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Inflammatory bowel disease (IBD), caused by environmental factors associated with the host’s genetic traits, is represented by Crohn’s disease and ulcerative colitis. Despite the increasing number of patients with IBD, the current treatment is limited to symptomatic therapy. A complex IBD model mimicking the human IBD etiology is required to overcome this limitation. Herein, we developed novel complex IBD models using interleukin 2 receptor subunit gamma (Il2rg)-deficient mice, high-fat diet, dextran sodium sulfate, and Citrobacter rodentium . The more IBD factors applied complexly, colon length shortened and inflammation worsened. The levels of pro-inflammatory cytokines increased with increased IBD factors. Anti-inflammatory cytokine decreased in all factors application but increased in Il2rg deficiency and Westernized diet combination. Additionally, the pro-inflammatory transcription factors and leaky intestinal epithelial marker were upregulated by a combination of IBD factors. Species diversity decreased with IBD factors. Phylogenetic diversity decreased as IBD factors were applied but increased with combined Il2rg deficiency and Westernized diet. The more IBD factors applied complexly, the more severe the dysbiosis. Finally, we developed a novel complex IBD model using various IBD factors. This model more closely mimic human IBD based on colonic inflammation and dysbiosis than the previous models. Based on these results, our novel complex IBD model could be a valuable tool for further IBD research.

Carcinogenicity tests predict the tumorigenic potential of various substances in the human body by studying tumor induction in experimental animals. There is a need for studies that explore the use of FVB/N-Trp53 em2Hwl /Korl (FVB-Trp53 +/- ) mice, created by TALEN-mediated gene targeting in Korea, in carcinogenicity tests. This study was performed to determine whether FVB-Trp53 +/- mice are a suitable model for short-term carcinogenicity studies. To compare the carcinogenicity at different concentrations, 25, 50, and 75 mg/kg of N-methyl-N-nitrosourea (MNU), a known carcinogen, were administered intraperitoneally to FVB-Trp53 +/- and wild-type male mice. After 26 weeks, the survival rate was significantly reduced in FVB-Trp53 +/- mice compared to the wild-type mice in the 50 and 75 mg/kg groups. The incidence of thymic malignant lymphoma (TML) in the 50 and 75 mg/kg groups was 54.2 and 59.1% in FVB-Trp53 +/- male mice, respectively. TML metastasized to the lungs, spleen, lymph nodes, liver, kidney, and heart in FVB-Trp53 +/- male mice. Furthermore, the incidence of primary lung tumors, such as adenomas and adenocarcinomas, was 65.4, 62.5, and 45.4% in the FVB-Trp53 +/- mice of the 25, 50, and 75 mg/kg groups, respectively. The main tumor types in FVB-Trp53 +/- mice were TML and primary lung tumors, regardless of the dose of MNU administered. These results suggest that systemic tumors may result from malfunctions in the p53 gene and pathway, which is an important factor in the pathogenesis of human cancers. Therefore, FVB-Trp53 heterozygous mice are suitable for short-term carcinogenicity tests using positive carcinogens, and that the best result using MNU, a positive carcinogen, might have a single dose of 50 mg/kg.

Coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is currently spreading globally. To overcome the COVID-19 pandemic, preclinical evaluations of vaccines and therapeutics using K18-hACE2 and CAG-hACE2 transgenic mice are ongoing. However, a comparative study on SARS-CoV-2 infection between K18-hACE2 and CAG-hACE2 mice has not been published. In this study, we compared the susceptibility and resistance to SARS-CoV-2 infection between two strains of transgenic mice, which were generated in FVB background mice. K18-hACE2 mice exhibited severe weight loss with definitive lethality, but CAG-hACE2 mice survived; and differences were observed in the lung, spleen, cerebrum, cerebellum, and small intestine. A higher viral titer was detected in the lungs, cerebrums, and cerebellums of K18-hACE2 mice than in the lungs of CAG-hACE2 mice. Severe pneumonia was observed in histopathological findings in K18-hACE2, and mild pneumonia was observed in CAG-hACE2. Atrophy of the splenic white pulp and reduction of spleen weight was observed, and hyperplasia of goblet cells with villi atrophy of the small intestine was observed in K18-hACE2 mice compared to CAG-hACE2 mice. These results indicate that K18-hACE2 mice are relatively susceptible to SARS-CoV-2 and that CAG-hACE2 mice are resistant to SARS-CoV-2. Based on these lineage-specific sensitivities, we suggest that K18-hACE2 mouse is suitable for highly susceptible model of SARS-CoV-2, and CAG-hACE2 mouse is suitable for mild susceptible model of SARS-CoV-2 infection.

Background Chronic obstructive pulmonary disease (COPD) is a significant respiratory disorder in humans characterized by persistent airway constriction or obstruction due to chronic bronchitis and pulmonary emphysema. Various methods of inducing COPD in mouse models are frequently used in COPD research; however, these cannot completely reproduce histopathologic lesions. This study aimed to establish a new COPD mouse model that reproduces histopathological lesions closely resembling clinical COPD within a shorter induction time. Methods The new strategy involved the co-administration of porcine pancreatic elastase (PPE) and lipopolysaccharide (LPS), with PPE intended to induce pulmonary emphysema and LPS intended to induce chronic bronchitis. Male C57BL/6J mice were administered PPE (8 U/kg) on days 0 and 3 and LPS (400 µg/kg) on days 6, 9, 12, and 15. Each administration was performed using a noninvasive intubation-mediated intratracheal instillation method with a laryngoscope. Results Postmortem examination on day 22 revealed that pulmonary emphysema and chronic bronchitis were simultaneously induced in 90.91% of the lung lobes. Molecular studies revealed higher messenger ribonucleic acid (mRNA) expression levels of interleukin-6(IL-6) and matrix metalloproteinase-12(MMP-12) associated with the pathogenesis of COPD. Conclusion A new method was developed to establish a COPD mouse model that displays a more severe representation of the histopathological findings of clinical COPD than previous COPD models. It also reduces the time required for model induction. This newly developed COPD mouse model is expected to be a valuable tool for the pathogenesis and therapeutic research on human COPD.

Coronavirus disease-2019 (COVID-19), attributed to the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), has posed global health challenges since it first emerged in 2019, and its impact continues to persist. The neurotropic nature of SARS-CoV-2 remains undisclosed, though researchers are proposing hypotheses on how the virus is transmitted to the central nervous system. One of the prevailing hypotheses is that SARS-CoV-2 travels through the olfactory nerve system via the olfactory epithelium (OE). Using a K18-human angiotensin converting-enzyme 2 (hACE2) transgenic mouse model with impaired olfactory sensory neurons (OSNs) induced by zinc sulfate, we examined the role of the olfactory nerve in the brain invasion by SARS-CoV-2. Mice lacking OSNs exhibited reduced levels of viral transmission to the brain, leading to significantly improved outcomes following SARS-CoV-2 infection. Moreover, a positive correlation was observed between viral persistence in the OE and brain infection. These results indicate that early inhibition of the olfactory nerve pathway effectively prevents viral invasion of the brain in K18-hACE2 mice. Our study underscores the significance of the olfactory nerve pathway in the transmission of SARS-CoV-2 to the brain.

The SARS-CoV-2 coronavirus, which causes a respiratory disease called COVID-19, has been declared a pandemic by the World Health Organization (WHO) and is still ongoing. Vaccination is the most important strategy to end the pandemic. Several vaccines have been approved, as evidenced by the ongoing global pandemic, but the pandemic is far from over and no fully effective vaccine is yet available. One of the most critical steps in vaccine development is the selection of appropriate antigens and their proper introduction into the immune system. Therefore, in this study, we developed and evaluated two proposed vaccines composed of single and multiple SARS-CoV-2 polypeptides derived from the spike protein, namely, vaccine A and vaccine B, respectively. The polypeptides were validated by the sera of COVID-19-vaccinated individuals and/or naturally infected COVID-19 patients to shortlist the starting pool of antigens followed by in vivo vaccination to hACE2 transgenic mice. The spike multiple polypeptide vaccine (vaccine B) was more potent to reduce the pathogenesis of organs, resulting in higher protection against the SARS-CoV-2 infection.

BackgroundThere have been concerns over the long-term outcomes of endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancer (UD EGC). We aimed to compare the long-term outcomes of ESD and surgery for patients with UD EGC.MethodsWe searched PubMed, Embase, and Cochrane Library databases through March 2021 to identify studies that compared the long-term outcomes of ESD and surgery for UD EGC meeting expanded criteria for curative resection. The risk of bias was assessed with the Cochrane tool for non-randomized studies. The risk ratio (RR) was estimated using a fixed-effect model.ResultsOverall, 1863 patients from five retrospective cohort studies, including 908 patients with propensity score matching (PSM), were eligible for meta-analysis. ESD was associated with inferior overall survival (OS) compared to surgery in the overall cohort (RR 2.11; 95% CI 1.26–3.55) but not in the PSM cohort (RR 1.18; 95% CI 0.60–2.32). In the PSM cohort, ESD had a lower disease-free survival (DFS) (RR 2.49; 95% CI 1.42–4.35) and higher recurrence (RR 12.61; 95% CI 3.43–46.37), gastric recurrence (RR 11.25; 95% CI 3.06–41.40), and extragastric recurrence (RR 4.23; 95% CI 0.47–37.93). Recurrence outcomes were similar between the overall and PSM cohorts. Disease-specific survival was not significantly different between the two groups in both the overall and PSM cohorts.ConclusionAlthough OS after curative ESD for UD EGC was not different from that after surgery in the PSM cohort, DFS and recurrence were inferior after ESD. Limitations included a lack of randomized trials. Further prospective studies comparing the long-term outcomes of ESD and surgery for UD EGC are needed (PROSPERO CRD 42021237097).

Aim This study identified and evaluated tested patient safety educational interventions. This study also described the content, curricular structures and teaching strategies of the educational interventions and determined the methods used for evaluating patient safety learning outcomes. Design The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines directed this review. Methods Searches for articles describing and evaluating patient safety educational interventions were conducted using four scholarly databases. Study quality was assessed using the McMaster Critical Review Form. Results Seven studies met the inclusion criteria. Educational interventions were either presented as stand‐alone courses or as lessons embedded in an existing course. All studies employed a mixture of various teaching modalities and several evaluation methods and outcomes. Mixed results were observed in terms of the effects of educational interventions. Future researchers should continue to develop patient safety curricula and examine their effect on student competencies with stronger methodological rigour.

Background Despite advancements in laboratory animal facility management, pinworm infections remain a persistent issue in immunodeficient mouse colonies. Rapid diagnosis and treatment are crucial to mitigating potential scientific and economic consequences. Effective control requires both the administration of anthelmintic agents and rigorous environmental decontamination. However, the safety and efficacy of these treatments in genetically modified mouse models remains uncertain. Case presentation Aspiculuris tetraptera infestation was identified in multiple immunodeficient mouse models housed in a laboratory facility. Diagnosis was confirmed through fecal flotation for egg detection and necropsy for adult worm examination in the large intestines. Mice received three subcutaneous ivermectin injections at two-week intervals, coupled with environmental decontamination using ivermectin spray for four consecutive weeks. Following treatment, all colonies tested negative for A. tetraptera without any mortality. Conclusions A combination of subcutaneous ivermectin injection and environmental spray application effectively eradicated A. tetraptera infestation in immunodeficient mouse colonies. The treatment protocol led to the complete elimination of eggs and adult worms, offering a practical strategy for managing pinworm infections in genetically modified mouse models. Limitations include the small sample size, and the lack of a comprehensive evaluation of physiological and metabolic safety in immunodeficient mice. Further validation will be required to confirm the broader applicability of this approach.

Background We review and analyze research on the application of machine learning (ML) and deep learning (DL) models to lymph node metastasis (LNM) prediction in patients with T1 colorectal cancer (CRC). Predicting LNM before radical surgery is important in patients with T1 CRC. However, current surgical treatment guidelines are limited. LNM prediction using ML or DL may improve predictive accuracy. The diagnostic accuracy of LNM prediction using ML- and DL-based models for patients with CRC was assessed. Methods We performed a comprehensive search of the PubMed, Embase, and Cochrane databases (inception to April 30th of 2022) for studies that applied ML or DL to LNM prediction in T1 CRC patients specifically to compare with histopathological findings and not related to radiological aspects. Results 33,199 T1 CRC patients enrolled across seven studies with a retrospective design were included. LNM was observed in 3,173 (9.6%) patients. Overall, the ML- and DL-based model exhibited a sensitivity of 0.944 and specificity of 0.877 for the prediction of LNM in patients with T1 CRC. Six different types of ML and DL models were used across the studies included in this meta-analysis. Therefore, a high degree of heterogeneity was observed. Conclusions The ML and DL models provided high sensitivity and specificity for predicting LNM in patients with T1 CRC, and the heterogeneity between studies was significant. These results suggest the potential of ML or DL as diagnostic tools. However, more reliable algorithms should be developed for predicting LNM before surgery in patients with T1 CRC.