JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Hou Yu,Zhu Lin,Ye Xiaofeng,Ke Qiaoying,Zhang Qibin,Xie Xiaowei,Piao Ji-gang,Wei Yinghui
Background Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies. Results In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang ( L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-β/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats. Conclusion In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation. Graphical Abstract
研究领域:
药学
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生物医学工程
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肾病学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Genes
·
2024
·Vol. 15
·期 5
·605
·
IF 2.8
Haijun Huang,Yuyan Liu,Qian Wang,Caichao Dong,Le Dong,Jingjing Zhang,Yu Yang,Xiancai Hao,Weijing Li,Ivana F. Rosa,Lucas B. Doretto,Xuebin Cao,Changwei Shao
It is widely known that all-female fish production holds economic value for aquaculture.Sebastes schlegelii, a preeminent economic species, exhibits a sex dimorphism, with females surpassing males in growth. In this regard, achieving all-female black rockfish production could significantly enhance breeding profitability. In this study, we utilized the widely used male sex-regulating hormone, 17α-methyltestosterone (MT) at three different concentrations (20, 40, and 60 ppm), to produce pseudomales ofS. schlegeliifor subsequent all-female offspring breeding. Long-term MT administration severely inhibits the growth ofS. schlegelii, while short term had no significant impact. Histological analysis confirmed sex reversal at all MT concentrations; however, both medium and higher MT concentrations impaired testis development. MT also influenced sex steroid hormone levels in pseudomales, suppressing E2 while increasing T and 11-KT levels. In addition, a transcriptome analysis revealed that MT down-regulated ovarian-related genes (cyp19a1aandfoxl2) while up-regulating male-related genes (amh) in pseudomales. Furthermore, MT modulated the TGF-β signaling and steroid hormone biosynthesis pathways, indicating its crucial role inS. schlegeliisex differentiation. Therefore, the current study provides a method for achieving sexual reversal using MT inS. schlegeliiand offers an initial insight into the underlying mechanism of sexual reversal in this species.
研究领域:
水产养殖
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内分泌学
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分子生物学
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生理学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
·
IF 5.4
Huilin Huang,Xue Song,Jiangjiang Zhang,Yan Fan,Ming Kong,Li Zhang,Hu Hou
Scaffolds with multiphasic structures are considered to be superior for guided tissue regeneration. Two types of tilapia skin collagen gradient membranes (stepped gradient and linear gradient) with multiphasic structures were prepared by controlling the collagen concentrations and the freezing rates. The results revealed that collagen gradient membranes were more capable of guiding tissue regeneration compared to homogeneous membranes. These two gradient membranes featured a dense outer layer and a loose inner layer, with good mechanical properties as indicated by tensile strengths of more than 250 Kpa and porosities exceeding 85%. Additionally, these membranes also showed good hydrophilicity and water absorption, with an inner layer contact angle of less than 91° and a water absorption factor greater than 40 times. Furthermore, the multiphasic scaffolds were proved to be biocompatible by the acute toxicity assay, the intradermal irritation test and so on. Gradient membranes could effectively promote the adhesion and proliferation of fibroblasts and osteoblasts, through elevating the TGF-β/Smad signaling pathway by TGF-β and Smads, and activating the Wnt/β-catenin signaling pathway by LRP5 and β-catenin, similar to homogenous membranes. Therefore, collagen gradient membranes from tilapia skin show important application value in guiding tissue regeneration.
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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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Yenan Wu,Haiwei Liang,Aiping Luo,Yong Li,Zhiqiang Liu,Xin Li,Wenxin Li,Kaini Liang,Junyang Li,Zhihua Liu,Yanan Du
Cancer stem cells (CSCs) are crucial for tumorigenesis, metastasis, and therapy resistance in esophageal squamous cell carcinoma (ESCC). To further elucidate the mechanism underlying characteristics of CSCs and develop CSCs-targeted therapy, an efficient culture system that could expand and maintain CSCs is needed. CSCs reside in a complex tumor microenvironment , and three-dimensional (3D) culture systems of biomimetic scaffolds are expected to better support the growth of CSCs by recapitulating the biophysical properties of the extracellular matrix (ECM). Here, we established gelatin-based 3D biomimetic scaffolds mimicking the stiffness and collagen content of ESCC, which could enrich ESCC CSCs efficiently. Biological changes of ESCC cells laden in scaffolds with three different viscoelasticity emulating physiological stiffness of esophageal tissues were thoroughly investigated in varied aspects such as cell morphology , viability, cell phenotype markers , and transcriptomic profiling. The results demonstrated the priming effects of viscoelasticity on the stemness of ESCC. The highly viscous scaffolds (G’: 6–403 Pa; G’’: 2–75 Pa) better supported the enrichment of ESCC CSCs, and the TGF-beta signaling pathway might be involved in regulating the stemness of ESCC cells. Compared to two-dimensional (2D) cultures, highly viscous scaffolds significantly promoted the clonal expansion of ESCC cells in vitro and tumor formation ability in vivo . Our findings highlight the crucial role of biomaterials’ viscoelasticity for the 3D culture of ESCC CSCs in vitro , and this newly-established culture system represents a valuable platform to support their growth, which could facilitate the CSCs-targeted therapy in the future.
研究领域:
生物材料
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癌症生物学
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细胞生物学
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组织工程
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干细胞研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Feng Sa,Liu Linyan,Cheng Yuelin,Zhou Mengmeng,Zhu Haoqiang,Zhao Xinyan,Chen Ziyu,Kan Shunli,Fu Xuanhao,Hu Wei,Zhu Rusen
Objective: The limited ability to regenerate axons after spinal cord injury (SCI) is influenced by factors such as astrocyte activation, reactive proliferation, and glial scar formation. The TGF-β/Smad (transforming growth factor-β/mothers against decapentaplegic homolog) pathway, associated with astrocytic scarring, plays a crucial role in recovery post-injury. This study aims to investigate how icariin (ICA) interacts with reactive astrocytes in the treatment of spinal cord injury.Methods: A rat SCI model was constructed, and the recovery of motor function was observed after treatment with ICA.HE staining, LFB staining, immunofluorescence staining, and Western blotting were employed to assess ICA's ability to inhibit astrocyte proliferation in rats following spinal cord injury by modulating YAP, as well as to evaluate the reparative effects of ICA on the injured spinal cord tissue. Primary astrocytes were isolated and cultured. Immunoprecipitation-Western Blot (IP-WB) ubiquitination and cytoplasm-nuclear separation were employed to assess PPM1B ubiquitination and nuclear translocation.Results: The CatWalk XT gait analysis, BBB (Basso, Beattie, and Bresnahan) score, electrophysiological measurements, HE staining, and LFB staining collectively demonstrated that ICA promotes motor function and tissue recovery following spinal cord injury in rats. Immunofluorescence staining and Western Blot analyses revealed that ICA inhibits astrocyte proliferation in rats post-spinal cord injury by suppressing YAP activity. Furthermore, the activation of YAP by XMU-MP-1 was shown to compromise the efficacy of ICA in these rats after spinal cord injury. Additional immunofluorescence staining and Western Blot experiments confirmed that ICA inhibits TGFβ1-induced astrocyte activation through the regulation of YAP. The knockdown of PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) in astrocytes was found to inhibit TGFβ signaling. Additionally, YAP was shown to regulate PPM1B ubiquitination and nuclear translocation through immunoprecipitation-Western blot analysis, along with the segregation of cytoplasm and nucleus.Conclusion: Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Bionic Engineering
·
2021
·Vol. 18
·期 6
·1378-1390
·
IF 2.682
Li Pengfei,Ruan Liming,Wang Ruofan,Liu Tianqi,Song Gao,Gao Xiaofei,Jiang Guohua,Liu Xiaoyan
Nanofibers (NFs) have been widely used in tissue engineering such as wound healing. In this work, the antibacterial ZnO quantum dots (ZnO QDs) have been incorporated into the biocompatible poly (ε-caprolactone)/collagen (PCL/Col) fibrous scaffolds for wound healing. The as-fabricated PCL-Col/ZnO fibrous scaffolds exhibited good swelling, antibacterial activity, and biodegradation behaviors, which were beneficial for the applications as a wound dressing. Moreover, the PCL-Col/ZnO fibrous scaffolds showed excellent cytocompatibility for promoting cell proliferation. The resultant PCL-Col/ZnO fibrous scaffolds containing vascular endothelial growth factor (VEGF) also exhibited promoted wound-healing effect through promoting expression of transforming growth factor-β (TGF-β) and the vascular factor (CD31) in tissues in the early stages of wound healing. This new electrospun fibrous scaffolds with wound-healing promotion and antibacterial property should be convenient for treating wound healing.
研究领域:
组织工程
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伤口愈合
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生物材料
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纳米技术
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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
Pharmaceuticals
·
2024
·Vol. 17
·期 11
·1420
·
IF 4.3
Xinlan Hu,Yan Wu,Hanyi Ouyang,Jiayan Wu,Mengmeng Yao,Zhuo Chen,Qianbin Li
Background/Objectives:Homeodomain-interacting protein kinase 2 (HIPK2) is critically involved in the progression of renal fibrosis. This study aims to identify and characterize a novel HIPK2 inhibitor, CHR-6494, and investigate its therapeutic potential.Methods:Using structure-based virtual screening and molecular dynamics simulations, we identified CHR-6494 as a potent HIPK2 inhibitor with an IC50of 0.97 μM. The effects of CHR-6494 on the phosphorylation of p53 in Normal Rattus norvegicus kidney cells (NRK-49F) induced by transforming growth factor-β (TGF-β) were assessed, along with its impact on TGF-β signaling and downstream profibrotic markers.Results:CHR-6494 significantly reduces p53 phosphorylation induced by TGF-β and enhances the interaction between HIPK2 and seven in absentia 2 (SIAH2), facilitating HIPK2 degradation via proteasomal pathways. Both CHR-6494 and Abemaciclib inhibit NRK-49F cell proliferation and migration induced by TGF-β, suppressing TGF-β/Smad3 signaling and decreasing profibrotic markers such as Fibronectin I (FN-I) Collagen I and α-smooth muscle actin (α-SMA). Additionally, these compounds inhibit nuclear factor kappa-B (NF-κB) signaling and reduce inflammatory cytokine expression.Conclusions:The study highlights the dual functionality of HIPK2 kinase inhibitors like CHR-6494 and Abemaciclib as promising therapeutic candidates for renal fibrosis and inflammation. The findings provide new insights into HIPK2 inhibition mechanisms and suggest pathways for the design of novel HIPK2 inhibitors in the future.
研究领域:
药理学
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分子生物学
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肾脏生理学
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药物发现
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
·
IF 5.7
Benyue Sun,Yunhui Wang,Jingjing Bai,Xuejiao Li,Long Ma,Shuli Man
Ulcerative colitis (UC) is a common chronic, relapsing inflammatory bowel condition. Procyanidins (PC) are known for their antiangiogenic, anti-inflammatory, antioxidant, and antimetastatic properties. However, there is comparatively limited information on how PC interacts with UC. In this study, 5 mg/10 mL/kg body weight of PC was administered to mice with dextran sulfate sodium (DSS)-induced colitis mice. PC treatment prolonged the survival period of mice, ameliorated UC symptoms, reduced damage to the intestinal mucosal barrier, and increased the protein expression of ZO-1 and occludin in the DSS-treated mice. Importantly, PC treatment significantly reduced gene expression related to Th17 cell differentiation, including STAT3, SMAD3, TGF-β, and JAK1. The results of the flow cytometry analysis indicated significant increase in the number of Treg cells and a concomitant decrease in the proportion of Th17 cells in the colon following PC treatment. Additionally, PC increased the abundance of gut microbiota such as Bacteroidota, Oscillospiraceae, Muribaculaceae, and Desulfovibrionaceae, as well as the concentrations of acetate acid, propionate acid, and butyrate acid in the feces. PC also activated short-chain fatty acid receptors, such as G-protein coupled receptor 43 in the colon, which promoted the proliferation of Treg cells. The depletion of gut microbiota and subsequent transplantation of fecal microbiota demonstrated that PC’s effects on gut microbiota were effective in improving UC and restoring intestinal Th17/Treg homeostasis in a microbiota-dependent manner. This suggests that PC could be a promising functional food for the prevention and treatment of UC in the future.
研究领域:
免疫学
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胃肠病学
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微生物学
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药理学
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营养学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Shuguang Wang,Kun Shi,Jiawei Lu,Weilian Sun,Qinghui Han,Lingbin Che,Dong Zhang
As a common complication of spine surgery, postoperative epidural fibrosis is an important cause of failed back surgery syndrome (FBSS), yet there is no effective clinical intervention to tackle it. Herein, for the first time, we develop a strategy of combining a gelatin methacryloyl (GelMA) hydrogel matrix with poly(lactic-co-glycolic acid) (PLGA) microsphere-encapsulated resveratrol (RSV), which aims to synergistically promote the inhibition effect on epidural fibrosis. The resultant RSV@PLGA-GelMA (8% w/v) hydrogels possess optimal mechanical properties and prompt the matrix sustainably and stably to release RSV for several weeks. It is further shown that the hybrid hydrogels without the drug exhibit good biosafety without distinct cytotoxicity, while RSV@PLGA-GelMA could prevent fibroblast proliferation and migration. Further rat laminectomy model indicates that the RSV@PLGA-GelMA hydrogels reduce epidural fibrosis by inhibiting fibroblast proliferation and extracellular matrix overexpression and deposition via a TGF-β/Smad signaling pathway. Consequently, we believe that such a creative structural combination will be a promising strategy for preventing postoperative epidural fibrosis of spine surgery.
研究领域:
生物医学工程
·
药学
·
神经外科
✓ 已验证
产品关联
DOI
PubMed
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 8
·1725-1738
·
IF 7
Xin Sun,Xin Jiao,Zengguang Wang,Jie Ma,Tianchang Wang,Dan Zhu,Han Li,Liang Tang,Heyue Li,Changde Wang,Yiming Li,Chen Xu,Jinwu Wang,Yaogai Gan,Wenjie Jin
Cellular bioactivity and tissue regeneration can be affected by coatings on tissue-engineered scaffolds. Using mussel-inspired polydopamine (PDA) is a convenient and effective approach to surface modification. Therefore, 3D-printed β-tricalcium phosphate (β-TCP) scaffolds were coated with PDA in this study. The effects of the scaffolds on the adhesion and osteogenic differentiation of seeded bone marrow mesenchymal stem cells (BMSCs) in vitro and on new-bone formation in vivo were investigated. The potential mechanisms and related differential genes were assessed using mRNA sequencing. It was seen that PDA coating increased the surface roughness of the 3D-printed β-TCP scaffolds. Furthermore, it prompted the adhesion and osteogenic differentiation of seeded BMSCs. mRNA sequencing analysis revealed that PDA coating might affect the osteogenic differentiation of BMSCs through the calcium signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway, etc. Moreover, the expression of osteogenesis-related genes, such as R-spondin 1 and chemokine c-c-motif ligand 2, was increased. Finally, both the 3D-printed β-TCP scaffolds and PDA-coated scaffolds could significantly accelerate the formation of new bone in critical-size calvarial defects in rats compared with the control group; and the new bone formation was obviously higher in the PDA-coated scaffolds than in β-TCP scaffolds. In summary, 3D-printed β-TCP scaffolds with a PDA coating can improve the physicochemical characteristics and cellular bioactivity of the scaffold surface for bone regeneration. Potential differential genes were identified, which can be used as a foundation for further research.
研究领域:
生物材料
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组织工程
·
干细胞生物学
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分子生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 16
·8587
·
IF 13.3
Wei-Jia Yu,Wen-Xi Jiang,Shu-Jing Liu,Hui-Hua Li,Qiu-Yue Lin
Rationale: Infiltration of immune cells into the heart plays a crucial role in the transition from adaptive hypertrophy to heart failure (HF) following chronic pressure overload. However, the key factors in myeloid cells that regulate this process are still not well defined. Here, we studied the functional role of S100A8/A9 in myeloid cells during this transition. Methods: Cardiac hypertrophy and HF models were induced by transverse aortic constriction (TAC) for 1 to 4 weeks. The heterogeneity of CD45 + immune cells and the cellular sources of S100A8/A9 were analyzed using published single-cell RNA sequencing datasets. The effects of S100A8/A9 on TAC-induced hypertrophy and HF were verified in S100A9 knockout (KO) and bone marrow (BM)-chimeric mice and in an in vitro coculture system. Results: S100A8/A9 levels were significantly increased in HF patients and in TAC-induced HF model mice. Moreover, the TAC-induced transition from adaptive hypertrophy to HF was significantly attenuated in S100A9-KO mice and WT mice transplanted with S100A9-KO BM cells. Mechanistically, TAC-stimulated upregulation of S100A8/A9 in neutrophils induced an early inflammatory response and adaptive hypertrophy through activation of the p38 MAPK/JNK/AP-1 pathway, leading to increased production of IL-1β and chemokines (CCL2 and CCL6). These chemokines promoted the infiltration of CCR2 + macrophages to the damaged heart. Therefore, they exhibited upregulation of S100A8/A9, which led to exacerbation of inflammation, cardiac hypertrophy and fibrosis via activation of the NF-κB/NLRP3, AKT/Calcineurin A and TGF-β/Smad2 signaling pathways. Additionally, treating WT mice with the S100A9 inhibitor ABR-238901 prevented TAC-induced cardiac hypertrophy-related dysfunction. Conclusion: The present findings establish an S100A8/A9-related axis between myeloid cells and cardiac cells that drives the pressure overload-induced transition from hypertrophy to HF, suggesting that S100A8/A9 is a promising therapeutic target for this disease.
研究领域:
心脏病学
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免疫学
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分子生物学
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基因组学
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生物医学研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Qi Ke,Xinyi Zhang,Yuan Yang,Qi Chen,Jianyu Su,Youhong Tang,Liming Fang
Magnetoelectric stimulation is a promising therapy for various disorders due to its high efficacy and safety. To explore its potential in chronic skin wound treatment, we developed a magnetoelectric dressing, CFO@CTAB/PVDF (CCP), by electrospinning cetyltrimethylammonium bromide-modified CoFe2O4 (CFO) particles with polyvinylidene fluoride. Cetyltrimethylammonium bromide (CTAB) serves as a dispersion surfactant for CFO, with its quaternary ammonium cations imparting antibacterial and hydrophilic properties to the dressing. Electrospinning polarizes polyvinylidene fluoride (PVDF) molecules and forms a fibrous membrane with flexibility and breathability. With a wearable electromagnetic induction device, a dynamic magnetic field is established to induce magnetostrictive deformation of CFO nanoparticles. Consequently, a piezoelectric potential is generated on the surface of PVDF nanofibers to enhance the endogenous electrical field in the wound, achieving a cascade coupling of electric–magnetic–mechanical–electric effects. Bacteria and cell cultures show that 2% CTAB effectively balances antibacterial property and fibroblast activity. Under dynamic magnetoelectric stimulation, the CCP dressing demonstrates significant upregulation of TGF-β, FGF, and VEGF, promoting L929 cell adhesion and proliferation. Moreover, it facilitates the healing of diabetic rat skin wounds infected with Staphylococcus aureus within 2 weeks. Histological and molecular biology evaluations confirm the anti-inflammatory effect of CTAB and the accelerated formation of collagen and vessel by electrical stimulation. This work provides insights into the application of magnetoelectric stimulation in the healing of chronic wounds.
研究领域:
生物医学工程
·
材料科学
·
伤口愈合
·
生物材料
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纳米技术
·
组织工程
✓ 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）