Biomaterials Advances
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2025
·
IF 6
Chen Shen,Xingyu Zhou,Junhui Jiang,Junbo Dang,Tong Lin,Ruibo Hu,Tianhao Zhao,Dahui Sun,Mei Zhang
Soft tissue fillers have received much attention for the treatment of skin aging and the restoration of missing or excised soft volumes. However, the development of fillers with both safety and applicability remains a challenge. This study presented a synergistic composite filler comprising aldehyde-modified hyaluronic acid (OHA), hydrazide-modified hyaluronic acid (NHA), amino-modified poly-L-lactic acid microspheres (NPLLA), and antioxidant copper peptide. The hydrogel formed in situ via Schiff base reaction exhibited excellent mechanical properties and immediate filling effect. The amino-modified PLLA microspheres were less likely to agglomerate, avoiding the occurrence of adverse reactions and further enhancing the mechanical properties of the filler. The timed-release platform provided protection for copper peptide stability, scavenged reactive oxygen species during the fibrotic encapsulation phase, and synergistically promoted collagen deposition. In a nude mice skin aging model, hydrogels stimulated collagen production through the TGF-β/Smad signaling pathway with good long-term filler efficacy. Therefore, NPLLA microspheres/hyaluronic acid-based composite hydrogels exhibit great potential as injectable soft tissue fillers.
研究领域:
生物材料
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组织工程
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生物医学工程
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皮肤科学
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药物递送
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2019
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IF 4.527
Gaofeng Cui,Haiqi Yuan,Zhiyan Jiang,Jing Zhang,Zhipeng Sun,Guohua Zhong
The widely distributed β-carboline alkaloids exhibit promising psychopharmacological and biochemical effects. Harmine, a natural β-carboline, can inhibit insect growth and development with unclear mechanisms. In this study, harmine (at 0-200 mg/L) showed a dose-dependent inhibitory effect on the pupal weight, length, height, pupation rate and eclosion rate of fruit flies Drosophila melanogaster , which was similar to the inhibition induced by the well-known botanical insect growth regulator azadirachtin . Moreover, the expression levels of major regulators from the developmental signaling network were down-regulated during the pupal stage except Numb , Fringe , Yorkie and Pten . The Notch, Wnt, Hedgehog and TGF-β pathways mainly played vital roles in coping with harmine exposure in pupae stage, while the Hippo, Hedgehog and TGF-β elements were involved in the sex differences. Notch , Hippo , Hedgehog , Dpp and Armadillo were proved to be suppressed in the developmental inhibition with fly mutants, while Numb and Punt were increased by harmine. In conclusion, harmine significantly inhibited the development of Drosophila by negatively affecting their developmental signaling network during different stages. Our results establish a preliminary understanding of the developmental signaling network subjected to botanical component-induced growth inhibition and lay the groundwork for further application.
研究领域:
昆虫学
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分子生物学
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发育生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Yuxiao Zhao,Xiaofang Cai,Jian Sun,Wei Bi,Youcheng Yu
Ethnopharmacological relevance Rhizoma Drynariae , as the dried rhizome of Drynaria fortunei (Kunze ex Mett.) J. Sm., is a traditional Chinese medicine for treating the injury and bone broken of falling and beating. Total flavonoids is considered as the major and effective compounds for the therapeutic efficacy of Rhizoma Drynariae . Aim of the study To explore the effect of total flavonoids from Rhizoma Drynariae (TFRD) on bone regeneration and the underlying mechanisms. Materials and methods The effect of TFRD in various doses on bone reconstruction in cranial bone defect rats was explored in vivo . The active ingredients in TFRD-medicated serum were characterized by serum pharmacochemistry and integrated by network pharmacology analysis and target prediction. To elucidate the underlying mechanism of TFRD on bone regeneration, experimental validation in vitro was executed to assess the influence of different concentrations of TFRD-medicated serum on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Results Micro-CT, histological examination, immunohistochemical analysis, and ELSA demonstrated that administration of TFRD could promote bone reconstruction in a rat cranial defect model. We identified 27 active components of TFRD using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Results from CCK8, ALP, and Alizarin Red S staining revealed that TFRD-medicated serum notably enhanced BMSCs proliferation and osteogenic differentiation. qRT-PCR and Western blot harvested results consistent with those predicted by network pharmacology, providing further evidence that TFRD activated the TGF-β signaling pathway to benefit bone regeneration. Conclusion The active components of TFRD modulate the TGF-β signaling pathway to facilitate osteogenesis, thereby repairing cranial bone defects.
研究领域:
药理学
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民族药理学
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骨生物学
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干细胞研究
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信号转导
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Tian Liu,Yun Zhang,Ze Wu,Chen-jing Zhao,Xi Dong,He-xin Gong,Bing Jin,Miao-miao Han,Jin-jia Wu,Yi-kai Fan,Nan Li,Ying-xia Xiong,Zi-qian Zhang,Zheng-qi Dong
The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-β. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment.
研究领域:
药理学
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肾病学
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分子生物学
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中医药学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Hai Li,Lingdi Niu,Jiaqing Wang,Qingru Chang,Shuhe Zhang,Jiaqi Wang,Jiankai Zeng,Mingchun Gao,Junwei Ge
Methicillin-resistant Staphylococcus aureus (MRSA) is rapidly spreading worldwide, emerging as a leading cause of bacterial infections in healthcare and community settings. This poses serious risks to human health. The shortage of novel antibiotics and the absence of effective vaccines make MRSA particularly challenging to treat. Existing vaccine development strategies often fail to provide early protection against infections, highlighting the urgent need for solutions. Herein, we propose a novel strategy combining trained immunity with a multi-epitope subunit vaccine to combat MRSA infections. We comprehensively evaluated the trained immune phenotypes induced by β-glucan from barley and curdlan. Macrophages trained with curdlan exhibited a more balanced inflammatory response compared to β-glucan from barley, expressing higher levels of IL-1β , IFN-β , TGF-β , and CCL2 upon secondary stimulation. Furthermore, curdlan-induced trained immunity rapidly provided excellent protection against S. aureus infection in mice. RNA-sequencing analysis revealed that curdlan modulates the Wnt signaling pathway in macrophages, resolves inflammation, and promotes tissue repair. When combined with one or two doses of S. aureus multivalent epitope antigen against MRSA infection, curdlan-induced trained immunity enhanced early protection and promoted recovery. Our study demonstrates the feasibility of combining trained immunity with vaccine protection against MRSA, providing a strategy against multi-drug resistant bacteria.
研究领域:
免疫学
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微生物学
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药理学
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疫苗学
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产品关联
DOI
PubMed
高影响因子
Mucosal Immunology
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2024
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IF 7.9
Jinzhe Tong,Simiao Chen,Xinyue Gu,Xuanqi Zhang,Fang Wei,Yingying Xing
Tissue-resident memory T cells (T RM ) can be induced by infection and vaccination, and play a key role in maintaining long-term protective immunity against mucosal pathogens. Our studies explored the key factors and mechanisms affecting the differentiation, maturation, and stable residence of gastric epithelial CD4 + T RM induced by Helicobacter pylori (Hp) vaccine and optimized Hp vaccination to promote the generation and residence of T RM .CD38 regulated mitochondrial activity and enhanced TGF-β signal transduction to promote the differentiation and residence of gastric epithelial CD4 + T RM by mediating the expression of CD105. Extracellular nucleotides influenced the long-term maintenance of T RM in gastric epithelium by P2RX7. Vitamin D3 and Gram-positive enhancer matrix particles (GEMs)as immune adjuvants combined with Hp vaccination promoted the production of CD69 + CD103 + CD4 + T RM .
研究领域:
免疫学
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微生物学
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分子生物学
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疫苗学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
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2017
·Vol. 233
·期 6
·4919-4925
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IF 4.08
Ji Li,Mincheng Zhang,Yong Mao,Yimao Li,Xiaoxia Zhang,Xuehan Peng,Feng Yu
Aristolochic acid I (AA-I), one of the main active components in Aristolochaia herbs, may induce aristolochic acid nephropathy (AAN). Renal interstitial fibrosis is one of the most typical features of AAN. To investigate the mechanism of Aristolochic acid I (AA-I) −induced renal epithelial-mesenchymal transition (EMT) and determine the role of aquaporin-1 (AQP1) in this process, we established an AA-I-induced EMT model in human proximal tubular epithelial cells (HK-2 cells). Morphological examination, MTT assay, and Western blot analysis were performed. Aquaporin 1 (AQP1) and several EMT-related proteins were detected, thereby suggesting the occurrence of AA-I-induced EMT. Two main pathways of transforming growth factor-β (TGF-β) signaling, namely, Smad-dependent and Smad-independent signaling pathways, were also detected. The results showed that the TGF-β / Smad-independent signaling pathways (β-catenin, Ras-Raf-Erk1/2 signaling pathways) were activated, and AQP1 expression was decreased during the AA-I induced EMT on HK-2 cells. With the presence of TGF-β1 receptor inhibitor (LY364947) and Erk1/2 inhibitor (PD98059), AQP1 expression was altered by PD98059, suggested that AQP1 could be adjusted by Erk1/2 signaling. Moreover, the inhibitory effect of AA-I on AQP1 was stronger than that of TGF-β1, suggested that AQP1 may be an important target on AAN clinical therapy.
研究领域:
肾病学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 10
·期 3
·753-769
·
IF 6.843
Zhiwei Yin,Lu Sun,Liyang Shi,Hemin Nie,Jianwu Dai,Can Zhang
Poor tendon repair remains a clinical problem due to the difficulties in replicating the complex multiscale hierarchical structure of native tendons. In this work, a bioinspired fibrous scaffold with bimodal micro-nanofibers and a teno-inductive aligned topography was developed to replicate microscale collagen fibers and nanoscale collagen fibrils that compose native tendons. The results showed indicated that the combination of micro- and nanofibers enhanced the mechanical properties. Furthermore, their biological performance was assessed using tendon stem/progenitor cells (TSPCs). Micro-nanofibers induced a higher cell aspect ratio and enhanced the tenogenic differentiation of TSPCs compared to micro- and nanocontrols. Interestingly, it was observed that scaffold nanotopography and microstructures promoted tenogenesis via activating the TGF-β/Smad2/3-mediated signaling pathway. The in situ implantation study confirmed that micro-nanofibrous scaffolds promoted the structural and mechanical properties of the regenerated Achilles tendon. Overall, our study shows that the bimodal micro-nanofibrous scaffold developed here presents a promising potential to improve the outcomes of tendon tissue engineering.
研究领域:
组织工程
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生物材料
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再生医学
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细胞生物学
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机械工程
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Qian Zhou,Haifei Kang,Monika Bielec,Xiaopei Wu,Qiao Cheng,Wenying Wei,Honglian Dai
Hydrogels are widely used as debriding agents on account of providing a moist environment for wound healing, however the lack of mechanical strength, angiogenesis and antibacterial property limits their applications. In this study, we synthesized novel divalent ion cross-liking hydrogels (copper, zinc, strontium and calcium) and compared the mechanical performance, swelling ratio, antibacterial properties and biocompatibility in vitro and vivo . Thereinto, among the four divalent ions cross-linked hydrogels, copper ion crosslinking exhibited the maximum breaking strength, while strontium and zinc ion cross-linked hydrogels exhibited an excellent mechanical strength. In addition, the swelling ratio and pore size of no-ion cross-linked hydrogels was larger than ion cross-kinked hydrogels. In vitro , the improvements on wound healing after hydrogel application were evaluated by histological and molecular assays by detecting VEGF and TGF-β expression. In vitro and in vivo study results showed that zinc cross-kinked hydrogel had a spectrum of antibacterial activities, cell viability, mechanical strength and the ability of wound closure by promoting fibroblasts migration, vascularization, collagen deposition and the formation of granulation tissue.
研究领域:
材料科学
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生物材料
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生物医学工程
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-22
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IF 9.429
Xia Jiaxuan,Zhang Shuya,Zhang Ru,Wang Anni,Zhu Ying,Dong Meichen,Ma Shaojie,Hong Chao,Liu Shengyao,Wang Dan,Wang Jianxin
The chemotherapy effect of docetaxel (DTX) against triple-negative breast cancer (TNBC) remains mediocre and limited when encapsulated in conventional cholesterol liposomes, mainly ascribed to poor penetration and immunosuppressive tumor microenvironment (TME) caused by tumor stroma cells, especially cancer-associated fibroblasts (CAFs). Many studies have attempted to address these problems but trapped into the common dilemma of excessively complicated formulation strategies at the expense of druggability as well as clinical translational feasibility. To better address the discrepancy, ginsenoside Rg3 was utilized to substitute cholesterol to develop a multifunctional DTX-loaded Rg3 liposome (Rg3-Lp/DTX). The obtained Rg3-Lp/DTX was proved to be preferentially uptake by 4T1 cells and accumulate more at tumor site via the interaction between the glycosyl moiety of Rg3 exposed on liposome surface and glucose transporter1 (Glut1) overexpressed on tumor cells. After reaching tumor site, Rg3 was shown to reverse the activated CAFs to the resting stage and attenuate the dense stroma barrier by suppressing secretion of TGF- β from tumor cells and regulating TGF- β /Smad signaling. Therefore, reduced levels of CAFs and collagens were found in TME after incorporation of Rg3, inducing enhanced penetration of Rg3-Lp/DTX in the tumor and reversed immune system which can detect and neutralize tumor cells. Compared with wooden cholesterol liposomes, the smart and versatile Rg3-Lp/DTX could significantly improve the anti-tumor effect of DTX, providing a promising approach for TNBC therapy with excellent therapeutic efficacy and simple preparation process.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Materials Horizons
·
2024
·
IF 12.2
Ziyang Zhou,Peiran Song,Yan Wu,Miaomiao Wang,Congyi Shen,Zhixin Ma,Xiaoxiang Ren,Xiuhui Wang,Xiao Chen,Yan Hu,Zuhao Li,Qin Zhang,Mengmeng Li,Zhen Geng,Jiacan Su
Osteoarthritis (OA) is a common joint disease known for cartilage degeneration, leading to a substantial burden on individuals and society due to its high disability rate. However, current clinical treatments for cartilage defects remain unsatisfactory due to the unclear mechanisms underlying cartilage regeneration. Tissue engineering hydrogels have emerged as an attractive approach in cartilage repair. Recent research studies have indicated that stem cells can sense the mechanical strength of hydrogels, thereby regulating their differentiation fate. In this study, we present the groundbreaking construction of dual-network DNA–silk fibroin (SF) hydrogels with controllable surface rigidity. The supramolecular networks, formed through DNA base-pairing, induce the development of β-sheet structures by constraining and aggregating SF molecules. Subsequently, SF was cross-linked via horseradish peroxidase (HRP)-mediated enzyme reactions to form the second network. Experimental results demonstrated a positive correlation between the surface rigidity of dual-network DNA–SF hydrogels and the DNA content. Interestingly, it was observed that dual-network DNA–SF hydrogels with moderate surface rigidity exhibited the highest effectiveness in facilitating the migration of bone marrow mesenchymal stem cells (BMSCs) and their chondrogenic differentiation. Transcriptome sequencing further confirmed that dual-network DNA–SF hydrogels primarily enhanced chondrogenic differentiation of BMSCs by upregulating the Wnt and TGF-β signaling pathways while accelerating collagen II synthesis. Furthermore, in vivo studies revealed that dual-network DNA–SF hydrogels with moderate surface rigidity significantly accelerated cartilage regeneration. In summary, the dual-network DNA–SF hydrogels represent a promising and novel therapeutic strategy for cartilage regeneration.
研究领域:
生物医学工程
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组织工程
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干细胞生物学
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骨科
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产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2018
·Vol. 14
·期 12
·2135-2145
·
IF 5.068
Chen Xiaoyu,Qin Zainen,Zhao Jinmin,Yan Xiaohui,Ye Jing,Ren En,Wang Junqing,Yang Xingchen,Heng Shujun,Zheng Li,Liu Gang
Mesenchymal stem cells (MSCs) have potential uses for cartilage repair due to the potential of chondrogenic differentiation. However, developing effective approaches to regulate chondrogenesis in vivo remains a big challenging. To address the limitations, we propose the application
of magnetic fields, which features excellent performance for tissue penetration, good biocompatibility even at high magnetic strength, and wireless remote control. To test this concept, a pulsed magnetic field (PMF) was used to enhance the chondrogenesis of SPIO-labeled MSCs in a rat model
of cartilage defects. The SPIO labeling not only efficiently strengthens the responsiveness of MSCs to the externally applied PMF but also enables in vivo non-invasive monitoring of MSCs with magnetic resonance imaging (MRI). Importantly, biochemical and gene expression analysis reveal
the upregulation of certain cartilage biomarkers (i.e., SOX9 and COL2A1), showing that the PMF improves the chondrogenesis of MSCs via activation of the TGF-β/SMAD signaling pathways. These results indicate a promising scheme for stem cell-based cartilage repair.
研究领域:
生物医学工程
·
干细胞生物学
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再生医学
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骨科
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）