Materials Today Bio
·
2026
·
IF 11
Chao Song,Yang Zhou,Yinjing Luo,Liquan Wang,Tao Liu,Daqian Zhou,Fei Liu,Jingwen Chen,Zhijiang Fu,Feng Chen,Guoyou Wang,Zongchao Liu
Background Infected bone defects are difficult to treat due to bacterial biofilms and chronic inflammation. Systemic antibiotics often fail and cause severe side effects. A dual-drug delivery system that combines antibacterial and osteo-immunomodulatory actions may offer a synergistic solution. Methods A gelatin-based microfluidic microsphere (GM@RES@VAN) co-loading vancomycin (VAN) and resveratrol (RES) was developed. The microspheres were characterized for morphology, drug release, and elemental composition. Antibacterial and biofilm-degrading effects were assessed in vitro against MRSA. A rat infected bone defect model was used to evaluate in vivo healing via micro-CT, histology, and immunofluorescence. Network pharmacology, molecular docking, and cellular assays (qPCR, Western blot, TEM, HIF inhibition) explored the molecular mechanism. Results GM@RES@VAN microspheres showed uniform size, smooth surface, and sustained dual-drug release. In vitro, the microspheres exhibited potent bactericidal activity and biofilm degradation (∗∗∗p < 0.001). In vivo, the GM@RES@VAN group significantly reduced local bacterial load, decreased inflammatory infiltration, and promoted collagen deposition and new bone formation, with increased bone mineral density and bone volume/tissue volume (∗p < 0.05). Mechanistically, resveratrol suppressed pro-inflammatory factors (IL6, TNF, IL1B), reduced HIF1A, MMP9, and PTGS2 expression, preserved mitochondrial ultrastructure, upregulated osteogenic markers (ALP, OCN, COL I) and the anti-apoptotic protein BCL2. Vancomycin primarily cleared the infection, while resveratrol acted through the TNF/HIF-1 axis to reshape the inflammatory microenvironment and promote osteogenesis—their synergy was confirmed by HIF inhibition tests. Conclusion The GM@RES@VAN dual-drug microspheres achieve programmed antibacterial and osteo-immunomodulatory effects via vancomycin-mediated infection clearance and resveratrol-driven TNF/HIF-1 pathway regulation. This combination offers a promising strategy for treating refractory infected bone defects.
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Yuwei Yang,Peng Ni,Lixue Ma,Haikang Tang,Jiaming Yang,Xiaoliang Zhou,Yikun Sun,Wenqing Xu
Ethnopharmacological relevance Radiation-Induced Skin Injury (RISI) is the major cutaneous side effect met by cancer patients who received radiotherapy. Disposed earthworm (Dilong) has been historically employed for treating various ailments in ancient China. Amputated-regeneration and high radiation-tolerant are two distinctive characteristics for earthworms. These features might due to their abundant biologically active substances (65 % composed of proteins), which make them attractive candidates for radioprotector development. Aim of the study This study aimed to investigate therapeutic mechanism of regenerated E. fetida protein extract (G90′-ES2) in mitigating RISI, and reveal therapeutic potential macromolecules by proteomic analysis. Materials and methods Protein salt precipitation method was firstly adopted to obtain G90′-ES2/G90-ES2 protein complex. Their radioprotective activities were evaluated in vitro by cell viability, migration, ROS accumulation, EdU proliferation, cell cycle and apoptosis assays. A combined radiogenic injury mice model was constructed to analyze radiotherapeutic function of G90′-ES2 in vivo . Its mechanism against RISI was illustrated by RNA-Seq analysis, qPCR, and HIF Luciferase Reporter Assay. Finally, a nanoElute UPLC-MS/MS method was used to elucidate therapeutic potential macromolecules in G90′-ES2. Results We discovered that G90′-ES2 displayed higher efficacy than G90-ES2 in mitigating RISI, mainly by activating radio-resistant HIF-1 pathway, redistributing cell cycle phases (S-phase preservation), accelerating re-epithelialization, and enhancing tissue angiogenesis. The significantly up-regulated proteins (including lumbrokinase, aquaporin, RAD51C, TCTP, and SCBP2) in G90′-ES2 might hold particular importance for its therapeutic effect against RISI. Conclusions This investigation will broaden our understanding of the radiation-tolerant and regenerative capacities for earthworm; also provide medical candidates for the development of skin-specific radioprotector.
研究领域:
放射生物学
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创伤修复与再生医学
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分子药理学
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蛋白质组学
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皮肤生物学
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天然药物开发
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转化医学
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产品关联
DOI
PubMed
高影响因子
Proteome Science
·
2019
·Vol. 17
·期 1
·1-11
·
IF 1.795
Li Qiwen,Luo Tao,Lu Wenxin,Yi Xiaoxiao,Zhao Zhihe,Liu Jun
Background The periodontal ligament is essential for homeostasis of periodontal tissue. A hypoxic milieu of the periodontal tissue is generated under periodontitis or during orthodontic treatment, which affects the periodontal and bone remodelling process. Here, we provide a comprehensive proteomic characterization of periodontal ligament cells under hypoxic conditions, aiming to reveal previously unappreciated biological changes and to help advance hypoxia-based therapeutic strategies for periodontal diseases.Methods Human periodontal ligament cells (hPDLCs) were characterized using immunohistochemistry (IHC) and flow cytometry (FACS). Successful hypoxia treatment of hPDLCs with 1% O2 was confirmed by qRT-PCR. Proliferation was evaluated using an MTT assay. The proteomic expression profile under hypoxia was studied with the isobaric tags for relative and absolute quantification (iTRAQ) approach followed by protein identification and bioinformatic analysis, and western blot verification was performed.Results The hPDLCs were positive for vimentin, CD73 and CD105 and negative for keratin, CD34 and CD45. After hypoxia treatment, the mRNA expression of hypoxia-inducible factor 1a (HIF1a) was upregulated. The proliferation rate was elevated during the first 6 h but decreased from 6 h to 72 h. A total of 220 differentially expressed proteins were quantified in hPDLCs under hypoxia (1% O2, 24 h), including 153 upregulated and 67 downregulated proteins, five of which were verified by western blot analysis. The Gene Ontology enriched terms included the energy metabolic process, membrane-bound organelle and vesicle, and protein binding terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated several involved pathways, including glycolysis/gluconeogenesis, biosynthesis of amino acids, the HIF-1 signalling pathway, and focal adhesion. A protein–protein interaction (PPI) network demonstrated the dominant role of autophagy over apoptosis under hypoxia.Conclusion The proteomic profile of hPDLCs under hypoxia was mainly related to energy metabolism, autophagy, and responses to stimuli such as adhesion and inflammation. Previously unrecognized proteins including solute carrier family proteins, heat shock proteins, ubiquitination-related enzymes, collagen and S100 family proteins are involved in adaptive response to hypoxia in hPDLCs and are thus of great research interest in future work.
研究领域:
牙科学
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分子生物学
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细胞生物学
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蛋白质组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Tao He,Mingshuang Wang,Jiao Kong,Qiang Wang,Yue Tian,Chaofeng Li,Qian Wang,Chuanxin Liu,Jianmei Huang
Ethnopharmacological relevance Coptis Categorized Formula (CCF) is one of the core prescriptions in Treatise on Febrile Diseases . Its efficacy can be available not only in exogenous diseases but widely in various internal injuries and miscellaneous diseases. CCF (i.e., Huanglian Jiedu Decoction, Huanglian Ejiao Decoction, Dahuang Huanglian Xiexin Decoction, Gegen Qinlian Decoction) is different in composition, but they all play a favorable role in curative effect on type 2 diabetes mellitus (T2DM). Therefore, it is of great significance to reveal the common mechanism of CCF in treating T2DM. Aim of the study Based on network pharmacology and non-targeted metabolomics research strategy, the common mechanism of the CCF treating T2DM was discussed. Materials and methods Firstly, Ultra-high performance liquid chromatography-quadrupole-time of flight/mass spectrometry was used to identify the chemical constituents of the CCF. Then, the targets of these chemical components were used for network pharmacology analysis associated with therapeutic effect. Finally, the diabetic zebrafish model was constructed to further verify the common mechanism of the CCF in treating T2DM. Results A total of 160 chemical compositions were identified and 16 of them were common chemical compositions of the four CCF, including berberine , baicalin , coptisine and so forth. Network pharmacology results showed that Dipeptidyl peptidase (DPP)-4, cysteinyl aspartate specific proteinase (CASP)3, nitric oxide synthase (NOS)2, NOS3, and other 37 targets were common targets of CCF, and advanced glycation end products (AGE)-receptor of advanced glycation end products (RAGE) signaling pathway in diabetic complications , mitogen-activated protein kinase (MAPK) signaling pathway and hypoxia inducible factor (HIF)-1 signaling pathway were critical pathways of four CCF in the treatment of T2DM. CCF can lessen the blood glucose of diabetic zebrafish. The contents of 25 differential metabolites in diabetic zebrafish were altered. These metabolites were mainly related to phenylalanine , tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, sphingolipid metabolism, and tyrosine metabolism. Conclusion Our research shows that the common mechanism of CCF in improving T2DM is as follows: berberine, baicalin, coptisine and other chemical components can directionally regulate DPP-4, CASP3, NOS2, NOS3 and other targets, which are mediated by AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and HIF-1 signaling pathway. The content of endogenous metabolites such as L-valine and L-sorbitose changes, and further regulates the metabolism of amino acid metabolism, lipid metabolism, purine metabolism, sphingosine metabolism and arachidonic acid metabolism, so as to play a significant role in regulating glycolipid metabolism, improving insulin resistance, inhibiting cell apoptosis, anti-oxidation and anti-inflammation, and finally ameliorating T2DM.
研究领域:
民族药理学
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网络药理学
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代谢组学
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生物医学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Wen Zhang,Menglei Ding,Yaru Feng,Shuhui Cai,Zichen Luo,Jinjun Shan,Liuqing Di
ABSTRACT Background Non-small cell lung cancer (NSCLC) is a highly prevalent and fatal form of lung cancer. In China, Aconiti Lateralis Radix Praeparata ( Fuzi in Chinese), derived from the lateral root of Aconitum carmichaeli Debx. (Ranunculaceae, Aconitum ), is extensively prescribed to treat cancer in traditional medicine and clinical practice. However, the precise mechanism by which Fuzi treats NSCLC remains unknown. Purpose This article aims to assess the efficacy of Fuzi against NSCLC and elucidate its underlying mechanism. Methods Marker ingredients of Fuzi decoction were quantified using UPLC-TSQ-MS. The effectiveness of Fuzi on NSCLC was evaluated using a xenograft mouse model. Subsequently, a comprehensive approach involving network pharmacology, serum metabolomics, and 16S rDNA sequencing was employed to investigate the anti-NSCLC mechanism of Fuzi . Results Pharmacological evaluation revealed significant tumour growth inhibition by Fuzi , accompanied by minimal toxicity. Network pharmacology identified 29 active Fuzi compounds influencing HIF-1, PI3K/Akt signaling, and central carbon metabolism in NSCLC. Integrating untargeted serum metabolomics highlighted 30 differential metabolites enriched in aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate metabolism, and the tricarboxylic acid (TCA) cycle. Targeted serum metabolomics confirmed elevated glucose content and reduced levels of pyruvate, lactate, citrate, α-ketoglutarate, succinate, fumarate, and malate following Fuzi administration. Furthermore, 16S rDNA sequencing assay showed that Fuzi ameliorated the dysbiosis after tumorigenesis, decreased the abundance of Proteobacteria, and increased that of Firmicutes and Bacteriodetes. PICRUSt analysis revealed that Fuzi modulated the pentose phosphate pathway of the gut microbiota. Spearman correlation showed that Proteobacteria and Escherichia_Shigella accelerated the TCA cycle, whereas Bacteroidota , Bacteroides, and Lachnospiraceae_NK4A136_group suppressed the TCA cycle. Conclusions This study firstly introduces a novel NSCLC mechanism involving Fuzi , encompassing energy metabolism and intestinal flora. It clarifies the pivotal role of the gut microbiota in treating NSCLC and modulating the TCA cycle. Moreover, these findings offer valuable insights for clinical practices and future research of Fuzi against NSCLC.
研究领域:
肿瘤学
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药理学
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代谢组学
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微生物组研究
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2023
·
IF 2.9
Sili Zheng,Dongning Zhang,Bailu Duan,Guoyan Mo,Jingjing Li,Hailing Huang,Shanshan Wang,Yan Ye,Zhuang Huang,Ping Huang,Fengyun Zhang,Fang Huang,Lintao Han
Acute enteritis (AE) is a type of digestive disease caused by biochemical factors that irritate the intestinal tract or pathogenic bacteria that infect it. In China, Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) have been applied against diarrhea caused by AE and bacillary dysentery for many years, but the underlying mechanisms of their beneficial effects are not known. In the present study, network pharmacology and metabolomics were performed to clarify the active ingredients of MMRAC and explore the specific mechanism of MMRAC on AE mice. A total of 43 active components of MMRAC with 87 anti-AE target genes were identified, and these target genes were enriched in IL-17 and HIF-1 signaling pathways. Integration analysis revealed that purine metabolism was the critical metabolic pathway by which MMRAC exerted its therapeutic effect against AE. Specifically, MAPK14, MMP9, PTGS2, HIF1A, EGLN1, NOS2 were the pivotal targets of MMRAC for the treatment of AE, and Western blot analysis revealed MMRAC to decrease protein levels of these pro-inflammatory signaling molecules. According to molecular docking, these key targets have a strong affinity with the MMRAC compounds. Collectively, MMRAC relieved the colon inflammation of AE mice via regulating inflammatory signaling pathways to reduce hypoxia and improved energy metabolism.
研究领域:
药理学
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代谢组学
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炎症
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Cheng Lu,Miao Chen,Yuanyuan Zhao,Yongxin Zhan,Xin Wei,Laijin Lu,Mingxi Yang,Xu Gong
Avoiding ischemic necrosis after flap transplantation remains a significant clinical challenge. Developing an effective pretreatment method to promote flap survival postoperatively is crucial. Cobalt chloride (CoCl 2 ) can increase cell tolerance to ischemia and hypoxia condition by stimulating hypoxia-inducible factor-1 (HIF-1) expression. However, the considerable toxic effects severely limit the clinical application of CoCl 2 . In this study, cobalt-based metal-organic frameworks (Co-MOF) encapsulated in a microneedle patch (Co-MOF@MN) was developed to facilitate the transdermal sustained release of Co 2+ for rapid, minimally invasive rapid pretreatment of flap transplantation. The MN patch was composed of a fully methanol-based two-component cross-linked polymer formula, with a pyramid structure and high mechanical strength, which satisfied the purpose of penetrating the skin stratum corneum of rat back to achieve subcutaneous vascular area administration. Benefiting from the water-triggered disintegration of Co-MOF and the transdermal delivery via the MN patch, preoperative damage and side effects were effectively mitigated. Moreover, in both the oxygen-glucose deprivation/recovery (OGD/R) cell model and the rat dorsal perforator flap model, Co-MOF@MN activated the HIF-1α pathway and its associated downstream proteins, which reduced reperfusion oxidative damage, improved blood supply in choke areas, and increased flap survival rates post-transplantation. This preprotection strategy, combining MOF nanoparticles and the MN patch, meets the clinical demands for trauma minimization and uniform administration in flap transplantation. Statement of significance Cobalt chloride (CoCl 2 ) can stimulate the expression of hypoxia-inducible factor (HIF-1) and improve the tolerance of cells to ischemia and hypoxia conditions. However, the toxicity and narrow therapeutic window of CoCl 2 severely limit its clinical application. Herein, we explored the role of Co-MOF as a biocompatible nanocage for sustained release of Co 2+ , showing the protective effect on vascular endothelial cells in the stress model of oxygen-glucose deprivation. To fit the clinical needs of minimal trauma in flap transplantation, a Co-MOF@MN system was developed to achieve local transdermal delivery at the choke area, significantly improving blood supply opening and flap survival rate. This strategy of two-step delivery of Co 2+ realized the enhancement of biological functions while ensuring the biosafety.
研究领域:
生物医学工程
·
药学
·
组织工程
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再生医学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Xue Li,Hao Liu,Wenqian Yu,Xiaomei Liu,Caixia Liu
Objective Congenital diaphragmatic hernia (CDH) is a common and often lethal birth defect characterized by congenital lung malformation, which severely affects neonate prognosis and mortality. This study aimed to investigate differences in protein expression in order to elucidate the mechanism of CDH-associated pulmonary hypoplasia during the early stage of lung development using tandem mass tag (TMT) quantitative proteomics. Methods Nitrofen was administered orally to establish a rat CDH model, and pathological changes were evaluated through hematoxylin-eosin (H&E), PCNA, and Ki67 staining at the pseudoglandular stage. Fetal lungs were then collected, pooled before TMT labeling, and subjected to mass spectrometry. Immunohistochemistry (IHC), Western blotting, and Q-PCR were used to further validate the candidate proteins. Results A total of 79 differentially expressed proteins (DEPs) were identified when CDH and control lungs were compared, and further bioinformatics analysis showed that these proteins play important roles in tight-junctions, phospholipase D signaling, and the HIF-1 signaling pathway. Three differentially expressed proteins, Cldn3, Magi1, and Myh9 are involved in the tight-junction pathway (P < 0.05), and their differential expressions were confirmed by IHC, Western blotting, and Q-PCR. Conclusion These findings indicate that alterations of tight-junction protein expression may play an important role in the pathogenesis of abnormal lung development in CDH. Further studies are warranted to verify the mechanism by which these tight-junction proteins influence the pathogenesis of CDH-associated pulmonary hypoplasia.
研究领域:
发育生物学
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蛋白质组学
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儿科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2025
·
IF 2.5
Zebin Huang,Wanying Zhang,Qi Shu,Xiao-Chun Guo,Xi Zheng,YuJing Lu
Inflammation is an important predisposing factor for many chronic diseases. The dietary flavonoid silibinin has excellent anti-inflammatory properties in cells, but its low bioavailability in the blood compromises its therapeutic potential. This study aims to investigate the potential of dibenzoylmethane (DBM) to synergistically enhance the anti-inflammatory benefits of silibinin (SB). The synergistic effects of DBM and SB in combination were evaluated in LPS-induced RAW264.7 cells and TPA-induced mice. In addition, a network pharmacology approach and molecular docking were used to explore the key targets and signaling pathways of DBM and SB in combination. The results showed that DBM and SB synergistically inhibited the production of NO, ROS, IL-1β, and TNF-α in a 1:1 concentration ratio. These two compounds may exert their synergistic effects by modulating the NF-κB and HIF-1 signaling pathways, among others. Molecular docking revealed that both compounds exhibited high binding affinities to iNOS and COX-2. Compared with single compound use, the two compounds in combination significantly reduced ear edema and inflammatory cell infiltration, and inhibited the protein expression of iNOS and COX-2 in TPA-induced mice. This research provides a rationale for the combination of DBM and SB as an effective anti-inflammatory agent.
研究领域:
药理学
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免疫学
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分子生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Beibei Zhang,Mengnan Zeng,Ru Wang,Qimei Tie,Ruyi Fan,Xuyuan Zhang,Xiaoke Zheng,Weisheng Feng
Ethnopharmacological relevance The Chinese herbal Plantaginis Herba (PL) is one of the most widely used plants for both medicinal and dietary purposes. Plantaginis Herba is the main medicine used in a traditional Chinese prescription called Cheqiancao decoction, and it is known for its liver and kidney protective properties. Aim of the study : The aim of the present study was to explore the interventions and mechanisms of PL in ADR nephropathy by performing an integrated analysis of in vitro and in vivo experiments. Materials and methods The ingredients of PL were analysed by Ultra High Performance Liquid Chromatography (UPLC). The biochemical indicators of renal injury in the serum and urine were detected by a Micronumerase assay and ELISA. The renal histopathology and ultrastructure were analysed by H&E staining, Masson’s trichrome staining and transmission electron microscopy (TEM), respectively. By identifying the targets of PL and ADR nephropathy, a network of PL–constituents–targets–ADR nephropathy was constructed, and a KEGG signaling pathway enrichment analysis was performed to complete the network pharmacology. A transcriptomic analysis was performed on a sequencing platform (Illumina). Results Plantaginis Herba significantly decreased the levels of BUN, Scr, ALB, MAU and KIM-1. Plantaginis Herba inhibited renal histopathological injury and alleviate foot process fusion and podocyte basement membrane thickening. In addition, the results of the transcriptomic analysis and network pharmacology analysis indicated that the HIF-1, TGF-β, and PI3K/AKT signaling pathways; apoptosis; and ECM–receptor interactions might be pivotal pathways for the effect of the PL intervention on ADR nephropathy. Moreover, the validation results revealed that PL could effectively attenuate collagen fibre deposition and inhibit oxidative stress. Plantaginis Herba could regulate the expression levels of pivotal proteins in the β-catenin/TGF-β1, HIF-1, and PI3K signaling pathways in renal tissues. Plantaginis Herba could reduce the level of apoptosis and the percentage of decrease in the mitochondrial membrane potential (MMP) in primary renal cells from rats with ADR nephropathy, and regulate key proteins involved in mitochondrial apoptosis. Furthermore, Luteolin from PL had good affinity for HIF-1α, and the ability of Luteolin to ameliorate in ameliorating ADR-induced MPC-5 cell injury was attenuated by overexpressing HIF-1α. Conclusions Plantaginis Herba alleviates ADR-induced nephropathy by regulating mitochondrial apoptosis via the HIF-1α signaling pathway. Luteolin may be one of the active ingredients responsible for these effects, and these findings provide an innovative strategy for the intervention and treatment of ADR nephropathy.
研究领域:
民族药理学
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药理学
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转录组学
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网络药理学
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肾病学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Chunhua Zhao,Zekun Liu,Chia-Che Chang,Yi-Chia Chen,Qize Zhang,Xiao-Dong Zhang,Chrysafis Andreou,Jiadong Pang,Ze-Xian Liu,Di-Yan Wang,Moritz F. Kircher,Jiang Yang
Triple-negative breast cancer (TNBC) is considered more aggressive with a poorer prognosis than other breast cancer subtypes. Through systemic bioinformatic analyses, we established the ferroptosis potential index (FPI) based on the expression profile of ferroptosis regulatory genes and found that TNBC has a higher FPI than non-TNBC in human BC cell lines and tumor tissues. To exploit this finding for potential patient stratification, we developed biologically amenable phototheranostic iron pyrite FeS2 nanocrystals (NCs) that efficiently harness near-infrared (NIR) light, as in photovoltaics, for multispectral optoacoustic tomography (MSOT) and photothermal ablation with a high photothermal conversion efficiency (PCE) of 63.1%. Upon NIR irradiation that thermodynamically enhances Fenton reactions, dual death pathways of apoptosis and ferroptosis are simultaneously triggered in TNBC cells, comprehensively limiting primary and metastatic TNBC by regulating p53, FoxO, and HIF-1 signaling pathways and attenuating a series of metabolic processes, including glutathione and amino acids. As a unitary phototheranostic agent with a safe toxicological profile, the nanocrystal represents an effective way to circumvent the lack of therapeutic targets and the propensity of multisite metastatic progression in TNBC in a streamlined workflow of cancer management with an integrated image-guided intervention.
研究领域:
癌症生物学
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纳米技术
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光疗
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分子生物学
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医学成像
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产品关联
DOI
PubMed
高影响因子
REPRODUCTIVE TOXICOLOGY
·
2021
·
IF 3.143
Jiadong Chen,Lian Kang,Junke Wang,Yuhao Wu,Lindong Han,Xiangqin Zheng,Yuexin Wei,Tianxin Zhao,Lianju Shen,Chunlan Long,Guanghui Wei,Shengde Wu
Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor that accumulates in organisms in various ways and induces male reproductive system disorders. In this study, we established a testicular injury model by gavage with different concentrations of DEHP. The testes were then collected for RNA sequencing (RNA-seq), and the results were analyzed by bioinformatics and verified by experiments. Our research results show that different concentrations of DEHP interfere with testicular development differently. Weighted gene coexpression network analysis (WGCNA) generated sixteen modules and identified the turquoise module as key. Then, estrogen receptor 1 (ESR1), filamin A (Flna) and Furin were identified as hub genes. qPCR and immunohistochemistry results revealed that all three hub genes were upregulated. We detected the locations of these genes by immunohistochemistry. ESR1 was mainly located in Leydig cells; Flna immunostaining is observed in the Leydig and some germ cells and Furin staining was seen in almost all types of testicular cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed enrichment mainly in MAPK signaling pathways, p53 signaling pathways, HIF-1 signaling pathways, protein processing in the endoplasmic reticulum, apoptosis, the cell cycle, RNA degradation, etc. This is the first study using WGCNA to investigate the mechanism of DEHP-induced injury in the prepubertal testis, providing new research angles to further understand the mechanism of DEHP-induced injury in the prepubertal testis.
研究领域:
毒理学
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生殖生物学
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分子生物学
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生物信息学
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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）