BIOMATERIALS
·
2021
·
IF 12.479
Liangliang Dai,Xiang Li,Xinmin Zheng,Zhenxiang Fu,Mengjiao Yao,Siyu Meng,Jiangong Zhang,Binbin Han,Quanli Gao,Jing Chang,Kaiyong Cai,Hui Yang
Immunosuppressive tumor microenvironment and low delivery efficiency severely impede the tumor chemotherapy effect. To address this issue, we develop a pH/ROS cascade-responsive prodrug micelle to deliver siTGF-β with size-shrinkage and charge-reversal property, leading to synergistical tumor microenvironment remodeling. The nanosystem highly improved endocytosis efficiency and tumor penetration depth through charge reversal and size reduction upon exposure to weakly acidic tumor microenvironment. Moreover, the nanocarrier would rapidly escape from endo/lysosome, disassemble and release siTGF-β and hydroxycamptothecin in response to high intracellular ROS. Furthermore, the nanosystem significantly boosted antitumor immune response and reduced immune tolerance with remodeling tumor microenvironment, which significantly prolonged the survival time of tumor-bearing mice (75% survival rate upon 35 days). It is realized by the combined effects of chemotherapy-enhanced immunogenicity and recruitment of effector T cells , TGF-β-blockade immunotherapy-activated inhibition immunosuppressive tumor microenvironment and epithelial-to-mesenchymal transition (EMT), and regulation physical tumor microenvironment via reducing the dense tumor extracellular matrix and the high tumor interstitial pressure obstacles. To this end, the nanosystem not only overcame biobarriers and reinforced antitumor immune response, but also effectively inhibited tumor growth, metastasis and recurrence in vivo .
研究领域:
肿瘤学
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药学
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SAUDI PHARMACEUTICAL JOURNAL
·
2023
·
IF 4.1
Chi-Ming Liu,ZiChen Shao,XuZhou Chen,HanWu Chen,MengQiao Su,ZiWen Zhang,ZhengPing Wu,Peng Zhang,LiJie An,YinJie Jiang,Ai-Jun Ouyang
Benign prostatic hyperplasia (BPH) is a common urinary disease among the elderly, characterized by abnormal prostatic cell proliferation. Neferine is a dibenzyl isoquinoline alkaloid extracted from Nelumbo nucifera and has antioxidant, anti-inflammatory and anti-prostate cancer effects. The beneficial therapeutic effects and mechanism of action of neferine in BPH remain unclear. A mouse model of BPH was generated by subcutaneous injection of 7.5 mg/kg testosterone propionate (TP) and 2 or 5 mg/kg neferine was given orally for 14 or 28 days. Pathological and morphological characteristics were evaluated. Prostate weight, prostate index (prostate/body weight ratio), expression of type Ⅱ 5α-reductase, androgen receptor (AR) and prostate specific antigen were all decreased in prostate tissue of BPH mice after administration of neferine. Neferine also downregulated the expression of pro-caspase-3, uncleaved PARP, TGF-β1, TGF-β receptor Ⅱ (TGFBR2), p-Smad2/3, N-cadherin and vimentin. Expression of E-cadherin, cleaved PARP and cleaved caspase-3 was increased by neferine treatment. 1–100 μM neferine with 1 μM testosterone or 10 nM TGF-β1 were added to the culture medium of the normal human prostate stroma cell line, WPMY-1, for 24 h or 48 h. Neferine inhibited cell growth and production of reactive oxygen species (ROS) in testosterone-treated WPMY-1 cells and regulated the expression of androgen signaling pathway proteins and those related to epithelial-mesenchymal transition (EMT). Moreover, TGF-β1, TGFBR2 and p-Smad2/3, N-cadherin and vimentin expression were increased but E-cadherin was decreased after 24 h TGF-β1 treatment in WPMY-1 cells. Neferine reversed the effects of TGF-β1 treatment in WPMY-1 cells. Neferine appeared to suppress prostate growth by regulating the EMT, AR and TGF-β/Smad signaling pathways in the prostate and is suggested as a potential agent for BPH treatment.
研究领域:
药理学
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泌尿学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Current Molecular Pharmacology
·
2024
·Vol. 17
·期 1
·e18761429315125
·
IF 2.4
YiDan Li,BingHua Tu,ZiTong Wang,ZiChen Shao,ChenHao Fu,JianQiang Hua,ZiWen Zhang,Peng Zhang,Hui Sun,ChenYan Mao,Chi-Ming Liu
Background Finasteride and doxazosin are used for the treatment of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Epithelial–mesenchymal transition (EMT) and TGF-β/Smad signaling pathway play an important role in BPH, little is known about the growth inhibition and anti-fibrosis effects of doxazosin on the regulation of EMT and morphology in the prostate. Objectives The present study examined the effects of doxazosin on testosterone propionate (TP)-induced prostate growth in vivo and in vitro and its impact on the EMT and TGF-β/Smad signaling pathway. Methods Mice were treated with TP. Doxazosin (5 or 10 mg/kg) and finasteride (10 mg/kg) were administered orally for 28 days in TP-induced mice. The prostate index (prostate/body weight ratio), morphological characteristics and the protein expression of the prostate were examined. We further examined the effects of doxazosin and finasteride on the EMT and TGF-β/Smad signaling pathway in mice and in human prostate stroma cell (WPMY-1). The protein expressions of TGF-β1, TGFBR2, p-Smad2/3, N-cadherin, vimentin, fibronectin and α-SMA, E-cadherin and prostate specific antigen (PSA) were determined after treatment by western blot. Results The prostate wet weight, prostate index decreased after treatment. Doxazosin (5 or 10 mg/kg), finasteride (10 mg/kg) or a combination treatment (doxazosin 10 mg/kg + finasteride 10 mg/kg) were shown to reverse the pathological and morphological characteristics of the prostate. Doxazosin and finasteride inhibited TP-induced prostate growth, EMT, and the TGF-β/Smad signaling pathway by downregulating the expression of TGF-β1, TGFBR2, p-Smad2/3, N-cadherin, vimentin, fibronectin and α-SMA, whereas expression of E-cadherin was increased after treatment with either doxazosin or finasteride. Doxazosin (1-50 μM) inhibited normal human prostate stroma cell growth (WPMY-1) after 48 h with or without testosterone treatment. Doxazosin also regulated the EMT and proteins related to the TGF-β/Smad signaling pathway in WPMY-1 cells after 24 h. Additionally, doxazosin decreased protein expression of the PSA both in vivo and in vitro. Conclusion This study demonstrated that doxazosin inhibits prostate growth by regulating the EMT and TGF-β/Smad signaling pathways in the prostate. This finding suggests that doxazosin has potential as a new signaling pathway for the treatment of BPH.
研究领域:
医学
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药理学
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分子生物学
✓ 已验证
DOI
高影响因子
Oncology Letters
·
2017
·Vol. 15
·期 1
·1362-1372
·
IF 1.39
Chun‑Yu Li,Qi Wang,Shen Shen,Xiao‑Lu Wei,Guo‑Xia Li
Epithelial‑mesenchymal transition (EMT) has been reported to play pivotal roles in tumor invasion and metastasis. Inhibition of EMT may exert beneficial effects in regulating metastasis. Oridonin (ORI), an active diterpenoid compound isolated from Rabdosia rubescens, was found to be a potent anti‑metastatic agent. However, the possible involvement of ORI in the EMT in malignant melanoma is unclear. The present study found that ORI inhibited cell migration, invasion, and adhesion in A375 and B16‑F10 melanoma cells. The transforming growth factor‑β1 (TGF‑β1)‑induced EMT was also inhibited in ORI‑treated cells, as reflected in the upregulation of E‑cadherin, and downregulation of vimentin and Snail. Similar results were observed in A375 and B16‑F10 melanoma cells treated with ORI. Furthermore, pre‑treatment with ORI blocked the TGF‑β1‑induced phosphoinositide 3‑kinase (PI3K)/AKT serine/threonine kinase (Akt)/glycogen synthase kinase (GSK)‑3β signaling pathway activation. These effects mimicked PI3 kinase inhibitor LY294002 treatment. ORI interfered with the PI3K/Akt/GSK‑3β pathway, and reversed TGF‑β1‑induced EMT, which suppressed the invasion and metastasis of melanoma cells. Taken together, the present study demonstrated that ORI inhibits melanoma cells migration, invasion, and adhesion and TGF‑β1‑induced EMT through the PI3K/Akt/GSK‑3β signaling pathway. These findings suggest that ORI is a promising anti‑metastasis agent for melanoma.
研究领域:
肿瘤学
·
细胞生物学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Huilun Xu,Ce Zhu,Zheng Liu,Hao Yang,Zhendong Zhang,Rui Xiao,Limin Liu,Ganjun Feng,Li Zhang
Once bone is damaged, a rapid surge of reactive oxygen species (ROS) and anaerobic glycolysis will create an oxidative stress and acidic microenvironment, thus inhibiting osteogenic factor expression and disrupting bone regeneration. To address this, we innovatively developed an alkaline hydrogel-coated poly(ether ether ketone) (PEEK) porous scaffold with VitaFlux functionality in this study. This decorated PEEK scaffold distinct from those hydrogel-perfused scaffolds with obstructed pores still kept its initial 3D-printed pore structure to allow the ingrowth of bone tissues. The results showed that the modified scaffold could not only exhibit significant efficacy in lowering oxidative stress, neutralizing acidic microenvironment, and activating TGF-β1 expression in serum through its inherent alkalinity but also recruit stem cells to the bone defect site and upregulate osteogenic factor expression via the TGF-β1/Smad signaling pathway. This study proved the obvious advantage of the modified scaffold in enhancing bone regeneration by the synergy of immune microenvironment remodeling and osteogenic factor expression enhancement, thus providing a facile method to modify bone scaffold which can facilitate a desirable bone repair process through self-activating the transfer of growth factors between the material and tissues.
研究领域:
生物材料
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组织工程
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再生医学
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生物医学工程
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免疫调节
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骨修复
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2017
·Vol. 43
·期 4
·1359-1368
·
IF 5.104
Du Lifen,Lei Yongfang,Chen Jinglou,Song Hongping,Wu Xinying
Background/Aims: Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. Method: Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and α-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. Results: It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-β1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. Conclusion: These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-β1/Smad pathways
研究领域:
药理学
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毒理学
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分子生物学
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生殖医学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 8
·期 1
·201-211
·
IF 5.251
Shuli Man,Miao Li,Jin Zhou,Haiyue Wang,Jinyan Zhang,Long Ma
Fe3O4 magnetic nanoparticles (MNPs), as one of the most intensively researched NPs, have a range of applications in cancer treatments. In current research, we have focused on the influences of MNPs on cancer cells. We chose polyethyleneimine (PEI) coated MNPs (PEI-MNPs) as a model and they are colloidally stable in biological media. It can be proved that PEI-MNPs result in autophagy induction via mTOR-Akt-p70S6 K and ATG7 signaling pathways. For the first time, we have reported that PEI-MNPs activate both NF-κB and TGF-β signaling, two key pro-inflammatory pathways, in cancer cells. More significantly, we have found that autophagy induction and NF-κB and TGF-β activation can be efficiently suppressed through the inhibition of PEI-MNP dependent reactive oxygen species (ROS) over-production. ROS are deemed as a ‘double edge sword’ for cancer cells, owing to the cancer-suppressing and cancer-promoting actions. Our findings would be useful for designing MNPs induced ROS anti-cancer strategies or diminishing long-term toxic effects.
研究领域:
纳米技术
·
癌症生物学
·
细胞信号传导
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2020
·
IF 3.701
Shan Shan Qi,Meng Li Shao,Sun Ze,Hong Xing Zheng
Salidroside from Rhodiola rosea L. has hypoglycemic effects, and has anti-osteoporosis effect in diabetic rats. Whether it has beneficial effects on diabetic nephropathy (DN) has not been fully reported. Here, a DN rat model was established by streptozotocin (STZ). Salidroside (10, and 20 mg kg −1 d −1 ) were orally giving for eight weeks. The purity of salidroside was 99%. The results showed that eight weeks salidroside supplementation dose-dependently decreased blood glucose, serum insulin, serum creatinine, blood urea nitrogen (BUN), as well as urinary albumin of DN rats, repaired the pathological changes of kidney tissue, the renal sclerosis and fibrosis in the kidney of DN rats were improved, and the activities of oxidative defense system associated enzyme such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were also improved. Serum inflammatory cytokines (including tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, and interleukin-6) were decreased significantly in DN rats after eight weeks salidroside supplementation. Immunohistochemical results showed that fibrosis related proteins such as transforming growth factor-β1 (TGF-β1), phospho-Smad2 (p-Smad2), and phospho-Smad3 (p-Smad3) expression levels were decreased significantly in the kidney of salidroside treated group. Our results indicate that daily salidroside consumption could alleviate DN in rats, the main mechanisms are anti-inflammatory, anti-oxidative stress, and inhibition of the TGF-β1/Smad2/3 pathway. This study suggested that salidroside could be used as a nutrient against DN, as well as diabetes.
研究领域:
药理学
·
糖尿病学
·
肾病学
✓ 已验证
产品关联
DOI
高影响因子
TOXICOLOGY LETTERS
·
2022
·
IF 4.271
Shuhong Guan,Hui Liu,Jun Zhou,Qiudi Zhang,Hui Bi
Transforming growth factor (TGF)-β1-induced fibrotic changes in alveolar epithelium is a critical event in pulmonary fibrosis . Herein, we recognized that lncRNA mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) was abnormally upregulated within human idiopathic pulmonary fibrosis (IPF) lung tissue, bleomycin (BLM)-caused pulmonary fibrotic model mice and TGF-β1-stimulated mice type II alveolar epithelial cells. In vivo , MIR100HG knockdown attenuated BLM-caused lung fibrogenesis in mice; in vitro , MIR100HG knockdown attenuated TGF-β1-induced fibrotic changes in mice type II alveolar epithelial cells. Through direct binding, MIR100HG knockdown upregulated microRNA-29a-3p (miR-29a-3p) expression; through serving as competing endogenous RNA for miR-29a-3p, MIR100HG knockdown downregulated TGF-beta activated kinase 1/MAP3K7 binding protein 1 (Tab1) expression. Finally, under TGF-β1 stimulation, Tab1 knockdown attenuated TGF-β1-induced fibrotic changes and partially attenuated the effects of miR-29a-3p inhibition. In conclusion, we demonstrated the aberrant upregulation of lncRNA MIR100HG in BLM-caused lung fibrogenesis and TGF-β1-stimulated MLE 12 cells. The MIR100HG/miR-29a-3p/Tab1 axis could modulate TGF-β1-induced fibrotic changes in type II alveolar epithelial cells and, thus, might be promising targets for pulmonary fibrosis therapy.
研究领域:
肺科学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2018
·Vol. 234
·期 3
·2537-2551
·
IF 3.923
Hai-Ming Xu,Feng-Hua Sui,Mei-Hua Sun,Gong-Liang Guo
Recent studies have shown that circulating microRNAs (miRNA) play a critical role in diagnosing acute coronary syndrome (ACS). This study aims to investigate the effect of miR-224 on atherosclerotic plaques forming and vascular remodeling in ACS and its relationship with TGF-β/Smad pathway. Myocardial infarction (MI) rat model was established and lentivirus vector of miR-224 inhibitor was prepared for investigating the effect of downregulated miR-224 on the contents of nitric oxide (NO) and endothelin-1 (ET-1), blood lipid levels and inflammatory factor levels in serum as well as the TGF-β/Smad pathway. The rats suffering from MI had decreased survival rates and exhibited reduced levels of NO, high-density lipoprotein cholesterol, and lumen diameter, and Smad7 messenger RNA (mRNA) and protein expression; while had significantly increased ratio of heart weight or body weight, levels of ET-1, inflammatory factors, blood lipid indexes, vascular remodeling indexes, collagen volume fraction, vulnerable atherosclerotic plaque area, VCAM-1 and MMP-2 protein expression, TGF-β, Smad2, Smad3, and Smad4 mRNA and protein expression. After inhibiting the TGF-β/Smad pathway, the rats suffering from MI showed notably opposite trend. In conclusion, downregulation of miR-224 expression promotes the formation of vulnerable atherosclerotic plaques and vascular remodeling in ACS through activation of the TGF-β/Smad pathway. Therefore, this study provides a new therapeutic target for ACS.
研究领域:
心脏病学
·
分子生物学
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2019
·
IF 2.197
YiXun Li,Huan Li,Yong Duan,XueMei Cai,DingYun You,Feng Zhou,ChuanQi Yang,XiaoYu Tuo,ZiJie Liu
Background. Xuanwei City in Yunnan province has been one of the towns with highest lung cancer mortality in China. The high content of amorphous silica in the bituminous coal from Xuanwei of Yunnan is mainly present as irregular and spherical silica nanoparticles (SiNPs). It has been reported that silica nanoparticles in bituminous coal correlated with the high incidence of lung cancer in Xuanwei. To explore the role and mechanism of SiNPs in the tumorigenesis of lung cancer in Xuanwei, human mononuclear cells (THP-1) and human bronchial epithelial cells (BEAS-2B) were cocultured in a transwell chamber. Combined with Benzo[a]pyrene-7, 8-dihydrodiol-9, and 10-epoxide (BPDE), SiNPs could significantly promote the proliferation and Epithelial-Mesenchymal Transition (EMT) and inhibit apoptosis of BEAS-2B cells and induce the release of TGF-α from THP-1 cells. After neutralizing TGF-α with antibody, the proliferation and EMT were decreased and enhanced apoptosis of BEAS-2B cells. Furthermore, the results showed that TGF-α in the sera of patients with lung adenocarcinoma in Xuanwei were significantly higher than in patients with benign pulmonary lesions in Xuanwei and those with lung adenocarcinoma in outside of Xuanwei of Yunnan. Taken together, our study found that SiNPs promoted the proliferation and EMT of BEAS-2B cells by inducing the release of TGF-α from THP-1 cells.
研究领域:
癌症研究
·
纳米技术
·
细胞生物学
·
分子生物学
·
环境健康
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2020
·Vol. 30
·期 43
·2004886
·
IF 16.836
Zilin Wang,Lili Liu,Wenhuan Bu,Mengdan Zheng,Nianqiang Jin,Kai Zhang,Xiaowei Xu,Ding Zhou,Bai Yang,Hongchen Sun
Skin lesions, as a relatively common clinical manifestation, not only damage the skin's barrier function, but also affect the skin's ability to feel temperature, pain and touch. However, a highly efficient method to restore the morphology and function of damaged skin remains an unmet goal. In this work, carbon dots (CDots) with excellent biocompatibility are synthesized via microwave-assisted heating ascorbic acid and polyethyleneimine. The synthesized CDots can induce the epithelial-mesenchymal transition (EMT) process by activating transforming growth factor-β/p-38 mitogen-activated kinase/Snail signaling pathway, leading to an increase of cell motility. Further, by assessing a series of in vivo wound healing assays and histological examinations, it is demonstrated that CDots can accelerate the migration of epithelial cells in the full-thickness cutaneous wounds through EMT. As a result, a rapid re-epithelialization covers the granulation tissue and epidermal barrier formed, leading to a block of the external stimuli, reduction of the inflammatory reaction and the granulation tissue area, and finally the promotion of the wound healing with fewer scars.
研究领域:
材料科学
·
生物材料
·
伤口愈合
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）