Journal of Animal Science and Biotechnology
·
2023
·Vol. 14
·期 1
·1-17
·
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
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Pei Wang,Lianguo Wang,Yifan Liu,Yuqing Mu,Yunyun Deng,Ao Jia,Yunyan Zhan,Jun Guo,Zhihua Li,Fei Tong
Given the inherent microbial environment of the oral cavity, therapeutic strategies necessitate transcending conventional antimicrobial approaches to prioritize the restoration of immune homeostasis in periodontal microenvironments. Specifically, excess reactive oxygen species (ROS) generated from the stimulation of periodontal pathogenic bacteria represent one of the most critical factors. Herein, we architecturally engineered core–satellite nanoarchitectures (PPAg) through polydopamine (PDA)-mediated integration of Prussian blue nanozymes (PB) with silver satellites, creating a dual-functional therapeutic platform. The platform integrates mild photothermal-enhanced bacterial eradication with enzymatic ROS scavenging, overcoming biofilm persistence and reprogramming the inflammatory microenvironment. The Prussian blue core’s multienzyme–mimetic activity cooperates with silver’s sustained antimicrobial action through the link and isolation effects of PDA coating, achieving mutual noninterference and enhanced stability. Crucially, the nanocomposites demonstrate mitigation of oxidative stress and inflammation through redox homeostasis restoration by sterilization and ROS scavenging. The developed nanocomposites significantly mitigated ROS-induced oxidative stress in Raw267.4 cells stimulated by lipopolysaccharide, owing to the multienzyme-like activities of PDA-coated PB nanozymes. In vivo experiments reveal a notable enhancement in bactericidal and anti-inflammatory effects, resulting from antibiofilm assays and Western blot analysis of inflammatory factors. The nanointegration strategy establishes a therapeutic paradigm that bridges antimicrobial precision and immune microenvironment remodeling, demonstrating the feasibility of concurrent biofilm eradication and modulation for inflammation.
研究领域:
纳米医学
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牙科医学
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免疫学
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材料科学
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生物工程
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微生物学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Zhicheng Tong,Yuanzhu Ma,Qiushi Liang,Tao Lei,Hongwei Wu,Xianzhu Zhang,Yishan Chen,Xihao Pan,Xiaozhao Wang,Huimin Li,Junxin Lin,Wei Wei,Chong Teng
Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in clinical settings, posing significant treatment challenges. Here, we fabricated a cartilage extracellular matrix mimic hydrogel (GHC, consisting of Gelatin, Hyaluronic acid, and Chondroitin sulfate) to avoid the exacerbation of cartilage deterioration, which is often driven by the accumulation of reactive oxygen species (ROS) and a pro-inflammatory microenvironment. The GHC hydrogel exhibited multifunctional properties, including in situ formation, tissue adhesiveness, anti-ROS capabilities, and the promotion of chondrogenesis. The enhancement of tissue adhesion was achieved by chemically modifying hyaluronic acid and chondroitin sulfate with o-nitrobenzene, enabling a covalent connection to the cartilage surface upon light irradiation. In vitro characterization revealed that GHC hydrogel facilitated chondrocyte adhesion, migration, and differentiation into cartilage. Additionally, GHC hydrogels demonstrated the ability to scavenge ROS in vitro and inhibit the production of inflammatory factors by chondrocytes. In the animal model of superficial cartilage injury, the hydrogel effectively promoted cartilage ECM regeneration and facilitated the interface integration between the host tissue and the material. These findings suggest that the multifunctional GHC hydrogels hold considerable promise as a strategy for cartilage defect repair. Statement of Significance : Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in the clinic. Previous cartilage tissue engineering materials are only suitable for full-thickness cartilage defects or osteochondral defects. Here, we developed a multifunctional GHC hydrogel composed of gelatin, hyaluronic acid, and chondroitin sulfate, which are natural cartilage extracellular matrix components. The drug-free and cell-free hydrogel not only avoids immune rejection and drug toxicity, but also shows good mechanical properties and biocompatibility. More importantly, the GHC hydrogel could adhere tightly to the superficial cartilage defects and promote cartilage regeneration while protecting against oxidation. This natural ingredients and multifunctional hydrogel is a potential material for repairing superficial cartilage defects.
研究领域:
组织工程
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生物材料
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骨科
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生物医学工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yu Liu,Meng Zhu,Jinzhao Ou,KeJia Li,Xiaoyan Ju,Ye Tian,Zhongwei Niu
Oxidative stress caused by excessive reactive oxygen species (ROS) accumulation significantly hinders wound healing in patients with diabetes. Scavenging ROS and reducing inflammation are crucial for rapid healing. In this work, a multi-responsive sodium hyaluronate (HA)/tannic acid (TA) hydrogel was developed based on boronate ester bonds. Sodium hyaluronate with 3-aminophenyl boronic acid modification (HA-APBA) was mixed and crosslinked with TA to form HA-APBA/TA hydrogels. These hydrogels are injectable, self-healing, and biocompatible. The HA-APBA/TA hydrogels could release free TA through the collapse of the structure at low pH, high H 2 O 2 concentration, and high glucose concentration, thus possessing good ROS scavenging ability. In full-thickness skin wounds of db/db mice, the HA-APBA/TA hydrogels promoted wound healing, collagen deposition, and significant angiogenesis. Furthermore, they have been shown to effectively reduce the levels of inflammatory factors in wounds and lower the expression of CD86, a pro-inflammatory macrophage surface marker. This resulted in a more effective transition of wound healing from the inflammatory phase to the proliferative phase. This study provides an optional strategy for alleviating oxidative stress and controlling excessive inflammation, thereby promoting diabetic wound healing.
研究领域:
材料科学
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生物材料
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药学
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伤口愈合
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
Small
·
2018
·Vol. 14
·期 38
·1802337
·
IF 9.598
Ting Wang,Jinhui Hu,Hao Luo,Huiyang Li,Jiahong Zhou,Lin Zhou,Shaohua Wei
Reactive oxygen species (ROS) generated during photodynamic therapy (PDT) can trigger autophagy. However, little research is focused on whether there is a synergistic anticancer effect with PDT if extra autophagy promoter or inhibitor is added. Here, it is found that autophagy promotion significantly enhances the PDT activity to cancer cells. Based on this preliminary result, a ROS-sensitive self-assembled dendrimer nanoparticle is exploited as a carrier to codeliver an autophagy promoter (rapamycin, Rapa) and photosensitizer (phthalocyanine, Pc) to the tumor. After entrapped by cancer cells and irradiated by light, the ROS generated in PDT process of Pc can trigger nanoparticle destruction to release Rapa, thus initiating the autophagy process and remarkably enhancing the efficacy of PDT, leading to efficient tumor suppression.
研究领域:
癌症研究
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纳米技术
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Mingqiao Li,Hedan Xu,Nan Zhao,Liangjun Zhang,Haihan Xia,Xiaoxun Zhang,Qiao Li,Min Liao,Qiong Pan,Zeng Yi,Jin Chai
Acute liver injury (ALI) is one of the most important causes of liver failure, and there are no FDA-approved drugs that could therapy late-stage ALI. It has been shown in this study that HA-PEI, a molecule formed by covalently combining HA and PEI, can effectively treat advanced ALI. Through the CD44 receptor, HA-PEI could target the liver actively, with the highest liver-targeting effect confirmed at 1000 K. The underlying mechanism of protection of HA-PEI is by increasing oxygen content, reducing ROS, and maintaining mitochondrial membrane potential. HA-PEI also inhibits the secretion of inflammatory factors and blocks the migration of immune cells to the liver, protecting the hepatocytes not suffer from secondary damage. More importantly, for late-stage ALI, NAC, as the only FDA-approved drug, is completely ineffective, whereas HA-PEI has an excellent therapeutic effect. This work provides a new safe therapeutic agent for ALI, which has a bright application prospect.
研究领域:
药理学
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肝病学
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药物递送系统
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炎症
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氧化应激
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
JunWei Feng,Xia Deng,Peng Hao,ZongDong Zhu,Tao Li,XinWei Yuan,Jiang Hu,Yue Wang
Reactive oxygen species (ROS)-mediated ferroptosis plays a critical role in the development of osteoarthritis (OA). Consequently, it is speculated that anti-ferroptosis agents could represent a novel therapeutic strategy for managing OA. In this study, a hydrogel incorporating platinum (Pt) nanozyme was synthesized by dispersing Pt nanoparticles (NPs) within a matrix of silk fibroin (SF) and oxidized pullulan (oxPL). This hydrogel allows for a substantial and sustained release of up to 30 days. The gelation time (from 140.3 ± 42.3 s to 460.0 ± 40.0 s), swelling capacity (from 57.7 ± 3.8 % to 24.0 ± 7.0 %), and degradation rate (from 60.3 ± 4.7 % to 32.0 ± 4.6 %) of the hydrogels can be modulated by adjusting the Pt NP content. The Pt@SF/oxPL hydrogel effectively eliminates ROS due to its catalase-like and superoxide dismutase-like enzymatic properties. In vitro studies demonstrated that Pt@SF/oxPL efficiently mitigated the process of ferroptotic cell death in chondrocytes. More critically, intra-articular administration of Pt@SF/oxPL showcased therapeutic advantages by both protecting and stimulating the regeneration of cartilage throughout the progression of OA. Collectively, this study suggests that Pt@SF/oxPL hydrogels could potentially serve as an effective treatment for OA, presenting a novel nanozyme-based therapeutic approach for this condition.
研究领域:
生物医学工程
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材料科学
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骨科
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Qingqiu Chen,Guang Xin,Shiyi Li,Yuman Dong,Xiuxian Yu,Chengyu Wan,Zeliang Wei,Yuda Zhu,Kun Zhang,Yilan Wang,Fan Li,Cuicui Zhang,E Wen,Yulong Li,Hai Niu,Wen Huang
Background Accumulation of age-associated senescent cells accompanied with increased reactive oxygen species (ROS) and inflammatory factors contributes to the progression of age-related macular degeneration (AMD), the main cause of blindness in the elderly. Berberine (BBR) has shown efficacy in the treatment of age-related diseases including diabetes and obesity by decreasing ROS. However, the pharmacological effect of BBR on alleviating retinal aging remains largely unknown. Purpose Our study aimed to investigate the pharmacological effect of BBR as an anti-aging agent in retinal aging and its further molecular mechanisms. Methods D-galactose (DG)-induced ARPE-19 cell senescence and retinal aging were employed to evaluate the anti-aging effect of BBR in vivo and in vitro . The siRNA transfection, Western-Blot analyses, SA-β-Gal assay and immunofluorescence were performed to investigate the potential mechanisms of BBR on anti-aging of RPE . Results In RPE-choroid of both natural aged and DG-induced accelerated aged mice, oxidative stress was increased along with the up-regulation of p21 expression, which was ameliorated by BBR treatment. BBR down-regulated the expression of REDD1 to decrease intracellular ROS content, attenuating DG-induced senescence in vitro and in vivo . Furthermore, p53 instead of HIF-1α was identified as the transcriptional regulator of REDD1 in DG-induced premature senescence. Importantly, NAC and BBR reversed the expression of p53 and the content of 8-OHdG, indicating that the positive feedback loop of ROS-DNA damage response (DDR) was formed, and BBR interrupted this feedback loop to alleviate DG-induced premature senescence by reducing REDD1 expression. In addition, BBR restored DG-damaged autophagy flux by up-regulating TFEB-mediated lysosomal biosynthesis by inhibiting REDD1 expression, thereby attenuating cellular senescence . Conclusion BBR down-regulates REDD1 expression to interrupt the ROS-DDR positive feedback loop and restore autophagic flux, thereby reducing premature senescence of RPE. Our findings elucidate the promising effects of REDD1 on cellular senescence and the great potential of BBR as a therapeutic approach.
研究领域:
药理学
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眼科学
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衰老
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Haiting Xu,Linxin Dai,Wenbiao Nie,Ruifeng Luo,Xiulan Pu,Lingling Dong,Qiyan Chen,Shanshan Qi,Xiaoqin Han,Jieshu You,Jinming Zhang,Fei Gao
Cyclodextrins (CDs) have been applied widely as an oral micro-nano drug delivery material for the treatment of ulcerative colitis (UC) because of their stability around the stomach. However, the further application of CDs is hindered due to their inherent poor targeting and controlled release properties. In this study, CD-supramolecular nanoparticles ( [email protected] ) were developed based on the structural characteristics of CDs (e.g., multi-group modifiability and hydrophobic cavity) to encapsulate rhein (RH) for oral delivery against UC. The [email protected] showed an average size of 154.70 ± 1.80 nm and exhibited high encapsulation efficiency (95.55 ± 2.37 %). When incubated in simulated gastric fluid for 2 h, [email protected] only released 20.3 ± 0.47 % RH due to the protection of supramolecular effects of CDs. However, RH was rapidly released from [email protected] (released 66.3 ± 2.50 %) after H 2 O 2 was treated with the assistance of the ROS-sensitive properties. Moreover, [email protected] were taken up by macrophages in 1.5 times higher amounts than preparations which did not have CD44-targeted effects. Notably, the results showed that [email protected] with an accurate on-demand drug release strategy achieved the best anti-inflammatory and antioxidant effects, and they are expected to be a promising carrier in the UC treatment.
研究领域:
药学
·
纳米技术
·
炎症性肠病
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产品关联
DOI
高影响因子
Biomaterials Science
·
2017
·Vol. 5
·期 6
·1174-1182
·
IF 4.21
Qiurong Deng,Xudong Li,Lipeng Zhu,Hua He,Donglai Chen,Yongbing Chen,Lichen Yin
The transfection performance of polycations is often hampered by various systemic barriers that pose conflicting requirements for material design. Herein, we developed fluorinated, ROS-cleavable polyethylenimine (PEI) for effective and serum-resistant gene delivery to cancer cells, by harmonizing the inconsistency between DNA condensation and release, and the inconsistency between cellular internalization and serum stability. Low-molecular weight (MW) PEI was cross-linked with a diselenide-containing linker and further modified with fluorocarbon chains. The obtained high-MW DSe-PEI-F has potent DNA condensation as well as intracellular DNA delivery capabilities, while in the cytoplasm of cancer cells, it can rapidly degrade into low-MW segments upon ROS treatment to promote DNA release and reduce the material toxicity. As such, DSe-PEI-F showed high transfection efficiencies in cancer cells in the presence of serum, outperforming the commercial reagent PEI 25k by several orders of magnitude. This study thus provides an effective approach to overcome various barriers against non-viral gene delivery, which contributes to the development of a new class of gene vectors with high efficiency and low toxicity.
研究领域:
材料科学
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生物医学工程
·
基因治疗
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2021
·
IF 6.025
Bangrong Cai,Mengya Liu,Jinxing Li,Dujuan Xu,Jiansheng Li
Chronic obstructive pulmonary disease (COPD) is widely recognized as a global public health problem and the third leading cause of mortality worldwide by 2020. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a dual-specificity protein and lipid phosphatase that plays an important role in COPD. However, the redox regulation of PTEN in the development of COPD was poorly studied. Our results showed that cigarette smoke extract (CSE) could oxidize PTEN in a time-dependent manner in BEAS-2B cells, whereas PTEN oxidation exposed to CSE was delayed compared to that of H 2 O 2. Additionally, we found that ROS derived from DUOX1 and 2 of NADPH oxidases were mainly responsible for oxidative inactivation PTEN, also simultaneously led to Trx-1 inactivation by dimerization . Oxidative mechanism of PTEN exposed to CSE was mediated by forming a disulfide bond between Cys 71 and Cys 124 , similar to H 2 O 2 . Inactivation of PTEN resulted in the increased phosphorylation of Akt. In conclusion, CSE exposure could elevate the intracellular ROS mainly from DUOX1 and 2 to oxidize PTEN and Trx-1 resulting in Akt activation, eventually cause the occurrence of COPD, suggesting that PTEN is a potential target for new therapies in COPD.
研究领域:
肺科学
·
分子生物学
·
细胞生物学
·
氧化应激
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Li Bingyi,He Mei,Xu Zichen,Zhang Qianting,Zhang Liyuan,Zhao Shuang,Cao Yu,Mou Nianlian,Wang Yi,Wang Guixue
Atherosclerosis (AS), an inflammatory disease characterized by lipid accumulation, has a high global incidence and mortality rate. Recently, nanotherapeutic approaches that target pathological sites and improve drug bioavailability and biocompatibility hold great promise for AS treatment. In this study, a biomimetic ROS-responsive hyaluronic acid–based nanomaterial was prepared for targeted anti-AS. Specifically, a safe ROS-responsive carrier based on hyaluronic acid (HSP) was prepared to load methotrexate (MTX), a drug known for its ability to enhance lipid excretion, resulting in the formation of MTX-loaded nanoparticles (MTXNPs). Furthermore, the macrophage membrane was coated on the surface of MTXNPs to obtain MM/MTXNPs. Both MTXNPs and MM/MTXNPs exhibited ROS responsiveness and demonstrated excellent biocompatibility. In vitro experiments revealed that MM/MTXNPs could evade macrophage phagocytosis and exhibited high uptake rates by inflamed endothelial cells. MM/MTXNPs also reduced lipid accumulation in foam cells. In vivo experiments showed that MM/MTXNPs exhibited superior accumulation at AS plaque sites, facilitated by the surface membrane layer containing integrin α4β1 and CD47, resulting in an enhanced therapeutic effect in inhibiting plaque development compared to free MTX and MTXNPs. Therefore, HSP represents a promising nanocarrier to load hydrophobic MTX, enabling effective and biocompatible enhancement of AS treatment.
研究领域:
纳米医学
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药学
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生物医学工程
·
心血管疾病
✓ 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）