Food & Function
·
2024
·Vol. 15
·期 11
·6068-6081
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IF 5.1
Haonan Yu,Zhenyou Lou,Tingbo Wu,Xiaochun Wan,Haitao Huang,Yuanyuan Wu,Bo Li,Youying Tu,Puming He,Junsheng Liu
Epigallocatechin gallate (EGCG), a prominent bioactive compound found in tea, offers numerous health benefits. Previous studies have highlighted its potential in mitigating hyperuricemia. In this study, hyperuricemic mice induced by potassium oxonate (PO) were treated with EGCG or the anti-hyperuricemia medication allopurinol (AP) to investigate the mechanisms underlying their anti-hyperuricemic effects. The results demonstrated that both EGCG and AP significantly reduced serum uric acid (UA) levels. Further analysis revealed that EGCG promoted the expression of UA secretion transporter genes (Oat1 and Oct1) while inhibiting the expression of UA reabsorption transporter genes (Urat1 and Glut9) in the kidney. By 16S rDNA sequencing, EGCG, but not AP, was found to alter the composition of the gut microbiota. Notably, EGCG induced significant changes in the relative abundance of specific bacteria such as Lactobacillus, Faecalibaculum, and Bifidobacterium, which displayed high correlations with serum UA levels and UA-related gene expression. Metabolomic analysis suggested that EGCG-induced modifications in bacterial metabolites might contribute to the alleviation of hyperuricemia. Transcriptomic analysis of the intestinal epithelium identifies 191 differentially expressed genes (DEGs) in EGCG-treated mice, including 8 purine-related genes. This study elucidates the anti-hyperuricemic mechanisms of EGCG, particularly its influence on the gut microbiota and gene expression in the intestinal epithelium.
研究领域:
药理学
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微生物学
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分子生物学
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营养学
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转录组学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR GENETICS AND GENOMICS
·
2022
·Vol. 297
·期 3
·801-815
·
IF 2.98
Zhang Yonglei,Gao Shanshan,Zhang Ping,Sun Haidi,Lu Ruixue,Yu Runnan,Li Yanxiao,Zhang Kunpeng,Li Bin
Eugenol, a plant-derived component possessing small side effects, has an insecticidal activity to Tribolium castaneum ; however, the underlying molecular mechanisms of eugenol acting on T. castaneum are currently unclear. Here, a nerve conduction carboxylesterase and a detoxifying glutathione S-transferase were significantly inhibited after eugenol exposure, resulting in the paralysis or death of beetles. Then, RNA-sequencing of eugenol-exposed and control samples identified 362 differentially expressed genes (DEGs), containing 206 up-regulated and 156 down-regulated genes. RNA-seq data were validated further by qRT-PCR. GO analysis revealed that DEGs were associated with 1308 GO terms of which the most enriched GO terms were catalytic activity, and integral component of membrane; KEGG pathway analysis showed that these DEGs were distributed in 151 different pathways, of which some pathways associated with metabolism of xenobiotics or drug were significantly enriched, which indicated that eugenol most likely disturbed the processes of metabolism, and detoxication. Moreover, several DEGs including Hexokinase type 2 , Isocitrate dehydrogenase , and Cytochrome b-related protein , might participate in the respiratory metabolism of eugenol-exposed beetles. Some DEGs encoding CYP , UGT , GST , OBP , CSP , and ABC transporter were involved in the xenobiotic or drug metabolism pathway, which suggested that these genes of T. castaneum participated in the response to eugenol exposure. Additionally, TcOBPC11/ TcGSTs7 , detected by qRT-PCR and RNA-interference against these genes, significantly increased the mortality of eugenol-treated T. castaneum , providing further evidence for the involvement of OBP/GST in eugenol metabolic detoxification in T. castaneum . These results aid eugenol insecticidal mechanisms and provide the basis of insect control.
研究领域:
昆虫学
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分子生物学
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基因组学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Endocrinology
·
2024
·
IF 3.9
Zhou Fang,Mao Jianhong
Objective: Precocious puberty (PP) is a prevalent endocrine disorder affecting the physical and mental wellbeing of children. Identifying the triggering factors of PP has become a central issue. This study seeks to investigate the metabolomic and transcriptomic alterations in PP.Material and methods: First, 37 school-aged girls diagnosed with PP and 25 age-matched prepubertal control girls were recruited, and the fecal samples were collected for non-targeted metabolomic analysis to screen for differentially expressed metabolites (DEMs). Subsequently, an animal model of PP was constructed by danazol administration to neonatal female rats, and both fecal non-targeted metabolomics and serum next-generation transcriptomic sequencing were performed to screen DEMs and differentially expressed genes (DEGs) in PP. Moreover, the DEM co-existing in clinical and animal models was administrated to PP rats to explore the role of the target metabolite in PP.Results: A total of 24 DEMs in PP clinical samples and 180 DEMs and 425 DEGs in PP animal samples were identified. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEMs and DEGs were enriched in disease-associated pathways, including fatty acid synthesis, glycerolipid metabolism, pyrimidine metabolism, steroid hormone biosynthesis, progesterone-mediated oocyte maturation, and gonadotropin-releasing hormone (GnRH) signaling pathway, forming a tight DEM–DEG pathway regulatory network. Further DEM validation demonstrated that thymine supplementation delayed the opening of the vagina and development of PP in model rats.Conclusion: This study reveals that the metabolomic and transcriptomic changes, along with enriched pathways, are implicated in PP based on clinical and animal analyses. The findings may provide new strategies and research avenues for PP treatment.
研究领域:
内分泌学
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分子生物学
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儿科
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代谢组学
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转录组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLANT PHYSIOLOGY AND BIOCHEMISTRY
·
2023
·
IF 6.5
Jiankang Xin,Tianmin Che,Xiaolong Huang,Huiqing Yan,Shan Jiang
Cytochrome P450 monooxygenase 98 (CYP98) is a critical rate-limiting enzyme of the phenylpropanoid pathway. One of the end-product of the phenylpropanoid pathway is a lignin monomer, although the occurrence of lignin in bryophytes is controversial. Here we investigated the functions of PpCYP98 in Physcomitrium patens by transcriptome and metabolome analyses. We identified 5266 differentially expressed genes (DEGs) and 68 differentially abundant secondary metabolites between wild-type and ΔPpCYP98 gametophores . Of the identified metabolites, 23 phenolic acids were identified, with only one showing upregulation. Among the phenolic acids, 4-coumaroyl tartaric acid and chlorogenic acid showed significant decreases. Declines were also observed in coniferylaldehyde and coniferin , precursor substances and downstream products of the lignin monomer coniferyl alcohol , respectively. Thus, the pre-lignin synthesis pathway already exists in bryophytes, and PpCYP98 plays vital roles in this pathway. Besides, most flavonoids show significant reductions, including eriodyctiol, dihydroquecetin, and dihydromyricetin, whereas naringenin chalone and dihydrokaempferol were increased after PpCYP98 knockout. Therefore, the synthesis of flavonoids shares the core pathway with phenylpropanoids and mainly starts from caffeoyl-CoA, that is the compound of divergence between the two pathways in moss. PpCYP98 showed systemic effects on metabolisms, including carbohydrate, fatty acid , and hormonal signaling transductions, suggesting that PpCYP9 8 might indirectly regulate carbon influx allocation. Our results demonstrated roles of PpCYP98 were essential for the development of the early landing plant.
研究领域:
植物生物学
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分子生物学
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代谢组学
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基因组学
✓ 已验证
DOI
PubMed
高影响因子
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
·
2023
·Vol. 22
·期 4
·905-917
·
IF 3.1
Wen Ying,Zeng Liyun,Chen Qitong,Li Yitong,Fu Mengdie,Wang Zixin,Liu Hong,Li Xiejia,Huang Peng,Wu Wei,Zou Qiongyan,Yi Wenjun
Background The aim of this study was to identify changes in gene expression before and after 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and to investigate the potential mechanism of 5-ALA-PDT based on ribonucleic acid sequencing (RNA-Seq) analysis. Methods Secondary hyperparathyroidism (SHPT) primary cells were isolated from surgically excised specimens and exposed to laser light. The transcription profiles of SHPT primary cells were identified through RNA-Seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to validate genes based on RNA-Seq results. Results In total, 1320 DEGs were identified, of which 1019 genes were upregulated and 301 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including TGF beta in extracellular matrix (ECM), negative regulation of triglyceride biosynthetic process, protein heterodimerization activity, systemic lupus erythematosus, ECM–receptor interaction, focal adhesion and protein digestion and absorption. Protein–protein interaction (PPI) network analyses identified potential heat shock protein (HSP) interactions among the DEGs. Eight HSP genes were also identified that were most likely involved in 5-ALA-PDT, which were further validated by RT-qPCR and western blotting. Conclusions The findings of this descriptive study reveal changes in the transcriptome profile during 5-ALA-PDT, suggesting that gene expression and mutation, signaling pathways, and the molecular network are altered in SHPT primary cells. The above findings provide new insight for further studies on the mechanisms underlying 5-ALA-PDT in SHPT. Graphical abstract
研究领域:
转录组学
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光动力疗法
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内分泌学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Pan-Pan Jia,Rohana Chandrajith,Muhammad Junaid,Tian-Yun Li,Yong-Zhi Li,Xing-Yi Wei,Li Liu,De-Sheng Pei
Chronic kidney disease with uncertain etiology (CKDu) in Sri Lanka has attracted much attention as a global health issue. However, how environmental factors in local drinking water induce kidney damage in organisms is still elusive. We investigated multiple environmental factors including water hardness and fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM) to elucidate their toxic effects on CKDu risk in zebrafish. Acute exposure affected renal development and inhibited the fluorescence of Na, K-ATPase alpha1A4:GFP zebrafish kidney. Chronic exposure influenced the body weight of both genders of adult fish and induced kidney damage by histopathological analyses. Furthermore, the exposure significantly disturbed differential expression genes (DEGs), diversity and richness of gut microbiota, and critical metabolites related to renal functions. The transcriptomic analysis revealed that kidney-related DEGs were linked with renal cell carcinoma, proximal tubule bicarbonate reclamation, calcium signaling pathway, and HIF-1 signaling pathway. The significantly disrupted intestinal microbiota was closely related to the environmental factors and H&E score, which demonstrated the mechanisms of kidney risks. Notably, the Spearman correlation analysis indicated that the changed bacteria such as Pseudomonas , Paracoccus , and ZOR0006 , etc were significantly connected to the DEGs and metabolites. Therefore, the assessment of multiple environmental factors provided new insights on “bio-markers” as potential therapies of the target signaling pathways, metabolites, and gut bacteria to monitor or protect residents from CKDu.
研究领域:
环境科学
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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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微生物学
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公共卫生
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Shuangliu Chen,Yalan Pan,Yang Guo,Xiaoxian Sun,Xue Bai,Mengmin Liu,Lining Wang,Jiřimutu Xiao,Cheng Chen,Yong Ma
This study utilized bioinformatics and data mining techniques to explore the molecular mechanism of curcumin in treating osteoporosis (OP) through the lens of ferroptosis, thereby identifying novel therapeutic targets. The datasets GSE35958, GSE35956, GSE7429, and GSE7158 were obtained from the Gene Expression Omnibus (GEO) database. GSE35958 and GSE35956 were employed as training sets for data integration, while GSE7429 and GSE7158 served as independent validation sets. Through retrieval from the FerrDb database, iron death-related genes (FRGs) were identified, and the differentially expressed genes (DEGs) were intersected to obtain differentially expressed FRGs (DEFRGs). Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted, followed by the construction of a Protein-Protein Interaction (PPI) network to identify Hub genes. The DGIdb database was utilized to predict candidate drugs associated with the Hub genes, and molecular docking and in vitro experiments confirmed that curcumin targets the Hub genes EGFR and PTGS2.Through in vitro testing of curcumin on BMSC cells, researchers examined cell vitality, iron death, osteogenic differentiation, mineralization, and the impact on EGFR and PTGS2 levels. The analysis yielded 2212 DEGs, 484 FRGs, with 45 FDEGs at the intersection. GO analysis revealed involvement in regulating mitochondrial proteins, amino acid transport across plasma membranes, and protein ubiquitination. KEGG pathway analysis indicated associations with iron death, FoxO signaling, mTOR signaling, cell aging, osteoclast differentiation, and GSH metabolism. Utilizing the MCC algorithm, five Hub genes were identified: MAPK3, PTGS2, TGFB1, CYBB, and EGFR, showing diagnostic potential for iron death. Curcumin displayed affinity for EGFR and PTGS2, mitigating iron-induced effects on BMSCs such as increased reactive oxygen species, Fe3+ levels, and decreased mitochondrial membrane potential. Furthermore, curcumin reversed these effects, suggesting EGFR and PTGS2 as targets for curcumin to inhibit BMSC ferroptosis and potentially delay osteoporosis development. Maintaining iron homeostasis and targeting BMSC ferroptosis could offer therapeutic avenues for iron overload-induced osteoporosis.
研究领域:
生物信息学
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药理学
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分子生物学
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医学遗传学
✓ 已验证
DOI
PubMed
高影响因子
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