BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
·
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
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2016
·
IF 4.035
Shanyue Guan,Ruizheng Liang,Chunyang Li,Min Wei
Recently, how to design a formulation system with simultaneous diagnosis and therapy toward cancer has attracted tremendous attention. Herein, a supramolecular material was prepared via a facile method by the co-intercalation of folic acid (FA) and doxorubicin (DOX) into the gallery of Gd 3+ -doped layered double hydroxides (LDHs), followed by surface adsorption of fluorescein isothiocyanate (FITC). This supramolecular agent was proved to exhibit excellent magnetic resonance imaging (MRI) and fluorescence imaging (FI) behavior, as well as chemotherapy toward cancer (KB cell). The co-intercalated FA enables an efficient and selective drug delivery with good specificity. This work provides a facile approach for the fabrication of a drug formulation with dual-modal imaging and targeted therapy, which could be potentially used in the practical chemotherapy and medical imaging.
研究领域:
药学
·
纳米技术
·
生物医学工程
·
癌症研究
·
材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.2
Hainan Song,Weiwei Cao,Xiushi Chen,Siqi Peng,Wenlong Sun,Xiaojun Yang,Mahmoud Salah,Mohamed A. Farag,Yajing Fang
Effects of four flavonoid inhibitors (FIs, quercetin, kaempferol, luteolin, and flavone) at different concentrations on dynamically increasing dihydroquercetin (DHQ) uptakes and regulating P-glycoprotein (P-gp)’s mRNA and protein levels were evaluated in KB/MDR1 cells. DHQ’s bidirectional transport was measured in Caco-2 monolayers. The low uptakes of DHQ were dynamically increased by four FIs (better than elacridar) in the order of quercetin > luteolin > kaempferol > flavone. Four FIs significantly increased DHQ40’s uptakes in a dose-independent manner. Four FIs alone or with DHQ significantly decreased P-gp’s mRNA and protein expressions. DHQ was poorly absorbed (efflux ratios >20) in Caco-2 monolayers, especially at high concentrations. Four FIs improved DHQ’s absorption by significantly increasing (reversing) its influx (efflux) at most time points (1, 2, 4, and 6 h), especially for DHQ100 rather than DHQ40. Docking results explained that quercetin competitively occupies DHQ’s binding site or binds to the inhibitor site of P-gp. These results were valuable for improving DHQ absorption.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Yajing Fang,Weiwei Cao,Mengmeng Xia,Siyi Pan,Xiaoyun Xu
This study aims to evaluate the interaction of flavonoid–flavonoid by inhibiting the function of P-glycoprotein (P-gp). The cellular uptake of seven substrates and eleven co-incubated inhibitors was measured in KB/MDR cells. The effect of galangin or morin on the absorption of silibinin or wogonin was carried out in the rat everted gut sacs. Docking was performed to evaluate the interactions between inhibitors and P-gp. Most substrates were greatly enhanced by at least five co-incubated inhibitors. Conversely, the increased uptake of substrates coincided with a decrease or without affecting the uptake of inhibitors, implying a competitive/non-competitive inhibition on P-gp. The enhancement effect by galangin or morin on the transport of silibinin or wogonin was verified in everted gut sacs. Docking explained the inhibition of flavonoids on P-gp by competitively binding to the ATP site. These results provide a strategy for increasing the absorption of flavonoids by co-administration.
研究领域:
药理学
·
细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Shuang Luo,Jinrong He,Shaowei Huang,Xiaojing Wang,Yulin Su,Yanyang Li,Yanping Chen,Guanghua Yang,Bin Huang,Shaoju Guo,Lian Zhou,Xia Luo
Background Emodin is an active ingredient of traditional Chinese medicine Rheum palmatum L. and Polygonum cuspidatum , which possesses anti-inflammatory and intestinal mucosal protection effects. Our previous study found that emodin significantly alleviated ulcerative colitis induced by sodium dextran sulfate (DSS). In this study, we found the underlying mechanism of emodin on ulcerative colitis (UC). Purpose We aimed to further explore the mechanism of emodin in the treatment of ulcerative colitis from the perspective of metabolism and intestinal flora . Methods Ulcerative colitis was induced by 3% sodium dextran sulfate (DSS) on mice, and the mice were respectively treated with mesalazine , rosiglitazone , emodin, and emodin combined with GW9662 (PPARγ inhibitor) simultaneously. Weight changes , the disease activity index (DAI), colonic length, and pathologic changes in colon were used to evaluate the efficacy of emodin. LC-MS/MS was performed for metabolomics analysis of colon. In addition, intestinal flora was assessed using 16S rDNA sequencing. A vector-based short hairpin RNA (shRNA) method was used to silence PPARγ gene expression in Caco-2 cells. Results Emodin binds to the active site of PPARγ protein and forms hydrogen bond interaction with ARG288 and CYS285 amino acids. Furthermore, Emodin significantly promotes the protein expression of PPARγ, while inhibiting iNOS and NF-kB p65 in UC mice, however, this effect is hardly shown when it is combined with GW9662 (the inhibitor of PPARγ). Meanwhile, emodin suppresses the expression of iNOS in Caco-2 cells induced with IFNγ and IL-22, but has no effect on its expression in shPPARγ-Caco-2 cells. In addition, through activating PPARγ signal pathway , emodin is capable of regulating colonic metabolism including oxidative phosphorylation and citrulline metabolism and effecting luminal availability of oxygen and nitrate. This promotes the recovery of anoxic environment of colon epithelial cells, which strains the growth and expansion of Enterobacteriaceae . Conclusion The mechanism of Emodin in the treatment of ulcerative colitis relies on its regulation of PPARγ signal pathway, which could modulate colonic metabolism and restore intestinal homeostasis .
研究领域:
药理学
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胃肠病学
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分子生物学
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免疫学
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微生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Zhehan Yang,Zhenjia Yang,Xiaoshu Lv,Guangming Jiang,Xiaolong Zhang,Xiaodan Li,Xiaoyu Li,Ruo Yuan,Ying Zhuo
Quantifying trace markers in clinical samples with electrochemical impedance spectroscopy (EIS) biosensors is limited mainly by ubiquitous biofouling because traditional antifouling coatings suffer from low stability and unsatisfactory antifouling capability etc. Herein, a simple and effective strategy was constructed to achieve a highly specific EIS biosensing platform for quantifying protein and DNA in serum by using single-stranded oligonucleotides (ssDNA) as antifouling coating. To achieve the optimized antifouling capability of ssDNA coating, the influence factors of ssDNA structure are investigated by combining electrochemical experiments with theoretical calculations. The results demonstrated that the chemical adsorption of adenine on the Au surface is stronger than that of the other three bases, which endows the poly adenine-ssDNA (polyAn) coating with outstanding antifouling capability. Importantly, we found that the capture ligand structure and ssDNA length remarkably affected the antifouling capability of polyAn because of steric hindrance. As a proof of concept, EIS biosensors based on polyAn antifouling coating were developed to detect target DNA and nuclear factor kappa b p65 (NF-kB p65), respectively, exhibiting outstanding capability of detecting DNA and NF-kB p65 in human serum with low interference and good accuracy. Overall, the presented work may contribute to a deeper understanding of the influence factors of ssDNA-based antifouling coating and holds great insight into the construction of highly specific biosensors for quantifying disease markers in clinical samples.
研究领域:
生物传感器
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分析化学
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生物化学
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分子生物学
·
临床诊断
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产品关联
DOI
高影响因子
CURRENT CANCER DRUG TARGETS
·
2022
·Vol. 22
·期 9
·771-783
·
IF 2.907
Cui Zhi,Sun Shiqun,Li Jia,Li Jianing,Sha Tong,He Jie,Zuo Linjing
Background: Inhibitor of growth 4 (ING4) level was reported to be decreased in head and neck squamous cell carcinoma (HNSC) tissue, however, it is unknown whether and how ING4 participates in regulating the development of oral squamous cell carcinoma (OSCC). Objective: This study
aimed to investigate the role and mechanism of ING4 in OSCC. Methods: ING4 was forced to up- or down-regulated in two OSCC cell lines, and its effects on the malignant behavior of OSCC cells were investigated in vitro. The ubiquitination level of NF-kB p65 in ING4 upregulated cells was
measured by co-immunoprecipitation. Moreover, the effects of ING4 on the methylation level of ALDH1A2 were evaluated by methylation-specific polymerase chain reaction (MSP) assay. The role of ING4 in OSCC growth in vivo was observed in nude mice. Results: Our results showed that the expression
of ING4 in OSCC cell lines was lower than that in normal oral keratinocyte cells. In vitro, ING4 overexpression inhibited the proliferation, migration, and invasion of OSCC cell lines and ING4 silencing exhibited opposite results. We also demonstrated that ING4 overexpression promoted the
ubiquitination and degradation of P65 and reduced DNA methyltransferase 1 (DNMT1) expression and Aldehyde dehydrogenase 1A2 (ALDH1A2) methylation. Moreover, overexpression of p65 rescued the suppression of malignant behavior, induced by ING4 overexpression. In addition, ING4 negatively regulated
the growth of OSCC xenograft tumors in vivo. Conclusion: Our data evidenced that ING4 played a tumor-repressing role in OSCC in vivo and in vitro via NF-ΚB/DNMT1/ALDH1A2 axis.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
·
癌症研究
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DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-17
·
IF 17.694
Wang Weili,Zheng Huizhen,Jiang Jun,Li Zhi,Jiang Dongpeng,Shi Xiangru,Wang Hui,Jiang Jie,Xie Qianqian,Gao Meng,Chu Jianhong,Cai Xiaoming,Xia Tian,Li Ruibin
While hypoxia promotes carcinogenesis, tumour aggressiveness, metastasis, and resistance to oncological treatments, the impacts of hyperoxia on tumours are rarely explored because providing a long-lasting oxygen supply in vivo is a major challenge. Herein, we construct micro oxygen factories, namely, photosynthesis microcapsules (PMCs), by encapsulation of acquired cyanobacteria and upconversion nanoparticles in alginate microcapsules. This system enables a long-lasting oxygen supply through the conversion of external radiation into red-wavelength emissions for photosynthesis in cyanobacteria. PMC treatment suppresses the NF-kB pathway, HIF-1α production and cancer cell proliferation. Hyperoxic microenvironment created by an in vivo PMC implant inhibits hepatocarcinoma growth and metastasis and has synergistic effects together with anti-PD-1 in breast cancer. The engineering oxygen factories offer potential for tumour biology studies in hyperoxic microenvironments and inspire the exploration of oncological treatments.
研究领域:
生物医学工程
·
肿瘤学
·
纳米技术
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Guangzhen Yang,Mengni Fan,Jingwu Zhu,Chen Ling,Lihuang Wu,Xin Zhang,Ming Zhang,Jiayi Li,Qingqiang Yao,Zhongwei Gu,Xiaojun Cai
Specifically inhibiting the proliferation of activated macrophages and clearing the high levels of reactive oxygen species (ROS) secreted by macrophages is crucial for osteoarthritis (OA) treatment. Moreover, if the clearance of these high levels of ROS can be simultaneously used to induce oxidation-responsive release of anti-inflammatory drugs, the therapeutic effect of OA may be further improved. Here, a multifunctional anti-inflammatory drug (CPHs) based on a peptide dendrimer nanogel was constructed by physically encapsulating CORM-401 and wrapping its surface with folic acid (FA)-modified hyaluronic acid (HA). CPHs is capable of efficiently entering activated macrophages via FA- and HA-mediated specific targeting effects and then rapidly release large amounts of CO by massive consumption of H 2 O 2 . The generated CO effectively suppresses the secretion of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α by inhibiting cell proliferation ; inducing the activation of heme oxygenase (HO-1), and downregulating the expression of p38 MAPK , NF-kB (p50/p65) and TLR-2. In vivo experiments further confirmed that CPHs can massively deplete ROS in OA joints and effectively suppress the degradation of articular cartilage and their extracellular matrix. More importantly, CPHs is non-toxic to normal macrophages, and the high levels of CO generated in the joints do not result in notable changes in the HbCO levels in blood. Together, these results show that CPHs is an effective and safe anti-inflammatory drug and has essential application prospects in OA treatment.
研究领域:
药理学
·
炎症
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纳米技术
·
骨科
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Jing Song,Fengyun Huang,Kun Ma,Rui Ding,Kai Tan,Dan Lv,Kiyoshi Soyano,Kai Zhao
Bifenthrin (BF) is a broad-spectrum insecticide that has gained widespread use due to its high effectiveness. However, there is limited research on the potential toxic effects of bifenthrin pollution on amphibians. This study aimed to investigate the 50 % lethal concentration (LC 50 ) and safety concentration of Chinese giant salamanders (CGS) exposed to BF (at 0, 6.25,12.5,25 and 50 μg/L BF) for 96 h. Subsequently, CGS were exposed to BF (at 0, 0.04, and 4 μg/L BF) for one week to investigate its toxic effects. Clinical poisoning symptoms, liver pathology, oxidative stress factors, DNA damage, and transcriptome differences were observed and analyzed. The results indicate that exposure to BF at 4 μg/L significantly decreased the adenosine-triphosphate (ATP), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) contents in the brain, liver, and kidney of CGS. Additionally, the study found that the malondialdehyde (MDA), reactive oxygen species (ROS), and 8-hydroxydeoxyguanosine (8-OHdG) contents were increased. The liver tissue exhibited significant inflammatory reactions and structural malformations. RNA-seq analysis of the liver showed that BF caused abnormal antioxidant indices of CGS. This affected molecular function genes such as catalytic activity, ATP-dependent activity, metabolic processes, signaling and immune system processes, behavior, and detoxification, which were significantly upregulated, resulting in the differential genes significantly enriched in the calcium signaling pathway, PPARα signaling pathway and NF-kB signaling pathway. The results suggest that BF induces the abnormal production of free radicals, which overwhelms the body's self-defense system, leading to varying degrees of oxidative stress. This can result in oxidative damage, DNA damage, abnormal lipid metabolism, autoimmune diseases, clinical poisoning symptoms, and tissue inflammation. This work provides a theoretical basis for the rational application of bifenthrin and environmental risk assessment, as well as scientific guidance for the conservation of amphibian populations.
研究领域:
环境毒理学
·
两栖生物学
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分子生物学
·
生态毒理学
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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）