MOLECULES
·
2023
·Vol. 28
·期 14
·5496
·
IF 4.6
Ting Li,Chaoyue Yang,Houkang Cao,Siyi Mo,Bo Li,Zhipeng Huang,Ruobing Zhang,Jianzhao Wu,Kefeng Zhang,Ya Gao
Bergenin (BER), a natural component of polyphenols, has a variety of pharmacological activities, especially in improving drug metabolism, reducing cholestasis, anti-oxidative stress and inhibiting inflammatory responses. The aim of this study was to investigate the effects of BER on liver injury induced by isonicotinic acid hydrazide (INH) and rifampicin (RIF) in mice. The mice model of liver injury was established with INH (100 mg/kg)+RIF (100 mg/kg), and then different doses of BER were used to intervene. The pathological morphology and biochemical indicators of mice were detected. Meanwhile, RNA sequencing was performed to screen the differentially expressed genes and signaling pathways. Finally, critical differentially expressed genes were verified by qRT-PCR and Western blot. RNA sequencing results showed that 707 genes were significantly changed in the INH+RIF group compared with the Control group, and 496 genes were significantly changed after the BER intervention. These differentially expressed genes were mainly enriched in the drug metabolism, bile acid metabolism, Nrf2 pathway and TLR4 pathway. The validation results of qRT-PCR and Western blot were consistent with the RNA sequencing. Therefore, BER alleviated INH+RIF-induced liver injury in mice. The mechanism of BER improving INH+RIF-induced liver injury was related to regulating drug metabolism enzymes, bile acid metabolism, Nrf2 pathway and TLR4 pathway.Keywords:bergenin;isonicotinic acid hydrazide;rifampicin;liver injury;RNA sequencing
研究领域:
药理学
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分子生物学
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毒理学
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DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2019
·
IF 3.298
Yafei Duan,Yun Wang,Dalin Xiong,Jiasong Zhang
The intestine is important for nutrition, metabolism and immunity. Succinate (SA) plays a vital role in the physiological homeostasis of animal intestines. However, the effects of dietary SA on the intestinal immunity and metabolism in shrimp are not clear. In this study, we investigated the immune and metabolic responses in the intestine of Litopenaeus vannamei that were fed diets consisting of different levels of SA: 0 g/kg (Con) and 10 g/kg (SA) for 56 days. The results from a RNA-seq analysis identified 6005 differentially expressed genes (DEGs), including 2728 upregulated genes and 3277 downregulated genes, which were grouped into 312 pathways. The DEGs were most enriched in pathways related to protein synthesis and amino acid metabolism , including “ribosome”, “aminoacyl-tRNA biosynthesis”, “pyrimidine metabolism”, and “arginine and proline metabolism”; additionally, carbohydrate and lipid metabolism pathways were also activated. A large number of immune-related genes were associated with mucus barrier modification, antimicrobial activity , pathogen attachment and recognition, antioxidant activity , and apoptosis. The expression patterns of several candidate genes involved in the immune response and nutrition metabolism were detected by qPCR. This study provides insight into the transcriptomic modulating mechanisms associated with intestinal immunity and the metabolism of L. vannamei in response to the intake of dietary SA.
研究领域:
水产养殖学
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分子生物学
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营养学
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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
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Fang-Fang Liu,Hai-Yan Ren,Feng Liu,Wen-Xuan Qi,Chao-Peng Liang,Bang-Xian Zhang,Xiang-Jun Rao
Insects mount robust immune responses to reduce the efficacy of biopesticides. Identification of critical immune targets for biocontrol strategies is thus essential. However, immune targets in the fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), a major pest of corn, remain largely unexplored. Here, we investigated the immune response of S. frugiperda to the entomopathogen Beauveria bassiana (Hypocreales: Cordycipitaceae). Time-series RNA sequencing revealed 863, 717, and 165 differentially expressed genes (DEGs) at 24, 48, and 60 h post-infection, respectively. GO and KEGG enrichment analyses revealed that DEGs were significantly enriched in immune-related terms and pathways. Among the DEGs, the gene encoding immulectin SfIML-1 , a C-type lectin with dual carbohydrate recognition domains, was significantly upregulated during the early and intermediate stages of infection. Genome-wide analysis identified nine IML genes, with SfIML-1 as the only one highly responsive to B. bassiana . Recombinant SfIML-1 binds pathogen-associated molecular patterns and pathogens, enhancing cellular responses. RNAi of SfIML-1 decreased survival after fungal infection, while injection of recombinant SfIML-1 increased survival. Suppression of the NF-κB and JAK-STAT pathways diminished SfIML-1 expression in both fat body and Sf9 cells. These results identify SfIML-1 as a key pattern recognition receptor and a promising target for developing novel biocontrol strategies.
研究领域:
昆虫学
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分子生物学
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生物防治
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 18
·10898
·
IF 6.208
Chenchen Guo,Ying Chen,Dengyun Wu,Yu Du,Mengyue Wang,Cunqi Liu,Jianzhou Chu,Xiaoqin Yao
Pinellia ternata(Thunb.) Druce is a traditional medicinal plant containing a variety of alkaloids, which are important active ingredients. Brassinolide (BR) is a plant hormone that regulates plant response to environmental stress and promotes the accumulation of secondary metabolites in plants. However, the regulatory mechanism of BR-induced alkaloid accumulation inP. ternatais not clear. In this study, we investigated the effects of BR and BR biosynthesis inhibitor (propiconazole, Pcz) treatments on alkaloid biosynthesis in the bulbil ofP. ternata. The results showed that total alkaloid content and bulbil yield was enhanced by 90.87% and 29.67% under BR treatment, respectively, compared to the control. We identified 818 (476 up-regulated and 342 down-regulated) and 697 (389 up-regulated and 308 down-regulated) DEGs in the BR-treated and Pcz-treated groups, respectively. Through this annotated data and the Kyoto encyclopedia of genes and genomes (KEGG), the expression patterns of unigenes involved in the ephedrine alkaloid, tropane, piperidine, pyridine alkaloid, indole alkaloid, and isoquinoline alkaloid biosynthesis were observed under BR and Pcz treatments. We identified 11, 8, 2, and 13 unigenes in the ephedrine alkaloid, tropane, piperidine, and pyridine alkaloid, indole alkaloid, and isoquinoline alkaloid biosynthesis, respectively. The expression levels of these unigenes were increased by BR treatment and were decreased by Pcz treatment, compared to the control. The results provided molecular insight into the study of the molecular mechanism of BR-promoted alkaloid biosynthesis.Keywords:alkaloid;brassinolide;ephedrine;secondary metabolism;RNA-seq
研究领域:
植物学
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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
Agronomy-Basel
·
2024
·Vol. 14
·期 3
·626
·
IF 3.3
Shuaiqi Zhao,Wanglong Miao,Sheng Sheng,Xin Pan,Ping Li,Weihong Zhou,Fuan Wu
Cadmium (Cd) is the most serious heavy metal pollutant in the agricultural soil of China and can transfer and accumulate through the food chain and affect the growth, development and physiological processes of phytophagous insect.Glyphodes pyloalisWalker (G. pyloalis) is one of the most important pests of mulberry, and there are few studies on the adverse effects of heavy metals on insects, especially mulberry pests. To understand the toxicology of Cd exposure onG. pyloalis, we investigated the effects of three different concentrations of Cd (0, 3.89 and 51.69 mg/kg, labeled as control check (CK), low dose (LD) and high dose (HD)) on the development and detoxification mechanism ofG. pyloalisand explored the molecular mechanism of Cd onG. pyloalislarvae using RNA-seq technology. Transcriptome analysis showed that compared with the CK, a total of 63 differentially expressed genes (DEGs) were identified in LD exposure, including 24 upregulated and 39 downregulated candidates. In CK versus HD groups, 395 upregulated DEGs and 436 downregulated DEGs were identified and the expression patterns of 12 genes related to detoxification and metabolism were verified using qPCR. These DEGs were relevant to multiple specific peroxisome and drug metabolism-cytochrome P450 pathways. Gene annotation and quantitative real-time PCR revealed that a high concentration of Cd significantly stimulated the expression of metabolic detoxification enzyme genes. The results revealed that Cd exposure changed the pupal weight, adult emergence rate and the activities of AKP, ACP and GST inG. pyloalisand induced notable adverse effects at the molecular level on detoxification and metabolism such as concentration and time differences. In addition, we silencedCYP12A2by RNA interference. Bioassays showed that after silencingCYP12A2, the survival rate ofG. pyloalisunder Cd exposure was lower than that of the control group.
研究领域:
环境毒理学
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昆虫学
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分子生物学
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产品关联
DOI
高影响因子
Clinical and Translational Medicine
·
2023
·Vol. 13
·期 6
·e1297
·
IF 10.6
Jie Yang,Hu Tan,Mengjia Sun,Renzheng Chen,Zhao Jian,Yuanbin Song,Jihang Zhang,Shizhu Bian,Bo Zhang,Yi Zhang,Xubin Gao,Zhen Chen,Boji Wu,Xiaowei Ye,Hailin Lv,Zhen Liu,Lan Huang
Background Atrial fibrillation (AF) is associated with an increased risk of thrombosis of the left atrial appendage (LAA). However, the molecular mechanisms underlying this site-specificity remain poorly understood. Here, we present a comparative single-cell transcriptional profile of paired atrial appendages from patients with AF and illustrate the chamber-specific properties of the main cell types. Methods Single-cell RNA sequencing analysis of matched atrial appendage samples from three patients with persistent AF was evaluated by 10× genomics. The AF mice model was created using Tbx5 knockout mice. Validation experiments were performed by glutathione S-transferase pull-down assays, coimmunoprecipitation (Co-IP), cleavage assays and shear stress experiments in vitro. Results In LAA, phenotype switching from endothelial cells to fibroblasts and inflammation associated with proinflammatory macrophage infiltration were observed. Importantly, the coagulation cascade is highly enriched in LAA endocardial endothelial cells (EECs), accompanying the up-regulation of a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) and the down-regulation of the tissue factor pathway inhibitor (TFPI) and TFPI2. Similar alterations were verified in an AF mouse model ( Tbx5 +/− ) and EECs treated with simulated AF shear stress in vitro. Furthermore, we revealed that the cleavage of both TFPI and TFPI2 based on their interaction with ADAMTS1 would lead to loss of anticoagulant activities of EECs. Conclusions This study highlights the decrease in the anticoagulant status of EECs in LAA as a potential mechanism underlying the propensity for thrombosis, which may aid the development of anticoagulation therapeutic approaches targeting functionally distinct cell subsets or molecules during AF.
研究领域:
心血管病学
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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
iScience
·
2024
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IF 4.6
Weijia Zhou,Chengjun Zhu,Peiliang Shen,Jacqueline F. Wang,Gaoshuang Zhu,Yuanyuan Jia,Yueyao Wu,Siliang Wang,Jia Sun,Fang Yang,Yanni Song,Xin Han,Xiaoxiang Guan
Circulating tumor cell clusters/micro-emboli (CTM) possess greater metastatic capacity and survival advantage compared to individual circulating tumor cell (CTC). However, the formation of CTM subtypes and their role in tumor metastasis remain unclear. In this study, we used a microfluidic Cluster-Chip with easy operation and high efficiency to isolate CTM from peripheral blood, which confirmed their correlation with clinicopathological features and identified the critical role of CTC-platelet clusters in breast cancer metastasis. The correlation between platelets and CTM function was further confirmed in a mouse model and RNA sequencing of CTM identified high-expressed genes related to hypoxia stimulation and platelet activation which possibly suggested the correlation of hypoxia and CTC-platelet cluster formation. In conclusion, we successfully developed the Cluster-Chip platform to realize the clinical capture of CTMs and analyze the biological properties of CTC-platelet clusters, which could benefit the design of potential treatment regimens to prevent CTM-mediated metastasis and tumor malignant progression.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 6
·e70089
·
IF 1.7
Chunhua Liu,Changli Fu,Luping Tang,Jieqi Li,Jia Sun,Yuan Lu,Jie Pan,Ting Liu,Yongjun Li,Yonglin Wang,Yong Huang,Yueting Li,Meng Zhou
Polygonum orientale L. (PO) represents significant bioactivities in treating myocardial ischemia (MI); however, its underlying mechanisms remain unclear. This study aims to elucidate PO's potential mechanisms in MI using an integrated approach that combines UHPLC–Q-Exactive Orbitrap HRMS, network pharmacology, and RNA-sequencing (RNA-seq). Initially, the chemical constituents of PO were identified using UHPLC–Q-Exactive Orbitrap HRMS. Subsequently, network pharmacology, molecular docking, and RNA-seq were employed to screen potential active components of PO targeting MI and predict their molecular mechanisms. Then, the molecular mechanisms were verified using western blotting and ELISA in MI mice. A total of 45 components were identified from PO, with 14 potential active compounds interacting with 204 MI-related genes. The findings suggest that PO could alleviate heart damage. The RNA-seq results indicated 244 potential targets regulated by PO. Integrating RNA-seq and network pharmacology analyses revealed that the toll-like receptor signaling pathway plays an important role, alongside the PI3K-Akt. Notably, PO reduced the expression of TLR4 and TLR2 while increasing p-Akt and p-PI3K levels in MI mice, leading to decreased inflammatory cytokines and apoptosis-related proteins. This study provides initial evidence that PO inhibits the toll-like signaling pathway and activates PI3K–Akt signaling pathway to exert protective effects against MI.
研究领域:
中药学
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分子生物学
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心血管病学
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产品关联
DOI
PubMed
高影响因子
Natural Product Communications
·
2024
·
IF 1.5
Zhang-lin Pu,Chi Zhang,Qian Yan,Zhou Liang,Zhi-Wei Xu,Ji-hu Wei,Hua Liu,Feng Chen
Objective: We explore the pharmacodynamic targets of kaempferol in treating osteoporosis using transcriptomics and animal experiment. Methods: Firstly, we constructed an ovariectomized rat model (OVX). The anti-osteoporosis effect of kaempferol was evaluated by bone mineral density (BMD) and hematoxylin-eosin staining comprehensively. Moreover, differential genes between groups were screened by RNA sequencing technology (RNA-seq) for transcriptomics and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways enrichment analysis were performed. Finally, partial results of transcriptomics were verified to detect the expression of the relevant gene expression by immunohistochemistry. Results: The pharmacodynamic findings indicated that the administration of kaempferol resulted in an elevation in BMD (P < .01) and a notable enhancement in tibia microstructural indices in the experimental rats (P < .01). The transcriptomic analysis revealed that NTN1, LTBP4, GSN, and EBF1 were identified as the principal targets for therapeutic intervention in osteoporosis. The results of animal experiments showed that kaempferol promoted osteogenesis and inhibited bone resorption by downregulating the protein expression of NTN1, LTBP4, GSN, and EBF1 (P < .01). Conclusion: Kaempferol enhances BMD levels, retards tibial bone loss with structural deterioration in OVX model rats, and promotes bone formation while curbing bone resorption through NTN1, LTBP4, GSN, and EBF1 protein down-regulation.
研究领域:
药理学
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分子生物学
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骨科医学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 2
·1081
·
IF 4.9
Yi Liu,Yang Ge,Yanfan Wu,Yongtong Feng,Han Liu,Wei Cao,Jinsong Xie,Jingzhong Zhang
Three-dimensional (3D) hepatocyte models have become a research hotspot for evaluating drug metabolism and hepatotoxicity. Compared to two-dimensional (2D) cultures, 3D cultures are better at mimicking the morphology and microenvironment of hepatocytes in vivo. However, commonly used 3D culture techniques are not suitable for high-throughput drug screening (HTS) due to their high cost, complex handling, and inability to simulate cell–extracellular matrix (ECM) interactions. This article describes a method for rapid and reproducible 3D cell cultures with ECM–cell interactions based on 3D culture instrumentation to provide more efficient HTS. We developed a microsphere preparation based on a high-voltage electrostatic (HVE) field and used sodium alginate- and collagen-based hydrogels as scaffolds for 3D cultures of HepG2 cells. The microsphere-generating device enables the rapid and reproducible preparation of bioactive hydrogel microspheres. This 3D culture system exhibited better cell viability, heterogeneity, and drug-metabolizing activity than 2D and other 3D culture models, and the long-term culture characteristics of this system make it suitable for predicting long-term liver toxicity. This system improves the overall applicability of HepG2 spheroids in safety assessment studies, and this simple and controllable high-throughput-compatible method shows potential for use in drug toxicity screening assays and mechanistic studies.Keywords:hepatocyte;3D cultures;hydrogel;microspheres;high-voltage electrostatic field;RNA-seq
研究领域:
细胞生物学
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药理学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Nature Protocols
·
2025
·
IF 16
Xu Ziye,Lyu Yuexiao,Chen Haide,Chen Yu,Wang Yongcheng
Formalin-fixed paraffin-embedded (FFPE) samples represent a vast and valuable resource of patient material, often linked to extensive clinical history and follow-up data. However, achieving single-cell or single-nucleus RNA (sc/snRNA) profiling in these archived tissues remains challenging. To address this, we have developed snRandom-seq, a droplet- and random primer–based single-nucleus total RNA sequencing technology specifically designed for FFPE tissues. This method captures total RNAs by using random primers and demonstrates a low doublet rate (0.3%), increased RNA coverage and enhanced detection of non-coding and nascent RNAs compared to state-of-the-art high-throughput sc/snRNA-seq technologies. This protocol provides a comprehensive guide to isolating single nuclei from FFPE samples; performing in situ DNA blocking, reverse transcription and dA tailing reactions; barcoding single-nucleus droplets; and preparing sequencing libraries. The entire snRandom-seq process can be completed in 4 d. This platform serves as a powerful tool for snRNA-seq of clinical specimens, with broad applications in studying complex biological systems.
研究领域:
分子生物学
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医学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
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