Laboratory Animal Research最新文献

Zebrafish (Danio rerio) have emerged as an influential model for studying human epithelial pathology, particularly because of their genetic similarity to humans and their unique physiological traits. This review explores the structural and functional homology between zebrafish and human epithelial tissues in organs, such as the gastrointestinal system, liver, and kidneys. Zebrafish possess significant cellular and functional homology with mammals, which facilitates the investigation of various diseases, including inflammatory bowel disease, nonalcoholic fatty liver disease, and polycystic kidney disease. The advantages of using zebrafish as a model organism include rapid external development, ease of genetic manipulation, and advanced imaging capabilities, allowing for the real-time observation of disease processes. However, limitations exist, particularly concerning the lack of organs in zebrafish and the potential for incomplete phenocopy of human conditions. Despite these challenges, ongoing research in adult zebrafish promises to enhance our understanding of the disease mechanisms and regenerative processes. By revealing the similarities and differences in epithelial cell function and disease pathways, this review highlights the value of zebrafish as a translational model for advancing our knowledge of human health and developing targeted therapies.

Hemorrhage is a prevalent side effect of various injuries and can be life-threatening in certain instances. It is categorized into compressible and non-compressible types, each necessitating distinct modeling, laboratory assessments, and hemostatic approaches. This study utilized the keywords Hemorrhage, Bleeding, Animal Modeling, and Hemostat in reputable databases. The findings indicate that femoral artery hemorrhage and hepatic parenchymal hemorrhage are the predominant modeling techniques for compressible and non-compressible bleeding, respectively. Furthermore, it is noted that animal models of compressible hemorrhages are primarily situated in superficial body areas to investigate dressing or additive hemostats, while non-compressible hemorrhage models, typically located in visceral organs, are employed to examine adhesive or surgical instrument-based hemostats.

Background: Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine. Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of transplanted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.

Results: In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats' left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within seven days after the injury, we found that arterial blood oxygen saturation (SpO₂) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO₂) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO₂) amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A histological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.

Conclusions: This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.

Background: Metabolic syndrome (MetS) refers to a group of risk factors that cause health problems, such as obesity, diabetes, dyslipidemia, and hyperglycemia. MetS is characterized by insulin resistance, which leads to abnormal insulin sensitivity. Cirsium japonicum var. maackii (CJ) is perennial herbaceous species found in Asia that exhibits antioxidant, antidiabetic, antitumor, antifungal, and anti-inflammatory activities. In this study, we aimed to measure the effects of CJ on MetS by improving insulin resistance in a db/db type 2 diabetes mouse model. After administrating CJ extract (CJE) for db/db mouse for 6 weeks, we measured with the evaluation of Insulin resistance, lipid profiles, histological analysis of liver, damage of liver and kideny.

Results: The results showed that CJE was effective in reducing body weight and fat mas and showed a positive effect on lowering blood glucose and improving insulin sensitivity. CJE improved dyslipidemia by increasing serum-HDL levels and decreasing serum-LDL levels. In addition, CJE reduced liver and kidney damage in histological analysis.

Conclusions: These results demonstrate the anti-diabetic effects of CJE and suggest its potential for improving MetS. Therefore, CJE may have potential values as a functional food material for managing MetS.

Background: The Microtubules-associated protein tau (MAPT), alpha-synuclein (SNCA), and leucine zipper tumor suppressor 3 (LZTS3) genes are implicated in neurodegeneration and tumor suppression, respectively. This study investigated the regulatory roles of eugenol on paraquat-altered genes.

Results: Forty male Wistar rats divided into five groups of eight rats were used. The control group received normal saline; the Paraquat (PQ)-untreated group received only Paraquat. The low dose of eugenol was 200 mg/kg, the medium dose of eugenol was 400 mg/kg, and the high dose of eugenol was 600 mg/kg. All groups except the control group received 10 mg/kg of PQ orally for 14 days at one-day intervals, allowing PQ in the rats for 28 days. Eugenol treatment started on the 29th and lasted 14 days. Motor impairments were determined using wire string and beam-walk; biomarkers were estimated using cerebellar homogenates, while frozen cerebellum was used to study LZTS3, MAPT, and SNCA gene expression. LZTS3 was significantly suppressed in the PQ-untreated group and highly expressed in the eugenol-treated group. The MAPT and SNCA genes were overexpressed in the PQ-untreated group compared to the control group. Eugenol significantly decreased the expression of these genes compared to that in the PQ-untreated group. Antioxidants were reduced considerably, and oxidative stress markers were increased significantly, which could have caused increased protein fibrillation and reduced limb functionality. Histology revealed that eugenol mitigated the alterations caused by Paraquat.

Conclusions: PQ can enhance tumor expression in addition to causing neurotoxicity, which decreases limb functionality, while eugenol, an antioxidant, can mitigate the effects of PQ.

Ischemic stroke (IS) is the most recorded case of stroke that is caused by decreased blood flow to the brain. Nowadays, therapeutical agents for IS are limited and they have not shown maximum clinical results. Therefore, the exploration of new candidates for IS treatment continues to be done. Zebrafish as one of the animal models has its advantages and currently is being developed to be incorporated into the drug discovery pipeline of IS. This review explores the latest applications of the zebrafish model in screening potential therapeutic agents for IS. Key factors related to the experimental design such as developmental stage and strain, routes of drug administration, induction methods, and experimental parameters are also elaborated. Finally, this review offers future recommendations for the use of zebrafish in the pre-clinical study of IS. This review is beneficial as a reference for establishing drug screening protocols using the zebrafish IS model.

Background: Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) Il2rg knockout (KO), Rag2 KO and Il2rg/Rag2 KO rats for 20 weeks.

Results: During experiments, Il2rg KO, Rag2 KO and Il2rg/Rag2 KO rats showed decreased white blood cells and systemic lymphopenia, with reduced CD4+, CD8+ T cells and CD161+ NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disappearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0 × 10⁶ cells/kg of NALM6 cells into Il2rg/Rag2 KO rats.

Conclusions: These findings indicate that Il2rg KO, Rag2 KO, and Il2rg/Rag2 KO rats exhibited SCID phenotypes, suggesting their potential application as immunodeficient animal models for tumor xenograft studies.

Background: In the last few decades, numerous efforts have been made to develop a better mouse model to overcome the current limitations of laboratory inbred mouse models such as have a weaker and simpler immune status. As part of these efforts, in Korea, the Hallym university medical genetics research team has been developing a new inbred strain of Korean wild mouse KWM/Hym. It was suggested that this strain, which is derived from wild mice, might be useful for genetic research and may become a valuable tool for overcoming some limitations seen in inbred mice that are currently used in the laboratory. Furthermore, for this study, we aimed to determine the visual phenotype of this unique strain KWM/Hym, and consider whether and if they are suitable for visual research. To analyze their visual phenotype, we performed the functional and morphological examinations in KWM/Hym mice and compared the results with laboratory mice which are the most common background strain.

Results: KWM/Hym had a thin corneal phenotype, thin but well-ordered retina due to their light body weight characteristic, and normal visual function similar to control mice. Unexpectedly, the KWM/Hym mice developed cataracts only at around 25 weeks old.

Conclusions: We suggest Korean wild mouse KWM/Hym is useful for visual experiments and could be an animal model of eye disease in humans.

We systematically reviewed the evidence from animal studies assessing the effects of pentoxifylline on neonatal hypoxic-ischemic encephalopathy (HIE). The PubMed, EMBASE, EMCARE, MEDLINE, Cochrane Library, and Google Scholar databases were searched for randomized and quasi randomized controlled trials (RCTs) in December 2023 to determine the effects of pentoxifylline in animal models of HIE. The quality of the included studies was assessed via the SYRCLE risk of bias (ROB) tool. The certainty of evidence was assessed via the GRADE methodology. All seven included studies (n = 248) involved a rat HIE model in which pentoxifylline (25-150 mg/kg) was administered intraperitoneally. The majority had unclear ROB. All the studies reported a protective effect of pentoxifylline on HIE-induced organ injury. Mortality was comparable at pentoxifylline doses between 25 and 75 mg/kg but higher at 150 mg/kg than in the control group. Three studies reported macroscopic changes in HIE-affected organs. There was a significant reduction in cerebral infarction (40 and 75 mg/kg), hippocampal atrophy, and visible gut injury (60 mg/kg). A significantly lower number of Caspase 3 immunoreactive cells and necrotic cells were observed at the 60 mg/kg dose, whereas the 100 mg/kg dose had a deleterious effect. Three other studies reported significantly reduced levels of proinflammatory markers including IL-6 and TNF-alpha. Current evidence (with low uncertainty) from a rat model suggests that pentoxifylline has the potential to improve mortality and attenuate organ injury following HIE. Adequately powered, well-designed human RCTs are needed to confirm our findings.

Background: Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensitization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups.

Results: In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05).

Conclusions: Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.