{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:19:57Z","timestamp":1780391997786,"version":"3.54.1"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      is a prominent pathogen capable of causing systemic infections and multi-organ damage, primarily driven by its high virulence and induction of oxidative stress. This study evaluated the therapeutic efficacy of tiamulin alone and in combination with bromhexine in a canine model of systemic\n                      <jats:italic>S. aureus<\/jats:italic>\n                      infection, focusing on oxidative stress biomarkers, bacterial burden, tissue histopathology, and the expression of cardiac and bacterial virulence-related genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Experimental infection was induced in dogs, except for a healthy control group. Animals were assigned to five groups: uninfected control, infected untreated, tiamulin-treated, bromhexine-treated, and tiamulin plus bromhexine-treated. Oxidative stress was assessed through measurements of malondialdehyde (MDA) and total antioxidant capacity (TAC) in cardiac, hepatic, and renal tissues. Bacterial load was quantified, and minimum inhibitory concentrations (MICs) of the treatments were determined. Quantitative PCR was performed to evaluate the expression of\n                      <jats:italic>S. aureus<\/jats:italic>\n                      virulence genes including\n                      <jats:italic>hla<\/jats:italic>\n                      (alpha-hemolysin),\n                      <jats:italic>ebpS<\/jats:italic>\n                      (extracellular matrix-binding protein S), and\n                      <jats:italic>icaA<\/jats:italic>\n                      (intercellular adhesion A). Histopathological analyses of heart, liver, and kidney tissues were conducted, and hematological and biochemical parameters (total protein, albumin, and globulin) were measured. Cardiac injury markers, cytochrome P450 1B1 (\n                      <jats:italic>CYP1B1<\/jats:italic>\n                      ) and interleukin-1 beta (\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      ), were also assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Infected untreated animals exhibited significantly elevated MDA, decreased TAC, high bacterial loads, severe histopathological alterations, and upregulated expression of\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      and\n                      <jats:italic>CYP1B1<\/jats:italic>\n                      . Tiamulin monotherapy produced moderate reductions in oxidative stress and bacterial burden. The combination of tiamulin and bromhexine resulted in a significant reduction in MDA, restoration of TAC, lower MIC values, suppressed expression of virulence genes (p &amp;lt; 0.05), and near-normal tissue architecture. Cardiac gene expression analysis showed substantial downregulation of\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      and\n                      <jats:italic>CYP1B1<\/jats:italic>\n                      in the combination-treated group, indicating alleviation of inflammation and cardiac injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      The combination therapy of tiamulin and bromhexine exhibited superior protective effects against\n                      <jats:italic>S. aureus<\/jats:italic>\n                      infection compared to monotherapy or untreated infection. These benefits appear to be mediated through synergistic antimicrobial, anti-virulence, and antioxidant mechanisms. The findings support the potential of this therapeutic approach for managing drug-resistant\n                      <jats:italic>S. aureus<\/jats:italic>\n                      infections and justify further clinical investigation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1679854","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:44:45Z","timestamp":1766040285000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Bromhexine hydrochloride enhances the therapeutic efficacy of tiamulin against experimental Staphylococcus aureus infection in dogs: targeting bacterial virulence, boosting antioxidant defense, and improving histopathology"],"prefix":"10.3389","volume":"16","author":[{"given":"Hanem F.","family":"El-Gendy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimaa R.","family":"Masoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagwa I.","family":"Sheraiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimaa S.","family":"Elnahriry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa A.","family":"Madkour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reda M. S.","family":"Korany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazim O.","family":"Khalifa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanaa Y.","family":"Elnagar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"734","DOI":"10.3390\/micro4040045","article-title":"Preparation and characterization of tiamulin-loaded niosomes for oral bioavailability enhancement in Mycoplasma-infected broilers","volume":"4","author":"Abonashey","year":"2024","journal-title":"Micro"},{"key":"B2","doi-asserted-by":"publisher","first-page":"122909","DOI":"10.1016\/j.lfs.2024.122909","article-title":"Beyond the lungs: exploring diverse applications of bromhexine and ambroxol","volume":"353","author":"Ahmadi","year":"2024","journal-title":"Life Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"924","DOI":"10.3967\/bes2015.128","article-title":"Seafood as a reservoir of Gram-negative bacteria carrying integrons and antimicrobial resistance genes in Japan","volume":"28","author":"Ahmed","year":"2015","journal-title":"Biomed. Environ. Sci."},{"key":"B4","first-page":"83","article-title":"Use of bromhexine in the management of respiratory diseases in chickens","volume":"4","author":"Ali","year":"2019","journal-title":"PSM Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"104","DOI":"10.15283\/ijsc.2012.5.2.104","article-title":"Adipose stem cells as alternatives for bone marrow mesenchymal stem cells in oral ulcer healing","volume":"5","author":"Aly","year":"2012","journal-title":"Int. J. Stem Cells"},{"key":"B6","doi-asserted-by":"publisher","first-page":"209","DOI":"10.34172\/bi.2020.27","article-title":"Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: a randomized clinical trial","volume":"10","author":"Ansarin","year":"2020","journal-title":"Bioimpacts"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.3390\/life14121658","article-title":"Histological findings in infective endocarditis\u2014A retrospective cohort study conducted at \u201cDr. Carol Davila\u201d Central Military Emergency University Hospital in Bucharest","volume":"14","author":"Anton","year":"2024","journal-title":"Life"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.14202\/vetworld.2021.1354-1362","article-title":"Biochemical and histopathological changes related to the topical application of Aloe vera ointment for canine pyoderma","volume":"14","author":"Arbaga","year":"2021","journal-title":"Veterinary World"},{"key":"B9","article-title":"Creatine phosphokinase","volume-title":"StatPearlsNatl. Libr. Med.","author":"Aujla","year":"2022"},{"key":"B10","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/s41598-024-83156-2","article-title":"Comparison of oxidative stress status in the kidney tissue of male rats treated with paraquat and nanoparaquat","volume":"15","author":"Bahramibanan","year":"2025","journal-title":"Sci. Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"115183","DOI":"10.1016\/j.biopha.2023.115183","article-title":"Sepsis-mediated renal dysfunction: pathophysiology, biomarkers and role of phytoconstituents in its management","volume":"165","author":"Balkrishna","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B12","volume-title":"Theory and practice of histological techniques","author":"Bancroft","year":"2008"},{"key":"B13","doi-asserted-by":"publisher","first-page":"390","DOI":"10.3390\/toxics13050390","article-title":"What do we know about Staphylococcus aureus and oxidative stress? Resistance, virulence, new targets, and therapeutic alternatives","volume":"13","author":"Bastos","year":"2025","journal-title":"Toxics"},{"key":"B14","volume-title":"Bromhexine: a comprehensive review","author":"Bhagat","year":"2018"},{"key":"B15","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1590\/S1517-83822009000200009","article-title":"Detection of methicillin resistance and slime factor production of Staphylococcus aureus in bovine mastitis","volume":"40","author":"Ciftci","year":"2009","journal-title":"Braz. J. Microbiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"5979","DOI":"10.3390\/molecules28165979","article-title":"Malondialdehyde as a potential oxidative stress marker for allergy-oriented diseases: an update","volume":"28","author":"Cordiano","year":"2023","journal-title":"Molecules"},{"key":"B17","doi-asserted-by":"publisher","first-page":"101584","DOI":"10.1016\/j.pdpdt.2019.101584","article-title":"Presence of biofilm and adhesin genes in Staphylococcus aureus strains taken from chronic wound infections and their genotypic and phenotypic antimicrobial sensitivity patterns","volume":"29","author":"Demir","year":"2020","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"B18","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1080\/17425255.2019.1578748","article-title":"Enhancement of lung levels of antibiotics by ambroxol and bromhexine","volume":"15","author":"Deretic","year":"2019","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1124\/jpet.103.058057","article-title":"Cardiovascular pharmacology of estradiol metabolites","volume":"308","author":"Dubey","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s00580-022-03371-z","article-title":"Trial for decreasing ifosfamide-induced hematological toxicity, oxidative stress, inflammation, and hepatotoxicity by beetroot extract in male albino rats","volume":"31","author":"El-Gendy","year":"2022","journal-title":"Comp. Clin. Pathol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"885","DOI":"10.3390\/ph17070885","article-title":"Unraveling the potential of Saccharum officinarum and Chlorella vulgaris towards 5-fluorouracil-induced nephrotoxicity in rats","volume":"17","author":"El-Gendy","year":"","journal-title":"Pharmaceuticals"},{"key":"B22","doi-asserted-by":"publisher","first-page":"74","DOI":"10.5455\/ajvs.18F6051","article-title":"Enhancement of the efficacy of Tylvalosin by administration with eucalyptus oil or bromhexine against Mycoplasma gallisepticum-infected broiler chickens","volume":"81","author":"El-Gendy","year":"","journal-title":"AJVS"},{"key":"B23","doi-asserted-by":"publisher","first-page":"12722","DOI":"10.1038\/s41598-019-48657-5","article-title":"Antimicrobial action of autologous platelet-rich plasma on MRSA-infected skin wounds in dogs","volume":"9","author":"Farghali","year":"2019","journal-title":"Sci. Rep."},{"key":"B24","article-title":"Study on the hemolysin phenotype and the genotype distribution of Staphylococcus aureus causing bovine mastitis in Shandong dairy farms","volume":"9","author":"Fei","year":"2011","journal-title":"Intern J. Appl. Res. Vet. Med."},{"key":"B25","first-page":"72","article-title":"Toxicity studies in rats fed nature cure bitters","volume":"4","author":"Gamanie","year":"2005","journal-title":"Afr. J. Biotechnol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1007\/s00125-017-4260-0","article-title":"Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids contribute to insulin sensitivity in mice and in humans","volume":"60","author":"Gangadhariah","year":"2017","journal-title":"Diabetologia"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3367","DOI":"10.3382\/ps\/pex105","article-title":"Efficacy of tiamulin alone or in combination with chlortetracycline against experimental Mycoplasma gallisepticum infection in chickens","volume":"96","author":"Garmyn","year":"2017","journal-title":"Poult. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"GPP3-0041","DOI":"10.1128\/microbiolspec.GPP3-0041-2018","article-title":"Extracellular matrix interactions with Gram-positive pathogens","volume":"7","author":"Hammerschmidt","year":"2019","journal-title":"Microbiol. Spectr."},{"key":"B29","article-title":"Determination of calcium by atomic absorption spectrophotometry","volume-title":"Clinical methods","author":"Henry","year":"1967"},{"key":"B30","volume-title":"Chemistry, principles and techniques","author":"Henry","year":"1974"},{"key":"B31","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s13620-014-0028-8","article-title":"Myocarditis in dogs: etiology, clinical and histopathological features (11 cases: 2007\u20132013)","volume":"67","author":"Janus","year":"2014","journal-title":"Ir. Vet. J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1161\/HYPERTENSIONAHA.110.154518","article-title":"Cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiology","volume":"56","author":"Jennings","year":"2010","journal-title":"Hypertension"},{"key":"B33","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s10557-014-6510-4","article-title":"Cytochrome P450 1B1 contributes to increased blood pressure and cardiovascular and renal dysfunction in spontaneously hypertensive rats","volume":"28","author":"Jennings","year":"2014","journal-title":"Cardiovasc Drugs Ther."},{"key":"B34","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.flm.2017.09.001","article-title":"High-sensitivity cardiac troponins I sandwich assay by immunomagnetic microparticle and quantum dots","volume":"1","author":"Jiang","year":"2017","journal-title":"Front. Lab. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.14202\/vetworld.2020.2371-2380","article-title":"The therapeutic efficacy of Aloe vera gel ointment on staphylococcal pyoderma in dogs","volume":"13","author":"Kamr","year":"2020","journal-title":"Vet. World"},{"key":"B36","doi-asserted-by":"publisher","first-page":"101606","DOI":"10.1016\/j.jafr.2024.101606","article-title":"Fire under the ashes: a descriptive review on the prevalence of methicillin-resistant Staphylococcus aureus in the food supply chain","volume":"2024","author":"Khalifa","year":"2024","journal-title":"J. Agric. Food Res."},{"key":"B37","volume-title":"Color Atlas and textbook of diagnostic microbiology","author":"Koneman","year":"2006"},{"key":"B38","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.mib.2020.02.005","article-title":"Staphylococcus aureus bloodstream infections: pathogenesis and regulatory mechanisms","volume":"53","author":"Kwiecinski","year":"2020","journal-title":"Curr. Opin. Microbiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/j.1365-2885","article-title":"Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs","volume":"1988","author":"Laber","year":"1988","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1331626","DOI":"10.3389\/fneur.2024.1331626","article-title":"The association of blood urea nitrogen-to-creatinine ratio and in-hospital mortality in acute ischemic stroke patients with atrial fibrillation: data from the MIMIC-IV database","volume":"15","author":"Li","year":"2024","journal-title":"Front. Neurol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jmii.2024.09.005","article-title":"High hemolytic activity in Staphylococcus aureus t1081\/ST45 due to increased hla protein production and potential RNAIII-independent regulation","volume":"58","author":"Lin","year":"2025","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"B42","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2-\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B43","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.prostaglandins.2011.12.003","article-title":"Contribution of cytochrome P450 1B1 to hypertension and associated pathophysiology: a novel target for antihypertensive agents","volume":"98","author":"Malik","year":"2012","journal-title":"Prostagl. Other Lipid Mediat"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3897\/pharmacia.72.e141543","article-title":"Effects of long-term prophylaxis with bromhexine hydrochloride and treatment with high colchicine doses of COVID-19","volume":"72","author":"Marinov","year":"2025","journal-title":"Pharmacia"},{"key":"B45","doi-asserted-by":"publisher","first-page":"3332","DOI":"10.1128\/JCM.39.9.3332-3338.2001","article-title":"Multiplex PCR protocol for the diagnosis of Staphylococcal infection","volume":"39","author":"Mason","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1007\/s42770-024-01320-2","article-title":"Antimicrobial efficiency of bromhexine hydrochloride against endometritis-causing Escherichia coli and Trueperella pyogenes in bovines","volume":"55","author":"Matzembacker","year":"2024","journal-title":"Braz. J. Microbiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"7","DOI":"10.23947\/2949-4826-2025-24-1-7-14","article-title":"Use of absolute weights and mass coefficients of beagle dog internal organs relative to body and brain weights in preclinical studies","volume":"24","author":"Mazukina","year":"2025","journal-title":"Russ. J. Veterinary Pathology"},{"key":"B48","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/s40203-024-00297-y","article-title":"Molecular detection of mecA gene from methicillin-resistant Staphylococcus aureus isolated from clinical and environmental samples and its potential inhibition by phytochemicals using in vitro and in silico approach","volume":"13","author":"Mohammed","year":"2025","journal-title":"Silico Pharmacol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"322","DOI":"10.21608\/jbaar.2025.420204","article-title":"Evaluating the Symphytum officinale effect against Staphylococcus aureus that induced liver pathochanges (histological study)","volume":"11","author":"Murshed","year":"2025","journal-title":"J. Biosci. Appl. Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"39","DOI":"10.5281\/zenodo.6481584","article-title":"A review of animal diseases caused by Staphylococci","volume":"17","author":"Mustafa","year":"2022","journal-title":"Rev. Latinoam. Hipertens."},{"key":"B51","doi-asserted-by":"publisher","first-page":"192","DOI":"10.5897\/AJMR2017.8679","article-title":"Pathological effects of staphylococcal species (S. aureus, S. xylosus and S. lentus) on some visceral organs (liver, kidney and bladder) of wistar rats following intraperitoneal inoculation","volume":"12","author":"Onyebueke","year":"2018","journal-title":"Afr. J. Microbiol. Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.12681\/jhvms.20826","article-title":"Staphylococcus aureus and bovine mastitis: molecular typing of methicillin resistance and clinical description of infected quarters","volume":"70","author":"Oreiby","year":"2019","journal-title":"J. Hell. Vet. Med. Soc."},{"key":"B53","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s12403-021-00419-3","article-title":"Polystyrene and polyethylene microplastics decrease cell viability and dysregulate inflammatory and oxidative stress markers of MDCK and L929 cells in vitro","volume":"14","author":"Palaniappan","year":"2022","journal-title":"Expo. Health"},{"key":"B54","doi-asserted-by":"publisher","first-page":"13542","DOI":"10.3390\/ijms252413542","article-title":"Protective action of cannabidiol on tiamulin toxicity in humans-in vitro study","volume":"25","author":"Pankowska","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B55","volume-title":"Saunders handbook of veterinary drugs: small and large animal","author":"Papich","year":"2016"},{"key":"B56","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s00281-011-0291-7","article-title":"Immunopathogenesis of Staphylococcus aureus pulmonary infection","volume":"34","author":"Parker","year":"2012","journal-title":"Semin. Immunopathol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"2374","DOI":"10.3390\/biomedicines12102374","article-title":"The expression of genes CYP1A1, CYP1B1, and CYP2J3 in distinct regions of the heart and its possible contribution to the development of hypertension","volume":"12","author":"Perepechaeva","year":"2024","journal-title":"Biomedicines"},{"key":"B58","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.3390\/ani12233279","article-title":"The importance of dietary antioxidants on oxidative stress, meat and milk production, and their preservative aspects in farm animals","volume":"12","author":"Ponnampalam","year":"2022","journal-title":"Animals"},{"key":"B59","doi-asserted-by":"publisher","first-page":"151","DOI":"10.36380\/jwpr.2020.20","article-title":"The effect of bromhexine and thyme oil on enhancement of the efficacy of tilmicosin against pasteurellosis in broiler chickens","volume":"10","author":"Radi","year":"2020","journal-title":"J. World Poult. Res."},{"key":"B60","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3390\/pathogens14020185","article-title":"Staphylococcus aureus in inflammation and pain: update on pathologic mechanisms","volume":"14","author":"Rasquel-Oliveira","year":"2025","journal-title":"Pathogens"},{"key":"B61","doi-asserted-by":"publisher","first-page":"100317","DOI":"10.1016\/j.vas.2023.100317","article-title":"Pharmacokinetics and antibacterial activity of tiamulin after single and multiple oral administrations in geese","volume":"21","author":"Sartini","year":"2023","journal-title":"Vet. Anim. Sci."},{"key":"B62","article-title":"The comparison of two samples","volume-title":"Statistical methods","author":"Sendecor","year":"1956"},{"key":"B63","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.ijid.2016.05.003","article-title":"Emergence of an NDM-5-producing clinical Escherichia coli isolate in Egypt","volume":"48","author":"Soliman","year":"2016","journal-title":"Int. J. Infect. Dis."},{"key":"B64","doi-asserted-by":"publisher","first-page":"e01601","DOI":"10.1128\/spectrum.01601-24","article-title":"Synergistic action of mucoactive drugs and phages against Pseudomonas aeruginosa and Klebsiella pneumoniae","author":"Sui","year":"2025","journal-title":"Microbiol. Spectr."},{"key":"B65","doi-asserted-by":"publisher","first-page":"569","DOI":"10.3390\/ani12050569","article-title":"Hepatoprotective effect of the Penthorum Chinense Pursh extract against the CCl4-induced acute liver injury via NF-\u03baB and p38-MAPK pathways in dogs","volume":"12","author":"Tao","year":"2022","journal-title":"Animals"},{"key":"B66","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/bmb.20461","article-title":"Real-time PCR primer design using free online software","volume":"39","author":"Thornton","year":"2011","journal-title":"Biochem. Mol. Biol. Educ."},{"key":"B67","doi-asserted-by":"publisher","first-page":"470","DOI":"10.3390\/antibiotics14050470","article-title":"Staphylococcus aureus: a review of the pathogenesis and virulence mechanisms","volume":"14","author":"Touaitia","year":"2025","journal-title":"Antibiotics"},{"key":"B68","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.vetmic.2004.09.002","article-title":"Genotypic and phenotypic screening of high and low virulence Staphylococcus aureus isolates from rabbits for biofilm formation and MSCRAMMs","volume":"103","author":"Vancraeynest","year":"2004","journal-title":"Vet. Microbiol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s10096-021-04391-3","article-title":"Acute kidney injury in Staphylococcus aureus bacteremia","volume":"41","author":"Westgeest","year":"2022","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B70","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/978-3-319-16009-2_6","article-title":"Cytochrome P450 enzymes in the bioactivation of polyunsaturated fatty acids and their role in cardiovascular disease","volume":"851","author":"Westphal","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.jdermsci.2022.05.006","article-title":"Tiamulin inhibits TNF-\u03b1 and alleviates psoriasis-like dermatitis","volume":"107","author":"Xiang","year":"2022","journal-title":"J. Dermatol Sci."},{"key":"B72","doi-asserted-by":"publisher","first-page":"265","DOI":"10.3389\/fmicb.2020.00265","article-title":"Anti-staphylococcus antibiotics interfere with the transcription of leucocidin ED Gene in Staphylococcus aureus strain newman","volume":"5","author":"Yang","year":"2020","journal-title":"Front. Microbiol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/1471-2105-7-85","article-title":"Statistical analysis of real-time PCR data","volume":"7","author":"Yuan","year":"2006","journal-title":"BMC Bioinforma."},{"key":"B74","doi-asserted-by":"publisher","first-page":"2752","DOI":"10.1038\/s41598-024-52830-w","article-title":"Zinc oxide resveratrol nanoparticles ameliorate testicular dysfunction due to levofloxacin-induced oxidative stress in rats","volume":"14","author":"Zaki","year":"2024","journal-title":"Sci. Rep."},{"key":"B75","doi-asserted-by":"publisher","first-page":"15267","DOI":"10.1038\/s41598-023-42621-0","article-title":"Anti-methicillin-resistant Staphylococcus aureus activity and safety evaluation of 14-O-[(5-ethoxycarbonyl-4,6-dimethylpyrimidine-2-yl) thioacetyl] mutilin (EDT)","volume":"13","author":"Zhou","year":"2023","journal-title":"Sci. Rep."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1679854\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:44:49Z","timestamp":1766040289000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1679854\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":75,"alternative-id":["10.3389\/fphar.2025.1679854"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1679854","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]},"article-number":"1679854"}}