NanoImpact
·
2025
·
IF 5.5
Yingqi Wang,Shen Zhao,Nengyi Ni,Hongyu Chen,Wenjian Zhao,Kuoran Xing,Xiao Sun,Xiuli Jing
Nanomaterials have been widely used in various fields due to their excellent properties. However, the long-term exposure of humans to the environment of nanomaterials may lead to some pathological and physiological changes, such as the disruption of the glomerular filtration barrier (GFB), which can lead to high permeability and filterable albumin. Glomerular albuminuria results from the failure of the GFB, which may be caused by activation of the Notch1 signaling pathway. The reduction of glomerular endocalyx results in the level of VE-cadherin being diminished between endothelial cells, leading to leakiness in the endothelium. As previously discovered, certain nanoparticles, such as negatively charged gold nanoparticles of appropriate size, can directly facilitate the onset of endothelial leakiness through disrupting connections between vascular endothelial cells, in a process known as nanomaterial-induced endothelial leakiness (NanoEL). In this study, the negatively charged Au NPs with a diameter of 20 nm were synthesized first. Through the co-incubation of 20 nm Au NPs with a single layer of continuous HUVECs, we revealed that the synthesized 20 nm Au NPs could break the tight junctions and cause endothelial cell leakage. In addition, by constructing an endothelial leakage model between glomerular vascular endothelial cells, we confirmed that 20 nm Au NPs can generate NanoEL between glomerular endothelial cells, involving downstream processes coinciding with Notch signaling activation, resulting in the increase of urinary protein. The results of this study add to the understanding of the behaviour of nanoparticles in complex biological systems.
研究领域:
医学
·
毒理学
·
纳米生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Biology
·
2025
·
IF 2.6
Xi-Ting Lv,Wen-Xiu Yang,Xiao Zhang,Bao-Ling Li,Wen-Ying Wang,Guo-En Wang
Guilongwan (GLW), a representative of traditional Chinese Medicine (TCM) has been utilized to treating diabetic foot ulcer (DFU)-related syndrome including an intolerance of cold with cold limbs, blood circulation disorder, and immune dysfunction for decades. However, the chemical and biological mechanisms of GLW remain unclear. This study aims to discover the biological mechanisms of GLW on DFU by using streptozotocin- and skin-puncher-induced DFU rat models, in vitro macrophage models, and in silico analysis. The alterations in pathology, Notch1 signaling, and macrophage polarization are detected. The results indicated that GLW promoted wound healing, cutaneous cell proliferation, and angiogenesis in DFU rats by inhibiting delta-like (DLL) 4/Notch1 signaling. In addition, GLW inhibited M1 polarization and promoted M2 polarization in diabetic wounds. Seventeen chemical compounds in GLW-medicated serum are identified. In silico analysis and in vitro experiments demonstrated that GLW-medicated serum and its main compounds inhibited the expression of DLL4 in matrix metalloproteinase-9-induced M1 macrophages. In conclusion, GLW ameliorated experimental DFU rats via the inhibition of DLL4/Notch1 signaling in M1 macrophages. This study provided a new biologic mechanism for GLW in the treatment of DFU.
研究领域:
药理学
·
分子生物学
·
中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Pengfei Yan,Junchao Wang,Xiyu Zhao,Liangyu Wang,Jia Xu,Weijia Li,Weihong Min,Dan Wu,Chunlei Liu
QMDDQ is peptide derived from shrimp that ameliorates scopolamine-induced memory impairment. In this study, behavioral experiments in mice showed that QMDDQ could reduce the latency, number of working memory errors of the total distance moved, number of reference memory errors, number of traversals of the original platform, and escape latency in mice. QMDDQ decreased AChE vitality and increased ACh, DA, and 5-HT content. HE staining revealed that the cells in the hippocampal areas exhibited a tight tissue structure, neat arrangement, clear outline, and no cell necrosis in the QMDDQ group. Immunohistochemistry showed that, the expression level of Notch1 protein was reduced, and that of the antibody antigen complex was reduced in the QMDDQ group. Immunofluorescence staining showed a decrease in the number of GFAP and Iba-1 of QMDDQ group. TEM revealed that the mitochondrial cristae are intact and clear of QMDDQ group. QMDDQ decreased expression levels of Notch 1, STAT3, HES1, GFAP, and Iba-1 and activated Notch1 signaling via western-blotting. Pharmacokinetic studies have shown that QMDDQ can be stably absorbed into the bloodstream, with absorption occurring within 12 h and metabolism being completed within 24 h. This study establishes a theoretical basis for active peptides to ameliorate memory impairment and initiates the development of memory-enhancing functional foods.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2023
·Vol. 80
·期 8
·1-19
·
IF 8
Dong Yuechao,Ma Guixing,Hou Xiaoting,Han Yingying,Ding Zhen,Tang Wanze,Chen Litong,Chen Yangshan,Zhou Bo,Rao Feng,Lv Kaosheng,Du Changzheng,Cao Huiling
Kindlin-2 is critical for development and homeostasis of key organs, including skeleton, liver, islet, etc., yet its role in modulating angiogenesis is unknown. Here, we report that sufficient KINDLIN-2 is extremely important for NOTCH-mediated physiological angiogenesis. The expression of KINDLIN-2 in HUVECs is significantly modulated by angiogenic factors such as vascular endothelial growth factor A or tumor necrosis factor α. A strong co-localization of CD31 and Kindlin-2 in tissue sections is demonstrated by immunofluorescence staining. Endothelial-cell-specific Kindlin-2 deletion embryos die on E10.5 due to hemorrhage caused by the impaired physiological angiogenesis. Experiments in vitro show that vascular endothelial growth factor A-induced multiple functions of endothelial cells, including migration, matrix proteolysis, morphogenesis and sprouting, are all strengthened by KINDLIN-2 overexpression and severely impaired in the absence of KINDLIN-2. Mechanistically, we demonstrate that KINDLIN-2 inhibits the release of Notch intracellular domain through binding to and maintaining the integrity of NOTCH1. The impaired angiogenesis and avascular retinas caused by KINDLIN-2 deficiency can be rescued by DAPT, an inhibitor of γ-secretase which releases the intracellular domain from NOTCH1. Moreover, we demonstrate that high glucose stimulated hyperactive angiogenesis by increasing KINDLIN-2 expression could be prevented by KINDLIN-2 knockdown, indicating Kindlin-2 as a potential therapeutic target in treatment of diabetic retinopathy. Our study for the first time demonstrates the significance of Kindlin-2 in determining Notch-mediated angiogenesis during development and highlights Kindlin-2 as the potential therapeutic target in angiogenic diseases, such as diabetic retinopathy.
研究领域:
分子生物学
·
细胞生物学
·
发育生物学
·
血管生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2020
·
IF 3.347
Xiaolei Wang,Kaiyan Lou,Xiaodong Song,Huijuan Ma,Xinyi Zhou,Huan Xu,Wei Wang
Mebendazole (MBZ) is a tubulin-suppressive antihelmintic agent with low toxicity, which has been repurposed to treat different types of tumors. Chemoresistance is quite common in refractory or relapsed T cell acute lymphoblastic leukemia (T-ALL), which leads to dismal chances of recovery. In this study, MBZ was found to suppress the proliferation and reduce the viability of T-ALL cell line, CCRF-CEM, and its chemoresistant derivative, CEM/C1, at nanomolar concentrations. The inhibitive effects were found to be dose-dependent and not to be affected by the chemoresistance of CEM/C1 cells. Cell cycle arrest, caspase 3/7 activation and tubulin disruption were found in the MBZ-treated T-ALL cells. Notch1 signaling, which is often aberrantly activated in T-ALL cells, was showed to be suppressed by MBZ treatments. MBZ administration in murine T-ALL models also suppressed the growth of CEM/C1 cells, indicating that MBZ may be developed as a therapeutic agent for chemoresistant T-ALLs. The mRNA levels of the Notch1 and Hes1 were also confirmed to be suppressed by MBZ in vivo, which was consistent with the in vitro observations. This study demonstrated, for the first time, that MBZ could inhibit chemoresistant T-ALL cells both in vitro and in vivo , and the Notch1 signaling pathway was suppressed by MBZ treatment.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）