Animal models and experimental medicine最新文献

{"title":"Disruption of the blood-brain barrier contributes to neurobehavioral changes observed in rheumatic heart disease.","authors":"Rukshan Ahamed Mohamed Rafeek, Riya Thapa, Samarjeet Saluja, Bipandeep Banga, David McMillan, Kadaba Sri Sriprakash, Nicholas M Andronicos, Adam Hamlin, Natkunam Ketheesan","doi":"10.1002/ame2.70012","DOIUrl":"https://doi.org/10.1002/ame2.70012","url":null,"abstract":"<p><p>Sydenham chorea (SC) is the neurological manifestation associated with acute rheumatic fever (ARF). ARF and rheumatic heart disease (RHD) are autoimmune complications triggered by a group A streptococcal (GAS) infection. In ARF/RHD and SC, tissue cross-reactive antibodies and T-cells generated against GAS antigens have been implicated in the pathogenesis. In SC, antibodies against GAS antigens are known to cross-react with neuronal proteins causing neurological manifestations including choreiform movements and neuropsychiatric symptoms such as irritability, attention deficit, and obsessive-compulsive disorder. Previous studies in a rat autoimmune valvulitis (RAV) model of RHD, have shown that injection of streptococcal M protein could cause both cardiac and neurological symptoms. In this study it was shown that adoptive transfer of serum with anti-GAS M antibodies to naive rats caused carditis but failed to demonstrate neurobehavioral symptoms. However, when the blood-brain barrier (BBB) was disrupted using lipopolysaccharide, all animals that received anti-GAS M protein antibodies, developed neurobehavioral defects in addition to carditis. This highlights that impaired BBB integrity is essential for the development of neurobehavioral symptoms. The use of the RAV model and the disruption of BBB required for the development of neurobehavioral changes provides a platform to further investigate the mechanisms that lead to antibodies binding to basal ganglia structures that cause SC.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astaxanthin ameliorates benzalkonium chloride-induced dry eye disease through suppressing inflammation and oxidative stress via Keap1-Nrf2/HO-1 signaling pathways.","authors":"Ziyu Liu, Yaqiong Li, Jiayu Bao, Siyuan Li, Ya Wen, Peng Zhang, Jun Feng, Yinghui Wang, Lei Tian, Ying Jie","doi":"10.1002/ame2.70000","DOIUrl":"https://doi.org/10.1002/ame2.70000","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Dry eye disease (DED) predominantly results from elevated tear film osmolarity, which can not only cause ocular inconvenience but may lead to visual impairments, severely compromising patient well-being and exerting substantial economic burdens as well. Astaxanthin (AST), a member of the xanthophylls and recognized for its robust abilities to combat inflammation and oxidation, is a common dietary supplement. Nonetheless, the precise molecular pathways through which AST influences DED are still poorly understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Therapeutic targets for AST were identified using data from the GeneCards, PharmMapper, and Swiss Target Prediction databases, and STITCH datasets. Similarly, targets for dry eye disease (DED) were delineated leveraging resources such as the Therapeutic Target Database (TTD), DisGeNET, GeneCards, and OMIM databases, and DrugBank datasets. Interactions among shared targets were charted and displayed using CytoScape 3.9.0. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted to elucidate the functions of pivotal targets within the protein-protein interaction network. Molecular interactions between AST and key targets were confirmed through molecular docking using AutoDock and PyMOL. Molecular dynamics simulations were performed using GROMACS 2022.3. Viability of human corneal epithelial cells (hCEC) was assessed across varying concentrations of AST. A mouse model of experimental DED was developed using 0.1% benzalkonium chloride (BAC), and the animals were administered 100 mg/kg/day of AST orally for 7 days. The efficacy of the treatments was assessed through a series of diagnostic tests to evaluate the condition of the ocular surface after the interventions. The levels of inflammation and oxidative stress were quantitatively assessed using methods such as reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence staining.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Network pharmacology suggests that AST may alleviate DED by influencing oxidation-reduction signaling pathways and reducing oxidative stress provoked by BAC. In vivo experiments demonstrated an improved overall condition in AST-administered mice in contrast to the control group. Immunofluorescence staining analyses indicated a decrease in Keap1 protein in the corneal tissues of AST-treated mice and a significant increase in Nrf2 and HO-1 protein. In vitro studies demonstrated that AST significantly enhanced cell viability and suppressed reactive oxygen species expression under hyperosmotic (HS) conditions, thereby protecting the human corneal epithelium.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;AST is capable of shielding mice from BAC-induced DED, decelerating the progression of DED, and mitigating oxidative stress damage under HS conditions in hCEC cells. The protective impact of AST on DED may operate through stimulating the Keap1-Nrf2/HO-1 signaling pathway","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a single-nucleotide polymorphism panel genotyping system for genetic analysis of Chinese hamsters.","authors":"Minghe Sun, Yafang Guo, Zhengnan Ren, Ang Song, Jing Lu, Changlong Li, Jianyi Lv, Meng Guo, Xin Liu, Xiaoyan Du, Zhaoyang Chen, Guohua Song, Yan He, Zhenwen Chen, Xueyun Huo","doi":"10.1002/ame2.70006","DOIUrl":"https://doi.org/10.1002/ame2.70006","url":null,"abstract":"<p><p>Chinese hamster with Chinese characteristics is used in experiments, and it is of great value in the field of medical biology research. However, at present, there is no high-efficiency method for evaluating the genetic quality of Chinese hamsters. Here, we developed a novel Chinese hamster genetic quality detection system using single-nucleotide polymorphism (SNP) markers. To find SNP loci, we conducted whole genome sequencing on 24 Chinese hamsters. Then, we employed an SNP locus screening criterion that we set up previously and initially screened 214 SNP loci with wide genome distribution and high polymorphism level. Subsequently, we developed the SNP detection system using a multitarget region capture technique based on second-generation sequencing, and a 55 SNP panel for genetic evaluation of Chinese hamster populations was developed. PopGen.32. analysis results showed that the average effective allele number, Shannon index, observed heterozygosity, expected heterozygosity, average heterozygosity, polymorphism information, and other genetic parameters of Chinese hamster population A were higher than those in population B. Using scientific screening and optimization, we successfully developed a novel Chinese hamster SNP genetic detection system that can efficiently and accurately analyze the genetic quality of the Chinese hamster population.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The protective effects of melatonin against electromagnetic waves of cell phones in animal models: A systematic review.","authors":"Mohammad Amiri, Habibolah Khazaie, Masoud Mohammadi","doi":"10.1002/ame2.12552","DOIUrl":"https://doi.org/10.1002/ame2.12552","url":null,"abstract":"<p><strong>Background: </strong>Due to the widespread use of cell phone devices today, numerous research studies have focused on the adverse effects of electromagnetic radiation on human neuropsychological and reproductive systems. In most studies, oxidative stress has been identified as the primary pathophysiological mechanism underlying the harmful effects of electromagnetic waves. This paper aims to provide a holistic review of the protective effects of melatonin against cell phone-induced electromagnetic waves on various organs.</p><p><strong>Methods: </strong>This study is a systematic review of articles chosen by searching Google Scholar, PubMed, Embase, Scopus, Web of Science, and Science Direct using the keywords 'melatonin', 'cell phone radiation', and 'animal model'. The search focused on articles written in English, which were reviewed and evaluated. The PRISMA process was used to review the articles chosen for the study, and the JBI checklist was used to check the quality of the reviewed articles.</p><p><strong>Results: </strong>In the final review of 11 valid quality-checked articles, the effects of melatonin in the intervention group, the effects of electromagnetic waves in the case group, and the amount of melatonin in the chosen organ, i.e. brain, skin, eyes, testis and the kidney were thoroughly examined. The review showed that electromagnetic waves increase cellular anti-oxidative activity in different tissues such as the brain, the skin, the eyes, the testis, and the kidneys. Melatonin can considerably augment the anti-oxidative system of cells and protect tissues; these measurements were significantly increased in control groups. Electromagnetic waves can induce tissue atrophy and cell death in various organs including the brain and the skin and this effect was highly decreased by melatonin.</p><p><strong>Conclusion: </strong>Our review confirms that melatonin effectively protects the organs of animal models against electromagnetic waves. In light of this conclusion and the current world-wide use of melatonin, future studies should advance to the stages of human clinical trials. We also recommend that more research in the field of melatonin physiology is conducted in order to protect exposed cells from dying and that melatonin should be considered as a pharmaceutical option for treating the complications resulting from electromagnetic waves in humans.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of humanized mice in the safety experiments of antibody drugs.","authors":"Zhimin Sun, Mengyun Gu, Zixuan Yang, Lei Shi, Liyuan Zhao, Minhui Zheng, Yan Wang, Wei Zhang, Kexin Han, Naping Tang","doi":"10.1002/ame2.12562","DOIUrl":"https://doi.org/10.1002/ame2.12562","url":null,"abstract":"<p><p>Therapeutic antibodies are valued for their high specificity and selectivity in immunotherapy. However, the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safety using suitable animal models. In this context, we review the various categories and applications of humanized mice, which have been engrafted with human cells or tissues to mimic the human immune system. These models are extensively utilized in the nonclinical assessment and development of various antibody drugs, acting as a conduit to clinical research. However, several challenges remain, including the limited lifespan of humanized mice, inadequate engraftment of human cells, and the rudimentary nature of the immune environment in these models. The development of humanized immune system models in mice presents both opportunities and challenges, potentially leading to new insights into the evolution and application of antibody therapeutics.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of BCG vaccine-induced novel granulomatous liver injury preclinical animal model.","authors":"Swati Sharma, Abhishek Moudgil, Jyoti Grewal, Pankaj Khatri, Vishal Sharma, Madhumita Premkumar, Amanjit Bal, Dibyajyoti Banerjee, Amol N Patil","doi":"10.1002/ame2.12559","DOIUrl":"https://doi.org/10.1002/ame2.12559","url":null,"abstract":"<p><strong>Background: </strong>Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB (tuberculosis) and autoimmune granulomatous liver diseases. Antitubercular (ATT) and other drugs' metabolism in the presence of a specific type of liver injury is not well understood. The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG (Bacillus Calmette-Guérin) vaccine, further studying it in the presence of ATT dosing, and analyze the pharmacokinetics of isoniazid, rifampicin, and their respective primary metabolites.</p><p><strong>Methods: </strong>We used 56 rats in seven equal groups. Group I functioned as a normal control (NC) receiving normal saline only. Groups II-IV received intravenous injections of low-, medium-, and high-dose BCG vaccine daily for 21 days. Groups V, VI, and VII received isoniazid (H) alone, rifampicin (R) alone, and isoniazid + rifampicin(HR) for a subsequent 15 days in addition to high dose BCG for the first 21 days, respectively. Liver function tests (LFT) were monitored on days 0, 21, 28, and 36. Rats were sacrificed later for oxidative stress and histopathological examination.</p><p><strong>Results: </strong>The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21 (p < 0.05). Isoniazid, rifampicin, and combination intervention groups demonstrated normalization of the BCG-led LFT changes. Histology and oxidative stress parameters confirmed model development and biochemical changes. Isoniazid area under the curve (AUC) showed a reduction of 16.9% in BCG + HR group in comparison to the BCG + H group (p = 0.01). Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG + HR group in comparison to the BCG + R group (p = 0.001).</p><p><strong>Conclusion: </strong>A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying the optimal dose of cannabidiol by intrabuccal administration in Kramnik (C3HeB/FeJ) mice.","authors":"Oluwadara Pelumi Omotayo, Siyethemba Bhengu, Kobus Venter, Yolandy Lemmer, Shayne Mason","doi":"10.1002/ame2.12569","DOIUrl":"https://doi.org/10.1002/ame2.12569","url":null,"abstract":"<p><strong>Background: </strong>Cannabidiol (CBD) has numerous therapeutic properties, and is used to treat neurological conditions, such as neuroinflammation. However, the optimal dose of CBD to penetrate the brain requires further investigation. The primary aim of this study was to use a mouse model and the intrabuccal route for CBD administration to determine the optimal dose at which CBD can penetrate the brain. The secondary aim was to determine whether sex is a confounding factor.</p><p><strong>Methods: </strong>Thirty adult Kramnik mice, divided equally into three groups, were administered CBD oil intrabuccally at three doses-10, 20, and 30 mg/kg, euthanized 6 h later, and whole brain, urine, and blood samples were collected. Liquid chromatography with tandem mass spectrometry was used to analyze the collected samples.</p><p><strong>Results: </strong>CBD and its three metabolites-7-carboxy cannabidiol (7-COOH-CBD), 7-hydroxy cannabidiol (7-OH-CBD) and 6-hydroxy cannabidiol (6-OH-CBD), were identified and quantified in all samples. The 10 and 20 mg/kg doses of CBD produced similar results in the brain, but the group given the 10 mg/kg dose had the least variation. The 30 mg/kg dose yielded the highest abundance of CBD and its metabolites in all samples, but also the greatest variation. Sex only became a confounding factor at 30 mg/kg.</p><p><strong>Conclusions: </strong>This study shows that the intrabuccal route of CBD administration is reliable and the 10 mg/kg dose of CBD is recommended in mice because there were good CBD metabolite concentrations in all samples, with the least variation among the doses, and sex was not a confounder at 10 mg/kg.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Description of unilateral kidney embolism and contralateral nephrectomy as a less invasive remnant kidney model in cats; a proof-of-concept study.","authors":"Chad W Schmiedt, Bianca N Lourenço, Lauren E Markovic, Meghan Lancaster, Sanjeev Gumber, Juliane Wannemacher, Peter Florian, Amanda E Coleman","doi":"10.1002/ame2.70001","DOIUrl":"https://doi.org/10.1002/ame2.70001","url":null,"abstract":"<p><strong>Background: </strong>Refined models of kidney disease are critical to better understand disease processes and study novel treatments while minimizing discomfort in research animals. The objective of this study was to report a technique for minimally invasive partial kidney embolism in cats and describe outcomes following transcatheter administration of embolic microspheres with subsequent contralateral nephrectomy.</p><p><strong>Methods: </strong>Eleven, apparently healthy, male, purpose-bred cats underwent unilateral kidney embolism with 0.25 or 0.5 mL of embolic microparticle (40-120 μm) suspension (0.2 mL microspheres/mL) delivered into the right renal artery under fluoroscopic guidance, followed 5 months later by contralateral nephrectomy. One month after nephrectomy, blood and urinary markers of kidney function were evaluated, and embolized kidneys were harvested for histopathology evaluation.</p><p><strong>Results: </strong>Renal artery embolization was possible in all cats. Two cats did not complete the study, one after experiencing congestive heart failure (n = 1) and the other following evidence of complete kidney embolism precluding nephrectomy (n = 1) post-embolization. At study end, compared to baseline, cats had significant increases in median (range) serum creatinine (159.1 μmol/L [141.4-530.4] versus 128.2 μmol/L [92.8-150.3]; p = 0.0004), urea nitrogen (15.71 mmol/L [9.29-47.85] versus 7.50 mmol/L [6.07-8.57]; p < 0.0001), and symmetric dimethylarginine (0.74 μmol/L [0.59-3.12] versus 0.67 μmol/L [0.54-0.72]; p = 0.0288) concentrations. No differences in markers of kidney function were documented between dose groups.</p><p><strong>Conclusions: </strong>Minimally invasive kidney embolism is a promising technique for modeling kidney disease in cats. Understanding optimal dose, timing of nephrectomy, and longer-term consequences requires additional work.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new CRISPR-mediated Apc knockout allele leads to pyloric gland adenoma-like gastric polyps in mice with C57BL/6;FVB/N mixed background.","authors":"Sarp Uzun, Özge Özcan, Ayşenur Gök, Aynur Işık, Sinem Bakır, Ayşen Günel-Özcan, İlyas Onbaşılar, Aytekin Akyol","doi":"10.1002/ame2.70002","DOIUrl":"https://doi.org/10.1002/ame2.70002","url":null,"abstract":"<p><p>Adenomatous polyposis coli (APC) mutations are the most frequently identified genetic alteration in sporadic colorectal cancer (CRC) cases, and a myriad of genetically engineered Apc-mutant CRC mouse models have been developed using various genetic manipulation techniques. The advent of the CRISPR/Cas9 system has revolutionized the field of genetic engineering and facilitated the development of new genetically engineered mouse models. In this study, we aimed to develop a novel Apc knockout allele using the CRISPR/Cas9 system and evaluate the phenotypic effects of this new allele in two different mouse strains. For this purpose, exon 16 of mouse Apc gene was targeted with a single-guide RNA, and the mouse carrying an Apc frameshift mutation at codon 750 (Δ750) was chosen as the founder. The mutant FVB-Apc^Δ750 mice were backcrossed with wild-type C57BL/6 mice, and the phenotypic effects of the knockout allele were evaluated in F8-FVB-Apc^Δ750, F4-B6;FVB-Apc^Δ750, and F1-B6;FVB-Apc^Δ750 by a macroscopic and microscopic examination of the gastrointestinal system. The result showed that the mean polyp number was significantly higher in F4-BL6;FVB-Apc^Δ750 than in F8-FVB-Apc^Δ750. Intestinal polyposis was more prominent in F4-BL6;FVB-Apc^Δ750, whereas a higher number of colon polyps than intestinal polyps were observed in F8-FVB-Apc^Δ750. Additionally, F1-BL6;FVB-Apc^Δ750 mixed background mice developed gastric polyps that morphologically resembled the pyloric gland adenoma of humans. In conclusion, we developed a novel CRISPR-mediated Apc knockout allele using two mouse strains. We showed that this allele can exert a strain-specific effect on the phenotype of mice and can cause gastric polyp formation.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quorum quenching enzymes disrupt bacterial communication in a sex- and dose-dependent manner.","authors":"Aneesh Syal, Maria Martell, Rakesh Sikdar, Matthew Dietz, Zachary Ziegert, Cyrus Jahansouz, Mikael H Elias, Christopher Staley","doi":"10.1002/ame2.12520","DOIUrl":"https://doi.org/10.1002/ame2.12520","url":null,"abstract":"<p><strong>Background: </strong>Over the past 50 years, the incidence of obesity has gradually increased, necessitating investigation into the multifactorial contributors to this disease, including the gut microbiota. Bacteria within the human gut microbiome communicate using a density-dependent process known as quorum sensing (QS), in which autoinducer (AI) molecules (e.g., N-acyl-homoserine lactones [AHLs]) are produced to enable bacterial interactions and regulate gene expression.</p><p><strong>Methods: </strong>We aimed to disrupt QS using quorum quenching (QQ) lactonases GcL and SsoPox, which cleave AHL signaling molecules in a taxa-specific manner based on differing enzyme affinities for different substrates. We hypothesized that QQ hinders signals from obesity-associated pathobionts, thereby slowing or preventing obesity.</p><p><strong>Results: </strong>In a murine model of diet-induced obesity, we observed GcL and SsoPox treatments have separate sex-dependent and dose-dependent effects on intestinal community composition and diversity. Notably, male mice given 2 mg/mL SsoPox exhibited significant changes in the relative abundances of gram-negative taxa, including Porphyromonadaceae, Akkermansiaceae, Muribaculaceae, and Bacteroidales (Kruskal-Wallis p < 0.001). Additionally, we used covariance matrix network analysis to model bacterial taxa co-occurrence due to QQ enzyme administration. There were more associations among taxa in control mice, particularly among gram-negative bacteria, whereas mice receiving SsoPox had the fewest associations.</p><p><strong>Conclusions: </strong>Overall, our study establishes proof of concept that QQ is a targetable strategy for microbial control in vivo. Further characterization and dosage optimization of QQ enzymes are necessary to harness their therapeutic capability for the treatment of chronic microbial-associated diseases.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}