Nutrients
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2022
·Vol. 14
·期 8
·1564
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IF 6.706
Hongbo Jiang,Pei Ma,Zhiguang Duan,Yannan Liu,Shihong Shen,Yu Mi,Daidi Fan
Gastric cancer (GC) is the leading causes of cancer-related death worldwide. Surgery remains the cornerstone of gastric cancer treatment, and new strategies with adjuvant chemotherapy are currently gaining more and more acceptance. Ginsenoside Rh4 has excellent antitumor activity. Conversely, the mechanisms involved in treatment of GC are not completely understood. In this study, we certified that Rh4 showed strong anti-GC efficiency in vitro and in vivo. MTT and colony formation assays were performed to exhibit that Rh4 significantly inhibited cellular proliferation and colony formation. Results from the wound healing assay, transwell assays, and Western blotting indicated that Rh4 restrained GC cell migration and invasion by reversing epithelial–mesenchymal transition (EMT). Further validation by proteomic screening, co-treatment with disitertide, and SIX1 signal silencing revealed that SIX1, a target of Rh4, induced EMT by activating the TGF-β/Smad2/3 signaling pathway. In summary, our discoveries demonstrated the essential basis of the anti-GC metastatic effects of Rh4 via suppressing the SIX1–TGF-β/Smad2/3 signaling axis, which delivers a new idea for the clinical treatment of GC.Keywords:ginsenoside Rh4;SIX1;TGF-β/Smad2/3 pathway;gastric cancer
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
ACTA PHARMACOLOGICA SINICA
·
2024
·
IF 6.9
Su Qi,Wang Jing-jing,Ren Jia-yan,Wu Qing,Chen Kun,Tu Kai-hui,Zhang Yu,Leong Sze Wei,Sarwar Ammar,Han Xu,Zhang Mi,Dai Wei-feng,Zhang Yan-min
Parkin ( PARK2 ) deficiency is frequently observed in various cancers and potentially promotes tumor progression. Here, we showed that Parkin expression is downregulated in liver cancer tissues, which correlates with poor patient survival. Parkin deficiency in liver cancer cells promotes migration and metastasis as well as changes in EMT and metastasis markers. A negative correlation exists between TMEFF1 and Parkin expression in liver cancer cells and tumor tissues. Parkin deficiency leads to upregulation of TMEFF1 which promotes migration and metastasis. TMEFF1 transcription is activated by Parkin-induced endogenous TGF-β production and subsequent phosphorylation of Smad2/3 and its binding to TMEFF1 promotor. TGF-β inhibitor and TMEFF1 knockdown can reverse shParkin-induced cell migration and changes of EMT markers. Parkin interacts with and promotes the ubiquitin-dependent degradation of HIF-1α/HIF-1β and p53, which accounts for the suppression of TGF-β production. Our data have revealed that Parkin deficiency in cancer leads to the activation of the TGF-β/Smad2/3 pathway, resulting in the expression of TMEFF1 which promotes cell migration, EMT, and metastasis in liver cancer cells.
研究领域:
肿瘤学
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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
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
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IF 2.2
Meng Zhang,Congyao Wang,Ruiqi Zhao,Jiabo Yuan
Background Asthma is a chronic disease characterized by airway remodeling, which results in a progressive decline in lung function. Senkyunolide A is one of the effective components of ligusticum chuanxiong Hort, it shows protective effects on many human diseases. However, the role of Senkyunolide A in asthma remains unclear. Results In our study, we established an asthma mouse model by ovalbumin (OVA) sensitization and challenge, and Senkyunolide A (20 mg/kg and 40 mg/kg) was given by intraperitoneal injection. For in vitro study, lung epithelial BEAS-2B cells were treated with TGF-β1 to induce epithelial mesenchymal transformation. Our study showed that Senkyunolide A (40 mg/kg) alleviated airway injury, inflammatory infiltration and airway remodeling induced by OVA in asthma mice. Meanwhile, Senkyunolide A (40 μM) recovered the high level of cell migration and profibrotic factors expression induced by TGF-β1. Mechanistically, Senkyunolide A abolished the effect of OVA or TGF-β1 on Smad2/3 phosphorylation at site Ser 465/467 /Ser 423/425 in mice or BEAS-2B cells and inhibited the activation of NLRP3 inflammasome induced by OVA. Conclusions In total, our study indicated that Senkyunolide A alleviated airway damage and airway remodeling in asthmatic mice and regulated the progress of asthma by inhibiting the TGF-β/Smad2/3 signaling pathway and NLRP3 activation.
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DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 10
·期 3
·753-769
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IF 6.843
Zhiwei Yin,Lu Sun,Liyang Shi,Hemin Nie,Jianwu Dai,Can Zhang
Poor tendon repair remains a clinical problem due to the difficulties in replicating the complex multiscale hierarchical structure of native tendons. In this work, a bioinspired fibrous scaffold with bimodal micro-nanofibers and a teno-inductive aligned topography was developed to replicate microscale collagen fibers and nanoscale collagen fibrils that compose native tendons. The results showed indicated that the combination of micro- and nanofibers enhanced the mechanical properties. Furthermore, their biological performance was assessed using tendon stem/progenitor cells (TSPCs). Micro-nanofibers induced a higher cell aspect ratio and enhanced the tenogenic differentiation of TSPCs compared to micro- and nanocontrols. Interestingly, it was observed that scaffold nanotopography and microstructures promoted tenogenesis via activating the TGF-β/Smad2/3-mediated signaling pathway. The in situ implantation study confirmed that micro-nanofibrous scaffolds promoted the structural and mechanical properties of the regenerated Achilles tendon. Overall, our study shows that the bimodal micro-nanofibrous scaffold developed here presents a promising potential to improve the outcomes of tendon tissue engineering.
研究领域:
组织工程
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生物材料
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再生医学
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细胞生物学
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机械工程
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2018
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IF 2.559
Qing Shu,Song Lai,Xiao-Mei Wang,Yun-Long Zhang,Xiao-Lei Yang,Hai-Lian Bi,Hui-Hua Li
Pathological cardiac hypertrophy is the main risk factor for heart diseases. The ubiquitin-proteasome system (UPS) is the major intracellular protein degradation system involved in the development of cardiac hypertrophic remodeling. Ubiquitin-activating enzyme E1, a key component of the UPS, catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation via proteasome . However, the functional role of E1 (UBA1) in regulation of hypertrophic remodeling in angiotensin II (Ang II)-infused mice remains unknown. In this study, male wild-type mice were treated with UBA1 inhibitor PYR-41 at two doses of 5 and 10 mg and infused with Ang II (1000 ng/kg/min) for 14 days. Systolic blood pressure was detected by using tail-cuff system. Cardiac function was assessed by echocardiography. Hypertrophic remodeling was analyzed examined by histological examinations. The expressions of genes and proteins were detected by quantitative real-time PCR and immunoblotting analysis. After 14 days, Ang II infusion significantly increased UBA1 expression at both mRNA and protein levels in the hearts. Furthermore, Ang II-infused mice showed a significant increase in systolic blood pressure compensatory cardiac function, hypertrophy, interstitial fibrosis, inflammation and oxidative stress compared with saline-treated controls, whereas these effects were dose-dependently attenuated in PYR-41-treated mice. These beneficial actions were associated mainly with inhibition of PTEN degradation and multiple downstream mediators (AKT, ERK1/2, STAT3 , TGF-β/Smad2/3 and NF-kB(p65)). In conclusion, these results indicate that inhibition of UBA1 suppresses Ang II-induced hypertrophic remodeling, and suggest that administration of low dose PYR-41 may be a new potential therapeutic approach for treating hypertensive heart diseases.
研究领域:
心脏病学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2022
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IF 3.246
Xiaomeng Zou,Tiantian Li,Yingxuan Mao,Mingwei Zhu,Xi Chen,Jiamei Niu,Tianxiu Dong,Jian Jiang,Xiuhua Yang
Objectives . Preparation of a multifunctional drug-loaded phase-change nanoparticle (NP), pirfenidone perfluoropentane liposome NPs (PPL NPs), and combined with low-intensity focused ultrasound (LIFU) to influence epithelial mesenchymal transition (EMT) for hepatocellular carcinoma (HCC) by inhibiting the activity of activated Hepatic Stellate Cells (a-HSCs ). Methods . PPL NPs were prepared by the thin film dispersion method. The appearance, particle size, zeta potential, encapsulation efficiency, drug loading rate, drug release in vitro, and stability of PPL NPs were tested. The role of a-HSCs in HCC metastasis was studied by CCK-8, colony formation assay, apoptosis, cellular uptake assay, wound healing assay, and Transwell assay. Western blot was used to detect the related protein expression levels. In vitro and vivo, the acoustic droplet vaporization (ADV) of PPL NPs was tested at different times and LIFU intensities. Biosafety of the PPL NPs was assessed by measuring nude mouse body weight and hematoxylin and eosin (H&E) staining . Results. The results showed that the PPL NPs had good biosafety, with an average particle size of 346.6 ± 62.21 nm and an average zeta potential of -15.23 mV. When the LIFU power is 2.4 W/cm 2 , it can improve the permeability of cells, further promote the uptake of drugs by cells, and improve the toxicity of drugs. In vitro experiments showed that PPL NPs could inhibit the proliferation of a-HSCs cells, thereby affecting the metastasis of HCC, and were related to the TGF β -Smad2/3-Snail signaling pathway. Both in vivo and in vitro PPL NPs enhanced ultrasound imaging by LIFU-triggered ADV . Conclusion. The PPL NPs designed and prepared in this study combined with LIFU irradiation could significantly alter the EMT of HCC by inhibiting LX2. Clinically, PPL NPs will also be considered a promising contrast agent due to their ultrasound imaging capabilities.
研究领域:
纳米技术
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肿瘤学
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药剂学
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超声成像
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
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