BMC Complementary Medicine and Therapies
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2024
·Vol. 24
·期 1
·1-15
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IF 3.3
He Yu,Liu Fei,He Mingjuan,Long Fayu,Hu Ding,Chen Jingwen,Fang Miao,Wang Zhenlong
The purpose of this study was to investigate the mechanism by which resveratrol (Res) inhibits apoptosis and promotes proliferation and differentiation of pre-osteoblastic MC3T3-E1 cells, laying the groundwork for the treatment of osteoporosis (OP). The TCMSP database was used to find the gene targets for Res. The GeneCards database acquire the gene targets for OP. After discovering the potential target genes, GO, KEGG, and Reactome enrichment analysis were conducted. Verifying the major proteins involved in apoptosis can bind to Res using molecular docking. CCK8 measured the proliferative activity of mouse pre-osteoblasts in every group following Res intervention. Alkaline phosphatase staining (ALP) and alizarin red staining to measure the ability of osteogenic differentiation. RT-qPCR to determine the expression levels of Runx2 and OPG genes for osteogenic differentiation ability of cells. Western blot to measure the degree of apoptosis-related protein activity in each group following Res intervention. The biological processes investigated for GO of Res therapeutic OP involved in cytokine-mediated signaling pathway, negative regulation of apoptotic process, Aging, extrinsic apoptotic signaling pathway in absence of ligand, according to potential therapeutic target enrichment study. Apoptosis, FoxO signaling pathway, and TNF signaling pathway are the primary KEGG signaling pathways. Recactome pathways are primarily engaged in Programmed Cell Death, Apoptosis, Intrinsic Apoptotic Pathway, and Caspase activation via extrinsic apoptotic signaling pathways. This research established a new approach for Res treatment of OP by demonstrating how Res controls the apoptosis-related proteins TNF, IL6, and CASP3 to suppress osteoblast death and increase osteoclastogenesis.
研究领域:
药理学
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细胞生物学
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分子生物学
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生物信息学
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骨生物学
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网络医学
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DOI
高影响因子
AQUACULTURE
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2025
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IF 3.9
Lukuan Li,Zhe Wang,Tong Wang,Nannan Zhou,Fang Qiao,Zhen-Yu Du,Mei-Ling Zhang
Short-chain fatty acids (SCFAs) can enhance the growth of aquatic animals and improve flesh quality through the gut-muscle axis. However, the effects of valeric acid, one of the SCFAs, on aquatic animals remain unreported. This study sought to explore the effects of valeric acid on Nile tilapia ( Oreochromis niloticus ). A total of 360 Juvenile tilapia (mean weight, 1.820 ± 0.007 g) with 3 tanks for each treatment were randomly assigned to 12 rectangular acrylic tanks and fed with four isolipidic (6 % lipid) and isonitrogenous (37 % protein) diets for 60 days, including a control diet (CK) and three experimental diets supplemented with 500 mg/kg (CK + LV), 1000 mg/kg (CK + MV), and 2000 mg/kg (CK + HV) of sodium valerate. The results discovered that the enhanced flesh hardness ( p < 0.01) of tilapia caused by valerate was attributed to decreased myofiber size ( p < 0.001). Transcriptome analysis revealed significant enrichment of the Forkhead box O (FOXO) signaling pathway in the valerate-treated group ( p < 0.001). Subsequent qPCR, western blot, immunohistochemistry, and immunofluorescence analyses demonstrated that valerate inhibited muscle cell proliferation by activating the FOXO signaling pathway, suppressing FOXO nuclear export, and consequently downregulating cyclins and cyclin-dependent kinases (CDKs) ( p < 0.01). Furthermore, valerate suppressed muscle differentiation by inhibiting the transcription and protein levels expression of myogenic regulatory factors (MRFs) ( p < 0.001). Additional validation in C2C12 myoblasts and myotubes confirmed that valerate indeed inhibited myoblasts proliferation and myotubes differentiation ( p < 0.001). These findings indicated that valerate reduced myofiber size by suppressing myoblasts proliferation and myotubes differentiation. This study elucidated the effects and mechanisms of valerate on skeletal muscle and introduced a novel approach to enhance fish flesh hardness.
研究领域:
水产养殖
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营养学
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分子生物学
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动物生理学
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产品关联
DOI
高影响因子
Evidence-based Complementary and Alternative Medicine
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2019
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IF 1.984
Yueying Tao,Kunming Tian,Ji Chen,Danfeng Tan,Yan Liu,Yongai Xiong,Zehui Chen,Yingbiao Tian
This study aims to predict the active ingredients, potential targets, signaling pathways and investigate the “ingredient-target-pathway” mechanisms involved in the pharmacological action of Danshiliuhao Granule (DSLHG) on liver fibrosis. Pharmacodynamics studies on rats with liver fibrosis showed that DSLHG generated an obvious anti-liver fibrosis action. On this basis, we explored the possible mechanisms underlying its antifibrosis effect using network pharmacology approach. Information about compounds of herbs in DSLHG was collected from TCMSP public database and literature. Furthermore, the oral bioavailability (OB) and drug-likeness (DL) were screened according to ADME features. Compounds with OB≥30% and DL≥0.18 were selected as active ingredients. Then, the potential targets of the active compounds were predicted by pharmacophore mapping approach and mapped with the target genes of the specific disease. The compound-target network and Protein-Protein Interaction (PPI) network were built by Cytoscape software. The core targets were selected by degree values. Furthermore, GO biological process analysis and KEGG pathway enrichment analysis were carried out to investigate the possible mechanisms involved in the anti-hepatic fibrosis effect of DSLHG. The predicted results showed that there were 108 main active components in the DSLHG formula. Moreover, there were 192 potential targets regulated by DSLHG, of which 86 were related to liver fibrosis, including AKT1, EGFR, and IGF1R. Mechanistically, the anti-liver fibrosis effect of DSLHG was exerted by interfering with 47 signaling pathways, such as PI3K-Akt, FoxO signaling pathway, and Ras signaling pathway. Network analysis showed that DSLHG could generate the antifibrosis action by affecting multiple targets and multiple pathways, which reflects the multicomponent, multitarget, and multichannel characteristics of traditional Chinese medicine and provides novel basis to clarify the mechanisms of anti-liver fibrosis of DSLHG.
研究领域:
药理学
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中药学
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分子生物学
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系统生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2022
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IF 15.304
Yuyu Zhao,Long Bai,Yi Zhang,Runhua Yao,Yonghua Sun,Ruiyue Hang,Xiangyang Chen,Huaiyu Wang,Xiaohong Yao,Yin Xiao,Ruiqiang Hang
Osseointegration of implants is a complex physiological process that requires temporal and spatial regulation of immune responses, angiogenesis , and osteogenesis. To achieve efficient and long-term osseointegration, type I collagen (COL1) decorated nanoporous network was developed on titanium substrates via alkali treatment , polydopamine coating, and layer-by-layer (LBL) self-assembly. It was noted that the simple physisorbed COL1 could be easily desorbed from the nanostructured surface , however, multilayer COL1 constructed by polydopamine and LBL self-assembly obscured the nanoporous network of the alkali-treated titanium surfaces. Interestingly, the nanostructured surface covalently immobilized with COL1 (T-ADC) could timely convert macrophages (MΦs) from pro-inflammatory M1 to pro-healing M2 phenotype, generating a beneficial osteoimmune microenvironment and promoting angio/osteo-genesis. RNA sequencing revealed that the nanostructure and COL1 could synergistically activate RhoA/ROCK, PI3K-AKT, and classical MAPK signaling pathways in MΦs to sustain the cell cycle, and trigger autocrine feedback-mediated JAK-STAT and FoxO signaling pathways, which in turn motivated autophagy and oxidative stress resistance and attenuated lipopolysaccharide-induced Toll-like receptor signaling pathway and its downstream NF-κB and JNK/p38 MAPK signaling cascades, leading to the inhibition of inflammation and osteoclastic-related gene expression of MΦs. Simultaneously, T-ADC prominently facilitated angiogenesis of endothelial cells and osteogenesis of osteoblasts as well as their cross-talks, further highlighting synergistically positive effects of the nanostructure and COL1 on osseointegration. In vivo experiments revealed that T-ADC could induce abundant new bone mass and ameliorative osseointegration, corroborating the in vitro results. The study elucidated that the COL1 decorated nanoporous network on titanium surfaces could significantly regulate early inflammatory reaction and subsequent angio/osteo-genesis processes, resulting in favorable osseointegration.
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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免疫学
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细胞生物学
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组织工程
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
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2023
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IF 29.4
Dingxin Liu,Fei Cao,Zhifeng Xu,Chunhua Zhao,Zekun Liu,Jiadong Pang,Ze-Xian Liu,Mahdieh Moghiseh,Anthony Butler,Shaoxia Liang,Weijun Fan,Jiang Yang
Radioprotective agents hold clinical promises to counteract off-target adverse effects of radiation and benefit radiotherapeutic outcomes, yet the inability to control drug transport in human organs poses a leading limitation. Based upon a validated rank-based multigene signature model, we evaluate radiosensitivity indices of diverse normal organs as a genomic predictor of radiation susceptibility. We rationally design S elective OR gan- T argeting (SORT) hafnium oxide nanoparticles (HfO 2 NPs) via modulated synthesis by α-lactalbumin, homing to top vulnerable organs. HfO 2 NPs like Hensify are commonly radioenhancers, but SORT HfO 2 NPs exhibit surprising radioprotective effects dictated by unfolded ligands and Hf(0)/Hf(IV) redox couples. Still, the X-ray attenuation patterns allow radiological confirmation in target organs by dual-beam spectral computed tomography. SORT HfO 2 NPs present potent antioxidant activities, catalytically scavenge reactive oxygen species, and mimic multienzyme catalytic activities. Consequently, SORT NPs rescue radiation-induced DNA damage in mouse and rabbit models and provide survival benefits upon lethal exposures. In addition to inhibiting radiation-induced mitochondrial apoptosis, SORT NPs impede DNA damage and inflammation by attenuating activated FoxO, Hippo, TNF, and MAPK interactive cascades. We propose a universal methodology to reverse radioenhancers into radioprotectors. SORT radioprotective agents with image guidance are envisioned as compelling in personalized shielding from radiation deposition. This article is protected by copyright. All rights reserved
研究领域:
辐射生物学
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纳米技术
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医学成像
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分子生物学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Shuangliu Chen,Yalan Pan,Yang Guo,Xiaoxian Sun,Xue Bai,Mengmin Liu,Lining Wang,Jiřimutu Xiao,Cheng Chen,Yong Ma
This study utilized bioinformatics and data mining techniques to explore the molecular mechanism of curcumin in treating osteoporosis (OP) through the lens of ferroptosis, thereby identifying novel therapeutic targets. The datasets GSE35958, GSE35956, GSE7429, and GSE7158 were obtained from the Gene Expression Omnibus (GEO) database. GSE35958 and GSE35956 were employed as training sets for data integration, while GSE7429 and GSE7158 served as independent validation sets. Through retrieval from the FerrDb database, iron death-related genes (FRGs) were identified, and the differentially expressed genes (DEGs) were intersected to obtain differentially expressed FRGs (DEFRGs). Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted, followed by the construction of a Protein-Protein Interaction (PPI) network to identify Hub genes. The DGIdb database was utilized to predict candidate drugs associated with the Hub genes, and molecular docking and in vitro experiments confirmed that curcumin targets the Hub genes EGFR and PTGS2.Through in vitro testing of curcumin on BMSC cells, researchers examined cell vitality, iron death, osteogenic differentiation, mineralization, and the impact on EGFR and PTGS2 levels. The analysis yielded 2212 DEGs, 484 FRGs, with 45 FDEGs at the intersection. GO analysis revealed involvement in regulating mitochondrial proteins, amino acid transport across plasma membranes, and protein ubiquitination. KEGG pathway analysis indicated associations with iron death, FoxO signaling, mTOR signaling, cell aging, osteoclast differentiation, and GSH metabolism. Utilizing the MCC algorithm, five Hub genes were identified: MAPK3, PTGS2, TGFB1, CYBB, and EGFR, showing diagnostic potential for iron death. Curcumin displayed affinity for EGFR and PTGS2, mitigating iron-induced effects on BMSCs such as increased reactive oxygen species, Fe3+ levels, and decreased mitochondrial membrane potential. Furthermore, curcumin reversed these effects, suggesting EGFR and PTGS2 as targets for curcumin to inhibit BMSC ferroptosis and potentially delay osteoporosis development. Maintaining iron homeostasis and targeting BMSC ferroptosis could offer therapeutic avenues for iron overload-induced osteoporosis.
研究领域:
生物信息学
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药理学
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分子生物学
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医学遗传学
✓ 已验证
DOI
PubMed
高影响因子
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