Frontiers in Oncology
·
2021
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IF 6.244
Yang Feng,Zhao Ziyu,Cai Shaoyi,Ling Li,Hong Leying,Tao Liang,Wang Qin
Carboplatin resistance in ovarian cancer (OV) is a major medical problem. Thus, there is an urgent need to find novel therapeutic targets to improve the prognosis of patients with carboplatin-resistant OV. Accumulating evidence indicates that the gene COL1A1 (collagen type I alpha 1 chain) has an important role in chemoresistance and could be a therapeutic target. However, there have been no reports about the role of COL1A1 in carboplatin-resistant OV. This study aimed to establish the detailed molecular mechanism of COL1A1 and predict potential drugs for its treatment. We found that COL1A1 had a pivotal role in carboplatin resistance in OV by weighted gene correlation network analysis and survival analysis. Moreover, we constructed a competing endogenous RNA network (LINC00052/SMCR5-miR-98-COL1A1) based on multi-omics data and experiments to explore the upstream regulatory mechanisms of COL1A1. Two key pathways involving COL1A1 in carboplatin resistance were identified by co-expression analysis and pathway enrichment: the “ECM-receptor interaction” and “focal adhesion” Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, combining these results with those of cell viability assays, we proposed that ZINC000085537017 and quercetin were potential drugs for COL1A1 based on virtual screening and the TCMSP database, respectively. These results might help to improve the outcome of OV in the future.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Yue Fei,Zhichen Ling,Qian Tong,Jun Wang
Purpose Angiogenesis is a tightly controlled process that initiates the formation of new vessels and its dysfunction can lead to life-threatening diseases. Apoptotic extracellular vesicles (ApoEVs) have emerged as a proangiogenic agent with high safety and isolation efficiency profile, and ApoEVs from supernumerary tooth-derived pulp stem cells (SNTSC-ApoEVs) have their unique advantages with an easily accessible parental cell source and non-invasive cell harvesting. However, the detailed characteristics of SNTSC-ApoEVs are largely unknown. This study aimed to investigate the proangiogenic capacity and function molecule of SNTSC-ApoEVs.Methods SNTSC-ApoEVs were isolated and characterized. In vitro effects of SNTSC-ApoEVs on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8, wound healing, transwell, and tube formation assays. The mRNA and protein levels of proangiogenic genes were quantified by qRT-PCR, Western blot, and immunofluorescence analysis. A Matrigel plug model was established in 6-week-old male nu/nu mice for one week, and the in vivo impact of SNTSC-ApoEVs on micro-vessel formation was assessed by histological analysis. Proteomic analysis and RNA sequencing were performed to explore the active ingredients and underlying mechanisms.Results SNTSC-ApoEVs enhanced the proliferation, migration, and angiogenesis of HUVECs in vitro. In the Matrigel plug model in vivo, SNTSC-ApoEVs promoted CD31-positive luminal structure formation. Apart from expressing general ApoEV markers, SNTSC-ApoEVs were enriched with multiple proteins related to extracellular matrix-cell interactions. Mechanistically, SNTSC-ApoEVs transferred COL1A1 to HUVECs and promoted endothelial functions by activating the PI3K/Akt/VEGF cascade.Conclusion SNTSC-ApoEVs can promote angiogenesis by transferring the functional molecule COL1A1 and activating the PI3K/Akt/VEGF pathway, making SNTSC-ApoEVs a promising strategy for the treatment of angiogenesis-related diseases.
研究领域:
干细胞生物学
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血管生成
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分子生物学
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细胞生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
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2025
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IF 4.3
Bin Wang,Peng He,Xiaowei Liu,Shunjie Wu,Xinlin Lu,Bin Xu
Muscles and bones are adjacent in spatial position and closely related in function. Exosomes can achieve communication between donor and receptor cells by carrying molecules, such as miRNAs. Therefore, the purpose of this study is to use exosome-miRNA as a bridge, explore the correlation between clinical manifestations, and use bioinformatics and machine learning to cluster and screen exosome-miRNA sequencing data. In vitro and in vivo experiments were conducted to validate the screened molecules. Three parts were explored to identify miRNAs that play a key regulatory role in the muscle–exosome–bone system. Ultimately, it was found that miR-92a-1-5p may play a crucial role in this system; that is, atrophic muscle cells can inhibit osteogenic differentiation by releasing exosomes carrying miR-92a-1-5p into osteoblasts and targeting Col1a1.
研究领域:
生物信息学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
HUMAN MUTATION
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2026
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IF 1.8
Xiaomei Nie,Gang Su,Ran Zhang,Han Wang,Mingbo Li,Qian Liang
Background Diabetic retinopathy is caused by chronic hyperglycemia, which damages the retina′s blood vessels and neurons. This study is aimed at identifying potential therapeutic targets for DR. Methods Transcriptomic and proteomic data were obtained from the Gene Expression Omnibus (GEO) and ProteomeXchange databases, respectively. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were intersected. An enrichment analysis of the overlapping genes was performed based on the DAVID database. A protein–protein interaction (PPI) network (STRING) was analyzed via Cytoscape/cytoHubba to identify key genes. Single‐cell RNA‐sequencing (scRNA‐seq) data were processed using Seurat. Gene set enrichment analysis (GSEA) (clusterProfiler) and molecular docking (EnrichR) were performed. High glucose‐induced retinal microvascular endothelial cells (RMECs) were used for functional assays. Results The intersection of DEGs and DEPs yielded shared genes, enriched in the PI3K–Akt signaling pathway, AGE–RAGE signaling pathway in diabetic complications, complement and coagulation cascades, and ECM–receptor interaction; a PPI network incorporating these genes revealed two key DR‐associated highly expressed genes, COL1A1 and SERPINE1. GSEA showed that samples with high expression of these key genes were enriched in pathways such as reactome signaling by TGFB family members, inflammatory response, TGF‐ β signaling, and reactome cell extracellular matrix interactions. Single‐cell and molecular docking analyses revealed high expression of the two key genes in fibroblasts and binding between SERPINE1 and paricalcitol, and HG induction increased their levels in RMECs, whereas knockdown of SERPINE1 repressed RMEC proliferation, migration, and invasion in vitro. Conclusion This study identifies SERPINE1 and COL1A1 as possible DR therapeutic targets, providing new insights into relevant therapeutic development.
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PubMed
高影响因子
Cell Discovery
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2024
·Vol. 10
·期 1
·1-14
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IF 13
Li Hao,Du Yu,Cheng Kaiwen,Chen Yuxi,Wei Ling,Pei Yujun,Wang Xiaoyu,Wang Lan,Zhang Ye,Hu Xiaoxin,Lu Yi,Zhu Xiangjia
High myopia (HM) is a leading cause of blindness worldwide with currently no effective interventions available. A major hurdle lies in its often isolated perception as a purely ocular morbidity, disregarding potential systemic implications. Recent evidence suggests the existence of a gut-eye axis; however, the role of gut microbiota in the pathogenesis of HM remains largely unexplored. Herein, we provide a potential crosstalk among HM’s gut dysbiosis, microbial metabolites, and scleral remodeling. Utilizing 16S rRNA gene sequencing, we observed an altered gut microbiota profile in HM patients with a significant reduction in probiotic abundance compared with healthy controls. Subsequent targeted metabolic profiling revealed a notable decrease in plasma levels of the gut microbiota-derived metabolite indole-3-acetic acid (3-IAA) among HM patients, which is closely associated with the reduced probiotics, both negatively correlated with HM severity. Genetic analyses determined that gut microbiota are causally associated with myopia risk. Importantly, when mice subjected to HM modeling receive fecal microbiota transplantation from healthy donors, there is an increase in 3-IAA plasma levels and simultaneous retardation of HM progression along with better maintenance of collagen type I alpha 1 (COL1A1) expression in the sclera. Furthermore, 3-IAA gavage achieves similar effects. Mechanistic investigations confirm the transcriptional activation of COL1A1 by 3-IAA via promoting the enrichment of SP1 to its promoter. Together, our findings provide novel insights into the gut microbiota-eye axis in the pathogenesis of HM and propose new strategies for HM intervention by remodeling the gut microbiota and indole supplementation.
研究领域:
眼科学
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微生物学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
MOLECULAR BIOLOGY REPORTS
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2024
·Vol. 51
·期 1
·1-15
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IF 2.6
Wumiti Taxi,Wang Lining,Xu Bin,Ma Yong,Zhu Yihua,Zuo Xinchen,Qian Weiqing,Chu Xudong,Sun Haitao
Background Promoting the balance between bone formation and bone resorption is the main therapeutic goal for postmenopausal osteoporosis (PMOP), and bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation plays an important regulatory role in this process. Recently, several long non-coding RNAs (lncRNAs) have been reported to play an important regulatory role in the occurrence and development of OP and participates in a variety of physiological and pathological processes. However, the role of lncRNA tissue inhibitor of metalloproteinases 3 (lncTIMP3) remains to be investigated. Methods The characteristics of BMSCs isolated from the PMOP rat model were verified by flow cytometry assay, alkaline phosphatase (ALP), alizarin red and Oil Red O staining assays. Micro-CT and HE staining assays were performed to examine histological changes of the vertebral trabeculae of the rats. RT-qPCR and western blotting assays were carried out to measure the RNA and protein expression levels. The subcellular location of lncTIMP3 was analyzed by FISH assay. The targeting relationships were verified by luciferase reporter assay and RNA pull-down assay. Results The trabecular spacing was increased in the PMOP rats, while ALP activity and the expression levels of Runx2, Col1a1 and Ocn were all markedly decreased. Among the RNA sequencing results of the clinical samples, lncTIMP3 was the most downregulated differentially expressed lncRNA, also its level was significantly reduced in the OVX rats. Knockdown of lncTIMP3 inhibited osteogenesis of BMSCs, whereas overexpression of lncTIMP3 exhibited the reverse results. Subsequently, lncTIMP3 was confirmed to be located in the cytoplasm of BMSCs, implying its potential as a competing endogenous RNA for miRNAs. Finally, the negative targeting correlations of miR-214 between lncTIMP3 and Smad4 were elucidated in vitro. Conclusion lncTIMP3 may delay the progress of PMOP by promoting the activity of BMSC, the level of osteogenic differentiation marker gene and the formation of calcium nodules by acting on the miR-214/Smad4 axis. This finding may offer valuable insights into the possible management of PMOP.
研究领域:
骨生物学
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干细胞生物学
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分子生物学
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非编码RNA
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骨质疏松症
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产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
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2022
·Vol. 20
·期 1
·1-15
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IF 8.44
Guan Huanshuai,Kong Ning,Tian Run,Cao Ruomu,Liu Guanzhi,Li Yiyang,Wei Qilu,Jiao Ming,Lei Yutian,Xing Fangze,Tian Peng,Wang Kunzheng,Yang Pei
Background Osteoporosis is a disease threatening the health of millions of individuals. Melatonin is found to be a potential anti-osteoporosis drug. However, whether melatonin plays a role against osteoporosis at different stages of the menopause and the underlying mechanisms are unknown. Methods Ovariectomy was utilized as a model of perimenopausal and postmenopausal osteoporosis. A total of 100 mg/kg melatonin, or solvent alone, was added to the drinking water of the rats over 8 weeks. Perimenopausal rats immediately received intervention following ovariectomy while postmenopausal rats received intervention 8 weeks after ovariectomy. All rats underwent overdose anesthesia following intervention after which blood samples and femurs were collected for further analysis. Rat femurs were scanned using micro-CT and examined histologically. The serum levels of melatonin and osteogenic biochemical markers were measured and the expression of osteogenesis-associated genes ( Runx2 , Sp7 ) were quantified by real-time quantitative PCR. Alkaline phosphatase (ALP) activity and the gene expression ( Col1a1 , Runx2 , Alpl , and Bglap ) were measured after bone marrow mesenchymal stem cells (BMSCs) were osteogenically induced, both with and without melatonin in vitro. ALP staining and Alizarin Red S staining were used to identify osteogenesis. Results Analysis by micro-CT and histological staining demonstrated that bone mass decreased and bone microarchitecture deteriorated over time after ovariectomy. Intervention with melatonin increased bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats. Serum levels of ALP continuously increased after ovariectomy while osteocalcin levels initially rose, then decreased. Melatonin increased the serum levels of ALP and osteocalcin and mRNA expression levels of Runx2 and Sp7 in normal and postmenopausal rats, the opposite of the markers in perimenopausal rats. In vitro study demonstrated that 100 μmol/L melatonin increased the mRNA expression of Col1a1 , Runx2 , and Alpl three and/or seven days after intervention, and Alpl and Bglap 14 d after intervention. Melatonin increased ALP activity and the extent of ALP and matrix mineralization in the late stage of osteogenesis. Conclusions Bone mass continuously decreased after ovariectomy, while melatonin increased bone mass and ameliorated bone metabolism in normal, perimenopausal, and postmenopausal osteoporotic rats due to the induction of osteogenic differentiation in BMSCs.
研究领域:
内分泌学
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骨科
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Scientific Reports
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2019
·Vol. 9
·期 1
·1-10
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IF 4.011
Wang Yaozong,Sun Naikun,Zhang Yinlong,Zhao Bin,Zhang Zheyi,Zhou Xu,Zhou Yuanyuan,Liu Hongyi,Zhang Ying,Liu Jianguo
This study explored the applicability, cellular efficacy, and osteogenic activities of porous nano-hydroxyapatite/Poly (glycerol sebacate)-grafted maleic anhydride (n-HA/PGS-g-M) composite scaffolds. Nuclear magnetic resonance (NMR) analyses indicated that approximately 43% of the hydroxide radicals in PGS were displaced by maleic anhydride. Resonance bands at 1036 cm −1 occurred in scaffolds containing nHA powders, and peak areas increased when n-HA weight increased in PGS-M-n-HA-0.4, PGS-M-n-HA-0.5, and PGS-M-n-HA-0.6 scaffolds. The n-HA/PGS-g-M composite scaffolds exhibited porous microstructure with average pore size of 150–300 µm in scanning electron microscopy (SEM) analysis. Differential scanning calorimetry (DSC) identified the glass transition temperature (Tg) as −25–30 °C, indicative of quality resilience. The modulus of compressibility increased when n-HA content increased. Interestingly, viability of human adipose-derived stem cells (hADSCs) in vitro and expression of the osteogenic related genes RUNX2 , OCN , and COL1A1 was enhanced in the n-HA/PGS-g-M composite scaffolds compared to those factors observed in PGS-g-M scaffolds. Finally, simulated body fluid (SBF) tests indicated more apatite deposits on the surface of n-HA/PGS-g-M scaffolds compared to PGS-g-M scaffolds. Overall, porous n-HA/PGS-g-M composite scaffolds possessed acceptable biocompatibility and mechanical properties, and they stimulated hADSC cell proliferation and differentiation. Given these qualities, the composite scaffolds have potential applications in bone tissue engineering.
研究领域:
组织工程
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生物材料科学
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干细胞研究
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材料科学
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产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2025
·Vol. 20
·期 1
·1-14
·
IF 5.7
Jiang Feng,Tang Jiayang,Wei Xiaoqi,Pan Hai,Fan Xinyi,Zhang Peng,Guo Shuzhen
Background Dilated cardiomyopathy (DCM) stands as one of the most prevalent and severe causes of heart failure. Inflammation plays a pivotal role throughout the progression of DCM to heart failure, while age acts as a natural predisposing factor for all cardiovascular diseases. These two factors often interact, contributing to cardiac fibrosis, which is both a common manifestation and a pathogenic driver of adverse remodeling in DCM-induced heart failure.MethodBulk RNA-seq, single-cell RNA-seq, Mendelian randomization analysis, animal model construction, and BMP6 knockdown were utilized to identify and validate potential specific markers and targets for intervention in DCM heart failure.Results We found that DCM hearts exhibit pronounced inflammatory cell infiltration and fibrosis. Both bulk RNA-seq and single-cell RNA-seq analyses revealed aberrant BMP6 expression specifically in fibroblasts. The ROC curve underscores the high specificity of BMP6 in relation to DCM, while Mendelian randomization analysis further confirms BMP6 as a protective factor against DCM. Notably, BMP6 knockdown led to a decrease in SMAD6 expression and a marked elevation in COL1A1 expression levels, indicating its antifibrotic role.Conclusion BMP6 emerges as a promising biomarker for DCM, and its functional role in exerting an antifibrotic effect underscores its potential as a therapeutic target.
研究领域:
心脏病学
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分子生物学
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基因组学
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医学遗传学
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DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR BIOLOGY
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2024
·Vol. 70
·期 3
·95-101
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IF 1.5
Shanfu Wang,Bing Xu,Heng Yin,Zhen Hua,Yang Shao,Jianwei Wang
Osteoporosis is a common chronic bone disorder in postmenopausal women. Ginsenosides are primary active components in ginseng and the effects of various ginsenoside variants in osteoporosis treatment have been widely revealed. We planned to explore the impact of ginsenoside Rc on bone resorption in an osteoporosis rat model. We used ovariectomized rats to assess the potential impact of ginsenoside Rc on osteoporosis. μ-CT was implemented for analyzing the microstructure of the distal left femur in rats. H&E staining together with Masson staining were applied for bone histomorphometry evaluation. ELISA kits were implemented to detect serum concentrations of TRACP-5b, OCN, CTX, as well as PINP. Ginsenoside Rc treatment lessened the serum levels of TRACP-5b as well as CTX, while increasing serum levels of OCN, and PINP of OVX rats. Moreover, we found that ginsenoside Rc contributed to the synthesis of type I collagen via increasing Col1a1 and Col1a2 levels in femur tissues of ovariectomized rats. Our findings also revealed that ginsenoside Rc activated the TGF-β/Smad pathway by increasing TGF-β as well as phosphorylated Smad2/3 protein levels. Ginsenoside Rc alleviates osteoporosis in rats through promoting the TGF-β/Smad pathway.
研究领域:
药理学
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骨科
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内分泌学
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分子生物学
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DOI
高影响因子
HUMAN GENE THERAPY
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2023
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IF 4.2
Dr. Zhiguang Chen,Ms. Qi Zhao,Mr. Ran Zhang,Dr. Lianghong Chen,Mr. Songlan Gao,Dr. Yu Wang,Dr. Tiegang Li,Dr. Jinqi Xue
Substantial advances have been made in understanding the role of partial PDZ and LIM domain (PDLIM) family’s proteins in skeletal-related diseases. Yet, little is known about the effect of Pdlim1 on osteogenesis and fracture repair. This study aimed to investigate whether direct gene delivery using an adenovirus vector carrying Pdlim1 (Ad-oePdlim1) or encoding shRNA-Pdlim1 (Ad-shPdlim1) could affect the osteogenic activity of pre-osteoblastic MC3T3-E1 cells in vitro, and influence the fracture healing of mice in vivo. We found that Ad-shPdlim1 transfection contributed to the calcified nodule formation in MC3T3-E1 cells. Downregulation of Pdlim1 enhanced the alkaline phosphatase (ALP) activity and increased the expression of osteogenic markers (Runx2, Col1A1, osteocalcin and osteopontin). Further analysis indicated that Pdlim1 knockdown could activate β-catenin signaling, as evidenced by the accumulation of β-catenin in the nucleus and the increase levels of downstream regulators such as Lef1/Tcf7, Axin2, Cyclin D1 and Sox9. By contrast, Pdlim1 overexpression resulted in inhibition of the osteogenic activity of MC3T3-E1 cells. In vivo, at day 3 after fracture, Ad-shPdlim1 adenovirus particles were injected into the fracture site of the femur of mice, and the process of fracture healing was evaluated by X-ray, Micro-CT and histological examination. Local injection of Ad-shPdlim1 promoted the early cartilage callus formation, restored bone mineral density and accelerated cartilaginous ossification, with the upregulation of osteogenic gene (Runx2, Col1A1, osteocalcin and osteopontin) expression and activation of β-catenin signaling. Thus, we concluded that inhibition of Pdlim1 contributed to osteogenesis and fracture healing by activating the β-catenin signaling pathway.
研究领域:
分子生物学
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骨科
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再生医学
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基因治疗
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Min Wu,Yitao Zhao,Meihan Tao,Meimei Fu,Yue Wang,Qi Liu,Zhihui Lu,Jinshan Guo
The latest advancements in cellular bioenergetics have revealed the potential of transferring chemical energy to biological energy for therapeutic applications. Despite efforts, a three-dimensional (3D) scaffold that can induce long-term bioenergetic effects and facilitate tissue regeneration remains a big challenge. Herein, the cellular energetic metabolism promotion ability of l-malate, an important intermediate of the tricarboxylic acid (TCA) cycle, was proved, and a series of bioenergetic porous scaffolds were fabricated by synthesizing poly(diol l-malate) (PDoM) prepolymers via a facial one-pot polycondensation of l-malic acid and aliphatic diols, followed by scaffold fabrication and thermal-cross-linking. The degradation products of the developed PDoM scaffolds can regulate the metabolic microenvironment by entering mitochondria and participating in the TCA cycle to elevate intracellular adenosine triphosphate (ATP) levels, thus promoting the cellular biosynthesis, including the production of collagen type I (Col1a1), fibronectin 1 (Fn1), and actin alpha 2 (Acta2/α-Sma). The porous PDoM scaffold was demonstrated to support the growth of the cocultured mesenchymal stem cells (MSCs) and promote their secretion of bioactive molecules [such as vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and basic fibroblast growth factor (bFGF)], and this stem cells-laden scaffold architecture was proved to accelerate wound healing in a critical full-thickness skin defect model on rats.
研究领域:
生物医学工程
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组织工程
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细胞生物能学
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再生医学
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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）