58,989 results on '"Animal model"'
Search Results
152. The Role of Social Stress in the Development of Mental Disorders
- Author
-
Yang, Shuya, Kacprzyk, Janusz, Series Editor, Samsonovich, Alexei V., editor, and Liu, Tingting, editor
- Published
- 2024
- Full Text
- View/download PDF
153. 数字化技术构建 SD 大鼠颞下颌关节骨关节炎动物模型.
- Author
-
刘鹏慧, 吴 凡, 王泽杰, 吴高义, and 周立波
- Abstract
BACKGROUND: Temporomandibular joint osteoarthritis is a common oral disease with a high incidence. However, temporomandibular joint osteoarthritis is not easy to be detected in the early stage, and it is difficult to obtain clinical pathological specimens, so it is difficult to carry out related research. The application of digital 3D printing technology to animal models of Temporomandibular joint osteoarthritis increases the consistency of the animal models, thus promoting the study of temporomandibular joint osteoarthritis. OBJECTIVE: To establish a standardized animal model of temporomandibular joint osteoarthritis using novel digital technology. METHODS: According to the different modeling methods of unilateral anterior crossbite, 30 female Sprague-Dawley rats were randomly divided into traditional model group, digital model group, and control group (n=10 per group). Cartilage specimens of the condyles were collected at 4 and 8 weeks after modeling. The apparent morphology was observed by stereoscopic microscope. The pathological morphology was observed by hematoxylin-eosin staining and Safranin O/fast green staining. Changes in the expression of interleukin-1β and tumor necrosis factor-α were observed by ELISA, and changes in the expression of aggrecan, type II collagen and matrix metalloproteinase-13 were observed by immunohistochemical staining. RESULTS AND CONCLUSION: Different degrees of degeneration were observed in the digital and traditional model groups. The body mass of rats in both the model groups decreased during the 1st week after intervention and subsequently demonstrated growth trend and were significantly lower than that in the control group. The results of stereoscopic microscope showed that at 4 and 8 weeks after modeling, the deformation and defect degree of the digital model group was significantly higher than that of the traditional model group. At these two time points, the Osteoarthritis Research Society International scores of the digital model group and the traditional model group were higher than those of the control group, and the Osteoarthritis Research Society International score of the digital model group was higher than that of the traditional model group (P < 0.05). Histopathological observation showed that the modified Mankin score and Osteoarthritis Research Society International score of the two model groups were significantly higher than those of the control group of the same age at 4 and 8 weeks after modeling (P < 0.05). Immunohistochemical staining results showed that at two time points, compared with the control group of the same age, the expression of aggrecan and type II collagen decreased in the traditional model group and the digital model group, while the expression of matrix metalloproteinase 13 increased (P < 0.05). ELISA results showed that the expression levels of inflammatory factors interleukin-1β and tumor necrosis factor-α in the traditional and digital model groups were higher than those in the control group at 8 weeks, and the expression levels of interleukin-1β and tumor necrosis factor-α in the digital model group were higher than those in the traditional model group (P < 0.05). To conclude, the personalized metal tube designed and produced by 3D printing technology can quickly guide the osteoarthritis-like lesions of the temporomandibular joint without repeated trial and adjustment, which is reproducible and suitable for promotion and application. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
154. 三种急性胰腺炎大鼠模型的制备及特点比较.
- Author
-
牛小龙, 陈佳靓, 郑华群, 杨桂媚, and 姚广涛
- Abstract
BACKGROUND: Establishing a stable and reliable animal model of acute pancreatitis is of great significance for understanding its pathogenesis, pathophysiological characteristics, and clinical medication. Domestic and foreign studies have shown that cerulein, L-arginine, and sodium taurocholate can induce acute pancreatitis, but their pathophysiological characteristics and model characteristics are still unclear. OBJECTIVE: To establish an acute pancreatitis rat model using cerulein, L-arginine, and sodium taurocholate and to observe the changing patterns of model features at different time points. METHODS: Ninety-six healthy male Sprague-Dawley rats were randomly divided into normal group, cerulein group, L-arginine group, and sodium taurocholate group, with 24 rats in each group. Within each group, there were three subgroups (n=8 per group): 12-, 24-, and 48-hour subgroups. Cerulein was administered via intraperitoneal injection six times with a 1-hour interval. L-arginine was administered through two intraperitoneal injections with a 1-hour interval. Sodium taurocholate was injected for inducing acute pancreatitis models through retrograde injection into the bile-pancreatic duct. By examining the rat survival rate, gross morphology of the pancreas, calculating the pancreatic organ index, and measuring levels of amylase, lipase, alanine transaminase, aspartate transaminase, blood urea nitrogen, and creatinine, as well as observing pancreatic tissue pathological features through hematoxylin-eosin staining and conducting a pancreatic injury scoring, we evaluated the changing patterns of model features at different time points. RESULTS AND CONCLUSION: Compared with the normal group, the overall survival rate of rats was 100% in the cerulein group, 88% in the L-arginine group, and 96% in the sodium taurocholate group. The pancreatic organ index was increased in all groups. Gross observation indicated that, In the cerulein group, pancreatic edema, blurred lobes, and looseness were visible. In the L-arginine group, the pancreatic glands were enlarged and thickened with patchy bleeding. In the sodium taurocholate group, pancreatic tissue showed varying degrees of congestion and edema accompanied by scattered flakes of hemorrhage and necrosis. The levels of serum alanine transaminase, aspartate transaminase, blood urea nitrogen, creatinine, amylase, and lipase in rats exhibited consistent changes. In the cerulein group, these parameters possibly peaked at 12 hours (P < 0.05) and then showed a declining trend. In the L-arginine group, they reached the highest levels at 24 hours (P < 0.05) and significantly decreased at 48 hours. In the sodium taurocholate group, serum amylase and lipase remained at higher levels at 12 hours with a slow decline trend (P < 0.05). Compared with the normal group, microscopic examination revealed mild acinar edema and widened interlobular spaces in the cerulein group, with a higher presence of inflammatory cells. In the L-arginine group, there was widening of interlobular spaces, extensive infiltration of inflammatory cells, and patchy necrotic areas. In the sodium taurocholate group, significant pancreatic edema, structural disarray, extensive necrotic foci, and inflammatory cell infiltration were observed. Compared with the normal group, the pathological scores of induced acute pancreatitis in all three models were significantly different at each time point (P < 0.05). Moreover, the pathological scores in each group increased over time, indicating a gradual worsening of pancreatic tissue damage. When comparing different models at the same time, there were differences in pathological scores, with the sodium taurocholate group having the highest scores, followed by the L-arginine group, and the cerulein group having the lowest scores. Analyzing the three models at the same time point, the most severe condition was in the sodium taurocholate group, which was characterized by pancreatic hemorrhage and necrosis, followed by the L-arginine group, which was characterized by necrosis, and the least severe condition was in the cerulein group, mainly characterized by edema. The serum biochemical index levels of the cerulein and L-arginine groups decreased at 48 hours, indicating that these two models may have a tendency to self-heal and belong to a self-limiting disease course. The serum biochemical index levels of the sodium taurocholate group decreased slowly after 12 hours. Therefore, pancreatic injury in the sodium taurocholate group might not be relieved after 48 hours or longer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
155. Recent Insights into Hippocampal Dysfunction and Neuroplasticity in Sleep Disorders: An Update from Preclinical Studies.
- Author
-
Weerasinghe-Mudiyanselage, Poornima D. E. and Moon, Changjong
- Subjects
- *
SLEEP interruptions , *SLEEP deprivation , *NEUROLOGICAL disorders , *SLEEP disorders , *MATERNAL deprivation - Abstract
Sleep disorders are prevalent neurological conditions linked to neurocognitive impairments. Understanding the neuroplasticity changes in the hippocampus, which plays a central role in regulating neurocognitive function, is crucial in the context of sleep disorders. However, research on neurodegenerative disorders and the influence of sleep disorders on hippocampal neuroplasticity remains largely unclear. Therefore, this review aims to highlight the latest advancements regarding hippocampal neuroplasticity and functional changes during sleep disorders, drawing insights from clinical and preclinical research involving sleep-deprived animal models. These articles were gathered through comprehensive literature searches across databases, including Google Scholar, PubMed, Web of Science, and Scopus. Maternal sleep deprivation has been observed to cause neurocognitive impairment in offspring, along with changes in protein expression levels associated with neuroplasticity. Similarly, sleep deprivation in adult mice has been shown to affect several cognitive functions and fear extinction without influencing the acquisition of fear conditioning. While mechanistic research on neurocognitive dysfunction induced by maternal and adult sleep deprivation is limited, it suggests the involvement of several signaling pathways, including neurotrophic factors, synaptic proteins, and inflammatory molecules, which are triggered by sleep deprivation. Further studies are needed to clarify the mechanistic pathways underlying hippocampal dysfunction and synaptic alterations associated with sleep disturbances. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
156. Sex-specific differences in SLE -- Significance in the experimental setting of inflammation and kidney damage in MRL-Faslpr mice.
- Author
-
Saurin, Sabrina, Meineck, Myriam, Claßen, Paul, Boedecker-Lips, Simone Cosima, Pautz, Andrea, and Weinmann-Menke, Julia
- Subjects
- *
AUTOIMMUNE diseases , *SYSTEMIC lupus erythematosus , *SJOGREN'S syndrome , *ANIMAL welfare , *MICE , *KIDNEYS - Abstract
Animal models are an important tool in the research of chronic autoimmune diseases, like systemic lupus erythematosus (SLE). MRL-Faslpr mice are one of different lupus models that develop spontaneously an SLE-like disease with autoantibodies and immune complex deposition that leads into damage of different organs. In contrast to human SLE, both sexes of MRL-Faslpr mice develop a similar autoimmune disease. Due to the sex bias in human and the delayed disease progression in male MRL-Faslpr mice, the majority of studies have been performed in female mice. To determine the suitability of male MRL-Faslpr mice for SLE research, especially with regard to the 3 R-principle and animal welfare, analyses of phenotype, inflammation and damage with focus on kidney and spleen were performed in mice of both sexes. Female mice developed lymphadenopathy and skin lesions earlier as males. At an age of 3.5 month, more immune cells infiltrated kidney and spleen in females compared to males. At the age of 5 months, however, substantially less sex-specific differences were detected. Since other studies have shown differences between both sexes on other manifestations like autoimmune pancreatitis and Sjögren syndrome in MRL-Faslpr mice, the use of male mice as part of 3 R-principle and animal welfare must be carefully considered. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
157. Research progress in the construction of animal models of autoimmune thyroiditis.
- Author
-
Ke Liu, Pei Zhang, Ling Zhou, Lin Han, Linhua Zhao, and Xiaotong Yu
- Subjects
- *
AUTOIMMUNE thyroiditis , *ANIMAL models in research , *AUTOIMMUNE diseases , *ANTIBODY titer , *THYROID diseases - Abstract
Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT), is an autoimmune disease that is characterised by elevated thyroid-specific antibody titres. The incidence of AIT is increasing year over year, making it urgent to establish a suitable animal model for this condition, in order to better explore its pathogenesis and potential pharmaceutical mechanisms for treatment. Owing to a lack of basic research on this disease, problems such as disparate modelling methods with unclear and varying success rates make it difficult for researchers to obtain effective information on AIT in the short term. This report summarises and analyzes the current literature on AIT and combines actual operability to explain the selection and specific implementation processes behind the uses of different modelling approaches, to provide a better overall understanding of autoimmune thyroid diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
158. Gut microbiota dynamics in KK-Ay mice: restoration following antibiotic treatment.
- Author
-
Hong, Jinni, Fu, Tingting, Liu, Weizhen, Yu, Miao, Lin, Yanshan, Min, Cunyun, and Lin, Datao
- Abstract
The primary aim of this study was to investigate the alterations in the microbial community of KK-Ay mice following antibiotic treatment. A comparative analysis of the gut microbiota was conducted between KK-Ay mice treated with antibiotics and those without treatment. The microbial community dynamics in antibiotic-treated KK-Ay mice were meticulously assessed over an eight-week period using 16S rDNA sequencing analysis. Simultaneously, dynamic renal function measurements were performed. The results demonstrated a marked decrease in bacterial DNA abundance following antibiotic intervention, coupled with a substantial reduction in bacterial diversity and a profound alteration in microbial composition. These observed microbiota changes persisted in the KK-Ay mice throughout the eight-week post-antibiotic treatment period. Particularly noteworthy was the reemergence of bacterial populations after two weeks or more, resulting in a microbiota composition resembling that of untreated KK-Ay mice. This transition was characterized by a significant increase in the abundance of clostridia at the class level, Lachnospirales and Oscillospirales at the order level, and Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae at the family level. Concurrently, there was a notable decrease in Clostridia_UCG-014. The observed alterations in the gut microbiota of antibiotic-treated KK-Ay mice suggest a dynamic response to antibiotic intervention and subsequent restoration towards the original untreated state. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
159. Establishment of intervertebral disc degeneration models; A review of the currently used models.
- Author
-
Elmounedi, Najah and Keskes, Hassib
- Subjects
BIOLOGICAL models ,RISK assessment ,BIOMECHANICS ,INTERVERTEBRAL disk ,NUTRITIONAL status ,INFLAMMATION ,HEALTH promotion ,SPINE diseases ,LUMBAR pain ,DISEASE progression - Abstract
One of the frequent causes of low back pain is intervertebral disc degeneration (IDD), which is followed by discogenic pain. Some significant risk factors that have been linked to the onset and progression of IDD include age, mechanical imbalance, changes in nutrition and inflammation. According to recent studies, five types of animal models are established for producing IDD: the spontaneous models, the puncture models, the biomechanical models, the chemical models and the hybrid models. These models are crucial in studying and understanding IDD's natural history and identifying potential treatment targets for IDD. In our study, we'll talk about the technical aspects of these models, the time between model establishment and the apparition of observable degradation, and their potential in various research. Each animal model should be compared to the human natural IDD pathogenesis to guide future research efforts in this area. By improving knowledge and appropriate application of various animal models, we seek to raise awareness of this illness and further translational research. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
160. Considerations for the use of porcine organ donation models in preclinical organ donor intervention research
- Author
-
Frazer I. Heinis, Shaheed Merani, Nicholas W. Markin, Kim F. Duncan, Michael J. Moulton, Lance Fristoe, William E. Thorell, Raechel A. Sherrick, Tami R. Wells, Matthew T. Andrews, and Marian Urban
- Subjects
animal model ,brain death ,circulatory death ,organ transplantation ,Medicine (General) ,R5-920 - Abstract
Abstract Use of animal models in preclinical transplant research is essential to the optimization of human allografts for clinical transplantation. Animal models of organ donation and preservation help to advance and improve technical elements of solid organ recovery and facilitate research of ischemia–reperfusion injury, organ preservation strategies, and future donor‐based interventions. Important considerations include cost, public opinion regarding the conduct of animal research, translational value, and relevance of the animal model for clinical practice. We present an overview of two porcine models of organ donation: donation following brain death (DBD) and donation following circulatory death (DCD). The cardiovascular anatomy and physiology of pigs closely resembles those of humans, making this species the most appropriate for pre‐clinical research. Pigs are also considered a potential source of organs for human heart and kidney xenotransplantation. It is imperative to minimize animal loss during procedures that are surgically complex. We present our experience with these models and describe in detail the use cases, procedural approach, challenges, alternatives, and limitations of each model.
- Published
- 2024
- Full Text
- View/download PDF
161. The incidence rate and histological characteristics of intimal hyperplasia in elastase‐induced experimental abdominal aortic aneurysms in mice
- Author
-
Meng Li, Panpan Wei, Kexin Li, Haole Liu, Naqash Alam, Haiwen Hou, Jie Deng, Baohui Xu, Enqi Liu, Sihai Zhao, and Yankui Li
- Subjects
abdominal aortic aneurysms ,animal model ,histology ,intimal hyperplasia ,Medicine (General) ,R5-920 - Abstract
Abstract Intimal hyperplasia (IH) is a negative vascular remodeling after arterial injury. IH occasionally occurs in elastase‐induced abdominal aortic aneurysm (AAA) mouse models. This study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice. A retrospective study was conducted by including 42 male elastase‐induced mouse AAA models. The IH incidence, aortic diameters with or without IH, and hyperplasia lesional features of mice were analyzed. Among 42 elastase‐induced AAA mouse models, 10 mice developed mild IH (24%) and severe IH was found in only 2 mice (5%). The outer diameters of the AAA segments in mice with and without IH did not show significant difference. Both mild and severe IH lesions show strong smooth muscle cell positive staining, but endothelial cells were occasionally observed in severe IH lesions. There was obvious macrophage infiltration in the IH lesions of the AAA mouse models, especially in mice with severe IH. However, only a lower numbers of T cells and B cells were found in the IH lesion. Local cell‐secreted matrix metalloproteinases (MMP) 2 was highly expressed in all IH lesions, but MMP9 was only overexpressed in severe lesions. In conclusion, this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastase‐induced mouse AAA model. This will help researchers better understand this model, and optimize it for use in AAA‐related research.
- Published
- 2024
- Full Text
- View/download PDF
162. Evaluation of Atherosclerosis Development by Vascular Duplex Ultrasonography in ApoE-deficient Dogs Fed with a High-fat Diet
- Author
-
Lingyun Jia, MD, PhD, Yuan Li, PhD, Yang Hua, MD, Yumei Liu, MD, Nan Zhang, MD, Mingjie Gao, MD, Ke Zhang, MD, Jingzhi Li, MD, Benchi Chen, BS, Jidong Mi, MS, Nan Zhao, PhD
- Subjects
atherosclerosis ,apoe-deficient dogs ,animal model ,high-fat diet ,ultrasound ,Medical technology ,R855-855.5 ,Medicine - Abstract
Objective This study aimed to evaluate the development of atherosclerosis in ApoE-deficient dogs fed with a high-fat diet (HFD) using vascular duplex ultrasonography (VDU). Methods Thirty beagle dogs were enrolled, including 10 wild-type, 16 heterozygous (ApoE-/+), and four homozygous (ApoE-/-) mutant dogs. The dogs were categorized into either the normal diet (ND) or HFD group. Plasma lipids levles were tested at baseline and then after feeding the dog a different diet for 6 months. The carotid arteries, abdominal aorta (AO) and iliac arteries were examined using VDU. Artery sections of the ApoE-/- dogs were analyzed. Results After HFD, lipids especially triglycerides, total cholesterol and low-density lipoprotein (LDL) in the wild type and ApoE-/+ dogs were significantly increased. Both the intima-media thickness (IMT) of the common carotid artery (CCA) and AO in the wild type and ApoE-/+ dogs significantly increased. In the ApoE-/+ dogs, the mean percentages increases in CCA-IMT and AO-IMT after HFD were higher than those in the ND dogs. The mean values of CCA-IMT and AO-IMT in the ApoE-/-dogs increased to 2-2.5 folds after HFD. Histological analysis confirmed that the carotid and iliac arteries had advanced atherosclerotic lesions in the ApoE-/- dogs. Conclusions HFD may accelerate the development of atherosclerosis in ApoE-deficient dogs, which is an optimal large-animal model of atherosclerosis.
- Published
- 2024
- Full Text
- View/download PDF
163. Beyond drug discovery: Exploring the physiological and methodological dimensions of zebrafish in diabetes research
- Author
-
Tamsheel Fatima Roohi, Syed Faizan, Mohd. Farooq Shaikh, Kamsagara Linganna Krishna, Seema Mehdi, Nabeel Kinattingal, and Alina Arulsamy
- Subjects
animal model ,anti‐diabetic drugs ,Danio rerio ,diabetes mellitus ,hyperglycaemic pathologies ,Physiology ,QP1-981 - Abstract
Abstract Diabetes mellitus is a chronic disease that is now considered a global epidemic. Chronic diabetes conditions include type 1 and type 2 diabetes, both of which are normally irreversible. As a result of long‐term uncontrolled high levels of glucose, diabetes can progress to hyperglycaemic pathologies, such as cardiovascular diseases, retinopathy, nephropathy and neuropathy, among many other complications. The complete mechanism underlying diabetes remains unclear due to its complexity. In this scenario, zebrafish (Danio rerio) have arisen as a versatile and promising animal model due to their good reproducibility, simplicity, and time‐ and cost‐effectiveness. The Zebrafish model allows us to make progress in the investigation and comprehension of the root cause of diabetes, which in turn would aid in the development of pharmacological and surgical approaches for its management. The current review provides valuable reference information on zebrafish models, from the first zebrafish diabetes models using genetic, disease induction and chemical approaches, to the newest ones that further allow for drug screening and testing. This review aims to update our knowledge related to diabetes mellitus by gathering the most authoritative studies on zebrafish as a chemical, dietary and insulin induction, and genetic model for diabetes research.
- Published
- 2024
- Full Text
- View/download PDF
164. Skilled reaching test for shoulder function assessment in a rat model of rotator cuff tear: a pilot study
- Author
-
Yang Liu, Sai-Chuen Fu, Shi-Yi Yao, and Patrick Shu-Hang Yung
- Subjects
Skilled reaching test ,Gait analysis ,Rotator cuff repair ,Shoulder function ,Animal model ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Functional assessments are crucial to evaluate treatment outcomes in clinical and animal studies on rotator cuff injuries. While gait analysis is commonly used to assess animal models of rotator cuff tears, it is less relevant for human patients as the human shoulder is typically assessed in a non-weight-bearing condition. The present study introduces the skilled reaching test as a shoulder functional assessment tool for rats, which allows for evaluation without weight bearing. Methods In the control group, 8 male Sprague–Dawley rats received rotator cuff tear surgery without repair. In the rotator cuff repair group, 20 rats received rotator cuff repair at 4 weeks post rotator cuff tear. For the skilled reaching test, rats were trained to extend their forelimbs to fetch food pellets, and the number of trials, number of attempts and the success rate were recorded. The gait analysis and skilled reaching test were performed at baseline, 4 weeks post-tear, 1, 2, 4, and 8 weeks post-repair. The repeated measures analysis of variance was used to evaluate the effects of time on the shoulder function. The significance level was set at 0.05. Results The skilled reaching test required 216 h to conduct, while the gait analysis took 44 h. In the rotator cuff repair group, gait performance significantly deteriorated at 1 week post-repair and restored to 4 weeks post-tear levels at 4 weeks post-repair. Regarding the skilled reaching test, the number of attempts, number of trials and the success rate decreased at 1 week post-repair. Subsequently, there was a brief rebound in performance observed at 2 weeks post-repair, followed by a continued decline in the number of attempts and trials. By 8 weeks post-repair, only the success rate had restored to levels similar to those observed at 4 weeks post-tear. Conclusion The skilled reaching test can detect functional deficiencies following rotator cuff tear and repair, while it requires high time and labour costs.
- Published
- 2024
- Full Text
- View/download PDF
165. Computer-aided design and 3D printing for a stable construction of segmental bone defect model in Beagles: a short term observation
- Author
-
Kai Cheng, Haotian Zhu, Yuanhao Peng, Xinghua Wen, and Huanwen Ding
- Subjects
Beagle dog ,Animal model ,Segmental bone defect ,Computer-aided design ,3D printing ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Abstract Objective Segmental bone defect animal studies require stable fixation which is a continuous experimental challenge. Large animal models are comparable to the human bone, but with obvious drawbacks of housing and costs. Our study aims to utilize CAD and 3D printing in the construction of a stable and reproducible segmental bone defect animal mode. Methods CAD-aided 3D printed surgical instruments were incorporated into the construction of the animal model through preoperative surgical emulation. 20 3D printed femurs were divided into either experimental group using 3D surgical instruments or control group. In Vitro surgical time and accuracy of fixation were analysed and compared between the two groups. A mature surgical plan using the surgical instruments was then utilized in the construction of 3 segmental bone defect Beagle models in vivo. The Beagles were postoperatively assessed through limb function and imaging at 1, 2 and 3 months postoperatively. Results In vitro experiments showed a significant reduction in surgical time from 40.6 ± 14.1 (23–68 min) to 26 ± 4.6 (19–36 min) (n = 10, p
- Published
- 2024
- Full Text
- View/download PDF
166. Generation and transcriptomic characterization of MIR137 knockout miniature pig model for neurodevelopmental disorders
- Author
-
Shengyun Xu, Jiaoxiang Wang, Kexin Mao, Deling Jiao, Zhu Li, Heng Zhao, Yifei Sun, Jin Feng, Yuanhao Lai, Ruiqi Peng, Yu Fu, Ruoyi Gan, Shuhan Chen, Hong-Ye Zhao, Hong-Jiang Wei, and Ying Cheng
- Subjects
Pig ,Neurodevelopmental disorder ,miR-137 ,Autism spectrum disorders ,Intellectual disorders ,Animal model ,Biotechnology ,TP248.13-248.65 ,Biology (General) ,QH301-705.5 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Neurodevelopmental disorders (NDD), such as autism spectrum disorders (ASD) and intellectual disorders (ID), are highly debilitating childhood psychiatric conditions. Genetic factors are recognized as playing a major role in NDD, with a multitude of genes and genomic regions implicated. While the functional validation of NDD-associated genes has predominantly been carried out using mouse models, the significant differences in brain structure and gene function between mice and humans have limited the effectiveness of mouse models in exploring the underlying mechanisms of NDD. Therefore, it is important to establish alternative animal models that are more evolutionarily aligned with humans. Results In this study, we employed CRISPR/Cas9 and somatic cell nuclear transplantation technologies to successfully generate a knockout miniature pig model of the MIR137 gene, which encodes the neuropsychiatric disorder-associated microRNA miR-137. The homozygous knockout of MIR137 (MIR137 –/– ) effectively suppressed the expression of mature miR-137 and led to the birth of stillborn or short-lived piglets. Transcriptomic analysis revealed significant changes in genes associated with neurodevelopment and synaptic signaling in the brains of MIR137 –/– miniature pig, mirroring findings from human ASD transcriptomic data. In comparison to miR-137-deficient mouse and human induced pluripotent stem cell (hiPSC)-derived neuron models, the miniature pig model exhibited more consistent changes in critical neuronal genes relevant to humans following the loss of miR-137. Furthermore, a comparative analysis identified differentially expressed genes associated with ASD and ID risk genes in both miniature pig and hiPSC-derived neurons. Notably, human-specific miR-137 targets, such as CAMK2A, known to be linked to cognitive impairments and NDD, exhibited dysregulation in MIR137 –/– miniature pigs. These findings suggest that the loss of miR-137 in miniature pigs affects genes crucial for neurodevelopment, potentially contributing to the development of NDD. Conclusions Our study highlights the impact of miR-137 loss on critical genes involved in neurodevelopment and related disorders in MIR137 –/– miniature pigs. It establishes the miniature pig model as a valuable tool for investigating neurodevelopmental disorders, providing valuable insights for potential applications in human research.
- Published
- 2024
- Full Text
- View/download PDF
167. Mis-localization of endogenous TDP-43 leads to ALS-like early-stage metabolic dysfunction and progressive motor deficits
- Author
-
Yiying Hu, Alexander Hruscha, Chenchen Pan, Martina Schifferer, Michael K. Schmidt, Brigitte Nuscher, Martin Giera, Sarantos Kostidis, Özge Burhan, Frauke van Bebber, Dieter Edbauer, Thomas Arzberger, Christian Haass, and Bettina Schmid
- Subjects
ALS ,TDP-43 ,Animal model ,Neurodegeneration ,Metabolic dysfunction ,Hypothalamus ,Neurology. Diseases of the nervous system ,RC346-429 ,Geriatrics ,RC952-954.6 - Abstract
Abstract Background The key pathological signature of ALS/ FTLD is the mis-localization of endogenous TDP-43 from the nucleus to the cytoplasm. However, TDP-43 gain of function in the cytoplasm is still poorly understood since TDP-43 animal models recapitulating mis-localization of endogenous TDP-43 from the nucleus to the cytoplasm are missing. Methods CRISPR/Cas9 technology was used to generate a zebrafish line (called CytoTDP), that mis-locates endogenous TDP-43 from the nucleus to the cytoplasm. Phenotypic characterization of motor neurons and the neuromuscular junction was performed by immunostaining, microglia were immunohistochemically localized by whole-mount tissue clearing and muscle ultrastructure was analyzed by scanning electron microscopy. Behavior was investigated by video tracking and quantitative analysis of swimming parameters. RNA sequencing was used to identify mis-regulated pathways with validation by molecular analysis. Results CytoTDP fish have early larval phenotypes resembling clinical features of ALS such as progressive motor defects, neurodegeneration and muscle atrophy. Taking advantage of zebrafish’s embryonic development that solely relys on yolk usage until 5 days post fertilization, we demonstrated that microglia proliferation and activation in the hypothalamus is independent from food intake. By comparing CytoTDP to a previously generated TDP-43 knockout line, transcriptomic analyses revealed that mis-localization of endogenous TDP-43, rather than TDP-43 nuclear loss of function, leads to early onset metabolic dysfunction. Conclusions The new TDP-43 model mimics the ALS/FTLD hallmark of progressive motor dysfunction. Our results suggest that functional deficits of the hypothalamus, the metabolic regulatory center, might be the primary cause of weight loss in ALS patients. Cytoplasmic gain of function of endogenous TDP-43 leads to metabolic dysfunction in vivo that are reminiscent of early ALS clinical non-motor metabolic alterations. Thus, the CytoTDP zebrafish model offers a unique opportunity to identify mis-regulated targets for therapeutic intervention early in disease progression.
- Published
- 2024
- Full Text
- View/download PDF
168. The integrin CD11b inhibits MSU-induced NLRP3 inflammasome activation in macrophages and protects mice against MSU-induced joint inflammation
- Author
-
Driss Ehirchiou, Ilaria Bernabei, Vishnuprabu Durairaj Pandian, Sonia Nasi, Veronique Chobaz, Mariela Castelblanco, Alexander So, Fabio Martinon, Xiaoyun Li, Hans Acha-Orbea, Thomas Hugle, Li Zhang, and Nathalie Busso
- Subjects
CD11b ,Integrin ,NLRP3 inflammasome ,MSU crystals ,Animal model ,CD11b agonist ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Objective In gout, monosodium urate crystals are taken up by macrophages, triggering the activation of the NLRP3 inflammasome and the maturation of IL-1β. This study aimed to investigate the role of integrin CD11b in inflammasome activation in macrophages stimulated by MSU. Methods BMDM from WT and CD11b KO mice were stimulated in vitro with MSU crystals. Cellular supernatants were collected to assess the expression of the inflammatory cytokines by enzyme-linked immunosorbent assay and western blot methods. The role of integrin CD11b in MSU-induced gouty arthritis in vivo was investigated by intra-articular injection of MSU crystals. Real-time extracellular acidification rate and oxygen consumption rate of BMDMs were measured by Seahorse Extracellular Flux Analyzer. Results We demonstrate that CD11b-deficient mice developed exacerbated gouty arthritis with increased recruitment of leukocytes in the joint and higher IL-1β levels in the sera. In macrophages, genetic deletion of CD11b induced a shift of macrophage metabolism from oxidative phosphorylation to glycolysis, thus decreasing the overall generation of intracellular ATP. Upon MSU stimulation, CD11b-deficient macrophages showed an exacerbated secretion of IL-1β. Treating wild-type macrophages with a CD11b agonist, LA1, inhibited MSU-induced release of IL-1β in vitro and attenuated the severity of experimental gouty arthritis. Importantly, LA1, was also effective in human cells as it inhibited MSU-induced release of IL-1β by peripheral blood mononuclear cells from healthy donors. Conclusion Our data identified the CD11b integrin as a principal cell membrane receptor that modulates NLRP3 inflammasome activation by MSU crystal in macrophages, which could be a potential therapeutic target to treat gouty arthritis in human patients.
- Published
- 2024
- Full Text
- View/download PDF
169. Benefits of Combining Antiepileptic Drugs with Vitamin B12 on Redox Balance: Penicillin-Induced Experimental Epilepsy Model
- Author
-
Taskin S, Ozsoy S, and Cakir Z
- Subjects
epilepsy ,animal model ,antiepileptic drug ,vitamin b12 ,oxidative stress ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Seyhan Taskin,1 Seyma Ozsoy,2 Ziya Cakir3 1Department of Physiology, Faculty of Medicine, Harran University, Sanliurfa, Turkey; 2Department of Physiology, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat, Turkey; 3Vocational Higher School of Health Services, Tokat Gaziosmanpasa University, Tokat, TurkeyCorrespondence: Seyhan Taskin, Department of Physiology, Faculty of Medicine, Harran University, Osmanbey Campus, Haliliye, Sanliurfa, 63300, Turkey, Tel +90 4143183000, Fax +90 414318 31 92, Email seyhan_taskin@yahoo.comPurpose: A combination of antiepileptic drugs and antioxidants may be an effective treatment by restoring the disrupted redox balance and reducing oxidative stress exposure to neurons. This study aims to evaluate the effects of valproate and vitamin B12 on oxidative stress in an experimental epilepsy model induced by penicillin when administered alone or in combination.Patients and Methods: 35 male Wistar rats were used in this study. The rats were divided into five groups, which were saline group, 1 mg/kg, 2 mg/kg Vit B12 groups and Sodium valproate group Sodium valproate + Vit B12 group. The epileptic activity was induced by 500 IU of penicillin injection. Sodium valproate and Vitamin B12 were administered 30 min after penicillin administration. Electrocorticogram recordings were taken for 2 hours post-treatment and serum parameters were assessed for oxidative stress markers using spectrophotometric method.Results: There is statistically significant difference between the groups in total antioxidant status, total oxidant status, and oxidative stress index value (p=0.013; p˂0.001; p˂0.001, respectively). The valproate+vitamin B12 group showed elevated total thiol and native thiol levels, along with reduced disulphide levels, resulting in the lowest OSI value.Conclusion: These findings suggest the combined treatment effectively reduces oxidative stress. This study provides valuable insights into the antioxidant properties of valproate and vitamin B12, positioning them as potential agents for managing epilepsy. Understanding the efficacy and reliability of antioxidant strategies in epilepsy management could contribute significantly to advancements in epilepsy therapeutics.Keywords: epilepsy, animal model, antiepileptic drug, Vitamin B12, oxidative stress
- Published
- 2024
170. Establishment of orthotopic osteosarcoma animal models in immunocompetent rats through muti-rounds of in-vivo selection
- Author
-
Mengyu Yao, Zehua Lei, Feng Peng, Donghui Wang, Mei Li, Guoqing Zhong, Hongwei Shao, Jielong Zhou, Chang Du, and Yu Zhang
- Subjects
Animal model ,Osteosarcoma ,Orthotopic transplantation ,Cell line ,Immune system ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Immunodeficient murine models are usually used as the preclinical models of osteosarcoma. Such models do not effectively simulate the process of tumorigenesis and metastasis. Establishing a suitable animal model for understanding the mechanism of osteosarcoma and the clinical translation is indispensable. The UMR-106 cell suspension was injected into the marrow cavity of Balb/C nude mice. Tumor masses were harvested from nude mice and sectioned. The tumor fragments were transplanted into the marrow cavities of SD rats immunosuppressed with cyclosporine A. Through muti-rounds selection in SD rats, we constructed orthotopic osteosarcoma animal models using rats with intact immune systems. The primary tumor cells were cultured in-vitro to obtain the immune-tolerant cell line. VX2 tumor fragments were transplanted into the distal femur and parosteal radius of New Zealand white rabbit to construct orthotopic osteosarcoma animal models in rabbits. The rate of tumor formation in SD rats (P1 generation) was 30%. After four rounds of selection and six rounds of acclimatization in SD rats with intact immune systems, we obtained immune-tolerant cell lines and established the orthotopic osteosarcoma model of the distal femur in SD rats. Micro-CT images confirmed tumor-driven osteolysis and the bone destruction process. Moreover, the orthotopic model was also established in New Zealand white rabbits by implanting VX2 tumor fragments into rabbit radii and femurs. We constructed orthotopic osteosarcoma animal models in rats with intact immune systems through muti-rounds in-vivo selection and the rabbit osteosarcoma model.
- Published
- 2024
- Full Text
- View/download PDF
171. The impact of hypovolemia and PEEP on recirculation in venovenous ECMO: an experimental porcine model
- Author
-
Lars Prag Antonsen, Andreas Espinoza, Per Steinar Halvorsen, Itai Schalit, Harald Bergan, Didrik Lilja, and Svein Aslak Landsverk
- Subjects
Extracorporeal membrane oxygenation ,Recirculation ,Intensive care ,Animal model ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Background Recirculation is a common problem in venovenous extracorporeal membrane oxygenation (VV ECMO) and may limit the effect of ECMO treatment due to less efficient blood oxygenation or unfavorable ECMO and ventilator settings. The impact of hypovolemia and positive end expiratory pressure (PEEP) on recirculation is unclear and poorly described in guidelines, despite clinical importance. The aim of this study was to investigate how hypovolemia, autotransfusion and PEEP affect recirculation in comparison to ECMO cannula distance and circuit flow. Methods In anesthetized and mechanically ventilated pigs (n = 6) on VV ECMO, we measured recirculation fraction (RF), changes in recirculation fraction (∆RF), hemodynamics and ECMO circuit pressures during alterations in PEEP (5 cmH2O vs 15 cmH2O), ECMO flow (3.5 L/min vs 5.0 L/min), cannula distance (10–14 cm vs 20–26 cm intravascular distance), hypovolemia (1000 mL blood loss) and autotransfusion (1000 mL blood transfusion). Results Recirculation increased during hypovolemia (median ∆RF 43%), high PEEP (∆RF 28% and 12% with long and short cannula distance, respectively), high ECMO flow (∆RF 49% and 28% with long and short cannula distance, respectively) and with short cannula distance (∆RF 16%). Recirculation decreased after autotransfusion (∆RF − 45%). Conclusions In the present animal study, hypovolemia, PEEP and autotransfusion were important determinants of recirculation. The alterations were comparable to other well-known factors, such as ECMO circuit flow and intravascular cannula distance. Interestingly, hypovolemia increased recirculation without significant change in ECMO drainage pressure, whereas high PEEP increased recirculation with less negative ECMO drainage pressure. Autotransfusion decreased recirculation. The findings are interesting for clinical studies.
- Published
- 2024
- Full Text
- View/download PDF
172. The Goettingen minipig as an experimental model in wound-healing studies
- Author
-
Dr. Wiebke Eisler, Prof. Dr. Manuel Held, Prof. Dr. Afshin Rahmanian-Schwarz, Dr. Jan-Ole Baur, Prof. Dr. Adrien Daigeler, and Dr. Markus Denzinger
- Subjects
Animal model ,Wound healing ,Tissue engineering ,Goettingen minipig ,Surgery ,RD1-811 - Abstract
Background: Deep dermal wounds in extensive burns and chronic wound-healing disorders represent a significant medical problem and require a high level of therapy to reduce the risk of infection and other long-term consequences, such as amputation. A better understanding of the wound-healing processes is essential, and animal models are indispensable to fundamental research. Objective: This study aimed to provide a transparent protocol and prove the effectiveness of an in vivo porcine model using Goettingen minipigs for wound-healing studies. Material and methods: Thirteen female Goettingen minipigs were kept in species-appropriate housing and were treated according to the German law for the protection of animals. The study was performed with permission from the local ethical review committee of animal welfare. The experimental procedure for studying dermal regeneration in 102 full-thickness wounds through clinical observation and histological analysis, focusing on neodermal formation, is described in detail. Results: The Goettingen minipig model proved to be suitable in wound-healing studies. The dermal regeneration was evident and viewable without wound contamination or any rejection reaction. The histological evaluations were also reliable and clearly presented the optimized wound healing of deep dermal wounds using the different therapeutic approaches. Conclusion: Given the great clinical need for alternative or complementary therapies, we considered the Goettingen minipig trial a reliable, ethically justifiable, effective, and reproducible in vivo model for wound-healing studies.
- Published
- 2024
- Full Text
- View/download PDF
173. Diverse functions and pathogenetic role of Crumbs in retinopathy
- Author
-
Xuebin Zhou, Liangliang Zhao, Chenguang Wang, Wei Sun, Bo Jia, Dan Li, and Jinling Fu
- Subjects
Crumbs ,Retinopathy ,Animal model ,Cell polarity ,Adherens junction ,Medicine ,Cytology ,QH573-671 - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
174. Autonomous precision resuscitation during ground and air transport of an animal hemorrhagic shock model
- Author
-
Michael R. Pinsky, Hernando Gomez, Francis X. Guyette, Leonard Weiss, Artur Dubrawski, Jim Leonard, Robert MacLachlan, Lisa Gordon, Theodore Lagattuta, David Salcido, and Ronald Poropatich
- Subjects
Animal model ,Closed-loop ,Hemorrhagic shock ,Resuscitation ,Transport ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
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
- Published
- 2024
- Full Text
- View/download PDF
175. Dynamical and individualised approach of transcranial ultrasound neuromodulation effects in non-human primates
- Author
-
Cyril Atkinson-Clement, Mohammad Alkhawashki, James Ross, Marilyn Gatica, Chencheng Zhang, Jerome Sallet, and Marcus Kaiser
- Subjects
Focused ultrasound stimulation ,Seed-based connectivity ,Whole brain ,Ultrasound ,Animal model ,Medicine ,Science - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
176. Immediate cardiopulmonary responses to consecutive pulmonary embolism: a randomized, controlled, experimental study
- Author
-
Mads Dam Lyhne, Jacob Gammelgaard Schultz, Christian Schmidt Mortensen, Anders Kramer, Jens Erik Nielsen-Kudsk, and Asger Andersen
- Subjects
Right ventricular function ,Pulmonary circulation ,Right ventricular afterload ,Ventilation-perfusion mismatch ,Gas exchange ,Animal model ,Diseases of the respiratory system ,RC705-779 - Abstract
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
- Published
- 2024
- Full Text
- View/download PDF
177. Comparison of the effect of Everolimus, Prednisolone, and a combination of both on experimentally induced peritoneal adhesions in rats
- Author
-
Kourosh Kazemi, Kamran Jamshidi, Reyhaneh Naseri, Reza Shahriarirad, Alireza Shamsaeefar, and Ahmad Hosseinzadeh
- Subjects
Peritoneal adhesion ,Everolimus ,Adhesion band ,Animal model ,Rats ,Prednisolone ,Medicine ,Science - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
178. Immune checkpoint inhibitors induce acute interstitial nephritis in mice with increased urinary MCP1 and PD-1 glomerular expression
- Author
-
Laura Martinez Valenzuela, Francisco Gómez-Preciado, Jordi Guiteras, Paula Antón Pampols, Montserrat Gomà, Xavier Fulladosa, Josep Maria Cruzado, Joan Torras, and Juliana Draibe
- Subjects
Acute interstitial nephritis ,Animal model ,Immune checkpoint inhibitors ,MCP1 ,Urinary biomarkers ,Medicine - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
179. The Effect of Barley Bran Polyphenol-Rich Extracts on the Development of Nonalcoholic Steatohepatitis in Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet
- Author
-
Katsuhisa Omagari, Juna Ishida, Konomi Murata, Ryoko Araki, Mizuki Yogo, Bungo Shirouchi, Kazuhito Suruga, Nobuko Sera, Kazunori Koba, Mayuko Ichimura-Shimizu, and Koichi Tsuneyama
- Subjects
nonalcoholic steatohepatitis ,barley bran ,animal model ,oxidative stress ,lobular inflammation ,Medicine (General) ,R5-920 - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
180. Effect of Enriched Environment on Cerebellum and Social Behavior of Valproic Zebrafish
- Author
-
Bernardo Flores-Prieto, Flower Caycho-Salazar, Jorge Manzo, María Elena Hernández-Aguilar, Alfonso Genaro Coria-Avila, Deissy Herrera-Covarrubias, Fausto Rojas-Dúran, Gonzalo Emiliano Aranda-Abreu, Cesar Antonio Pérez-Estudillo, and María Rebeca Toledo-Cárdenas
- Subjects
ASD ,cerebellum ,zebrafish ,social behavior ,valproic acid ,animal model ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
181. Progress in animal model research on obstructive sleep apnea
- Author
-
SHEN Yubin, OU Xiwen, and LIU Song
- Subjects
obstructive sleep apnea ,intermittent hypoxia ,sleep deprivation ,animal model ,Medicine - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
182. Advances in Comparative Medical Research on Anatomy and Histological Structure of Intervertebral Discs in Humans and Other Animals
- Author
-
ZHANG Li, HAN Lingxia, and KUANG Yu
- Subjects
intervertebral disc ,degeneration ,comparative medicine ,animal model ,anatomy and histology ,Medicine - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
183. Advances in Research on Pathological and Molecular Mechanism of Hyperuricemic Nephropathy Based on Animal Models
- Author
-
BAO Fangqi, TU Haiye, FANG Mingsun, ZHANG Qian, and CHEN Minli
- Subjects
hyperuricemia ,hyperuricemic nephropathy ,pathological mechanism ,animal model ,Medicine - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
184. HDACi vorinostat protects muscle from degeneration after acute rotator cuff injury in mice
- Author
-
Lara Gil-Melgosa, Rafael Llombart-Blanco, Leire Extramiana, Isabel Lacave, Gloria Abizanda, Estibaliz Miranda, Xabier Agirre, Felipe Prósper, Antonio Pineda-Lucena, Juan Pons-Villanueva, and Ana Pérez-Ruiz
- Subjects
fibro-adipogenic progenitors ,satellite cells ,fatty infiltration ,rotator cuff ,hdaci vorinostat ,histone acetylation ,infraspinatus muscles ,tenotomy ,muscle degeneration ,skeletal muscle ,rotator cuff injury ,ruptured tendon ,animal model ,histological analysis ,tendon repair ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
185. A review of animal models utilized in preclinical studies of approved gene therapy products: trends and insights
- Author
-
Parham Soufizadeh, Vahid Mansouri, and Naser Ahmadbeigi
- Subjects
Animal model ,Preclinical study ,Gene therapy ,Trends ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
186. A novel rabbit model of atherosclerotic vulnerable plaque established by cryofluid-induced endothelial injury
- Author
-
Huaizhi Lu, Yiran Xu, Hui Zhao, and Xuesheng Xu
- Subjects
Vulnerable plaque ,Animal model ,Endothelial injury ,Coronary heart disease ,Medicine ,Science - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
187. RNA-Based Antipsoriatic Gene Therapy: An Updated Review Focusing on Evidence from Animal Models
- Author
-
Lin ZC, Hung CF, Aljuffali IA, Lin MH, and Fang JY
- Subjects
psoriasis ,animal model ,gene therapy ,sirna ,mirna ,Therapeutics. Pharmacology ,RM1-950 - Abstract
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
- Published
- 2024
188. Swallowing-related muscle inflammation and fibrosis induced by a single dose of radiation exposure in mice
- Author
-
Shuntaro Soejima, Chia-Hsien Wu, Haruna Matsuse, Mariko Terakado, Shinji Okano, Tsuyoshi Inoue, and Yoshihiko Kumai
- Subjects
Radiation-induced fibrosis ,Radiation-associated dysphagia ,Animal model ,Mouse ,Strap muscle ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
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
- Published
- 2024
- Full Text
- View/download PDF
189. Establishment of stellate ganglion block in mice
- Author
-
Qirui Duan, Ying Zhou, Juan Zhi, Quanle Liu, Jin Xu, and Dong Yang
- Subjects
Stellate ganglion block ,Mice ,Horner’s syndrome ,Autonomic nervous regulation (ANR) ,Animal model ,Medicine - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
190. A novel magnetic compression technique for establishment of a vesicovaginal fistula model in Beagle dogs
- Author
-
Miaomiao Zhang, Yingying Zhuang, Jianqi Mao, Linxin Shen, Xin Lyu, Yi Lyu, and Xiaopeng Yan
- Subjects
Magnetic compression technique ,Vesicovaginal fistula ,Magnetosurgery ,Beagle dog ,Animal model ,Medicine ,Science - Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
191. Unveiling the fibrotic puzzle of endometriosis: An overlooked concern calling for prompt action [version 1; peer review: awaiting peer review]
- Author
-
Megha M Anchan, Guruprasad Kalthur, Ratul Datta, Kabita Majumdar, Karthikeyan P, and Rahul Dutta
- Subjects
Review ,Articles ,Endometriosis ,pelvic pain ,etiology ,animal model ,Epithelial-mesenchymal transition ,fibrosis - Abstract
Endometriosis is a benign, estrogen-dependent, persistent chronic inflammatory heterogeneous condition that features adhesions caused by estrogen-dependent periodic bleeding. It is characterised by a widely spread fibrotic interstitium that comprising of fibroblasts, myofibroblasts, collagen fibres, extracellular proteins, inflammatory cells, and active angiogenesis found outside the uterus. Thus, fibrosis is recognized as a critical component because of which current treatments, such as hormonal therapy and surgical excision of lesions are largely ineffective with severe side effects, high recurrence rates, and significant morbidity. The symptoms include dysmenorrhea (cyclic or non-cyclic), dyspareunia, abdominal discomfort, and infertility. The significant lack of knowledge regarding the underlying root cause, etiology, and complex pathogenesis of this debilitating condition, makes it challenging to diagnose early and to implement therapeutic approaches with minimal side effects presenting substantial hurdles in endometriosis management. Research on understanding the pathogenesis of endometriosis is still ongoing to find biomarkers and develop non-hormonal therapeutic approaches. Current clinical research indicates a close relationship between endometriosis and fibrosis, which is thought to be tightly linked to pain, a major factor for the decline in the patient’s quality of life but little is known about the underlying pathophysiological cellular and molecular signaling pathways that lead to endometriosis-related fibrosis. The available experimental disease models have tremendous challenges in reproducing the human characteristics of the disease to assess treatment effectiveness. Future translational research on the topic has been hindered by the lack of an adequate fibrotic model of endometriosis emphasizing the necessity of etiological exploration. This review article’s goal is to examine recent developments in the field and pinpoint knowledge gaps that exist with a focus on the development of novel fibrotic mouse models for the early diagnosis and treatment of endometriosis and how this knowledge aids in the development of novel anti-fibrotic treatments which opens fresh avenues for a thorough investigation and extended research in the field of endometriosis.
- Published
- 2024
- Full Text
- View/download PDF
192. Az autoimmun gyulladás hátterében álló folyamatok megismerésének lehetőségei.
- Author
-
Oláh, Katalin and Németh, Tamás
- Abstract
Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2024
- Full Text
- View/download PDF
193. Generation and transcriptomic characterization of MIR137 knockout miniature pig model for neurodevelopmental disorders.
- Author
-
Xu, Shengyun, Wang, Jiaoxiang, Mao, Kexin, Jiao, Deling, Li, Zhu, Zhao, Heng, Sun, Yifei, Feng, Jin, Lai, Yuanhao, Peng, Ruiqi, Fu, Yu, Gan, Ruoyi, Chen, Shuhan, Zhao, Hong-Ye, Wei, Hong-Jiang, and Cheng, Ying
- Subjects
- *
INDUCED pluripotent stem cells , *AUTISM spectrum disorders , *SOMATIC cell nuclear transfer , *TRANSCRIPTOMES , *NEURAL development , *SWINE - Abstract
Background: Neurodevelopmental disorders (NDD), such as autism spectrum disorders (ASD) and intellectual disorders (ID), are highly debilitating childhood psychiatric conditions. Genetic factors are recognized as playing a major role in NDD, with a multitude of genes and genomic regions implicated. While the functional validation of NDD-associated genes has predominantly been carried out using mouse models, the significant differences in brain structure and gene function between mice and humans have limited the effectiveness of mouse models in exploring the underlying mechanisms of NDD. Therefore, it is important to establish alternative animal models that are more evolutionarily aligned with humans. Results: In this study, we employed CRISPR/Cas9 and somatic cell nuclear transplantation technologies to successfully generate a knockout miniature pig model of the MIR137 gene, which encodes the neuropsychiatric disorder-associated microRNA miR-137. The homozygous knockout of MIR137 (MIR137–/–) effectively suppressed the expression of mature miR-137 and led to the birth of stillborn or short-lived piglets. Transcriptomic analysis revealed significant changes in genes associated with neurodevelopment and synaptic signaling in the brains of MIR137–/– miniature pig, mirroring findings from human ASD transcriptomic data. In comparison to miR-137-deficient mouse and human induced pluripotent stem cell (hiPSC)-derived neuron models, the miniature pig model exhibited more consistent changes in critical neuronal genes relevant to humans following the loss of miR-137. Furthermore, a comparative analysis identified differentially expressed genes associated with ASD and ID risk genes in both miniature pig and hiPSC-derived neurons. Notably, human-specific miR-137 targets, such as CAMK2A, known to be linked to cognitive impairments and NDD, exhibited dysregulation in MIR137–/– miniature pigs. These findings suggest that the loss of miR-137 in miniature pigs affects genes crucial for neurodevelopment, potentially contributing to the development of NDD. Conclusions: Our study highlights the impact of miR-137 loss on critical genes involved in neurodevelopment and related disorders in MIR137–/– miniature pigs. It establishes the miniature pig model as a valuable tool for investigating neurodevelopmental disorders, providing valuable insights for potential applications in human research. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
194. Skilled reaching test for shoulder function assessment in a rat model of rotator cuff tear: a pilot study.
- Author
-
Liu, Yang, Fu, Sai-Chuen, Yao, Shi-Yi, and Yung, Patrick Shu-Hang
- Subjects
- *
ROTATOR cuff , *LABORATORY rats , *ANIMAL disease models , *SHOULDER , *FUNCTIONAL assessment , *TOTAL shoulder replacement - Abstract
Background: Functional assessments are crucial to evaluate treatment outcomes in clinical and animal studies on rotator cuff injuries. While gait analysis is commonly used to assess animal models of rotator cuff tears, it is less relevant for human patients as the human shoulder is typically assessed in a non-weight-bearing condition. The present study introduces the skilled reaching test as a shoulder functional assessment tool for rats, which allows for evaluation without weight bearing. Methods: In the control group, 8 male Sprague–Dawley rats received rotator cuff tear surgery without repair. In the rotator cuff repair group, 20 rats received rotator cuff repair at 4 weeks post rotator cuff tear. For the skilled reaching test, rats were trained to extend their forelimbs to fetch food pellets, and the number of trials, number of attempts and the success rate were recorded. The gait analysis and skilled reaching test were performed at baseline, 4 weeks post-tear, 1, 2, 4, and 8 weeks post-repair. The repeated measures analysis of variance was used to evaluate the effects of time on the shoulder function. The significance level was set at 0.05. Results: The skilled reaching test required 216 h to conduct, while the gait analysis took 44 h. In the rotator cuff repair group, gait performance significantly deteriorated at 1 week post-repair and restored to 4 weeks post-tear levels at 4 weeks post-repair. Regarding the skilled reaching test, the number of attempts, number of trials and the success rate decreased at 1 week post-repair. Subsequently, there was a brief rebound in performance observed at 2 weeks post-repair, followed by a continued decline in the number of attempts and trials. By 8 weeks post-repair, only the success rate had restored to levels similar to those observed at 4 weeks post-tear. Conclusion: The skilled reaching test can detect functional deficiencies following rotator cuff tear and repair, while it requires high time and labour costs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
195. Establishment of an acute arterial mesenteric ischaemia model in canines with an endovascular approach.
- Author
-
Yadong Shi, Yangyi Zhou, Yuan Yuan, Jie Kong, Maofeng Gong, Liang Chen, Xu He, Haobo Su, and Jianping Gu
- Subjects
MESENTERIC ischemia ,MESENTERIC artery ,INTESTINAL mucosa ,C-reactive protein ,MICROSCOPES - Abstract
Purpose: This study aimed to evaluate the feasibility of establishing an arterial acute mesenteric ischemia (AMI) model in canines using transcatheter autologous thrombus administration. Materials and methods: Ten canines were divided into the experimental group (Group A, n = 5) and the sham group (Group B, n = 5). The canines in Group A received thrombus administration to the superior mesenteric artery (SMA) through a guiding catheter, while the canines in Group B received normal saline administration. Blood samples were collected and tested at baseline and 2 h after modelling. Canines in Group A underwent manual thromboaspiration after blood and intestine samples were collected. Ischaemic grades of intestinal mucosa were evaluated under light microscopes. Results: The AMI models were successfully conducted in all canines without procedure-related vessel injury or death. At the 2-h follow-up, the highsensitivity C-reactive protein and D-dimer in Group A were significantly higher than in Group B (5.72 ± 1.8 mg/L vs. 2.82 ± 1.5 mg/L, p = 0.024; 2.25 ± 0.8 μg/ mL vs. 0.27 ± 0.10 μg/mL, p = 0.005; respectively). The mean histopathologic intestinal ischaemic grade in Group A was significantly higher than in Group B (2.4 ± 0.5 vs. 0.8 ± 0.4, p < 0.001). After a median of 2 times of thromboaspiration, 80% (4/5) of the canines achieved complete SMA revascularisation. Conclusion: This experimental study demonstrated that establishing an arterial model in canines using endovascular approaches was feasible. The present model may play an important role in the investigation of endovascular techniques in the treatment of arterial AMI. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
196. Anti-aging effects of dietary phytochemicals: From Caenorhabditis elegans, Drosophila melanogaster, rodents to clinical studies.
- Author
-
Chen, Ju-Chi, Wang, Reuben, and Wei, Chia-Cheng
- Subjects
- *
CAENORHABDITIS elegans , *DROSOPHILA melanogaster , *AGING prevention , *PHYTOCHEMICALS , *EPIGALLOCATECHIN gallate , *OLDER people , *LABORATORY rats , *RODENTS - Abstract
Anti-aging research has become critical since the elderly population is increasing dramatically in this era. With the establishment of frailty phenotype and frailty index, the importance of anti-frailty research is concurrently enlightened. The application of natural phytochemicals against aging or frailty is always intriguing, and abundant related studies have been published. Various models are designed for biological research, and each model has its strength and weakness in deciphering the complex aging mechanisms. In this article, we attempt to show the potential of Caenorhabditis elegans in the study of phytochemicals' effects on anti-aging by comparing it to other animal models. In this review, the lifespan extension and anti-aging effects are demonstrated by various physical, cellular, or molecular biomarkers of dietary phytochemicals, including resveratrol, curcumin, urolithin A, sesamin, fisetin, quercetin, epigallocatechin-3-gallate, epicatechin, spermidine, sulforaphane, along with extracts of broccoli, cocoa, and blueberry. Meanwhile, the frequency of phytochemicals and models studied or presented in publications since 2010 were analyzed, and the most commonly mentioned animal models were rats, mice, and the nematode C. elegans. This up-to-date summary of the anti-aging effect of certain phytochemicals has demonstrated powerful potential for anti-aging or anti-frailty in the human population. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
197. Computer-aided design and 3D printing for a stable construction of segmental bone defect model in Beagles: a short term observation.
- Author
-
Cheng, Kai, Zhu, Haotian, Peng, Yuanhao, Wen, Xinghua, and Ding, Huanwen
- Subjects
THREE-dimensional printing ,COMPUTER-aided design ,SURGICAL instruments ,INTRAMEDULLARY fracture fixation ,BEAGLE (Dog breed) ,ANIMAL models in research - Abstract
Objective: Segmental bone defect animal studies require stable fixation which is a continuous experimental challenge. Large animal models are comparable to the human bone, but with obvious drawbacks of housing and costs. Our study aims to utilize CAD and 3D printing in the construction of a stable and reproducible segmental bone defect animal mode. Methods: CAD-aided 3D printed surgical instruments were incorporated into the construction of the animal model through preoperative surgical emulation. 20 3D printed femurs were divided into either experimental group using 3D surgical instruments or control group. In Vitro surgical time and accuracy of fixation were analysed and compared between the two groups. A mature surgical plan using the surgical instruments was then utilized in the construction of 3 segmental bone defect Beagle models in vivo. The Beagles were postoperatively assessed through limb function and imaging at 1, 2 and 3 months postoperatively. Results: In vitro experiments showed a significant reduction in surgical time from 40.6 ± 14.1 (23–68 min) to 26 ± 4.6 (19–36 min) (n = 10, p < 0.05) and the accuracy of intramedullary fixation placement increased from 71.6 ± 23.6 (33.3–100) % to 98.3 ± 5.37 (83–100) %, (n = 30, p < 0.05) with the use of CAD and 3D printed instruments. All Beagles were load-bearing within 1 week, and postoperative radiographs showed no evidence of implant failure. Conclusion: Incorporation of CAD and 3D printing significantly increases stability, while reducing the surgical time in the construction of the animal model, significantly affecting the success of the segmental bone defect model in Beagles. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
198. Mis-localization of endogenous TDP-43 leads to ALS-like early-stage metabolic dysfunction and progressive motor deficits.
- Author
-
Hu, Yiying, Hruscha, Alexander, Pan, Chenchen, Schifferer, Martina, Schmidt, Michael K., Nuscher, Brigitte, Giera, Martin, Kostidis, Sarantos, Burhan, Özge, van Bebber, Frauke, Edbauer, Dieter, Arzberger, Thomas, Haass, Christian, and Schmid, Bettina
- Subjects
- *
METABOLIC disorders , *HYPOTHALAMUS , *AMYOTROPHIC lateral sclerosis , *MOTOR neurons , *MUSCULAR atrophy , *MYONEURAL junction , *EMBRYOLOGY , *WEIGHT loss - Abstract
Background: The key pathological signature of ALS/ FTLD is the mis-localization of endogenous TDP-43 from the nucleus to the cytoplasm. However, TDP-43 gain of function in the cytoplasm is still poorly understood since TDP-43 animal models recapitulating mis-localization of endogenous TDP-43 from the nucleus to the cytoplasm are missing. Methods: CRISPR/Cas9 technology was used to generate a zebrafish line (called CytoTDP), that mis-locates endogenous TDP-43 from the nucleus to the cytoplasm. Phenotypic characterization of motor neurons and the neuromuscular junction was performed by immunostaining, microglia were immunohistochemically localized by whole-mount tissue clearing and muscle ultrastructure was analyzed by scanning electron microscopy. Behavior was investigated by video tracking and quantitative analysis of swimming parameters. RNA sequencing was used to identify mis-regulated pathways with validation by molecular analysis. Results: CytoTDP fish have early larval phenotypes resembling clinical features of ALS such as progressive motor defects, neurodegeneration and muscle atrophy. Taking advantage of zebrafish's embryonic development that solely relys on yolk usage until 5 days post fertilization, we demonstrated that microglia proliferation and activation in the hypothalamus is independent from food intake. By comparing CytoTDP to a previously generated TDP-43 knockout line, transcriptomic analyses revealed that mis-localization of endogenous TDP-43, rather than TDP-43 nuclear loss of function, leads to early onset metabolic dysfunction. Conclusions: The new TDP-43 model mimics the ALS/FTLD hallmark of progressive motor dysfunction. Our results suggest that functional deficits of the hypothalamus, the metabolic regulatory center, might be the primary cause of weight loss in ALS patients. Cytoplasmic gain of function of endogenous TDP-43 leads to metabolic dysfunction in vivo that are reminiscent of early ALS clinical non-motor metabolic alterations. Thus, the CytoTDP zebrafish model offers a unique opportunity to identify mis-regulated targets for therapeutic intervention early in disease progression. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
199. Blebbistatin as a novel antiviral agent targeting equid herpesvirus type 8.
- Author
-
Liangliang Li, Xiu Cui, Yue Yu, Qi Sun, Wenjing Li, Yubao Li, Shuwen Li, Li Chen, Khan, Muhammad Zahoor, Changfa Wang, and Tongtong Wang
- Subjects
ANTIVIRAL agents ,MYOSIN ,HORSE diseases ,INFECTION control ,DRUG efficacy ,RESPIRATORY diseases - Abstract
Introduction: Equid herpesvirus type 8 (EqHV-8) poses a significant threat to equine health, leading to miscarriages and respiratory diseases in horses and donkeys, and results in substantial economic losses in the donkey industry. Currently, there are no effective drugs or vaccines available for EqHV-8 infection control. Methods: In this study, we investigated the in vitro and in vivo antiviral efficacy of Blebbistatin, a myosin II ATPase inhibitor, against EqHV-8. Results: Our results demonstrated that Blebbistatin significantly inhibited EqHV-8 infection in Rabbit kidney (RK-13) and Madin-Darby Bovine Kidney (MDBK) cells in a concentration-dependent manner. Notably, Blebbistatin was found to disrupt EqHV-8 infection at the entry stage by modulating myosin II ATPase activity. Moreover, in vivo experiments revealed that Blebbistatin effectively reduced EqHV-8 replication and mitigated lung pathology in a mouse model. Conclusion: Collectively, these findings suggest that Blebbistatin holds considerable potential as an antiviral agent for the control of EqHV-8 infection, presenting a novel approach to addressing this veterinary challenge. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
200. The zebrafish model requires a standardized synthetic microbial community analogous to the oligo-mouse-microbiota (OMM12).
- Author
-
Garibay-Valdez, Estefania, Martínez-Porchas, Marcel, Vargas-Albores, Francisco, Medina-Félix, Diana, and Rafael Martínez-Córdova, Luis
- Subjects
MICROBIAL communities ,BRACHYDANIO ,SALMONELLA enterica serovar typhimurium ,SCIENTIFIC knowledge ,ANIMAL communities ,VIBRIO parahaemolyticus ,BIFIDOBACTERIUM ,BACTERIAL diversity - Abstract
This article discusses the importance of using a standardized synthetic microbial community, such as the oligo-mouse-microbiota (OMM12), in zebrafish models for research purposes. It highlights the advantages of the OMM12 consortium and explores the potential use of other synthetic microbiota in zebrafish research. The article also mentions the benefits of using zebrafish as a model organism in scientific research, including their external embryonic development, well-developed immune system, and anatomical and genetic similarities to humans. It discusses the challenges of developing a synthetic microbial community for zebrafish and provides a list of references related to the study of gut microbiota in zebrafish and other animal models. These references cover various topics, including the diversity of gut microbiota in zebrafish, the use of zebrafish as a model for studying xenobiotics and toxic agents, and the impact of probiotics on the gut microbiota. Overall, this article and the accompanying references provide valuable information for researchers interested in studying the gut microbiota and its role in various biological processes. [Extracted from the article]
- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.