Human Cell
·
2025
·Vol. 38
·期 3
·1-15
·
IF 3.1
Li Chenhao,Wang Xin,Shi Dongliang,Yang Meng,Yang Wenhua,Chen Liang
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by high recurrence rates, low survival rates, and a lack of therapeutic targets. Regulatory Factor X5 (RFX5) is a critical transcription factor during tumor progression. However, the role of RFX5 involving breast cancer or TNBC has not been studied. This study obtained 60 tumor samples of TNBC for analysis and ascertained that RFX5 is linked with the severe stage. We constructed RFX5 knockdown and overexpression models involving TNBC cells. RFX5 overexpression enhanced TNBC cell proliferation by detecting cell vitality and replication of DNA and analyzing cell cycle data. RFX5 facilitated cell migration and invasion, which were determined by wound healing and Transwell assays. The anti-apoptotic RFX5 properties were confirmed with Hoechst staining and Annexin V/PI apoptosis assays. The Notch pathway was activated in TNBC, and Jagged canonical Notch ligand 1 (JAG1) could enhance TNBC growth and metastasis. RFX5 upregulation elevated JAG1 mRNA and protein levels. Chromatin immunoprecipitation and luciferase reporter assays indicated that RFX5 promoted the transcriptional activation of JAG1 by binding the promoter (− 1890/+ 15 or − 1359/+ 15 area). JAG1 knockdown reduced RFX5-induced expression of Notch signaling-related factors Notch1, NICD, and Hes1. This paper indicated that RFX5 is a transcription factor for JAG1 and established that RFX5 could activate the Notch pathway via transcriptional activation of JAG1 and promote TNBC progression. Targeting RFX5 could be a promising therapeutic approach against TNBC.
研究领域:
肿瘤学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
CytoJournal
·
2024
·
IF 2.5
Xinghua Liang,Xuelian Liu,Long Zhang,Junhao Liu,Rong Yan,Haiyan Li,Xiancheng Zeng,Hong Wang
Objective:
Colorectal cancer is severely challenging because of the insufficient understanding of the mechanism underlying its resistance to clinical chemotherapy. The purpose of our study is to investigate the role of the LIM protein Ajuba (JUB) in the chemoresistance of colon cancer and its potential effect on clinical treatment.
Material and Methods:
The protein levels of JUB in colon cancer tissues were evaluated using Western blot analysis and immunohistochemistry assays. The correlation between JUB and the prognosis of patients with colorectal cancer was determined using Kaplan–Meier plot analysis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were employed to determine the 50% inhibitory concentration of 5-fluorouracil (5-FU) and thus assess the effect of JUB on the effectiveness of 5-FU. In addition, the rate of cellular apoptosis was measured using fluorescence-activated cell sorting assays. Side population and sphere formation analyses were conducted to determine the role of JUB in promoting the stem cell-like traits of colon cancer cells. In vivo assays were performed and detect whether the downregulation of JUB induces 5-FU sensitivity. Moreover, luciferase and Western blot assays were employed to uncover the mechanism through which JUB promotes chemoresistance in colon cancer.
Results:
JUB expression was upregulated in chemoresistant colon cancer (P < 0.001) and correlated with relapse-free survival (P = 0.000002). Functionally, the upregulation of JUB conferred 5-FU resistance to colon cancer cells in vitro, whereas the downregulation of JUB induced 5-FU sensitivity in colon cancer cells in vivo. The high expression of JUB promoted the tumorigenic capability of colon cancer cells. Furthermore, the increased expression of JUB activated multiple downstream genes of the Notch signaling pathway with increased expression in JUB-overexpressing cells but reduced expression in JUB-silenced cells. Importantly, the inhibition of Notch signaling using a small-molecule inhibitor significantly suppressed JUB-induced chemoresistance.
Conclusion:
Results suggest that JUB plays an important role and may serve as a biomarker for the clinical treatment of patients with 5-FU-resistant colon cancer.
研究领域:
肿瘤学
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分子生物学
·
药理学
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DOI
PubMed
高影响因子
RESEARCH IN VETERINARY SCIENCE
·
2020
·
IF 1.892
Jing Dong,Yuelei Chen,Wenhui Yang,Xi Zhang,Lin Li
Breast cancer is a high incidence disease in humans. Artemisinin is an important extract that is widely used as an antimalarial drug which also serve as effective treatments for cancer. 32 nude mice were injected with 0.2 ml of MDA-MB-231 cell suspension of 2 × 10 7 cells/ml respectively. The nude mice models were randomly divided into four groups of 8 in each group. Each group was given daily gavage, high dose group: 200 mg/kg/0.1 ml, middle dose group 100 mg/kg/0.1 ml, low dose group 50 mg/kg/0.1 ml, control group: 0.1 ml vegetable oil was fed continuously for 21 days. ELISA was used to detect serum vascular endothelial growth the content of factor VEGF and hypoxia-inducible factor HIF-1α were detected. The expression of Notch pathway-related factors in tumor tissue was detected by fluorescence quantitative assay. ELISA results showed that the serum VEGF decreased significantly in the high dose group compared with the control group ( p < .01), while the other dose groups did not have significant ( p > .05). The serum HIF-1α in the high dose group compared with the control group, the decrease in HIF-1α was significant ( p < .05), and the other groups were not significant ( p > .05). The result of fluorescence quantitative section showed that artemisinin could down-regulate the expression of notch signaling related factors notch1, Dll4 and Jagged1, and 200 mg/kg dose group had the most significant effect. It may inhibit the development of tumors by reducing serum angiogenesis-related factors VEGF, HIF-1ɑ and inhibiting the activity of notch1 signaling pathway related factors.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Yixin Li,Tiancheng Li,Cheng Zhu,Hairui Li,Runzhe Fang,Ruomei Li,Yu Jin,Zhiyu Zhu,Lunguo Xia,Bing Fang
Cartilage regeneration requires a specialized biomechanical environment. Macroscopically, cartilage repair requires a protracted, stable mechanical environment, whereas microscopically, it involves dynamic interactions between cells and the extracellular matrix. Therefore, this study aims to design a hydrogel that meets the complex biomechanical requirements for cartilage repair. Dynamic hybrid hydrogels with temporal stability at the macroscale and dynamic properties at the microscale are successfully synthesized. The dynamic hybrid hydrogel simulates the stress relaxation and viscoelasticity of the pericellular matrix, facilitating effective interactions between the extracellular matrix and cells. The in vitro and in vivo experiments demonstrated that the hybrid hydrogel significantly promoted cartilage repair. The dynamic hybrid hydrogel alleviates abnormal actin polymerization, reduces intracellular stress, and increases the volume of individual cells. By modulating the cytoskeleton, the hybrid hydrogel inhibits Notch signal transduction in both the receptor and ligand cells, resulting in an improved cartilage phenotype. This study introduces an effective hybrid hydrogel scaffold that modulates the chondrocyte cytoskeleton and Notch signaling pathways by establishing an appropriate biomechanical environment, thus offering a promising material for cartilage repair.
研究领域:
生物材料学
·
再生医学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2024
·
IF 12.4
Yitian Shi,Jiayin Peng,Mengfan Liu,Xiling Qi,Siyu Li,Qiangqiang Li,Qing Jiang,Liming Zheng,Jiankun Xu,Yun Zhao,Yifeng Zhang
The process of skeletal regeneration initiated by stem cells following injury, especially in fractures, is significantly impaired by aging and adverse factors. Nicotinamide mononucleotide (NMN), a critical endogenous precursor of nicotinamide adenine dinucleotide (NAD), has garnered extensive attention for its multifaceted regulatory functions in living organisms and its wide-ranging therapeutic potential. However, whether NMN contributes to trauma-induced skeletal regeneration remains unclear. Methods : The transverse femoral shaft fracture model was employed to evaluate the potential advantages of NMN administration for overall repair during the initial fracture stages in male mice through micro-CT analysis, histochemistry, and biomechanical testing. The pro-proliferative function of NMN on skeletal stem cells (SSCs) was investigated through flow cytometry, qRT-PCR, NAD content measurement, and cell proliferation assay. Results : In this study, we observed that the administration of NMN during the initial phase of fracture in mice led to a larger callus and corresponding improvement in micro-CT parameters. NMN enhances the cartilaginous component of the callus by elevating the NAD content, consequently accelerating subsequent endochondral ossification and the fracture healing process. Subsequent analyses elucidated that NMN was beneficial in promoting the expansion of diverse stem cells in vivo and in vitro potentially via modulation of the Notch signaling pathway. Moreover, the depletion of macrophages profoundly obstructs the proliferation of SSCs. Conclusion : Our discoveries provide a potential strategy for enhancing fracture healing through stimulation of callus SSC proliferation at an early stage, shedding light on the translational value of NMN as an enhancer for skeletal regeneration and highlighting the pivotal role of macrophage-stem cell interactions in governing the regenerative influence of NMN on stem cells.
研究领域:
再生医学
·
干细胞生物学
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骨科
·
分子生物学
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DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2024
·
IF 3.1
Liu Junhao,Yong Shuangshuang,Yin Sisi,Feng Jinhong,Lian Caihua,Chen Jie
Background Psoriasis is a common immune-related chronic inflammatory skin disease, often accompanied by significant itching, and once diseased, the course of the disease lasts for most of the lifetime. Tanshinol (TAN) is an active ingredient of Salvia miltiorrhiza , which possesses pharmacological effects such as anti-inflammatory and antioxidant properties. However, the effects of TAN on psoriasis have not been widely reported. Therefore, the aim of this study was to investigate the therapeutic effects and mechanisms of TAN in psoriasis. Methods An imiquimod (IMQ)-induced psoriasis mouse model was constructed and treated with different doses of TAN to observe the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. Further removal of macrophages or inhibition or activation of Notch signaling pathway was performed to examine the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. In addition, in vitro experiments verified that TAN regulates RAW264.7 macrophage polarization and cytokine secretion through the Notch pathway. Results The results showed that TAN alleviated IMQ-induced skin lesions and pathological phenotypes in psoriasis mice and inhibited Notch signaling pathway and M1-type macrophage polarization. Moreover, macrophage clearance and Notch signaling pathway activation inhibited the effect of TAN on psoriasis. Further in vitro experiments showed that Notch agonists reversed the effects of TAN on macrophage polarization and inflammatory cytokines. Conclusions Collectively, these findings suggest that TAN may exert a therapeutic effect on psoriasis by inhibiting the Notch signaling pathway and thus M1-type macrophage polarization.
研究领域:
药理学
·
免疫学
·
皮肤科
·
炎症
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Weike Shaoyong,Lu Sun,Yujie Gan,Hongli Jin,Wusu Wang,Lin Yin,Yizhen Wang,Mingliang Jin
Contaminant-bearing polystyrene microplastics (PSMPs) may exert significantly different toxicity profiles from their contaminant-free counterparts, with the role of PSMPs in promoting contaminant uptake being recognized. However, studies investigating the environmentally relevant exposure and toxic mechanisms of aged PSMPs binding to Cr are limited. Here, we show that loading of chromium (Cr) markedly alters the physicochemical properties and toxicological profiles of aged PSMPs. Specifically, Cr-bearing aged PSMPs induced severe body weight loss, oxidative stress (OS), autophagy, intestinal barrier injury, inflammation–pyroptosis response, and enteropathogen invasion in mice. Mechanistic investigations revealed that PSMPs@Cr exacerbated the OS, resulting in intestinal barrier damage and inflammation–pyroptosis response via overactivated Notch signaling and autophagy/cathepsin B/IL-1β pathway, respectively, which ultimately elevated mortality related to bacterial pathogen infection. In vitro experiments confirmed that autophagy-mediated reactive oxygen species (ROS) overproduction resulted in severe pyroptosis and impaired intestinal stem cells differentiation alongside the overactivation of Notch signaling in PSMPs@Cr-exposed organoids. Overall, our findings provide an insight into autophagy-modulated ROS overproduction within the acidic environment of autophagosomes, accelerating the release of free Cr from PSMPs@Cr and inducing secondary OS, revealing that PSMPs@Cr is a stable hazard material that induces intestinal injury. These findings provided a potential therapeutic target for environmental MPs pollution caused intestinal disease in patients.
研究领域:
环境科学
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毒理学
·
胃肠病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Genes & Diseases
·
2024
·
IF 6.9
Nan Wang,Xiaoyu Shen,Huakun Huang,Runhan Zhao,Habu Jiwa,Zongxin Li,Pei Li,Jixing Ye,Qiang Zhou
Amyloid precursor protein (APP), especially Swedish mutant APP (APPswe), is recognized as a significant pathogenic protein in Alzheimer's disease, but limited research has been conducted on the correlation between APPswe and the osteogenic differentiation of mesenchymal stem cells (MSCs). The effects of APPswe and its intracellular and extracellular segments on the osteogenic differentiation of bone morphogenetic protein 2 (BMP2)-induced MSCs were analyzed in this study. Our analysis of an existing database revealed that APP was positively correlated with the osteogenic differentiation of MSCs but negatively correlated with their proliferation and migration. Furthermore, APPswe promoted BMP2-induced osteogenic differentiation of MSCs, while APPswe-C (APPswe without an intracellular segment) had the opposite effect; thus, the intracellular domain of APPswe may be a key factor in promoting the osteogenic differentiation of MSCs. Additionally, both APPswe and APPswe-C inhibited the proliferation and migration of MSCs. Furthermore, the intracellular domain of APPswe inhibited the activity of the Notch pathway by regulating the expression of the Notch intracellular domain to promote the osteogenic differentiation of MSCs. Finally, APPswe-treated primary rat bone marrow MSCs exhibited the most favorable bone repair effect when a GelMA hydrogel loaded with BMP2 was used for in vivo experiments, while APPswe-C had the opposite effect. These findings demonstrate that APPswe promotes the osteogenic differentiation of MSCs by regulating the Notch pathway, but its extracellular segment blocks the self-renewal, proliferation, and migration of MSCs, ultimately leading to a gradual decrease in the storage capacity of MSCs and affecting long-term bone formation.
研究领域:
生物医学
·
细胞生物学
·
分子生物学
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DOI
高影响因子
Advanced Science
·
2025
·
IF 14.1
Dongjian Song,Qiuliang Liu,Zechen Yan,Qi Wang,Meng Su,Hui Zhang,Longyan Shi,Yingzhong Fan,Qian Zhang,Heying Yang,Da Zhang
This study investigates the molecular mechanisms by which superparamagnetic iron oxide nanoparticles (SPIONs) loaded with the WSGC peptide (WSGC@FA@PEG/PEI-SPIONs)—a 40-amino acid polypeptide derived from apoC-III—modulate chemotherapy resistance in gastric adenocarcinoma (GA). Emphasis is placed on their role in regulating mitophagy and mitochondrial homeostasis via the Notch signaling pathway. The physicochemical properties of WSGC@FA@PEG/PEI-SPIONs are thoroughly characterized, demonstrating favorable biocompatibility, stable size distribution, and efficient peptide loading. In vitro experiments show that these nanoparticles significantly inhibit GA cell proliferation, migration, and invasion by downregulating mitophagy-associated proteins (LC3, PINK1, and Parkin), primarily through modulation of the Notch pathway. In vivo studies, using a GA nude mouse model, confirm the therapeutic potential of WSGC@FA@PEG/PEI-SPIONs, revealing marked tumor growth inhibition and increased apoptotic activity. Collectively, the findings highlight the WSGC peptide as a promising therapeutic agent for overcoming chemotherapy resistance in GA by targeting the Notch signaling pathway and suppressing mitophagy, thereby presenting a novel strategy for polypeptide-based cancer therapy.
研究领域:
纳米医学
·
肿瘤学
·
分子生物学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2024
·
IF 2.8
Lu Yan,Yin-Sen Song,Jian Zhou,Lin Zhu,Tian-Wei Shi,Hui-Qian Yu,Zi-Qing Dong,Wei Wang,Ting Long,Hao-Ying Liu,Zhe-Ye Shi,Jian-Guo Li
Background Nicastrin, a subunit of the γ-secretase complex, is encoded by the NCSTN gene and regulates notch signaling, it is involved in the pathogenesis of hidradenitis suppurativa (HS), Alzheimer disease (AD), and liver cancer. However, the animal models for studying HS are relatively scarce. Methods CRISPR/Cas-mediated genetic engineering was used to generate targeted knockout offspring mice (C57BL/6J). Different doses (10 mg/kg, 20 mg/kg, and 30 mg/kg) and injection methods (subcutaneous/intraperitoneal/gavage injection) of tamoxifen were used to induce the construction of NCSTN knockout mice (mice model). The expressions of nicastrin, NICD1, hes1 in skin, brain, and liver tissue in mice model and wild-type (WT) mice were measured by qRT-PCR and IHC. Results The construction of mice model was successfully induced by tamoxifen, knockout efficiency was 93%, there was no difference in knockout efficiency among three doses, injection methods, genders ( P > 0.05). HS-like lesions appeared on the skin of NCSTN knockout mice after 1 month of treatment with tamoxifen, male mice had a higher number of skin lesions compared to female mice (male vs female = 76.5% vs 41.7%, P = 0.027). Compared with WT mice, the expressions of nicastrin (skin P = 0.0009, brain P = 0.0194, liver P = 0.0066), NICD1 (skin P = 0.0115, brain P = 0.0307, liver P = 0.008), hes1 (skin P = 0.0476, brain P = 0.0143, liver P = 0.0003) in mice model all decreased. Conclusions The NCSTN knockout mouse might be employed as HS animal model; Reducing nicastrin may affect the expression of notch1–hes1 pathway molecules in skin, brain, and liver tissues; low dose (10 mg/kg/d) tamoxifen could be used to induce the deletion of the target gene in mice.
研究领域:
分子生物学
·
遗传学
·
病理学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 21
·
IF 5.1
Junxia Ma,Yingshan Jiang,Yue Teng,Ting Ren,Yanchao Xing,Aoyun Li,Zhongmei He,Weijia Chen,Ying Zong,Rui Du
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and current treatments are limited by significant side effects. Deer bone, which is rich in proteins and various active compounds, possesses anti-inflammatory and bone-health-promoting properties. However, its fermented product’s effects on RA treatment remain unexplored. In this study, we evaluated the therapeutic effects of probiotic-fermented deer bone aqueous extract (BbF) in an adjuvant arthritis (AA) rat model, combined with LPS-stimulated RAW264.7 macrophage models. In vivo experiments showed that BbF significantly reduced paw swelling, arthritis index, and improved bone mineral density. BbF also alleviated synovial hyperplasia and inflammatory cell infiltration. It suppressed pro-inflammatory cytokines (TNF-α, IL-1β, etc.) and inhibited macrophage migration and invasion. Transcriptomic analysis revealed significant enrichment of the Notch signaling pathway, and Western blot confirmed the downregulation of Notch3, Notch4, DLL4, and Jagged1 proteins. BbF also restored gut microbiota homeostasis, increasing beneficial bacteria such asFirmicutesandClostridia, while decreasing potential pathogens likeProteobacteria,Gammaproteobacteria, andEscherichia-Shigella. Furthermore, BbF enhanced short-chain fatty acids (SCFCs) production, including butyrate and caproic acid. These results indicate that BbF alleviates RA by inhibiting the Notch signaling pathway and regulating gut microbiota, providing new insights for the development of functional foods with immune-modulatory properties.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2024
·
IF 4.8
Xiaoli Tang,Yanqing Geng,Rufei Gao,Zhuxiu Chen,Xinyi Mu,Yan Zhang,Xin Yin,Yidan Ma,Xuemei Chen,Fangfang Li,Junlin He
As a broad-spectrum and efficient insecticide, beta-Cypermethrin (β-CYP) poses a health risk to pregnancy. It matters the mechanisms of maternal exposure to β-CYP for impacting reproductive health. The placenta, a transient organ pivotal for maternal-fetal communication during pregnancy, plays a crucial role in embryonic development. The effect of β-CYP exposure on the placenta and its underlying molecular mechanisms remain obscure. The objective of this study was to investigate the effect of β-CYP exposure on placental development and the function of trophoblast, as well as the underlying mechanisms through CD-1 mouse model (1, 10, 20 mg/kg.bw) and in vitro HTR-8/SVneo cell model (12.5, 25, 50, 100 μM). We found slower weight gain and reduced uterine wet weight in pregnant mice with maternal exposure to β-CYP during pregnancy, as well as adverse pregnancy outcomes such as uterine bleeding and embryo resorption. The abnormal placental development in response to β-CYP was noticed, including imbalanced placental structure and disrupted labyrinthine vascular development. Trophoblasts, pivotal in placental development and vascular remodeling, displayed abnormal differentiation under β-CYP exposure. This aberration was characterized by thickened trophoblast layers in the labyrinthine zone, accompanied by mitochondrial and endoplasmic reticulum swelling within trophoblasts. Futher researches on human chorionic trophoblast cell lines revealed that β-CYP exposure induced apoptosis in HTR-8/SVneo cells. This induction resulted in a notable decrease in migration and invasion abilities, coupled with oxidative stress and the inhibition of the Notch signaling pathway. N-acetylcysteine (an antioxidant) partially restored the impaired Notch signaling pathway in HTR-8/SVneo cells, and mitigated cellular functional damage attributed to β-CYP exposure. Collectively, exposure to β-CYP induced oxidative stress and then led to inhibition of the Notch signaling pathway and dysfunction of trophoblast cells, ultimately resulted in abnormal placenta and pregnancy. These findings indicate Reactive Oxygen Species as potential intervention targets to mitigate β-CYP toxicity. The comprehensive elucidation contributes to our understanding of β-CYP biosafety and offers an experimental basis for preventing and managing its reproductive toxicity.
研究领域:
生殖毒理学
·
药理学
·
细胞生物学
·
分子生物学
✓ 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）