Journal of Functional Biomaterials
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2025
·Vol. 16
·期 2
·52
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IF 5.2
He Bai,Wei Zhang,Xuanxuan Yan,Lin Qiu,Pengfei Cui,Weiyang Chen
In recent years, factors such as the postponement of childbearing and the relaxation of the childbearing policy have led to an increase in the proportion of cesarean sections and other intrauterine surgeries among pregnant women, further increasing the incidence of uterine scars. Currently, there is a lack of effective clinical treatment methods for uterine scars. In this study, a suture loaded with gene medicine was designed for the repair of uterine scars. Specifically, the non-viral vector Lipo8000 was first used to form a complex solution with the plasmid TGF-β3. Then, it was mixed and adsorbed with the surgical sutures pretreated with recombinant human type III collagen (RhCol III). In vitro experiments confirmed that RhCol III and the plasmid were successfully loaded onto the sutures and could be released and expressed. In vivo experiments were carried out using a rat model simulating uterine scars. The section results showed that compared with the scar model group, the expression level of TGF-β3 in the RhCol III+TGF-β3 group increased by 39%, the expression level of TGF-β1 decreased by 62.8%, and the fibrosis rate decreased by 16.8%, which has a positive effect on the prevention of uterine scars. This study integrates the therapeutic medicine into the sutures, ensuring that the medicine can come into contact with the wound site after suturing. Moreover, RhCol III and the gene medicine work synergistically to promote the repair of uterine wounds.
研究领域:
妇产科学
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分子生物学
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生物医学工程
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DOI
PubMed
高影响因子
BMC MUSCULOSKELETAL DISORDERS
·
2024
·Vol. 25
·期 1
·1-11
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IF 2.2
Du Xiao,Zang Chuanyi,Wang Qinglei
Background Osteoporosis is a genetic disease caused by the imbalance between osteoblast-led bone formation and osteoclast-induced bone resorption. However, further gene-related pathogenesis remains to be elucidated.Methods The aberrant expressed genes in osteoporosis was identified by analyzing the microarray profile GSE100609. Serum samples of patients with osteoporosis and normal group were collected, and the mRNA expression of candidate genes was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The mouse cranial osteoblast MC3T3-E1 cells were treated with dexamethasone (DEX) to mimic osteoporosis in vitro. Alizarin Red staining and alkaline phosphatase (ALP) staining methods were combined to measure matrix mineralization deposition of MC3T3-E1 cells. Meanwhile, the expression of osteogenesis related genes including alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), Osterix, and bone morphogenetic protein 2 (BMP2) were evaluated by qRT-PCR and western blotting methods. Then the effects of candidate genes on regulating impede bone loss caused by ovariectomy (OVX) in mice were studied.Results Cyclin A1 (CCNA1) was found to be significantly upregulated in serum of osteoporosis patients and the osteoporosis model cells, which was in line with the bioinformatic analysis. The osteogenic differentiation ability of MC3T3-E1 cells was inhibited by DEX treatment, which was manifested by decreased Alizarin Red staining intensity, ALP staining intensity, and expression levels of ALP, OCN, OPN, Osterix, and BMP2. The effects of CCNA1 inhibition on regulating osteogenesis were opposite to that of DEX. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that genes negatively associated with CCNA1 were enriched in the TGF-beta signaling pathway. Inhibitor of TGF-beta signaling pathway partly reversed osteogenesis induced by suppressed CCNA1. Furthermore, suppressed CCNA1 relieved bone mass of OVX mice in vivo.Conclusion Downregulation of CCNA1 could activate TGF-beta signaling pathway and promote bone formation, thus playing a role in treatment of osteoporosis.
研究领域:
骨生物学
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分子生物学
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遗传学
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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
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IF 4.8
Tangfei Guan,Xin Yang,Canhui Hong,Jiali Zhu,Peiyun Xiao,Yongshou Yang,Chenggui Zhang,Zhengchun He
Introduction: Alopecia areata (AA), an autoimmune hair-loss disease due to follicular inflammatory cell infiltration, lacks an ideal cure. The Periplaneta Americana (PA) extract (PA-011), a traditional Chinese medicine with anti-inflammatory, antioxidant, tissue-repair-promoting, and immune-regulating properties, was studied for its AA-treating effects.Methods: Guided by network pharmacology, AA model mice were treated with PA-011. Hair growth, skin tissue, inflammatory factors, and Wnt protein levels were examined. Transcriptomics, metabolomics, and 16S rRNA sequencing explored the hair-growth-promoting mechanisms.Results: Network pharmacology showed PA-011 could regulate AA-related targets and pathways. PA-011 intervention promoted hair follicle cell proliferation and hair growth in AA mice, reduced skin TNF-α, IL-23, and VCAM-1 expression. Transcriptomics and WB analysis indicated PA-011 downregulated inflammatory genes, activated Wnt3a, and modulated the TGF-β pathway. Metabolomics found PA-011 regulated metabolic pathways. 16S rRNA analysis showed it reversed AA-induced skin microbiota changes, inhibiting pathogens and promoting probiotics. Multi-omics analysis revealed PA-011 regulated skin microbiota and metabolic balance for hair growth.Discussion: In conclusion, PA-011 alleviates AA by reducing skin inflammation and modulating skin microbiota, suggesting its potential as an AA therapeutic.
研究领域:
药理学
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皮肤病学
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免疫学
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微生物学
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中医药学
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系统生物学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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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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PubMed
高影响因子
MOLECULAR IMMUNOLOGY
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2024
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IF 3.2
Chaonan Zhu,Zhiquan Chen,Shuai Wang,Junmei Cao,Yuan Cheng,Maogen Zheng
Lung adenocarcinoma (LUAD) is a highly heterogeneous disease that threaten human life with serious incidence and high mortality. High heterogeneity of tumor microenvironment (TME) was reported in multiple studies. However, the factor of controlling the tumor migration progression between eary and late-stage LUAD is still not fully understood. In this study, we conducted a comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data of LUAD obtained from the GEO database. The identification of cell clusters revealed significant expansion of epithelial cells in late-stage patients. Interpretation of the cell-cell communication results between early-stage and late-stage patient samples indicated that early tumor cells may interact with epithelial cells through the TGF-β pathway to promote tumor progression. The cell cycle analysis demonstrated a significant increase in the number of cells in the G2 and M phases in late-stage lung cancer. Further analysis using Non-negative Matrix Factorization (NMF) revealed early-stage cell-specific gene features involved in cell adhesion-related biological processes. Among these, the Tensin (TNS) gene family, particularly TNS1, showed high expression in epithelial cells and fibroblasts of early-stage samples, specifically associated with cell adhesion. Survival analysis using TCGA database for LUAD demonstrated that patients with high expression of TNS1 exhibited significantly higher overall survival rates compared to those with low expression. Immunofluorescence experiments have demonstrated co-expression of TNS1 with fibroblast and tumor cell markers (α-SMA and EPCAM). Immunohistochemistry experiments further validated the significantly higher expression levels of TNS1 in early-stage LUAD tissues compared to late-stage lung cancer tissues (P<0.05). Pathway experiments have shown that early-stage tumor patients with high expression of TNS1 exhibit stronger phosphorylation levels of Akt and mTOR, indicating a more potent activation of the Akt/mTOR signaling pathway. In conclusion, the results of this study demonstrate that TNS1 is an adhesive molecule in the immune microenvironment of early-stage tumor cells, and it may serve as a novel prognostic marker for lug cancer.
研究领域:
肿瘤学
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分子生物学
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基因组学
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细胞生物学
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癌症生物学
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DOI
PubMed
高影响因子
Stem Cell Research & Therapy
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2019
·Vol. 10
·期 1
·1-11
·
IF 4.627
Kong Yuanyuan,Hu Xiaoli,Zhong Yingqun,Xu Ke,Wu Buling,Zheng Jianmao
Background Magnesium (Mg 2+ )-enriched microenvironment promotes odontogenic differentiation in human dental pulp stem cells (DPSCs), but the regulatory mechanisms remain undefined. The aim of this work was to assess magnesium’s function in the above process and to explore the associated signaling pathway. Methods DPSCs underwent culture in odontogenic medium with the addition of 0, 1, 5, or 10 mM MgCl 2 . Intracellular Mg 2+ levels in DPSCs were evaluated flow cytometrically using Mag-Fluo-4-AM. Mg 2+ -entry was inhibited by TRPM7 inhibitor 2-aminoethoxydiphenyl borate (2-APB). RNA-Sequencing was carried out for assessing transcriptome alterations in DPSCs during odontogenic differentiation associated with high extracellular Mg 2+ . KEGG pathway analysis was performed to determine pathways related to the retrieved differentially expressed genes (DEGs). Immunoblot was performed for assessing magnesium’s role and exploring ERK/BMP2/Smads signaling. Results Mg 2+ -enriched microenvironment promoted odontogenic differentiation in DPSCs via intracellular Mg 2+ increase. Consistently, the positive effect of high extracellular Mg 2+ on odontogenic differentiation in DPSCs was blocked by 2-APB, which reduced Mg 2+ entry. RNA-sequencing identified 734 DEGs related to odontogenic differentiation in DPSCs in the presence of high extracellular Mg 2+ . These DEGs participated in many cascades such as MAPK and TGF-β pathways. Consistently, ERK and BMP2/Smads pathways were activated in DPSCs treated with high extracellular Mg 2+ . In agreement, ERK signaling inhibition by U0126 blunted the effect of high extracellular Mg 2+ on mineralization and odontogenic differentiation in DPSCs. Interestingly, BMP2, BMPR1, and phosphorylated Smad1/5/9 were significantly decreased by U0126, indicating that BMP2/Smads acted as downstream of ERK. Conclusions Mg 2+ -enriched microenvironment promotes odontogenic differentiation in DPSCs by activating ERK/BMP2/Smads signaling via intracellular Mg 2+ increase. This study revealed that Mg 2+ -enriched microenvironment could be used as a new strategy for dental pulp regeneration.
研究领域:
牙科研究
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干细胞生物学
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分子生物学
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细胞信号传导
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DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2022
·
IF 7.392
Yi Wang,Linhao Hou,Yiqian Huang,Pengfei Wei,Liya Sun,Yan Zhang,Xueqiao Yu,Shiqing Ma,Wei Jing,Bo Zhao,Huachong Ma
Chronic wounds in diabetes take a lifetime risk of developing into diabetic foot ulcers (DFUs). Conventional wound dressings and commercial products fail for ideal tissue regeneration in DFUs due to the incapacity to promote vascularization and prevent bacterial infections during wound repair. In this study, the small intestinal submucosa (SIS) with enriched vascularized bioactive factors, was chemically decorated by 2-methacryloyloxy ethyl phosphorylcholine (MPC) through Michael-type addition to be endowed anti-fouling ability, in order to treat chronic wound regeneration in diabetes. In the diabetic skin injury experiment, we established the animal model by 5-mm diameter defects in the SD rats and implanted the bio-patches to the located sites. The SIS-MPC bio-patch showed superior advantages in bacterial anti-adhesion (100-fold foul resistance than commercial patches), while maintained affinity for fibroblast growth and collagen formation, as demonstrated by immunohistochemical staining from the local tissues, outperforming commercial wound dressings in tissue regeneration, which was attributed to acceleration in neovascularization and inflammation modulation through TGF-β and MAPK pathway. This novel SIS-MPC bio-patch would be a promising candidate for medical translations into diabetes and chronic wound treatments.
研究领域:
生物医学工程
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组织工程
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伤口愈合
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糖尿病研究
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2021
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IF 9.229
Jun Zhang,Tiantian Zuo,Jie Yang,Zongwei Hu,Zhihua Wang,Rui Xu,Siyu Ma,Yawen Wei,Qi Shen
The aggressive progression of breast cancer is impacted significantly by the tumor microenvironment (TME). The current chemotherapy normally causes cytotoxicity to tumor cells, while does not effectively modulate the TME. Thus, the chemotherapy effect of breast cancer is usually dissatisfactory. In this study, a kind of hierarchically releasing bio-responsive nanoparticles (R(D)/H(S) NPs), constructed by β-cyclodextrin-grafted heparin and pH-sensitive pseudorotaxane, were investigated to enhance the breast cancer chemotherapeutic efficacy through TME modulation. Doxorubicin (DOX) and transforming growth factor-β (TGF-β) receptor inhibitor (SB431542) loaded onto R(D)/H(S) NPs were released rapidly for the respective response to low pH in endosomes/lysosomes and heparanase (HPSE) in TME. Our results showed that R(D)/H(S) NPs effectively inhibited the formation of tumor-associated fibroblasts (TAFs) and reduced TGF-β and collagen I secretion. Besides, the immunosuppressive microenvironment was effectively reversed into immunogenic, characterized by increased CD8+ and CD4+ T cell infiltration, which distinctly inhibited breast cancer metastasis. Therefore, R(D)/H(S) NPs remodeled the TME by downregulating TAFs, TGF-β, and collagen I; activating the immune microenvironment; and then amplifying the chemotherapeutic efficacy of DOX.
研究领域:
肿瘤学
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纳米技术
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
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