and intact sides, proximal and distal anastomoses.Results. No increase in creatinine level, metabolic disorders were detected in animals. According to ultrasound data, hydronephrosis developed in all animals on day 2 and remained unchanged during the entire follow-up. Group A: no complications were detected. Histologically, the renal parenchyma showed moderate signs of chronic inflammation, single foci of lymphoid infiltration, but there were no irreversible processes in the form of necrosis and sclerosis. Group B: complications — stricture in the anastomosis area of the detubularised fragments and necrosis of the small intestine due to compression of the mesentery by the graft vascular stem. Histologically there were marked dilatation of the tubules at all levels, enlargement of the Bowman-Shumlansky capsule, as well as signs of moderate inflammatory process, there were hydropic and hyaline-droplet dystrophy, tubular necrosis foci. Group C: complications — accumulation of a significant amount of grit, mucus, and fibrin in the colocystoanastomosis area. Histologically, the renal parenchyma showed a marked inflammatory process, in particular, purulent inflammation with demarcation zones, infiltration with polymorphonuclear leukocytes and bacterial cells, foci of necrosis and sclerosis of both stroma and tubules, dilatation of tubules and Bowman-Schumlansky capsules.Conclusion. The use of an unchanged ileal-graft reconstruction of an extended ureteral defect showed acceptable histological results in an animal model, which confirms the feasibility of its use in clinical practice. The absence of foci of necrosis and fibrosis in the renal parenchyma indicates the preserved functional potential, which suggests the stabilization of renal function in the long term.

Abstract In this report, we described a new technique of gasless V-NOTES for hysterectomy and salpingectomy on a robotic platform with flexible devices in a porcine model. As a result, the gynecological procedures were successfully completed. The total operative time was 110 min, while the docking time was 10 min. The estimated blood loss was estimated to be 10 mL with no intraoperative complications. It revealed that gasless V-NOTES for hysterectomy and salpingectomy on a robotic platform with flexible devices appeared to be feasible and safe in the porcine model and has the potential for clinical use in human beings.

Abstract Calcific Aortic Valve Disease (CAVD) is prevalent among the elderly as the most common valvular heart disease. Currently, no pharmaceutical interventions can effectively reverse or prevent CAVD, making valve replacement the primary therapeutic recourse. Extensive research spanning decades has contributed to the establishment of animal and in vitro cell models, which facilitates a deeper understanding of the pathophysiological progression and underlying mechanisms of CAVD. In this review, we provide a comprehensive summary and analysis of the strengths and limitations associated with commonly employed models for the study of valve calcification. We specifically emphasize the advancements in three-dimensional culture technologies, which replicate the structural complexity of the valve. Furthermore, we delve into prospective recommendations for advancing in vivo and in vitro model studies of CAVD.