Laboratory Animal Research最新文献

Background: Despite the availability of various therapeutic strategies, the prognosis for patients with metastatic breast cancer remains poor. Epithelial-mesenchymal transition (EMT) is a critical mechanism driving metastasis in breast cancer, enabling tumor cells to lose epithelial characteristics and acquire enhanced motility and invasiveness.

Results: This study investigates the role of 11alpha-hydroxyprogesterone (11α-OHP), a steroid hormone with an incompletely understood biosynthesis and metabolic pathway, in regulating lung metastasis in breast cancer. Using the MMTV-PyMT FVB mouse model, which spontaneously develops breast tumors we administered 11α-OHP for five weeks starting at 10 weeks of age. At 15 weeks, histological analysis revealed a significant reduction in lung metastasis in 11α-OHP-treated mice compared to controls, with notably smaller metastatic tumor areas in the lungs. Additionally, treated mice exhibited increased expression of epithelial cell adhesion proteins and decreased levels of focal adhesion kinase (FAK) in lung tissues. In vitro experiments using MDA-MB-231 cells corroborated these findings, showing that 11α-OHP significantly inhibited cell motility and invasiveness in scratch wound, transwell migration, and invasion assays. Notably, 11α-OHP did not significantly alter primary tumor growth in the MMTV-PyMT model.

Conclusions: These findings suggest that 11α-OHP may suppress breast cancer metastasis by modulating EMT, highlighting its potential as a therapeutic target for preventing metastatic progression.

Background: With aging, the canonical histone H3.1/3.2 in skeletal muscle is progressively replaced by the non-canonical variant H3.3. Although H3.3 is thought to be involved in age-related epigenetic regulation due to its role as a histone variant, its functional characteristics remain largely unknown. Serine 31 (S31) is a unique amino acid residue of H3.3 that undergoes phosphorylation. Therefore, the present study aimed to investigate the relationship between skeletal muscle aging and H3.3 phosphorylation at S31 (H3.3S31ph).

Results: We first demonstrated that H3.3S31ph levels were significantly reduced in the tibialis anterior muscle of 75-wk-old mice compared to 8-wk-old mice. We then examined the effects of viral vector-mediated expression of wild-type H3.3 or a phosphorylation-mimicking H3.3 mutant (H3.3S31E) on gene responsiveness to acute exercise in aging skeletal muscle. In muscles expressing wild-type H3.3, which simulates epigenetic alterations observed during skeletal muscle aging, the transcriptional response to acute exercise was lost by 30 weeks post-treatment (60 weeks of age). In contrast, expression of H3.3S31E successfully rescued the gene responses to acute exercise. This rescue was accompanied by increased enrichment of H3K4me3 and H3K27me3 following acute exercise in the H3.3S31E group, whereas no such histone modification changes were observed in the wild-type H3.3 group. Additionally, robust involvement of exogenous H3.3 in exercise-related histone turnover was observed in the wild-type H3.3 group, but not in the H3.3S31E group, suggesting that phosphorylation at S31 limits the dynamic behavior of H3.3.

Conclusions: Impaired transcriptional responsiveness to exercise in a simulated epigenetic aging model induced by exogenous H3.3 expression was rescued by the phosphorylation-mimicking H3.3S31E variant in middle-aged skeletal muscle. The findings of the present study demonstrate that H3.3S31ph plays a critical role in regulating the stability of H3.3 within chromatin.

Numerous rodent research models of attention-deficit/hyperactivity disorder (ADHD) have been proposed, including pharmacological, environmental, and genetically generated models. A rodent model for studying ADHD should demonstrate similarities to the disorder by mimicking its three core symptoms (face validity), should align with a theoretically justified pathophysiological basis (construct validity), and should provide insights into unknown aspects of ADHD neurobiology while offering potential new treatments (predictive validity). This review provides an overview of rodent research models, which vary in their pathophysiological alterations, ability to replicate behavioural symptoms, and response to pharmacological treatments. Given this heterogeneity, it remains challenging to determine which rodent model best represents ADHD or its different subtypes. Consequently, validating these models against contemporary medication therapies and testing candidate natural compounds as potential adjuvant treatments is essential. Additionally, combining models induced by neurotoxins, environmental substances, and genetic modifications may help evaluate potential interactions and their impact on ADHD development.

Background: Histiocytic proliferative disorders in the central nervous system are rare, and their potential association with viral infections remains largely unexplored. This case is relevant because it suggests a potential interaction between SARS-CoV-2 neuroinvasion and tumor development, providing insights into how viral infections might influence oncogenesis.

Case presentation: A 4.5-month-old male k18-hACE-2 mouse, part of an experimental study of SARS-CoV-2, displayed a small mass in leptomeningeal area composed by neoplastic round cells. This process is associated with typical acute inflammatory and neurodegenerative lesions according to viral neuroinvasion. Histopathology revealed a well-demarcated tumor composed of lymphoblasts and intermixed with abundant histiocytic-like cells. Immunohistochemistry showed high expression of Iba-1 in histiocytes but negative PAX5, CD3 and IRF-4 labeling. Due to the critical role of PAX-5 in maintaining B-cell function, its reduction or inactivation may favor this loss of identity and differentiation to macrophages, which supports the possibility of a lymphoma undergoing transdifferentiation into a histiocytic/dendritic cells neoplasm. Additionally, SARS-CoV-2 was detected within the tumor histiocytes and adjacent neurons, raising questions about potential interactions between viral infection and tumor development.

Conclusions: While the underlying mechanisms remain uncertain, this finding highlights the need for further investigation into the interplay between SARS-CoV-2 infection and oncogenesis. This case represents the first report of a primary brain histiocytic lymphoproliferative disorder associated with SARS-CoV-2 in k18-hACE2 mouse.

Asthma is a chronic and heterogeneous airway disease characterized by a variety of respiratory symptoms associated with airflow limitation. Asthma patients exhibit altered immunological and physiological features in the airways, including inflammation, hyperresponsiveness, and, in severe cases, permanent structural changes that lead to airway obstruction. Among the different types of asthma, allergic asthma mediated by Th2 cells is the most prevalent phenotype worldwide. The diversity of etiological factors involved, the variability in symptom intensity, and the high global incidence have increased interest in studying this phenomenon. Due to the ethical constraints associated with studying asthma in humans, the development of animal models has emerged as an alternative for investigating the disease's pathophysiology. In particular, the guinea pig (Cavia porcellus) has become one of the most commonly used species, as it closely resembles the inflammatory, pharmacological, and physiological responses observed in the human airway. This article provides a comprehensive description of the development of an allergic asthma model in the guinea pig. The processes involved in each methodological phase are described in detail from an immunological and physiological perspective, emphasizing their importance in understanding the disease's pathophysiological mechanisms. It is argued that the airway inflammation, obstructive responses, and remodeling processes observed in this model are consistent with features seen in asthma patients, establishing the guinea pig as a reliable model for studying allergic asthma in humans.

Background: Allergic asthma is a chronic inflammatory disease in which bronchial inflammation causes narrowing of the bronchi when exposed to allergens, resulting in coughing, wheezing, and difficulty breathing. Gastrodia elata Blume (GEB) is a perennial Orchidaceae plant native to alpine areas and is known to be effective in anti-inflammatory and anticonvulsants. This study evaluated the anti-inflammatory and anti-allergic effects of GEB extract in a rat model of allergic asthma induced by ovalbumin. This study evaluated the anti-inflammatory and anti-allergic effects of GEB extract in a rat model of allergic asthma induced by ovalbumin. Twenty-four 6-week-old Wistar rats were divided into three groups: control group (CON), ovalbumin (OVA) -induced group, and GEB treatment group. Except for the CON group, the remaining groups were sensitized to OVA by intraperitoneal injection, and asthma was induced by OVA intranasal instillation. The CON and OVA groups were administered distilled water, and the GEB group was administered 7 g/kg of GEB extract for 11 days.

Results: Serum total IgE levels were decreased in the GEB group compared to the OVA group. Also, lung IL-4, IL-5, and IL-13 levels were significantly lower in the GEB group than in the OVA group. Histopathological analysis using hematoxylin and eosin and periodic acid Schiff staining, the tracheal and alveolar walls of the OVA group were thickened, and there was increased infiltration of inflammatory cells in the bronchi, perivascular, and alveolar spaces. As for lung damage caused by OVA, GEB treatment reduced the infiltration of inflammatory cells into the bronchi and blood vessels, and the alveolar spaces were maintained, showing a structure similar to that of the CON group. Immunohistochemical analysis showed that IL-4, IL-5, CD206, and MPO expression levels were reduced in the GEB group compared to the OVA group.

Conclusions: This suggests that GEB treatment has an anti-inflammatory and anti-allergic effect by reducing the levels of IgE and the cytokines IL-4, IL-5, and IL-13 and ameliorating histopathological changes in an asthma rat model.

Background: Stroke-prone spontaneously hypertensive rats (SHRSP) exhibit slow-twitch muscle-specific hypotrophy compared with normotensive Wistar-Kyoto rats (WKY). Because slow-twitch muscles are prone to disuse atrophy, SHRSP may experience both disuse atrophy and impaired recovery from it. This study investigated the response of SHRSP to disuse atrophy and subsequent recovery, using WKY as a control.

Results: WKY and SHRSP were subjected to a 7-day tail suspension followed by reloading for 1, 3, and 7 days. The soleus of WKY and SHRSP showed similar atrophic rates following tail suspension; however, the recovery after reloading was delayed in SHRSP. Moreover, WKY, but not SHRSP, exhibited sarcomere structure disruption after tail suspension, followed by necrosis, inflammatory cell infiltration, and edema upon reloading. Phosphorylation of ribosomal protein S6 (RPS6), an indicator of protein translation, was significantly higher in tail-suspended WKY-but not SHRSP-than those in non-tail-suspended groups after reloading. p70-S6 kinase 1 (S6K1), an upstream protein of RPS6, was phosphorylated at Thr389 in a mechanistic target of rapamycin complex 1-dependent manner to the same extent in both WKY and SHRSP; however, the expression of p60-S6K1-a shorter isoform of p70-S6K1 that activates RPS6 without p60-S6K1 phosphorylation-significantly increased only in tail-suspended WKY compared with those in non-tail-suspended WKY and tail-suspended SHRSP. Previously, p60-S6K1 protein expression was thought to result from an alternative translation of the full-length S6K1 transcript that also produces other S6K1 isoforms. However, recent studies have identified a p60-S6K1-specific transcript, and our PCR results showed that this p60-S6K1-specific transcript, but not the full-length S6K1 transcript, was significantly increased only in tail-suspended WKY corresponding with the increase of p60-S6K1 protein expression.

Conclusions: SHRSP exhibited different phenotypes in disuse atrophy and recovery from it compared with WKY, which could be related to suppressed RPS6 phosphorylation associated with the lack of upregulation in p60-S6K1 expression. These findings suggest that p60-S6K1, in cooperation with p70-S6K1, activates RPS6 and promotes rapid recovery from disuse atrophy by enhancing the transcription of the p60-S6K1-specific transcript. The study also suggests a potential involvement of hypertension in disuse atrophy and its recovery.

Background: Laboratory animal veterinarians play a crucial role as a bridge between the ethical use of laboratory animals and the advancement of scientific and medical knowledge in biomedical research. They alleviate pain and reduce distress through veterinary care of laboratory animals. Additionally, they enhance animal welfare by creating environments that mimic natural habitats through environmental enrichment and social associations. This approach reduces errors caused by improper animal management and enhances the reproducibility of animal experiments, thereby contributing significantly to scientific progress.

Results: The Korean College of Laboratory Animal Medicine, established in 2006, aims to formalize the status of laboratory animal veterinarians. The revised Animal Protection Act of April 2022 mandates the employment of attending veterinarians in animal research facilities exceeding prescribed standards by Presidential Decree. This underscores the increasing importance of laboratory animal veterinarians in Korean society. Consequently, the Korean College of Laboratory Animal Medicine initiated efforts to raise awareness of laboratory animal veterinarians, leading to the creation of an infographic. Infographics combine textual and graphical elements to effectively convey information, data, and knowledge. These veterinarians collaborated with infographic specialists to research, check, classify, refine, analyze, and structure content on laboratory animal veterinarians.

Conclusion: This infographic represents the first comprehensive initiative worldwide on laboratory animal veterinarians. It will be disseminated globally to animal research facilities to enhance awareness and promote the professional standing of laboratory animal veterinarians.

Background: Feline infectious peritonitis is a viral disease caused by feline coronavirus an enveloped virus with a single-stranded RNA genome that is approximately 30 kb long. Although FCoV generally causes mild symptoms, approximately 5% of cases progress to death in cats worldwide. FCoV shares certain virological features with severe acute respiratory syndrome coronavirus 2 that causes COVID-19, indicating that common therapeutic strategies may be applicable. GS-441524 the parent drug of remdesivir and a competitive inhibitor of nucleoside triphosphates in viral RNA synthesis is a well-known treatment for FIP. However, comparative transcriptome and gene ontology analyses of normal (Normal), FIP-diseased (FIPD), and FIP-recovered (FIPR) cats have not yet been conducted.

Results: In this study, we compared the mRNA expression profiles of peripheral blood mononuclear cells from Normal, FIPD, and FIPR cats to identify immunological alterations. We identified 677 (FIPD/Normal) and 431 (FIPR/FIPD) differentially expressed genes with statistical significance. These data were input into the bioinformatics program. As a result, the analysis revealed statistically significant and contrasting patterns of canonical pathways of neutrophil degranulation and interleukin-8 (IL-8) signaling pathways. Additionally, we observed that kruppel-like factor 6 (KLF6) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were upstream molecules of IL-8, promoting neutrophil activation and function.

Conclusions: This study identified immunological alterations in PBMCs of Normal, FIPD, and FIPR cats. KLF-6 and NF-κB were found to regulate IL-8-mediated neutrophil activation.

Background: Lutein offers undoubted hope for preventing doxorubicin uncharacteristic reproductive function which remains a worldwide health concern in cancer chemotherapy. However, the mechanisms underlying the effect of lutein on maintaining the male reproductive milieu have not yet been fully identified. The current study investigates the preventive effect of lutein in doxorubicin-induced testicular toxicity.

Methods: Twenty male Wistar rats were randomly assigned into four groups of five animals (n = 5) and were pretreated with lutein (40 mg/kg i.p) prior to doxorubicin treatment (15 mg/kg i.p). Following the end of the experiment, animals were euthanized and the testes were collected and processed for semen and biochemical analysis.

Results: The results revealed that exposure to doxorubicin caused hormonal imbalance, reduced semen quality and elicited oxidative stress, inflammatory reactions, apoptosis as well as dysregulation of autophagic process which was accompanied by fibrosis and histomorphological aberrations. Interestingly, pretreatment with lutein significantly restored hormonal balance and protected against the adverse effects of doxorubicin.

Conclusions: The findings of this study showed that lutein prevents doxorubicin-mediated testicular toxicity via modulation autophagic pathways accompanied with inhibition of oxidative stress, inflammation and apoptosis.