INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Jinjin Tong,Zezheng Liu,Kexuan Zhou,Kaiming Wang,Shijiao Guo,Hua Zhang
The overuse of antibiotics in livestock production poses a significant threat to public health, primarily by accelerating the emergence of antibiotic-resistant bacteria—a critical global issue. Therefore, the development of effective alternatives to antibiotics is urgently required to address this problem. In this study, BLfcin-NPs@CS/β-GP thermosensitive hydrogels were developed by incorporating bovine lactoferricin-loaded chitosan nanoparticles into a chitosan/β-GP hydrogel matrix. Scanning electron microscopy (SEM) revealed the formation of a three-dimensional porous structure. Fourier-transform infrared (FTIR) spectroscopy confirmed successful synthesis, while X-ray diffraction (XRD) analysis indicated that nanoparticle incorporation did not alter the crystallinity of the hydrogel. The rheological properties, in vitro degradation, biocompatibility, and antibacterial activity of the composite hydrogels were systematically evaluated, and the results demonstrated that the composite hydrogels exhibited temperature sensitivity, enhanced degradation rates, low cytotoxicity, and strong antibacterial activity. These findings suggest that BLfcin-NPs@CS/β-GP hydrogels present a promising alternative to antibiotics for treating bacterial infections, such as bovine mastitis, offering an innovative and effective strategy to reduce antibiotic use and mitigate the risk of antibiotic resistance in livestock production.
研究领域:
兽医学
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生物材料学
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微生物学
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产品关联
DOI
PubMed
高影响因子
RESEARCH IN VETERINARY SCIENCE
·
2023
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IF 2.4
Jirao Shen,Feng Yang,Guibo Wang,Xiaoqing Mou,Jinyu Li,Xuezhi Ding,Xurong Wang,Hongsheng Li
Staphylococcus haemolyticus ( S. haemolyticus ) is one of the most common coagulase-negative staphylococci (CoNS) isolates from bovine mastitis . Paeoniflorin (PF) shows anti-inflammatory effects on different inflammatory diseases in vitro studies and in vivo animal experiments. In this study, the viability of bovine mammary epithelial cells (bMECs) was detected by the cell counting kit-8 experiment. Subsequently, bMECs were induced with S. haemolyticus , and the induction dosage was determined. The expression of pro-inflammatory cytokines and toll-like receptor (TLR2) and nuclear factor kappa-B (NF-κB) signaling pathway-related genes were investigated by quantitative real-time PCR. The critical pathway proteins were detected by western blot . The results showed that the multiplicity of infection (MOI; the ratio of bacteria to bMECs) 5:1 of S. haemolyticus for 12 h could cause cellular inflammation, which was selected to establish the inflammatory model. Incubation with 50 μg/ml PF for 12 h was the best intervention condition for cells stimulated by S. hemolyticus . Quantitative real-time PCR and western blot analysis showed that PF inhibited the activation of TLR2 and NF-κB pathway-related genes and the expression of related proteins. Western blot results showed that PF suppressed the expression of NF-κB unit p65, NF-κB unit p50, and MyD88 in bMECs stimulated by S. haemolyticus . The inflammatory response pathway and molecular mechanism caused by S. haemolyticus on bMECs are related to TLR2-mediated NF-κB signaling pathways. The anti-inflammatory mechanism of PF may also be through this pathway. Therefore, PF is expected to develop potential drugs against CoNS-induced bovine mastitis.
研究领域:
兽医学
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免疫学
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药理学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
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IF 5.714
Shiyuan Feng,Yihao Zhang,Shaodong Fu,Zhi Li,Jinqiu Zhang,Yuanyuan Xu,Xiangan Han,Jinfeng Miao
Mastitis affects animal welfare and causes economic losses in the dairy industry. It is caused mainly by bacterial pathogens, among which Escherichia coli ( E. coli ) is one of the prominent causative agents. To treat bovine mastitis, antibiotics were widely used. However, their extensive and uncontrolled use has led to the emergence of multi-antibiotic-resistant strains. Indeed, a superbug of E. coli was successfully isolated from a mastitis-suffering cow and found resistant to at least 10 antibiotics. Therefore, the development of a universal therapeutic agent used as a replacement for the antibiotic is an immediate need in the dairy industry. To do so, we examined whether chlorogenic acid (CGA), a natural and herbal extract, could be a perfect alternative in mastitis treatment. In this study, we observed that the combination of CGA and antibiotic had an additive or synergistic effect; CGA fought against the superbug by directly targeting bacterial cell wall and membrane; CGA can significantly alleviate the mastitis caused by the superbug E. coli via its antimicrobial, antioxidant and anti-inflammatory activities. Collectively, these data indicated that CGA had a true potential to replace antibiotics during mastitis treatment.
研究领域:
兽医学
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微生物学
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药理学
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乳品科学
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DOI
PubMed
高影响因子
MOLECULAR BIOLOGY REPORTS
·
2025
·Vol. 53
·期 1
·82
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IF 2.8
Qi Xue,Hu Yanjun,Yang Jinghan,Jiang Mingxuan,Zhang Junhao,Du Yanting,Hu Changmin
Background The pathogenesis of bovine mastitis involves inflammation and cell death, with pyroptosis being a key factor in its development. Currently, antibiotics remain the primary therapeutic option for bovine mastitis, however, the increasing prevalence of antibiotic resistance constitutes a major public health threat. Selenium (Se) has been reported to alleviate inflammation primarily through its antioxidant properties, but the mechanism by which Se regulates pyroptosis in bovine mastitis remains unclear. Methods and results In this study, an in vitro mastitis model was established by infecting MAC-T cells with inactivated Staphylococcus aureus ( S. aureus ) (MOI = 10, 12 h). The results revealed that the mitochondrial membrane potential of the MAC-T cells in the infection group decreased significantly. Moreover, the accumulation of Reactive oxygen species (ROS) was accompanied by the activation of NOD-like receptor family containing pyrin domain 3 (NLRP3), the expression of the pyroptosis-related genes gasdermin D amino terminal fragment (GSDMD-N), and cysteine aspartate specific protease 1 (cleaved-caspase 1). Pretreatment with Se, the NLRP3 inhibitor MCC950 and the antioxidant N-acetylcysteine (NAC) attenuated mitochondrial damage, ROS accumulation, and the inhibition of pyroptosis. An in vivo mastitis model was established in mice fed a high-selenium diet (containing 1.5 mg/kg Se) and intramammarily injected with inactivated S. aureus (1 × 10 8 CFU/mL). Histological analysis revealed intact alveolar structure and reduced inflammatory cell infiltration in mice fed the high-selenium diet. The expression of the inflammasome NLRP3 downregulated, and the expression of GSDMD-N, a direct executor of pyroptosis, upregulated. Conclusion Our in vitro and in vivo results confirmed that Se alleviate mitochondrial damage and pyroptosis by inhibiting the NLRP3 pathway, ultimately alleviating mastitis. Graphical
研究领域:
兽医学
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免疫学
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分子生物学
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炎症与感染
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营养与代谢
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DAIRY SCIENCE
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2021
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IF 4.034
Xiao Ma,Manman Li,Guicong Lu,Ruihong Wang,Yunmin Wei,Yanfeng Guo,Yongxiong Yu,Caode Jiang
ABSTRACT Epicatechin (EC) has significant antiinflammation, antioxidation, and anticancer activities. It also provides a new alternative treatment for mastitis, which can result in great economic losses in the dairy industry if left untreated. The purpose of this study was to investigate the anti-inflammatory effects of EC on mastitis and the underlying mechanism using in vivo and in vitro systems. The use of ELISA and immunohistochemistry assays showed that EC treatment at 1.5, 7.5, 15, and 30 mg/mL decreased protein expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase; inflammatory cytokines, which were composed of IL-1β, TNF-α, and IL-6 in lipopolysaccharide (LPS)-stimulated bovine mammary epithelial cell line (MAC-T); and mouse mammary gland, together with reduced filtration of T lymphocytes in the mouse mammary gland. Furthermore, EC treatment reduced LPS-induced phosphorylation levels of p65 and inhibitor of NF-κB, and blocked nuclear translocation of p65 as revealed by western blot and immunofluorescence test in MAC-T cells and the mouse mammary gland. Epicatechin also attenuated LPS-induced phosphorylation levels of mitogen-activated protein kinase members (i.e., p38, c-Jun N-terminal kinase 1/2 and extracellular regulated protein kinases 1/2). Using RNA-seq and tandem mass tag analyses, upregulation of TMEM35A and TMPO proteins was disclosed in MAC-T cells cotreated with LPS and EC. Although clustered regularly interspaced short palindromic repeats/Cas9-based knockdown of TMEM35A and TMPO attenuated abundance of phosphorylated (p)-p65, p-p38, TNF-α, and iNOS, overexpression of TMEM35A reversed EC-mediated effects in TMPO knockdown cells. Moreover, interaction between TMEM35A and TMPO was detected using the co-immunoprecipitation method. In conclusion, our data demonstrated that EC inhibited LPS-induced inflammatory response in MAC-T cells and the mouse mammary gland. Importantly, TMEM35A mediated the transmembrane transport of EC, and the interaction between TMEM35A and TMPO inhibited MAPK and NF-κB pathways.
研究领域:
药理学
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免疫学
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兽医学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
VETERINARY JOURNAL
·
2025
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IF 3.1
Tianyu Yang,Jiangang Bai,Yucan Wu,Cuicui Zhuang
Escherichia coli , an opportunistic pathogen, induces acute bovine mastitis, leading to severe milk yield reduction, dairy product discard, and substantial economic losses. This not only jeopardizes cow health and farm profitability but also raises food safety concerns, highlighting the need for effective treatments . Lycopene (LYC), a natural carotenoid with potent anti-inflammatory and antioxidant properties, has shown potential in mitigating inflammatory diseases. This study investigated the therapeutic mechanism of LYC against E. coli -induced bovine mastitis using network pharmacology, molecular docking, and a mice model. Potential targets of LYC were screened from TargetNet, GeneCards, CTD and SwissTargetPrediction, while mastitis and E. coli infections-related genes were obtained from GeneCards and CTD, respectively. PPI networks were constructed via STRING and Cytoscape, and core targets were analyzed using GO and KEGG in Metascape database. Molecular docking was performed to validate binding affinities between LYC and key targets. An E. coli -induced mastitis mice model was established to evaluate LYC's efficacy, with inflammatory markers and MAPK pathway proteins assessed via ELISA and Western blot. Network pharmacology identified 165 overlapping targets among LYC, mastitis and E. coli infections. KEGG analysis highlighted the MAPK pathway as a critical signalling axis, with 15 core regulators. Molecular docking confirmed strong binding of LYC to these core regulators. In vivo experiments demonstrated that LYC significantly reduced mammary tissue damage, decreased pro-inflammatory cytokines, and suppressed MAPK pathway in E. coli -infected mice. Therefore, LYC alleviates E. coli infection-induced bovine mastitis by modulating the MAPK pathway, offering a promising natural alternative for mastitis treatment.
研究领域:
药理学
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兽医学
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生物信息学
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Animal Science and Biotechnology
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2023
·Vol. 14
·期 1
·1-17
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IF 7
He Zhaoqi,Zhao Caijun,He Yuhong,Liu Zhuoyu,Fan Guyue,Zhu Kun,Wang Yiqi,Zhang Naisheng,Fu Yunhe,Hu Xiaoyu
Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in ‘gastroenterogenic mastitis’. However, the mechanism has not been fully clarified. Recently, we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows, and the abundance of Stenotrophomonas maltophilia (S. maltophilia) was significantly increased in both the rumen and milk microbiota. Accordingly, we hypothesized that ‘gastroenterogenic mastitis’ can be induced by the migration of endogenous gut bacteria to the mammary gland. Therefore, this study investigated the mechanism by which enterogenic S. maltophilia induces mastitis.Results First, S. maltophilia was labelled with superfolder GFP and administered to mice via gavage. The results showed that treatment with S. maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier, leading to intestinal inflammation and intestinal leakage. Furthermore, tracking of ingested S. maltophilia revealed that S. maltophilia could migrate from the gut to the mammary gland and induce mastitis. Subsequently, mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S. maltophilia. Then, using mouse mammary epithelial cells (MMECs), we verified that S. maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.Conclusion sIn conclusion, the results showed that enterogenic S. maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis. Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.
研究领域:
兽医学
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微生物学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2019
·Vol. 11
·期 10
·524
·
IF 4.773
Kaixiang Zhou,Xiaofang Wang,Dongmei Chen,Yuanyuan Yuan,Shuge Wang,Chao Li,Yuanyuan Yan,Qianying Liu,Liwei Shao,Lingli Huang,Zonghui Yuan,Shuyu Xie
TheStaphylococcus aureus(S. aureus) cow mastitis causes great losses to the cow industry. In order to improve the treatment effect of tilmicosin against cow mastitis, the combination of solid lipid nanoparticle (SLN) technology with in situ hydrogel technology was used to prepare the self-assembly tilmicosin nanogel (TIL-nanogel). The physicochemical characteristics, in vitro release, antibacterial activity and in vivo treatment efficacy of TIL-SLNs and TIL-nanogel were studied, respectively. The results showed the loading capacity (LC), encapsulation efficiency (EE), size, zeta potential and poly dispersion index (PDI) of TIL-nanogel were 23.33 ± 0.77%, 67.89 ± 3.01%, 431.57 ± 12.87 nm, 8.3 ± 0.06 mv and, 0.424 ± 0.032, respectively. The TIL-nanogel showed stronger sustained release in vitro than TIL-SLNs and commercial injection. The cure rate of half dosage and normal dosage of TIL-nanogel was 58.3% and 75.0%, which was higher than that of commercial injection (50.0%) at normal dosage. The results suggest that the treatment dosage of tilmicosin for cow mastitis could be reduced by TIL-nanogel. The novel TIL-nanogel will be beneficial by decreasing the usage of tilmicosin and the treatment costs of cow mastitis.Keywords:tilmicosin;solid lipid nanoparticles;sodium alginate-chitosan nanogel;Staphylococcus aureus;cow mastitis
研究领域:
兽医学
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制药技术
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纳米技术
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Current Research in Food Science
·
2024
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IF 6.2
Yuyang Li,Weiwei Chen,Jinxin Ma,Guoying Huang,Guangquan Li,Qiumei He,Xiangyu Kong,Ling Tang,Jinqing Chen,Wenyou Ding,Zhongbin Zhang,Wenya Ding
Currently, dairy mastitis caused by Staphylococcus xylosus poses a serious challenge for dairy farming. In this study, we explored the role and mechanism of rhein against S. xylosus with the hope of providing new research ideas to solve mastitis in dairy cows and ensure the source safety of dairy products. Through in vitro antimicrobial studies, we found that the minimum inhibitory concentration (MIC) of rhein was 64 μg/mL, and it significantly interfered with the formation of S. xylosus biofilm at sub-MIC. In experiments on mastitis in mice, rhein alleviated inflammation in mammary tissue, reduced the levels of TNF-α and IL-6, and decreased the number of S. xylosus . To explore the anti- S. xylosus mechanism of rhein, we identified the relevant proteins involved in carbon metabolism (Glycolysis/gluconeogenesis, TCA cycle, Fatty acid degradation) through proteomics. Additionally, proteins associated with the respiratory chain, oxidative stress (proteins of antioxidant and DNA repair), and nitrate respiration were also found to be upregulated. Thus, rhein may act as an antibacterial agent by interfering with the respiratory metabolism of S. xylosus and inducing the production of ROS, high levels of which alter the permeability of bacterial cell membranes and cause damage to them. We measured the concentrations of extracellular β-galactosidase and nucleic acids. Additionally, SEM observation of S. xylosus morphology showed elevated membrane permeability and damage to the cell membrane. Finally, RT-PCR experiments showed that mRNAs of key proteins of the TCA cycle (odhA, mqo) and nitrate respiration (nreB, nreC, narG) were significantly up-regulated, consistent with proteomic results. In conclusion, rhein has good anti- S. xylosus effects in vitro and in vivo, by interfering with bacterial energy metabolism, inducing ROS production, and causing cell membrane and DNA damage, which may be one of the important mechanisms of its antimicrobial activity.
研究领域:
微生物学
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药理学
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兽医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CELL STRESS & CHAPERONES
·
2023
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IF 3.8
He Xin,Wang Juan,Sun Lei,Ma Wenqi,Li Miao,Yu Shanshan,Zhou Qi,Jiang Jue
Mastitis is a disease involved in inflammation of breast which affects human and animals. Wogonin is one bioactive compound from many Chinese herbal medicines, which have multiple properties, including anti-inflammatory activity. However, the roles of wogonin in mastitis progression are largely undefined. Mastitis models were established using LPS-treated mice and mammary epithelial cells (MECs). Infiltration of inflammatory cells was analyzed by hematoxylin-eosin staining and myeloperoxidase (MPO) activity. Inflammatory cytokine (TNF-α and IL-1β) levels were detected via ELISA. The phosphorylation and total of Akt and NF-κB levels and content of Nrf2 and HO-1 were measured via western blot. Cell viability was examined by CCK-8 assay. Oxidative stress was assessed by ROS generation and levels of MDA, GSH, and SOD. Wogonin attenuated LPS-induced infiltration of inflammatory cells, increase of MPO activity and levels of TNF-α and IL-1β, and activation of the Akt/NF-κB pathway in murine mammary gland tissues, and promoted activation of Nrf2/HO-1 signaling. Wogonin did not affect MEC viability, but mitigated LPS-induced inflammation in MECs by reducing TNF-α and IL-1β levels. Wogonin relieved LPS-induced oxidative stress in MECs through decreasing ROS generation and MDA level and increasing GSH and SOD levels. Wogonin repressed LPS-induced activation of the Akt/NF-κB pathway in MECs and increased Nrf2/HO-1 signaling activation. Activated Akt/NF-κB signaling or Nrf2/HO-1 signaling inactivation reversed the suppressive effects of wogonin on LPS-induced inflammation and oxidative stress in MECs. Wogonin mitigates LPS-induced inflammation and oxidative stress of MECs via suppressing activation of the Akt/NF-κB signaling and activating Nrf2/HO-1 pathway, indicating the therapeutic potential of wogonin in mastitis.
研究领域:
药理学
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免疫学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
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2022
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IF 6.78
Tingyu Liang,Guiguo Huo,Lele Chen,Ling Ding,Jianping Wu,Ji Zhang,Rongmin Wang
Streptococcus agalactiae is among the major causative pathogens of bovine mastitis, as well as crucial pathogen leading to human morbidity and mortality. Being a promising natural antibacterial agent, linalool has been broadly applied in medicine and food processing. However, its antibacterial effect against S. agalactiae has barely been elucidated. This study is the first to investigate the antibacterial activity and action mechanism of linalool against S. agalactiae causing bovine mastitis. Linalool exhibited significant antibacterial activity against S. agalactiae , with an inhibition zone diameter of 23 mm and a minimum inhibitory concentration of 1.875 μL/mL. In addition, linalool damaged cell structural integrity of S. agalactiae , leading to the leakage of intracellular components (alkaline phosphatase, nucleic acids and protein). Linalool also exhibited a scavenging effect on biofilm. Moreover, untargeted metabolomics analysis revealed that linalool stress substantially disrupted intracellular metabolism of S. agalactiae . Linalool caused energy metabolism disorder, and obstructed nucleic acid synthesis in S. agalactiae . Furthermore, downregulation of amino acids (e.g., proline, alanine) and upregulation of saturated fatty acids provide strong evidence for linalool induced cell wall and membrane damage. Overall, linalool exhibited strong antibacterial activity against S. agalactiae by destroying the cell structure and disrupting intracellular metabolism. This study provides a new insight and theoretical foundation for linalool application in preventing S. agalactiae infection.
研究领域:
微生物学
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药理学
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代谢组学
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兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2024
·
IF 2.3
Huafeng Yang,Hui Liu,Yuan Zheng,Bo Li,Shujing Wang,Jun Zhang,Jiandong Wang
Cornus officinalis total glycosides (COTG) derived from the traditional Chinese medicine Cornus officinalis, is a natural immunosuppressant and has been extensively studied in immunomodulation and immunosuppression. This study aimed to explore the effects of COTG on granulomatous lobular mastitis (GLM) and its associated mechanisms. Compared to the model group, COTG effectively ameliorated histopathological damage to breast tissue, reduced mammary gland suppuration, and enhanced the blood-milk barrier. Additionally, COTG treatment reduced the total number of T cells and B cells in GLM rats, significantly improving clinical indicators such as P-selectin, E-selectin, and intercellular cell adhesion molecule-1. We also observed downregulation of CD28 and B7 expression levels, an upregulation of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) expression, and a significant decrease in inflammatory marker levels in the COTG group. COTG exerts an anti-inflammatory effect in GLM by stimulating CTLA-4, inhibiting the B7-CD28 signaling pathway affecting T cell activation, and promoting the blood-milk barrier. These findings suggest that COTG could be a promising therapeutic option for managing GLM, potentially improving patient outcomes by modulating immune responses and reinforcing the blood-milk barrier.
研究领域:
药理学
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免疫学
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病理学
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中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）