Genes & Genomics
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2022
·Vol. 44
·期 11
·1375-1384
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IF 2.164
Wang Yazhuo,Ren Yanan,Li Na,Zhao Jing,Zhao Sufen
Background Rab11a is a novel identified tumorigenic factor involved in different cancers. Objective This study aimed to assess the biological function of Rab11a in ovarian cancer (OC). Methods GEPIA database and real-time PCR were used to determine Rab11a expression in OC tissues and normal ovarian tissues. CCK-8, cell cycle, wound healing, transwell, and enzyme linked immunosorbent assay were used to detect the effects of Rab11a knockdown or overexpression on the proliferation, migration, and invasion of OC cells. Western blot analysis of autophagy-related markers and immunofluorescence staining of LC3 were performed to determine autophagy induction in Rab11a-silenced or overexpressed OC cells. Moreover, autophagy inhibitor 3-MA was employed to clarify the effects of Rab11a-regulated autophagy on the malignant phenotypes of OC cells. Results The mRNA level of Rab11a was increased in tumor tissues from OC patients as compared to the normal ovarian tissues. Knockdown of Rab11a in OVCAR-3 cells inhibited the growth of OC cells and led to cell cycle arrest, accompanied by reduced expression of PCNA and Cyclin D1. Rab11a deficiency suppressed migration and invasion of OC cells, accompanied by decreased secretion of MMP-2 and MMP-9. Silence of Rab11a impeded autophagy induction, as evidenced by decreased LC3 puncta formation, reduced abundance of LC3II and Beclin1, and increased p62 protein expression. In contrast, the ectopic expression of Rab11a in A2780 cells exerted opposite effects. Interestingly, autophagy inhibitor 3-MA abolished the effects of Rab11a overexpression on autophagy, proliferation, migration, and invasion. Conclusions Rab11a promotes the malignant phenotypes of OC cells by inducing autophagy.
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
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PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-19
·
IF 9.429
Jia Tao,Li Dan,Du Jiarui,Fang Xikui,Gerasimov Valeriy,Ågren Hans,Chen Guanying
Nanozymes are promising for precise cancer treatment, but are typically limited in terms of the low catalytic efficiency and the complexity in tumor microenvironment (TME). Herein, we describe a bimodal type of AgPd plasmonic blackbody (AgPd PB) nanozyme of compact sizes (< 30 nm), which presents not only boosted enzyme efficacy but also efficient photothermal therapy (PTT) for synergized therapy through tissue-penetrating light in the second biological window (1000–1700 nm). The synthesized hyperbranched AgPd PB nanozymes possess intense and broadband localized surface plasmonic resonance absorption of 400–1300 nm, entailing prominent photothermal efficiency (η = 45.1% at 1064 nm) for PTT. Importantly, PTT was found to significantly boost the nanozyme efficacy of both catalase (CAT) and peroxidase (POD) processes, which correspondingly decompose H2O2 to into O2 to relieve tumor hypoxia, and activate H2O2 to generate oxidative •OH radical. While the generated •OH was found to be able to minimize heat shock proteins (HSPs), which plays a vital role to counterbalance PTT effect both in vitro and in vivo. As compared to control ground without treatment, the synergized nanozyme and PTT activities resulted in about 7-fold reduction of tumor volume, thus elevating the survival rate from 0 to 80% at 30 days posttreatment. Besides the synergistic therapy, the AgPd PB nanozyme were shown to own fluorescence, computed tomography (CT), and photoacoustic (PA) imaging abilities, thus having implications for uses in imaging-guided precise cancer therapy. This study provides a paradigm of TME responsive theranostics under NIR-II light irradiation.Graphical Abstract
研究领域:
癌症治疗
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材料科学
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纳米医学
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生物医学工程
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DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2022
·
IF 4.369
Ying Wang,Jiyu Yang,Yu Wang,Yao Chen,Yiran Wang,Hongying Kuang,Xiaoling Feng
Polycystic ovary syndrome (PCOS) is a complex endocrine disease . Thioredoxin-interacting protein (TXNIP) promotes oxidative stress and triggers inflammation. Herein, we investigated the role and potential mechanism of TXNIP in PCOS. In a mouse model of dehydroepiandrosterone (DHEA)-induced PCOS, we found that TXNIP was upregulated in the ovaries , especially in granulosa cells (GCs). TXNIP was also upregulated in testosterone (T)-treated GCs in vitro. Knockdown of TXNIP by lentivirus-constructed shRNA attenuated T-induced GC injury and oxidative stress, as well as inflammation and the NLRP3 inflammasome . The mechanism by which TXNIP promotes inflammation may involve TXNIP dissociation from the TXNIP-TRX complex and binding to NLRP3 to form the inflammasome. Additionally, we verified that knockdown of TXNIP ameliorated ovarian injury and inflammation in mice with DHEA-induced PCOS in vivo. Collectively, we demonstrated that TXNIP is involved in GC inflammation by promoting NLRP3 inflammasome activation in PCOS.
研究领域:
内分泌学
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生殖医学
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分子生物学
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炎症
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DOI
PubMed
高影响因子
Foods
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2022
·Vol. 11
·期 15
·2360
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IF 5.561
Haiyan Zheng,Yu Pei,Yuan-Lin He,Yi Liu,Minqi Chen,Pengzhi Hong,Chunxia Zhou,Zhong-Ji Qian
Sulfated polysaccharides from red algae have a variety of biological activities, especially antitumor activities. Matrix metalloproteinase-9 (MMP-9) is a proteolytic metalloenzyme that degrades the central part of the extracellular matrix (ECM) and promotes tumor metastasis. In this research, we have investigated the influence and mechanism of GNP (sulfated polysaccharide fromGelidium crinale) on tumor metastasis and MMP-9 expression of human fibrosarcoma (HT1080) cells. The results inflected that the concentration of GNP below 100 μg/mL has no toxicity to HT1080 cells, but showed excellent activity in inhibiting cells migration and invasion. In addition, GNP effectively inhibits the mRNA of MMP-9 and reduces its expression and activity by regulating nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPK) and mTOR/PI3K/Akt signaling pathways. GNP has great potential as MMP-9 inhibitor and could be developed as a functional food or drug to prevent tumor metastasis.Keywords:sulfated polysaccharides;Gelidium crinale;MMP-9;migration;invasion
研究领域:
药理学
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肿瘤学
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海洋生物学
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PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2022
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IF 6.064
Li Yali,Wang Jing,Huang Fenghong,Zhang Yufei,Zheng Mingming
The artificial multienzyme systems developed by mimicking nature has attracted much interest. However, precisely controlled compositions and ratios of multienzymatic co-immobilization systems are still limited by the indistinguishable nature of enzymes. Herein, a strategy for fabricating DNA-directed immobilization of horseradish peroxidase (HRP) and glucose oxidase (GOx) on hybrid DNA nanoflowers (GOx-HRP@hDFs) is presented. The preparation of micron-sized hybrid DNA flowers (hDFs) begins with the predetermined repeatable polymer-like DNA sequences which contained two strands. The hDFs structure is generated through one-pot rolling circle amplification (RCA) and self-assembly with magnesium pyrophosphate inorganic crystals. Based on the rigid-base pairing, GOx and HRP conjugated with sequences complementary to strands would be anchored to the predesigned locations, respectively. By adjusting the loading amount/ratio of enzymes properly, the maximal catalytic efficiency can be precisely regulated. The reaction activity of GOx-HRP@hDFs was 7.4 times higher than that of the free GOx-HRP under the optimal mole ratio (GOx/HRP 4:1). In addition, this multienzyme catalyst system exhibits excellent precision, specificity, reproducibility, and long-term storage stability when applied to real human blood samples. The preceding results validate that GOx-HRP@hDFs are promising candidates for personal diabetes detection.
研究领域:
生物化学
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纳米生物学
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医学诊断
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PubMed
高影响因子
RESPIRATORY RESEARCH
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2022
·Vol. 23
·期 1
·1-16
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IF 7.162
Liu Haitao,Zhang Sha,Liu Yi,Ma Jing,Chen Wei,Yin Tao,Li Tongbin,Liang Bin,Tao Ling
Background Pulmonary hypertension (PH) is a progressive and fatal cardiopulmonary disease characterized by pulmonary vascular remodeling and increased pulmonary vascular resistance and artery pressure. Vascular remodeling is associated with the excessive cell proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). In this paper, the effects of heat shock protein-110 (HSP110) on PH were investigated.Methods The C57BL/6 mice and human PASMCs (HPASMCs) were respectively exposed to hypoxia to establish and simulate PH model in vivo and cell experiment in vitro. To HSP110 knockdown, the hypoxia mice and HPASMCs were infected with adeno-associated virus or adenovirus carring the shRNAs (short hairpin RNAs) for HSP110 (shHSP110). For HSP110 and yes-associated protein (YAP) overexpression, HPASMCs were infected with adenovirus vector carring the cDNA of HSP110 or YAP. The effects of HSP110 on PH development in mice and cell proliferation, migration and autophagy of PASMCs under hypoxia were assessed. Moreover, the regulatory mechanisms among HSP110, YAP and TEA domain transcription factor 4 (TEAD4) were investigated.Results We demonstrated that expression of HSP110 was significantly increased in the pulmonary arteries of mice and HPASMCs under hypoxia. Moreover, knockdown of HSP110 alleviated hypoxia-induced right ventricle systolic pressure, vascular wall thickening, right ventricular hypertrophy, autophagy and proliferation of PASMCs in mice. In addition, knockdown of HSP110 inhibited the increases of proliferation, migration and autophagy of HPASMCs that induced by hypoxia in vitro. Mechanistically, HSP110 knockdown inhibited YAP and transcriptional co-activator with PDZ-binding motif (TAZ) activity and TEAD4 nuclear expression under hypoxia. However, overexpression of HSP110 exhibited the opposite results in HPASMCs. Additionally, overexpression of YAP partially restored the effects of shHSP110 on HPASMCs. The interaction of HSP110 and YAP was verified. Moreover, TEAD4 could promote the transcriptional activity of HSP110 by binding to the HSP110 promoter under hypoxia.Conclusion sOur findings suggest that HSP110 might contribute to the development of PH by regulating the proliferation, migration and autophagy of PASMCs through YAP/TAZ-TEAD4 pathway, which may help to understand deeper the pathogenic mechanism in PH development.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2021
·
IF 13.273
Yang Liu,Rui Guo,Tengling Wu,Yuanning Lyu,Meng Xiao,Binbin He,Guanwei Fan,Jianhai Yang,Wenguang Liu
Conventional strategies for constructing an injectable conductive hydrogel for treatment of myocardial infarction (MI) are mostly involved with complicated bioactive modification and incorporation of external conductive materials or cells/therapeutic drugs, severely restraining its medical translation. Herein, a cell-free and therapeutic drug-free injectable zwitterionic hydrogel is fabricated by thiol-acrylate Michael addition reaction between acrylate modified polycarboxybetaine macromonomer and dithiothreitol (DTT), where the free DTT and the tethered-DTT endow the hydrogel with an antioxidant ability. The zwitterionic hydrogel is optimized to exhibit an appropriate gelation time and injectability. Intriguingly, the cation-anion ion pair on the side chain affords an intrinsic conductive property similar to the native myocardium. After injection into the infarcted region of rats, the hydrogel can downregulate level of inflammatory factors, and upregulate the expressions of cardiac-related factors, angiogenic factors, and transmission electrical signal-relevant Cx-43, accompanied by suppression of oxidant stress and cardiac fibrosis and increased vessel density, supposedly due to inherent antifouling, vascularization-promoting and conductive properties. Echocardiography and histological analyses demonstrate a remarkable improvement of the functions and structure of infarcted myocardium in rats in terms of 2.17/2.80-fold increase in ejection fraction/fractional shortening, 3.62-fold decline in end-systolic volume, and 2.39-fold decrease in fibrosis area, compared to MI group. This cell-free and therapeutic drug-free injectable zwitterionic hydrogel represents a new approach to seek a simplified but holistic biomaterial for treating myocardial infarction.
研究领域:
生物医学工程
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心血管病学
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
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IF 4.932
Jin Zhang,Changsong Wang,Hongliang Wang,Xueting Li,Jingjing Xu,Kaijiang Yu
Sepsis is a systemic inflammatory response syndrome resulted from severe infection. Excessive inflammation response plays an important role in sepsis-induced acute lung injury (ALI). Loganin is an iridoid glycoside isolated from Corni fructus and exerts an anti-inflammatory effect in multiple inflammatory diseases; however, the role of loganin in sepsis-induced ALI remains unknown. In the current study, the cecal ligation and puncture (CLP)-induced murine sepsis model was constructed to investigate the anti-inflammatory property of loganin in sepsis-induced ALI. Lipopolysaccharide (LPS)-treated Raw 264.7 cells and primary murine peritoneal macrophages were established to further explore underlying mechanism of loganin. Results showed that intragastrical administration of loganin significantly increased murine survival, reduced the alveolar structure damage and inflammatory cell infiltration. Loganin suppressed the release of the M1 macrophage-associated pro-inflammatory cytokines and induced the activation of M2-type anti-inflammatory cytokines. Besides, loganin dramatically inhibited NLRP3 inflammasome-mediated caspase-1 activation and subsequent IL-1β secretion. Further in vitro studies confirmed that loganin efficiently inhibited M1 macrophage polarization and NLRP3 inflammasome activation by blocking the extra-cellular signal-regulated kinase (ERK) and nuclear factor-kappa B (NF-κB) pathways. Taken together, the anti-inflammatory effect of loganin in sepsis-induced ALI was associated with the ERK and NF-κB pathway-mediated macrophage polarization and NLRP3 inflammasome activation. Our study offers a favorable mechanistic basis to support the therapeutic potential of loganin in anti-inflammatory diseases, such as sepsis-induced ALI.
研究领域:
药理学
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免疫学
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传染病学
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炎症研究
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PubMed
高影响因子
Polymer Chemistry
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2021
·Vol. 12
·期 16
·2397-2403
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IF 5.582
Huan-Huan Ding,Mu-Han Zhao,Le Zhai,Jian-Bin Zhen,Le-Yun Sun,Jia-Zhu Chigan,Cheng Chen,Jia-Qi Li,Han Gao,Ke-Wu Yang
The drug resistance caused due to the overuse of antibiotics has grown into an emerging threat. It is urgent to develop novel strategies to combat bacterial resistance. In this work, a quinine-based quaternized polymer with amphiphilicity (QMTA) was prepared by free-radical copolymerization of quinine and (2-methacryloyloxyethyl) trimethyl ammonium chloride (MTA). Biological activity assays revealed that the polymer sterilized the drug-resistant Gram-negative E. coli and non-resistant Gram-positive bacteria B. subtilis, exhibiting a MIC value of 2 μg mL−1 and a bactericidal rate of more than 95%. Most importantly, both E. coli and B. subtilis treated with the polymer didn't develop resistance even after their 16th passages. Also, the polymer has low toxicity at a dose of up to 128 μg mL−1. The mechanism studies through SEM and 3D-SIM images, fluorescence staining and membrane potential determination reveal that the positively charged QMTA initially concentrates on the surface of bacteria by electrostatic adsorption, changes the membrane potential, binds to the bacteria by its quinine chain, and destroys the membrane structure of the bacteria. This study provides a potential approach through the existing drug to develop new bactericidal reagent/polymer materials without resistance.
研究领域:
聚合物化学
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微生物学
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材料科学
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药剂学
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DOI
高影响因子
Inorganic Chemistry Frontiers
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2021
·Vol. 8
·期 10
·2624-2633
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IF 6.569
Man Zou,Yajie Zhao,Binbin Ding,Fan Jiang,Yeqing Chen,Ping'an Ma,Jun Lin
The generation of reactive oxygen species (ROS) is often limited by the overexpression of glutathione (GSH) in the tumor microenvironment (TME) and the penetration depth of visible light. In view of this, we designed biodegradable Cu/ZIF-8 shell-coated lanthanide-doped nanoparticles and loaded with a photosensitizer (Rose Bengal), and fabricated a NIR-triggered nanocomposite NaYF4:20%Yb, 2%Er@Cu/ZIF-8/RB@F127 (UCZRF) for the synergistic treatment of CDT and PDT. Interestingly, the UCZRF nanostructures can specifically release RB and Cu2+ in the acidic tumor microenvironment (TME). Cu2+ depletes GSH to effectively change the amount of ROS produced by RB under 980 nm laser irradiation, and Cu+ from the reduction reaction of GSH reacts with excess hydrogen peroxide (H2O2) in the TME to generate hydroxyl radicals (⋅OH) with high oxidation activity. In such a simple nanosystem, we enhance the anti-tumor effect of CDT and PDT by improving the efficiency of ROS generation.
研究领域:
纳米医学
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肿瘤治疗
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材料科学
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生物化学
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DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2022
·
IF 3.322
Jing Cong,Yuehui Zhang,Xinming Yang,Yu Wang,Hui He,Mengying Wang
Polycystic ovary syndrome (PCOS) is a complicated endocrinopathy affecting women at reproductive age. Increasing evidence has shown the anti-PCOS effect of electroacupuncture (EA), a modified approach of traditional Chinese medical therapy “acupuncture”. However, the underlying mechanism of EA-alleviated PCOS waits further explored. In this study, experimental PCOS were induced in rats by dehydroepiandrosterone (DHEA) injection. Testosterone (T)-induced human ovarian granulosa cell (GC) line KGN was used to mimic PCOS in vitro . EA significantly alleviated histological changes and hormone disruption in PCOS rats. Besides, EA inhibited cell apoptosis, autophagy and the activation of endoplasmic reticulum (ER) stress-related PERK/eIF2α/ATF4/CHOP signaling in ovaries of PCOS rats. More interestingly, intermedin (IMD), a member of calcitonin gene-related peptide (CGRP), was evidently up-regulated in ovarian GCs after EA treatment, and its main bioactive form IMD 1-53 suppressed cell apoptosis, autophagy and PERK/eIF2α/ATF4/CHOP signaling in T-induced KGN cells. Consistent with IMD 1-53 , ER stress inhibitor 4-PBA exerted an inhibitory effect on T-induced cell apoptosis and autophagy in KGN cells. Collectively, this study validates the protective effect of EA on DHEA-induced PCOS, and proposes that IMD relieved apoptosis and autophagy in T-induced granulosa cells via inhibiting ER stress.
研究领域:
生殖医学
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内分泌学
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分子生物学
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中医学
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DOI
PubMed
高影响因子
IUBMB LIFE
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2021
·Vol. 73
·期 9
·1180-1190
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IF 3.885
Jing Wang,Tao Wang,Yang Zhang,Jiaqi Liu,Jie Song,Yanlong Han,Lihong Wang,Shuang Yang,Lili Zhu,Rui Geng,Weimin Li,Xiaoguang Yu
The induction of ferroptosis is considered a new strategy for cancer treatment. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) is a post-transcriptional regulatory factor, whose low expression has been reported to link to the enhanced metastasis and angiogenesis of gastric cancer (GC). In this study, to explore the role of CPEB1 in ferroptosis, GC cells with overexpressed or silenced CPEB1 expression were treated with erastin, a classic ferroptosis inducer. The results showed that erastin dose-dependently decreased the viability of four GC cell lines (AGS, SNU-1, Hs-746 T, and HGC-27), suggesting that ferroptosis could be triggered in these GC cells. Interestingly, HGC-27 cells overexpressing CPEB1 were more sensitive to erastin, generated more lipid reactive oxygen species (ROS) and malondialdehyde (MDA), and their glutathione peroxidase 4 (Gpx4) expression and GSH content were reduced. Contrarily, CPEB1-silenced AGS cells were more resistant to erastin. Mechanically, we demonstrated that CPEB1 overexpression reduced the expression of twist1, an inhibitor of activating transcription factor 4 (ATF4), thereby activating the ATF4/ChaC Glutathione Specific Gamma-Glutamylcyclotransferase 1 (CHAC1) pathway (CHAC1, a molecule known to induce GSH degradation). Furthermore, re-expression of twist1 in GC cells impaired the effects of CPEB1 overexpression in presence of erastin. Additionally, similar to the in vitro results, the growth-inhibiting effects of erastin on GC xenografted tumors were also augmented by CPEB1 overexpression in vivo. Collectively, we demonstrate that CPEB1 facilitates erastin-induced ferroptosis by inhibiting twist1.
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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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）