Animal models and experimental medicine最新文献

Background: Indole phytoalexins, plant-derived compounds present in cruciferous vegetables, have demonstrated anticancer properties. Brassinin (BSN), derived from Brassica campestris L. var. campestris, is known for its potent antitumor effects on various cancers. However, the role of ferroptosis in regulating the antitumor effects of BSN has not been fully elucidated.

Methods: The components of B. campestris L. against colorectal cancer (CRC) were analyzed by network pharmacology. CCK-8 assay and colony formation assay detected cell viability induced by BSN. Molecular docking verified the binding of BSN to the target protein. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay revealed whether BSN can inactivate the NRF2 signaling and inhibit the expression of p62 and HO-1. The RKO-xenograft tumor models were established and then were treated by 75 or 150 mg/kg BSN to verify the antitumor efficacy and side effects of BSN.

Results: Network pharmacology suggested that BSN is the most important component of B. campestris L. against CRC. BSN inhibits CRC cell viability in a dose- and time-dependent manner. Furthermore, this inhibitory effect is associated with the induction of ferroptosis, as BSN suppresses the cell viability of CRC by inducing GPX4-regulated ferroptosis. BSN may bind to NRF2 protein to inactivate the NRF2 signaling, inhibiting the expression of p62 and HO-1. Importantly, a low dose or a high dose of BSN significantly reduced the tumor growth in vivo.

Conclusions: Our findings reveal that BSN blocks CRC growth by inducing p62/NRF2/GPX4-regulated ferroptosis, which may be a novel lead compound for tumor treatment.

Cisplatin chemotherapy has been used as the main treatment for different types of cancer. However, cisplatin chemotherapy-induced peripheral neuropathic pain (CIPNP) seriously affects the treatment process and quality of life of patients. In addition, it impacts the underlying mechanism and prevention and treatment strategies, indicating that drug selection and efficacy evaluation need to be further investigated. Furthermore, an animal model that is more consistent with the pathological mechanism needs to be developed. In this study, we describe and discuss the methods of developing and detecting CIPNP models in rats and mice induced by cisplatin chemotherapy. The aim was to improve the modeling rate and develop animal models that are more consistent with the developmental pattern of the disease. In addition, the study provides ideal reference animal models for clinical research and drug discovery and development.

Background: Subcortical ischemic vascular dementia (SIVD) is a common subtype of vascular dementia. Currently, the bilateral common carotid artery stenosis (BCAS) mouse model is the most suitable SIVD rodent model. In this study, we investigated the functional and structural impairments in the hippocampus 1 month after BCAS.

Methods: We used behavioral tests, laser speckle flowmetry, long-term potentiation, histochemical staining, molecular experiments, and voxel-based morphometry to evaluate the hippocampal impairments.

Results: Behavioral studies revealed that BCAS mice exhibited worse performance. Laser speckle flowmetry detected an obvious decrease in cerebral blood flow. The synaptic plasticity of the perforant path-dentate gyrus pathway was inhibited. Decreased fractional anisotropy and increased mean diffusivity were detected in the hippocampus via diffusion tensor imaging data. A reduction in gray matter volume, which was most prominent in the hippocampus and its surrounding areas, was detected via voxel-based morphometry analysis. Impairments in cell morphology and myelin integrity were validated using histochemical staining and molecular biology techniques. In addition, the numbers of GFAP⁺ astrocytes and Iba1⁺ microglia increased in the hippocampus.

Conclusions: Overall, our study demonstrates early functional and structural impairments in the hippocampus contributing to learning and memory deficits after 1 month of BCAS, indicating that the hippocampus is vulnerable to chronic cerebral ischemia.

This study aimed to investigate the impact of administration routes in establishing the Adriamycin (ADR)-induced chronic kidney disease (CKD) model. Using BALB/c mice, we compared the effects of conventional tail-vein injection (TV10, 10 mg/kg) to those of retro-orbital sinus (orbital vein) injection (OV10, 10 mg/kg; OV8, 8 mg/kg). The results indicated that the OV10 group exhibited CKD pathology similar to the TV10 group, with both groups demonstrating significantly higher urinary albumin/creatinine ratio (p < 0.05), tubular injury (p < 0.05), and degree of renal fibrosis (p < 0.05) than the OV8 group. No significant differences were observed between the OV10 and TV10 groups in urinary albumin/creatinine ratio, tubular injury, and degree of renal fibrosis. These findings demonstrated that retro-orbital administration of 10 mg/kg ADR induces comparable effects to conventional tail-vein administration. This technique's technical simplicity may improve experimental efficiency, reproducibility, and animal welfare in CKD research. In conclusion, this study validates the utility of retro-orbital injection in CKD model establishment, demonstrating its potential to standardize and improve the reliability of future CKD research protocols.

Background: Neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, and Huntington's disease, are complex and challenging due to their intricate pathophysiology and limited treatment options.

Methods: This review systematically sourced articles related to neurodegenerative diseases, neurodegeneration, quercetin, and clinical studies from primary medical databases, including Scopus, PubMed, and Web of Science.

Results: Recent studies have included quercetin to impact the cellular and molecular pathways involved in neurodegeneration. Quercetin, a flavonoid abundant in vegetables and fruits, is gaining attention for its antioxidant, anti-inflammatory, and antiapoptotic properties. It regulates signaling pathways such as nuclear factor-κB (NF-κB), sirtuins, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt). These pathways are essential for cellular survival, inflammation regulation, and apoptosis. Preclinical and clinical studies have shown that quercetin improves symptoms and pathology in neurodegenerative models, indicating promising outcomes.

Conclusions: The study explores the potential of incorporating laboratory research into practical medical treatment, focusing on quercetin's neuroprotective effects on NDs and its optimal dosage.

Backgroud: Intervertebral disc degeneration (IDD) is one of the common degenerative diseases. Due to ethical constraints, it is difficult to obtain sufficient research on humans, so the use of an animal model of IDD is very important to clarify the pathogenesis and treatment mechanism of the disease.

Methods: In this study, thirty 2-month-old mice were selected for operation to establish a coccygeal IDD model. The distal tail portion of the tail (beyond the 17th coccygeal vertebra) and a small piece of skin above the 8th coccygeal vertebra were excised, and the two incisions were brought together after flexion, and secured with sutures. The heights and signal intensities of the intervertebral discs (IVDs) were assessed using microcomputed tomography (μCT) and magnetic resonance imaging (MRI) at 0, 6, 12 weeks postoperatively. The overall tissue morphology, cell distribution and density, and extracellular matrix of the IVDs were also assessed using Hematoxylin and Eosin (HE), Safranin O-Fast Green and immunohistochemical staining.

Results: All mice in the experimental group survived after the operation, and there were no complications such as wound infection, tail necrosis and suture shedding. The experimental results demonstrated that the suturing method can successfully initiate IDD. Different severity levels of IDD can be induced by controlling the bending angle of the IVDs within the tail loop; however, for consistency, histologic and imaging results should be obtained at the same bending angle and looping period.

Conclusions: This IDD model is an effective method for studying the etiology and treatment of degenerative IVD disease.

Background: Non-human primates (NPHs), such as rhesus macaques, cynomolgus monkeys, and Assamese macaques, play a crucial role in biomedical research. However, baseline cytokine and electrolyte data for these three species, particularly data stratified by age and sex, are limited. Therefore, the aim of this study was to establish and analyze age- and sex-specific cytokine and electrolyte profiles in these three species.

Methods: This study included 40 rhesus macaques (21 males, 19 females), 33 cynomolgus monkeys (17 males, 16 females), and 45 Assamese macaques (25 males, 20 females) classified by age (1-5 years, 6-12 years, >13 years) and sex. The levels of 23 immune function indicators and 5 electrolyte indicators were measured.

Results: Among the three monkey species, the levels of sCD40L, IL-18, MCP-1, MIP-1β, TGFa, K⁺, Na⁺, and Cl^- exhibited species-, sex-, and age-related differences. Comparison within the same species，sex had no significant impact on cytokine levels in NHPs but did affect electrolyte levels, particularly Cl^- and Na⁺ levels, in cynomolgus monkeys and Assamese macaques. Electrolyte levels in NHPs were not affected by age, whereas the levels of certain cytokines, particularly sCD40L, GM-CSF, and IL-10, varied with age. The remaining 21 cytokines demonstrated no significant age-related changes.

Conclusions: Significant variations in cytokine and electrolyte levels exist among different monkey species, sexes, and age groups. This research provides valuable resources for NHP researchers and sets the stage for further exploring the impacts of sex and age on NHP physiology and immune function.

The increasing incidence of neurodegenerative diseases (NDs) and the constraints of existing treatment methods have spurred a keen interest in investigating alternative therapies. Medicinal plants, renowned for their long-standing use in traditional medicine, offer a hopeful avenue for discovering new neuroprotective agents. This study emphasizes the potential neuroprotective characteristics of edible fruit plants in Bangladesh, specifically focusing on their traditional folk medicine uses for neurological disorders. This study provides an in-depth overview of the different types of edible fruit trees in Bangladesh and their phytochemicals, including flavonoids, terpenoids, and phenolic acids. This work examines the scientific data supporting the neuroprotective properties of bioactive chemicals from plants. It further explores the mechanisms by which these compounds work to counteract oxidative stress, decrease inflammation, and stimulate neurogenesis. Moreover, the study investigates toxicological characteristics and bioactive components of some fruits, emphasizing the importance of further investigation to measure their safety profile comprehensively. This thorough study highlights the potential benefits of Bangladesh's edible fruit trees as a rich source of neuroprotective chemicals. It also shows that additional research might lead to novel approaches for improving brain functioning and preventing NDs.

Polyphenols, a diverse group of naturally occurring compounds found in plants, have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases (NDs). The Wnt/β-catenin (WβC) signaling pathway, a crucial player in neurogenesis, neuronal survival, and synaptic plasticity, is involved in several cellular mechanisms related to NDs. Dysregulation of this pathway is a hallmark in the development of various NDs. This study explores multiple polyphenolic compounds, such as flavonoids, stilbenes, lignans, and phenolic acids, and their potential to protect the nervous system. It provides a comprehensive analysis of their effects on the WβC pathway, elucidating their modes of action. The study highlights the dual function of polyphenols in regulating and protecting the nervous system, providing reassurance about the research benefits. This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research, shedding light on how these substances influence the various components of the pathway. The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress, inflammation, and apoptotic processes, ultimately improving the function and survival of neurons. This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway, which could lead to the development of innovative therapeutic options for NDs.

This study developed an animal model with internal and external urethral sphincter insufficiency by bypassing the sphincter without major damage so that the animal under study can return to normal life after the study. There is a need for a reliable, applicable, and reproducible animal model for studying urinary incontinency disease due to incorrect sphincter function. Seven adult male dogs were used for this study. The urethral sphincter was bypassed by inserting a catheter between the bladder neck and the distal sphincter. The animals' physical condition was closely monitored for 9 weeks, and standard urodynamic and radiologic studies were performed before and 1-2 months after surgery. The animals were killed at 9 weeks after surgery for pathological assessment. Catheter placement caused complete incontinence in the animal, with urodynamic assessments indicating that the animal was unable to control urination and radiological assessments indicating an empty bladder with a residual volume of 50 ± 10 cc. Tissue analysis did not show significant histological damage and inflammation. The study shows that by bypassing the urethral sphincter, which is a reliable and reproducible method, an animal model of urinary incontinence can be developed, which can be used in various studies such as assessing the adequacy of artificial sphincter function. The animals under study did not have any permanent defect, so they were able to return to their normal life.