Laboratory Animal Research最新文献

{"title":"Possible involvement of p60-S6K1 in accelerating RPS6 phosphorylation for rapid recovery from skeletal muscle disuse atrophy.","authors":"Takao Inoue, Yuji Kanazawa, Nobuyuki Mizuguchi, Osamu Maenishi, Masatomo Kimura, Man Hagiyama, Azusa Yoneshige, Takaaki Chikugo, Tatsuki Itoh, Takao Satou, Akihiko Ito","doi":"10.1186/s42826-025-00250-w","DOIUrl":"10.1186/s42826-025-00250-w","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"20"},"PeriodicalIF":2.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An infographic on laboratory animal veterinarians.","authors":"Ji-Young Kim, Young-Shin Joo, Yujin Kim, On Shim, Jae-Hun Ahn, Jae-Eun Lee, Jiwon Lee, Jinha Jeon, Da In On, Yu Gang Kim, Bora Kim, Seung-Yeon Kim, Insook Yang, Kyoung-Sun Lee, Jungmin Lee, Ji-Yeon Hwang, Hyunjhung Jhun, Jun-Won Yun, Jeong-Hwan Che, Byeong-Cheol Kang, Ki Taek Nam, Seung Hyun Oh, Je Kyung Seong","doi":"10.1186/s42826-025-00244-8","DOIUrl":"10.1186/s42826-025-00244-8","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"19"},"PeriodicalIF":2.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative transcriptome analysis of PBMCs in cats diagnosed with and recovered from FIPV.","authors":"Ju Young Lee, Hyeong Ryeol Cho, Hong-Geun Oh, Jeong Ho Hwang","doi":"10.1186/s42826-025-00247-5","DOIUrl":"10.1186/s42826-025-00247-5","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"18"},"PeriodicalIF":2.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Doxorubicin-mediated testicular toxicity is associated with dysregulated mTOR/Beclin-1 pathways, oxidative stress, inflammation and apoptosis in Wistar rats: preventive role of lutein.","authors":"Jennifer Efe Jaiyeoba-Ojigho, Jerome Ndudi Asiwe, Joseph Chimezie, Blessing Oluwakemi Abe, Oghenemarho Monalisa Ataikiru, Taniyohwo Mamerhi Enaohwo, Alexander Obidike Naiho, Lilian Ebele Chris-Ozoko, Godstime Jesukobiruo Ibada, Sylvester Ifeakachukwu Okuepusu, Favour Isioma Ikukaiwe, Winnie Taiye Ogwu","doi":"10.1186/s42826-025-00249-3","DOIUrl":"10.1186/s42826-025-00249-3","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"17"},"PeriodicalIF":2.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of H1N1 strain A/PR/8/34 influenza to build a mouse model of viral respiratory sepsis.","authors":"Yaqing Jiao, Yuee Cai, Yilin Zhang, Ka-Tim Choy, Ka-Man Cheng, John M Nicholls, Pui-Kin Lam, Hui-Ling Yen, Timothy H Rainer","doi":"10.1186/s42826-025-00248-4","DOIUrl":"10.1186/s42826-025-00248-4","url":null,"abstract":"<p><strong>Background: </strong>Community-acquired respiratory infections are a prevalent cause of sepsis. Current animal models simulate peritoneal rather than respiratory sepsis. This study sought to appraise an influenza model for its ability to develop sepsis.</p><p><strong>Methods: </strong>Twenty-four six-week-old male BALB/c mice were intranasally inoculated with H1N1 strain A/PR/8/34 virus at 3.7 × 10^- 1, 3.7 × 10⁰, 3.7 × 10¹, 3.7 × 10², 3.7 × 10³, 3.7 × 10⁴ median tissue culture infectious dose (TCID50) to acquire different levels of clinical severity. Murine Sepsis Score (MSS) was recorded daily over 14 days. Platelets, serum bilirubin and creatinine levels were measured to reflect coagulopathy, liver and renal dysfunction. These three parameters are from the Sequential Organ Failure Assessment (SOFA) score which is routinely used for monitoring human sepsis. The primary outcome is organ dysfunction.</p><p><strong>Results: </strong>Out of 24 infected mice, seven (29%) did not survive beyond 9 days. MSS predicted mortality with an AUC of 0.989 (95%CI: 0.978-1.000; P < 0.001). Liver and renal dysfunction were detected in one non-survived and six survived mice. Histological examination revealed inflammation in lung and liver but not kidney tissues.</p><p><strong>Conclusions: </strong>This study demonstrates the potential of influenza to cause organ dysfunction, providing a basis for building a murine model specific for viral respiratory sepsis, and more closely simulating human viral sepsis.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"16"},"PeriodicalIF":2.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of commercial diets on fecal consistency and defecation frequency in rhesus macaques (Macaca mulatta) with chronic intermittent idiopathic diarrhea.","authors":"Annemiek Maaskant, Niels R Blees, Antoine Smits, Ronald J Corbee, Jaco Bakker, Jan A M Langermans, Edmond J Remarque","doi":"10.1186/s42826-025-00246-6","DOIUrl":"10.1186/s42826-025-00246-6","url":null,"abstract":"<p><strong>Background: </strong>Recurrent diarrhea is common health and welfare problem in captive rhesus macaques (Macaca mulatta). Aside from infectious causes, dietary factors have been implicated in diarrhea. Therefore, the main objective of this study was to evaluate commercially available pelleted diets in rhesus macaques with chronic intermittent idiopathic diarrhea. The main differences between these diets were lactose and fiber content. A randomized cross-over diet study was conducted to investigate the influence of each diet on fecal consistency and defecation frequency as indicators of diarrhea. Nine animals with chronic intermittent diarrhea and four controls were included. Each diet was fed for approximately three months, with a similar wash-out period after each diet cycle. The fecal consistency was graded using the Waltham Faeces Scoring system, with a cutoff score of > 3.5 indicating diarrhea. Both groups and diets were compared by both mixed and fixed effect models.</p><p><strong>Results: </strong>Descriptive data showed that the mean fecal consistency score was highest in the diarrhea group in the standard diet at 3.71 ± 0.456 whereas the lowest mean fecal consistency scores were observed for lactose-free and high fiber diet in both diarrhea (3.25 ± 0.423) and control group (3.04 ± 0.346). A significant improvement of the fecal consistency score was detected in the diarrhea group when fed lactose-free diets (-0.41(-0.65 - -0.16, P < 0.01) and -0.47(-0.68 --0.25, P < 0.0002), respectively). Lactose-free and high fiber content showed the best outcome regarding improvement of the fecal consistency score -0.47(CL -0.68-- 0.25, P < 0.0002). Defecation frequency increased in both groups with 1.21(CL 0.65 - 1.78, P < 0.00001) per observation day when fed a lactose-free, high-fiber diet.</p><p><strong>Conclusions: </strong>Lactose-free and high-fiber showed overall the best improvement of the fecal consistency in animals with diarrhea. Switching to commercially available lactose-free diets may decrease diarrhea incidence in rhesus macaques suffering from chronic intermittent idiopathic diarrhea. Nevertheless, additional nutritional research is warranted and establishing optimal nutritional requirements for captive macaques will add to our ability to understand and improve dietary interventions.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"15"},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ventilator-induced lung injury in rat models: are they all equal in the race?","authors":"Jon Petur Joelsson, Sigurbergur Karason","doi":"10.1186/s42826-025-00240-y","DOIUrl":"10.1186/s42826-025-00240-y","url":null,"abstract":"<p><p>Risk of ventilator-induced lung injury (VILI) is an inevitable and precarious accompaniment of ventilator treatment in critically ill patients worldwide. It can both instigate and aggravate acute respiratory distress syndrome (ARDS) where the only prevention or treatment so far has been empirical approach of what is considered to be lung protective ventilator settings in an attempt to shield the lung tissues against the mechanical stress that unavoidably follows ventilator treatment. The weakened state of the patients limits clinical drug research and pushes for drug discovery in animal models. Mice and rats are often the choice of small animal model, representing about 95% of all laboratory animal studies, as their physiology can mimic that which is found in humans. Mice have been a more popular choice for ventilator studies but due to technical issues, there is some advantage gained in using rats as they are substantially larger. Inducing VILI and ARDS in these models can prove challenging and often the acute nature of the injury used to produce similar tissue damage as in humans does not necessarily fully reflect clinical reality. The aim of this review was to analyse and summarize methods of recent publications in the field, describing what approaches have been utilized to simulate these conditions, possibly identifying a common track enabling comparison of results between studies. However, the study shows a high variety of methods employed by researchers causing comparisons of results difficult and perhaps implying that a more standardized approach should be used.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"14"},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asian sand dust exacerbates airway inflammation in a mouse model of asthma.","authors":"Se-Jin Lee, So-Won Pak, Woong-Il Kim, Sin-Hyang Park, Young-Kwon Cho, Tae-Won Kim, Je-Won Ko, Joong-Sun Kim, Jong-Choon Kim, In-Hyeon Kim, Sung-Hwan Kim, In-Sik Shin","doi":"10.1186/s42826-025-00243-9","DOIUrl":"https://doi.org/10.1186/s42826-025-00243-9","url":null,"abstract":"<p><strong>Background: </strong>Asian sand dust (ASD), generated from the deserts of China and Mongolia, mainly affects the human health of several countries in Northeast Asia including China, Korea, and Japan. In this study, we investigated the toxic effects of ASD on respiratory tract and explored the effects of ASD exposure on allergic asthma using ovalbumin-induced asthma model. C57BL/6 male mice were used for both the toxicity and allergic asthma studies. ASD (10, 20, and 40 mg/kg) was administered intranasally on days 1, 3, and 5. For allergic asthma, mice were sensitized with OVA (20 µg/mouse) and aluminum hydroxide (2 mg) on days 1 and 15, followed by OVA inhalation (1%, w/v) on days 22, 24, and 26, with subsequent ASD instillation on days 21, 23, and 25.</p><p><strong>Results: </strong>ASD exposure showed the elevation of respiratory inflammation including inflammatory cell infiltration, cytokine production, and mucus secretion with the increase in phosphorylated (p)-nuclear factor-kappa B (NF-κB) p65 expression. In addition, ASD exposure to asthma model significantly increased airway responsiveness, inflammatory cell count and mucus secretion with the elevation of cytokines and immunoglobulin E, which were accompanied with the increases in p-NF-κB p65, p-p38 and cyclooxygenase 2 (COX2).</p><p><strong>Conclusions: </strong>Therefore, ASD exposure induces respiratory inflammation and aggravates the progression of allergic asthma, which was closely associated with the phosphorylation of NF-κB. Respiratory exposure to ASD causes inflammation, upregulation of cytokines, p-NF-κB, and COX2, which can exacerbate asthma.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"13"},"PeriodicalIF":2.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fludarabine attenuates inflammation and dysregulated autophagy in alveolar macrophages via inhibition of STAT1/IRF1 pathway.","authors":"Jooyeon Lee, Jeong-Ran Park, Hanbyeol Lee, Seok-Ho Hong, Woo Jin Kim, Oliver Eickelberg, Sung-Min Park, Semin Ryu, Sung Joon Cho, Seung-Jin Kim, Se-Ran Yang","doi":"10.1186/s42826-025-00245-7","DOIUrl":"https://doi.org/10.1186/s42826-025-00245-7","url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury (ALI), including its most severe form, acute respiratory distress syndrome (ARDS), is a common cause of acute hypoxemic respiratory failure. Although its clinical characteristics have been well characterized, the relevant mechanism remains unclear. An imbalance in autophagy leads to alveolar remodeling and triggers the pathogenesis of ARDS. In this study, we assessed the therapeutic efficacy of the STAT1 inhibitor fludarabine (Fluda) in ALI. C57BL6 mice were exposed to lipopolysaccharide (LPS), and their lung tissues were analyzed via next-generation transcriptome sequencing.</p><p><strong>Results: </strong>Western blotting revealed that interferon regulatory factor 1 (IRF1) was highly expressed and STAT1 was phosphorylated following LPS exposure. Fluda significantly decreased the protein expression of STAT1/IRF1 and inhibited the alveolar infiltration of neutrophils and macrophages. Nitric oxide (NO), inducible nitric oxide synthase, tumor necrosis factor-α (TNF-α), interferon-γ, and interleukin-6 (IL-6) release was decreased in the lungs of mice and RAW264.7 macrophages following Fluda treatment. In LPS-induced GFP-LC3 transgenic mice treated with Fluda, the counts of LC3-expressing neutrophils and macrophages in bronchoalveolar (BAL) fluid were significantly decreased. Furthermore, Fluda decreased LC3 and p62 protein expression, thereby inhibiting the release of NO, IL-6, and TNF-α in BAL. In RAW264.7 cells, the inhibition of STAT1/IRF1 by Fluda decreased LPS-induced ERK and NF-κB p65 phosphorylation.</p><p><strong>Conclusions: </strong>The inhibition of STAT1/IRF1 by Fluda plays a pivotal role in modulating dysregulated autophagy by suppressing the MAPK and NF-κB p65 pathways in ALI.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"12"},"PeriodicalIF":2.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential responses of lung and intestinal microbiota to SARS-CoV-2 infection: a comparative study of the Wuhan and Omicron strains in K18-hACE2 Tg mice.","authors":"Chae Won Kim, Keun Bon Ku, Insu Hwang, Hi Eun Jung, Kyun-Do Kim, Heung Kyu Lee","doi":"10.1186/s42826-025-00241-x","DOIUrl":"https://doi.org/10.1186/s42826-025-00241-x","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic, caused by SARS-CoV-2, has led to the emergence of viral variants with distinct characteristics. Understanding the differential impacts of SARS-CoV-2 variants is crucial for effective public health response and treatment development. We investigated the differential effects of the original Wuhan strain and the emergent Omicron variant of SARS-CoV-2 using a K18-hACE2 transgenic mouse model. We compared the mortality rates, viral loads, and histopathological changes in lung and tracheal tissues, as well as alterations in the lung and intestinal microbiota following infection.</p><p><strong>Results: </strong>Our findings revealed significant differences between the variants, with the Wuhan strain causing higher mortality rates, severe lung pathology, and elevated viral loads compared to the Omicron variant. Microbiome analyses uncovered novel and distinct shifts in the lung and intestinal microbiota associated with each variant, providing evidence for variant-specific microbiome alterations. These changes suggest microbiome-related mechanisms that might modulate disease severity and host responses to SARS-CoV-2 infection.</p><p><strong>Conclusions: </strong>This study highlights critical differences between the Wuhan strain and Omicron variant in terms of mortality, lung pathology, and microbiota changes, emphasizing the role of the microbiome in influencing disease outcomes. Novel findings include the identification of variant-specific microbiota shifts, which underscore potential microbiome-related mechanisms underlying differences in disease severity. These insights pave the way for future research exploring microbiome-targeted interventions to mitigate the impacts of SARS-CoV-2 and other viral infections.</p>","PeriodicalId":17993,"journal":{"name":"Laboratory Animal Research","volume":"41 1","pages":"11"},"PeriodicalIF":2.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}