MICROCHIMICA ACTA
·
2017
·Vol. 184
·期 9
·3121-3130
·
IF 4.58
Yuan Guolin,Wang Lei,Mao Dayong,Wang Fang,Zhang Jicai
The β1 receptor blocker metoprolol targets the hypertension-carrying adrenergic receptor gene (ADRB1), but therapy is often hindered by a lack of evidence-based medical information. The authors describe an assay for the ADRB1 gene. It is based on the electrocatalytic oxidation of H 2 O 2 by a nanocomposite consisting of hemin and platinum nanoparticles in an amino-modified metal-organic framework of the type Fe-MIL-88-NH 2 and heavily loaded with Cu(II) ions. The nanocomposite was placed on a glassy carbon electrode (GCE), and the resulting sensor displays increased electrocatalytic activity with the addition of H 2 O 2 because of the synergistic effects of hemin and the platinum nanoparticles (Pt NPs). Next, a capture DNA probe for the target ADRB1 gene was immobilized on the modified GCE. Binding of the target gene results in a distinct change in the electrocatalytic activity of H 2 O 2 . The amperometric i–t curves were recorded at −0.4 V in 5 mL of phosphate buffered saline at room temperature. The electrode responds to ADRB1 in the 1 f. to 10 nM concentration range and has a 0.21 f. detection limit (at a S/N ratio of 3). In our perception, this detection scheme can simplify and accelerate the identification of drug response and therapeutic efficacy. Conceivably, it may be applied to other mutations, and it may enable a more precise clinical prognosis and thus facilitate personalized medical diagnostics.
Schematic presentation of an electrode for the determination of the adrenergic receptor gene (ADRB1). The assay is based on the electrooxidation of added H 2 O 2 by using a glassy carbon electrode (GCE) coated with a composite prepared from platinum nanoparticles (Pt NPs), hemin and a metal-organic framewok of type Fe-MIL-88NH 2 loaded with Cu(II). This versatile platform simplifies studies on the response of hypertension drugs and the effectiveness of therapy.
研究领域:
生物化学
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医学诊断
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纳米材料科学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Canchao Jia,Minjuan Yang,Guanlin Xiao,Zhihao Zeng,Lingjie Li,Yangxue Li,Jieyi Jiang,Aili Xu,Jinyan Qiu,Ruiyin Tang,Dongmei Li,Dezheng Jia,Canhui Xie,Guangying Wu,Dake Cai,Xiaoli Bi
Backgrounds Idiopathic pulmonary fibrosis (IPF) is a persistent and advanced pulmonary ailment. The roles of innate immunity and adaptive immunity are pivotal in the evolution of IPF. An ill-adjusted interaction between epithelial cells and immune cells is responsible for initiating the epithelial–mesenchymal transition (EMT) process and sustaining chronic inflammation, thereby fostering fibrosis progression. The intricacy of IPF pathogenesis has hindered the availability of efficacious agents. Elephantopus scaber Linn. (ESL) is a canonical Chinese medicine with significant immunoregulatory effects, and its aqueous extract has been proven to attenuate IPF symptoms in bleomycin (BLM)-induced mice. However, the underlying mechanism through which ESL relieves IPF remains unclear. Aim To validate whether ESL reverses IPF by mediating the immune response and EMT. Methods : Ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and UPLC were used to identify the components and determine the concentrations of the specific compounds in the ESL. Network pharmacology and molecular docking were applied to predict the potential mechanism underlying the anti-IPF effect of ESL. BLM-induced IPF mice were used to validate the anti-IPF effect of ESL, and lung tissue was collected to test putative pathways involved in inflammation and EMT via immunohistochemistry (ICH), real-time quantitative polymerase chain reaction (RT–qPCR) and Western blotting. Results Sixty-one compounds were identified, and thirteen main ingredients were quantified in the ESL. In silico experiments predicted that the IPF-mediated reversal of adverse effects by ESL would be related to interruption of the Toll-like receptor 4 (TLR4)/nuclear factor-k-gene binding (NF- ĸ B) inflammatory pathway and the transforming growth factor-beta l (TGF-β1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O3 (FOXO3a) fibrosis pathway. In vivo experiments showed that ESL alleviates BLM-induced lung inflammation and fibrosis by reducing neutrophil aggregation and fibroblast foci, similar to the effects of the positive control drug pirfenidone (PFD). ESL markedly inhibited the transcription of TNF-α, IL-1 β, and IL-6, which are downstream genes of the NF-κB signaling pathway. Furthermore, the protein levels of TLR4 and p-NF- κ B were correspondingly inhibited in response to ESL treatment. Additionally, ESL reverses BLM-induced changes in the expression of EMT-related biological characteristic indicators (collagen I [COLIA1], E-cadherin, and alpha smooth muscle actin [ α -SMA]) at the messenger ribonucleic acid (mRNA) level and markedly inhibits the expression of EMT-related upstream proteins (TGF- β 1, p-PI3K, p-Akt, and p-FOXO3a). Conclusion Our research suggested that ESL attenuates BLM-induced IPF through mediating the EMT process via the TGF-β1/PI3K/Akt/FOXO3a signaling pathway and inhibiting inflammation through the TLR4/NF-κB signaling pathway, highlighting that ESL can serve as an immunoregulator for relieving the abnormal immune response and reversing the EMT in IPF.
研究领域:
药理学
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免疫学
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呼吸医学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Fujing Wang,Rong Hu,Jiaxing Zhang,Tingting Pei,Zhuo'en He,Liliang Ju,Zhongxiao Han,Mingqing Wang,Wei Xiao
Renal fibrosis is the pathological consequence of progressive chronic kidney disease . Although it has been reported that vitamin D3 exerts antifibrotic effects, the underlying mechanisms remain unclear. This study is aimed at investigating the effects and molecular mechanisms in high-dose vitamin D3 treatment on renal fibrosis. A model of chronic kidney disease was established by 5/6 nephrectomy in rats characterised by high levels of serum creatine, urea nitrogen, and urinary protein. Serum 25-dihydroxyvitamin D3, calcium and parathormone levels were measured to evaluate vitamin D levels. Hematoxylin and eosin , periodic acid Schiff and Mallory's Trichrome staining were used to evaluate histopathological changes in rats. Moreover, the expression of vimentin , collagen I, α-smooth muscle actin and E-cadherin were analyzed at molecular and histopathological levels. Our results showed that exposure to vitamin D3 decreased the levels of serum creatine, urea nitrogen and urine protein and restored the homeostasis of calcium and parathormone. Vitamin D3 also downregulated the expression of vimentin, collagen I and α-smooth muscle actin and attenuated renal fibrosis and epithelial to mesenchymal transition in the kidney. Importantly, vitamin D3 treatment increased the expression of the vitamin D receptor and inhibited Transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathway in rats kidneys with chronic kidney disease. Mechanistically, the upregulation of TGF-β1 and phosphorylation of Smad3 induced by vitamin D3 was reversed by activation of the vitamin D receptor. Our findings indicated that vitamin D3 is a potential antifibrotic drug in chronic kidney disease via the vitmin D receptor and inhibiting TGF-β1/Smad3 signaling pathway.
研究领域:
肾病学
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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
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Chenggong Yu,Qingwen Xu,Xiaoling Cao,Shengnan Cheng,Zhijun Zhang,Jie Huang
Idiopathic pulmonary fibrosis (IPF) is a challenging interstitial lung disease characterized by heterogeneous manifestations and significant mortality. Due to the relative complexity of IPF pathogenesis, currently approved clinical drugs mainly for anti-inflammatory or anti-fibrotic present limited disease containment and insufficient damage repair, falling far short of previous expectations. To address this limitation, we developed an ionizable liposome nanodrug (named as TPNPs) co-loaded with small interfering RNA targeting TGF-β1 (si TGF-β1 ) and pirfenidone (PFD) for enhanced IPF therapy. The si TGF-β1 (blocking TGF-β signaling pathway) and PFD were carefully selected and integrated in consideration of their crucial roles in endothelial mesenchymal transition, alveolar epithelial cell apoptosis, and fibroblast differentiation and migration, which are closely related to IPF development. As a result, TPNPs exhibited synergistic enhancement effects against the damage of alveolar epithelial cells and fibroblasts in vitro . Notably, repeated administration of TPNPs mitigated the injury to alveolar epithelium, inhibited the excessive accumulation of extracellular matrix (ECM), and alleviated the destruction of lung, thereby synergistically ameliorating the lung function in a bleomycin (BLM)-induced murine model. This work provides a promising therapeutic strategy that combines nucleic acid with small molecule for enhanced treatment of IPF.
研究领域:
药理学
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肺科学
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2020
·Vol. 9
·期 6
·2090-2102
·
IF 6.183
Rui Shi,Jingshuang Zhang,Kun Niu,Weiyang Li,Ni Jiang,Jianlin Li,Qingsong Yu,Chengai Wu
Deferoxamine (DFO), an iron chelator regarded as a hypoxic analogue, has been reported to be involved in angiogenesis and osteogenic differentiation. In this study, DFO was loaded into nanospheres, Then, DFO-loaded NPs and free DFO were co-encapsulated in nanofibers through coaxial electrospinning and its effects on cell viability, migration, and osteogenic differentiation, and the potential mechanisms were investigated. The results suggested that DFO maintained cell viability and promoted the migration of human mesenchymal stem cells (hMSCs) and MC3T3-E1 cells. ALP activity, calcium deposition, and expression of osteogenesis-related markers, including collagen, osteocalcin, and osteopontin, were all increased with DFO. Moreover, hypoxia-inducible factor-1α, transforming growth factor-β, and Smad2 were upregulated with DFO, which indicated activation of the TGF-β1/Smad2 signalling pathway. This may contribute to osteogenic differentiation of cells.
研究领域:
生物材料
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组织工程
·
再生医学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER GENE THERAPY
·
2022
·Vol. 29
·期 12
·1939-1950
·
IF 5.854
Yang Fan,Li Lin,Mu Zhenzhen,Liu Pengyue,Wang Ying,Zhang Yue,Han Xiuping
The nuclear import receptor karyopherin β1 (KPNB1), a member of the Karyopherin protein family, is reported to be overexpressed in various cancers and promote carcinogenesis. By analyzing the correlation between the expression of KPNB1 and the overall survival rate of melanoma patients, we found that melanoma patients with higher expression of KPNB1 had worse survival. Furthermore, the database analyzed that the KPNB1 mRNA level was higher in melanoma samples than that in skin nevus tissues. We thus proposed that KPNB1 played a role in promoting melanoma development, and conducted gain-of- and loss-of-function experiments to test our hypothesis. We found that KPNB1 knockdown significantly retarded the growth and metastasis of melanoma cells in vitro and in vivo, and increased their sensitivity towards the anti-tumor drug cisplatin. KPNB1 overexpression had opposite effects. Notably, in melanoma cells, KPNB1 overexpression significantly decreased Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) protein level, which was also overexpressed in melanoma samples and enhanced malignant behaviors of melanoma cells. We further demonstrated that KPNB1 overexpression induced deubiquitination of G3BP1, and prevented its degradation. However, KPNB1 overexpression hardly affected the nuclear translocation of G3BP1. Additionally, alterations induced by KPNB1 overexpression were partly reversed by G3BP1 inhibition. Therefore, the results suggest that KPNB1 may promote melanoma progression by stabilizing the G3BP1 protein. KPNB1-G3BP1 axis represents a potential therapeutic targetable node for melanoma.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2022
·
IF 4.145
Runze Zhao,Li Yang,Shuangjian He,Tingting Xia
Intervertebral disc degeneration (IVDD) is a main contributor to induce low back pain, and the pathogenic mechanism of IVDD remains unclear. The nucleus pulposus (NP) is a component of the intervertebral disc (IVD) that provides protection from mechanical stimuli. The matrix stiffness of NP tissue increases during the process of disc degeneration. Although several studies have found that pathological mechanical stimuli induce NP cell senescence, which is relevant for NP degeneration, however, the effect of matrix stiffness on NP cell senescence is not clear. Therefore, in the present study, we used polyvinyl alcohol (PVA) hydrogel with controllable stiffness to mimic the matrix stiffness of normal (4 kPa) and severely degenerated (20 kPa) NP tissue. Rat NP cells were isolated and cultured on substrates with different stiffness, and the cell proliferation , SA-β-gal activity, cell cycle, telomerase activity and the phenotype markers of NP cells were analyzed. Moreover, cytoskeleton staining and NP cellular Young's modulus on different substrates were also measured. To further investigate how substrate stiffness affects NP cell senescence, lysyl oxidase (LOX) was used to restore the extracellular matrix (ECM) synthesis of NP cells. The expression levels of integrin β1 and p38 MAPK were then measured. Our results showed that the 20 kPa substrate significantly induced NP cell senescence compared to the 4 kPa substrate. NP cells cultured on the 20 kPa substrate failed to maintain the expression of their phenotype markers. Furthermore, the 20 kPa substrate induced an increase of Young's modulus of NP cells, which possibly through up regulating the expressions of integrin β1 and p38 MAPK. These results indicated that the integrin β1-p38 MAPK signaling pathway may participated in substrate stiffness induced senescence of NP cells. LOX significantly increased ECM synthesis and inhibited substrate stiffness induced NP cell senescence, which indicated that matrix mechanics may be essential for maintaining the function of NP cell. Our results may provide a new perspective on the mechanism of IVDD by pathological matrix mechanics.
研究领域:
骨科
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细胞生物学
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生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Jinxia Zhang,Xinxin Xie,Yuanjing Li,Haonan Wang,Lijuan Zhang,Peiqi Shi,Jing Wei,Ling Zhang,Yingdong Lu,Ligang Cui,Xiaoning Liu,Xiaolong Liang
Introduction Emodin alleviates renal interstitial fibrosis (RIF) and reduces inflammation by inhibiting the TGF-β1/Smad pathway, thus improving CKD outcomes. However, its clinical use is limited due to poor solubility and side effects. This study developed a targeted drug delivery system using αKIM-1 modified microbubbles carrying Emodin to enhance accumulation in renal tissues with high KIM-1 expression.Methods Emo@KP MBs were characterized by TEM and DLS, and their drug loading and encapsulation rates were measured by UV-VIS-NIR spectroscopy. Biocompatibility was assessed in vitro with HK-2 cells and in vivo via hematological and pathological markers. Contrast-enhanced ultrasound (CEUS) and fluorescence imaging were used for real-time visualization of treatment. Therapeutic experiments were performed on a unilateral ureteral obstruction (UUO) mouse model treated with Emo@KP MBs + US on days 1 and 3 post-surgery. Renal function, cytokine levels, and histological analysis were detected to evaluate therapeutic effects.Results Emo@KP MBs exhibited spherical structures (2 ~ 4 μm) with good stability. Ultrasound targeted microbubble destruction (UTMD) enabled controlled release of Emodin. CEUS and fluorescence imaging showed enhanced drug accumulation in diseased kidneys. In the UUO + Emo@KP MBs/US group, renal function was improved, inflammatory cytokines (IL-1β, TNF-α) were decreased, and renal lesions and collagen deposition were reduced. Immunohistochemistry revealed the downregulation of TGF-β, Smad2/3, and α-SMA, and upregulation of E-cadherin.Conclusion Emo@KP MBs enhanced drug delivery efficiency and therapeutic efficacy through αKIM-1 targeting and UTMD, while providing real-time imaging capabilities, suggesting good potential as a therapeutic approach to reduce renal inflammation and fibrosis in UUO.
研究领域:
药理学
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肾脏病学
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分子生物学
✓ 已验证
产品关联
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
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
·
分子生物学
·
药理学
✓ 已验证
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
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糖尿病学
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肾病学
✓ 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）