ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2020
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IF 4.872
Yuhao Wu,Junke Wang,Tianxin Zhao,Yuexin Wei,Lindong Han,Lianju Shen,Chunlan Long,Shengde Wu,Guanghui Wei
Di-(2-ethylhexyl) phthalate (DEHP), one of the most commonly used endocrine-disrupting chemicals, has been shown to cause reproductive dysfunction in humans and animal models. However, very few studies have investigated the impact of DEHP at the post-transcriptional level in mouse testes, and the underlying mechanisms remain unclear. In the present research, TM3 Leydig cells were treated with 200 µM phthalic acid mono-2-ethylhexyl ester (MEHP, bio-metabolite of DEHP), and then the mRNA and lncRNA sequencing of TM3 Leydig cells was performed. Mice were exposed prepubertally to 0 or 500 mg DEHP/kg/day. RNA sequencing of mouse testes was performed to verify the RNA-seq results in vitro . The expression patterns of relevant genes and proteins were verified using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. DEHP and MEHP exposure led to testicular damage and accelerated cell aging via ROS accumulation. RNA sequencing analyses indicated that FOXO signaling and longevity regulation pathways were activated in resistance to ROS accumulation. FOXO signaling and longevity regulation pathway-related genes and proteins were also activated. By constructing a competing endogenous RNA (ceRNA) network, we observed that the ceRNA network might play a role in regulating FOXO signaling and longevity regulation pathways in response to excessive ROS accumulation and cell aging. In summary, our data here suggests that the ceRNA network may play a role in regulating FOXO signaling and longevity pathways in response to DEHP exposure in mouse testes.
研究领域:
生殖生物学
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毒理学
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分子生物学
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基因组学
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DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2025
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IF 4
Xudong Zhao,Yuting Ding,Zirou Duan,Di Deng,Zhiyue Mao,Yan Zhu,Xiaoxi Fan,Guohui Yu,Linquan Ge
The brown planthopper (BPH), Nilaparvata lugens is a typical pesticide-induced resurgent rice pest. A previous study showed that a fungicide, jinggangmycin (JGM)-treated rice led to markedly increased sugar content and (Insulin-like Peptide 2) ILP2 in response to sugar-mediated TOR signaling and stimulated fecundity in BPH. However, the role of the other ILPs in response to types of carbohydrate compounds remained poorly understood. The present studies showed that JGM treatment led to strongly increased glucose content and slightly increased sucrose and trehalose contents in rice plants. The 5th instar nymphs feeding with JGM-treated rice or exogenous glucose-supplied artificial diets markedly upregulated transcription of ILP2 and ILP3 , triggered ILP/Foxo signaling transduction, and further induced ILP3 secretion in the female brain. Moreover, silencing of ILP3 in the nymphal stage through RNAi led to a significant decrease of ILP3 secretion in the brain compared with dsGFP-treated females and inhibited ILP/Foxo signaling transduction. Suppression of ILP3 decreased soluble protein content in the ovary and fat body, inhibited Vg expression and protein synthesis, and further blocked ovarian development in female adults. Finally, depletion of ILP3 significantly influenced reproductive parameters, including the number of laid eggs, oviposition period, number of offspring, hatching rate, and population growth indexes of BPH. The current study revealed the mechanism of diet glucose regulating BPH reproduction by inducing ILP3 expression, which complements the theory of pesticide-induced resurgence of rice pests and also provides an important gene target for green control of BPH.
研究领域:
昆虫学
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农药毒理学
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分子生物学
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信号转导
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植物保护
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农业科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Danping Liu,Yi Wang,Hongyi Zhao,Xiuwen Xia,Jie Zhou,Li Xie,Pei Guo,Weihong Li
Ethnopharmacological relevance Wenyang-Tianjing-Jieyu Decoction (WTJD) is a traditional Chinese herbal formula with a history of ethnopharmacological use for depression, specifically targeting the Kidney-Yang deficiency (KYD) subtype. Its therapeutic rationale is well-documented in classical Chinese materia medica. However, the molecular mechanisms underpinning its clinical efficacy remain largely unelucidated. Aim of the study This study aimed to investigate the therapeutic effects and elucidate the underlying molecular mechanisms of WTJD, a traditional herbal formula, in ameliorating KYD-type depression in a rat model. Materials and methods The chemical profile of WTJD was characterized using UPLC-Q-Exactive/MS. Using a rat model of KYD-type depression established by combining Phellodendri chinensis Cortex decoction gavage, cold exposure, and chronic unpredictable mild stress (CUMS), we evaluated the therapeutic effects of WTJD. This randomized controlled study included five groups (n = 7/group): Control, Model, Fluoxetine, WTJD-Medium, and WTJD-High, with a 3-week intervention period. Furthermore, we integrated network pharmacology with hippocampal transcriptomics to identify key therapeutic targets, which converged on the FOXO signaling pathway. Finally, the predicted mechanism was validated by assessing key protein phosphorylation, nuclear translocation, hippocampal neurogenesis, and synaptic plasticity. Moreover, the regulatory mechanism was further corroborated in vitro using LPS-induced PC12 cells treated with WTJD-containing serum and the AKT inhibitor MK-2206. Results WTJD administration significantly ameliorated both the KYD phenotype and depressive-like behaviors in the rat model. Strikingly, both network pharmacology and hippocampal transcriptomic analyses converged on the FOXO signaling pathway as the central therapeutic target. Mechanistically, it was confirmed that WTJD activated the FOXO pathway by inhibiting AKT phosphorylation, which in turn promoted the nuclear translocation of FOXO4. Consistently, in vitro assays demonstrated that WTJD-containing serum protected PC12 cells and rescued downstream gene expression by modulating the FOXO signaling pathway, effects that were mimicked by AKT inhibition. This cascade of molecular events ultimately restored impaired adult hippocampal neurogenesis and synaptic plasticity. Conclusion WTJD ameliorates KYD-type depression by modulating the hippocampal FOXO signaling pathway to restore neurogenesis and synaptic plasticity. These results validate the FOXO pathway as a high-value target for subtype-specific antidepressant drug design.
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
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2025
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IF 2.8
Nian Liu,Shuchao Zhang,Yiliang Liu,Xing Lu,Xiaozhen He
Carbimazole, a first-line antithyroid agent, alleviates hyperthyroidism by inhibiting thyroid hormone synthesis. However, its clinical use is complicated by adverse effects such as cardiotoxicity and hepatotoxicity, underscoring the need to elucidate its mechanisms in model organisms. In this study, zebrafish embryos at 6-h postfertilization (hpf) were continuously exposed to increasing carbimazole concentrations, with systematic assessment of developmental and physiological parameters. Results demonstrated that concentrations above 3.5 μg/mL caused significant mortality and delayed hatching. Dose-dependent developmental abnormalities included shortened body length, reduced swim bladder area, and pericardial edema. Further analyses indicated carbimazole-induced cardiotoxicity characterized by impaired cardiac development, decreased heart rate, and dysregulation of apoptosis-related genes. A diminished fluorescence area suggested compromised cardiac tissue integrity. Concurrently, hepatotoxicity manifested as yolk sac enlargement and altered expression of liver-specific genes, indicating disrupted hepatic function. RNA sequencing (RNA-seq) analyses indicated that at 120 hpf, the 5-μg/mL carbimazole-treated group exhibited 158 upregulated genes and 562 downregulated genes compared with the wild-type (WT) group. GO and KEGG enrichment analyses revealed disruptions in several signaling pathways associated with liver metabolism and cardiac development, including metabolism, FoxO signaling, and the p53 signaling pathway. These findings demonstrate that carbimazole induces early embryonic developmental abnormalities, cardiotoxicity, and hepatotoxicity in zebrafish. This research provides new insights into carbimazole toxicity and valuable perspectives for optimizing its clinical dosing regimen.
研究领域:
药理学
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毒理学
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发育生物学
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分子生物学
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基因组学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2024
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IF 5.1
Zhen Dai,Yanhong Lin,Guandi Chen,Peng Yu,Haotian Wu,Ming Ning,Chris Blanchard,Zhongkai Zhou
The potential effects of probiotics on lowering lipid accumulation and alleviating gut microbiota perturbation have been extensively substantiated, but whether Lactobacillus rhamnoses-fermented oyster mushroom (FOM) could more pronouncedly attenuate obesity remains unclear. In this study, the anti-obesity effect of FOM was estimated based on the gut microbiota profile and analysis of hepatic lipid metabolic characteristics. The results revealed that FOM intervention dramatically improved hepatic lipid accumulation, characterized by reduction in fat-related factor metabolism levels and liver lesion enzymatic activities and down-regulation of the expression of genes associated with glycolipid metabolism (Foxo1, Gck, G6pd, Il6r and IL-β). Metabolomics analysis indicated HFD-induced dysglycaemia and disturbed amino acid metabolism, characterized by significant enrichment of pathways (butanoate metabolism, arginine biosynthesis, etc.) and elevated levels of D-mannose, succinate and β-D-fructose, followed by a decreased galactitol content. Furthermore, FOM intervention showed significant enrichment of specific pathways, particularly transcriptional misregulation in cancer and FoxO signaling pathways, while the MAPK signaling pathway demonstrated consistent enrichment across all experimental groups. FOM intervention reshaped the gut microbiota structure by facilitating the proliferation of SCFA producers (Romboutsia, Ruminococcaceae and Allobaculum), together with the depletion of Lachnospiraceae population. The current study strengthened our understanding of FOM prebiotic activities and obesity alleviation mechanisms.
研究领域:
营养学
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微生物学
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代谢组学
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分子生物学
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胃肠病学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2024
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IF 3.1
Jiayue Wang,Feixu Qin,Hongjin Wang,Lu Wang,Caihong Li,Lixin Sun
Senecio scandens Buch.-Ham., a traditional Chinese medicine commonly used clinically, exhibits various pharmacological properties, including anti-inflammatory, anti-tumor, antiviral, and antibacterial activities. However, its water extracts' chemical components and metabolites are inadequately understood, limiting further research. In this study, the chemical components and metabolism processes of Senecio scandens, both in vivo (plasma, feces, urine, and bile) and in vitro (gut microbiota and liver microsomes), were characterized based on ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry. Additionally, metabolites detectable in fecal samples and intestinal microbiota incubated but absent in liver microsomes were identified as characteristic metabolites of intestinal microbiota. The targets of the characteristic metabolites of intestinal microbiota were collected, followed by exploration of potential pathways through KEGG enrichment analysis. As a result, a total of 133 chemical components were preliminarily identified, including 35 organic acids, 21 alkaloids, 19 flavonoids and their glycosides, 17 phenylpropanoids, 10 jacaranda ketones, and 31 other compounds. Notably, 12 of these were potentially novel compounds. In addition, 39 prototype components in rats and 109 metabolites were identified and characterized, including 102 in vivo and 52 metabolites in vitro (51 in rat gut microbiota and 24 in rat liver microsomes). The main metabolic pathways include oxidation, reduction, hydrolysis, methylation, glucuronidation, sulfonation, and acetylation reactions. Furthermore, KEGG enrichment analysis revealed that the characteristic metabolites of intestinal microbiota may be related to the ErbB, FoxO, mTOR, and MAPK signaling pathways, exhibiting anti-inflammatory and anti-tumor effects. In summary, the chemical components and metabolites of Senecio scandens were comprehensively identified using a rapid and accurate method, providing a scientific basis for the in-depth study of the material basis and its clinical application of Senecio scandens .
研究领域:
药理学
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代谢组学
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生物信息学
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中药学
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化学生物学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
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
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
✓ 已验证
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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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
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
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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
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DOI
PubMed
高影响因子
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