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Propranolol enhances the oncolytic effect of newcastle disease virus on canine mammary tumor cell by modulating the IFN-I-mediated JAK-STAT signaling pathway. 心得安通过调节ifn - i介导的JAK-STAT信号通路增强新城疫病毒对犬乳腺肿瘤细胞的溶瘤作用。
IF 5.2 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2026-12-31 Epub Date: 2026-03-22 DOI: 10.1080/01652176.2026.2648283
Yunjie Zhu, Muyao Xu, Meng Li

Canine mammary tumors (CMT), the most common neoplasms in intact female dogs, lack effective treatments for advanced cases. Newcastle disease virus (NDV), an oncolytic virus, kills tumor cells directly and stimulates antitumor immunity. However, NDV also activates Type I interferon (IFN-I) signaling, which restricts its replication via the JAK-STAT pathway. This study investigated whether propranolol, known to suppress antiviral responses, could enhance NDV's oncolytic effect in CMT. In vitro, using the CMT-U27 cell line, the combination reduced cell viability, migration, and invasion. Propranolol increased NDV replication and suppressed NDV-induced IFN-I release and JAK-STAT signaling pathway activation. In the CMT-U27 xenograft model, both NDV alone and the combination therapy prolonged the survival and suppressed tumor growth, with no significant difference between the two. However, the combination markedly enhanced intratumoral NDV replication by inhibiting IFN-I production and the JAK-STAT signalling pathway. These findings indicate that propranolol enhances NDV-mediated oncolysis in CMT by inhibiting the IFN-I/JAK-STAT pathway, increasing viral load, and represents a promising combined therapeutic strategy.

犬乳腺肿瘤(CMT),最常见的肿瘤在完整的雌性犬,缺乏有效的治疗晚期病例。新城疫病毒(NDV)是一种溶瘤病毒,能直接杀死肿瘤细胞并刺激抗肿瘤免疫。然而,NDV也激活I型干扰素(IFN-I)信号,通过JAK-STAT途径限制其复制。本研究探讨了已知能抑制抗病毒反应的心得安是否能增强NDV在CMT中的溶瘤作用。在体外,使用CMT-U27细胞系,该组合降低了细胞活力,迁移和侵袭。心得安可增加NDV复制,抑制NDV诱导的IFN-I释放和JAK-STAT信号通路激活。在CMT-U27异种移植模型中,NDV单独和联合治疗均能延长生存期,抑制肿瘤生长,两者无显著差异。然而,该组合通过抑制IFN-I的产生和JAK-STAT信号通路显著增强了肿瘤内NDV的复制。这些研究结果表明,心得安通过抑制IFN-I/JAK-STAT通路,增加病毒载量,增强ndv介导的CMT肿瘤溶解,是一种很有前景的联合治疗策略。
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引用次数: 0
Equine genital and ocular squamous cell carcinomas: clinical, histopathological, molecular and viral characterization with proposed histopathological classification system. 马生殖器和眼部鳞状细胞癌:临床,组织病理学,分子和病毒特征与提出的组织病理学分类系统。
IF 5.2 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2026-12-31 Epub Date: 2026-03-24 DOI: 10.1080/01652176.2026.2648939
Kevin O'Brien, Tim Mair, Hardeep S Mudhar, Patricia Pesavento, Henry Miller, Simon L Priestnall, Alejandro Suárez-Bonnet

Equine squamous cell carcinomas (eSCCs) are common, and a proportion are likely induced by Equus caballus papillomavirus 2 (EcPV-2). Accurate prediction of clinical outcomes is challenging with no recognized prognostic criteria or consistent histopathological classification scheme for eSCC. The aims of this study were to histopathologically subtype a large case series of eSCCs (genital and ocular) and correlate them with p16 and HER-2 expression, equine papillomavirus infection status, and various clinical and histopathological parameters to predict tumour behavior and prognosis. One hundred and eighty-five samples were examined and subtyped histologically. HER-2 and p16 immunohistochemistry (IHC) and in situ hybridization (ISH) for the EcPV-2 E6/E7 oncogenes were performed on a subset of cases, and follow-up survival data were analyzed. The results were compared and correlated with published guidelines on the categorization of human SCC. Six histopathological subtypes of SCC, according to the WHO, were identified for the first time in horses: usual/invasive (most common), verrucous, pseudoglandular, papillary, warty, and basaloid, with different histological subtypes demonstrating prognostic significance. HER-2 and EcPV-2 statuses were not associated with prognosis in horses with SCC. p16 expression is not associated with EcPV-2 status but could be a potential prognostic factor. ISH demonstrated EcPV-2 genetic material in the majority of eSCCs, except for the papillary subtype, which includes mature, not just pre-cancerous, eSCCs. Widespread HER-2 expression in eSCCs could suggest a role for this cell receptor as a potential therapeutic target.

马鳞状细胞癌(eSCCs)很常见,其中一部分可能是由马尾乳头状瘤病毒2 (EcPV-2)诱导的。由于没有公认的预后标准或一致的eSCC组织病理学分类方案,准确预测临床结果具有挑战性。本研究的目的是对大量escc病例(生殖器和眼部)进行组织病理学分型,并将其与p16和HER-2表达、马乳头瘤病毒感染状态以及各种临床和组织病理学参数相关联,以预测肿瘤行为和预后。对185个样本进行了检查和组织学分型。对一部分病例进行HER-2和p16免疫组化(IHC)和原位杂交(ISH)检测EcPV-2 E6/E7癌基因,并对随访生存数据进行分析。结果与已发表的人类SCC分类指南进行了比较和关联。根据世界卫生组织,首次在马身上发现了六种SCC的组织病理学亚型:通常/侵袭性(最常见)、疣状、假腺状、乳头状、疣状和基底样,不同的组织病理学亚型显示出预后意义。HER-2和EcPV-2状态与SCC马的预后无关。p16表达与EcPV-2状态无关,但可能是一个潜在的预后因素。ISH在大多数escc中发现了EcPV-2遗传物质,除了乳头状亚型,包括成熟的escc,而不仅仅是癌前escc。HER-2在escc中的广泛表达可能表明这种细胞受体作为潜在的治疗靶点的作用。
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引用次数: 0
Prognostic relevance of short-term changes in body weight, renal indices, and echocardiographic variables after intravenous diuretic therapy in dogs with myxomatous mitral valve disease hospitalized for pulmonary edema. 因肺水肿住院的二尖瓣黏液瘤病犬在静脉利尿剂治疗后体重、肾脏指数和超声心动图变量的短期变化与预后的相关性
IF 5.2 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2026-12-31 Epub Date: 2026-03-24 DOI: 10.1080/01652176.2026.2648250
Sin-Wook Park, Kyung-Ho You, Keon Kim, Woong-Bin Ro, Chang-Min Lee

Congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD) is managed with diuretics, yet the prognostic value of short-term hemodynamic responses remains unclear. This retrospective study evaluated 50 dogs with ACVIM stage C or D MMVD hospitalized for CHF. We assessed changes in body weight, echocardiographic parameters, and renal values before and after intravenous (IV) diuretic therapy to determine their association with survival. IV diuretic therapy led to significant reductions in body weight and echocardiographic indices, including the left atrium-to-aortic root ratio (LA/Ao), normalized left ventricular internal diameter in diastole (LVIDDN), and early diastolic transmitral flow velocity (all P < 0.005). Conversely, blood urea nitrogen and creatinine concentrations significantly increased (P < 0.001). However, neither short-term changes in these variables nor post-treatment values were associated with long-term survival. Baseline LA/Ao and LVIDDN were related to survival in univariable analysis, while prior oral diuretic therapy was the only independent predictor in the multivariable model (Hazard Ratio 4.21; P < 0.001). Dogs with prior diuretic use had shorter median survival (194 days) than those without (459 days). Thus, short-term echocardiographic improvements reflect effective decongestion rather than long-term prognosis. Prognostic evaluation should prioritize baseline assessments and treatment history.

二尖瓣黏液瘤病(MMVD)继发的充血性心力衰竭(CHF)采用利尿剂治疗,但短期血流动力学反应的预后价值尚不清楚。本回顾性研究评估了50只因CHF住院的ACVIM C期或D期MMVD犬。我们评估了患者在静脉(IV)利尿剂治疗前后体重、超声心动图参数和肾脏值的变化,以确定它们与生存的关系。静脉利尿剂治疗导致体重和超声心动图指标显著降低,包括左心房与主动脉根比(LA/Ao)、舒张期正常化左室内径(LVIDDN)和舒张期早期透射血流速度(均P P P P
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引用次数: 0
Perfect diagnostic agreement between canine- and feline-specific parvovirus PoC antigen kits in feline panleukopenia. 犬和猫特异性细小病毒PoC抗原试剂盒对猫泛白细胞减少症的诊断完全一致。
IF 5.2 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2026-12-01 Epub Date: 2025-12-22 DOI: 10.1080/01652176.2025.2604234
Mahmoud S Safwat, Manar M Farouk, Ahmad Zaki Anwer, M E Ali, Nehal M Shahen, Dina A Abdelwahed, Rabab T Hassanien, Ahmed F Afify, M H Ali, Samah Eid, Othman N O Mansour, Mary A N Sargious, Mohamed I Abdallah, Reham Karam, Samah El-Sayed M

Timely diagnosis is essential for managing feline panleukopenia (FPL), a devastating disease of cats caused by feline parvovirus (FPV) or canine parvovirus variants (CPV-2a, -2b, -2c). To support swift clinical decisions, point-of-care (PoC) antigen kits offer frontline tools. Given their cost and availability advantages, CPV-specific kits are often used off-label in cats; however, their interchangeability with manufacturer-matched FPV-specific kits remains unverified. This study assessed the diagnostic agreement between paired canine- and feline-specific PoC parvovirus antigen tests from two manufacturers. Fifty cats (30 with acute gastroenteritis, 20 healthy) were tested using all test formats. All cats underwent PCR and sequencing for parvovirus typing. Tests from the same manufacturer showed near-perfect or perfect agreement for result interpretation (Cohen's κ: 0.919 and 1.000). This strong inter-kit concordance also extended to test line intensity (κ = 0.908 and 1.000). Antigen-positive results were limited to diseased cats, mirroring the distribution of PCR positives. The latter included all the 30 cases, and were typed by sequencing as follows: 28 FPV, 1 CPV-2a, and 1 CPV-2c. All kit types detected FPV and CPV variants, and agreement within each manufacturer's paired kits was consistent across detected viral types. This preliminary evidence suggests that for two manufacturers, CPV antigen tests were non-inferior to their FPV counterparts, supporting flexible, cost-effective FPL diagnosis in cats, regardless of implicated parvovirus types.

猫泛白细胞减少症(FPL)是由猫细小病毒(FPV)或犬细小病毒变体(CPV-2a, -2b, -2c)引起的猫的一种毁灭性疾病,及时诊断对于治疗猫泛白细胞减少症(FPL)至关重要。为了支持快速的临床决策,即时抗原试剂盒提供了一线工具。鉴于其成本和可用性优势,cpv特异性试剂盒通常在标签外用于猫;然而,它们与制造商匹配的fpv特定套件的互换性仍未得到验证。本研究评估了来自两家制造商的犬和猫特异性PoC细小病毒抗原配对检测之间的诊断一致性。50只猫(30只患有急性胃肠炎,20只健康)采用所有测试形式进行测试。对所有猫进行PCR和细小病毒分型测序。来自同一制造商的测试显示结果解释接近完美或完美一致(科恩κ: 0.919和1.000)。这种强烈的试剂盒间一致性也扩展到测试系强度(κ = 0.908和1.000)。抗原阳性结果仅限于病猫,反映了PCR阳性的分布。后者包括所有30例病例,通过测序分型如下:28例FPV, 1例CPV-2a和1例CPV-2c。所有试剂盒类型检测到FPV和CPV变体,并且每个制造商配对试剂盒的一致性在检测到的病毒类型中是一致的。这一初步证据表明,对于两家制造商来说,CPV抗原检测并不亚于FPV检测,支持灵活、具有成本效益的猫FPL诊断,无论涉及的细小病毒类型如何。
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引用次数: 0
CMLPS-N1: a novel preclinical cell line model for canine mammary tumor and its application in therapeutic screening. CMLPS-N1:一种新的犬乳腺肿瘤临床前细胞系模型及其在治疗筛选中的应用
IF 5.2 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2026-12-01 Epub Date: 2026-01-10 DOI: 10.1080/01652176.2026.2614697
Xiao Wang, Han Zhou, Qian Zhang, Yihan Liu, Lixin He, Wenxuan Li, Bin Ma, Lihong Luo, Lijun Guo, Changwei Qiu

Canine mammary tumor is the most common tumor in intact female dogs and poses a growing health burden due to its high malignancy rate and increasing canine populations. However, research on sarcomatous subtypes has been hindered by a lack of representative cell lines. Here, we successfully established a novel canine mammary liposarcoma cell line, designated CMLPS-N1, which represents the first such model derived from a spontaneous tumor. This cell line has been stably maintained for over 80 passages and exhibits an abnormal karyotype, high proliferative and migratory capacity, and strong tumorigenicity in mouse xenografts. Molecular profiling confirmed a phenotype consistent with liposarcoma (MDM2+) and mesenchymal origin (Vimentin+/N-cadherin+), alongside high-risk markers (p53+/Ki67+/Notch1), and hormone receptor expression (ER/PR), while being negative for epithelial (PCK) and HER-2 markers. We used functional assays, including cell proliferation, colony formation, wound healing, and transwell invasion, to confirm its aggressive phenotype. Furthermore, cytotoxicity testing with four chemotherapy agents further supports its utility as a preclinical model for therapeutic screening and mechanistic research. The establishment of CMLPS-N1 enriches the canine mammary tumor cell line repository and provides a valuable experimental model for studying disease mechanisms, developing therapies, and facilitating translational applications.

犬乳腺肿瘤是完整母犬中最常见的肿瘤,由于其高恶性率和犬群的增加,造成了越来越大的健康负担。然而,对肉瘤亚型的研究一直受到缺乏代表性细胞系的阻碍。在这里,我们成功地建立了一个新的犬乳腺脂肪肉瘤细胞系,命名为CMLPS-N1,这是第一个从自发肿瘤中衍生的这种模型。该细胞系在小鼠异种移植物中表现出异常核型、高增殖和高迁移能力和强致瘤性,已稳定维持了80多代。分子分析证实了表型与脂肪肉瘤(MDM2+)和间质起源(Vimentin+/N-cadherin+)一致,以及高风险标志物(p53+/Ki67+/Notch1)和激素受体表达(ER/PR),而上皮(PCK)和HER-2标志物呈阴性。我们使用功能分析,包括细胞增殖、菌落形成、伤口愈合和跨井侵袭,来确认其侵袭性表型。此外,四种化疗药物的细胞毒性测试进一步支持其作为治疗筛选和机制研究的临床前模型的效用。CMLPS-N1的建立丰富了犬乳腺肿瘤细胞系库,为研究疾病机制、开发治疗方法和促进转化应用提供了有价值的实验模型。
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引用次数: 0
Machine learning-assisted screening for canine Cushing's syndrome. 机器学习辅助犬库欣综合征筛查。
IF 5.2 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2026-12-01 Epub Date: 2025-12-22 DOI: 10.1080/01652176.2025.2604643
Young-Jae Yoo, Kyungchang Jeong, Hanbit Seo, Ha-Suk Nam, Yeon Chae, Taesik Yun, Byung-Teck Kang, Euijong Lee, Hakhyun Kim

Cushing's syndrome (CS) is a common endocrine disorder in dogs that can significantly impair their quality of life. Diagnosis is often challenging because of its variable clinical presentation, making it difficult to identify suitable candidates for further diagnostic tests. This study employed machine learning algorithms to assist in CS diagnosis using routinely available screening diagnostics, including complete blood count, serum chemistry panel, and urinalysis parameters such as urine specific gravity and urine protein-to-creatinine ratio. Data were collected from 153 control dogs initially suspected of CS but later excluded and 152 dogs with confirmed CS. A boosted tree algorithm (gradient boosting) was trained on 80% of the collected data, with the remaining 20% reserved for testing. The developed model demonstrated an accuracy of 88.5% [95% confidence interval (CI): 80.5-96.5%], a sensitivity of 83.3% (95% CI: 70.7-96.7%), a specificity of 93.5% (95% CI: 84.9-100%), and an area under the receiver operating characteristic curve of 0.912 (95% CI: 0.835-0.988), indicating excellent discriminatory ability. A user-friendly graphical interface was also developed to facilitate clinical implementation, potentially improving diagnostic efficiency and owner satisfaction.

库欣综合征(CS)是一种常见的狗内分泌紊乱,会严重影响它们的生活质量。诊断往往具有挑战性,因为它的临床表现多变,使得难以确定合适的候选人进行进一步的诊断测试。本研究采用机器学习算法辅助CS诊断,使用常规筛查诊断,包括全血细胞计数、血清化学检查和尿液分析参数,如尿比重和尿蛋白与肌酐比。收集了153只最初怀疑患有CS但后来被排除的对照犬和152只确诊患有CS的犬的数据。在80%的收集数据上训练增强树算法(梯度增强),剩下的20%用于测试。该模型准确率为88.5%[95%置信区间(CI): 80.5 ~ 96.5%],灵敏度为83.3% (95% CI: 70.7 ~ 96.7%),特异性为93.5% (95% CI: 84.9 ~ 100%),受试者工作特征曲线下面积为0.912 (95% CI: 0.835 ~ 0.988),具有良好的鉴别能力。还开发了一个用户友好的图形界面,以促进临床实施,潜在地提高诊断效率和业主满意度。
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引用次数: 0
A bivalent subunit bovine herpesvirus 1 vaccine based on the ectodomains of glycoproteins D and B elicits robust protective immunity against infection in a rabbit model. 一种基于糖蛋白D和B外结构域的二价亚单位牛疱疹病毒1疫苗在兔模型中引起了对感染的强大保护性免疫。
IF 5.2 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2026-12-01 Epub Date: 2026-01-05 DOI: 10.1080/01652176.2025.2607414
Wenxiao Liu, Chun Yang, Jijing Tian, Jing Cheng, Linyi Zhou, Munir Iqbal, Arslan Mehboob, Rebecca Daines, Sui Zhang, Mengjiao Chen, Xiaoying Wang, Yongqing Li

Bovine alphaherpesvirus 1 (BoHV-1) is the causative agent of infectious bovine rhinotracheitis and reproductive disorders causing significant economic losses in the cattle industry. Both BoHV-1 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and desirable antigens for subunit vaccine. In this study, a bivalent subunit vaccine was generated based on the ectodomain of gD and gB expressed by baculoviruses system. Compared with the inactivated vaccine, the bivalent subunit vaccine induced higher neutralizing antibody levels against both the BoHV-1 reference strain and the virulent BoHV-1 field strain. Following intranasally challenge with BoHV-1 J2303, the clinical signs and virus excretion were significantly reduced in rabbits vaccinated with this subunit vaccine whereas severe clinical symptoms appeared in the non-vaccinated rabbits, indicating that the bivalent subunit vaccine provides complete protection against virulent BoHV-1 infection. Considering that the respiratory symptoms caused by J2303 in rabbits is highly similar and even identical to those of cattle, our findings suggest that the bivalent subunit vaccine based on combination of gD with gB protein have promising application to BoHV-1control programs.

牛甲疱疹病毒1 (BoHV-1)是传染性牛鼻气管炎和生殖障碍的病原体,给养牛业造成重大经济损失。BoHV-1糖蛋白B (gB)和D (gD)都是中和抗体和亚单位疫苗所需抗原的靶标。本研究利用杆状病毒系统表达的gD和gB的外结构域制备了二价亚单位疫苗。与灭活疫苗相比,二价亚单位疫苗对BoHV-1参比株和BoHV-1毒株均产生较高的中和抗体水平。经鼻内攻毒BoHV-1 J2303后,接种该亚单位疫苗的家兔临床症状和病毒排泄量显著减少,而未接种该亚单位疫苗的家兔出现严重的临床症状,表明二价亚单位疫苗可完全保护家兔免受BoHV-1强毒感染。考虑到J2303引起家兔的呼吸道症状与牛的呼吸道症状高度相似,甚至完全相同,我们的研究结果表明,基于gD与gB蛋白联合的二价亚单位疫苗在bohv -1控制方案中具有良好的应用前景。
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引用次数: 0
Animal biosecurity framework development, implementation and evaluation in a veterinary education establishment. 兽医教育机构动物生物安全框架的开发、实施和评估。
IF 5.2 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2026-12-01 Epub Date: 2026-02-05 DOI: 10.1080/01652176.2026.2626257
Claude Saegerman, Constance Wielick, Véronique Renault, Priscilla Burnotte, Christine Grignet, Laurent Leinartz, Maxime Harmegnies, Sophie Tasnier, Christiaen Remy, Calixte Bayrou, Nicolas Ochelen, Tatiana Art, Pierre Lekeux, Jason W Stull, Marie-France Humblet

Over the last decades, biosecurity has received increasing attention in veterinary medicine and was recently integrated as a competency for One Health field epidemiology framework by international bodies. It is also a standard in the European System of Evaluation of Veterinary Training and in the accreditation of veterinary colleges by the American Veterinary Medical Association Council on Education. To help veterinary students and staff acquire biosecurity skills within veterinary education establishments, we first develop animal biosecurity research, and we spread its results through four interconnected instruments: biosecurity standard operating policies and procedures, a dedicated biosecurity website, an annual biosecurity day, and the production of checklists to assess the biosecurity level of compliance. The use of biosecurity standard operating procedures, the number of visits on the faculty biosecurity website, the number of people trained, and regular biosecurity audits performed are all factors that have contributed to the animal biosecurity to comply with the requirements of the European Association of Establishments for Veterinary Education and by the Council on Outcomes-based Veterinary Education, in the CBVE 2.0 book published by the American Association of Veterinary Medical Colleges. These approaches also contribute to the acquisition and maintenance of the accreditation delivered by the ad hoc bodies. The participation of students in the process allows a better comprehension and appropriation of animal biosecurity.

在过去的几十年里,生物安全在兽医学领域受到越来越多的关注,最近被国际机构纳入“一个健康领域流行病学框架”的一项能力。它也是欧洲兽医培训评估体系和美国兽医医学协会教育委员会对兽医学院的认证标准。为了帮助兽医学生和工作人员在兽医教育机构中获得生物安全技能,我们首先开展动物生物安全研究,并通过四个相互关联的工具传播其成果:生物安全标准操作政策和程序,专门的生物安全网站,年度生物安全日,以及制作检查清单以评估生物安全合规水平。生物安全标准操作程序的使用、教师生物安全网站的访问次数、受过培训的人数以及定期进行的生物安全审计都是促进动物生物安全符合欧洲兽医教育机构协会和基于结果的兽医教育委员会(美国兽医学院协会出版的CBVE 2.0书)要求的因素。这些办法也有助于取得和维持特设机构所提供的认证。学生在这个过程中的参与可以更好地理解和利用动物生物安全。
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引用次数: 0
Microbiota-bile acid-host axis dysregulation drives enteropathogenesis in Escherichia coli K99-induced neonatal calf diarrhea. 微生物-胆汁酸-宿主轴失调驱动大肠杆菌k99诱导的新生儿小牛腹泻的肠病发生。
IF 5.2 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2026-12-01 Epub Date: 2026-01-30 DOI: 10.1080/01652176.2026.2617460
Haihui Gao, Xiaodong Kang, Zhijie Liu, Yuqiong Li, Libing Bai, Kangkang Guo, Meizhou Huang

Neonatal calf diarrhea caused by Escherichia coli K99 remains a critical challenge in livestock health, yet its precise pathogenic mechanisms are poorly defined. In this study, we identify bile acid (BA) metabolic dysregulation as a key pathogenic mechanism in E. coli K99-induced diarrhea. Using a neonatal calf infection model integrated with multi-omics profiling (including 16S rRNA sequencing, untargeted metabolomics, and targeted bile acid metabolomics), we demonstrate that E. coli K99 infection leads to significant disruption of the gut microbiota, compromises intestinal barrier integrity, and causes region-specific alterations in BA receptor signaling pathways (including FXR, TGR5, RAR, and ABST). Targeted metabolomic analysis revealed the accumulation of toxic primary and secondary BAs, driven by microbial shifts favoring BA-transforming pathogens and depleting BA-sensitive commensals. This microbial dysbiosis-BA imbalance-receptor dysfunction axis provokes immune activation, metabolic disturbances, and epithelial damage. Our study is the first to establish a mechanistic link between E. coli K99 infection and intestinal dysfunction via a microbiota-bile acid-host signaling cascade. These findings uncover a previously unrecognized pathophysiological pathway in bacterial diarrhea and suggest that modulation of gut microbiota and bile acid metabolism represents a promising therapeutic strategy for managing enteric infections in veterinary and potentially human medicine.

由大肠杆菌K99引起的新生儿小牛腹泻仍然是家畜健康的一个重大挑战,但其确切的致病机制尚不清楚。在这项研究中,我们确定胆汁酸(BA)代谢失调是大肠杆菌k99诱导腹泻的关键致病机制。利用结合多组学分析(包括16S rRNA测序、非靶向代谢组学和靶向胆汁酸代谢组学)的新生小牛感染模型,我们证明大肠杆菌K99感染会导致肠道微生物群的显著破坏,损害肠道屏障的完整性,并导致BA受体信号通路(包括FXR、TGR5、RAR和ABST)的区域特异性改变。有针对性的代谢组学分析显示,在有利于转化ba的病原体和消耗ba敏感共生菌的微生物转变的驱动下,有毒的初级和次级ba积累。这种微生物生态失调- ba失衡-受体功能障碍轴引起免疫激活、代谢紊乱和上皮损伤。我们的研究首次通过微生物-胆汁酸-宿主信号级联建立了大肠杆菌K99感染与肠道功能障碍之间的机制联系。这些发现揭示了细菌性腹泻中以前未被认识的病理生理途径,并表明肠道微生物群和胆汁酸代谢的调节代表了兽医和潜在的人类医学中管理肠道感染的有前途的治疗策略。
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引用次数: 0
Fisetin alleviates lipopolysaccharide-induced mastitis by inhibiting ferroptosis and modulating the gut microbiota. 非西汀通过抑制铁下垂和调节肠道微生物群来减轻脂多糖诱导的乳腺炎。
IF 5.2 2区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2026-12-01 Epub Date: 2026-03-17 DOI: 10.1080/01652176.2026.2642789
Chao Tong, Li Wang, Haojie Wen, Xinhui Yao, Jiang Tong, Ruya Zhang, Xiao Li, Yuqiang Xiang, Xuebing Wang

Bovine mastitis poses an enormous challenge to the dairy industry. At present, dependence on antibiotic therapy has led to problems such as antibiotic-resistant bacteria and drug residues. Therefore, it is very important to seek alternative therapies for the treatment of bovine mastitis. Fisetin (FIS) with antioxidant and anti-inflammatory properties is found in various fruits and vegetables, although its regulatory role in mastitis treatment remains unclear. In the present study, we employed lipopolysaccharide (LPS)-induced cellular and animal mastitis models to investigate the regulatory effects of FIS on oxidative stress and ferroptosis pathways in mastitis treatment, utilizing techniques such as western blot, quantitative real-time PCR (qRT-PCR), immunofluorescence, hematoxylin-eosin (HE) staining, ROS, MDA, SOD, T-AOC, tissue total iron content analysis, mouse gut microbiota sequencing, and untargeted metabolomics. The results demonstrated that FIS modulates oxidative stress and ferroptosis pathways, leading to a reduction in intracellular and mouse mammary tissue inflammatory cytokines level. Furthermore, FIS treatment altered the gut microbiota structure and metabolites in LPS-induced mice, increasing short-chain fatty acid (SCFA) levels, which contributed to the restoration of the blood-milk barrier and alleviation of mastitis. This study could lead to novel therapeutic strategies for bovine mastitis based on traditional Chinese medicine.

牛乳腺炎对乳制品行业构成了巨大的挑战。目前,对抗生素治疗的依赖导致了耐药菌和药物残留等问题。因此,寻找治疗牛乳腺炎的替代疗法是非常重要的。具有抗氧化和抗炎特性的非瑟酮(FIS)存在于各种水果和蔬菜中,尽管其在乳腺炎治疗中的调节作用尚不清楚。在本研究中,我们采用脂多糖(LPS)诱导的细胞和动物乳腺炎模型,利用western blot、定量实时PCR (qRT-PCR)、免疫荧光、苏木精-伊红(HE)染色、ROS、MDA、SOD、T-AOC、组织总铁含量分析、小鼠肠道微生物群测序和非靶向代谢组学等技术,研究FIS对乳腺炎治疗中氧化应激和铁上垂通路的调节作用。结果表明,FIS调节氧化应激和铁下垂途径,导致细胞内和小鼠乳腺组织炎症细胞因子水平降低。此外,FIS治疗改变了lps诱导小鼠的肠道微生物群结构和代谢物,增加了短链脂肪酸(SCFA)水平,这有助于恢复血乳屏障和减轻乳腺炎。本研究为牛乳腺炎的中药治疗提供了新的思路。
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Veterinary Quarterly
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