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
EUROPEAN JOURNAL OF HISTOCHEMISTRY
·
2023
·
IF 2
Jing Guo,Chang-Yong Tong,Jian-Guang Shi,Xin-Jian Li,Xue-Qin Chen
Lung cancer is prone to bone metastasis, and osteopontin (OPN) has an important significance in maintaining bone homeostasis. The goal of this study was to explore the impact of OPN level on bone metabolism and the molecular mechanism of inhibiting bone metastasis in non-small cell lung cancer (NSCLC). The expression of OPN in NSCLC was ascertained by Western blot and immunohistochemistry, and the correlation between the expression level of OPN and survival of patients was analyzed. Then the shRNA technology was applied to reduce the expression of OPN in NSCLC cells, and CCK-8 assay was carried out to investigate the effect of low expression of OPN on the proliferation of NSCLC cells. In addition, the effects of low expression of OPN on osteoclast differentiation, osteoblast generation and mineralization were studied using osteoclast precursor RAW264.7 and human osteoblast SaOS-2 cells, and whether OPN could regulate miR-34c/ Notch pathway to affect bone metabolism was further explored. The findings showed that the high level of OPN in NSCLC was closely related to the poor prognosis of patients and the abnormal proliferation of NSCLC cell lines. The suppression of OPN was beneficial to inhibit the differentiation of osteoclasts and promote the mineralization of osteoblasts. Besides, this study confirmed that the deletion of OPN can regulate bone metabolism through the regulation of miR-34c/Notch1 pathway, which will contribute to inhibiting the occurrence of osteolytic bone metastasis in NSCLC.
研究领域:
肿瘤学
·
分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ULTRASOUND IN MEDICINE AND BIOLOGY
·
2020
·
IF 2.514
Yao Liu,Yijin Fan,Huajun Tang,Chengzhi Li
The purpose of this study was to investigate the therapeutic effects of focused ultrasound on the expression of notch1, c-fos and transforming growth factor-β3 (TGF-β3) in genital skin of SD rats with vulvar lichen simplex chronicus (LSC). Fifty-six female SD rats with LSC were randomly divided into therapy and sham groups. The therapy group was exposed to focused ultrasound. The sham group received the same therapy with an instrument that had no power output. Four wk after a singly focused ultrasound therapy, histologic analyses revealed that recovered SD rats accounted for 75% of SD rats in the therapy group and 10.7% in the sham group. Total collagen fiber density in the superficial layer of dermis in the therapy group was significantly lower than that in the sham group. Notch1 and c-fos protein expression in the therapy group was significantly lower than that in the sham group, with the opposite effect present for TGF-β3. Focused ultrasound therapy may inhibit superficial collagen fibrosis in the dermis by affecting expression of notch1, c-fos and TGF-β3 in vulvar skin tissue and consequently reduce the recurrence rate of LSC.
研究领域:
皮肤病学
·
治疗超声
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
IMMUNOBIOLOGY
·
2023
·
IF 2.8
Zepeng Chen,Qinglong Gu,Ruichao Chen
Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon that can be influenced by microRNAs (miRNAs). This study aims to investigate the impact of miR-146a-5p on lipopolysaccharide (LPS)-induced Caco-2/HT-29 cell autophagy and NLRP3 inflammasome activation and the underlying mechanism, with the aim of identifying potential therapeutic targets. We used LPS to establish Caco-2/HT-29 cell models and measured cell viability by CCK-8. The levels of miR-146a-5p, RNF8, markers of NLRP3 inflammasome activation and autophagy, proteins involved in the Notch1/mTORC1 pathway, and inflammatory factors were assessed by RT-qPCR, Western blot, and ELISA. Intestinal epithelial barrier function was evaluated by measuring transepithelial electrical resistance. Autophagic flux was measured using tandem fluorescent-labeled LC3. miR-146a-5p was highly-expressed in LPS-induced Caco-2/HT-29 cells, and autophagy flux was blocked at the autolysosomal stage after LPS induction. Inhibition of miR-146a-5p suppressed NLRP3 inflammasome activation, reduced intestinal epithelial barrier damage, and facilitated autophagy inhibition in LPS-induced Caco-2/HT-29 cells. The autophagy inhibitor NH4Cl partially nullified the inhibitory effects of miR-146a-5p inhibition on NLRP3 inflammation activation. miR-146a-5p targeted RNF8, and silencing RNF8 partly abrogated the action of miR-146a-5p inhibition on promoting autophagy and inhibiting NLRP3 inflammasome activation. miR-146a-5p inhibition suppressed the Notch1/mTORC1 pathway activation by upregulating RNF8. Inhibition of the Notch1/mTORC1 pathway partially nullified the function of silencing RNF8 on inhibiting autophagy and bolstering NLRP3 inflammasome activation. In conclusion, miR-146a-5p inhibition may be a potential therapeutic approach for UC, as it facilitates autophagy of LPS-stimulated Caco-2/HT-29 cells, inhibits NLRP3 inflammasome activation, and reduces intestinal epithelial barrier damage by upregulating RNF8 and suppressing the Notch1/mTORC1 pathway.
研究领域:
炎症性肠病
·
分子生物学
·
细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2022
·
IF 5.195
Ningbo Cai,Bingtian Xu,Xing Li,Yunyun Qin,Mengfan Li,Kechun Chen,Jiangping Xu,Haitao Wang
The loss of tight junction (TJ) and adherens junction (AJ) proteins leads to the damage of the blood-brain barrier (BBB) during cerebral ischemia . Inhibition of cyclic nucleotide phosphodiesterase 4 (PDE4) by roflumilast (Roflu) protects against ischemic stroke-induced neuronal damage. However, the effects of Roflu on vascular endothelial injury and BBB integrity remain unknown. Here, we investigated whether and how Roflu protects against cerebrovascular endothelial injury caused by cerebral ischemia/reperfusion. We demonstrated that PDE4B knocking-down increased the expression of TJ and AJ proteins in human brain microvascular endothelial cells (HBMECs) subjected to oxygen-glucose deprivation reperfusion (OGD/R). Inhibition of PDE4 by Roflu (1.0 μM) showed similar effects as PDE4B knocking-down. We then found that Roflu activated Notch1/Hairy and enhancer of split 1 (Hes1) signaling. Consistently, the effects of Roflu on TJ and AJ proteins were reversed by the γ-secretase inhibitor DAPT or Hes1 knocking-down. Furthermore, Roflu (1.0 mg/kg) improved neurobehavioral outcomes and ameliorated BBB disruption in rats following ischemic stroke. Roflu also increased the levels of TJ proteins and AJ proteins in vivo . Collectively, these data suggest that Roflu is a promising compound for the prevention of BBB damage. The protective effects of Roflu are mediated through activation of the Notch1/Hes1 pathway.
研究领域:
神经科学
·
药理学
·
脑血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF MICROBIOLOGY
·
2024
·Vol. 206
·期 6
·1-11
·
IF 2.3
Zhuang Cuicui,Zhang Ruoqing,Bai Jiangang,Zhang Xinying,Zhao Jinhui
Escherichia coli ( E. coli ) can induce severe clinical bovine mastitis, which is to blame for large losses experienced by dairy farms. Macrophage polarization into various states is in response to pathogen infections. Lycopene, a naturally occurring hydrocarbon carotenoid, relieved inflammation by controlling M1/M2 status of macrophages. Thus, we wanted to explore the effect of lycopene on polarization states of macrophages in E. coli -induced mastitis. Macrophages were cultivated with lycopene for 24, before E. coli inoculation for 6 h. Lycopene (0.5 μmol/L) significantly enhanced cell viabilities and significantly reduced lactic dehydrogenase (LDH) levels in macrophages, whereas 2 and 3 μmol/L lycopene significantly enhanced LDH activities. Lycopene treatment significantly reduced the increase in LDH release, iNOS, CD86, TNF-α, IL-1β and phosphatase and tensin homolog (PTEN) expressions in E. coli group. 0.5 μmol/L lycopene significantly increased E. coli -induced downregulation of CD206, arginase I (ARG1), indoleamine 2,3-dioxygenase (IDO), chitinase 3-like 3 (YM1), PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, jumonji domain-containing protein-3 (JMJD3) and interferon regulatory factor 4 (IRF4) levels. Moreover, Ginkgolic acid C17:1 (a specific PTEN inhibitor), 740YPDGFR (a specific PI3K activator), SC79 (a specific AKT activator) or CHPG sodium salt (a specific NF-κB activator) significantly decreased CD206, AGR1, IDO and YM1 expressions in lycopene and E. coli -treated macrophages. Therefore, lycopene increased M2 macrophages via inhibiting NOTCH1-PI3K-mTOR-NF-κB-JMJD3-IRF4 pathway in response to E. coli infection in macrophages. These results contribute to revealing the pathogenesis of E. coli -caused bovine mastitis, providing the new angle of the prevention and management of mastitis.
研究领域:
免疫学
·
微生物学
·
药理学
·
细胞生物学
·
兽医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Zheng Wang,Mingyu Zhao,Yue Su,Qiangsen Zhao,Zhenhua Ma,Qiaoxian Yue,Zhiwei Zhu,Lihuan Zhang,Zhuocheng Hou,Huifeng Li
Excessive abdominal fat deposition negatively impacts poultry meat production and carcass yield. Identification of novel adipogenesis regulators may help improve production performance declines caused by excessive fat deposition. NUMB Endocytic Adaptor Protein ( NUMB ) typically functions as a cell fate determinant and plays a significant role in cell development and various diseases. Here, we found that NUMB is abundantly expressed in chicken abdominal fat depots and is induced in cultured adipocytes following adipogenic treatment. The gain- and loss-of-function experiments demonstrated that NUMB promotes the proliferation and G1/S transition of chicken adipocytes, enhances adipocyte differentiation, and increases the expression of PPARγ1 transcript. Through mRNA-seq analysis and molecular experiments, we further confirmed that NUMB inhibits the transcriptional activation of the NOTCH1 pathway and the expression of the downstream transcription factor HES1 by inducing NOTCH1 degradation. Nevertheless, the inhibition of the NOTCH1 / HES1 axis alone cannot fully explain NUMB 's role in adipogenesis, as NUMB also regulates the expression of multiple adipogenic transcription factors such as E2F1 , EGR2 , and NR4A3 . Our data suggest that NUMB is a potent activator of adipogenesis and enhances our understanding of its regulatory mechanisms in chicken abdominal fat deposition.
研究领域:
动物科学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Wang Yajun,Tan Jianxin,Du Hongmei,Liu Xue,Wang Siliang,Wu Simeng,Yuan Zhe,Zhu Xike
Adipocyte deposition is believed to be a primary characteristic of age-related thymic involution. Herein, we cultured primary thymic stromal cells (TSCs), used rosiglitazone, a potent peroxisome proliferator-activated receptor γ (PPARγ) agonist, to induce adipogenic differentiation, and investigated the differentially expressed genes during adipogenic differentiation by using RNA-sequencing analysis. Furthermore, the effects of Notch1 on rosiglitazone-induced adipogenic differentiation of TSCs as well as the underlying mechanisms were also investigated. As a result, we identified a total of 1737 differentially expressed genes, among which 965 genes were up-regulated and 772 genes were down-regulated in rosiglitazone-treated cells compared with control cells. Gene ontology (GO) enrichment analysis showed that the GO terms were enriched in metabolic process, intracellular, and protein binding. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that a number of pathways, including ubiquitin mediated proteolysis, PPAR signaling pathway, and mammalian target of rapamycin (mTOR) signaling pathway were predominantly over-represented. Meanwhile, overexpression of Notch1 suppressed and inhibition of Notch1 promoted rosiglitazone-induced adipogenic differentiation in TSCs, and the pro-adipogenic effects of the Notch inhibitor DAPT were associated with the activation of autophagy. Taken together, our results suggest that Notch1 is a key regulator in thymic adipogenesis and may serve as a potential target to hinder thymic adiposity in age-related thymic involution.
研究领域:
免疫学
·
分子生物学
·
细胞生物学
·
衰老研究
✓ 已验证
DOI
PubMed
高影响因子
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
Regenerative Biomaterials
·
2025
·
IF 8.1
Xia Hangbin,Yang Chen,Li Huili,Huang Lingwei,Zeng Zhen,Chi Runrun,Yang Ziwei,Wang Yuzen,Chang Jiang,Jiao Yiren,Li Wenzhong
Muscle satellite cells (MuSCs) play a vital role in skeletal muscle regeneration. However, in intractable muscle diseases such as volumetric muscle loss (VML), the quantity and function of MuSCs are significantly reduced, severely limiting the body's inherent muscle regeneration capability. In this study, we propose a novel strategy to modulate the fate of MuSCs using a combination of bioactive magnesium (Mg) and silicon (Si) ions, sustainably delivered through magnesium silicate (MgSiO3, MS) bioceramic-based scaffolds. In vitro, Mg and Si ions synergistically promote the proliferation and differentiation of MuSCs. Similarly, Mg and Si ions derived from MS/poly (L-lactic acid) (MS/PLLA) composite scaffold also increases the proliferation and differentiation ability of MuSCs. Furthermore, MS/PLLA composite scaffolds facilitate the activation of MuSCs, regeneration of muscle fiber, and neovascularization, while inhibiting fibrosis, thereby effectively restoring muscle function and promoting tibialis anterior muscle functional regeneration in a VML mouse model. Mechanistically, the combination of Mg and Si ions promotes the activation and proliferation of MuSCs by activating the Notch1-Hes1 pathway. Besides, the combination of Mg and Si ions also improves the differentiation of MuSCs by up-regulating Myod and Myog, and enhances fusion by up-regulating Mymk and Mymx expression. The outcomes of our research introduce a promising approach to the treatment of skeletal muscle injuries and related diseases.
研究领域:
再生医学
·
生物材料学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT NEUROVASCULAR RESEARCH
·
2022
·Vol. 19
·期 1
·61-72
·
IF 2.294
Xu Shu-Ying,Zeng Chun-Li,Ni Si-Ming,Peng Yong-Jun
Background: Acupuncture has been recommended as an alternative and complementary therapy for preventing and treating cerebral ischemia by the World Health Organization (WHO) for years. However, the mechanisms remain unclear. Accumulating evidence has shown that acupuncture can promote
angiogenesis to attenuate brain damage after ischemic stroke. In recent years, exosome- carried microRNAs (miRNAs) activated by acupuncture have proven effective in regulating pathological changes. We, therefore, investigated whether electro-acupuncture (EA) enhanced angiogenesis in cerebral
stroke via exosome-carried miR-210. Methods: We extracted and identified the exosomes from the serum of MCAO with EA treatment and injected them into MCAO rats for further observation. Simultaneously, miR-120 siRNA and HIF-1α inhibitor were transfected. Then, we evaluated the volume
of infarction, pathological changes, and expression levels of angiogenic related factors of each group of rats by TTC and HE staining, transmission electron microscope (TEM), western blot, and quantitative PCR (qPCR). Results: Compared with the MCAO group, EA-Exosome (EA-EXO) treatment
significantly decreased the infarct volume and the pathological damage, but miR-210 siRNA or HIF-1α inhibitor reversed the protective outcomes induced by EA-EXO. Moreover, EA-EXO treatment upregulated miR-210 and increased CD34, HIF-1α, VEGF, Notch1 protein, and mRNA expressions
compared to the MCAO group. MiR-210 siRNA or HIF-1α inhibitor treatments both down-regulated those angiogenic related proteins and mRNAs. Conclusion: EA treatment could activate the HIF-1α/VEGF/Notch 1 signal pathway to facilitate angiogenesis after ischemic stroke via exosomal
miR-210.
研究领域:
神经科学
·
分子生物学
·
中医药学
·
中风研究
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2019
·
IF 3.361
Shan Xu,Yong-Gang Kong,Wo-Er Jiao,Rui Yang,Yue-Long Qiao,Yu Xu,Ze-Zhang Tao,Shi-Ming Chen
Background and objective Tangeretin demonstrates broad anti-inflammatory effects. The present study aimed to assess whether tangeretin functions in regulating T-regulatory cells (Tregs) and alleviating allergic rhinitis (AR). Methods An ovalbumin (OVA)-induced AR animal model was constructed to monitor the changes in the allergic symptom score, OVA-specific IgE titers, histopathological characteristics and T-helper cell (Th1, Th2, and Th17)-related cytokine levels under tangeretin or dexamethasone (DXM) administration. The expression levels of Notch1/Jagged1 and FOXP3, and the proportion of Tregs in the spleens of these animals, were also detected. Furthermore, purified naive CD4 + T cells were utilized to assess the effects of tangeretin on Notch1 expression and their differentiation in vitro. Results Both tangeretin and DXM administration alleviated airway inflammation , decreased the production of serum OVA-induced IgE, but only tangeretin administration restored the balance of cytokine profiles compared with those in the AR group. The abundance of splenic CD4 + CD25 + FOXP3 + Treg cells and the transcription factor FOXP3 were significantly increased under tangeretin treatment , either in AR mice or in naïve CD4 + T-cell differentiation, followed by a concomitant reduction in Notch1/Jagged1 expression. However, as a positive control, the treatment of allergic rhinitis with dexamethasone was not related to the expression of Notch1/Jagged1 or the differentiation of Treg cells. Conclusion Tangeretin could promote regulatory T cell responses by inhibiting Notch1/Jagged1 expression, followed by promoting FOXP3/Treg cell differentiation and thus could serve as a novel curative therapeutic for AR.
研究领域:
免疫学
·
药理学
·
过敏
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
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