BIOMETALS
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2019
·Vol. 32
·期 2
·251-264
·
IF 2.455
Liu Xiao-Li,Ye Sen,Li Hua-Wei,Lu Bo,Yu Yan-Qin,Fan Yu-Peng,Yang Wei-Jun,Yang Jin-Shu
Rimicaris exoculata (Decapoda: Bresiliidae) is one of the dominant species among hydrothermal vent communities along the Mid-Atlantic Ridge. This shrimp can tolerate high concentrations of heavy metals such as iron, but the mechanisms used for detoxification and utilization of excess metals remain largely unknown. Ferritin is a major iron storage protein in most living organisms. The central heavy subunit of ferritin (H-ferritin) possesses ferroxidase activity and converts iron from Fe 2+ to Fe 3+ , the non-toxic form used for storage. In the present study, the H-ferritin RexFrtH was identified in the hydrothermal vent shrimp R. exoculata , and found to be highly expressed in the gill, the main organ involved in bioaccumulation of metals, at both RNA and protein levels. Accumulation of RexFrtH decreased from efferent to afferent vessels, coinciding with the direction of water flow through the gills. Fe 3+ was localized with RexFrtH, and in vitro iron-binding and ferroxidase assays using recombinant RexFrtH confirmed the high affinity for iron. Based on these results, we propose a model of iron metabolism in R. exoculata gills; ferrous iron from ambient hydrothermal water accumulates and is converted and stored in ferric form by RexFrtH as an iron reservoir when needed for metabolism, or excreted as an intermediate to prevent iron overload. The findings expand our understanding of the adaptation strategies used by shrimps inhabiting extreme hydrothermal vents to cope with extremely high heavy metal concentrations.
研究领域:
海洋生物学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Pan Yu,Liu Zhao,Wang Yijie,Zhang Linshen,Chua Niying,Dai Lei,Chen Jun,Ho Chun Loong
Chronic inflammation is considered a pressing health issue that needs resolving. Inflammatory disease such as inflammatory bowel disease requires a long-term medical regimen to prevent disease progression. Conventionally, lactoferrin is used to treat mild gastrointestinal tract and skin inflammation. Protease-digested lactoferrin fragments often exhibit improved therapeutic properties compared to full-length lactoferrin (flHLF). However, there are no studies on the use of protease-digested lactoferrin fragments to treat inflammation. Herein, we assess the anti-inflammatory properties of engineered recombinant lactoferrin fragments (rtHLF4, rteHLF1, and rpHLF2) on non-malignant colonic fibroblast cells and colorectal cancer cells. We found that rtHLF4 is 10 times more effective to prevent inflammation compared to flHLF. These results were investigated by looking into the reactive oxygen species (ROS) production, angiogenesis activity, and cellular proliferation of the treated cells. We have demonstrated in this study the anti-inflammatory properties of the flHLF and the various lactoferrin fragments. These results complement the anti-cancer properties of these proteins that were demonstrated in an earlier study.
研究领域:
药理学
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免疫学
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分子生物学
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胃肠病学
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DOI
PubMed
高影响因子
Chinese Herbal Medicines
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2020
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IF 0
Xin Li,Xiao-wen Jiang,Hai-xiao Chu,Qing-chun Zhao,Huai-wei Ding,Chao-hong Cai
Objective Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra (SN). Our previous study demonstrated kukoamine A (KuA) to exhibit strong neuroprotective effects through antioxidative stress, and autophagy in MPTP/MPP + -induced PD models in vivo and in vitro . It is necessary to evaluate the efficacy of the anti-PD effects under various models. Methods In the present study, total chemical synthesis was used to obtain KuA, which performed low content in Lycii Cortex . Then, 6-OHDA-induced PD model of PC12 cells was used to investigate the effects of KuA on PD. Results Our results demonstrated that KuA ameliorated cell loss and mitochondrial membrane potential (MMP) loss, and inhibited Bax/Bcl-2 ratio increase that were induced by 6-OHDA. Iron accumulation in SN is thought to participate in neuronal death in PD, which subsequently resulted in oxidative stress and overexpression of α-synuclein caused by iron metabolism protein disorder. In our study, KuA could chelate cellular iron content and decrease iron influx. Moreover, KuA could upregulate the expression of ferroportin1 and Hephaestin, downregulate the expression of DMT1, TfR, and Ferritin to maintain cellular iron homeostasis avoiding neuronal death from cellular iron deposition. Moreover, KuA could decrease the expression of a-synuclein in cells. All the results indicated that KuA protected against neurotoxin-induced PD due to the apoptosis inhibition and iron homeostasis maintaining. Conclusion KuA treatment might represent a neuroprotective treatment for PD.
研究领域:
神经科学
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药理学
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细胞生物学
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神经退行性疾病
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产品关联
DOI
PubMed
Biomaterials Research
·
2023
·Vol. 27
·期 1
·1-17
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IF 11.3
Xiao Youmei,Xu Zhanxue,Cheng Yuan,Huang Rufan,Xie Yuan,Tsai Hsiang-i,Zha Hualian,Xi Lifang,Wang Kai,Cheng Xiaoli,Gao Yanfeng,Zhang Changhua,Cheng Fang,Chen Hongbo
Background Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells. Methods To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe 3+ and encapsulated SOR (SOR@TF-Fe 3+ NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe 3+ and enhanced SOR efficacy by inhibiting the SLC7A11. Results In vivo and in vitro experiments revealed that SOR@TF-Fe 3+ NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe 3+ NVs accelerated Fe 3+ absorption and transformation in HCC cells. Importantly, SOR@TF-Fe 3+ NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe 3+ NVs alone. Conclusions The present work provides a promising therapeutic strategy for the targeted treatment of HCC. Graphical abstract
研究领域:
肿瘤学
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药理学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
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2019
·Vol. 55
·期 2
·729-741
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IF 2.281
Junmeng Lu,Piaohan Tu,Yanwen Feng,Na Li,Xiankang Xu,Kexuan Li,Yixin Yao,Jianzhong Han,Weilin Liu
Summary In this study, the influence of dietary compounds, including antioxidants (ethylenediaminetetraacid, ascorbic acid, catechin), chitosan and lactoferrin, on the stability of liposomes during in vitro adult and infant digestion was investigated in terms of formation of thiobarbituric acid-reactive substances (TBARS) and free fatty acid release. Liposomes were more sensitive to degradation in adults than in infants, suggesting lower pH (1.5) and higher concentration of pancreatic enzymes (3.2 mg mL −1 ) and bile salts (5 mg mL −1 ) that indicated greater damage to the structure of liposomes. Compared to ethylenediaminetetraacid and ascorbic acid, catechin presented the most apparent protective effect against liposomal oxidation by scavenging free radicals. Chitosan promoted the formation of TBARS, while lactoferrin facilitated the hydrolysis rate of liposomes under both adult and infant conditions. This study provided an insight into the development of healthcare products and functional foods related to liposomes for special populations.
研究领域:
食品科学
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营养学
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产品关联
DOI
高影响因子
Theranostics
·
2019
·
IF 8.063
Qiuhong Zhang,Jingwen Chen,Jie Shen,Shixiong Chen,Kaicheng Liang,Han Wang,Hangrong Chen
Rationale : Ferritin with unique hollow cavity is an emerging protein-based nanoplatform for anticancer-drug delivery, but the in vivo chemotherapeutic effectiveness is still unsatisfactory with such a monotherapy modality, which is urgently in need of improvement. Methods : Here a novel ferritin nanotheranostic with anticancer-drug doxorubicin encapsulated into its hollow interior and nanoradiosensitizer bismuth sulfide nanocrystals inlayed onto its polypeptide shell was synthesized for combinational therapeutic benefits. The formation mechanism of bismuth sulfide nanocrystals based on ferritin has been analyzed. The in vitro and in vivo treatment effects were carried out on HeLa cancer cells and tumor-bearing mice, respectively. The biocompatibility and excretion of the ferritin nanotheranostic have also been evaluated to guarantee their biosafety. Results : The polypeptide shell of ferritin provides nucleation sites for the bismuth sulfide nanocrystals through coordination interaction, and simultaneously inhibits the further growth of bismuth sulfide nanocrystals, rendering the bismuth sulfide nanocrystals like rivets inlaying onto the polypeptide firmly, which can not only strengthen the architectural stability of ferritin to prevent drug burst leakage during systemic circulation, but also act as excellent computed tomography contrast agents and nanoradiosensitizers for in vivo imaging-guided cancer combinational treatments. Conclusions : The design concept of inlaying bismuth sulfide nanocrystals onto the polypeptide shell of doxorubicin-encapsulated ferritin significantly inhibits the tumor growth and simultaneously further broadens the application of ferritin in nanomedicine.
研究领域:
生物医学工程
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纳米医学
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肿瘤治疗
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产品关联
DOI
PubMed
高影响因子
Analytical Methods
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2014
·Vol. 6
·期 13
·4742-4745
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IF 1.938
Liqiang Liu,Dezhao Kong,Changrui Xing,Xun Zhang,Hua Kuang,Chuanlai Xu
Lactoferrin (LF) content in infant milk powder has been strictly regulated by many governments and there is a need for convenient and reliable assays. Using hybridoma techniques, fourteen monoclonal antibodies (mAbs) active against LF were prepared. Two antibodies (mAb2 and mAb3), recognizing spatially distant epitopes of LF, were selected to establish a sandwich enzyme-linked immunosorbent assay (ELISA). A solution of mAb3 (1 μg mL−1) was coated onto micro-titer plates for LF capture while mAb2 labeled with horseradish peroxidase (2.2 μg mL−1) was used as a detection antibody. Under optimized conditions, the proposed sandwich ELISA was evaluated, and linearly responded to LF standards in a range of 5–600 ng mL−1 and the limit of detection was 3.23 ng mL−1. Lactoferrin samples were able to be determined after simple dilution, and the recovery in fortified milk powder averaged between 98% and 109%. The developed assay showed both high specificity (with no obvious cross-reactivity with related proteins) and reproducibility (the coefficient of variation ranged from 4.5% to 7.1%), indicating the utility of this sandwich ELISA in LF monitoring.
研究领域:
免疫学
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食品科学
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分析化学
✓ 已验证
产品关联
DOI
高影响因子
Algal Research-Biomass Biofuels and Bioproducts
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2021
·
IF 4.401
Xuehua Liu,Lijun Wang,Songcui Wu,Lu Zhou,Shan Gao,Xiujun Xie,Lepu Wang,Wenhui Gu,Guangce Wang
The formation of resting cells/spores in marine diatoms helps them to survive in environmental changes, whose sedimentation characteristics also drive enhanced carbon fluxes export to the deep ocean. However, the molecular mechanism underlying the transformation remains unclear. Based on the upregulation of ferritin during dormancy in microorganism and its' crucial role in coping with environmental stress, we constructed the ferritin overexpression and silence strains in model marine diatom, Phaeodactylum tricornutum (FTN-OE and FTN Si, respectively). The morphological transformation from fusiform to ovoid were observed among the FTN-OE strains but not the wide type and FTN-Si strains. These FTN-OE oval cells exhibited typical characteristics of resting cells and benthic adaptation, such as lower growth rates, low-light adaptation, silicified valves, the excretion of exopolymeric substances, upregulation of stress-resistant proteins and increased nitrate reserves. Furthermore, FTN-OE oval cells showed increased abscisic acid synthesis and signaling pathways in the transcriptome and proteome . And the abscisic acid signal was detected in FTN-OE oval cells exclusively (2.96 ng g −1 FW), but absent in the FTN Si, FTN-OE fusiform or WT cells. Overall, our results demonstrate that ferritin overexpression in marine diatom have a close relationship with morphological transformation from fusiform to ovoid morphotype , after which they enter a resting stage, which is accompanied by abscisic acid accumulation. This improves our understanding of the molecular processes in diatom resting cells/spores' formation and suggests that ferritin accumulation might improve the sequestration of photosynthetically fixed atmospheric CO 2 into the deep sea.
研究领域:
海洋生物学
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分子生物学
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产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Jiaping Zhou,Qiaomei Zhou,Gaofeng Shu,Xiaojie Wang,Yuanfei Lu,Haiyan Chen,Tingting Hu,Jinsong Cai,Yongzhong Du,Risheng Yu
Propose The early diagnosis of hepatocellular carcinoma (HCC) with ferritin heavy chain (Fth) modified by alpha-fetoprotein (AFP) promoter has been studied. However, no study has focused on the considerable upregulation and specific targeting effects of transferrin receptors (TfR) caused by the transfection of plasmids encoded with the AFP promoter. Thus, the objective of our study was to investigate whether the transfection of Fth gene modified with AFP promoter (AFP@Fth) could be used for early diagnosis and enhanced treatment of HCC.Methods The AFP@Fth plasmid was transfected into AFP positive cells. The expression of intracellular Ferritin was verified by Western blot, and the upregulation of TfR was confirmed by immunofluorescence and flow cytometry analysis. Cellular iron accumulation resulting in decreased imaging signals was examined by magnetic resonance imagining. Doxorubicin liposome modified with transferrin (Tf-LPD) was prepared to investigate the efficiency of the subsequent treatment after transfection. The enhanced drug distribution and effects were investigated both in vitro and in vivo.Results Both Ferritin and TfR were overexpressed after transfection. The transfected cells showed higher intracellular iron accumulation and resulted in a lower MR T2-weighted imaging (T2WI) intensity, suggesting that the transfection of AFP@Fth could be a potential strategy for early diagnosis of liver cancer. The following treatment efficacy was revealed by Tf-LPD. As compared with un-transfected cells, transfected cells exhibited higher uptake of transferrin-modified liposomes (Tf-LP), which was due to the specific interaction between Tf and TfR overexpressed on the transfected cells. This is also the reason why Tf-LPD showed better in vitro and in vivo anticancer ability than doxorubicin loaded liposome (LPD). These results suggested that transfection of AFP@Fth could result in enhanced therapy of liver cancer.Conclusion Transfection of AFP@Fth could be used for early diagnosis and for enhanced treatment of live cancers.
研究领域:
肿瘤学
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分子生物学
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医学影像学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2018
·
IF 0
Qingqing Tan,Ruirui Zhang,Weisu Kong,Fengli Qu,Limin Lu
A novel “turn-on” fluorescent trypsin detection platform dependant on carbon dot-MnO2 (CD-MnO2) nanocomposites and ascorbic acid-loaded apoferritin (APOAA) was fabricated. The detection mechanism relied on trypsin-catalyzed enzymolysis of APOAA, which released ascorbic acid (AA) as a reducing agent to disintegrate the MnO2 nanosheets, causing the recovery of the fluorescence of CDs. An excellent performance and high sensitivity of trypsin determination were observed with a detection limit (LOD) of 0.3411 ng/mL. This work provides us with a unique strategy for trypsin detection in human serum samples, which reveals the potential applications in clinical detection.
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
PubMed
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Chencheng Xue,Hui Zhang,Xuan Wang,Haoyu Du,Lu Lu,Yang Fei,Yanan Li,Yuchen Zhang,Menghuan Li,Zhong Luo
Nanotechnology-enabled ferroptosis therapy is an emerging paradigm for tumor treatment, but amplifying ferroptotic damage in tumor cells in a safe and selective manner is still challenging, which severely hinders its clinical translation. In this study, we constructed a bio-inspired protein nanocomplex based on natural-occurring bovine serum albumin (BSA) and ferritin for efficient tumor elimination via cooperatively enhanced ferroptosis therapy. The long-circulating BSA molecules provided multiple anchoring points for the efficient loading of the GPX4-inhibiting ferroptosis inducer (1S, 3R) RAS-selective lethal 3 (RSL3), which was further complexed with ferritin via acidity-responsive glutaraldehyde linkers. The ferritin moieties may not only bind to transferrin receptor 1 overexpressed on tumor cell membrane for targeted endocytic uptake but also be degraded in lysosomes to induce iron overload, which could substantially promote the lipid peroxidation in tumor cells and cooperate with the glutathione peroxidase 4 (GPX4)-inhibiting capability of RSL3 to induce pronounced ferroptosis. The in vitro and in vivo results collectively demonstrated that the albumin-ferritin-based nanocomplex could present superior antitumor effects with no obvious adverse effects, which may open new avenues for the clinical translation of ferroptosis-dependent therapeutic modalities.
研究领域:
肿瘤学
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纳米医学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2022
·Vol. 14
·期 17
·6449-6464
·
IF 8.307
Ziwei Yuan,Bin Wang,Yilong Teng,William Ho,Bin Hu,Kofi Oti Boakye-Yiadom,Xiaoyang Xu,Xue-Qing Zhang
Gene therapy holds tremendous potential for the treatment of incurable brain diseases including Alzheimer's disease (AD), stroke, glioma, and Parkinson's disease. The main challenge is the lack of effective gene delivery systems traversing the blood–brain barrier (BBB), due to the complex microvessels present in the brain which restrict substances from the circulating blood passing through. Recently, increasing efforts have been made to develop promising gene carriers for brain-related disease therapies. One such development is the self-assembled heavy chain ferritin (HFn) nanoparticles (NPs). HFn NPs have a unique hollow spherical structure that can encapsulate nucleic acid drugs (NADs) and specifically bind to cancer cells and BBB endothelial cells (BBB ECs) via interactions with the transferrin receptor 1 (TfR1) overexpressed on their surfaces, which increases uptake through the BBB. However, the gene-loading capacity of HFn is restricted by its limited interior volume and negatively charged inner surface; therefore, these drawbacks have prompted the demand for strategies to remould the structure of HFn. In this work, we analyzed the three-dimensional (3D) structure of HFn using Chimera software (v 1.14) and developed a class of internally cationic HFn variants (HFn+ NPs) through arginine mutation on the lumenal surface of HFn. These HFn+ NPs presented powerful electrostatic forces in their cavities, and exhibited higher gene encapsulation efficacy than naive HFn. The top-performing candidate, HFn2, effectively delivered siRNA to glioma cells after traversing the BBB and achieved the highest silencing efficacy among HFn+ NPs. Overall, our findings demonstrate that HFn+ NPs obtained by this genetic engineering method provide critical insights into the future development of nucleic acid delivery carriers with BBB-crossing ability.
研究领域:
生物医学工程
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分子生物学
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神经科学
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药学
✓ 已验证
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）