Science Advances
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2024
·Vol. 10
·期 40
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IF 11.7
Yijie Fang,Dantian Zhu,Jingyue Wei,Lei Qian,Rongmao Qiu,Taoyu Jia,Kui Huang,Suwen Zhao,Jun Ouyang,Man Li,Shaolin Li,Yang Li
Achilles tendinopathy is often attributed to overuse, but its pathophysiology remains poorly understood. Disruption to the molecular structure of collagen is fundamental for the onset and progression of tendinopathy but has mostly been investigated in vitro. Here, we interrogated the in vivo molecular structure changes of collagen in rat Achilles tendons following treadmill running. Unexpectedly, the tendons’ collagen molecules were not mechanically unfolded by running but denatured through proteolysis during physiological post-run remodeling. We further revealed that running induces inflammatory gene expressions in Achilles tendons and that long-term running causes prolonged, elevated collagen degradation, leading to the accumulation of denatured collagen and tendinopathy development. For applications, we demonstrated magnetic resonance imaging of collagenase-induced Achilles tendon injury in vivo using a denatured collagen targeting contrast agent. Our findings may help close the knowledge gaps in the mechanobiology and pathogenesis of Achilles tendinopathy and initiate new strategies for its imaging-based diagnosis.
研究领域:
运动医学
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生物力学
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分子生物学
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医学影像学
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2014
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IF 2.736
Shizhu Chen,Cuimiao Zhang,Guang Jia,Jianlei Duan,Shuxiang Wang,Jinchao Zhang
Lanthanide-doped sodium yttrium fluoride (NaYF 4 ) nanoparticles exhibit novel optical properties which make them be widely used in various fields. The extensive applications increase the chance of human exposure to these nanoparticles and thus raise deep concerns regarding their riskiness. In the present study, we have synthesized europium doped NaYF 4 (NaYF 4 :Eu 3 + ) nanoparticles with three diameters and used endothelial cells (ECs) as a cell model to explore the potential toxic effect. The cell viability, cytomembrane integrity, cellular uptake, intracellular localization, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), apoptosis detection, caspase-3 activity and expression of inflammatory gene were studied. The results indicated that these nanoparticles could be uptaken into ECs and decrease the cell viability, induce the intracellular lactate dehydrogenase (LDH) release, increase the ROS level, and decrease the cell MMP in a size-dependent manner. Besides that, the cells were suffered to apoptosis with the caspase-3 activation, and the inflammation specific gene expressions (ICAM1 and VCAM1) were also increased. Our results suggest that the damage pathway may be related to the ROS generation and mitochondrial damage. The results provide novel evidence to elucidate their toxicity mechanisms and may be helpful for more rational applications of these compounds in the future.
研究领域:
纳米技术
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毒理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2024
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IF 4.1
Yuan-Xin Qian,Feng-Feng Zhou,Qiang Chen,Fen Dong,Han-Ying Xu,Yu-Long Sun,Ji-Teng Wang,Tao Han
Arginine plays a key role in regulating the immune function of fish. To evaluate the effect of arginine on the immune response of largemouth bass ( Micropterus salmoides ), the effects of arginine on cell viability, NADPH oxidase activity, respiratory burst activity, and NO production of leukocytes were analyzed both in vitro and in vivo . In this study, we found that arginine could promote the respiratory burst activity of leucocytes both in vivo and in vitro . By incubating leukocytes with the combination of LPS and arginine, we found that arginine supplementation inhibited the expression of inflammatory genes ( tumor necrosis factor-alpha , tnfα ; interleukin ( il ) 8 and il10 ) and apoptotic genes ( caspase 3 , caspase 8 , and caspase 9 ) induced by LPS, as well as promoted the arginine metabolism. Arginine supplementation significantly induced ( cd4-like ) cd4 gene expression after LPS challenge. Further studies showed that LPS could significantly increase nucleotide-binding oligomerization domain containing 1 ( nod1 ) gene expression, but decreased the nod2 gene. The arginine supplementation increased nuclear factor kappa-B (NF-κB) protein level. In conclusion, arginine can alleviate LPS-induced inflammatory response and apoptosis as well as induce cd4 gene expression against LPS challenge via adjusting the expression of NODs signaling.
研究领域:
免疫学
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水产养殖
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Current Research in Food Science
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2022
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IF 6.269
Xuan Chen,Liufeng Zheng,Bing Zhang,Zeyuan Deng,Hongyan Li
Oxidative stress is a potential factor in the promotion of endothelial dysfunction. In this research, flavonoids (quercetin, luteolin) combined with carotenoids (lycopene, lutein), especially quercetin-lycopene combination (molar ratio 5:1), prevented the oxidative stress in HUVEC cells by reducing the reactive oxygen species (ROS) and suppressing the expression of NADPH oxidase 4 (Nox4), a major source of ROS production. RNA-seq analysis indicated quercetin-lycopene combination downregulated inflammatory genes induced by H 2 O 2 , such as IL-17 and NF-κB. The expression of NF-κB p65 was activated by H 2 O 2 but inhibited by the quercetin-lycopene combination. Moreover, the quercetin and lycopene combination promoted the thermostability of Sirtuin 1 (SIRT1) and activated SIRT1 deacetyl activity. SIRT1 inhibitor EX-527 attenuated the inhibitory effects of quercetin, lycopene, and their combination on the expression of p65, Nox4 enzyme, and ROS. Quercetin-lycopene combination could interact with SIRT1 to inhibit Nox4 and prevent endothelial oxidative stress, potentially contributing to the prevention of cardiovascular disease.
研究领域:
药理学
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分子生物学
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细胞生物学
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心血管研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Ting Tai,Yuan-Yuan Shao,Yu-Qi Zheng,Li-Ping Jiang,Hao-Ru Han,Na Yin,Hao-Dong Li,Jin-Zi Ji,Qiong-Yu Mi,Li Yang,Lei Feng,Fu-Yang Duan,Hong-Guang Xie
Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) frequently confers an increased risk of vascular thrombosis; however, the marketed antiplatelet drugs are investigated for the prevention and treatment of MASLD in patients with these coexisting diseases.Methods: To determine whether clopidogrel could ameliorate high-fat diet (HFD)-induced hepatic steatosis in mice and how it works, mice were fed on normal diet or HFD alone or in combination with or without clopidogrel for 14 weeks, and primary mouse hepatocytes were treated with palmitate/oleate alone or in combination with the compounds examined for 24 h. Body weight, liver weight, insulin resistance, triglyceride and total cholesterol content in serum and liver, histological morphology, transcriptomic analysis of mouse liver, and multiple key MASLD-associated genes and proteins were measured, respectively.Results and discussion: Clopidogrel mitigated HFD-induced hepatic steatosis (as measured with oil red O staining and triglyceride kit assay) and reduced elevations in serum aminotransferases, liver weight, and the ratio of liver to body weight. Clopidogrel downregulated the expression of multiple critical lipogenic (Acaca/Acacb, Fasn, Scd1, Elovl6, Mogat1, Pparg, Cd36, and Fabp4), profibrotic (Col1a1, Col1a2, Col3a1, Col4a1, Acta2, and Mmp2), and proinflammatory (Ccl2, Cxcl2, Cxcl10, Il1a, Tlr4, and Nlrp3) genes, and enhanced phosphorylation of AMPK and ACC. However, compound C (an AMPK inhibitor) reversed enhanced phosphorylation of AMPK and ACC in clopidogrel-treated primary mouse hepatocytes and alleviated accumulation of intracellular lipids. We concluded that clopidogrel may prevent and/or reverse HFD-induced hepatic steatosis in mice, suggesting that clopidogrel could be repurposed to fight fatty liver in patients.
研究领域:
药理学
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肝病学
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代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-14
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IF 10.2
Ren Yiming,Chen Yi,Chen Wei,Deng Haotian,Li Peiqi,Liu Yubo,Gao Cangjian,Tian Guangzhao,Ning Chao,Yuan Zhiguo,Sui Xiang,Liu Shuyun,Guo Quanyi
Successful biomaterial implantation requires appropriate immune responses. Macrophages are key mediators involved in this process. Currently, exploitation of the intrinsic properties of biomaterials to modulate macrophages and immune responses is appealing. In this study, we prepared hydrophilic nanofibers with an aligned topography by incorporating polyethylene glycol and polycaprolactone using axial electrospinning. We investigated the effect of the nanofibers on macrophage behavior and the underlying mechanisms. With the increase of hydrophilicity of aligned nanofibers, the inflammatory gene expression of macrophages adhering to them was downregulated, and M2 polarization was induced. We further presented clear evidence that the inflammasome NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was the cellular sensor by which macrophages sense the biomaterials, and it acted as a regulator of the macrophage-mediated response to foreign bodies and implant integration. In vivo, we showed that the fibers shaped the implant-related immune microenvironment and ameliorated peritendinous adhesions. In conclusion, our study demonstrated that hydrophilic aligned nanofibers exhibited better biocompatibility and immunological properties.
研究领域:
生物材料科学
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免疫学
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组织工程
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生物医学工程
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DOI
PubMed
高影响因子
Biomaterials Science
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2023
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IF 6.6
Xiaoxia Zhang,Changkai Yang,Xin Guo,Chun Yang,Guoying Li
The development of antibacterial dressings has attracted much attention to address the disordered wound healing caused by bacterial infection. Constructing dressings that have desirable antibacterial activity and could promote wound healing is important for infected wound repair. Inspired by the role of the key regulator collagen fibrils with D-periodic functional domains in physiological wound healing process, we developed an antibacterial and wound healing-promoting collagen fibril with a structure highly similar to natural collagen in ECM and inherent antibacterial activity by the simultaneous strategy of fibril reconstitution and the antibacterial agent ε-polylysine (ε-PL) anchoring. Accompanied by the fibrillogenesis of collagen molecules, the anchorage of ε-PL into collagen fibrils was actualized through the formation of the covalent bond catalyzed by transglutaminase (TGase) between ε-PL and collagen. The collagen fibril possessed natural D-periodicity and achieved 20% ε-PL graft yield by co-assembling collagen/ε-PL mediated by TGase of 25 U/g, which showed a satisfactory proliferation of L929 fibroblasts and sustained inhibition rates above 90% against E. coli and S. aureus. The rats’ S. aureus-infected dermal wound model further demonstrated that the antibacterial reconstituted collagen fibril visibly promoted re-epithelialization, new collagen deposition, and angiogenesis by down-regulating the inflammatory-relative genes IL-6 and up-regulating relative activity factor expression of CD31, achieving accelerated infected wound healing with 61.89% ± 3.96% wound closure on postoperative day 7 and full closure on day 14.
研究领域:
生物材料
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伤口愈合
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生物医学工程
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组织工程
✓ 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）