PLoS Pathogens
·
2026
·Vol. 22
·期 7
·e1014425
·
IF 4.9
Hanbo Li,Yu Li,Bowen Yin,Xinming Zhang,Zheng Xu,Changxu Song,Kang Li,Ling Tian
Quercetin is recognized for diverse pharmacological activities. However, the mechanism underlying its broad-antiviral effects has not been elucidated. Herein, we identified quercetin as a potent inhibitor of both double-stranded DNA virus Bombyx mori nucleopolyhedrovirus (BmNPV) and single-stranded RNA virus porcine reproductive and respiratory syndrome virus (PRRSV). Surface plasmon resonance (SPR) revealed that quercetin targets host ubiquitin-activating enzyme 1 (Uba1) homologs. Uba1 knockdown reduced viral proliferation and enhanced the antiviral effect of quercetin, whereas Uba1 overexpression functioned oppositely. Quercetin bound Uba1 homologs with high affinity. Notably, mutation of two binding residues, Q977 and G978, significantly disrupted the binding between BmUba1 and quercetin, and abolished quercetin’s antiviral activity. Quercetin obstructed the transfer of ubiquitin from Uba1 to the E2 enzyme Ubc6, impairing the ubiquitination process. Similarly, quercetin inhibited PRRSV proliferation via targeting Uba1 in mammals. These findings elucidate the molecular mechanism underlying the pharmacological effects of quercetin, providing a theoretical basis for the development of novel antiviral agents against both DNA and RNA viruses.
Focusing on BmNPV and PRRSV, this study reveals that quercetin inhibits both DNA and RNA viruses by targeting Uba1 homologs, disrupting ubiquitin transfer between E1 and E2 enzymes. Mutations in key residues on Uba1 impair the binding with quercetin, thus lost the antiviral effect of quercetin. The conserved mechanism across species underscores quercetin’s broad-spectrum antiviral potential, providing a theoretical basis for developing effective antiviral drugs against diverse viral infections.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BREEDING SCIENCE
·
2022
·
IF 2.014
Yusuke Imoto,Shoko Yoshikawa,Yuki Horiuchi,Takumi Iida,Taisei Oka,Shuichi Matsuda,Yoshihiko Tokuji,Masahiko Mori,Kiyoaki Kato
Adzuki bean is an important legume crop originating in temperate regions, with photoperiod in sensitivity being a key factor in its latitudinal adaptation. The Flowering Date1 (FD1) gene has a large effect on the photoperiodic response of flowering time, but the molecular basis for the effect of this locus is undetermined. The present study delimited the FD1 locus to a 17.1 kb sequence, containing a single gene, an E1 ortholog (VaE1). A comparison between Vigna angularis ‘Shumari’ (photoperiod insensitive) and ‘Acc2265’ (photoperiod sensitive) identified 29 insertions/deletions and 178 SNPs upstream of VaE1 in the FD1 locus. VaE1 expression in ‘Acc2265’ was greater under long-day than short-day conditions, whereas VaE1 expression in ‘Shumari’ was lower regardless of day length. These findings suggested that responsible gene of FD1 is a VaE1, which acts as a floral repressor by being upregulated in response to long-day conditions. The inability to upregulate VaE1 under long-day conditions was linked to its ability to flower under these conditions. These results provide greater understanding of the molecular control of a flowering date and clues enabling the breeding of adzuki bean at higher latitudes.
研究领域:
植物生物学
·
遗传学
·
农业科学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 55
·34415-34424
·
IF 3.108
Weibo Jie,Fuxiang Song,Xiaocheng Li,Wen Li,Rui Wang,Yanjiao Jiang,Libo Zhao,Zengjie Fan,Jizeng Wang,Bin Liu
In bone tissue engineering, the 3D macro-scaffold plays an indispensable role as a matrix for cell proliferation, differentiation and tissue formation, for which a bioactive surface is required. Previously, we successfully prepared the 3D macro-reduced graphene oxide/polypyrrole (3D rGO/PPY) scaffold; in the present study, by using casein phosphopeptide (CPP) as a bioactive molecule, we have developed a 3D rGO/PPY/CPP composite scaffold through a simple, but low-cost electrostatic self-assembly method and have explored the application of the composite scaffold in bone tissue engineering. The results have indicated that the CPP successfully modified the backbone of the scaffold, and demonstrated that the developed 3D rGO/PPY/CPP scaffold has excellent hydrophilic behavior and water uptake performance, much better than that of 3D rGO/PPY. In the biomimetic mineralization experiment, the CPP-modified matrix, particularly 3D rGO/PPY/CPP20, could promote the rapid formation of hydroxyapatite in simulated body fluid solution on just the 1st soaking day. On co-culturing with the MC3T3-E1 cells, the 3D rGO/PPY/CPP20 kept the cells at a higher proliferation state of 5.07 times that of the control group, superior to that of the 3D rGO/PPY/CPP10 (3.88 times) and the 3D rGO/PPY group (2.07 times). The excellent osteoblastic performance of the 3D rGO/PPY/CPP20 composite scaffold can be attributed to the good biological properties of CPP, and the unique 3D macro-structure with a high specific surface area. Our findings suggest that the 3D rGO/PPY/CPP20 can be considered as an attractive scaffold for bone healing and regeneration in the future.
✓ 已验证
产品关联
DOI
高影响因子
DISEASE MARKERS
·
2022
·
IF 3.464
Jia Yu,Xinxin Zhang,Rongfang He,Xiaoyan Yang,Juan Hu,Fang Tan,Jinyu Yao,Xiaoyong Lei,Gebo Wen
Backgrounds. Long noncoding RNAs (lncRNAs) are strongly associated with the development of breast cancer (BC). As yet, the function of LINC01234 in BC remains unknown. Methods. Using biological information, the potential lncRNA, miRNA, and target gene were predicted. LINC01234 and miR-525-5p expression in BC tissues was detected using quantitative real-time reverse transcription polymerase chain reaction. Fluorescence in situ hybridization was used to determine the distribution of LINC01234. Cell proliferation was analyzed using CCK-8 assay, colony formation, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and apoptosis evaluated using flow cytometry. Western blotting was used to evaluate protein expression. Dual-luciferase® reporter, RNA pull-down, and RNA immunoprecipitation assays were performed to analyze the binding relationships among LINC01234, miR-525-5p, and cold shock domain-containing E1 (CSDE1). Results. We screened out LINC01234, found to be significantly increased in BC tissues, associated with a poor prognosis, and positively correlated with tumor size of BC. Knockdown of LINC01234 suppressed BC cell growth and facilitated apoptosis. Dual-luciferase reporter®, RNA pull-down, and RNA immunoprecipitation assays confirmed that LINC01234 and CSDE1 directly interacted with miR-525-5p. Upregulation of miR-525-5p and suppression of CSDE1 inhibited BC cell growth and induced cell apoptosis. Conclusion. Upregulation of LINC01234 contributes to the development of BC through the miR-525-5p/CSDE1 axis. LINC01234 may be one of the potential diagnostic and treatment targets for BC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2014
·
IF 5.9
Na Li,Gang Chen,Jue Liu,Yang Xia,Hanbang Chen,Hui Tang,Feimin Zhang,Ning Gu
The effects of bioactive properties and surface topography of biomaterials on the adhesion and spreading properties of mouse preosteoblast MC3T3-E1 cells was investigated by preparation of different surfaces. Poly lactic-co-glycolic acid (PLGA) electrospun fibers (ES) were produced as a porous rough surface. In our study, coverslips were used as a substrate for the immobilization of 3,4-dihydroxyphenylalanine (DOPA) and collagen type I (COL I) in the preparation of bioactive surfaces. In addition, COL I was immobilized onto porous electrospun fibers surfaces (E-COL) to investigate the combined effects of bioactive molecules and topography. Untreated coverslips were used as controls. Early adhesion and growth behavior of MC3T3-E1 cells cultured on the different surfaces were studied at 6, 12, and 24 h. Evaluation of cell adhesion and morphological changes showed that the all the surfaces were favorable for promoting the adhesion and spreading of cells. CCK-8 assays and flow cytometry revealed that both topography and bioactive properties were favorable for cell growth. Analysis of β1, α1, α2, α5, α10 and α11 integrin expression levels by immunofluorescence, real-time RT-PCR, and Western blot and indicated that surface topography plays an important role in the early stage of cell adhesion. However, the influence of topography and bioactive properties of surfaces on integrins is variable. Compared with any of the topographic or bioactive properties in isolation, the combined effect of both types of properties provided an advantage for the growth and spreading of MC3T3-E1 cells. This study provides a new insight into the functions and effects of topographic and bioactive modifications of surfaces at the interface between cells and biomaterials for tissue engineering.
研究领域:
生物材料
·
组织工程
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Keming Jiang,Dong Huang,Dawei Zhang,Xinluan Wang,Huijuan Cao,Qian Zhang,Chunyan Yan
Scope In China, the root of M . officinalis has been widely used over thousands of years against a wide range of bone disease such as lumbago, limb-ache, sciatica and rheumatic arthralgia, and has tremendous medicinal value. But the bioactive constituents responsible for the osteoprotective effects in M . officinalis remain unknown. Methods and results M . officinalis polysaccharides were extracted, isolated and purified via DEAE-cellulose 52 and Sephacryl S-100HR column to obtain two saccharides (MOP70-1 and MOP70-2). The results of osteogenic activity assays revealed that MOP70-1 and MOP70-2 significantly promoted the proliferation, differentiation and mineralization of MC3T3-E1 cells. Furthermore, MOP70-2 also upregulated gene expression of runt-related transcription factor 2, osterix, osteocalcin, osteopontin, bone sialoprotein and osteoprotegerin, which implied that MOP70-2 stimulated osteoblastic differentiation by up-regulating osteogenic differentiation-related marker genes. In addition, structural analysis indicated that MOP70-2 contained (2 → 1)-linked- β -D-Fru f residues and terminated with a glucose residue. Morphological and conformational analyses indicated that MOP70-2 exhibited spherical structure of conglomeration and had no triple helix structure. Conclusion Our studies reported the osteogenic inulins obtained from root of M . officinalis for the first time. The systematical investigation including extraction, purification, biological activities and structural characterization provide a strong evidence for future therapeutic applications as anti-osteoporosis agent.
研究领域:
药理学
·
生物化学
·
中医药学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS ENGINEERING AND PERFORMANCE
·
2021
·Vol. 30
·期 10
·7214-7222
·
IF 1.819
Cai Hong,Li Xuan,Xue Feng,Chu Chenglin,Guo Chao,Bai Jing,Zhang Xiaobo
Abstract In order to ensure the safety of materials used in the field of orthopedic internal fixation, cytocompatibility was evaluated by culturing MC3T3-E1 cells with the extracts of Mg-2Zn rods, poly(lactic acid) (PLA) rods, hot pressed and hot drawn Mg wire/PLA composite rods. The adhesion, spread, and growth states of cells on each group of sample were analyzed according to SEM images. The fluorescent micromorphology was analyzed, and the relative growth ratio was calculated to quantitatively evaluate the influence of these extracts on the cell viability. Results displayed that moderate and severe cytotoxicity appeared after cells incubated with extracts of Mg-2Zn rod for 3 and 5 days, but it returned to normal phenomenon after the extracts diluted by 10 times. Extracts of other three groups of sample displayed good cytocompatibility. The growth and proliferation of cells were closely related to the pH value and concentration of Mg 2+ . The osmolality changes of extracts had little influence on cytocompatibility of samples at the early stage. Therefore, we can predict the effect of degradation products of Mg wire/PLA composites on their cytocompatibility during the degradation process, on the basis of pH value, concentration of Mg 2+ , as well as osmolality changes. The good cytocompatibility of Mg wire/PLA composites provided experimental valid and valuable guideline for further material design and scheme selection. Graphical Abstract
研究领域:
材料科学
·
生物医学工程
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR BIOTECHNOLOGY
·
2023
·
IF 2.6
Liu Hu,Li Tao,Ma Ben,Wang Yue,Sun Jun
Osteoblast regeneration, characterized by osteoblast differentiation, is the basis of fracture healing and accelerates fracture repair. It has been reported that hyaluronan and proteoglycan link protein 1 (HAPLN1) is overexpressed during osteoblast differentiation and regulates cartilage regeneration, but its function in fracture healing remains unclear. To elucidate this issue, we collected clinical blood samples of fracture healing, established a femoral fracture rat model, and induced an osteoblast differentiation cell model. We found that HAPLN1 was overexpressed in the serum of patients with fracture healing and the bone tissues of rats with fracture healing. Furthermore, the expression of HAPLN1 was increased time dependently during the osteogenic differentiation of MC3T3-E1 cells. HAPLN1 silencing prevented osteoblast differentiation and mineralization in MC3T3-E1 cells as evidenced by decreased osteoblast differentiation-related factors, suppressed alkaline phosphatase activities, and reduced alizarin red positive staining. Mechanically, the bone morphogenic protein 4 (BMP4)/Smad1/5/8 pathway, a facilitator of osteoblastic differentiation, was found to be inhibited by HAPLN1 knockdown, and inhibition of BMP4/Smad1/5/8 signaling enhanced the effects caused by HAPLN1 silencing. These findings demonstrated that HAPLN1 might promote fracture healing by facilitating osteogenic differentiation through the BMP4/Smad1/5/8 pathway, indicating that targeting HAPLN1 may be a feasible therapeutic candidate for fracture repair. Graphical Abstract
研究领域:
骨科
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Haiyan Yao,Jun Luo,Yunyun Deng,Zhihua Li,Junchao Wei
Mesoporous bioactive glass (MBG) is widely used in bone tissue repairing and drug loading. However, burst release of drug and poor compatibility with other materials limited its application. It is an effective way to modify MBG with a polymer brush to improve the properties. Herein, an alginate-modified MBG was prepared, and then, the effects of ALG on the properties of MBG were investigated. The results demonstrate that ALG could improve the drug loading efficiency, prolong drug release times, and make orderly deposition of apatite on the surface of MBG. Furthermore, MBG@ALG significantly promoted the osteogenic differentiation of MC3T3-E1 cells, demonstrating that surface modification of MBG by ALG can improve its properties, which will further broaden the application of MBG in tissue engineering.
研究领域:
材料科学
·
生物医学工程
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Dong Huang,Xin Hou,Dawei Zhang,Qian Zhang,Chunyan Yan
Cibotium barometz , an important traditional Chinese medicine, is used in strengthening bones and tendons. We found that C. barometz crude polysaccharides (CB70) could alleviate bone loss and markedly improve the biomechanical properties of OVX rats. Thus, to clarify biological active ingredient(s) of CB70, two homogeneous polysaccharides (CBP70-1-1 and CBP70-1-2) were purified from CB70. A combination of monosaccharide composition, FT-IR, GC–MS and NMR analysis indicated that CBP70-1-1 was composed of →6)-D-Gal p -(1→, D-Glc p -(1→, →3,6)-D-Man p -(1→, →4)-D-Glc p -(1→ and →6)-D-Glc p -(1→ with relative molecular weights of 12,724 Da, and CBP70-1-2 was composed of →4)-D-Glc p -(1→, D-Glc p -(1→, →3,6)-D-Man p -(1→, →6)-D-Gal p -(1→, →4,6)-D-Glc p -(1→ and →3)-L-Ara f -(1→ with relative molecular weights of 3611 Da. Morphological analyses revealed that CBP70-1-1 and CBP70-1-2 appeared as a sheet that were irregular in size and shape, while the surface of CBP70-1-1 was full of sharp protuberances and CBP70-1-2 was smooth. Furthermore, the effects of CBP70-1-1 and CBP70-1-2 on the proliferation, differentiation and mineralization of mouse pre-osteoblastic MC3T3-E1 cells were assessed via CCK-8 assay, alkaline phosphatase activity assay, and alizarin red-based assay, respectively. These results revealed that CBP70-1-1 and CBP70-1-2 significantly promoted the proliferation, differentiation and mineralization of MC3T3-E1 cells, even better than E2. More importantly, quantitative real-time PCR and Western blot analysis indicated that CBP70-1-2 pronouncedly promoted the expression of osteogenic-related marker genes ( Runx2, Osx, Ocn and Opn ) and proteins (BMP2, RUNX2, OSX and p-SMAD1), which implies that the osteogenic activity of CBP70-1-2 is accomplished mainly by activating the BMP2/SMAD1 signaling pathway. These findings suggest CBP70-1-2 as a potential natural anti-osteoporotic agent for pharmacotherapy.
研究领域:
药理学
·
分子生物学
·
中医药学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2019
·
IF 2.442
Xiaoling Yang,Xue Liu,Qianqian Wu,Xu Lv,Bo Li,Hongzhe Sun,Wenfeng Xu,Xiaoling Liao
Due to their excellent biocompatibility and suitable elastic modulus, carbon–carbon composites have excellent prospects for a wide range of applications such as artificial joints and bone replacements. However, the hydrophobicity and poor bioactivity limit their application in bone repair and substitution. Herein, a two-step surface modification of carbon–carbon composites was proposed to overcome these disadvantages. A polydopamine (PDA) layer was first deposited on the surface of carbon–carbon composites, followed by covalent coupling with arginine–glycine–aspartic acid (RGD) in varying concentrations. The surface-modified materials were characterized using a variety of techniques including water contact angle, scanning electron microscopy, atomic force microscopy, and protein adsorption. In addition, the cellular proliferation, alkaline phosphatase activity, and real-time quantitative PCR (RT-PCR) analysis were further tested in vitro. The results indicated that polydopamine and RGD nanoparticles formed on the surface, which significantly enhanced the hydrophilicity following modification. The RGD–PDA-coated carbon–carbon composites exhibited excellent roughness, protein adsorption behavior, and uniform morphology when a concentration of 50 µg/mL RGD was used, unlike blank and polydopamine-modified carbon–carbon composites. The in vitro cell co-culture experiments demonstrated that proliferation and alkaline phosphatase expression in osteoblasts was greatly improved after RGD–PDA coating. The RT-PCR results revealed that the expression of differentiation markers (alkaline phosphatase and osteocalcin) in cells on the RGD–PDA-coated carbon–carbon composites was higher than that on the blank and polydopamine-modified carbon–carbon composites, indicating that the RGD–PDA coating could support cell proliferation and promote osteogenic differentiation of MC3T3-E1 cells. In particular, the cells cultured on this material grew linearly along the morphological features of the material, which was effective for the subsequent regulation of cell growth. Our study suggested that the RGD–PDA coating was an effective method of enhancing the hydrophobicity and the cellular bioactivity of carbon–carbon composites, thus extending applications of carbon–carbon composites to the bone repair field.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2024
·Vol. 19
·期 1
·1-13
·
IF 2.8
Huang Fenglan,Wang Yiteng,Liu Jinzhu,Cheng Ye,Zhang Xiaonan,Jiang Haoli
Background Osteoporosis is a metabolic bone disease that has a common occurrence in postmenopausal women. Asperuloside (ASP) has been reported to exert anti-inflammatory and anti-oxidative effects in numerous diseases, such as rheumatoid arthritis and acute lung injury. However, whether ASP plays a role in osteoporosis has not been addressed.Methods In vivo, ovariectomy (OVX) was used to induce mouse osteoporosis. Then, the mice were treated with 20 and 40 mg/kg ASP. In vitro, MC3T3-E1 cells were treated with 0, 1, 10, 20, 40 and 80 µM ASP. We chose 20 and 40 µM for further experiments due to no significant effects on cell viability.Results The data indicated that ASP reduced osteoporosis in OVX mice and promoted osteogenic differentiation and mineralization in MC3T3-E1 cells. In addition, we explored that ASP protected against osteoporosis via inducing autophagy and activating Nrf2.Conclusion ASP alleviates OVX-induced osteoporosis by promoting autophagy and regulating Nrf2 activation.
研究领域:
药理学
·
骨骼生物学
·
医学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）