JOR Spine
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2024
·Vol. 7
·期 4
·e70004
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IF 3.4
Daqian Zhou,Tao Liu,Yongliang Mei,Jiale Lv,Kang Cheng,Weiye Cai,Silong Gao,Daru Guo,Xianping Xie,Zongchao Liu
Background Intervertebral disc degeneration (IVDD) is an age-related orthopedic degenerative disease characterized by recurrent episodes of lower back pain, the pathogenesis of which is not fully understood. This study aimed to identify key biomarkers of IVDD and its causes. Methods We acquired three gene expression profiles from the Gene Expression Omnibus (GEO) database, GSE56081, GSE124272, and GSE153761, and used limma fast differential analysis to identify differentially expressed genes (DEGs) between normal and IVDD samples after removing batch effects. We applied weighted gene co-expression network (WGCNA) to identify the key modular genes in GSE124272 and intersected these with DEGs. Next, A protein–protein interaction network (PPI) was constructed, and Cytoscape was used to identify the Top 10 hub genes. Functional enrichment analyses were performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Three key genes were validated using Western Blot (WB) and qRT-PCR. Additionally, we predicted miRNAs involved in hub gene co-regulation and analyzed miRNA microarray data from GSE116726 to identify four differentially expressed miRNAs. Results We identified 10 hub genes using bioinformatics analysis, gene function enrichment analysis revealed that they were primarily enriched in pathways, such as the TNF signaling pathway. We chose JUNB, SOCS3, and CEBPB as hub genes and used WB and qRT-PCR to confirm their expression. All three genes were overexpressed in the IVDD model group compared to the control group. Furthermore, we identified four miRNAs involved in the co-regulation of the hub genes using miRNet prediction: mir-191-5p, mir-20a-5p, mir-155-5p, and mir-124-3p. Using limma difference analysis, we discovered that mir-191-5p, mir-20a-5p, and mir-155-5p were all down-regulated and expressed in IVDD samples, but mir-124-3p showed no significant change. Conclusion JUNB, SOCS3, and CEBPB were identified as key genes in IVDD, regulated by specific miRNAs, providing potential biomarkers for early diagnosis and therapeutic targets.
研究领域:
分子生物学
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生物信息学
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骨科医学
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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Li Zou,Caiyan Sheng,Dongzhou Xia,Jixin Zhang,Yuming Wei,Jingming Ning
Withering is a crucial process that determines the quality of white tea (WT). Solar withering (SW) is reported to contribute to the aroma quality of WT. However, the mechanism by which aroma is formed in WT subjected to SW remains unclear. In this study, through headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC–MS) and transcriptomics, we found that 13 key genes enriched in the mevalonic acid and methylerythritol phosphate pathways, such as those of 1-deoxy- D -xylulose-5-phosphate synthase and terpineol synthase, were significantly upregulated, promoting the accumulation of α -terpinolene, geraniol, and nerolidol, which imparted floral and fruity odors to WT subjected to SW. Additionally, the significant upregulation of lipoxygenases enriched in the lipoxygenase pathway promoting the accumulation of hexanol, 1-octen-3-ol, ( E , Z )-3,6-nonadien-1-ol, and nonanal, which contributed to the green and fresh odor in WT subjected to SW. This study provided the first comprehensive insight into the effect mechanism of SW on aroma formation in WT.
研究领域:
植物学
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食品科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL GENETICS
·
2025
·
IF 1.6
Tang Zhiqi,Nong Jiacong,Qiu Xue,Huang Junwen,Feng Xueyi,Tu Guangpeng,Li Lang
Acute myocardial infarction (AMI) continues to pose a substantial risk to human lives worldwide. Endoplasmic reticulum stress (ERS) is increasingly recognized as one of the potential mechanisms of myocardial injury following AMI. The primary goal of this study is to investigate the correlation between ERS and AMI through machine learning-based bioinformatics analysis, explore key genes, and conduct in vivo and in vitro experimental validation. We performed differential analysis and Weighted Gene Co-expression Network Analysis (WGCNA) on gene expression data from the GEO database (GSE62646). The intersection with ERS-related genes (ERSRGs) was taken to obtain AMI-ERS-related genes (MIEGs), and machine learning algorithms were further used to identify key genes (Hubs) from the MIEGs. The validation set GSE59867 was used to assess the expression levels and predictive capabilities of the Hubs for AMI. An AMI rat model was established to detect the mRNA and protein expression levels of the Hubs. The protein inhibitor of the key gene FURIN was used to treat H9C2 cells under oxygen–glucose deprivation (OGD) to explore the effects of FURIN on ERS and apoptosis. Bioinformatics analysis identified 27 MIEGs, and machine learning further determined 5 Hubs highly associated with AMI and ERS: RELA, FURIN, ERGIC3, TPP1, and BGLAP. The expression of these Hubs was significantly elevated in AMI patients within both the training and validation sets, and the area under the curve (AUC) indicated good diagnostic value. Our experiments confirmed that the mRNA levels of Furin and RelA were significantly elevated in AMI rats. Furin protein was increased in AMI rats and OGD H9C2. Furin inhibitor could alleviate OGD-induced ERS and apoptosis in H9C2. Our study demonstrates that Hubs play a pivotal role in myocardial infarction. Notably, Furin and its mediated ERS and apoptosis are significant in the pathogenesis of AMI, potentially serving as target for AMI diagnosis and treatment.
研究领域:
医学
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生物信息学
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DOI
PubMed
高影响因子
PeerJ
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2021
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IF 2.984
Wenwen Wang,Wenwen Zhang,Yuanjing Hu
Background Chemotherapy resistance, especially platinum resistance, is the main cause of poor prognosis of ovarian cancer. It is of great urgency to find molecular markers and mechanism related to platinum resistance in ovarian cancer. Methods One mRNA dataset ( GSE28739 ) and one miRNA dataset ( GSE25202 ) were acquired from Gene Expression Omnibus (GEO) database. The GEO2R tool was used to screen out differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) between platinum-resistant and platinum-sensitive ovarian cancer patients. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for DEGs were performed using the DAVID to present the most visibly enriched pathways. Protein–protein interaction (PPI) of these DEGs was constructed based on the information of the STRING database. Hub genes related to platinum resistance were visualized by Cytoscape software. Then, we chose seven interested hub genes to further validate using qRT-PCR in A2780 ovarian cancer cell lines. And, at last, the TF-miRNA-target genes regulatory network was predicted and constructed using miRNet software. Results A total of 63 upregulated DEGs, 124 downregulated DEGs, four upregulated miRNAs and six downregulated miRNAs were identified. From the PPI network, the top 10 hub genes were identified, which were associated with platinum resistance. Our further qRT-PCR showed that seven hub genes (BUB1, KIF2C, NUP43, NDC80, NUF2, CCNB2 and CENPN) were differentially expressed in platinum-resistant ovarian cancer cells. Furthermore, the upstream transcription factors (TF) for upregulated DE-miRNAs were SMAD4, NFKB1, SMAD3, TP53 and HNF4A. Three overlapping downstream target genes (KIF2C, STAT3 and BUB1) were identified by miRNet, which was regulated by hsa-miR-494. Conclusions The TF-miRNA–mRNA regulatory pairs, that is TF (SMAD4, NFKB1 and SMAD3)-miR-494-target genes (KIF2C, STAT3 and BUB1), were established. In conclusion, the present study is of great significance to find the key genes of platinum resistance in ovarian cancer. Further study is needed to identify the mechanism of these genes in ovarian cancer.
研究领域:
肿瘤学
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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
BIOCHEMICAL ENGINEERING JOURNAL
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2024
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IF 3.7
Zhimei Zhang,Chao Zhao,Tianming Wu,Yanfeng Xu,Lu Wang,Yusheng Niu
The accumulation of glyphosate during its application in agriculture and its toxicity seriously threaten ecosystems and human health. Currently, glyphosate residual contamination is mainly accomplished through bioremediation techniques based on enhanced microbial degradation activity. However, there are drawbacks, such as poor environmental adaptability of strains and low degradation efficiency. Therefore, in this study, an efficient glyphosate-degrading strain, Pseudomonas alcaligenes Z1–1, was isolated from herbicide-contaminated environments and was capable of completely degrading glyphosate at a concentration of 200 mg/L within 7 days. Kinetics analysis showed that glyphosate degradation was concentration-dependent, with a maximum tolerant concentration of 800 mg/L. Mass spectrometric analysis indicated that AminoMethylPhosphonic acid (AMPA) was the predominant intermediate produced in the degradation pathway of glyphosate, revealing that glyphosate destruction began with breaking the C-N bond. Whole genome sequencing identified the key genes potentially involved in glyphosate degradation, including the thiO , glpA , aroA , soxB , and argA genes. Furthermore, in contrast to the majority of the metabolic pathways previously reported for glyphosate degradation via glyphosate oxidoreductase , the breaking of the C-N bond was primarily catalyzed by glycine oxidase . Overall, this research provides novel insights into the mechanisms of glyphosate degradation, offering valuable degradation enzyme resources for future applications.
研究领域:
环境科学
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微生物学
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分子生物学
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DOI
高影响因子
Journal of Inflammation Research
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2024
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IF 4.2
Jianmin Gong,Bo Shi,Ping Yang,Adeel Khan,Tao Xiong,Zhiyang Li
Background Hypertrophic cardiomyopathy (HCM) is a dominantly inherited disease associated with sudden immune cell associations that remain unclear. The aim of this study was to comprehensively screen candidate markers associated with HCM and immune cells and explore potential pathogenic pathways.Methods First, download the GSE32453 dataset to identify differentially expressed genes (DEGs) and perform Gene Ontology and pathway enrichment analysis using DAVID and GSEA. Next, construct protein-protein interaction (PPI) networks using String and Cytoscape to identify hub genes. Afterward, use CIBERSORT to determine the proportion of immune cells attributed to key genes in HCM and conduct ROC analysis based on the external dataset GSE36961 to evaluate their diagnostic value. Finally, validate the expression of key genes in the hypertrophic cardiomyocyte model through qRT-PCR using data from the HPA database.Results Comprehensive analysis revealed that there were 254 upregulated genes and 181 downregulated genes in HCM. The enrichment study underscored pathways of inflammatory signaling, including MAPK and PI3K-Akt pathways. Pathways abundant in genes associated with HCM encompassed myocardial contraction and NADH dehydrogenase activity. Additionally, the analysis of immune infiltration revealed a notable increase in macrophages, NK cells, and monocytes in the HCM group, showing statistically significant variances in CD4 memory resting T cell infiltration when compared to the healthy control group. Within the validation dataset GSE36961, the Area Under the Curve (AUC) scores for eight crucial genes (FOS, CD86, CD68, BDNF, PIK3R1, PLEK, RAC2, CCL2) each exceeded 0.8. The HPA database revealed the positioning traits and paths of these eight crucial genes in smooth muscle cells, myocardial cells, and fibroblasts. The outcomes of the qRT-PCR were aligned with the sequencing findings.Conclusion Bioinformatics analysis unveiled pivotal genes, pathways, and immune involvement, illuminating the molecular underpinnings of HCM. These findings suggest promising therapeutic targets for clinical applications.
研究领域:
医学
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遗传学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
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2023
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IF 5.8
Jing Wen,Tong Ren,Jinzhen Zheng,Xing Jiang,Yingxia Li,Xilin Jiang,Xin Jin,Hongying Zhao,Jingwen Li
As the main pathological basis for the development of cardiovascular and cerebrovascular diseases, atherosclerosis (AS) seriously affects human health. The key targets of biological information analysis of AS can help exploit therapeutic targets. The expression data of early and progressive atherosclerotic tissues were downloaded from the Gene Expression Omnibus (GEO) database. Based on GSE28829 and GSE120521, 74 key genes were obtained through differential expression analysis and weighted correlation network analysis (WGCNA) analysis, which were mainly enriched in the regulating of inflammatory response, chemokine signalling pathway, apoptosis, lipid and AS, Toll-like receptor signalling pathway and so on according to the results of the enrichment analysis. Cytoscape software was applied to screen four pivotal genes (TYROBP, ITGB2, ITGAM and TLR2) based on PPI. The results of the correlation analysis showed that the expression level of pivotal genes was positively related to macrophages M0, and was negatively related to T cells follicular helper. In addition, the expression of ITGB2 was positively related to Tregs. In this study, bioinformatics was applied to screen pivotal genes affecting the progress of AS, which were significantly related to immune-related biological functions and signal pathways of atherosclerotic tissues and the infiltration level of immune cells. Therefore, pivotal genes were expected to become therapeutic targets for AS.
研究领域:
心血管病学
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生物信息学
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DOI
PubMed
高影响因子
Frontiers in Plant Science
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2025
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IF 4.8
Qingyan Ling,Beihong Zhang,Junfei Jiang,Zufei Xiao,Zhipeng Zhu,Lina Huang,Yuanqiu Liu,Zhinong Jin
Camphora officinarum Nees ex Wall ( C. officinarum ), a citral-rich aromatic plant, is recognized as an unrivalled natural source of citral for spice production. Its large-scale cultivation in China via the sustainable coppice-rotation system has markedly revitalized rural economies. Nevertheless, the genetic basis driving its prolific citral accumulation remains elusive. We conducted an integrated transcriptomic and metabolomic analysis comparing three citral type accessions (C1, C2, C3) with a non-citral type control (C0). Metabolomic profiling identified 904 leaf metabolites, with terpenoids representing the most abundant class (19.49%). Strikingly, GC-MS analysis unveiled a monoterpene-dominated essential oil composition in citral type C. officinarum leaves , characterized by four dominant constituents: geranial (36.9%-44.7%), neral (30.7%-34.1%), E-isocitral (2.2%-2.9%), and Z-isocitral (1.5%-2.1%). Integrated transcriptomic and metabolomic analysis highlighted critical key genes, acetyl-CoA C-acetyltransferase ( CoAACT ), hydroxymethylglutaryl-CoA synthase ( CoHMGS) , hydroxymethylglutaryl-CoA reductase ( CoHMGR ), phosphomevalonate decarboxylase ( CoMVD ), 1-deoxy-D-xylulose-5-phosphate synthase ( CoDXS ), geranylgeranyl diphosphate synthase, type Ⅲ ( CoGGPS) , farnesyl diphosphate synthase ( CoFDPS ) showed elevated expression, enhancing precursor availability. The geraniol synthase ( CoGES ) and alcohol dehydrogenase ( CoADH ) involved in citral synthesis were significantly up-regulated in citral type C. officinarum . These findings demonstrate that the quantitative disparities in terpenoid distribution and concentration collectively define the species’ unique aromatic identity, underscoring chemotype-specific metabolic regulation mechanisms, while also screening key genetic determinants of citral biosynthesis preliminarily, thereby laying the groundwork for precision breeding programs in aromatic C. officinarum .
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产品关联
DOI
PubMed
高影响因子
PLANT PHYSIOLOGY AND BIOCHEMISTRY
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2023
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IF 6.5
Ruiyi Fan,Congyi Zhu,Diyang Qiu,Genlin Mao,Bernd Mueller-Roeber,Jiwu Zeng
As a well-recognized traditional Chinese medicine (TCM), immature fruits of Citrus grandis ‘Tomentosa’ (CGT) serve to cure chronic cough in humans. Specialized metabolites including flavonoids may have contribute to this curing effect. Knowledge about the molecular mechanisms underlying flavonoid biosynthesis in ‘Tomentosa’ fruits will, therefore, support the breeding of varieties with improved medicinal properties . Hence, we profiled the transcriptomes and metabolites of the fruits of two contrasting C. grandis varieties, namely ‘Zheng-Mao’ (‘ZM’) used in TCM production, and a locally cultivated pomelo, namely ‘Guang-Qing’ (‘GQ’), at four developmental stages. A total of 39 flavonoids, including 14 flavanone/flavone, 5 isoflavonoids , 12 flavonols, and 6 anthocyanins , were identified, and 16 of which were quantitatively determined in the fruits of the two varieties. We found that ‘ZM’ fruits contain more flavonoids than ‘GQ’. Specifically, rhoifolin levels were significantly higher in ‘ZM’ than in ‘GQ’. We annotated 31,510 genes, including 1,387 previously unknown ones, via transcriptome sequencing of ‘ZM’ and ‘GQ.’ A total of 646 genes were found to be differentially expressed between ‘ZM’ and ‘GQ’ throughout at all four fruit developmental stages, indicating that they are robust expression markers for future breeding programs. Weighted gene co-expression network analysis identified 18 modules. Combined transcriptional and metabolic analysis revealed 25 genes related to flavonoid biosynthesis and 16 transcriptional regulators (MYBs, bHLHs, WD40) that may be involved in the flavonoids biosynthesis in C. grandis ‘Tomentosa’ fruits.
研究领域:
植物生物学
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分子遗传学
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药理学
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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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